Drug-induced Renal Dysfunction Research Articles

Efficacy of S-Flurbiprofen Plaster for Analgesia Following Total Hip Arthroplasty.

S-flurbiprofen (SFP) plaster, a non-steroidal anti-inflammatory drug preparation that penetrates effectively into deep tissue, is currently used as a conservative treatment for osteoarthritis. We investigated the analgesic and adverse effects of SFP plaster after total hip arthroplasty (THA). A retrospective comparative study identified 100 patients who underwent primary THA in our department. Group A consisted of 50 patients who received the selective cyclooxygenase-2 inhibitor celecoxib for 14 days after surgery, while Group B consisted of 50 patients who received SFP plaster for 14 days after surgery. We noted the numerical rating pain intensity scale (NRS) score, body temperature, and adverse effects of the analgesics. Groups A and B showed no significant difference in NRS scores (p > 0.05). The body temperature was significantly higher in Group B than in Group A on days one, two, three, and five (p < 0.01). In Group A, two patients (4%) showed drug-induced renal dysfunction, and one patient (2%) showed gastrointestinal disturbance. Patients in Group B showed no systemic or local adverse effects. The application of SFP plaster after THA provided an analgesic effect similar to that obtained with oral celecoxib without causing obvious side effects. Applying an SFP plaster may be an effective solution for postoperative analgesia.

An exploratory pharmacogenetic screening of SLC22A6, SLC22A8, ABCC4 and ABCC10 genes in a cohort of Ghanaian HBV patients

BackgroundOrganic anion transporters and efflux transporters are involved in the metabolism of drugs such as tenofovir disoproxil fumarate (TDF). Given the important role of organic anions and efflux transporters in drug disposition, genetic variations lead to interindividual differences in drug response. Variations in the SLC and ABC transporters have been associated with drug-induced renal dysfunction. Looking at the prevalence of HBV infection in our population and the use of drugs such as TDF in managing this condition, this study aimed to undertake an exploratory analysis of genetic variation in renal transporters SLC22A6, SLC22A8, ABCC10 and ABCC4 in a Ghanaian HBV infected cohort.MethodsWe genotyped 160 HBV infected patients for SNPs in SLC22A6 (rs12293966, rs4149170, rs6591722, rs955434), SLC22A8 (rs11568487), ABCC10 (rs700008, rs831311) and ABCC4 (rs9282570) genes. Clinicodemographic data was taken, and glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Genotyping was undertaken using Iplex gold SNP genotyping protocol on the Agena MassARRAY® system. Statistical analysis was undertaken using packages in Stata SE (v17) and GraphPad prism. Hardy–Weinberg equilibrium, haplotype inference, and linkage disequilibrium (LD) were evaluated using web-based tools LDlink and Shesis.ResultsThe average eGFR was 79.78 ± 33.08 mL/min/1.73 m2 with 31% classified as stage 1 with normal or high GFR (eGFR > 90 mL/min/1.73 m2) and 45% with stage 2 CKD (> 60–89.99 mL/min/1.73 m2). All variants were in HWE except rs4149170, rs9282570 and rs700008 where p < 0.05. Strong LD was observed in the variants rs6591722, rs4149170, rs12293966, rs955434 and rs11568487. There was significant association between rs12293966 and eGFR stage under crude dominant inheritance model (OR 0.27, 95% CI 0.08–0.81; p = 0.019). Under crude model (OR 0.21, 95% CI 0.07–0.66; p = 0.008), adjusted model 1 (OR 76, 95% CI 0.39–7.89; p = 0.014) and adjusted model 2 (OR 0.30, 95% CI 0.12–0.78; p = 0.013) there was significant association observed between rs12293966 and eGFR stage in a codominant inheritance.ConclusionThe associations observed in this study point to the need for further evaluation with the population of HBV patients on TDF treatment in addition to other factors that would lead to unfavorable outcomes. This exploratory finding may require confirmation in a larger cohort with proper phenotyping to investigate the exact pharmacogenetic mechanisms.

Drug-induced renal dysfunction due to antibiotics during treatment of spinal infections

Drug-induced renal dysfunction due to antibiotics during treatment of spinal infections

Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats.

