Drug-induced Acute Renal Failure Research Articles

The NLRP3 Inflammasome Is a Major Cause of Acute Renal Failure Induced by Polypeptide Antibiotics.

Drug-induced acute renal failure (ARF) is a public health concern that hinders optimal drug therapy. However, pathological mechanisms of drug-induced ARF remain to be elucidated. Here, we show that a pathological process of drug-induced ARF is mediated by proinflammatory cross-talk between kidney tubular cells and macrophages. Both polymyxin B and colistin, polypeptide antibiotics, frequently cause ARF, stimulated the ERK and NF-κB pathways in kidney tubular cells, and thereby upregulated M-CSF and MCP-1, leading to infiltration of macrophages into the kidneys. Thereafter, the kidney-infiltrated macrophages were exposed to polypeptide antibiotics, which initiated activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Interestingly, blockade of the NLRP3 activation clearly ameliorated the pathology of ARF induced by polypeptide antibiotics, suggesting that a combination of the distinct cellular responses to polypeptide antibiotics in kidney tubular cells and macrophages plays a key role in the pathogenesis of colistin-induced ARF. Thus, our results provide a concrete example of how drugs initiate ARF, which may give insight into the underlying pathological process of drug-induced ARF.

A Case Report of Drug-Induced Acute Renal Failure Treated with Herbal Medicine

A Case Report of Drug-Induced Acute Renal Failure Treated with Herbal Medicine

Nephroprotective activity of Bilvādi agada in gentamicin induced nephrotoxicity in male Wistar rats.

Background:Gentamicin (GM) nephrotoxicity accounts for 10–30% of the acute renal failure (ARF) among drug-induced ARF. In Ayurveda such side effects are considered as the poisonous effects of low potent poisons called gara viṣa. Bilvādi agada (BA), a classical formulation is indicated in gara viṣa and most of its ingredients have proven for their nephroprotective activity.Aim:The aim was to evaluate the effect of BA in GM-induced nephrotoxicity in male Wistar rats.Materials and Methods:BA, GM, normal saline were procured from standard companies.Settings and Designs:Eighteen male Wistar rats were randomly divided into three groups, viz. Control group which received normal saline intraperitoneal (i.p.) daily for 8 days; toxic group received GM 80 mg/kg/day i.p. for 8 days, and trial group received both GM 80 mg/kg/day i.p. and BA 216 mg/each rat weighing ~200 g orally 1 h after administration of GM.Statistics:All the values were expressed as mean ± standard error and data were analyzed by applying one-way analysis of variance followed by Dunnett's test for multiple comparison.Results:BA treated group showed a significant change (P < 0.05) in levels of serum creatinine, urine creatinine, and urine potassium. There was no significant change (P > 0.05) seen in serum potassium, sodium, chloride, calcium and phosphorus and urine sodium, chloride in all three groups. Glomerular congestion, interstitial edema, tubular necrosis, interstitial hemorrhage was reduced in BA treated group. The results of this study indicate that BA reduces GM-induced nephrotoxicity and it may be due to anti-inflammatory, immunomodulatory, diuretic and anti-oxidant properties of drugs. Further studies are necessary to explore the exact mechanism of BA in nephroprotection.

Limitations of Conventional Parameters and Role of Urinary Protein Biomarkers in the Determination of Drug Induced Acute Kidney Injury in Very Early Stage

Drug-induced Acute Kidney Injury (AKI) constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice. Drug-induced acute renal failure (ARF) accounted for 20% of all ARF in an Indian study. The incidence and prevalence of chronic kidney disease (CKD) has dramatically increasing worldwide. Progression of AKI from mild or moderate to end stage may be prevented by selecting potentially effective therapies, if it is detected in very early stage. But early detection of AKI is often difficult due to paucity of early predictive noninvasive biomarkers. Development of omics technology has led to the identification of several urinary protein biomarkers and transcriptional biomarkers, which enable earlier detection of kidney injury. Urinary protein biomarkers have great benefit due to the easy or non-invasive availability of urine and many showing good predictive power. Several urinary protein biomarkers have been identified and have demonstrated superiority in detecting kidney injury in comparison to conventional parameters like serum creatinine (SCr), blood urea nitrogen (BUN) etc. These promising experimental biomarker of kidney damage require further confirmation of its use in routine clinical use.

