indinavir-sulfate and Kidney-Diseases

The introduction of potent combination antiretroviral therapy (ART) in the treatment of HIV infection has permitted reliable control of disease progression and has markedly improved survival among people with HIV. As a result, health care providers and patients have shifted clinical priorities; whereas once delaying opportunistic illness was a primary focus, increasing emphasis is now placed on preventative health, management of comorbid chronic disease and avoiding long-term toxicities of ART. Although renal disease is common in people with HIV, renal disease specifically due to ART remains relatively rare. Still, as the use of ART continues to increase, health care providers are likely to encounter this potentially serious complication with increasing frequency. Distinguishing ART-related nephrotoxicity from the myriad of other potential causes of renal disease in people with HIV is important in order to avoid unnecessary discontinuation of an appropriate ART regimen. This review focuses on the early recognition of renal disease associated with ART and suggests strategies for management and prevention.

Topics: Adenine; Anti-Retroviral Agents; Atazanavir Sulfate; HIV Infections; Humans; Indinavir; Kidney Diseases; Oligopeptides; Organophosphonates; Pyridines; Tenofovir

Topics: Crystallization; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases

Data from clinical trials present numerous problems for the data analyst. These include non-compliance with the prescribed dosing regimen and inaccurate recollection of dosing history by patients as well as mistakes in recording data. Several methods have been proposed to address these issues. One such technique by Lu et al. (Selecting reliable pharmacokinetic data for explanatory analyses of clinical trials in the presence of possible noncompliance. J. Pharmacokinet. Pharmacodyn. 28:343-362 (2001)) identifies occasions in pharmacokinetic (PK) data where the preceding dosing history is likely to be unreliable. We used this method, implemented in the software program NONMEM (beta) VI, to clean a dataset containing indinavir (IDV) plasma concentrations from HIV-1 infected patients. The data was also cleaned by inspection in Microsoft Excel using clinical PK criteria. A one-compartment model with first order absorption and elimination was fit to both sets of cleaned data. IDV population PK parameters obtained from these analyses were similar to those reported previously. It is established that IDV nephrotoxicity is related to high IDV exposure. However, no relationships were found between any PK parameters and nephrotoxicity in the "compliance cleaned" dataset. In the "PK cleaned" dataset, the oral clearance and apparent volume were lower by 9.1% and 6.6%, respectively in patients with any type of nephrotoxicity and the maximum IDV concentration (C(max)) was 12.1% higher. In patients suffering from nephrolithiasis in particular, C(max) was 15.5% higher. Accordingly, the use of the non-compliance detection method did not improve the reliability of our dataset over the usual method of applying clinical criteria. In fact, analyses on the compliance-cleaned dataset missed some exposure-toxicity relationships. Thus, automated methods must be tested rigorously with 'real life' datasets, used with caution, and always in conjunction with clinical reasoning to avoid overlooking a signal in noisy data.

Topics: Adult; Data Interpretation, Statistical; Databases as Topic; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Kidney Diseases; Male; Models, Biological; Patient Compliance; Reproducibility of Results; Research Design; Software

Treatment with indinavir/ritonavir (IDV/RTV) is very effective but hampered by frequent development of IDV-associated adverse events (mainly nephrotoxicity and skin changes). We tested whether dose reduction of IDV guided by therapeutic drug monitoring resulted in improved tolerability without compromising antiviral efficacy.. HIV-infected patients with any IDV/RTV regimen who suffer from IDV-related adverse events were included. Viral load had to be adequately controlled for at least 2 months prior to inclusion. Dose reduction from 800 mg to 600 or 400 mg IDV b.i.d. followed a specified protocol. IDV-related toxicity and IDV plasma concentrations were monitored for 24 weeks. IDV concentrations were quantified with a validated high performance liquid chromatography method.. Twenty patients were included. Reasons for inclusion were: skin abnormalities 11, nephrotoxicity five, metabolic disturbances three, and hypertension one. IDV dose could be lowered to 400 mg b.i.d. in 13, to 600 mg b.i.d. in two patients. Five patients discontinued the treatment. Overall tolerability improved with respect to incidence and severity of adverse events. Median trough concentrations decreased from 1.02 mg/l (range 0.08-7.1) at baseline to 0.48 mg/l (0.11-1.4) after 24 weeks (p = 0.03) and remained above the critical threshold of 0.1 mg/l at any time after dose reduction. There was no change of CD4 cell counts or viral suppression. There were no significant changes in other laboratory parameters (creatinine, bilirubin, triglycerides, cholesterol, blood count, and urinalysis).. Dose reduction of IDV improved tolerability of IDV-containing highly active antiretroviral treatment (HAART). Sufficient IDV trough concentrations were maintained in all patients as was virologic control.