The kidney normally functions to maintain hemodynamic homeostasis and is a major site of damage caused by drug toxicity. Drug-induced nephrotoxicity is estimated to contribute to 19- 25% of all clinical cases of acute kidney injury (AKI) in critically ill patients. AKI detection has historically relied on metrics such as serum creatinine (sCr) or blood urea nitrogen (BUN) which are demonstrably inadequate in full assessment of nephrotoxicity in the early phase of renal dysfunction. Currently, there is no robust diagnostic method to accurately detect hemodynamic alteration in the early phase of AKI while such alterations might actually precede the rise in serum biomarker levels. Such early detection can help clinicians make an accurate diagnosis and help in in decision making for therapeutic strategy. Rats were treated with Cisplatin to induce AKI. Nephrotoxicity was assessed for six days using high-frequency sonography, sCr measurement and upon histopathology of kidney. Hemodynamic evaluation using 2D and Color-Doppler images were used to serially study nephrotoxicity in rats, using the sonography. Our data showed successful drug-induced kidney injury in adult rats by histological examination. Color-Doppler based sonographic assessment of AKI indicated that resistive-index (RI) and pulsatile-index (PI) were increased in the treatment group; and peak-systolic velocity (mm/s), end-diastolic velocity (mm/s) and velocity-time integral (VTI, mm) were decreased in renal arteries in the same group. Importantly, these hemodynamic changes evaluated by sonography preceded the rise of sCr levels. Sonography-based indices such as RI or PI can thus be useful predictive markers of declining renal function in rodents. From our sonography-based observations in the kidneys of rats that underwent AKI, we showed that these noninvasive hemodynamic measurements may consider as an accurate, sensitive and robust method in detecting early stage kidney dysfunction. This study also underscores the importance of ethical issues associated with animal use in research.

Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats

The kidney normally functions to maintain hemodynamic homeostasis and is a major site of damage caused by drug toxicity. Drug-induced nephrotoxicity is estimated to contribute to 19- 25% of all clinical cases of acute kidney injury (AKI) in critically ill patients. AKI detection has historically relied on metrics such as serum creatinine (sCr) or blood urea nitrogen (BUN) which are demonstrably inadequate in full assessment of nephrotoxicity in the early phase of renal dysfunction. Currently, there is no robust diagnostic method to accurately detect hemodynamic alteration in the early phase of AKI while such alterations might actually precede the rise in serum biomarker levels. Such early detection can help clinicians make an accurate diagnosis and help in in decision making for therapeutic strategy. Rats were treated with Cisplatin to induce AKI. Nephrotoxicity was assessed for six days using high-frequency sonography, sCr measurement and upon histopathology of kidney. Hemodynamic evaluation using 2D and Color-Doppler images were used to serially study nephrotoxicity in rats, using the sonography. Our data showed successful drug-induced kidney injury in adult rats by histological examination. Color-Doppler based sonographic assessment of AKI indicated that resistive-index (RI) and pulsatile-index (PI) were increased in the treatment group; and peak-systolic velocity (mm/s), end-diastolic velocity (mm/s) and velocity-time integral (VTI, mm) were decreased in renal arteries in the same group. Importantly, these hemodynamic changes evaluated by sonography preceded the rise of sCr levels. Sonography-based indices such as RI or PI can thus be useful predictive markers of declining renal function in rodents. From our sonography-based observations in the kidneys of rats that underwent AKI, we showed that these noninvasive hemodynamic measurements may consider as an accurate, sensitive and robust method in detecting early stage kidney dysfunction. This study also underscores the importance of ethical issues associated with animal use in research.

Perioperative Management and Outcomes of Patients Treated With Antithrombotics Submitted To Elective Surgery

August 2015 e33 analyser (Roche) respectively. Creatinine clearance was calculated using the Cockcroft-Gault equation. The Research Ethics Committee approved this study and subjects signed consent forms. Results: Serum netrin-1 levels were reduced following aspirin treatment (66.06 ± 22.98 pg/mL versus 79.79 ± 34.91 pg/mL at baseline; P = 0.0022). There was a linear association between the percentage change in netrin-1 and level of serum salicylate (r = 0.413, P = .0013). TXB2 levels fell in all subjects post-treatment, confirming adherence to treatment (32.99 ± 18.35 ng/mmol creatinine versus 143.7 ± 54.25 ng/mmol creatinine at baseline; P < 0.0001). Serum ICAM-1 and E-selectin levels were not modified by treatment. Creatinine clearance decreased following aspirin (103.2 ± 26.13 mL/min versus 110.5 ± 26.95 mL/min at baseline; P = 0.0011). Conclusion: This study demonstrates that serum netrin-1 is reduced following treatment with aspirin. The TXB2 measurements show effective platelet inhibition in the whole population. We observed no change in ICAM-1 or E-selectin levels suggestive of an effect on the vascular endothelial function. Netrin-1 is a known biomarker of renal impairment. We propose that the reduction in netrin-1 is secondary to drug-induced renal dysfunction, as evidenced by a decrease in creatinine clearance.