Drug-induced nephrotoxicity

Drug-induced nephrotoxicity is an extremely common condition and is responsible for a variety of pathological effects on the kidneys. Drug-induced acute renal failure (ARF) accounted for 20% of all ARF cases. Drugs showed to cause nephrotoxicity exert their toxic effects by one or more common pathogenic mechanisms. Although it is impossible to present all the drugs causing the nephrotoxicity, this article will summarize the mechanism of injury associated with particular common medications, discuss clinical presentations, renal markers, and evaluate strategies that prevent or minimize renal injury. Drug-induced nephrotoxicity tends to be more common among certain patients and in specific clinical situations. Therefore, successful prevention requires knowledge of pathogenic mechanisms of renal injury, patient-related risk factors, drug-related risk factors, and preemptive measures, coupled with vigilance and early intervention. General preventive measures include using alternative non-nephrotoxic drugs whenever possible; correcting risk factors, if possible; assessing baseline renal function before initiation of therapy, followed by adjusting the dosage; monitoring renal function and vital signs during therapy, and avoiding nephrotoxic drug combinations. Surprisingly, little information is available to guide us with respect to avoiding complications in critical illness; therefore, it is necessary to follow the guidelines.

Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway

Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.

Successful mitral valve replacement for infective endocarditis in a patient with liver cirrhosis and acute renal failure

Patients with liver cirrhosis and acute renal failure are considered high risk for open cardiac surgery under cardiopulmonary bypass. A 58-year-old female patient with severe mitral regurgitation due to bacterial endocarditis associated with moderate liver cirrhosis was admitted to our clinic for the treatment of acute pulmonary edema. Preoperative hepatic function state was estimated as Child- Pugh class B. Intravenous gentamicin and vancomycin were initiated for the treatment of acute infective endocarditis. During antimicrobial therapy, the patient developed druginduced acute renal failure. We immediately performed mitral valve replacement under cardiopulmonary bypass due to progressive heart failure. The postoperative course was problem-free and the patient was discharged. With careful preoperative preparation and good perioperative management, open heart surgery can be performed with a positive outcome in acute infective endocarditis patients with moderate liver cirrhosis and acute renal failure.

A Case Report of Acute Renal Failure Associated With Bee Pollen Contained in Nutritional Supplements

We report a case of renal failure associated with the ingestion of bee pollen containing nutritional supplement. A 49-year-old male patient who had been ingesting a nutritional supplement for more than five months had breathing difficulties, anuria, exceptional weight gain (20 kg) due to systemic edema, and loss of appetite. A renal biopsy confirmed interstitial nephritis with the presence of eosinophils, which is suggestive of drug-induced acute renal failure. The nutritional supplement was ceased and hemodialysis begun. The patient's condition improved after several hemodialysis sessions, which were then stopped. Current information regarding the adverse effects of bee pollen is not very robust, therefore potential damage should be kept in mind before ingesting nutritional supplements in which it is contained. This report serves as an important reminder to the public as well as healthcare providers of the potential of renal failure related to nutritional supplements.

