minocycline and Kidney-Diseases

Kidney diseases need specialized health care and still are a reason of death. There is a large body of evidence that indicates minocycline possesses some cytoprotective effects beside of antibacterial properties. In this review, we aimed to explain cytoprotective mechanisms and kidney protection of minocycline. In order to find the effects of minocycline on kidney diseases a systematic literature search was performed, according to the guidelines proposed at the PRISMA statement in the electronic databases, including: PubMed, Scopus, and Web of Science up to August 2016, using the term 'minocycline' combined either by 'kidney' or 'renal' and published in English language. The following criteria were included: (1) studies that used minocycline in renal diseases; (2) full-text articles; (3) English language; (4) no limitation in publications with in-vivo or in-vitro and human or animal subjects. Our search provided a total of 1056 articles which 1045 of them were discarded due to not meeting the inclusion criteria. It has been clear that several factors, including apoptosis, oxidative stress, mitochondrial dysfunction and inflammation have pivotal roles in the development and progression of kidney diseases. Minocycline protective properties are via several ways, including anti-apoptotic, free radical scavenging, anti-inflammatory, effect on mitochondrial functions and inhibition of matrix metalloproteinase. This systematic review confirmed that minocycline could have significant effects on treatment of renal malfunctions. However, regarding any possible adverse effects of antibiotics, it appears that more investigation is still needed in this context.

Topics: Animals; Anti-Bacterial Agents; Humans; Kidney Diseases; Minocycline

The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, adverse events, dosage and administration, drug interactions, and place in therapy of tigecycline are reviewed.. Tigecycline is the first of a new class of antimicrobials, the glycylcyclines, to receive approved labeling from the Food and Drug Administration. Similar to tetracyclines, glycylcyclines contain the central four-ring carbocyclic skeleton, with a substitution at the D-9 position. This substitution confers expanded broad-spectrum activity and defense against antimicrobial efflux pumps and ribosomal protection mechanisms. Tigecycline covers a broad spectrum of gram-positive (including resistant isolates), gram-negative (including extended-spectrum beta-lactamase producing organisms), and anaerobic pathogens. It does not exhibit activity against Pseudomonas aeruginosa and Proteus species. Clinical efficacy has been demonstrated in complicated skin and skin structure infections and intraabdominal infections. Tigecycline is administered intravenously and exhibits linear pharmacokinetics. The drug does not undergo extensive metabolism and works independently of the cytochrome P-450 isoenzyme system and therefore does not affect medications metabolized by these enzymes. Tigecycline is administered as a 100-mg i.v. loading dose followed by 50 mg i.v. every 12 hours. Hepatic dosage adjustment is necessary for severe disease; however, no dosage adjustments are necessary for patients with renal impairment.. Tigecycline is an alternative agent available for the treatment of resistant gram-negative and gram-positive infections, especially in patients with a history of a penicillin allergy or antimicrobial-related toxicities.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Drug Interactions; Drug Resistance, Multiple, Bacterial; Humans; Kidney Diseases; Liver Diseases; Minocycline; Tigecycline

We report four cases of the side effects of minocycline seen during the last two years in our department. There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia. Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world. During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe. Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Drug Hypersensitivity; Eosinophilia; Female; Humans; Kidney Diseases; Lung Diseases; Lupus Vulgaris; Male; Minocycline

Two double-blind, randomized, placebo-controlled feasibility trials of minocycline in ALS were conducted. In Trial 1, 19 subjects received 200 mg/day or placebo for 6 months; there were no significant differences in adverse events (AE). In Trial 2, 23 subjects received up to 400 mg/day in an 8-month crossover trial. The mean tolerated dose was 387 mg/day, there was a trend toward more gastrointestinal AE (p = 0.057), and blood urea nitrogen and liver enzymes became elevated (p < 0.05). Using these data, the authors have designed and launched a phase III trial.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Chemical and Drug Induced Liver Injury; Double-Blind Method; Drug Therapy, Combination; Female; Gastrointestinal Diseases; Hand Strength; Humans; Kidney Diseases; Male; Middle Aged; Minocycline; Neuroprotective Agents; Respiratory Muscles; Riluzole; Treatment Outcome

