muramidase and Nephritis--Interstitial

Karyomegalic interstitial nephropathy (KIN) has been reported as an incidental finding in patients with childhood cancer treated with ifosfamide. It is defined by the presence of tubular epithelial cells (TECs) with enlarged, irregular, and hyperchromatic nuclei. Cellular senescence has been proposed to be involved in kidney fibrosis in hereditary KIN patients. We report that KIN could be diagnosed 7-32 months after childhood cancer diagnosis in 6/6 consecutive patients biopsied for progressive chronic kidney disease (CKD) of unknown cause between 2018 and 2021. The morphometry of nuclear size distribution and markers for DNA damage (γH2AX), cell-cycle arrest (p21+, Ki67-), and nuclear lamina decay (loss of lamin B1), identified karyomegaly and senescence features in TECs. Polyploidy was assessed by chromosome fluorescence in situ hybridization (FISH). In all six patients the number of p21-positive TECs far exceeded the typically small numbers of truly karyomegalic cells, and p21-positive TECs contained less lysozyme, testifying to defective resorption, which explains the consistently observed low-molecular-weight (LMW) proteinuria. In addition, polyploidy of TEC was observed to correlate with loss of lysozyme staining. Importantly, in the five patients with the largest nuclei, the percentage of p21-positive TECs tightly correlated with estimated glomerular filtration rate loss between biopsy and last follow-up (R

Topics: Biopsy; Cellular Senescence; Child; Humans; Ifosfamide; In Situ Hybridization, Fluorescence; Kidney; Muramidase; Neoplasms; Nephritis, Interstitial; Polyploidy; Proteinuria; Renal Insufficiency, Chronic

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a severe hypersensitivity drug reaction affecting the skin and multiple internal organ systems. We report a 47-year-old man with DIHS/DRESS and comorbidities (fulminant type 1 diabetes mellitus, valsartan-induced photosensitivity, vitiligo and acute interstitial nephritis). Although acute interstitial nephritis usually appears in the early phase, his is a rare case of acute interstitial nephritis more than 2 years after the onset of DIHS/DRESS.

Topics: Acetaminophen; Biopsy; Carbocysteine; Clarithromycin; Creatinine; Drug Hypersensitivity Syndrome; Drug Therapy, Combination; Drugs, Chinese Herbal; Fatigue; Humans; Kidney; Male; Middle Aged; Muramidase; Nephritis, Interstitial; Prednisolone; Skin; Time Factors

Some peptide growth factors produced by macrophages play a role in fibrosis following tissue injury, through the induction of myofibroblasts. In the present study, the appearance of macrophages and myofibroblast development in hepatic and renal fibrosis was determined by immunohistochemical analysis of tissue from 15 dogs. The hepatic and renal fibrosis was classified as grade I, II or III, depending on the extent (percentage) of fibrotic areas per unit area measured by morphometry with Azan-stained sections. The presence of alpha-smooth muscle actin-immunolabelled myofibroblasts was directly related to advancing grade of both hepatic and renal fibrosis. Lysozyme-immunolabelled macrophages also increased in number with increasing grade of hepatic and renal fibrosis. These findings indicate that myofibroblasts and lysozyme-positive macrophages may contribute to progressive fibrosis in canine liver and kidney disease. Interestingly, the number of macrophages recognized by AM-3K, a newly generated monoclonal antibody capable of labelling exuded macrophages and resident tissue macrophages in dogs, fell significantly in grades II and III of renal fibrosis. By contrast, in hepatic fibrosis there were no marked differences in the number of AM-3K-positive macrophages between grades. These findings suggest that there are functional differences between lysozyme- and AM-3K-positive macrophages.

