muramidase and Kidney-Diseases

Lysozyme amyloidosis is a rare hereditary systemic amyloidosis with amyloid deposits in various tissues leading to progressive organ failure. It has been mainly reported in developed countries since 1993. Here we report a lysozyme amyloidosis family with variant lysozyme p.Trp82Arg in a Chinese family.. The main clinical manifestation of this case was dominant kidney involvement presenting with proteinuria and decreased renal function. Biopsy of the kidney showed massive amyloid deposits in the glomerular mesangium and subendothelium. Immunohistochemistry and mass spectrometry of renal tissue confirmed the lysozyme nature of the amyloid. DNA sequencing of the peripheral blood leukocytes revealed a single base-pair transition from T to C (TGG/ CGG) of codon 82, leading to the replacement of tryptophan by arginine in the mature protein (p.Trp82Arg). The affected patients in this family also presented with dominant kidney involvement, one of them has been confirmed by IHC and mass spectrometry on his renal biopsy and gene testing as well. As there is no radical therapy for lysozyme amyloidosis, patients were given symptomatic treatment such as antihypertensive drugs and antibiotics. To our knowledge, this is the first report of lysozyme amyloidosis in a Chinese family.. Hereditary amyloidosis with a variant lysozyme of p.Trp82Arg presented with dominant kidney involvement was firstly reported in a Chinese family.

Topics: Adult; Amino Acid Substitution; Amyloid; Amyloidosis, Familial; Biopsy; China; Exons; Humans; Kidney; Kidney Diseases; Male; Muramidase; Mutation; Pedigree; Proteinuria; Sequence Analysis, Protein

A 65-year-old man was diagnosed with systemic sclerosis on the basis of skin thickening and positivity of anti-Scl-70 antibodies. Because myogenic enzymes, such as creatinine phosphokinase and aldorase, were also elevated, myopathy or myositis associated with systemic sclerosis was considered. Muscle magnetic resonance imaging and gallium scintigraphy did not show abnormalities. Findings of muscle biopsy demonstrated presence of noncaseating granulomas with multinucleated giant cells. In addition, serum angiotensin-converting enzyme and lysozyme were elevated, and therefore a diagnosis of sarcoid myopathy was made. Further, renal sarcoidosis was revealed with renal biopsy. Prednisolone (40 mg/day) improved both the myopathy and nephritis. Sarcoid myopathy is a rare condition, but it should be considered when myogenic enzymes are elevated in the patient with systemic sclerosis. Further, muscle biopsy may be essential to make an accurate diagnosis in such condition.

Topics: Aged; Biopsy; Giant Cells; Granuloma; Humans; Kidney Diseases; Male; Muramidase; Muscle, Skeletal; Muscular Diseases; Prednisolone; Renin; Sarcoidosis; Scleroderma, Systemic; Treatment Outcome

Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tubular cells and reduced unwanted systemic effects. In our approach kinase inhibitors are linked to the renal carrier lysozyme using a platinum-based linker that binds drugs via a coordinative linkage. Many kinase inhibitors contain aromatic nitrogen atoms able to bind to this linker without the need of prior derivatization. The resulting drug-lysozyme conjugates are rapidly filtered in the glomerulus into the tubular lumen and subsequently reabsorbed via the endocytic pathway for clearance of low-molecular weight proteins. An important property of the formed conjugates is their in vivo stability and the sustained drug release profile within target cells. This review summarizes the state-of-the-art of drug targeting to the kidney. Furthermore, we will highlight recent results obtained with kinase inhibitor-lysozyme conjugates targeted to different kinases, i.e. the transforming growth factor (TGF)-beta-receptor kinase, p38 MAPkinase and Rho-associated kinase. Both in vitro and in vivo results demonstrated their efficient tubular uptake and beneficial therapeutic effects, superior to treatment with free kinase inhibitors. These proof-of-concept studies clearly indicate the feasibility of drug targeting for improving the renal specificity of kinase inhibitors.

Topics: Animals; Drug Delivery Systems; Fibrosis; Gene Targeting; Humans; Kidney; Kidney Diseases; Kidney Tubules; Muramidase; Protein Kinase Inhibitors

Autosomal dominant hereditary amyloidosis represents not 1 disease but a group of diseases, each the result of mutations in a specific protein. The most common form is transthyretin amyloidosis, which has been recognized clinically for over 50 years as a familial polyneuropathy. Nonneuropathic amyloidoses (Ostertag type amyloidosis) include those due to abnormalities in lysozyme, fibrinogen Aalpha-chain, and apolipoprotein A-I and A-II. The role of lysozyme in amyloid-related human disorders was first described in 1993; to date, there have been only 9 publications describing this disorder, which is a nonneuropathic form of hereditary amyloidosis. Reported cases have involved 7 unrelated families. We describe here our own experience with 4 families suffering from lysozyme amyloidosis: the first had prominent renal manifestations with sicca syndrome, the second and third had prominent gastrointestinal symptoms, and the fourth had a dramatic bleeding event due to rupture of abdominal lymph nodes. To our knowledge, this last symptom has not been reported previously, but is reminiscent of the hepatic hemorrhage seen in a previously reported case of a patient with lysozyme amyloidosis. To characterize the manifestations of this disorder, we performed an exhaustive literature review.Although hereditary amyloidosis is thought to be a rare disease, it is probably not as rare as we think and may well be underdiagnosed. Moreover, some cases of lysozyme amyloidosis are probably confused with acquired monoclonal immunoglobulin light-chain (AL) amyloidosis, formerly known as primary amyloidosis, which is the most frequent type of amyloidosis. Because treatment for each type of amyloidosis is different, and because therapy directed at 1 type may worsen symptoms of the other types, it is important to determine precisely the nature of the amyloid protein. Thus, hereditary lysozyme amyloidosis should be considered in all patients with systemic amyloidosis, particularly in patients who present with renal, gastrointestinal, or bleeding complications without evidence of AL or AA (secondary) amyloidoses.

Topics: Adult; Aged; Amyloidosis; Female; Gastrointestinal Diseases; Hemorrhage; Humans; Kidney Diseases; Lymph Nodes; Male; Middle Aged; Muramidase; Rupture

Topics: Amyloidosis; Apolipoproteins A; Cardiomyopathies; Dialysis; Fibrinogen; Humans; Kidney Diseases; Liver Diseases; Muramidase; Organ Transplantation; Prealbumin

Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.

Topics: Alpha-Globulins; beta 2-Microglobulin; Child, Preschool; Glomerular Filtration Rate; Humans; Immunoenzyme Techniques; Kidney; Kidney Diseases; Muramidase; Proteinuria; Reference Values; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma; Serum Globulins; Specimen Handling

Topics: Acetylglucosaminidase; Aminopeptidases; CD13 Antigens; Environmental Exposure; Hexosaminidases; Humans; Kidney; Kidney Diseases; Muramidase; Time Factors

The adverse and beneficial effects of metals have occupied a great concern in many branches of biology for centuries, but their biochemical roles have been studied systematically only in the last four decades. Almost all the metals, especially those of high toxicity, bind readily to mercapto groups, and these are frequently important in enzyme systems. Furthermore, a large number of in vitro and in vivo studies have shown that toxic metals can replace essential metals in many of their metalloenzymes, with resultant changes in activity. Metals also bind to protein, phospholipid and nucleic acid, and have been shown to effect a change in the conformation of enzymes required for normal function, or to uncouple oxidative phosphorylation. This review, of necessity brief, will focus on the biochemical and enzymatic effects of metals, emphasizing meanings available to occupational medicine. The present knowledge on enzymatic toxicology of metals can provide for access to three main problems. These include an exposure evaluation, a health injury evaluation and a pathogenic understanding of workers exposed to metals. In this article, these problems are discussed in general, and the recent developments made in the enzymatic toxicology of cadmium and lead are presented with pertinent literatures.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Cadmium; Cadmium Poisoning; Environmental Exposure; Humans; Kidney Diseases; Lead Poisoning; Metals; Muramidase; Occupational Diseases; Porphobilinogen Synthase; Rabbits; Rats

Topics: Adult; Animals; Bence Jones Protein; Blood Urea Nitrogen; Calcium; Carcinoma; Electrolytes; Fanconi Syndrome; Humans; Kidney; Kidney Diseases; Leukemia; Lymphoma; Multiple Myeloma; Muramidase; Neoplasms; Nephrotic Syndrome; Phosphorus; Potassium; Proteinuria; Sodium

Topics: Acetylglucosaminidase; Acute Disease; Alanine; Alkaline Phosphatase; Chronic Disease; gamma-Glutamyltransferase; Glucosidases; Glucuronidase; Graft Rejection; Humans; Kidney Diseases; Kidney Transplantation; L-Lactate Dehydrogenase; Leucine; Muramidase; Peptide Hydrolases; Postoperative Care; Transplantation, Homologous

Topics: Amyloidosis; Blood Vessels; Diabetes Insipidus; Humans; Hypercalcemia; Hyponatremia; Kidney; Kidney Diseases; Lactates; Leukemia; Lymphoma; Muramidase; Nephrotic Syndrome; Uric Acid; Urinary Tract

Topics: Age Factors; Body Surface Area; Child; Child, Preschool; Creatinine; Edetic Acid; Evaluation Studies as Topic; Female; Glomerular Filtration Rate; Humans; Infant; Infant, Newborn; Kidney Concentrating Ability; Kidney Diseases; Kidney Function Tests; Kidney Tubules, Distal; Kidney Tubules, Proximal; Male; Mathematics; Muramidase; Osmolar Concentration; Potassium; Proteinuria; Serum Albumin; Sodium

Topics: Amyloidosis; Blood Protein Disorders; Bone Neoplasms; gamma-Globulins; Humans; Karyotyping; Kidney Diseases; Kinetics; Leukemia; Leukemia, Lymphoid; Leukemia, Plasma Cell; Lung Neoplasms; Lymph Nodes; Lymphoma; Microscopy, Electron; Multiple Myeloma; Muramidase; Plasmacytoma

Topics: Aminopeptidases; Amylases; Anaphylaxis; Animals; Catalase; Clinical Laboratory Techniques; Deoxyribonucleases; Diuresis; Enzyme Activation; Enzyme Inhibitors; Enzymes; Esterases; Fibrinolytic Agents; Glycoside Hydrolases; Humans; Kallikreins; Kidney Diseases; L-Lactate Dehydrogenase; Muramidase; Myocardial Infarction; Pepsinogens; Phosphoric Monoester Hydrolases; Proteinuria; Rats; Ribonucleases; Sulfatases; Transaminases; Water-Electrolyte Balance

Topics: Animals; Blood Cells; Dogs; Graft Rejection; Humans; Iodine Isotopes; Kidney Diseases; Kidney Transplantation; Leukemia; Muramidase; Rats

