indinavir-sulfate and Renal-Insufficiency

Introduction of several classes of antiviral agents for the treatment of immunodeficiency virus has led to increased survival and improved quality of life for patients with HIV infection. Protease inhibitors have become the mainstays of current therapy in patient with AIDS. Renal intolerance of indinavir is a rare but important complication in HIV positive patients. The renal function of patients receiving indinavir should be closely monitored. Benign and asymptomatic crystalluria occurs in 4-13% of HIV positive patients. Several cases of acute renal failure, renal atrophy and interstitial nephritis have also been reported. A hydration protocol consisting of one to two liters of fluid should be initiated three hours after each indinavir dose. If significant renal insufficiency persists, temporary indinavir withdrawal or switching to another protease inhibitor should be considered.

Topics: Crystallization; HIV Protease Inhibitors; Humans; Indinavir; Nephritis; Renal Insufficiency; Urinary Calculi

The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors.. A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (<15). Logistic regression models were used to investigate factors associated with RI.. The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was<50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age >50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI) <22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for <1 year and OR=1.5: 1.2-2.0 for >1 year). Advanced RI (CC <60 mL/min) was associated with age >50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI <22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure >1 year (OR=2.3: 1.5-3.6).. This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.

Topics: Adenine; Adult; Anti-HIV Agents; Body Mass Index; CD4 Lymphocyte Count; Creatinine; Epidemiologic Methods; Female; France; HIV Infections; Humans; Hypertension; Indinavir; Kidney; Kidney Function Tests; Male; Middle Aged; Organophosphonates; Renal Insufficiency; Tenofovir

Treatment with indinavir (IDV), a protease inhibitor, is frequently associated with renal abnormalities. We determined the incidence of renal failure (creatinine clearance <80 mL min-1 1.73 (m(2))-1) in HIV patients treated with highly active antiretroviral therapy, including IDV, and investigated the possible mechanisms and risk factors of IDV nephrotoxicity. Thirty-six patients receiving IDV were followed for 3 years. All were assessed for age, body weight, duration of infection, duration of IDV treatment, sulfur-derivative use, total cholesterol, triglycerides, magnesium, sodium, potassium, creatinine, and urinalysis. We also determined renal function in terms of creatinine clearance, urine osmolality and fractional excretion of sodium, potassium, and water. Urinary nitrate (NO3) excretion was measured in 18 IDV-treated patients and compared with that of 8 patients treated with efavirenz, a drug without renal side effects. Sterile leukocyturia occurred in 80.5% of the IDV-treated patients. Creatinine clearance <80 mL min-1 1.73 (m(2))-1 was observed in 22 patients (61%) and was associated with low body weight and the use of sulfur-derivatives. These patients also had lower osmolality, lower urine volume and a higher fractional excretion of water compared to the normal renal function group. Urinary NO3 excretion was significantly lower in IDV-treated patients (809 +/- 181 microM NO3-/mg creatinine) than in efavirenz-treated patients (2247 +/- 648 microM NO3-/mg creatinine, P < 0.01). The lower NO3 excretion suggests that IDV decreases nitric oxide production.

Topics: Adult; Alkynes; Antiretroviral Therapy, Highly Active; Benzoxazines; Biomarkers; Creatinine; Cyclopropanes; Female; Glomerular Filtration Rate; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Function Tests; Male; Middle Aged; Nitrates; Nitrites; Oxazines; Prospective Studies; Renal Insufficiency; Reverse Transcriptase Inhibitors; Risk Factors

Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics.. The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well.. Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy.. A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Topics: Adult; Cohort Studies; Developing Countries; Female; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Kidney; Kidney Calculi; Leukocytosis; Male; Pain; Prevalence; Radiography; Renal Insufficiency; Thailand; Ultrasonography; Urologic Diseases

Risk factors associated with the occurrence of protease inhibitor (PI)-related severe and serious adverse drug reactions (SADRs) were analyzed in a prospective cohort of 1155 patients who initiated PI-containing therapy. During a total follow-up of 2037 patient-years, 169 SADRs were reported, yielding a rate of 8 incidents per 100 patient-years (95% confidence interval [CI], 6.8-8.6). The most frequent SADRs were elevated transaminase levels (in 49 events); renal colic (27); abnormal hematological findings (23); and metabolic (18), neuromuscular (7), pancreatic (6), cutaneous (6), cardiovascular (5), and psychiatric disorders (5). Among baseline characteristics, plasma human immunodeficiency virus RNA levels of >or=5 log(10) copies/mL (hazard ratio [HR], 1.5; 95% CI, 1.1-2.2), elevated aspartate aminotransferase levels (HR, 1.1 for each 20 IU of elevation; 95% CI, 1.1-1.2), creatinine clearance levels of <70 mL/min (HR, 2.1; 95% CI, 1.2-3.7), test results positive for hepatitis C virus antibodies or hepatitis B surface antigenemia (HR, 2.6; 95% CI, 1.8-3.7), and receipt of indinavir (HR, 1.7; 95% CI, 1.2-2.4) were independently predictive of a SADR. SADRs were frequent in the first 4 months after initiation of highly active antiretroviral therapy but continued to occur after that time period.

Topics: Adult; Colic; Female; Hepatitis, Viral, Human; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Indinavir; Kidney Diseases; Male; Probability; Prospective Studies; Renal Insufficiency; Risk Factors; Time Factors; Transaminases

We report the case of a 38-year-old male who developed renal insufficiency while on the protease inhibitor, indinavir. This patient had an increase in serum creatinine over a period of approximately one year, along with persistently abnormal urinalysis. A renal biopsy was performed and showed marked tubular crystal deposition. The indinavir was discontinued, and after two months the patient's serum creatinine and urinalysis returned to normal. To our knowledge this is the second case of indinavir associated nephropathy.

Topics: Adult; Biopsy; Clinical Trials, Phase I as Topic; Creatinine; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Glomerulus; Male; Renal Insufficiency

Topics: Adult; Anti-HIV Agents; Crystallization; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Renal Insufficiency; Stavudine

Topics: Abdominal Pain; Adult; Anti-HIV Agents; Dermatitis, Exfoliative; Fever; HIV Infections; Humans; Indinavir; Male; Renal Insufficiency