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Monitoring; Female; Germany; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hypertension; Indinavir; Kidney Diseases; Male; Metabolic Diseases; Middle Aged; Prospective Studies; Ritonavir; Severity of Illness Index; Skin Diseases; Time Factors; Treatment Outcome; Viral Load

To describe the pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in human immunodeficiency virus (HIV)-infected Thai patients.. Thirty-six HIV-1-infected patients who participated in HIV-NAT 005 study gave informed consent to record a pharmacokinetic curve 4 weeks after starting a regimen containing either indinavir 800 mg every 8 h (n = 19) or indinavir 800 mg + ritonavir 100 mg every 12 h (n = 17). Indinavir plasma concentrations were measured by HPLC. Pharmacokinetic parameters were calculated by non-compartmental methods.. The median (interquartile range; IQR) body weight of the 36 patients (11 females and 25 males) was 60 (54-72) kg. Median and IQR values for indinavir AUC, Cmax and Cmin were 20.9 (13.1-27.0) mg x h/L, 8.1 (6.6-9.4) mg/L and 0.13 (0.09-0.27) mg/L, respectively, for indinavir 800 mg every 8 h, and 49.2 (42.5-60.4) mg x h/L, 10.6 (8.5-13.2) mg/L and 0.68 (0.43-0.77) mg/L, respectively, for indinavir 800 mg + ritonavir 100 mg every 12 h. These values are not largely different from values found in Caucasian patients, with the exception of relatively high peak levels of indinavir in Thai subjects. Cut-off values for optimal virological efficacy were an indinavir Cmin of 0.10 and 0.25 mg/L for the every 8 h and the every 12 h regimen, respectively; patients with an indinavir AUC greater than 30 (every 8 h regimen) or 60 (every 12 h regimen) mg x h/L were at increased risk of developing nephrotoxicity.. Indinavir pharmacokinetics and pharmacodynamics in Thai HIV-1-infected patients are similar to those described in Caucasian patients, despite an overall lower body weight in this population

Topics: Adult; Area Under Curve; Body Weight; Chromatography, High Pressure Liquid; Drug Interactions; Female; Half-Life; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Male; Ritonavir; Thailand

The objective of this study was to compare indinavir peak plasma (Cmax) values after administration of indinavir/ritonavir 800/100 mg on an empty stomach or with food. High indinavir Cmax values have been associated with indinavir-related nephrotoxicity.. This was an open-label, randomized, two-treatment, two-period, cross-over pharmacokinetic study performed at steady state. HIV-infected patients who had been using indinavir/ritonavir 800/100 mg twice daily for at least 4 weeks were randomized to take this combination with a light breakfast (two filled rolls and 130 ml of fluid) on a first study day, and without food on a second day, or in the reverse order. The pharmacokinetics of indinavir and ritonavir were assessed after plasma and urine sampling during 12 h.. Data for nine patients were evaluated. Administration of indinavir/ritonavir 800/100 mg on an empty stomach resulted in a higher indinavir Cmax [geometric mean (GM) ratio - fasting/fed and 95% confidence interval (CI): 1.28 (1.08-1.52), P=0.01] and a trend to a shorter indinavir tmax (P=0.07) compared to administration with food. The mode of administration of indinavir/ritonavir did not affect plasma indinavir Cmax and AUC values, parameters that have been associated with the antiviral efficacy of indinavir, nor the urinary excretion of indinavir.. Administration of indinavir/ritonavir 800/100 mg on an empty stomach results in a higher indinavir Cmax compared to ingestion with a light meal. Stated the other way round, intake with a light meal reduces indinavir Cmax, which probably reflects a food-induced delay in the absorption of indinavir. It is recommended to administer indinavir/ritonavir 800/100 mg with food, as a possible means to prevent indinavir-related nephrotoxicity in patients who start or continue with this regimen.