Topics: Acute Kidney Injury; Animals; Body Fluids; Cell Wall; Clinical Enzyme Tests; Humans; Hydrolysis; Immunodiffusion; Kidney Diseases; Kidney Tubules; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Micrococcus; Molecular Weight; Muramidase; Rats; Spectrophotometry

Topics: Alanine Transaminase; Aldehyde-Lyases; Alkaline Phosphatase; Aminopeptidases; Amylases; Aspartate Aminotransferases; Blood Proteins; Carbonic Anhydrases; Clinical Enzyme Tests; Enzymes; Erythrocytes; Glucosephosphate Dehydrogenase; Glucuronidase; Glutamate Dehydrogenase; Humans; Hydroxybutyrate Dehydrogenase; Isocitrate Dehydrogenase; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Leucine; Leukocytes; Muramidase; Pyruvates

Thirty-six patients with preoperative renal dysfunction were studied to evaluate the effects of dopamine (D) and dopamine-nitroprusside (DN) on renal function during cardiopulmonary bypass (CPB). No differences from the control group (C) were found in creatinine clearance, fractional sodium excretion, osmolarity and free-water clearance. Sodium output/intake ratio during CPB was higher in group D than in groups C and DN (P less than 0.05); water output/intake ratio was higher in group D than in group C (P less than 0.05). Urine lysozime levels and alpha-glycosidase/creatinine ratios increased similarly in the three groups, suggesting ischemic tubular cell damage. No patients showed acute postoperative renal failure or a worsening of their renal dysfunction. The data suggest an increased water and sodium excretion during CPB with a dopamine infusion, possibly resulting from a renal vasodilator effect that was abolished by simultaneous nitroprusside administration.

Topics: Aged; Body Water; Cardiopulmonary Bypass; Creatinine; Diuresis; Dopamine; Drug Synergism; Drug Therapy, Combination; Glomerular Filtration Rate; Glycoside Hydrolases; Heart Diseases; Humans; Infusions, Intravenous; Kidney Diseases; Kidney Tubules; Middle Aged; Muramidase; Nitroprusside; Osmolar Concentration; Prospective Studies; Sodium

To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and gamma-glutamyl transferase (gamma-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of gamma-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone.

Topics: Adolescent; Adult; Aged; Bicarbonates; Fasting; Female; gamma-Glutamyltransferase; Glycosuria; Humans; Hydrogen-Ion Concentration; Insulin; Kidney Calculi; Kidney Diseases; Kidney Tubules; Magnesium; Male; Middle Aged; Muramidase; Phosphates; Potassium

An attempt is made in this study to provide an answer to the question whether glomerular diseases are accompanied by tubular disorders. The urinary lysozyme activity was determined by means of a turbidimetric assay method in 10 healthy children as controls, 10 patients with glomerulonephritis, 8 patients with Alport's syndrome (hereditary glomerulonephritis with deafness) and 12 children with idiopathic nephrotic syndrome. In most of the cases a significant increase in urinary lysozyme excretion, indicative of tubular damage, was found and this finding correlates well with the tubular morphology of the patients.

Topics: Child; Child, Preschool; Clinical Trials as Topic; Glomerulonephritis; Humans; Infant; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Muramidase; Nephritis, Hereditary; Nephrotic Syndrome

Lysozyme-derived (ALys) amyloidosis is a rare type of hereditary amyloidosis. Nine amyloidogenic variants and ∼30 affected families have been described worldwide. The most common manifestations are renal dysfunction, gastrointestinal tract symptoms, and sicca syndrome. We report on the clinical course of ten patients from six families representing one of the largest cohorts published so far. Seven patients carried the W64R variant showing the whole spectrum of ALys-associated symptoms. Two patients-a mother-son pair-carried a novel lysozyme variant, which was associated with nephropathy and peripheral polyneuropathy. In accordance with previous findings, the phenotype resembled within these families but did not correlate with the genotype. To gain insights into the effect of the variants at the molecular level, we analysed the structure of lysozyme and performed comparative computational predictions on aggregation propensity and conformational stability. Our study supports that decreased conformational stability is a key factor for lysozyme variants to be prone to aggregation. In summary, ALys amyloidosis is a very rare, but still heterogeneous disease that can manifest at an early age. Our newly identified lysozyme variant is associated with nephropathy and peripheral polyneuropathy. Further research is needed to understand its pathogenesis and to enable the development of new treatments.

Topics: Amyloidosis; Amyloidosis, Familial; Gastrointestinal Diseases; Humans; Kidney Diseases; Muramidase; Polyneuropathies

Topics: Aged; Biopsy; Female; Humans; Kidney Diseases; Kidney Tubules; Leukemia, Myelomonocytic, Chronic; Lysosomes; Microscopy, Electron; Muramidase

The anticancer drug imatinib is an inhibitor of the platelet-derived growth factor receptor (PDGFR) kinases, which are involved in the pathogenesis of fibrotic diseases. In the current study we investigated the delivery of imatinib to the proximal tubular cells of the kidneys and evaluated the potential antifibrotic effects of imatinib in tubulointerstitial fibrosis. Coupling of imatinib to the low molecular weight protein lysozyme via the platinum (II)-based linker ULS yielded a 0.8:1 drug-carrier conjugate that rapidly accumulated in the proximal tubular cells upon intravenous and intraperitoneal administration. The bioavailability of intraperitoneally administered imatinib-ULS-lysozyme was 100%. Renal imatinib levels persisted for up to 3 days after a single injection of imatinib-ULS-lysozyme. Compared with an equal dose imatinib mesylate, imatinib-ULS-lysozyme resulted in a 30- and 15-fold higher renal exposure of imatinib, for intravenous and intraperitoneal administration respectively. Imatinib-ULS-lysozyme could not be detected in the heart, which is the organ at risk for side-effects of prolonged treatment with imatinib. The efficacy of imatinib-ULS-lysozyme in the treatment of tubulointerstitial fibrosis was evaluated in the unilateral ureteral obstruction (UUO) model in mice. Three days UUO resulted in all signs of early fibrosis, i.e. an increased deposition of matrix and production of profibrotic factors. Although a moderately increased activity of PDGFR-β was observed, the profibrotic phenotype could not be inhibited with imatinib mesylate or with imatinib-ULS-lysozyme. Further evaluation of imatinib mesylate and imatinib-ULS-lysozyme is therefore warranted in an animal model of renal disease in which the activation of PDGFR-β is more pronounced.

Topics: Animals; Benzamides; Cell Line; Cell Survival; Drug Delivery Systems; Humans; Imatinib Mesylate; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Male; Mice; Mice, Inbred C57BL; Muramidase; Myocardium; Piperazines; Protein Kinase Inhibitors; Pyrimidines

Activated proximal tubular cells play an important role in renal fibrosis. We investigated whether sunitinib and a kidney-targeted conjugate of sunitinib were capable of attenuating fibrogenic events in tubulointerstitial fibrosis.. A kidney-targeted conjugate was prepared by linkage of a sunitinib analog (named 17864) via a platinum-based linker to the kidney-specific carrier lysozyme. Pharmacological activity of 17864-lysozyme was evaluated in human kidney proximal tubular cells (HK-2); the capability of the kidney-directed conjugate to accumulate in the kidneys was studied in mice. Potential antifibrotic effects of a single-dose treatment were evaluated in the unilateral ureteral obstruction (UUO) model in mice.. The 17864-lysozyme conjugate and its metabolites strongly inhibited tyrosine kinase activity. Upon intravenous injection, 17864-lysozyme rapidly accumulated in the kidneys and provided sustained renal drug levels for up to 3 days after a single dose. Renal drug level area under the curve was increased 28-fold versus an equimolar dose of sunitinib malate. Daily treatment of UUO mice with a high dose of sunitinib malate (50 mg/kg) resulted in antifibrotic responses, but also induced drug-related toxicity. A single dose of 17864-lysozyme (equivalent to 1.8 mg/kg sunitinib) was safe but showed no antifibrotic effects.. Multikinase inhibitors like sunitinib can be of benefit in the treatment of fibrotic diseases, provided that their safety can be improved by strategies as presented in this paper, and sustained renal levels can be achieved.

Topics: Animals; Area Under Curve; Cell Line; Cell Survival; Drug Carriers; Drug Delivery Systems; Fibrosis; Humans; Immunohistochemistry; Indoles; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Male; Mice; Mice, Inbred C57BL; Muramidase; Organoplatinum Compounds; Protein-Tyrosine Kinases; Pyrroles; Receptor, Platelet-Derived Growth Factor beta; Sunitinib

Topics: Acute Kidney Injury; Aged; Comorbidity; Diagnosis, Differential; Fanconi Syndrome; Glycosuria; Humans; Kidney Diseases; Kidney Tubules, Proximal; Male; Muramidase; Renal Insufficiency; Sarcoidosis

A rapid, low cost and selective chemiluminescence method coupled with magnetic molecularly imprinted polymers extraction was developed to detect lysozyme in human urine samples. Compared with traditional solid-phase extraction, this method could achieve selective extraction for the lysozyme, avoid the time consuming elution from a column or centrifugation steps, and then showed great potential in the high-throughput screening of clinical samples. The parameters affecting the performance of extraction and chemiluminescence were investigated. Under optimal conditions, the whole analytical procedure was completed within 12 min and spiked recovery ranged from 90.1% to 103.7% (R.S.D.≤6.7%). The limit of quantitation was 5 ng mL(-1). Furthermore, the results obtained by the proposed method were linearly correlated to those by commercial lysozyme detection kit (r=0.9595). Finally, the validated method was used to measure the urinary lysozyme of renal disease patients and healthy controls. The results confirmed the reliability and practicality of the protocol and revealed a good perspective of this method for biological sample analysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Luminescent Measurements; Magnetics; Male; Middle Aged; Molecular Imprinting; Muramidase; Polymers; Reproducibility of Results; Sodium Chloride; Time Factors; Urinalysis; Young Adult

We have synthesized a renal-specific drug carrier, 14-succinyl triptolide-lysozyme (TPS-LZM) conjugate for targeted delivery of TP to the PTECs. TPS-LZM could be taken up by HK-2 cells, free TP would be degraded and released, mainly from basolateral side of the cells. Compared with TP, the overall targeting efficiency (TE) of TPS-LZM was significantly enhanced from 11.74% to 95.54% and its MRT was moderately prolonged from 3.08h to 4.10h. At very low concentration, TPS-LZM could significantly reverse the disease progression in renal ischemia-reperfusion (I/R) injury animal models, while the mixture of free TP and LZM was ineffective. Further, TPS-LZM conjugate presented much lower hepatotoxicity (0.78 folds lower than TP) and no adverse effect on the immune (1.13 folds higher than TP) and genital system. Thus, TPS-LZM represents a very effective drug candidate for specific treatment of immunological renal diseases with low adverse side effect.