Topics: Actins; Animals; Antibodies, Monoclonal; Cell Count; Dogs; Female; Fibroblasts; Fibrosis; Immunohistochemistry; Liver Cirrhosis; Macrophages; Male; Muramidase; Muscle, Smooth; Nephritis, Interstitial

We studied the role of proteinase inhibitors (Pls) alpha 1-antitrypsin and alpha 1-antichymotrypsin in relation to lysozyme (LZM), and membrane attack complex (C5b-9) in renal tubular damage by immunohistochemical techniques. Fifty-five cases, including 45 patients with glomerular diseases, and 10 controls were studied. The patients were divided into two groups; one with tubulo-interstitial lesions (TILs; 30 cases), and the other without (15 cases). Significant antiproteinase response was observed in the proximal tubules in both disease groups, indicating that they were subjected to proteolytic attack. This response correlated with proteinuria and occurred in tubules which showed protein reabsorption as demonstrated by the presence of LZM staining in consecutive serial sections. Increased deposition of membrane attack complex (C5b-9) was observed in the disease group with TILs, indicating direct damage to cell membranes. C5b-9 may also generate oxygen species, potent inhibitors of Pls, which allow the proteases to cause tubular damage.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Basement Membrane; Blood Vessels; Complement Membrane Attack Complex; Humans; Immunohistochemistry; Kidney Glomerulus; Kidney Tubules; Muramidase; Nephritis, Interstitial; Staining and Labeling

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

Topics: Albuminuria; Autoantigens; beta 2-Microglobulin; Diagnosis, Differential; Epithelium; Glomerulonephritis; Humans; Immunoglobulin G; Kidney Tubules; Muramidase; Nephritis, Interstitial; Nephrotic Syndrome; Proteinuria

To shed more light on the immunopathogenesis of drug-induced acute interstitial nephritis, a combined histologic, immunopathologic, and ultrastructural study of renal biopsy specimens from nine patients with drug-induced renal disease was performed. None of the patients had pre-existing renal disease or evidence of sarcoidosis or tuberculosis. The principal drugs included a hydrochlorothiazide-triamterene combination (Dyazide), hydrochlorothiazide, fenoprofen, and furosemide and triamterene. Renal insufficiency developed approximately four to ten weeks after initiation of drug therapy. In all cases, withdrawal of the drug(s) with or without steroid therapy resulted in restoration of normal or near-normal renal function. Histologically, all biopsy specimens showed acute interstitial nephritis characterized by an intense but patchy mononuclear cell interstitial infiltrate consisting of lymphocytes, monocytes, and plasma cells, modest numbers of eosinophils, patchy tubular atrophy, interstitial edema, and normal glomeruli. All biopsy specimens contained interstitial (and, in two cases, perivascular) non-caseating granulomas, which were numerous in one case, moderate in four cases, and rare in the remainder. Direct immunofluorescence was negative for IgG, IgM, IgA, C1q, C4, and C3 along glomerular and tubular basement membranes. Immunoperoxidase staining for lysozyme (performed in three cases) demonstrated many positive cells in the infiltrate. In two cases in which granulomas were present in prepared sections, the epithelioid and multinucleated giant cells did not stain for lysozyme. Electron microscopy of the granulomas in two cases revealed that the epithelioid and giant cells had "secretory" features characteristic of hypersensitivity granulomas. These findings provide further evidence for the participation of cell-mediated immunity in the pathogenesis of at least some cases of drug-induced acute interstitial nephritis.

Topics: Adult; Aged; Drug Hypersensitivity; Female; Fenoprofen; Fluorescent Antibody Technique; Furosemide; Granuloma; Humans; Hydrochlorothiazide; Hypersensitivity, Delayed; Immunity, Cellular; Immunoenzyme Techniques; Immunoglobulin E; Kidney; Macrophages; Male; Middle Aged; Monocytes; Muramidase; Nephritis, Interstitial; Triamterene

In an effort to identify new diagnostic features of tubulointerstitial nephritis (TIN), urinary total protein concentrations and urinary excretion rates of four serum proteins and of proximal renal tubular epithelial antigens were determined for five normal subjects and for 44 patients with well-characterized renal diseases. Four urinary protein indices correlated with TIN: clearance of lysozyme/clearance of albumin > 20; clearance of immunoglobulin G/clearance of albumin % > 55 per cent; renal tubular epithelial antigen excretion > 10 units per min; urinary albumin/urinary total protein concentrations < 50 per cent. Of TIN patients, 86 per cent were (+) to one or more of these criteria whereas 89 per cent of glomerular disease patients were (-) to all criteria. By combining these criteria into multiphasic testing profiles, 88 per cent of patients could be successfully categorized as having either tubulointerstitial or glomerulonephritis. This finding suggests the potential diagnostic value of these new testing parameters.

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