Topics: Adult; Cross-Over Studies; Drug Administration Schedule; Drug Therapy, Combination; Fasting; Food; Food-Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Middle Aged; Ritonavir

Low-dose ritonavir can boost plasma levels of indinavir, thereby enhancing its antiretroviral activity despite less frequent dosing. In this open-label, noncomparative, 24-week trial with a 24-week extension phase, HIV-infected protease inhibitor (PI)- and lamivudine-naive adults received indinavir/ritonavir 800 mg/100 mg plus stavudine and lamivudine every 12 hours. The proportions of patients achieving plasma HIV RNA (vRNA) <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Eighty-nine patients (80% men) with a median age of 36 years and mean baseline vRNA levels and CD4 counts of 5.01 log(10) copies/mL and 269 cells/mm(3) were enrolled. The proportions (95% confidence interval [CI]) of patients achieving vRNA <400 copies/mL were 93% (84%, 98%), 78% (67%, 86%), and 68% (57%, 78%) at week 24 for DAO, GEE, and NC = F analyses, respectively; the corresponding results at week 48 were 95% (84%, 99%), 65% (53%, 76%), and 45% (35%, 57%). Most patients with vRNA <400 had <50 copies/mL. At week 48, baseline vRNA decreased by >2 log(10) copies/mL and CD4 counts increased by approximately 200 cells/mm(3). Five patients (6%) experienced serious drug-related adverse experiences. Twenty patients (23%) discontinued therapy due to adverse experiences. In this study, twice-daily indinavir 800 mg/ritonavir 100 mg with two nucleoside reverse transcriptase inhibitors provided potent viral suppression and immunologic reconstitution in many PI-naive patients.

Topics: Adult; Aged; Anemia; Anti-HIV Agents; CD4 Lymphocyte Count; Dehydration; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Lipoproteins; Logistic Models; Male; Middle Aged; Pneumonia; Ritonavir; RNA, Viral; Virus Replication

To compare adherence and clinical outcome with two modalities of highly active antiretroviral therapy (HAART), in HIV-infected patients.. Randomized, open-label, prospective study.. Tertiary care centre in Spain.. A total of 112 non-naive HIV-infected patients, recruited from March 1998 through August 1998, were studied.. Triple drug therapy with stavudine and lamivudine, plus indinavir or nelfinavir.. Adherence, side-effects, and immunological, virological, and clinical efficacy of treatment were assessed at 3-month intervals.. After a median follow-up of 9 months, 32% of patients in the indinavir group versus 50% of those in the nelfinavir group showed adequate adherence in all clinical appointments (P= 0.0559). Adherence was superior in the nelfinavir group in every visit. After 6 months of treatment 48% of subjects in the indinavir group and 70% of those in the nelfinavir group exhibited adequate adherence (P= 0.0311). After 9 months 35% of patients in the indinavir group and 59% of those in the nelfinavir group showed adequate adherence (P= 0.0291). Side-effects provoked discontinuation of treatment in 34% of patients in the indinavir group and 12% of patients in the nelfinavir group (P= 0.0073). Immunological and virological efficacy were similar in both groups.. Adherence to a HAART regimen with stavudine plus lamivudine plus nelfinavir was superior to a regimen with stavudine plus lamivudine plus indinavir. Side-effects provoked more discontinuation of treatment in the indinavir group than in the nelfinavir group.

