Drug-induced nephrotoxicity. Aetiology, clinical features and management

There is a growing number of hospitalised patients who develop a drug-induced renal problem because increasing numbers of potent drugs have been added to the therapeutic arsenal in recent years. The 3 clinical syndromes that can be recognised in drug-induced nephropathy are acute renal failure, chronic interstitial nephritis and the nephrotic syndrome. The first can be caused by prerenal problems, acute interstitial nephritis, acute tubular necrosis and intratubular obstruction. The most important drugs that cause prerenal failure are NSAIDs, captopril and cyclosporin. NSAIDs inhibit the synthesis of prostaglandins, and consequently vasoconstriction of the afferent arteriole leads to lowering of the glomerular filtration rate (GFR); captopril blocks the formation of angiotensin II (which also leads to a lower GFR), and should be used with caution in patients with stenotic renal arteries; cyclosporin causes vasoconstriction of the afferent arteriole, which is probably mediated by the sympathetic system. Combinations of these drugs result in increased nephrotoxicity. The drugs most likely to cause acute interstitial nephritis are antibiotics and NSAIDs. Normally, signs of an allergic reaction are also present. Acute interstitial nephritis is usually self-limiting, but in some studies it is claimed that steroids may promote recovery. Four important causal agents of acute tubular necrosis are aminoglycosides, amphotericin B, radiocontrast agents and cyclosporin. Approximately half of the cases of drug-induced renal failure are related to the use of aminoglycosides: generally, 10 days after start of treatment a nonoliguric renal failure develops, with recovery after withdrawal of the drug in almost all cases. The aminoglycosides are particularly nephrotoxic when combined with other nephrotoxic drugs. 80% of amphotericin B-treated patients develop renal insufficiency, a percentage that increases as the cumulative dose exceeds 5g. It is because of its unique antifungal properties that there are still some indications for the use of this highly nephrotoxic drug; the high percentage of nephrotoxicity can probably be prevented in part by sodium loading. The nephrotoxicity of radiocontrast agents is largely dependent on renal function: from 0.6% in patients with normal renal function to 100% in patients with a serum creatinine above 400 mumol/L. Diabetes mellitus does not add greatly to the risk of radiocontrast nephrotoxicity. The nephrotoxicity of cyclosporin is dose-dependent and reversible, although there are some reports of irreversibility after long term use. Cyclosporin can also result in nephrotoxicity in combination therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Acute nephrotoxicity of NSAID from the foetus to the adult

NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.     

Drug-induced nephropathy: an update

Medications cause renal disease by promoting various types of injury in the kidney. Several drugs reduce renal perfusion and cause prerenal azotemia. Vascular disease can develop following exposure to various medications through direct and indirect effects. A number of glomerular lesions have been described with therapeutic agents and illicit drugs. Acute interstitial nephritis occurs from a drug-induced allergic reaction, which promotes interstitial inflammation and tubular damage. Acute tubular necrosis is a dose-dependent process that occurs from direct drug toxicity on tubular epithelia. Other less common patterns of drug-induced tubular injury include osmotic nephropathy, crystal nephropathy and acute nephrocalcinosis. Finally, postrenal azotemia from structural or functional obstruction of the urinary tract also complicates therapy with a number of medications.     

Drug-induced nephropathy: an update

Medications cause renal disease by promoting various types of injury in the kidney. Several drugs reduce renal perfusion and cause prerenal azotemia. Vascular disease can develop following exposure to various medications through direct and indirect effects. A number of glomerular lesions have been described with therapeutic agents and illicit drugs. Acute interstitial nephritis occurs from a drug-induced allergic reaction, which promotes interstitial inflammation and tubular damage. Acute tubular necrosis is a dose-dependent process that occurs from direct drug toxicity on tubular epithelia. Other less common patterns of drug-induced tubular injury include osmotic nephropathy, crystal nephropathy and acute nephrocalcinosis. Finally, postrenal azotemia from structural or functional obstruction of the urinary tract also complicates therapy with a number of medications.     