Topics: Animals; Diterpenes; Drug Carriers; Epithelial Cells; Epoxy Compounds; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Male; Molecular Structure; Muramidase; Phenanthrenes; Rats; Rats, Wistar; Reperfusion Injury; Succinates; Tissue Distribution

Activation of tubular epithelial cells by transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally accumulating conjugate of a TGF-beta type-I receptor kinase inhibitor (TKI) and evaluated its efficacy in vitro and in vivo.. TKI was conjugated to the protein Lysozyme (LZM) via a platinum-based linker. TKI-LZM was evaluated in human tubular cells (HK-2) for its anti-fibrotic activity. Plasma, kidney and urine drug levels after a single intravenous dose of TKI-LZM in rats were determined by HPLC or immunodetection. Anti-fibrotic effects of TKI-LZM were examined in the unilateral ureteral obstruction (UUO) model.. TKI-LZM conjugate was successfully synthesized at an 1:1 drug/carrier ratio, and inhibited TGF-beta1-induced procollagen-1alpha1 gene expression in HK-2 cells. In vivo, TKI-LZM accumulated rapidly in tubular cells and provided a local depot for 3 days. Interestingly, a single dose of TKI-LZM inhibited the activation of tubular cells and fibroblasts in UUO rats and reduced renal inflammation. In contrast, free TKI at an equimolar (low) dosage exhibited little effects.. Inhibition of TGF-beta signaling by local drug delivery is a promising antifibrotic strategy, and demonstrated the important role of tubular activation in renal fibrosis.

Topics: Animals; Cell Line; Collagen Type I; Collagen Type I, alpha 1 Chain; Disease Models, Animal; Drug Carriers; Epithelial Cells; Fibroblasts; Fibrosis; Humans; Injections, Intravenous; Kidney Diseases; Kidney Tubules, Proximal; Male; Muramidase; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pyrazoles; Rats; Rats, Wistar; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Recombinant Proteins; Transforming Growth Factor beta1; Ureteral Obstruction

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucose Oxidase; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Kidney Diseases; Lactoperoxidase; Male; Melphalan; Middle Aged; Models, Theoretical; Multiple Myeloma; Muramidase; Myeloablative Agonists; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

The potential antiparasitic and immunomodulatory effect of three treatments against myxosporean parasites on the innate immune system of sharpsnout sea bream (Diplodus puntazzo) was investigated. Fish naturally infected with Myxobolus sp. (Bivalvulida/Platysporina), a histozoic parasite mainly affecting the renal interstitial tissue, were treated by oral administration of a combination of salinomycin with amprolium, Origanum essential oil or fumagillin in a small-scale field trial. Various leucocyte functions influenced by myxosporean infection were examined in order to determine treatment effects on leucocyte immunocompetence of treated fish. One month post treatment all drugs caused a significant decrease in prevalence and intensity of infection in comparison to untreated, infected fish. The effect was most prominent in salinomycin with amprolium treated fish, which 1-month post treatment contained either no cysts at all or a few spores free in melanomacrophage centres revealing almost total elimination of the parasite and the antiparasitic action of the treatment. There was no histopathological evidence of drug toxicity. Antiparasitic action was accompanied by a significant enhancement of phagocytic activity demonstrated by ingestion of large numbers of latex beads and the secretion of high levels of reactive nitrogen intermediates by phagocytes in vitro. Complete restoration of the diminished mitogenic responses and serum lysozyme secretion was also detected in salinomycin with amprolium-treated fish compared to untreated, infected fish. These data suggest that salilomycin with amprolium may be a promising treatment for myxosporean infections in intensively cultured warm-water fish, exhibiting action partially via the enhancement of host, innate immune functions and leading to parasite elimination.

Topics: Amprolium; Animals; Antiprotozoal Agents; Cell Proliferation; Cyclohexanes; Eukaryota; Fatty Acids, Unsaturated; Fish Diseases; Histocytochemistry; Kidney Diseases; Leukocytes; Mediterranean Sea; Muramidase; Oils, Volatile; Phagocytosis; Protozoan Infections, Animal; Pyrans; Reactive Nitrogen Species; Sea Bream; Sesquiterpenes

High-sodium intake blunts the renoprotective efficacy of angiotensin-converting enzyme (ACE) inhibitors. We investigated whether targeting the drug to the kidneys may attenuate the inferior response to ACE inhibitor (ACE-I) under high-sodium conditions. The ACE-I, captopril, was coupled to the low molecular weight protein (LMWP) lysozyme, yielding captopril-lysozyme conjugates that accumulate specifically in the proximal tubular cells of the kidneys. We compared the antiproteinuric efficacy of captopril to that of the captopril-lysozyme conjugate in adriamycin-induced proteinuric rats fed with a high-sodium diet.. Rats with adriamycin (single injection 2 mg/kg)- induced proteinuria were put on a high-sodium diet (HS; 3% NaCl). When stable proteinuria developed at 5.5 weeks, animals were assigned to the following subcutaneous treatments: (1) vehicle (n=7); (2) lysozyme (equivalent to the amount in conjugate) (n=7); (3) captopril (5 mg/kg/24 hours) (n=8); (4) captopril-lysozyme conjugate (captopril content equivalent to 1mg captopril/kg/24 hours) (n=7). Blood pressure and proteinuria were monitored. After 10 days of treatment the rats were sacrificed and kidneys and plasma were removed.. Results are given as mean + S.E.M. After injection with adriamycin at t=0, stable proteinuria developed, amounting to 547+79 mg/24 hours at week 5.5. Subsequently, after seven and nine days of treatment, no reduction of proteinuria was observed in the captopril-treated group. In contrast, a significant reduction in proteinuria, amounting to 35+4% (day seven) and 25+2% (day nine), was observed in the captopril-lysozyme conjugate group (p<0.05 compared with the captopril group). In contrast, blood pressure was reduced in the captopril-treated group by 13.9+2.9 mmHg, while in the captopril-lysozyme treated group, an increase of 7.9+3.3 mmHg was found. Renal ACE activity was lowered by 30% in the captopril, as well as in the captopril-lysozyme conjugate treated group, compared with control. Furthermore, the ratio of kidney: plasma levels of captopril almost doubled as a consequence of coupling to lysozyme.. In proteinuric rats fed with a high-sodium diet, captopril induced a reduction in blood pressure without an effect on proteinuria. In contrast, renal targeting of a five times lower dose of the ACE-I with the captopril-lysozyme conjugate reduced proteinuria without reducing blood pressure. Therefore, renal targeting of ACE-I may be a promising strategy to optimise the therapeutic response of ACE-I.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Dose-Response Relationship, Drug; Doxorubicin; Drug Delivery Systems; Kidney; Kidney Diseases; Male; Muramidase; Peptidyl-Dipeptidase A; Proteinuria; Rats; Rats, Wistar; Sodium, Dietary

Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in three patients in one Italian Canadian family.. The proband was a 52-year-old woman who developed renal failure at the age of 42 years. Renal biopsy demonstrated replacement of glomeruli by amyloid. Her younger sister and her younger daughter who underwent renal transplantation also had renal amyloidosis. The proband's older daughter and her niece were in good health. To elucidate pathogenesis of this hereditary renal amyloidosis, DNA analyses of the lysozyme gene, including single strand confirmation polymorphism, direct DNA sequence, and restriction fragment length polymorphism analyses, were performed.. DNA analyses of the lysozyme gene revealed a T to A transversion at the first position of codon 57 of the lysozyme gene in the proband, her sister, and her affected and unaffected daughters, indicating a replacement of Phe by Ile at residue 57. In addition, DNA sequencing demonstrated a C to A transversion at the second position of codon 70, denoting a replacement of Thr by Asn at residue 70, in the proband's sister and her niece. Thus, the proband's sister is compound heterozygous for the Phe57Ile and Thr70Asn alleles.. Distinctive clinical features in patients of this family are nephropathy due to renal amyloidosis. Our results indicate that the novel lysozyme variant Phe57Ile is associated with renal amyloidosis in this family. From our results, a clear relation between the Thr70Asn polymorphism and renal amyloidosis could not be demonstrated.

Topics: Amyloidosis; Family Health; Female; Humans; Kidney Diseases; Middle Aged; Muramidase; Pedigree; Point Mutation; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; White People

The number of proteins with mutations resulting in amyloidosis has continued to increase. Five proteins--transthyretin, fibrinogen alpha-A chain, apolipoprotein AI, lysozyme, apolipoprotein AII, cystatin C and gelsolin--can be associated with hereditary amyloidosis involving the kidney.. A French family with a history of autosomal dominant hereditary amyloidosis with early sicca syndrome and nephropathy leading to renal failure after the fifth to the seventh decade was studied. Several tissue specimens obtained from the proband and his relatives were examined. Immunohistochemistry was performed on paraffin embedded sections using the indirect immunoperoxidase technique. We searched for mutations in the five exons and flanking introns of the lysozyme gene.. Amyloid deposits from the bowel, labial salivary gland and kidney were intensively stained by anti-lysozyme antibody. Sequence analysis of lysozyme exon 2 from the affected individuals revealed a nucleotide substitution predicting a substitution of the amino acid at position 64 in the mature protein from tryptophane, an aromatic residue to the cationic residue arginine (W64R).. We report a novel mutation (W64R) of the lysozyme that is associated with hereditary amyloidosis and prominent nephropathy. Since the treatment of hereditary amyloidosis greatly varies with the nature of the amyloid protein, thorough characterization of the latter is crucial for the management of the disease.