Dysfunction of mitochondria is involved in podocyte injury in some kidney diseases, but the relationship between abnormal mitochondrial morphology and podocyte injury as well as the underlying mechanism is still unclear. This study aims to investigate dynamic changes of mitochondrial morphology and the potential molecular events in an adriamycin (ADR)-induced podocyte injury model.. Podocyte apoptosis was evaluated by annexin V assay. Podocyte mitochondrial membrane potential (MMP) was measured with MitoCapture kit. Double staining was used to show the distribution changes of mitochondria and actin filament as well as mitofusin proteins and podocin. Mitochondrial shape descriptors were obtained using analySIS Image system. Effects of cyclosporine A (CsA) or minocycline (Mcy) on mitochondrial morphology were explored in ADR-induced nephropathy rats.. ADR caused podocyte damage displaying as induction of cellular apoptosis and increase of activated caspase 3 and cytochrome c. The MMP level was decreased remarkably in ADR-treated podocytes. Mitochondrial morphological changes induced by ADR occurred rapidly from large and ellipsoid shape to the small, long and irregular. ADR significantly decreased surface area, perimeter and circularity, while increasing aspect ratio of mitochondria. In addition, mitochondria number transiently increased at 6 h following ADR application. Mitochondria intensity was increased along with punctate mitochondria formation, which co-localized with polymerized actin cytoskeleton in ADR podocytes. In ADR-induced nephropathy rats, 24-h proteinuria was decreased significantly by CsA or Mcy. ADR-induced abnormal changes of mitochondrial morphology were restored by CsA or Mcy. The induction of mitofusin proteins and the reduction of podocin in ADR rat glomeruli were rescued by CsA or Mcy.. Mitochondrial dysfunction may be an early event in ADR-induced podocyte damage, and the protective role of CsA or Mcy may be mediated partially by improving mitochondrial function through inhibiting the induction of mitofusin proteins.

Topics: Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Apoptosis; Caspase 3; Cyclosporine; Doxorubicin; Fluorescent Antibody Technique; Immunosuppressive Agents; Kidney Diseases; Male; Membrane Potential, Mitochondrial; Minocycline; Mitochondria; Podocytes; Proteinuria; Rats; Rats, Sprague-Dawley

Involvement of the renal parenchyma in the acute phase of brucellosis is very rare. Only two cases of renal brucelloma have been reported in the English language literature to date. We report a case of renal abscess caused by Brucella in the acute phase. A 45-year-old Chinese man presented with a high fever, urine occult blood, and a low density lesion in the right kidney. Ultrasound-guided aspiration was done. Brucella melitensis was isolated from both blood and puncture fluid culture. Minocycline combined with moxifloxacin was prescribed for 4 months. The infection relapsed at 6 months after discontinuation. Minocycline combined with rifampin was administered for another 2 months. The brucellosis had not relapsed at more than 20 months later. It is possible to cure renal brucelloma with antibiotics and ultrasound-guided aspiration. Treatment should not be discontinued until the abscess has disappeared and two consecutive blood cultures taken 1 month apart are negative.

Topics: Abscess; Anti-Bacterial Agents; Brucella melitensis; Brucellosis; Drug Therapy, Combination; Fluoroquinolones; Humans; Kidney Diseases; Male; Middle Aged; Minocycline; Moxifloxacin; Rifampin

Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2⁺/⁺) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2⁻/⁻) and MMP-2⁺/⁺ mice treated with minocycline (inhibitor of MMPs). In MMP-2⁺/⁺ mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, α-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-β1, Smad, Wnt, β-catenin, and Snail). In contrast, the kidneys of MMP-2⁻/⁻ mice and minocycline-treated MMP-2⁺/⁺ mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis.

Topics: Animals; Collagen; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibrosis; Gene Expression Regulation; Histocytochemistry; Kidney Diseases; Kidney Tubules; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Transgenic; Minocycline; Phenotype; RNA, Messenger; S100 Calcium-Binding Protein A4; S100 Proteins; Ureteral Obstruction

Bacterial infections in patients with hematological neoplasms carry high morbidity and mortality. Gram-positive microorganisms can cause more than half of the bacterial infections in patients with febrile neutropenia, especially bacteremias. Effective coverage against these infections in these hosts, especially the immunodepressed, is required.. We reviewed the literature published in the last decade on infections in patients with hematological malignancies, with or without febrile neutropenia. Emphasis was placed on publications analyzing the processes caused by Gram-positive microorganisms and the management of these infections (whether bacteremic or otherwise) through traditional drugs (glycopeptides) and the new antibiotics (linezolid, tigecycline and daptomycin).. There was a notable scarcity of studies on the treatment of infections due to Gram-positive microorganisms in patients with cancer through treatment with the new antimicrobial drugs. Especially striking was the lack of comparative studies. Specifically, in the case of daptomycin, there were no randomized comparative trials in patients with febrile neutropenia, although there were observational retrospective studies or case studies [European Cubicin(®) Outcome Registry and Experience (EUCORE)] with a large number of patients (around 200) with oncological malignancies. In the three main studies, the overall favorable response rates were between 65% and 90%, with a therapeutic success rate of 85% in patients with severe febrile neutropenia. At the same time, the safety profile of daptomycin was shown to be highly favorable with good tolerability and a low rate of adverse effects (< 10% for those directly related to the antibiotic) which, on very few occasions, were severe or led to treatment withdrawal. The nephrotoxicity rate was much lower than that caused by vancomycin in historical control groups, although there were no statistically significant differences.. Daptomycin is a safe and effective therapeutic alternative in the treatment of bacterial infections due to Gram-positive microorganisms in patients with cancer, with or without neutropenia. However, further studies are required to support the use of this drug in the empirical treatment of febrile neutropenia.