Topics: Adult; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Lamivudine; Male; Nelfinavir; Patient Compliance; Prospective Studies; Reverse Transcriptase Inhibitors; Stavudine; Treatment Outcome

To describe protease inhibitor-induced urinary stone disease in patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) who are taking indinavir sulfate (Crixivan), a protease inhibitor, for the treatment of AIDS.. Patients with HIV/AIDS and symptomatic renal colic temporally related to the initiation of indinavir sulfate therapy were prospectively identified. Seven patients (mean age 42 years; all men) with HIV and renal colic who were taking indinavir were identified. Retrospective chart reviews and patient interviews were performed.. Indinavir therapy averaged 5.7 months prior to presentation with renal colic. All patients had microscopic hematuria. One patient presented with acute azotemia from bilateral urinary obstruction. Six patients had no history of urinary stones prior to initiating indinavir. The median number of symptomatic urinary stone episodes after initiating indinavir was two stones per patient. All patients had moderate- to high-grade urinary obstruction from radiolucent calculi. Abdominal computed tomography (CT) demonstrated hydronephrosis without urinary calcifications. Three patients spontaneously passed stones and 4 required intervention. Yellow debris and/or brown matrix-like material was seen endoscopically. Stone analysis revealed pure protease inhibitor. Six patients (86%) eventually discontinued protease inhibitor therapy.. Protease inhibitor-induced urinary stones are radiolucent and can cause high-grade ureteral obstruction. Protease inhibitor-induced urinary stones were not identified on unenhanced abdominal CT scans. The radiolucent gelatinous nature of such stones makes lithotripsy a poor choice of treatment. Ureteral stenting may allow spontaneous stone passage if symptomatic obstruction occurs. Urologists may encounter a greater number of patients with symptomatic protease inhibitor-induced urinary calculi as these medications become more popular.

Topics: Adult; Colic; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Kidney Diseases; Male; Prospective Studies

Kidney injury is a serious comorbidity among HIV-infected patients. Intravenous drug use is listed as one of the risk factors for impaired renal function; however, this group is rarely assessed for specific renal-related risks.. Patients attending methadone program from 1994 to 2015 were included in the study. Data collected included demographic data, laboratory tests, antiretroviral treatment history, methadone dosing and drug abstinence. Patients' drug abstinence was checked monthly on personnel demand. We have evaluated two study outcomes: (1) having at least one or (2) three eGFR < 60 ml/min (MDRD formula).. In total, 267 persons, with 2593 person-years of follow-up were included into analyses. At the time of analyses, 251 (94%) were on antiretroviral therapy (ARV). Fifty-two (19.5%) patients had 1eGFR and 20 (7.5%) 3eGFR < 60. In univariate analysis, factors significantly increasing the odds of impaired renal function were: female gender, detectable HIV RNA on ART, age at registration per 5 years older, atazanavir use and time on antiretroviral treatment per 1 year longer. In the multivariate model, only female gender (OR 4.7; p = 0.002), time on cART (OR 1.11; p = 0.01) and baseline eGFR (OR 0.71; p = 0.001) were statistically significant.. We have demonstrated a high rate of kidney function impairment among HIV-1 positive patients in the methadone program. All risk factors for decreased eGFR in this subpopulation of patients were similar to those described for general HIV population with very high prevalence in women. These findings imply the need for more frequent kidney function monitoring in this subgroup of patients.

Topics: Adult; Anti-HIV Agents; Atazanavir Sulfate; Drug Therapy, Combination; Female; Glomerular Filtration Rate; HIV Infections; Humans; Indinavir; Kidney Diseases; Male; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Poland; Risk Factors; Sex Factors; Tenofovir; Time Factors

Topics: Chemically-Induced Disorders; Diagnosis, Differential; HIV Protease Inhibitors; Humans; Indinavir; Kidney; Kidney Diseases; Long Term Adverse Effects; Risk Factors