Analysis of drug-induced acute renal failure in Shanghai

To investigate the incidence and prognosis of drug-induced acute renal failure (ARF) in Shanghai. The registration forms of ARF patients admitted in 17 hospitals of and over the middle class in Shanghai from January 1, 2004 to December 31, 2006 were screened prospectively. The data, such as epidemiology, survival, mortality, and morbidity were analyzed. 347 of the 1200 ARF patients (28.9%), 224 males and 123 females, aged (58+/-20), suffered from drug-induced ARF. 51.0% of the 347 patients were older than 60. 60.2% of the drug-induced ARF in the non-surgical departments were community-acquired, while 55.7% of the drug-induced ARF in the surgical departments were hospital-acquired. Among the non-surgical departments, the incidence of hospital-acquired drug-induced ARF was the lowest in the department of nephrology (9.5%), while higher in the departments of hematology, cardiology, and neurology, and among the surgical departments, it was the lowest in department of renal surgery, while higher in the departments of liver transplantation, neurosurgery, and cardiovascular surgery. The most common complication was chronic kidney disease (CKD) (n=69, 19.9%), followed by cerebrovascular disease (n=59, 17.0%), diabetes mellitus (n=43, 12.4%), and hypertension (n=41, 11.8%). Renal biopsy showed acute tubular necrosis (18, 37.5%), acute interstitial nephritis (11, 22.9%), and acute infectious tubulo-interstitial nephritis (6, 12.5%). Antibiotics (47.8%) were the head causes of drug-induced ARF, especially aminoglycoside (17.0%) and cephalosporins (12.7%), followed by diuretics (22.2%) and radiocontrasts (13.3%). 22.5% of the drug-induced ARF patients had used two or more drugs. 119 patients (34.3%) needed renal replacement treatment. 100 of the 347 patients (28.8%) died. 188 of the surviving patients (54.2%) had their renal function recovered completely, the renal function of 42 of them (12.1%) was recovered partially, and 17 of then (4.9%) required dialysis when discharged. Drug-induced ARF is common with higher incidence in the patients with complications. Antibiotics, diuretic agents, and contrast medium are the main causes.

Serum magnesium in recovering acute renal failure

We studied the manifestations of hypomagnesemia in 50 patients with acute renal failure who had been admitted in our hospital over a period of ten months. All patients with serum creatine ≥ 2 mg/dL and normal baseline levels of serum calcium, magnesium, and potassium as well as normal ECG were included in the study. Patients with multi-organ failure, drug-induced acute renal failure, obstructive uropathy, and alcohol addiction were excluded. The mean age of our study population was 40 ± 15 years, 37 of the patients were male and 13 were female. Hypomagnesemia was observed in 31 patients out of 50 during the recovery period of acute renal failure with symptomatic hypomagnesemia being seen in 23 patients. Serum magnesium levels on the day of admission and during the recovery phase were 2.11 ± 0.38 mg/dL and 1.64 ± 0.41 mg/dL respectively. Paresthesia, irritability, agitation, dysartharia, vertigo, and associated hypokalemia and hypocalcemia were noted in symptomatic hypomagnesemic patients. Treatment of hypomagnesaemia and hypokalemia ameliorated the symptoms. We conclude that these abnormalities produce clinically significant manifestations in recovery phase of acute renal failure and clinicians should pay attention to these.

Acute renal failure in chronic kidney disease – clinical and pathological analysis of 104 cases

Acute renal failure in chronic kidney disease (A/C) constitutes an important part of acute renal failure (ARF), but until now there has been no research focusing on this entity. Clinical data were collected from all patients diagnosed as A/C by clinical materials and renal biopsy over a 12-year period (January 1990 - December 2001) in the renal department of a teaching hospital, and the incidence, etiology, pathological and clinical features of A/C, and factors predicting prognosis were studied. Altogether, 104 patients of A/C were identified, which accounted for 35.5% of biopsied acute renal failure cases during the same period. Drug-induced acute renal interstitial/tubular-interstitial disease, prerenal ARF and flare-up of lupus nephritis were the most common causes of ARF in A/C patients. More than one third of A/C were associated with drugs, which occurred more commonly in older patients. After an average hospitalization of 28.5 days, about 39 patients required dialysis, 23 patients became dialysis-independent. The mortality was 1.9%. Furthermore, serum creatinine (Scr) returned to normal level (< 133 micromol/l) in 46.2% of all patients; Scr decreased by 15%, yet not normal in 26.0%. Multivariate logistic regression analysis indicated that hypertension, requirement of dialysis therapy and high Scr level were independent predictors of poor renal outcome. A/C constitutes an important part of ARF, and drug-induced ARF is prominent in China. Because early diagnosis and correct treatment may obviously affect prognosis, enough attention should be paid to this entity.