Nephrotoxicity Associated with Concomitant Use of Ledipasvir‐Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

Direct‐acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, with superior efficacy and safety compared to interferon‐based therapies. Despite these improvements, drug interactions with DAAs exist and may be clinically relevant in human immunodeficiency virus (HIV)‐coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (TDF) and ledipasvir‐sofosbuvir (LDV‐SOF). A 56‐year‐old woman with HIV infection who had been taking efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) for 6 years developed acute kidney injury 8 weeks after initiating LDV‐SOF for the treatment of HCV infection. Her serum creatinine concentration peaked at 10 mg/dL, compared with her baseline concentration of 0.9–1 mg/dL. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both LDV‐SOF and TDF were discontinued, and the patient's serum creatinine concentration decreased to 1.3 mg/dL over the following 6 weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and TDF, which results in increased TDF exposure. Despite knowledge of this interaction, LDV‐SOF is commonly prescribed in patients with HIV‐HCV coinfection, as patients who received LDV‐SOF– and TDF‐containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from TDF toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both LDV‐SOF and TDF. Clinicians prescribing LDV‐SOF to HCV‐HIV–coinfected patients receiving TDF should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative DAAs may also have a role in the management of patients at high risk for renal adverse effects from TDF.     

Cephalexin-induced acute tubular necrosis

A 24-year-old woman with a history of penicillin allergy developed reversible acute renal failure after receiving cephalexin for 4 days. The patient experienced nausea, vomiting, diarrhea, pruritus, cough, and an elevated creatinine level of 2.2 mg/dl. The patient's creatinine level continued to rise, peaking at 5.3 mg/dl on hospital day 3. Nephrotoxic acute tubular necrosis was confirmed by electron microscopy. Within 1 month of discharge from the hospital, the patient's creatinine level decreased to 0.6 mg/dl. Although the renal injury most commonly associated with the cephalosporin class of antibiotics is allergic interstitial nephritis, currently available cephalosporins infrequently can cause direct tubular toxicity.     

Antiretroviral therapy and the kidney: balancing benefit and risk in patients with HIV infection

The widespread introduction of highly active antiretroviral therapy (HAART) has revolutionised the treatment and course of HIV infection, with complications of chronic HIV infection and HAART playing an increasingly important role in morbidity and mortality. Both HIV infection and HAART have been associated with the development of acute and chronic kidney disease. The incidence of HIV-associated nephropathy, the classic kidney disease of HIV, reached a plateau following the introduction of HAART, consistent with the pathogenic role of direct viral infection of the kidney. At the same time, antiretroviral agents and related therapies have demonstrated a range of nephrotoxic effects, including crystal-induced obstruction, lactic acidosis, tubular toxicity, interstitial nephritis and electrolyte abnormalities. This article reviews the impact of HAART on the epidemiology of HIV-related kidney disease, the potential nephrotoxicity of specific antiretroviral agents and related medications, and guidelines for monitoring kidney function in HAART-treated patients.     

Ochratoxin and Kidney Disease in the Human

Abstract

Ochratoxin A (OTA), produced by several species of Aspergillus and Penicillium, is known for its nephrotoxicity in pigs and rats. Human exposure to this toxin, essentially by consumption of contaminated food and drinks derived from cereals, could be potentially nephrotoxic. There is a paradox between the risk of OTA for human renal disease, due to the wide distribution of this mycotoxin throughout the world, and the rarity of reported cases demonstrating its role in chronic renal disease. Possible OTA-induced acute renal failure was recently reported in Italy after a farmer and his wife worked 8 hours in a granary closed for several months. Renal biopsy in the woman who developed nonoliguric acute renal failure revealed lesions of acute tubular necrosis. A strain of Aspergillus ochraceus producing OTA was isolated from the wheat. Chronic nephrotoxicity due to OTA is probably more usual and makes the diagnosis more difficult. Balkan Endemic Nephropathy, a chronic tubulo-interstitial renal disease, could be due to OTA. Epidemiologic studies showed that in areas where high OTA levels are reached in food and in the blood of the population, there is a high incidence of nephropathy and renal tumours. The demonstration of DNA adducts in kidneys of animals exposed to OTA and similar adducts in renal tissue and tumours from individuals in the endemic region of the Balkan countries highlights a new molecular epidemiological approach. Karyomegalic interstitial nephritis, characterized by karyomegaly in proximal and distal tubular epithelial cells, has been reported in nine patients. Karyomegaly could be due to an environmental toxin that interferes with DNA replication. Involvement of the oxidative pathway in genotoxicity of OTA is known and oxidant stress induces DNA damage. Therefore, karyomegaly could be a histological marker of interstitial nephritis due to OTA. In developing countries where the prevalence of end stage renal failure due to nephropathy of uncertain etiology is high. OTA and probably other mycotoxins could be major environmental factors in the occurrence of renal disease.     

Anticancer drug-induced kidney disorders.