Topics: Aged; Amino Acid Substitution; Amyloid; Amyloidosis; Base Sequence; France; Genetic Variation; Humans; Immunohistochemistry; Kidney Diseases; Male; Muramidase; Pedigree; Tissue Distribution

Targeting of anti-tumor drugs to the urinary bladder for the treatment of bladder carcinoma may be useful, since these agents generally have a low degree of urinary excretion and are highly toxic elsewhere in the body. The anti-tumor drug doxorubicin was coupled to the low-molecular weight protein lysozyme via the acid-sensitive cis-aconityl linker. All free amino groups of the lysozyme were used for drug attachment to achieve intact excretion of the doxorubicin-aconityl-lysozyme conjugate into the bladder. In the bladder, the cytotoxic drug should be regenerated through acidification of the urine. First, the doxorubicin-aconityl-lysozyme conjugate was tested in rats for its target specificity and general toxicity. Wistar rats were injected intravenously with 2 mg/kg free doxorubicin or 10 mg/kg lysozyme-conjugated doxorubicin. Total urinary excretion of doxorubicin was about 10 times higher if the drug was coupled to lysozyme (39 +/- 3% versus 4.4 +/- 0.4%). Free doxorubicin had no detectable toxic effects on heart, liver and lung but caused severe renal damage (proteinuria, N-acetylglucosaminidase excretion and glomerulosclerosis). None of the rats injected with doxorubicin-lysozyme conjugate showed such renal toxicity. Second, we tested whether doxorubicin could be released from the conjugate in the bladder through acidification of the urine and if the released doxorubicin could still exert a cytotoxic effect. Doxorubicin-aconityl-lysozyme (2 mg/kg conjugated doxorubicin, i.v.) was administered in rats with acidified urine (pH 6.1 +/- 0.1) and in rats with a high urinary pH (8.2 +/- 0.4). Ten times more doxorubicin was released from the conjugate in the group with acidified urine (15 +/- 7% versus 1.7 +/- 0.1%). In agreement with this, cytotoxicity was also higher in the low pH group (IC50 of 255 +/- 47 nM versus 684 +/- 84 nM doxorubicin). In conclusion, a specific delivery of doxorubicin to the urinary bladder combined with a reduced toxicity of doxorubicin in the kidneys can be achieved by coupling this anti-tumor drug to the low-molecular weight protein lysozyme via an acid-labile linker. A release of cytotoxic doxorubicin in the urinary bladder can be achieved by acidification of the urine. This technology, after further optimization, may provide an interesting tool for the treatment of bladder carcinoma.

Topics: Aconitine; Animals; Antibiotics, Antineoplastic; Doxorubicin; Drug Delivery Systems; Kidney Diseases; Male; Muramidase; Rats; Rats, Wistar; Urinary Bladder

Two kindreds with hereditary systemic amyloidosis caused by the first two mutations to be described in the human lysozyme gene were discovered recently and study of the variant lysozyme has been powerfully informative about mechanisms of amyloid fibrillogenesis. However, the clinical manifestations in these families, additional members of which have lately been identified, have not previously been reported in detail.. The proband presented with proteinuria aged 50 and a family history of amyloidosis, and underwent renal biopsy, whole-body serum amyloid P component (SAP) scintigraphy, and sequencing of the lysozyme gene. Her family history and the phenotype of hereditary lysozyme amyloidosis were thoroughly documented and compared with the presentation and natural history of all other known patients with this condition.. The proband belonged to an extended English family other members of which were known to have hereditary lysozyme amyloidosis. Those with amyloid in previous generations presented with renal involvement, frequently developed complications due to gastrointestinal amyloid, and died before age 60. All amyloid deposits were composed of lysozyme and complete concordance was established between amyloid and heterozygosity for a point mutation in the lysozyme gene, encoding the previously reported Asp67His substitution in the mature protein.. The phenotype, reported for the first time in this extended kindred, contrasts with that of an apparently unrelated family carrying the same mutation who presented with spontaneous hepatic haemorrhage and rupture, and with the manifestations in a family with the lysozyme Ile56Thr variant who presented with dermal petechiae before proceeding to fatal visceral amyloidosis. A remarkably wide spectrum of disease can be caused by the same amyloid fibril protein, although renal involvement predominates in all cases except those dying of hepatic rupture.

Topics: Amyloidosis; England; Female; Genetic Variation; Humans; Immunohistochemistry; Kidney; Kidney Diseases; Male; Middle Aged; Muramidase; Mutation; Pedigree; Radionuclide Imaging; Serum Amyloid P-Component

A renal-specific controlled release of an active drug may enable a reduction of the required dose and may provide a reduction of extra-renal toxicity. To achieve renal specific targeting of the NSAID naproxen, the low-molecular-weight protein (LMWP) lysozyme was employed as carrier since it is mainly taken up and catabolized in the proximal tubules of the kidney. A conjugate was synthesized with an average coupling degree of 2 mol naproxen per 1 mol lysozyme in which the drug was directly coupled to the protein via a peptide bond. First, we investigated whether naproxen conjugation affects the renal disposition of lysozyme. As native lysozyme, the conjugate was predominantly and rapidly (within 20 min) taken up by the kidney. The subsequent decrease in renal content reflecting the renal degradation of the conjugated lysozyme molecules appeared also to be similar to that of native lysozyme with a half life of four hours. Second, the effect of lysozyme conjugation on the body distribution of naproxen was studied. An important observation with regard to the aimed reduction in extra-renal side effects was that no detectable amounts of free naproxen were present in the plasma after administration of conjugate. Conjugation of naproxen to lysozyme resulted in a pronounced (70-fold) increase of naproxen accumulation in the kidney. In agreement with the protein disposition study, the conjugate was rapidly taken up by the kidney and subsequently degraded. In conclusion, renal selective targeting of the NSAID naproxen can be obtained by conjugation with the LMWP lysozyme. This concept of drug delivery to the kidney has the potential to improve drug efficacy and safety.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dinoprostone; Female; Iodine Radioisotopes; Kidney Diseases; Kidney Tubules, Proximal; Kinetics; Male; Muramidase; Naproxen; Rats; Rats, Wistar; Tissue Distribution

The presence of monocytes/macrophages (MPs) in renal glomeruli was investigated in 86 dogs with different types of glomerulopathies. The identification of MPs in tissue sections was based on cytological criteria and the immunohistochemical demonstration of lysozyme. The highest numbers of MPs in glomeruli were observed in focal and diffuse mesangial proliferative glomerulonephritis (MesPGN), diffuse endocapillary proliferative glomerulonephritis (DEPGN), and diffuse mesangiocapillary glomerulonephritis (DMCGN). In cases of minor glomerular abnormalities (MGA), focal and segmental hyalinosis and sclerosis (FGS), diffuse membranous glomerulonephritis (DMemGN), and diffuse sclerosing glomerulonephritis (DSGN) the presence of glomerular MPs was low. Particularly in MesPGN, the number of MPs was correlated with glomerular hypercellularity and, additionally in DMCGN, with the degree of proteinuria. The results of this study suggest that MPs may be involved in functional and morphological alterations in different types of canine glomerulopathies.

Topics: Animals; Cell Count; Dog Diseases; Dogs; Female; Immunohistochemistry; Kidney Diseases; Kidney Glomerulus; Macrophages; Male; Monocytes; Muramidase

Some urinary enzymes (NAG, AAP, lysozyme) considered to be sufficiently sensitive and reliable markers of renal damage were controlled in 20 patients with cirrhosis of the liver and in 20 healthy control subjects. The results, stated as mean +/- SD, showed a statistically very significant increase (p < 0.01) of NAG and lysozyme in cirrhotics. Furthermore, this increase could be at least in part related with the seriousness of clinical condition. On the basis of these results, we think the urinary dosage of NAG and lysozyme is, in the subjects with liver cirrhosis, a bloodless method to show an early renal damage.

Topics: Acetylglucosaminidase; Adult; Aged; Aged, 80 and over; Aminopeptidases; Ascites; Butyrylcholinesterase; CD13 Antigens; Clinical Enzyme Tests; Diabetes Mellitus; Female; Humans; Kidney Diseases; Liver Cirrhosis; Male; Middle Aged; Muramidase; Time Factors

We tested the diagnostic sensitivity of various urinary analytes for detecting cadmium-induced nephropathy at an early stage. We investigated 73 healthy persons (control group 1) and individuals exposed to cadmium, either environmentally (n = 36, risk group 2) or occupationally (n = 62, exposed group 3). All data were related to limits of the central 95% reference intervals of the control group. The serum creatinine and ribonuclease values, indicators of the glomerular filtration rate, were not different in the three groups. In the exposed persons (group 3), proximal tubular indicators (low-M(r) proteins lysozyme, ribonuclease, retinol-binding protein, and alpha 1-microglobulin) were more often increased than the glomerular indices (higher-M(r) proteins transferrin, IgG, and albumin). Both the low-M(r) proteins and tubular enzymes were differently altered in their excretion rates. Alanine aminopeptidase, alkaline phosphatase, and N-acetyl-beta-D-glucosaminidase increased even in the risk group 2. alpha 1-Microglobulin was increased in the exposed persons whose cadmium excretion was < 5 mumol/mol creatinine. The combined determination of alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase exceeded the corresponding upper reference limits in 30% of group 2 and 39% of group 3. We recommend screening for these two analytes to detect cadmium-induced renal dysfunction at an early stage.

Topics: Acetylglucosaminidase; Adult; Aged; Alkaline Phosphatase; Alpha-Globulins; Aminopeptidases; Cadmium Poisoning; CD13 Antigens; Creatinine; Environmental Exposure; Female; Humans; Kidney Diseases; Male; Middle Aged; Muramidase; Occupational Diseases; Proteinuria; Reference Values; Retinol-Binding Proteins; Ribonucleases

To identify possible hazards of combined exposure to chemicals with the same target organ, a 24-hr single dose experiment was carried out in which the renal toxicity of mercuric chloride, potassium dichromate, d-limonene and hexachloro-1:3-butadiene administered simultaneously was compared with the nephrotoxicity of the individual compounds, using a total of 11 groups each consisting of five 12-wk-old male Wistar rats. The dose levels used were based on the results of a range-finding study with the individual compounds in the same strain of rats kept under similar experimental conditions, and comprised the 'Minimum-Nephrotoxic-Effect Level' (MNEL) and the 'No-Nephrotoxic-Effect Level' (NNEL) of each of the four compounds alone and in combination. A group of vehicle-treated rats served as controls. At the MNEL of the combination, antagonism of effects was encountered, seen for example as less severely increased activity of gamma-glutamyl transferase in the urine. Synergism of effects was also observed, for example increased severity of renal tubular necrosis, and more markedly increased activity of urinary lysozyme, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-glucosaminidase. More importantly, however, at the NNEL of the combination no signs of impaired renal function or renal damage were observed, suggesting absence of both dose additivity and potentiating interaction at the tested subeffective levels of the individual nephrotoxicants.