Topics: Acetamides; Anti-Bacterial Agents; Antineoplastic Agents; Daptomycin; Databases, Factual; Europe; Glycopeptides; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Immunocompromised Host; Kidney Diseases; Linezolid; Microbial Sensitivity Tests; Minocycline; Multicenter Studies as Topic; Neutropenia; Oxazolidinones; Registries; Retrospective Studies; Risk Factors; Tigecycline; Treatment Outcome

Topics: Administration, Oral; Adult; Choroid Diseases; Conjunctival Diseases; Female; Humans; Kidney Diseases; Lacrimal Apparatus Diseases; Minocycline; Obesity, Morbid; Peptidyl-Dipeptidase A; Sarcoidosis; Sarcoidosis, Pulmonary; Skin Diseases; Tomography, X-Ray Computed

Tetracyclines exhibit significant anti-inflammatory properties in a variety of rheumatologic and dermatologic conditions. They have also been shown to inhibit apoptosis in certain neurodegenerative disorders. Because ischemic renal injury is characterized by both apoptosis and inflammation, we investigated the therapeutic potential of tetracyclines in a rat model of renal ischemia-reperfusion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion and received either minocycline or saline for 36 h before ischemia. Minocycline reduced tubular cell apoptosis 24 h after ischemia as determined by terminal transferase-mediated dUTP nick end-labeling staining and nuclear morphology. It also decreased cytochrome c release into the cytoplasm and reduced upregulation of p53 and Bax after ischemia. The minocycline-treated group showed a significant reduction in tubular injury and cast formation. In addition, minocycline reduced the number of infiltrating leukocytes, decreased leukocyte chemotaxis both in vitro and ex vivo, and downregulated the expression of ICAM-1. Serum creatinine 24-h postischemia was significantly reduced in the minocycline-treated group. We conclude that minocycline has potent antiapoptotic and anti-inflammatory properties and protects renal function in this model of ischemia-reperfusion. Tetracyclines are among the safest and best-studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; bcl-2-Associated X Protein; Chemotaxis, Leukocyte; Cytochromes c; Cytosol; Disease Models, Animal; Kidney; Kidney Diseases; Leukocytes; Male; Minocycline; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tumor Suppressor Protein p53; Up-Regulation

Kinetic analysis of minocycline concentrations in plasma and urine resulted in the following findings: In normal subjects the biological half-life is about 17 hours after the first dose and 21 hours after repeated administration. The renal drug clearance is only about 8% of the overall plasma clearance which is independent of renal function with a mean value of 47 ml/min. The fraction of the absorbed dose eliminated unchanged in the urine is only 9--19%. As a consequence the elimination rate of the drug is practically independent of renal function and decreases only 9--19% in anuric patients. The renal drug clearance depends linearly on renal function. The gastro-intestinal bio-availability of minocycline from the coated tablet preparation is incomplete. The cumulative behaviour of the drug corresponds to the kinetic parameters determined after repeated administration. It is suggested that the usual dosage regimen should be used in patients with renal disease.

Topics: Adult; Aged; Creatinine; Half-Life; Humans; Kidney Diseases; Kinetics; Mathematics; Middle Aged; Minocycline; Tetracyclines; Time Factors

In the present studies, we had an opportunity to review the effects of minocycline intravenous instillation for the treatment of moderate disorder of renal functions. No accumulation of minocycline was observed in the repeated administration of this drug instilled intravenously up to 7 days in the patients with moderate disorder of the renal functions. Also, no particular abnormality was observed in the tests of the liver, kidney and hematology. For patients with moderate Ccr 30 approximately 60 ml/min, as entered into the present study, the usual dosage of minocycline intravenous instillation for less than 7 days would not cause adverse reaction on renal functions.

Topics: Adult; Aged; Animals; Dogs; Female; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged; Minocycline; Tetracyclines

Topics: Acute Kidney Injury; Chronic Disease; Female; Humans; Kidney; Kidney Diseases; Male; Minocycline; Regression Analysis; Tetracyclines; Time Factors