PP.07.13

Objective: Pro-inflammatory stimuli and pro-atherogenic factors are known to reduce the level of endothelial-derived netrin-1, a secreted laminin-like protein that attenuates recruitment of circulating monocytes within atherosclerotic plaques. This study investigated the effect of aspirin, routinely used for the prevention of cardiovascular disease, on serum netrin-1 levels in healthy subjects. Design and method: Serum netrin-1 was measured using an enzyme-linked immunosorbent assay (ELISA) in samples collected from 60 subjects before and after 28 days of treatment with 300 mg aspirin daily. ELISAs were performed to assess serum levels of intercellular adhesion molecule-1 (ICAM-1), E-selectin, and urinary 11-dehdyro-thromboxane B2 levels (TXB2). Serum creatinine and salicylate levels were measured using the creatininase enzymatic method on a Roche C8000 analyser and a Cobas Fara automated analyser (Roche) respectively. Creatinine clearance was calculated using the Cockcroft-Gault equation. The Research Ethics Committee approved this study and subjects signed consent forms. Results: Serum netrin-1 levels were reduced following aspirin treatment (66.06 ± 22.98pg/ml versus 79.79 ± 34.91pg/ml at baseline; p = 0.0022). There was a linear association between the percentage change in netrin-1 and level of serum salicylate (r2 = 0.413, p = 0.0013). TXB2 levels fell in all subjects post-treatment, confirming adherence to treatment (32.99 ± 18.35ng/mmol creatinine versus 143.7 ± 54.25ng/mmol creatinine at baseline; p < 0.0001). Serum ICAM-1 and E-selectin levels were not modified by treatment. Creatinine clearance decreased following aspirin (103.2 ± 26.13 ml/min versus 110.5 ± 26.95 ml/min at baseline; p = 0.0011). Conclusions: This study demonstrates that serum netrin-1 is reduced following treatment with aspirin. The TXB2 measurements show effective platelet inhibition in the whole population. We observed no change in ICAM-1 or E-selectin levels suggestive of an effect on the vascular endothelial function. Netrin-1 is a known biomarker of renal impairment. We propose that the reduction in netrin-1 is secondary to drug-induced renal dysfunction, as evidenced by a decrease in creatinine clearance.

Contrast between innovator drug- and generic drug-induced renal dysfunction on coronary angiography (CONTRAST study)

Contrast-induced nephropathy (CIN) has gained increasing attention in clinical practice, particularly during coronary angiography (CAG). However, some "bioequivalent" generic (GE) drugs are less effective than the innovator (IN) drug. Therefore, the aim of this study was to compare contrast media (IN drug)-induced renal dysfunction with contrast media (GE drug)-induced dysfunction. We enrolled 44 patients who underwent elective CAG or percutaneous coronary intervention (PCI) and randomly divided them into two groups that received contrast media (Iohexol, nonionic and low-osmolality contrast agent) containing either IN drug (Omnipaque) or GE drug (Iopaque). Blood and urine sampling were performed before and after (24 and 48 h) CAG or PCI. Biochemical parameters in blood (serum creatinine, cystatin C, high-sensitivity C-reactive protein, and pentraxin-3) and urine (urinary albumin/Cr and liver-type fatty acid binding protein/Cr) were measured. There were no significant differences in the biochemical parameters at baseline between the groups. In addition, there were no differences in changes in biochemical parameters in blood and urine before and after CAG or PCI between the groups, although one patient in the GE group had CIN. The degree of contrast in Iopaque-induced renal dysfunction was comparable with that in Omnipaque-induced dysfunction.

Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report

We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi’s syndrome.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249

Toxicité rénale des médicaments

Drug-induced renal dysfunction is frequent in clinical practice. Outcomes may be severe, with increased morbidity and mortality. Kidneys are particularly vulnerable to drug toxicity, especially since they are highly vascularized, thus receiving about 25% of cardiac output. Furthermore, interstitial accumulation of toxic agents in papilla and the medulla often occurs due to the existence of a corticomedullary osmotic gradient. Moreover, the key role played by the renal tubule in the reabsorption processes of a number of endogenous and exogenous substances further increases the exposure of the kidney to high concentrations of potentially toxic agents, both in the tubular lumen and cells. As a result, drugs may be toxic to all of the four structures of the kidney: glomerulus, tubule, interstitium, and blood vessels. This chapter reviews the main mechanisms of drug-induced renal toxicity and then focuses on the nephrotoxicity of anti-infectious drugs: antibacterial drugs, antifungal agents, antimalariae, and antiviral drugs. NSAID and anticancer drugs renal toxicity are detailed elsewhere in this textbook. Methods used to prevent drug-induced nephrotoxicity, when known, are detailed. Risk factors are also listed, such as high-risk populations, identification and elimination of risk factors, and drug dosage adjustment in patients with baseline abnormal renal function.