Nephrotoxicity is an inherent adverse effect of certain anticancer drugs. Renal dysfunction can be categorised as prerenal uraemia, intrinsic damage or postrenal uraemia according to the underlying pathophysiological process. Renal hypoperfusion promulgates prerenal uraemia. Intrinsic renal damage results from prolonged hypoperfusion, exposure to exogenous or endogenous nephrotoxins, renotubular precipitation of xenobiotics or endogenous compounds, renovascular obstruction, glomerular disease, renal microvascular damage or disease, and tubulointerstitial damage or disease. Postrenal uraemia is a consequence of clinically significant urinary tract obstruction. Clinical signs of nephrotoxicity and methods used to assess renal function are discussed. Mechanisms of chemotherapy-induced renal dysfunction generally include damage to vasculature or structures of the kidneys, haemolytic uraemic syndrome and prerenal perfusion deficits. Patients with cancer are frequently at risk of renal impairment secondary to disease-related and iatrogenic causes. This article reviews the incidence, presentation, prevention and management of anticancer drug-induced renal dysfunction. Dose-related nephrotoxicity subsequent to administration of certain chloroethylnitrosourea compounds (carmustine, semustine and streptozocin) is commonly heralded by increased serum creatinine levels, uraemia and proteinuria. Additional signs of streptozocin-induced nephrotoxicity include hypophosphataemia, hypokalaemia, hypouricaemia, renal tubular acidosis, glucosuria, aceturia and aminoaciduria. Cisplatin and carboplatin cause dose-related renal dysfunction. In addition to increased serum creatinine levels and uraemia, electrolyte abnormalities, such as hypomagnesaemia and hypokalaemia, are commonly reported adverse effects. Rarely, cisplatin has been implicated as the underlying cause of haemolytic uraemic syndrome. Pharmaceutical antidotes to cisplatin-induced nephrotoxicity include amifostine, sodium thiosulfate and diethyldithiocarbamate. Dose- and age-related proximal tubular damage is an adverse effect of ifosfamide. In addition to renal wasting of electrolytes, glucose and amino acids, Fanconi syndrome, rickets and osteomalacia have occurred with ifosfamide treatment. High dose azacitidine causes renal dysfunction manifested by tubular acidosis, polyuria and increased urinary excretion of electrolytes, glucose and amino acids. Haemolytic uraemia is a rare adverse effect of gemcitabine. Methotrexate can cause increased serum creatinine levels, uraemia and haematuria. Acute renal failure is reported following administration of high dose methotrexate. Urinary alkalisation and hydration confer protection against methotrexate-induced renal dysfunction. Dose-related nephrotoxicity, including acute renal failure, are reported subsequent to treatment with pentostatin and diaziquone. Acute renal failure is a rare adverse effect of treatment with interferon-alpha. Haemolytic uraemic syndrome occurs with mitomycin administration. A mortality rate of 50 to 100% is reported in patients developing mitomycin-induced haemolytic uraemic syndrome. Capillary leak syndrome occurring with aldesleukin therapy can cause renal dysfunction. Infusion-related hypotension during infusion of high dose carmustine can precipitate renal dysfunction.     

Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients

Antiretroviral therapy (ART) has made a significant impact on the morbidity and mortality of patients with HIV infection. However, many of these agents have nephrotoxic potential and are implicated in causing both acute and chronic kidney disease. Safely employing these medications requires a thorough understanding of risk factors that predispose to kidney injury, which include both patient-related characteristics as well drug-related factors. Acute tubular toxicity, crystal nephropathy, and acute interstitial nephritis are among the common renal manifestations of these drugs. Adefovir and tenofovir are associated with tubular toxicity. Crystalluria, crystal nephropathy and nephrolithiasis have been established with indinavir. Acute interstitial nephritis, although not common among antiretroviral agents, is seen with indinavir and atazanavir in these immunocompromised patients. Rarely, enfuvirtide may promote a glomerulopathy. Frequent exposure to other nephrotoxic non-antiretroviral drugs also contributes to kidney disease. Identification and reversal of potentially modifiable risk factors prior to drug administration is important to limiting kidney injury. Recognition of drug-related nephrotoxicity will promote earlier resolution of acute kidney injury and reduce the development of chronic kidney disease.     

Comparative tolerability of treatments for inflammatory bowel disease.

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.     