Diminished insulin sensitivity is a characteristic feature of various pathological conditions such as hypertension and activation of peroxisome proliferator activated receptor α (PPARα) has been shown to enhance insulin resistance and reduce capacity for glucose uptake in muscles. The present study was designed to evaluate the interactions of PPARα and GLUT4 in a model of hypertensive renal injury by studying deoxycorticosterone acetate (DOCA)-salt induced hypertension in wild-type (WT) and PPARα knockout (KO) mice. PPARα WT and KO mice were uninephrectomized (UNx) and implanted subcutaneously DOCA and drank 1% sodium chloride/1% potassium chloride with or without a GLUT4 antagonist, indinavir (20 mg/kg/day, s.c) or PPARα ligand, fenofibrate (100 mg/kg/day, orally). DOCA/salt treatment increased urinary sodium excretion and urine volume (p<0.05) in PPARα KO mice compared to WT littermates. Indinavir increased proteinuria (p<0.01) in DOCA/salt-treated PPARα KO mice compared to WT littermates but did not affect heart and kidney weight index in DOCA/salt KO or WT-treated mice. Urinary sodium excretion (UNaV) and urine volume (UV) were increased by indinavir (p<0.01) and fenofibrate (p<0.05) in DOCA/salt-treated PPARα KO mice compared to WT mice. Urinary nitric oxide was greater in both fenofibrate (p<0.05) and indinavir-treated WT mice (p<0.05) compared to KO mice. These data suggest that in hypertensive nephropathy, GLUT4 probably exerts a renoprotective role that was enhanced with the activation of PPARα receptors by a mechanism that may be related to increased nitric oxide production.

Topics: Animals; Desoxycorticosterone Acetate; Disease Models, Animal; Fenofibrate; Glucose Transporter Type 4; Indinavir; Kidney; Kidney Diseases; Male; Mice, Knockout; Nephrectomy; Nitric Oxide; Potassium Chloride; PPAR alpha; Sodium; Sodium Chloride; Time Factors; Urination

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

Symptomatic nephrotoxicity is a well-known complication of indinavir treatment. However, little is known about the relevance of other abnormalities, such as leukocyturia during use of indinavir. We determined the prevalence, risk factors, and consequences of persistent leukocyturia in a prospectively monitored cohort of indinavir users in three adult outpatient clinics. Patients were monitored for nephrotoxicity at regular visits (every 3 months) between August 1998 and September 2000. Monitoring involved urine dipstick analysis and microscopy for pH, erythrocytes, leukocytes, and indinavir crystals. The urine albumin concentration/creatinine concentration ratio and serum creatinine and indinavir plasma concentrations were measured, and urinary tract infection was excluded. Urologic symptoms were retrieved from medical records. Of 184 patients with at least one assessment, 35% had leukocyturia (i.e., >75 cells/microL) at least once during the study period, which coincided with mild increase in the serum albumin level, erythrocyturia, and crystalluria. Thirty-two (24%) of 134 patients with two or more assessments had persistent leukocyturia (i.e., on two or more occasions). Risk factors were indinavir plasma concentration of >9 mg/L, urine pH of >5.7, and crystalluria. Persistent leukocyturia was associated with a gradual loss of renal function but not with urologic symptoms. The data show that leukocyturia is a frequent finding and emphasize the need for monitoring renal function during indinavir treatment, even in the absence of urologic symptoms.

Topics: Adult; Albuminuria; Cohort Studies; Creatinine; Crystallization; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Diseases; Leukocytosis; Male; Middle Aged; Prospective Studies; Risk Factors

Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl2 x 6H2O (1%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/- 0.10; IDV+NF, 1.94 +/- 0.07 vs IDV, 1.15 +/- 0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/- 0.09; IDV+NF, 7.63 +/- 0.14 vs IDV, 6.17 +/- 0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/- 0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/- 0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity.

Topics: Animals; Arginine; HIV Protease Inhibitors; Indinavir; Kidney Diseases; Kidney Function Tests; Magnesium; Male; Nifedipine; Rats; Rats, Wistar; Vasodilator Agents

Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children.. A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir.. Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir.. The cumulative incidence of persistent sterile leukocyturia (> or =75 cells/ micro L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg/L x h or a peak serum level of indinavir >12 mg/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months.. Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir-associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg/L x h, and a C(max) >12 mg/L.