Topics: Acetylglucosaminidase; Alkaline Phosphatase; Animals; Butadienes; Cyclohexenes; Drug Interactions; gamma-Glutamyltransferase; Kidney; Kidney Diseases; Kidney Tubular Necrosis, Acute; L-Lactate Dehydrogenase; Limonene; Male; Mercuric Chloride; Muramidase; Potassium Dichromate; Rats; Rats, Wistar; Terpenes

Renal function was assessed in 20 (11 female and 9 male, age 21-76 years, mean 53) renal patients with a creatinine clearance 25-145 ml/min, mean 95, to evaluate the effects of iohexol, a non-ionic low-osmolar contrast medium. Intravenous urography was performed in 16 patients and computed body tomography in 4, using a dose of iohexol ranged between 0.6-3.3 (mean 1.17) g/kg b.w. Different parameters of renal function were determined in the week preceding and 1, 3 and 5 days after the administration of iohexol. The principal renal effect of iohexol was an increase of urinary alanine aminopeptidase, gamma-glutamyltransferase, lactate dehydrogenase, alkaline phosphatase and N-acetyl-beta-D-glucosaminidase. The maximum increase of enzymuria was observed on day 1 after the administration of iohexol. In most cases enzymes returned to base-line values within 3 days. No relevant variation of renal hemodynamics (glomerular filtration rate and effective renal plasma flow) was observed after iohexol. In conclusion, iohexol can increase of urinary enzymes, but the effect is rapidly reversible and is not accompanied by a clinically significant impairment of renal hemodynamics.

Topics: Acetylglucosaminidase; Adult; Aged; Alkaline Phosphatase; Aminopeptidases; CD13 Antigens; Female; gamma-Glutamyltransferase; Glomerular Filtration Rate; Hemodynamics; Humans; Iohexol; Kidney Diseases; L-Lactate Dehydrogenase; Male; Middle Aged; Muramidase; Osmolar Concentration; Radiography; Renal Circulation

Few data are yet available comparing the histological patterns of cadmium nephropathy with the values of urinary enzyme excretions, useful indexes of renal tubular damage. 40 Wistar rats, divided into four groups (A-D), were intoxicated with cadmium chloride (CdCl2) at 16 ppm in drinking water for 4, 16, 40 and 60 weeks, respectively. At the end of each period all the intoxicated rats and 5 controls were assessed for creatinine clearance, fractional excretion of gamma-glutamyltransferase (UfrGGT) and alpha-glucosidase (UfrAGL), indexes of anatomical tubular damage, and for fractional clearance of lysozyme (CfrLys), index of functional tubular damage. Thereafter, the rats were sacrificed and their kidneys examined with light and electron microscopy. Control rats and group A and B rats did not show any histological impairment. A widespread vesiculation of proximal tubular cells with mitochondrial and lysosomal alterations was found in the group C rats and was more evident in group D. The brush border never showed any damage in all groups in accordance with the finding of a normal excretion pattern of UfrGGT, an enzyme situated in this structure. The UfrAGL was increased only in group D rats (p less than 0.025), who showed the most severe anatomical damages. The CfrLys, an index of tubular function, was elevated in group C and D rats (p less than 0.02 and p less than 0.002, respectively). It was possible to detect the initial renal tubular damage.

Topics: alpha-Glucosidases; Animals; Cadmium; gamma-Glutamyltransferase; Kidney; Kidney Diseases; Microscopy, Electron; Muramidase; Rats; Rats, Inbred Strains

Nephritic functionality has been studies, making use of same nephritic enzymes dosage (NAG, AAP, alpha-glucosidase, lysozyme) in three groups of workers (varnishers, metallurgists, plastic manufacture employees) professionally exposed to nephritic damage, and in a control group made up of not professionally exposed to the same hazard subjects. The aim was to precociously detect possible nephritic damage, i.e. before classic nephritic functionality indexes were distorted. An increased enzymuria appeared in those subjects that were exposed to nephrotoxic hazard. Increased enzymuria have been found in only one subject of the control group. We deem it should be useful, to customarily measure out nephritic enzymes as trusted index of tabular damage, in hiring and pensionary control examinations.

Topics: Acetylglucosaminidase; Adult; alpha-Glucosidases; Aminopeptidases; CD13 Antigens; Clinical Enzyme Tests; Humans; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Muramidase; Occupational Diseases

The diagnostical relevance of the low-molecular proteins ribonuclease, beta 2-microglobulin and lysozyme in serum and urine to detect a reduced glomerular filtration rate was examined in 52 patients with chronic renal diseases. The radioisotope clearance using 99mTc-DTPA was the base reference; the reference values of the low-molecular proteins were estimated in a control group. Ribonuclease was increased above the upper borderline value, if the glomerular filtration rate was lower than 1.24 ml s-1. Creatinine, beta 2-microglobulin and lysozyme remain yet in part in the normal range. The estimation of the ribonuclease in serum is suitable to detect an impaired glomerular filtration rate if the creatinine value is still not increased. Thereby, the diagnostics in renal diseases may be improved in the creatinine-blind area.

Topics: Adult; beta 2-Microglobulin; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Function Tests; Male; Molecular Weight; Muramidase; Pyelonephritis; Ribonucleases

Topics: Colitis, Ulcerative; Humans; Kidney Diseases; Muramidase; Nephelometry and Turbidimetry; Radioimmunoassay

The diagnostic value of the low-molecular mass proteins ribonuclease, beta 2-microglobulin, and lysozyme in serum for the detection of reduced glomerular filtration rates was evaluated. The values of these proteins and of serum creatinine investigated in 52 patients suffering from chronic renal diseases were plotted against 99m-Tc-diethylenetriaminopentaacetate clearance as an indicator of glomerular filtration rate. Log-transformed data showed a good fit of linearity. Considering the 95% confidence limits of the regression equations, ribonuclease increased above the normal range when the glomerular filtration rate was lower than 1.24 ml/s whereas the other analytes partly remained within their normal limits. Out of those 18 patients with glomerular filtration rates lower than 1.24 ml/s, all patients showed elevated ribonuclease levels. beta 2-Microglobulin, creatinine, and lysozyme were increased in 17, 14, and 12 cases, respectively. Ribonuclease and beta 2-microglobulin showed similar results when other diagnostic criteria (specificity, efficiency and predictive values) were taken into account. We recommend ribonuclease determination in serum for the detection of reduced glomerular filtration rate in the normal range of creatinine. The test is diagnostically powerful, cheap and easy to perform.

Topics: Adult; beta 2-Microglobulin; Blood Proteins; Creatinine; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Muramidase; Ribonucleases

During the acute renal tubular dysfunction of Fanconi syndrome and type 2 renal tubular acidosis (FS/RTA2) induced by maleic acid in the unanesthetized dog, we observed: 30 minutes after the onset of FS/RTA2, the urinary excretion of lysosomal enzymes, N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc) and beta-galactosidase (beta-galac), increased simultaneously with the anticipated increase in renal clearance of lysozyme; the severities of all these hyperenzymurias increased rapidly, progressively, and in parallel, all reaching a peak some 60 to 80 minutes after their onset; thereafter, while the FS/RTA2 continued undiminished in severity, the severity of the hyperenzymurias decreased rapidly, greatly, progressively, and in parallel; and sodium phosphate loading strikingly attenuated the FS/RTA2 and the hyperenzymurias. Thus, the maleic acid-induced FS/RTA2 is attended by an acute reversible-complex derangement in the renal tubular processing of proteins that: affects not only lysozyme which is normally filtered, but also NAG and other lysosomal enzymes, which are not; and is to some extent functionally separable from that of FS/RTA2. The findings suggest that the derangements in renal processing of lysozyme and lysosomal enzymes are linked, and that a phosphate-dependent metabolic abnormality in the proximal tubule can participate in the pathogenesis of both these derangements and the FS/RTA2.

Topics: Acetylglucosaminidase; Acidosis, Renal Tubular; Animals; beta-Galactosidase; Dogs; Fanconi Syndrome; Female; Galactosidases; Glucuronidase; Hexosaminidases; Injections, Intravenous; Kidney Diseases; Kidney Function Tests; Maleates; Metabolic Clearance Rate; Muramidase; Phosphates

In 51 dogs with predominantly massive urinary protein loss, the daily loss was quantified and glomerular and tubulointerstitial lesions from renal biopsies were characterised and graded using histology, immune fluorescence and electron microscopy. The highest median daily urinary protein loss occurred in dogs with membranous glomerulonephritis (median 380 mg kg-1 d-1) and renal amyloidosis (median 257 mg kg-1 d-1). Although in nine febrile dogs the urinary protein loss was transient, both glomerular and tubular lesions were diagnosed in five and seven of these dogs, respectively. The pattern of urinary proteins was determined using sodium dodecyl-sulphate polyacrylamide gel electrophoresis. The albumin fractional clearance (FC) was raised in 46 dogs, whereas the FCS of the low molecular weight (MW) protein fraction (MW less than 66,000) and high molecular weight protein fraction (MW more than 66,000) were raised in 42 and 28 dogs, respectively. Both the high molecular weight protein FC and albumin FC significantly correlated to the grade of glomerular lesions, whereas the low molecular weight protein FC only moderately significantly correlated to the grade of tubular lesions. The selectivity index, calculated as (formula; see text) did not differentiate between the various forms of glomerulopathies. The urinary lysozyme concentration was significantly correlated to the grade of tubular lesions. It is concluded that although quantitative and qualitative measurements of urinary proteins can provide additional clinical information, they do not have a reliable predictive value and histopathological examination of renal tissue is still necessary for the final diagnosis.

Topics: Animals; Biopsy; Dog Diseases; Dogs; Electrophoresis, Polyacrylamide Gel; Female; Fluorescent Antibody Technique; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Male; Microscopy, Electron; Muramidase; Proteins; Proteinuria

Effect of latamoxef (LMOX) against tobramycin (TOB)-induced nephrotoxicity was studied in rats. Treatment with TOB (90 mg/kg/day, s.c.) alone resulted in marked increases in the activities of urinary enzymes such as lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase and lysozyme, urinary protein content and blood urea nitrogen, which peaked on the 7th or 10th day. The combination with LMOX (500, 1000 or 2000 mg/kg/day, s.c.) significantly suppressed increases in the parameters with TOB alone. The extent of this suppression roughly depended on the LMOX dosage. Although TOB alone caused pronounced histological changes such as extensive cortical proximal tubular cell necrosis, residual tubular basement membrane and cast formations in the renal cortex and medulla on the 7th day, these changes were apparently suppressed by combination with LMOX. In addition, intrarenal TOB concentrations in the rat given TOB alone were about 350, 500 and 1000 micrograms/g tissue wet weight at 3 hr, on day 3 and on day 5, respectively. On the other hand, there was a significant reduction (30-60%) in intrarenal TOB concentration by combination with LMOX. These results indicate that combination with LMOX obviously protects the rat kidney from TOB nephrotoxicity, and the protective effect may be partially due to suppression of intrarenal accumulation of TOB by LMOX.