内科常用药物相关的急性肾衰竭

药源性急性肾衰竭（DARF）是指药物引起的以急性水、电解质紊乱和酸碱平衡失调及氮质血症为主要特征的一组临床综合征。DARF是一种常见的药源性疾病，约占肾实质性急性肾衰竭的19％～40％。其临床特点是在用药数日或数周内出现少尿或非少尿型ARF，部分患者可同时出现药疹、药物热、贫血、肝功能损害、神经系统损害等表现。DARF最常见的临床病理类型有急性肾小管坏死、急性间质性肾炎。DARF的发病机制主要为药物引起肾血流动力学改变导致肾灌注量减少、对肾小管细胞的毒性作用导致急性肾小管坏死、免疫反应导致急性间质性肾炎、药物结晶沉积导致管腔阻塞或免疫介导的肾小球肾炎等。DARF的相关危险因素包括药物的肾毒性作用、剂量、疗程，以及患者的机体状态如：高龄、血容量不足、糖尿病、既往肾损害或肾功能不全等。DARF的常见致病药物有抗生素、非甾体抗炎药、利尿剂及某些中药等。本文重点介绍内科常用的心血管系统药物、消化系统药物及抗病毒药导致DARF的临床特点及其防治。     

Mechanisms of lead and cadmium nephrotoxicity

Exposure to lead results in accumulation in proximal renal tubular lining cells in the form of morphologically discernible inclusion bodies which are lead-protein complexes. Acute nephrotoxicity consists of proximal tubular dysfunction and can be reversed by treatment with chelating agents. Chronic lead nephrotoxicity consists of interstitial fibrosis and progressive nephron loss, azotaemia and renal failure. Potential complications of lead nephropathy include gout and hypertension. Cadmium accumulates in renal tubular lining cells bound to metallothionein, a small protein containing 30% cystine. Metallothionein protects against nephrotoxicity by binding cadmium in a nontoxic form. Renal tubular dysfunction and chronic interstitial fibrosis occur when cadmium levels in the renal cortex exceed the critical concentration of about 200 micrograms/g. Recommendations are made for specific research needs.     

The effects of nanoparticles on the renal system

Through a process of translocation across biological barriers, nanoparticles can reach and deposit in secondary target organs where they may induce adverse biological reactions. Therefore, a correct assessment of nanoparticle-induced adverse effects should take into account the different aspects of toxicokinetics and tissues that may be targeted by nanoparticles. For this reason, a comprehensive evaluation of renal nanotoxicity is urgently needed as kidneys are particularly susceptible to xenobiotics and renal excretion is an expected and possible elimination route of nanoparticles in living organisms. On one hand, summarizing the findings of in vitro and in vivo studies that have investigated the adverse effects of nanoparticles on the kidney, this review intends to provide a thorough insight into the nephrotoxicity of these substances. The evaluation of the in vitro studies revealed that different types of nanoparticles (carbon, metal and/or silica nanoparticles) are able to exert significant cytotoxic effects (i.e., decreased cell viability, induction of oxidative stress, mitochondrial or cytoskeleton dysfunction and cell membrane and DNA damage). On the other hand, in vivo studies demonstrated that nanoparticles exhibited an important nephrotoxic potential both at tubular (i.e., degeneration of tubular epithelial cell, cellular fragments and proteinaceous liquid in tubule lumen, renal interstitial fibrosis) and glomerular level (i.e., swollen glomeruli, changes in Bowman’s space and proliferation of mesangial cells). Although the data currently available indicate that nanoparticles may adversely impact the renal system, further studies are needed in order to clarify all the potential molecular mechanisms of nephrotoxicity induced by these xenobiotics, in particular at glomerular level.     

Adverse reactions to β-lactam antimicrobials

INTRODUCTION: Beta-lactam antibiotics are among the most clinically useful antimicrobials used in medicine. Unfortunately, adverse events related to their use remain poorly understood by many clinicians and, in particular, the misdiagnosis of β-lactam allergy and misunderstanding of crossreactivity among members of the β-lactam antibiotics may effectively eliminate a whole class of antimicrobials from use and require the use of broader spectrum agents with less well-established safety profiles. AREAS COVERED: This review describes the range, diagnosis and management of adverse events associated with β-lactam antimicrobials, particularly focusing on recognition, diagnosis and management of true allergy and risk of cross-sensitivity between β-lactam antibiotics. A literature review was undertaken using PubMed, focusing primarily on literature published in the past 10 years relating to β-lactam adverse events and allergy. EXPERT OPINION: Beta-lactams are generally safe drugs and serious adverse events are rare and allergy is overdiagnosed. Accurate diagnosis can usually be achieved through careful history and in some instances skin or in vitro testing is required. Even among individuals with true immediate-type allergy to penicillin, most cephalosporins are readily tolerated and desensitization is usually an option in cases where no alternate antimicrobials are available. Other allergic reactions (Type II, III and IV) are rare and avoidance of the culprit agent is generally recommended. Nonallergic or morbilliform rashes are generally not allergic in nature and should not prompt drug or class avoidance. Other adverse events are frequently dose-related and can be avoided by appropriate dosing and consideration of renal function.     