Topics: Child; Child, Preschool; Creatinine; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Kidney Diseases; Leukocytosis; Male; Prospective Studies; Urinalysis

In a prospective study evaluating risk factors for indinavir-related renal colic in 555 HIV-infected patients receiving highly active antiretroviral therapy, followed-up fir 24 months, 23.6% developed one or more renal colic episodes, and 50 patients stopped indinavir. No correlation was observed between renal colic onset and sex, age, CD4 cell count, history, and hepatitis B or C virus co-infection, but baseline anthropometric values were significantly related to the onset of renal colic.

Topics: Adult; Body Mass Index; Colic; Dose-Response Relationship, Drug; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Kidney Diseases; Male; Predictive Value of Tests; Prospective Studies; Risk Factors

Indinavir is a widely prescribed protease inhibitor in the treatment of HIV infection. It has been associated with nephrolithiasis, crystalluria and tubulointerstitial nephritis. Nelfinavir is another protease inhibitor used successfully in AIDS treatment. The objective of this study was to evaluate the effect of both indinavir and nelfinavir individually, and in association with trimethoprim-sulfamethoxazole (TMP/SMX), on renal function in Wistar rats.. Doses of indinavir (80 mg/kg body weight [BW] daily), nelfinavir (75 mg/kg BW daily) and TMP/SMX (100 mg TMP/kg BW daily) were given by gavage for 15 days. Seven groups were studied: control, vehicle, TMP/SMX, indinavir, indinavir+TMP/SMX, nelfinavir, and nelfinavir+TMP/SMX.. No changes were observed in body weight, urine volume and blood pressure. The vehicle group did not differ from the control group. TMP/SMX induced a small decrease in inulin clearance with no tubular alterations. Indinavir decreased inulin clearance (indinavir: 0.48 +0.03 vs control: 0.93 +/- 0.08, P < 0.001) and renal blood flow (indinavir: 6.2 +/- 0.2 vs control: 8.0 +/- 0.3, P < 0.05). These effects were potentiated by TMP/SMX, which produced high vasoconstriction associated with alterations in tubular functions, characterised by increased fractional excretion of sodium (indinavir+TMP/SMX: 1.14 +/- 0.16 vs control: 0.39 +/- 0.07, P < 0.01). Nelfinavir either alone or in combination with TMP/SMX did not change the renal function of the rats.. These results suggest that indinavir nephrotoxicity in rats is potentiated by TMP/SMX and that nelfinavir alone or in combination with TMP/SMX is not nephrotoxic.

Topics: Animals; Anti-Infective Agents; Drug Interactions; Glomerular Filtration Rate; HIV Protease Inhibitors; Indinavir; Kidney Diseases; Male; Nelfinavir; Rats; Rats, Wistar; Renal Circulation; Trimethoprim, Sulfamethoxazole Drug Combination; Vasoconstriction

To describe the incidence and risk factors for the development of indinavir-associated renal complications (IRC), and subsequent clinical outcome.. This was a retrospective cohort study based on two large HIV centres in London. Eligible patients received indinavir for at least 1 week between 1 December 1995 and 28 February 1999. Development of IRC was ascertained by case-note review. Multivariate logistic regression and Cox Proportional Hazard's model analysis were used to determine independent risk factors for the development of IRC.. 781 patients were eligible. Median CD4 count and viral load at indinavir initiation were 117 x 10(6) cells/L and 47 332 copies/mL, respectively. Median indinavir exposure was 53 weeks (IQR: 20-83). Many patients received other potentially nephrotoxic drugs during indinavir treatment: co-trimoxazole (46%), aciclovir (33%) or both (20%). Overall IRC incidence was 7.3% (6.7 per 100 person-years indinavir exposure). Cases presented with loin pain (58%), renal colic (42%) or dysuria (19%). Identified precipitating events (26%) included fluid depletion or altered indinavir regimen. In the majority of cases indinavir therapy was continued and there was no progressive rise in creatinine levels. In the multivariate analysis, for indinavir treatment >74 weeks there was a reduced risk of developing IRC (OR = 0.23, 95% CI 0.09-0.57, P = 0.001). Concomitant aciclovir increased the IRC risk (OR = 1.99, 95% CI 1.14-3.51, P = 0.016). Factors not associated with outcome were age, gender, ethnicity, baseline CD4 count and viral load, concomitant co-trimoxazole, or use of specific antiretrovirals.. An overall IRC incidence of 7.3% was identified. Concomitant aciclovir doubled the risk of IRC and we therefore recommend careful monitoring when prescribing aciclovir with indinavir. A precipitating event was identified in 26% of IRC cases, many of which could have been avoided.