Plasma Nitric Oxide Status in Patients with Drug-Induced Acute Renal Failure

Plasma Nitric Oxide Status in Patients with Drug-Induced Acute Renal Failure

Insuffisances rénales aiguës médicamenteuses

Drug-induced acute renal failure (ARF) is common. Many therapeutic agents may induce ARF and there are numerous mechanisms that cause drug-induced ARF. The mechanisms may act at the vascular, glomerular or tubular levels. Drug toxicity may be related to the effects of the treatment itself or caused by hypovolaemia or disturbances of intrarenal haemodynamics. During the course of ARF, diagnosis should systematically include consideration of drug-related precipitating or predisposing factors. Drug-induced ARF is an undesirable iatrogenic occurrence that is largely avoidable and which has a more favourable prognosis than ARF of different pathogenesis. Treatment of this type of ARF is based on prevention. Any drug that is potentially toxic to the kidney should be prescribed in strict accordance with the indications and contraindications of the therapy. Prescription must take into account drug interactions and constitutional susceptibility (pre-exciting chronic renal failure, cirrhosis, old age). Dosage must be adapted to the glomerular filtration rate as estimated by the formula of Cockcroft-Gault. Hypovolaemia must be prevented or corrected.

Telithromycin-induced acute interstitial nephritis: A first case report

Telithromycin, a ketolide antibiotic used for the treatment of community-acquired respiratory infections, is widely prescribed in primary care practice. Treatment-related adverse events are mainly of gastrointestinal origin and generally mild in intensity. The authors report the first case of telithromycin-induced severe acute interstitial nephritis. Practitioners should be aware of the possibility that telithromycin therapy could result in this form of drug-induced acute renal failure.

Acute Tubulo-Interstitial Nephritis Requiring Dialysis Associated with Intermittent Rifampicin Use: Case Report

Rifampicin is one of the most effective antibiotics used for the treatment of tuberculosis and severe staphylococcal infections. Intermittent administration of high doses of rifampicin has been associated with frequent adverse reactions, including hepatotoxicity and nephrotoxicity, sometimes resulting in acute renal failure. We describe a case of rifampicin-associated acute renal failure, with biopsy findings of tubulointerstitial nephritis; inflammatory cells were characterized by immunohistochemistry, which showed immunoreactivity for CD3 and CD5 (T lymphocytes) and for CD68 (macrophages). The patient presented with a very rapid systemic reaction to the offending drug and rapid deterioration of renal function, which required dialysis treatment. The response to rifampicin discontinuation was excellent: no further therapy was required, as renal function began to improve within several days and returned to normal values (serum creatinine 1.17 mg/dl) seven months after the onset of symptoms. When prescribing rifampicin the physician should investigate previous use of the drug, because re-exposure is a critical factor in predicting the possibility of drug-induced acute renal failure.

Drugs and the kidney in the elderly.

The high rates of drug-induced acute renal failure, worsening chronic renal dysfunction and systemic toxicity of renally excreted drugs in the elderly can be minimised by carefully assessing renal function, avoiding potentially nephrotoxic drugs as much as possible and closely monitoring drug concentrations and renal function when they must be used. The co-existence of impaired renal function, degenerative vascular disease or cardiac failure in the elderly substantially increases the risk of renal toxicity. When in doubt about potential nephrotoxicity or an increased risk of systemic toxicity from renally excreted drugs in the elderly, the practitioner should consult the numerous published guidelines.

Prevention and attenuation of acute renal failure.