Systematic review: Proton pump inhibitor-associated acute interstitial nephritis

BACKGROUND: A number of recent case reports and case series suggest that proton pump inhibitors may cause acute interstitial nephritis. AIM: To establish the nature of the relationship (cause or association) between proton pump inhibitor use and development of interstitial nephritis. METHODS: Data collection: Two researchers independently searched electronic databases (MEDLINE, EMBASE, GOOGLE, LILACS, COCHRANE) for articles from 1970 to 2006, including all study designs, populations and languages. Two independent reviewers assessed study quality and collected the data. Selection criteria: absence of baseline renal failure, development of interstitial nephritis after proton pump inhibitor exposure, nephritis confirmed by creatinine plus either renal biopsy or recurrence upon reinitiating proton pump inhibitor. RESULTS: Sixty four cases (60% females, mean age 78 years) of proton pump inhibitor-associated interstitial nephritis were found, 60 included in this review (59 confirmed by renal biopsy, one by recurrence upon reinitiating proton pump inhibitor). The most common symptoms were non-specific. The mean proton pump inhibitor treatment duration before diagnosing nephritis was 13 weeks, average recovery time was 35.5 weeks, one patient required permanent dialysis, there were no deaths. CONCLUSION: Proton pump inhibitor-related interstitial nephritis is rare, idiosyncratic and difficult to predict. It requires a high level of clinical suspicion. While there is not sufficient evidence to establish a causal relationship with certainty, there does appear to be a low-prevalence association.     

Protective effects of oral arabic gum administration on gentamicin-induced nephrotoxicity in rats.

Arabic gum (AG) is a complex polysaccharide used as suspending agent. It has been widely used by eastern folk medicine practitioners as a restorative agent and is thought to be an excellent curative for renal failure patients. We therefore tested these folkloric claims using a rat model of gentamicin (GM)-induced nephrotoxicity. AG (7.5g 100ml(-1), in drinking water) was administered orally for 8 days concurrently with GM (80mgkg(-1) per day, i.p.). Estimation of urine volume, serum creatinine and urea concentrations, kidney tissue malondialdehyde (MDA) contents and glutathione (GSH) were carried out after the last dose of GM. Kidneys were also examined for histological changes. GM caused a marked nephrotoxicity as evidenced by significant increases in urine volume (295%), serum creatinine (318%) and urea (258%) and a significant decrease in creatinine clearance (Ccr) (26%). Treatment with AG protected the rats from GM-induced nephrotoxicity as evident by normalisation of these parameters. In addition there was about 187% increase in kidney tissue MDA contents above the control with GM treatment. AG totally prevented the GM-induced rise in kidney tissue contents of MDA. Kidney histology of the tissue from GM-treated rats showed necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis. Whereas it was very much comparable to control when AG was co-administered with GM. In conclusion, AG protected the rats from GM-induced nephrotoxicity, possibly, at least in part through inhibition of the production of oxygen free radicals that cause lipid peroxidation.     

Autologous immune complex nephritis associated with sickle cell trait: diagnosis of the haemoglobinopathy after renal structural and immunological studies.

A renal tubular epithelial antigen (RTE)--anti-RTE autologous immune complex nephritis associated with sickle cell anaemia (SS) has been reported, but immune complex nephritis has never been described in patients with sickle cell trait (SA). During investigation of a child with "asymptomatic proteinuria" cryoprecipitable complexes of RTE-anti-RTE were detected in the serum and granular deposits of RTE, immunoglobulins, and complement localised on the glomerular basement membranes. Morphological and ultrastructural studies showed increased mesangial matrix, sickled red blood cells in the glomeruli and vessels, and tubular and interstitial abnormalities. These findings prompted haemoglobin electrophoretic studies, which showed previously undiagnosed haemoglobin SA in this patient and her family. These observations suggest that nephritis mediated by similar immunopathogenic mechanisms may be associated with SS and SA haemoglobinopathy. Under some conditions patients with sickle cell trait may experience haemodynamic and oxygenation abnormalities, which may be aetiological factors in the immune complex nephritis associated with SS disease.     

质子泵抑制剂致肾脏不良反应研究进展

随着质子泵抑制剂在临床的广泛应用,近年来质子泵抑制剂致急性间质性肾炎和慢性肾脏病的不良反应报道也越来越多,引起了专家的广泛关注。本文主要对质子泵抑制剂致肾脏不良反应的研究进展进行综述。从案例报道和病例回顾角度总结了近年来质子泵抑制剂致肾脏不良反应的临床特点、发病率、发病机制及治疗等,为临床安全用药提供依据。