Topics: Adult; Cohort Studies; Female; HIV Protease Inhibitors; Humans; Incidence; Indinavir; Kidney Diseases; Male; Retrospective Studies; Risk Factors

Indinavir is a well-known cause of crystal-induced acute renal failure, dysuria and flank pain, and nephrolithiasis. Recently a more insidious tubulointerstitial lesion has been recognized as secondary to the drug. We report a case of a hepatitis C-positive patient on long-term indinavir therapy for human immunodeficiency virus (HIV) who developed a slowly progressive rise in serum creatinine. Renal biopsy revealed a diffuse interstitial infiltrate with numerous eosinophils and scarring. The tubules showed focal necrosis and dilation with elongated crystals present within their lumina. The elevated serum creatinine decreased to a new baseline over several months with the discontinuation of indinavir. We review the literature of renal syndromes associated with indinavir focusing on chronic progressive tubulointerstitial injury and speculate on risk factors and potential mechanisms of indinavir-induced renal injury.

Topics: Adult; Biomarkers; Blood Urea Nitrogen; Creatinine; Hepatitis C; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Male

Indinavir therapy is associated with a continuum of crystal-related syndromes, including nephrolithiasis, renal colic, flank pain without recognizable stone formation, dysuria and asymptomatic crystalluria. A frank nephropathy has been recognized recently as part of the spectrum.. A retrospective analysis of 72 HIV-infected individuals receiving indinavir was performed to identify the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals treated with nucleoside analogues alone served as controls.. Mean serum creatinine levels rose from 1.03 +/- 0.16 mg/dl to 1.11 +/- 0.22 mg/dl at week 12 and 1.15 +/- 0.27 mg/dl at week 24 (both, p < 0.01). Thirteen individuals developed serum creatinine levels > or =1.4 mg/dl. Increased serum creatinine levels were found more frequently in women (p < 0.01) and were associated with pyuria and microhematuria (p < 0.01). Frank renal colic and/or nephrolithiasis (seven patients) and urinary pH were not associated with serum creatinine levels > or =1.4 mg/dl. The mean duration of indinavir treatment, until sterile pyuria occurred, were 22 weeks and 32 weeks until the first rise of serum creatinine levels to > or =1.4 mg/dl. Ten patients showed both findings, pyuria preceded the first rise in serum creatinine levels to > or = 1.4 mg/dl (18 vs. 27 weeks, p = 0.02). Renal biopsy, done in three patients, revealed tubulointerstitial disease with crystals in collecting ducts. In 21 patients, among them 11 with pyuria, indinavir was replaced for various reasons and pyuria disappeared in nine. In these patients mean serum creatinine levels decreased from 1.43 mg/dl at withdrawal of indinavir to 1.04 mg/dl three months later (p < 0.01).. Indinavir therapy is associated with a decrease in renal function which is reversible after withdrawal. In addition, indinavir-associated tubulointerstitial disease does no in patients taking indinavir may help to identify patients being at risk for nephrotoxicity.