Recent progress in our understanding of the pathogenetic processes involved in ischemic acute renal failure is considerable. Blockade of the production of endothelium-derived relaxing factor may markedly improve survival in patients with septic shock. Atrial natriuretic peptide and growth factors enhance renal recovery in animal models of acute renal failure, even when administered well after the ischemic insult. Aminoglycosides and radiocontrast agents are the most common causes of drug-induced acute renal failure. Once-daily administration of aminoglycosides is an effective treatment modality that may limit the occurrence of nephrotoxicity. Awareness of the patient's volume status has decreased the incidence of radiocontrast-induced acute renal failure. The new, expensive, nonionic, low-osmolar radiocontrast agents do not offer apparent benefits in patients with normal or slightly decreased renal function. However, use of such agents may decrease the incidence of radiocontrast-induced renal failure in diabetic patients with severe renal failure. The prognosis for patients with renal vasculitis has improved greatly in the past decade. The discovery of antibodies directed against antigenic targets in the cytoplasm of neutrophils has facilitated the diagnosis of renal vasculitides, has improved our knowledge of the pathogenesis of these diseases, and may guide rational treatment.

Aminoglycoside nephrotoxicity

The high incidence of associated nephrotoxicity represents an important concern in the use of aminoglycoside antibiotics, which have been implicated as one of the primary causes of drug-induced acute renal failure. Several factors, including the underlying health of the patient, criteria used to define nephrotoxicity, and the specific aminoglycoside administered, may contribute to the nephrotoxic potential of these agents. The development of aminoglycoside-induced nephrotoxicity is a complex problem. These drugs appear to be only minimally metabolized within the body and undergo nearly exclusive renal excretion, primarily by glomerular filtration. Ultimately, reabsorption and accumulation within the kidney results in proximal tubular cell damage; several possible mechanisms have been proposed, both for the development of such cell damage and for its subsequent role in the evolution of nephrotoxicity. The pathology and the clinical pattern of aminoglycoside-induced kidney damage have been extensively studied in animal models and in humans. Although the data often conflict, many of these studies have attempted to identify some of the factors associated with a higher risk for aminoglycoside nephrotoxicity. Of the factors generally agreed upon to influence risk, correction of volume depletion and diminished renal perfusion, as well as dose adjustment for level of renal function, have been identified as critical measures for prevention of renal damage by aminoglycosides. Recent studies have indicated that newer agents, such as third-generation cephalosporins and aztreonam, often may be as therapeutic and cost-effective as the aminoglycosides without the nephrotoxicity associated with the latter agents. Clearly, such a safe and effective alternative, if confirmed, would be preferable to aminoglycoside therapy in patients at high risk for nephrotoxicity.

Health impact of renal disease due to nephrotoxicity

Both acute and chronic renal failure are reported in the context of nephrotoxicity. This overview of some major nephrotoxins reflects both the magnitude and the cost of this preventable health problem. Aminoglycosides and other antibiotics, contrast media and nonsteroidal anti-inflammatory drugs are the best documented nephrotoxins related to acute renal failure. Analgesic nephropathy is the best known drug-induced chronic renal disease. The cost of renal failure due to nephrotoxicity is not easy to compute. Drug-induced acute renal failure costs more than 2750 ECU per patient, depending on whether dialysis is required or not, and chronic renal failure costs at least 128 000 000 ECU annually in the European Communities. Recent epidemiological evidence, however, indicates that the cost may be even higher.

Immunologically mediated drug-induced acute renal failure.

(1) AIN is the most frequent pattern of drug-induced immunologically mediated renal injury. A number of drugs may be responsible for AIN, namely methicillin and other penicillin derivatives, rifampicin, phenindione and sulfonamides. Particular clinical and pathological features often suggest an immune pathogenetic mechanism. IgG anti-TBM and IgE antibodies have been found in only a few cases and it is likely that antibody-mediated and cell-mediated injury may operate in the same patient. (2) Only few examples of drug-induced vasculitis and glomerulonephritis are known, and the pathophysiology of this kind of renal damage is poorly understood.