Topics: Acetylglucosaminidase; Aminoglycosides; Animals; Anti-Bacterial Agents; Blood Urea Nitrogen; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Male; Moxalactam; Muramidase; Proteinuria; Rats; Rats, Inbred Strains; Tobramycin

A fluorescence polarization (FP) technique was applied to the assay of lysozyme activity in human urine. In this assay system, reaction between enzyme and fluorescein-labelled substrate produced a decrease in the fluorescein polarization (P) value. Enzyme activity and rate of decrease of P value exhibited a hyperbolic proportionality between 0.01 mg/L and 10.0 mg/L of lysozyme concentration. The method was compared with a turbidimetric method and the results were comparable with each other. Urinary lysozyme activity in patients with various renal diseases whose renal function had deteriorated was 1.04 +/- 2.55 mg/L (mean +/- S.D.), whereas that of normal controls was 0.13 +/- 0.14 mg/L.

Topics: Fluorescein-5-isothiocyanate; Fluoresceins; Fluorescence Polarization; Humans; Ions; Kidney Diseases; Muramidase; Nephelometry and Turbidimetry; Peptidoglycan; Thiocyanates

Topics: Acetylglucosaminidase; Adolescent; Adult; Aged; Aminopeptidases; CD13 Antigens; Child; Female; Glomerulonephritis; Hexosaminidases; Humans; Kidney Diseases; Male; Middle Aged; Muramidase; Nephritis, Interstitial; Nephrosclerosis; Pyelonephritis

Topics: Acetylglucosaminidase; Alkaline Phosphatase; alpha-Glucosidases; Aminopeptidases; beta-Galactosidase; beta-Glucosidase; CD13 Antigens; Clinical Enzyme Tests; gamma-Glutamyltransferase; Glucuronidase; Humans; Isoenzymes; Kidney Diseases; Kidney Neoplasms; L-Lactate Dehydrogenase; Muramidase; Syndrome

Topics: Adult; Albuminuria; Child; Creatinine; Glomerular Filtration Rate; Humans; Kidney Diseases; Muramidase; Proteinuria

Topics: Clinical Enzyme Tests; Humans; Kidney Diseases; Muramidase

I describe an improved turbidimetric assay for lysozyme in urine. This method is simple, reproducible, linear over a 100-fold concentration range, sensitive to concentrations as low as 10 micrograms/L, and only commercially available products are required. Evaluation of urinary lysozyme concentration with this assay demonstrated a within-run and between-run CV of 9.9% and 4.8%, respectively, for normal urine, minimal chemical interference, and a mean analytical recovery of 104.8%. There were differences in the rate of clearing and in the linearity of the assay with use of three commercial preparations of Micrococcus lysodeikticus, and significant differences in results when different lysozyme standards were used. Reference values were established by use of data on 169 healthy subjects, ages six months to 61 years. Clinical efficacy of the assay was demonstrated in children with renal disorders, especially those associated with chronic renal failure or tubular dysfunction.

Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Kidney Diseases; Kidney Failure, Chronic; Micrococcus; Middle Aged; Muramidase; Nephelometry and Turbidimetry; Reference Values; Statistics as Topic

Topics: alpha-Glucosidases; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Betamethasone; Biomarkers; Bleomycin; Cisplatin; Diuresis; Fluid Therapy; Humans; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Methotrexate; Mouth Neoplasms; Muramidase; Neoplasm Proteins; Predictive Value of Tests; Sensitivity and Specificity; Vincristine

Topics: alpha-Glucosidases; Antineoplastic Combined Chemotherapy Protocols; beta 2-Microglobulin; Biomarkers; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Lymphoma, Non-Hodgkin; Muramidase; Neoplasm Proteins; Predictive Value of Tests; Prednisone; Sensitivity and Specificity; Vincristine

In theory it can be accepted today that the analysis of urinary enzymes has a certain diagnostic value; this enables the diagnosis and observation of kidney damage to be improved without any more drastic measures. Thus it should be possible to recognize new aspects of kidney diseases which cannot be recognized using other, intensive methods. In future urologists and nephrologists should strive to investigate the following problems, relying on adequate documentation of the respective state of the urorenal system: --induction of functional and lesional changes using diagnostic and therapeutic means--evaluation of the effects of medicaments on urinary enzymes--the response of urinary enzymes to infections of the urorenal system--the correlation between the functioning of a transplant and the enzyme pattern in the urine--the search for enzyme markers in patients with cancers of the urogenital tract. The analysis of urinary enzymes is not to be recommended as a method of searching for kidney disease today. Diagnosis through urinary enzymes should not be used as a rule. Our aim for the future should be to use automated biochemical methods with the aid of computer analysis and programming for studies on urinary enzymes.

Topics: Alkaline Phosphatase; Enzymes; gamma-Glutamyltransferase; Glucuronidase; Graft Rejection; Humans; Kidney; Kidney Diseases; Kidney Neoplasms; Kidney Transplantation; L-Lactate Dehydrogenase; Muramidase

Early signs of aminoglycoside - induced renal tubular damage were detected in 26 patients given gentamicin and 23 given sisomicin. The urinary elimination of 3 low molecular weight proteins (LMWP) - beta 2 microglobulin, retinol binding protein and lysozyme (LZM), and the urinary activity of 2 enzymes - alanine aminopeptidase and N-acetyl-beta-glucosaminidase - was measured before, during and after treatment. In gentamicin - treated patients LMWP elimination increased, especially LZM which rose markedly during treatment and returned to normal values after its end. Enzyme activities also rose while gentamicin was being given. Sisomicin produced smaller changes. As neither the mean serum creatinine nor the mean urinary elimination of transferrin were increased, glomerular function was probably not affected. However, tubular damage was detected, as shown by the LMWP output (especially LZM) and increased enzyme activity. Urinary LMWP and enzyme measurements are presented as sensitive and reliable methods to monitor early aminoglycoside - induced tubular impairment. It is suggested that the different renal toxicities of gentamicin and sisomicin are related to differences in their accumulation in the renal cortex.

Topics: Acetylglucosaminidase; Aminopeptidases; CD13 Antigens; Female; Gentamicins; Humans; Kidney Diseases; Kidney Tubules; Male; Middle Aged; Muramidase; Proteinuria; Sisomicin; Time Factors

The presence of tubular involvement, as a marker for the detection of urinary tract infection (UTI) site, was examined in 19 patients with pyelonephritis and in 15 patients with cystitis or asymptomatic bacteriuria. The urinary excretion of four markers of tubular proteinuria, beta 2-microglobulin (beta 2M), lysozyme (LZ), lactic dehydrogenase isoenzyme V (LAD-5) and N-acetyl-beta D-glucosaminidase (NAG), was investigated. LAD-5 appeared particularly valuable for the early detection of upper UTI. However, the overall diagnostic accuracy appeared to be further strengthened using, besides LAD-5, one additional variable. A set of simple and noninvasive biochemical tests on urine samples can reliably help to identify the site of UTI.

Topics: Acetylglucosaminidase; Adult; beta 2-Microglobulin; Clinical Enzyme Tests; Humans; Isoenzymes; Kidney Diseases; Kidney Tubules; L-Lactate Dehydrogenase; Muramidase; Proteinuria; Urinary Tract Infections

Topics: Clinical Enzyme Tests; Enzymes; Humans; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Lysosomes; Models, Biological; Molecular Weight; Muramidase

The renal effect of the daily administration of gentamicin to male albino rats (20 mg/kg body weight) for 6 consecutive days on some biochemical systems of the kidney was examined. Urine volume and urinary protein levels were found to be progressively raised following gentamicin. Urinary alkaline phosphatase, acid phosphatase, muramidase and glutamate dehydrogenase (GDH) activities were found to be markedly elevated. Acid phosphatase and GDH activities in urine were raised 24 h and 48 h, respectively, from the onset of gentamicin administration. The sequence in which some regions of the renal cells were involved in gentamicin nephrotoxicity was determined and the probable mechanism of interaction of gentamicin antibiotic with the renal tubular cells is proposed.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Gentamicins; Glutamate Dehydrogenase; Kidney Diseases; Male; Muramidase; Rats; Time Factors

Topics: Abdomen; Esterases; Hepatomegaly; Humans; Kidney Diseases; Leukemia, Monocytic, Acute; Monocytes; Muramidase; Pain; Splenomegaly

Topics: beta 2-Microglobulin; Beta-Globulins; Humans; Kidney Diseases; Muramidase; Nephelometry and Turbidimetry; Retinol-Binding Proteins

In two patients who had malignant histiocytosis, renal involvement was present at an early stage of their diseases and consisted clinically of proteinuria and renal failure. The associated renal lesion was characterized by a diffuse and global endocapillary hypercellularity of the glomeruli imputable to atypical cells occluding the capillary loops. Immunoglobulins were absent from this lesion. The atypical cells were positively identified by lysozyme immunoperoxidase study as malignant histiocytes. It is suggested that renal biopsy complemented by marker study could play a role in the diagnosis of malignant histiocytosis.

Topics: Aged; Basement Membrane; Bone Marrow; Erythrocytes; Humans; Immunoenzyme Techniques; Kidney Diseases; Kidney Glomerulus; Lymphatic Diseases; Male; Middle Aged; Muramidase; Phagocytosis; Spleen

Topics: Animals; Blood Urea Nitrogen; Creatinine; Dogs; Furosemide; Gentamicins; Glucuronidase; Hexosaminidases; Kidney Diseases; Male; Muramidase; Netilmicin

Topics: Adult; Aged; Gentamicins; Humans; Kidney Diseases; Middle Aged; Muramidase

Topics: alpha-Glucosidases; beta 2-Microglobulin; Beta-Globulins; Diuresis; Humans; Kidney Diseases; Liver Cirrhosis; Muramidase

Lysozyme activity was determined in the serum, urine and leukocytes of 53 patients with immunocytoma and 24 patients with lymphoproliferative syndromes without associated monoclonal gammapathy. In patients with multiple myeloma the frequency of low serum lysozyme activity and high leukocyte lysozyme activity was higher. In the cases with renal failure, lysozyme activity was raised in serum and urine, and the 24-hour urinary lysozyme excretion was increased. In 7 patients with increased urinary lysozyme excretion no clinical or laboratory evidence of renal complications was found. Relative monocytosis in peripheral blood was observed in half of the cases of multiple myeloma, and in these patients also in about half of the cases the lysozyme activity was raised in the leukocytes and urine, and the 24-hour urinary lysozyme excretion was increased. In patients with Hodgkin's disease, lymphosarcoma and chronic lymphatic leukemia the frequency of low serum lysozyme activity was increased.