The epidemiology of drug-induced disorders: the kidney

The epidemiology of drug-induced renal disorders is a complex topic. Drug-associated nephrotoxicity accounts for 18 – 27% of all acute kidney injury cases in US hospitals. Medications can affect all aspects of the kidney, and drugs that are associated with renal dysfunction are used commonly in clinical practice. The article reviews six major mechanisms of drug-induced renal dysfunction as well as lists the major medications involved. NSAIDs, aminoglycosides, amphotericin B and calcineurin inhibitors are just some examples of drugs that contribute to renal dysfunction. The medical community must be aware of patient risk factors for nephrotoxicity, as well as the drug's inherent nephrotoxic potential, when prescribing and administering medications.

Role of Tissue Kallikrein in Prevention and Recovery of Gentamicin-Induced Renal Injury

Gentamicin is an aminoglycoside antibiotic that induces severe nephrotoxicity and acute renal failure. In the current project, we investigated the protective effects of tissue kallikrein (TK) protein administration (1 mug/h via osmotic minipumps) on kidney damage, apoptosis, and inflammation both during and after a 10-day regimen of gentamicin (80 mg/kg body weight/day sc) in Sprague-Dawley rats. TK infusion during gentamicin treatment significantly attenuated drug-induced renal dysfunction, cortical damage, and apoptosis. Moreover, TK reduced inflammatory cell accumulation in conjunction with diminished superoxide production and decreased expression of tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1. The protective effects of TK were blocked by coinfusion of icatibant (1.3 mug/h), indicating a kinin B2 receptor-mediated signaling event. After cessation of gentamicin treatment, TK infusion for 2 weeks completely restored kidney histology and morphology comparable to that of saline-treated animals. Furthermore, TK reduced gentamicin-induced renal dysfunction and fibrosis as evidenced by decreased myofibroblast and collagen accumulation in the kidney. In vitro, gentamicin increased the number of apoptotic cells and caspase-3 activity, but decreased phosphorylation of the prosurvival kinase Akt, in immortalized rat proximal tubular cells; addition of TK and bradykinin prevented these effects. In conclusion, our findings indicate that kallikrein/kinin prevents and promotes recovery of gentamicin-induced renal injury by inhibiting apoptosis, inflammatory cell recruitment, and fibrotic lesions through suppression of oxidative stress and proinflammatory mediator expression in animals during and after gentamicin treatment.

Toxicité rénale des médicaments

Summary Drug-induced renal dysfunction is frequent in clinical practice. Outcomes may be severe, with increased morbidity and mortality. Kidneys are particularly vulnerable to drug toxicity, especially since they are highly vascularized, thus receiving about 25% of cardiac output. Furthermore, interstitial accumulation of toxic agents in papilla and the medulla often occurs due to the existence of a corticomedullary osmotic gradient. Moreover, the key role played by the renal tubule in the reabsorption processes of a number of endogenous and exogenous substances further increases the exposure of the kidney to high concentrations of

The hepatic and intestinal metabolic activities of P450 in rats with surgery- and drug-induced renal dysfunction.

The hepatic and intestinal metabolic activities of P450 were evaluated in rats with surgery- and drug-induced renal dysfunction. Renal failure was induced by five-sixths nephrectomy (NR), bilateral ureter ligation (BUL), the intramuscular injection of glycerol (GL), and the intraperitoneal injection of cisplatin (CDDP). Phenytoin 4-hydroxylation, debrisoquine 4-hydroxylation, and testosterone 6beta-hydroxylation were estimated to evaluate the metabolic activities of cytochrome P450 (CYP) 2C, 2D, and 3A, respectively. The hepatic CYP3A metabolic activities were decreased by 65.9% and 60.2% in NR and GL rats, respectively. The hepatic CYP2C metabolic activity was decreased by 48.8% in CDDP rats. No alteration in hepatic drug-metabolizing activities was observed in BUL rats. On the other hand, the intestinal CYP3A metabolic activity was weakly increased in GL rats but not significantly altered in NR, CDDP, and BUL rats. This study suggested (a) that only selected P450 metabolic activity in the liver is decreased in renal failure, (b) that extent of the decrease in hepatic metabolic activities of P450 is dependent on the etiology of renal failure, and (c) that alteration of CYP3A metabolic activity in the intestine is not always correlated with that in the liver.

Analysis of urinary donor-derived DNA in renal transplant recipients with acute rejection.

In renal transplantation we usually diagnose an acute rejection by based on the results of a needle biopsy; however, this takes time and findings in some cases are not definite. We analysed the urine of renal recipients for the presence of donor DNA in an attempt to establish a diagnostic means of acute rejection. Sixty-four renal transplant recipients were examined. Thirty-seven patients had no trouble after transplantation and 22 patients developed acute rejection, diagnosed based on serum creatinine levels and/or needle biopsy findings of the graft. Five patients had drug-induced renal dysfunction. In female recipients with a male graft we examined urine for the presence of Y-chromosome (SRY and DYZ-1) and in recipients receiving a HLA mismatched graft we investigated the HLA-DR gene (DRB1) by the polymerase chain reaction (PCR) method. Among female recipients with a male graft there were 14 patients with stable renal function and SRY and DYZ-1 on Y-chromosome were negative in 13 (93%) and positive in one, whereas SRY and DYZ-1 of urine were positive in the four female patients with acute rejection and these DNA fragments disappeared in three after rejection therapy. One patient was subjected to haemodialysis. Among 23 recipients of a graft from HLA mismatched donors with stable renal function, DRB1 was negative in 21(91%). Among 18 patients with acute rejection DRB1 was positive in 16 (93%) and negative in two. These DNA fragments disappeared in 13 patients after rejection therapy. In all patients with drug-induced renal dysfunction donor-derived DNA was negative. Presence of donor-specific DNA in the urine of the recipient is associated strongly with acute rejection and analysis of DNA derived from donor cells in urine might be an effective and accurate method for the diagnosis of acute rejection of a renal transplant.

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.

Use of anti-CD25 monoclonal antibody in combination with rapamycin to eliminate cyclosporine treatment during the induction phase of immunosuppression.

Cyclosporine and tacrolimus are associated with drug-induced renal dysfunction that may exacerbate recovery from ischemic injuries during the first month posttransplant. We sought to use anti-CD25 (anti-interleukin-2 receptor) monoclonal antibodies in combination with sirolimus (rapamycin) to avoid cyclosporine therapy during the early postoperative period in six renal transplant recipients deemed to be at high risk for delayed graft function. Six consecutive patients deemed to be at high risk for delayed graft function were treated with rapamycin (2-12 mg/day), anti-CD25 monoclonal antibodies, and steroids, withholding inception of cyclosporine therapy until the serum creatinine fell below 3.0 mg/dl. During the first 2 months posttransplant, none of the patients displayed clinical or histopathological evidence of acute allograft rejection episodes, cytokine release syndrome, or hypersensitivity reactions. None of the patients received even empiric bolus or high-dose steroid therapy for a presumed rejection episode. All patients recovered renal graft function within 8 weeks posttransplant. To date all patients have stable renal graft function. Five patients have serum creatinine levels between 0.8 to 1.3 mg/dl at 6 months and the other patient has a serum creatinine level of 1.7 mg/dl at present follow-up of 2 months posttransplant. During the early posttransplant period anti-CD25 monoclonal antibodies combined with rapamycin and steroids offer a promising baseline therapy to avoid cyclosporine exposure and facilitate recovery from ischemic/reperfusion injuries.

DRUG-INDUCED NEPHROTOXICITY

Drug-induced renal dysfunction is not an uncommon event, which can cause significant morbidity and can be easily overlooked. Many medications can lead to renal dysfunction through various mechanisms. The most common medications or classes of medications along with their clinical presentations are discussed in this article. As can be noted, many drugs can cause nephropathy in more than one way. Because it is difficult to discuss nephrotoxicities of every reported medication, Tables 1, 2, and 3 are provided; although these tables are by no means comprehensive, they may serve as further reference. This article is intended to provide a broad overview of the spectrum of presentation associated with drug-induced nephrotoxicity to guide the clinician to familiarity with this entity.

Effects of cyclosporine on renal function in psoriasis patients

Several prospective studies have documented the effectiveness of oral cyclosporine in the treatment of psoriasis. Despite this, the use of cyclosporine has heen limited because of concern about the possibility of drug-induced renal dysfunction. We review the effects of cyclosporine on renal function.

Phase I — Preliminary phase II trial of iproplatin, a cisplatin analogue

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.