Topics: Adult; Aged; Humans; Kidney Diseases; Kidney Failure, Chronic; Leukocytes; Lymphoproliferative Disorders; Middle Aged; Multiple Myeloma; Muramidase; Waldenstrom Macroglobulinemia

Topics: Alanine; Aminopeptidases; Clinical Laboratory Techniques; Disease; Enzymes; Glucuronidase; Humans; Kidney Diseases; Muramidase; Proteinuria

The automated fluorimetric assay of N-acetyl-beta-D-glucosaminidase (NAG) has proved to be of value in the detection of rejection in transplant patients and in monitoring the course of renal disease. The urine can be diluted prior to assay, due to the sensitivity of the fluorimetric method and this reduces the effect of endogenous inhibitors. Time consuming dialysis or gel filtration steps are therefore unnecessary. Results are available to the physician within hours of the collection of the urine sample, since factoring the enzyme activity by the creatinine concentration avoids the necessity of collecting twenty-four hour or timed urine samples. Over one hundred samples can be assayed in a day using the automated procedure. The excretion of NAG in normal individuals varies with age and the activity found in pathological samples should always be compared with age-matched controls. The development of a new series of colorimetric substrates has allowed the production of a simple 'Dipstick' which should be of value in the screening of at-risk populations for renal disease. The diagnostic potential of the estimation of urinary NAG activity is enhanced by the separation of its isoenzymic forms by ion-exchange chromatography on DEAE-cellulose.

Topics: Acetylglucosaminidase; Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Creatinine; Female; Hexosaminidases; Humans; Infant; Kidney Diseases; Male; Middle Aged; Muramidase; Reference Values; Sex Factors

In order to assess to what extent glomerular or tubular function is involved in the renal handling of amylase and the lysozyme to creatine clearance ratios (CAm/CCr and CLys/CCr) were evaluated in 22 healthy volunteers and in 71 patients with different renal diseases. In normal controls, the mean CAm/CCr was 2.55 +/-1.54 SD, with an upper normal limit of 5.56. A normal ratio was found in patients with glomerulonephritis, with or without a nephrotic syndrome, and in patients with pyelonephritis. A significantly elevated ratio (P less than 0.001) was instead found in patients with uremia and in patients with uremia and in patients with either chronic or acute tubular damage. The CLus/CCr ratio was elevated in all the groups, except in patients with glomerulonephritis and minimal proteinuria. These results show that in humans, as in animals, the amylase filtered load undergoes partial tubular reabsorption. In renal diseases, an increase of the CAm/CCr is caused by either a marked reduction of functioning nephrons or a severe tubular damage, while the glomerular permeability does not seem to be involved. Some other mechanism is probably involved in the elevation of the CAm/CCr during acute pancreatitis.

Topics: Acute Disease; Amylases; Creatinine; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Muramidase; Nephrotic Syndrome; Pancreatitis; Proteinuria; Pyelonephritis

Topics: Adult; Aged; beta 2-Microglobulin; Beta-Globulins; Humans; Kidney Diseases; Middle Aged; Muramidase; Retinol-Binding Proteins

Topics: Agaricales; Amanita; Anuria; Blood Volume; Creatinine; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Liver; Muramidase; Mushroom Poisoning; Water; Water-Electrolyte Balance

The mean rate of excretion of neurophysins in the urine of 16 patients with kidney disease but without tubular dysfunction was 0.48 +/- 0.14 (S.E.M.) ng/min, whereas the rate in 16 patients with tubular dysfunction was 3.64 +/- 1.56 ng/min (significantly different; 2P less than 0.01). In the whole group of 32 patients there was a relationship (r = 0.57) between the rate of excretion of neurophysins in the urine and the clearance of lysozyme. The increased rate of urinary excretion of neurophysins observed in some patients with kidney disease therefore appears to be related to a disorder of renal tubular function. It is shown that the raised levels of neurophysins observed in the serum of some patients with kidney disease are not attributable to a decrease in the urinary clearance of neurophysins.

Topics: Creatinine; Humans; Kidney Diseases; Muramidase; Neurophysins

Observations conducted on a group of workers exposed to chromium (who showed a rapid urinary excretion of the metal and progressive increase of clearance with cumulative years of exposure), induced the authors to evaluate the nephrotoxic action of chromium in rats exposed to acute and chronic intoxication. The progressive Cr accumulation in the renal cortex during the course of testing explains the increase of the excreted fraction of filtered Cr, and therefore, the clearance, of the metal through the reduction of the tubular lumen-epithelium gradient. Paralleling the anatomical lesions (demonstrated only at the level of the proximal tubular cells), are the increasing modifications of the cellular lesion or altered reabsorption registered by several urinary indicators. Similar changes were found in subjects chronically exposed to the metal; their reversibility is linked to the possibility of repairing the epithelial damage by stopping exposure.

Topics: Animals; Chromium; Environmental Exposure; Female; Glucuronidase; Humans; Kidney; Kidney Cortex; Kidney Diseases; Kidney Tubules; Muramidase; Potassium Dichromate; Proteinuria; Rats; Time Factors

The serum and urine LZM levels were determined with the lysoplate assay in 26 normal experimental dogs and in 21 dogs with various renal diseases. In the dogs with decreased glomerular filtration the serum LZM levels were higher than in normal dogs (less than or equal to 1.3 mg/l). No LZM could be demonstrated in the urine of normal dogs. The presence of LZM in urine was associated with proximal tubular damage, which indicates that LZM-uria can be used as an index of renal tubular damage.

Topics: Animals; Clinical Enzyme Tests; Dog Diseases; Dogs; Female; Kidney Diseases; Kidney Glomerulus; Male; Muramidase; Urine

Serum lysozyme (muramidase) estimation is a simple, convenient and useful laboratory investigation. A review of the literature shows that lysozyme has been implicated as an aetiological factor in various disorders, and credited with being a prognostic indicator in acute myeloid leukaemia, but these promises have not been fulfilled. This low molecular weight protein is found in the urine of some patients with renal tubular disorders, but some workers have emphasized its importance as a causal agent in hypokalaemia of acute myeloid leukaemia. Research should be concentrated on muramidase as an expression of cell functions rather than as an aetiological factor. Hypokalaemia in acute myeloid leukaemia may be caused by an unidentified substance of molecular weight similar to that of lysozyme.

Topics: Animals; Humans; Hypokalemia; Kidney Diseases; Leukemia, Myeloid, Acute; Muramidase; Prognosis

SLL's were tested by turbidometric assay on 33 male patients with multiple myeloma with three to 58 tests (mean 11) for each patient over a 7-year period. The age of the patients ranged from 31 to 83 years, with a median age of 58 years. SLL's in the normal controls were 14.4 +/- 3.5 microgram/ml. Patients with myeloma had a median lysozyme level of 16 microgram/ml and mean of 16.5. The SLL's in patients with lgG1,2,3,4, Iga, and kappa and lambda light-chain myeloma were similar. Slightly higher mean SLL'S were noted in older patients. Patients with severe renal disease also had higher SLL'S. No significant changes in SLL's were seen during infections or during mild granulocytopenia (granulocyte count greater than 500 cells/mm3). In severe granulocytopenia (granulocyte count less than 500 cells/mm3) the SLL's decreased and returned to normal levels when the white blood cell counts improved. In eight patients surviving for more than 5 years, the SLL's were not different from those of the other patients. SLL values in patients with multiple myeloma did not differ significantly by statistical test from those of controls when those patients with impaired renal function are excluded.

Topics: Adult; Aged; Blood Cell Count; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Kidney Diseases; Male; Middle Aged; Multiple Myeloma; Muramidase

Topics: Child; Colitis, Ulcerative; Humans; Infections; Kidney Diseases; Leukemia; Muramidase; Sarcoidosis

Topics: Child; Humans; Kidney Diseases; Muramidase

Topics: Adolescent; Child; Child, Preschool; Humans; Kidney Diseases; Muramidase

Topics: Alkaline Phosphatase; Animals; Cephaloridine; Kidney; Kidney Diseases; L-Lactate Dehydrogenase; Male; Muramidase; Rats

Topics: Humans; Kidney Diseases; Kidney Transplantation; Muramidase; Transplantation, Homologous

Topics: Amino Acid Sequence; Animals; Dogs; Hematologic Diseases; Humans; Kidney Diseases; Molecular Weight; Muramidase; Rats

Urinary excretion of lysozyme was investigated in a group of 66 patients with various renal diseases, nephrolitiasis and urinary tract infections. The results obtained demonstrate that the amount of the enzyme excreted is related to the entity of tubular damage whereas is not with glomerular damage. No correlation was found between lysozyme excretion neither to the degree of proteinuria neither to the amount of leukocytes and bacteria in the urine. In patients with urinary infections urinary lysozyme increases only when there is a tubular injury of some entity. In 90 pediatric patients with urinary infection and pyelonephritis lysozyme in the urine was found only in two cases. Therefore urinary lysozyme determination cannot be considered for the detection of early tubular injury and is not a helpful diagnostic tool in urinary tract infections.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Kidney Diseases; Male; Middle Aged; Muramidase; Urinary Tract Infections

Lysozyme [EC 3.2.1.17] was purified from human tears, serum, and urine of acute monocytic leukemia patients, renal disease patients, and residents in cadmium-polluted areas of Tsushima Island using an affinity adsorbent containing lysozyme-lysate of Micrococcus lysodeikticus cell walls as the ligand. By means of this procedure, leukemia lysozyme was purified 100- to 200-fold with an activity recovery of 80%. It was crystallized at pH 10. This purified preparation appeared homogeneous in disc electrophoresis and showed a specific activity 2.5-fold higher than that of crystalline lysozyme from hen egg-white. Tear lysozyme was also purified to a nearly homogeneous state while the enzymes from normal serum and urine of a nephrosis patient and of residents in cadmium-polluted area were still disc electrophoretically heterogeneous and showed low specific activity as compared with purified leukemia lysozyme.

Topics: Amino Acids; Chromatography, Affinity; Crystallization; Humans; Kidney Diseases; Leukemia, Monocytic, Acute; Muramidase; Tears

Probenecid in doses of 640 mg/kg was administered to rats by the oral route, and the changes in five important enzymatic activities of urine were recorded thereafter for two days. The resluts exclude that probenecid impairs tubular reabsorption of low molecular weight protein, as urinary muramidase activity was not found increased. On the other hand, increased activities were encountered in those enzymatic activities in urine which derive from the renal tubular cells (ALD, G-6-PDH, LDH). These observations point towards a nephrotoxic effect of probenecid, which, however, is only of very low degree, as other "standard" enzymatic activities of urine, such as alkaline phosphatase, remained unchanged.

Topics: Animals; Fructose-Bisphosphate Aldolase; Kidney Diseases; Kidney Tubules; Male; Muramidase; Probenecid; Rats

Topics: Adolescent; Adult; Aged; Female; Humans; Kidney Diseases; Male; Middle Aged; Muramidase

Topics: Humans; Kidney Diseases; Muramidase; Nephelometry and Turbidimetry

Topics: Bacteriuria; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension; Kidney Diseases; Muramidase; Pyelonephritis; Uremia; Urinary Calculi

Topics: Adolescent; Adult; Aged; Blood Urea Nitrogen; Child; Creatinine; Glomerular Filtration Rate; Glomerulonephritis; Humans; Kidney Diseases; Kidney Failure, Chronic; Middle Aged; Muramidase; Renal Dialysis

Topics: Enzymes; Glucuronidase; Isoenzymes; Kidney Diseases; Muramidase; Peptide Hydrolases; Sulfatases

Topics: Acute Disease; Amylases; Chronic Disease; Creatinine; Humans; Kidney Diseases; Lipase; Muramidase; Pancreatic Neoplasms; Pancreatitis; Proteinuria

Topics: Adolescent; Adult; Child; Clinical Enzyme Tests; Female; Hodgkin Disease; Humans; Kidney Diseases; Leukemia, Myeloid; Male; Muramidase

Two patients with acute myeloid leukaemia developed hypouricaemia during the period of their illness. Renal clearance studies showed that the hypouricaemia was associated with an increased urate clearance, renal aminoaciduria, and an episodic increase in phosphate clearance. These findings together with an inadequate suppression of urinary urate exceretion after the administration of pyrazinamide suggest proximal tubular dysfunction affecting reabsorption of a wide variety of substances. Ten more patients with acute leukaemia were studied and the results indicate that this lesion develops in a large proportion of patients with acute myeloid leukaemia.

Topics: Amino Acids; Calcium; Creatinine; Cytarabine; Daunorubicin; Female; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Kidney Tubules, Proximal; Leukemia, Myeloid, Acute; Middle Aged; Muramidase; Phosphates; Phosphorus; Pyrazinamide; Uric Acid

Topics: Animals; Antibodies; Antigen-Antibody Reactions; Blood Protein Electrophoresis; Cytoplasm; Electrophoresis; Fluorescent Antibody Technique; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Leukemia, Experimental; Leukemia, Myeloid; Methylcholanthrene; Microscopy, Electron; Muramidase; Rats

Topics: Adult; Animals; Beta-Globulins; Creatinine; Female; Humans; Immune Sera; Immunodiffusion; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Macroglobulins; Male; Mass Screening; Methods; Middle Aged; Muramidase; Proteinuria; Rabbits; Specific Gravity; United States; Urine; Yugoslavia

On the assumption that increased urinary lysozyme concentration (;lysozymuria') indicates tubular proteinuria and therefore impaired tubular function, urinary lysozyme has been estimated in acute disorders where transient disturbances of renal function might be expected, in cases diagnosed clinically as extrarenal uraemia, and in a few examples of acute renal disease. Reversible lysozymuria occurred with hypokalaemia, postoperative ;collapse', electrolyte depletion, severe extrarenal infection, acute pyelonephritis, the nephrotic syndrome, after a few apparently uncomplicated surgical operations, and very transiently after ventricular fibrillation abolished by DC shock. There was no lysozymuria with severe uraemic heart failure, aspirin and paracetamol poisoning, or severe jaundice, nor in two cases of acute glomerulonephritis. Although lysozymuria may occasionally be useful in the clinical diagnosis of acutely disordered renal function, the results suggest that its value is limited; on the other hand, they have provided information on renal pathophysiology in acute disease.

Topics: Acetaminophen; Acute Disease; Aspirin; Electroshock; Glomerulonephritis; Heart Failure; Humans; Hypokalemia; Jaundice; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules; Muramidase; Myocardial Infarction; Nephrotic Syndrome; Pneumonia; Postoperative Complications; Proteinuria; Pyelonephritis; Uremia; Ventricular Fibrillation

Topics: Adolescent; Adult; Aged; Female; Humans; Kidney Diseases; Male; Middle Aged; Muramidase

Topics: Adult; Child; Creatinine; Humans; Kidney Diseases; Muramidase; Proteinuria

Topics: Adolescent; Adult; Aged; Animals; Chronic Disease; Dogs; Female; Glomerular Filtration Rate; Glomerulonephritis; Humans; Hypertension; Hypertension, Renal; Immunoelectrophoresis; Kidney Diseases; Male; Middle Aged; Muramidase; Myeloma Proteins; Nephritis, Interstitial; Nephrocalcinosis; Nephrotic Syndrome; Pyelonephritis; Rabbits; Vascular Diseases

Topics: Albuminuria; Bence Jones Protein; Blood Proteins; Chromatography, Gel; Electrophoresis, Disc; Fructose-Bisphosphate Aldolase; gamma-Globulins; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; L-Lactate Dehydrogenase; Methods; Molecular Weight; Muramidase; Ovalbumin; Pepsin A; Protein Binding; Proteinuria; Sodium Dodecyl Sulfate

Topics: Adult; Aged; Alpha-Globulins; Beta-Globulins; Blood Protein Electrophoresis; Female; Humans; Immune Sera; Kidney Diseases; Male; Metabolic Clearance Rate; Middle Aged; Muramidase; Uremia

Lysozyme turnover studies with (125)I-labeled human lysozyme were carried out on 22 patients, viz. nine control patients, seven nephrological patients with varying degrees of renal insufficiency, including three bilaterally nephrectomized patients, and six hematological patients with disturbed turnover of the neutrophilic granulocytes. It was found that plasma lysozyme has a rapid turnover with a fractional catabolic rate of 76%/hr of the plasma content. Lysozyme catabolism varied with the endogenous creatinine clearance; in addition however, extrarenal sites of catabolism were demonstrated since lysozyme could be broken down in the anephric patients, although only at a rate amounting to about 15% of the rate found in persons with intact kidneys. In the uremic patients the increased plasma lysozyme concentration was due to decreased rates of catabolism; in the hematological patients the increased plasma lysozyme level was due to increased rates of synthesis which supports the hypothesis that plasma lysozyme mainly stems from disintegrating neutrophilic granulocytes. Furthermore, it was shown that in the nonhematological patients examined, the rate of synthesis varied with the endogenous creatinine clearance.

Topics: Adolescent; Adult; Aged; Creatinine; Female; Glomerular Filtration Rate; Humans; Iodine Isotopes; Kidney Diseases; Leukemia, Myeloid; Male; Middle Aged; Muramidase; Nephrectomy; Time Factors

Topics: Arthritis, Rheumatoid; Electrophoresis; Humans; Kidney Diseases; Kidney Function Tests; Kidney Glomerulus; Kidney Tubules; Leukemia; Lupus Erythematosus, Systemic; Multiple Myeloma; Muramidase; Neoplasms; Proteinuria

Topics: Bence Jones Protein; Blood Protein Disorders; gamma-Globulins; Heavy Chain Disease; Humans; Kidney Diseases; Kidney Tubules; Multiple Myeloma; Muramidase

Topics: Diagnosis, Differential; Humans; Kidney Diseases; Kidney Tubular Necrosis, Acute; Muramidase; Nephrosclerosis; Pyelonephritis

Topics: Biological Assay; Humans; Kidney Diseases; Muramidase

Topics: Hematologic Diseases; Humans; Iodine Isotopes; Kidney Diseases; Muramidase

Topics: Adult; Aged; Child; Creatinine; Electrophoresis, Paper; Female; Humans; Kidney; Kidney Diseases; Kidney Neoplasms; Leukemia, Myeloid; Leukocyte Count; Male; Middle Aged; Muramidase; Proteinuria

Topics: Alkaline Phosphatase; Glucuronidase; Humans; Kidney Diseases; L-Lactate Dehydrogenase; Muramidase

Topics: Acute Kidney Injury; Clinical Enzyme Tests; Diagnosis, Differential; Glomerulonephritis; Humans; Kidney Diseases; Kidney Tubules; Muramidase; Nephritis; Nephrosclerosis; Proteinuria

Topics: Acute Kidney Injury; Diagnosis, Differential; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Tubules; Male; Muramidase; Nephritis, Interstitial

Topics: Adolescent; Body Temperature; Child; Child, Preschool; Complement System Proteins; Humans; Kidney Diseases; Leukocyte Count; Muramidase; Phagocytosis; Pneumonia; Prednisolone; Rheumatic Fever

Topics: Antibodies, Anti-Idiotypic; Basement Membrane; Biopsy; Blood Cell Count; Complement System Proteins; Edema; gamma-Globulins; Glomerular Filtration Rate; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Microscopy, Electron; Microscopy, Fluorescence; Muramidase; Proteinuria; Transplantation Immunology; Transplantation, Autologous; Transplantation, Homologous

Topics: Acidosis, Renal Tubular; Adult; Aged; Ammonia; Calcium; Chlorides; Creatinine; Female; Humans; Hydrogen-Ion Concentration; Hypokalemia; Kidney Diseases; Kidney Tubules; Leukemia, Myeloid; Magnesium; Male; Middle Aged; Muramidase; Phosphates; Uric Acid; Urine

Topics: Aged; Cadmium; Creatinine; Humans; Kidney Diseases; Male; Metallurgy; Middle Aged; Muramidase; Occupational Diseases; Osteomalacia; Proteinuria; Radiography; Ribonucleases; Spirometry

Topics: Adult; Aged; Blood Urea Nitrogen; Female; Humans; Kidney Diseases; Male; Middle Aged; Muramidase; Urologic Diseases

Topics: Acute Kidney Injury; Diagnosis, Differential; Glomerular Filtration Rate; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Tubules; Muramidase

Topics: Blood Proteins; Cadmium Poisoning; Creatine; Fanconi Syndrome; Female; Glomerulonephritis; Humans; Kidney Diseases; Kidney Tubules; Male; Molecular Weight; Muramidase; Proteinuria; Ribonucleases

Topics: Acute Kidney Injury; Blood Urea Nitrogen; Glomerulonephritis; Humans; Kidney Diseases; Kidney Tubules; Leukemia; Muramidase; Nephritis; Nephrocalcinosis; Nephrotic Syndrome; Urinary Calculi

Topics: Acute Disease; Animals; Clinical Enzyme Tests; Dogs; Enzymes; Ischemia; Isoenzymes; Kidney Diseases; Kidney Function Tests; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Methods; Muramidase; Renal Artery Obstruction

Topics: Kidney Diseases; Muramidase; Proteinuria; Ribonucleases

Topics: Animals; Cadmium; Electrophoresis; Kidney; Kidney Diseases; Kidney Function Tests; Kidney Tubules; Liver; Muramidase; Proteinuria; Rabbits; Urine

Topics: Adult; Female; Humans; Hypertension; Kidney Diseases; Muramidase; Pre-Eclampsia; Pregnancy

Topics: Blood; Humans; Kidney Diseases; Muramidase; Proteinuria; Rats; Research; Urea; Uremia; Urine