Topics: Adult; Creatinine; Female; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Kidney Diseases; Male; Middle Aged; Pyuria; Time Factors

We evaluate the clinical, diagnostic and radiographic findings in patients on indinavir therapy who presented with renal colic, and propose appropriate treatment options for indinavir urolithiasis.. A total of 16 patients positive for human immunodeficiency virus on indinavir were evaluated for 18 episodes of severe renal colic requiring hospitalization. Laboratory evaluation was performed in all patients followed by an imaging study. Conservative treatment included intravenous hydration, narcotic analgesics and temporary cessation of indinavir. Intervention was elected only in patients with persistent fever or intractable pain. A month after hospital discharge an excretory urogram and metabolic stone evaluation were performed. Mean followup was 9.3 months and 2 patients had recurrent symptoms.. All patients presented with nausea or vomiting and hematuria. Imaging studies confirmed obstruction in all patients with 13 radiolucent (indinavir) and 3 radiopaque (calcium oxalate) stones. Patients with radiolucent and radiopaque stones demonstrated significant differences in urinary pH (p = 0.002) and serum creatinine (p = 0.03). Conservative therapy was successful in 11 patients (68.8%) within 48 hours and 4 patients (25%) with radiolucent calculi required endoscopic stenting for persistent fever. Metabolic stone evaluation demonstrated significant hypocitruria (less than 50 mg./24 hours) in all patients with radiolucent calculi.. The urologist should be familiar with this growing cause of renal colic in patients on indinavir therapy. Pure indinavir stones are radiolucent and have a soft, gelatinous endoscopic appearance. Conservative treatment is successful in most patients and if intervention is deemed medically necessary, endoscopic stent placement should be the procedure of choice.

Topics: Acquired Immunodeficiency Syndrome; Adult; Colic; Female; Follow-Up Studies; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Kidney Calculi; Kidney Diseases; Male; Middle Aged; Severity of Illness Index

Topics: Anti-HIV Agents; HIV Infections; Humans; Indinavir; Infectious Disease Transmission, Patient-to-Professional; Kidney Diseases; Occupational Diseases; Occupational Exposure

Evaluate the frequency and assess curative and preventive measures against urinary lithiasis in patients treated with indinavir.. Fourteen HIV seropositive patients who developed severe and acute flank pain were included. Four of the patients receiving 800 mg indinavir t.i.d. had fever (38.5 degrees C) or delayed secretion (> 2 h). Delay from indinavir treatment onset was 1 to 321 days. During the same period, 155 patients had been treated with indinavir. Clinical features, radiology and laboratory results were recorded in addition to an analysis of the lithiasis if possible.. Transient moderate renal failure occurred in 8 patients. Mean urine pH was 6. Serum phosphorus, calcium, and uric acid, liver tests and urinalysis were normal. A JJ ureteral stent was inserted in 4 cases due to complications. In all cases, fluids, analgesics and antispasmodics provided favorable outcome. Inversely, nonsteroid antiinflammatory drugs given in 2 patients had a deleterious effect on renal function. The lithiasis was eliminated in 3 cases and infrared spectrophotometry demonstrated a structure compatible with indinavir monohydrate.. The formation of urinary lithiasis is a frequent complication of indinavir therapy (9%). Hyperhydration and urine acidification are usually successful but emergency drainage is required in approximately 3% of cases. Nonsteroidal antiinflammatory drugs should be avoided due to the risk of renal toxicity. A precise evaluation of fluid intake and diet, drug associations and personal history is needed to recognize patients at risk of recurrent lithiasis formation.

Topics: Acute Kidney Injury; Adult; Aged; Analgesics; Anti-HIV Agents; Anti-Inflammatory Agents, Non-Steroidal; Calcium; Colic; Evaluation Studies as Topic; Female; Fluid Therapy; HIV Protease Inhibitors; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Calculi; Kidney Diseases; Male; Middle Aged; Parasympatholytics; Phosphorus; Spectrophotometry, Infrared; Uric Acid; Urine

Aspergillus abscesses of the kidneys are very rare complications of AIDS which usually have fatal outcome. The 4 patients described in the literature, 2 of whom had bilateral involvement, died due to this opportunistic infection.. Case report of a 33-year-old patient with AIDS in stage C3 and aspergillus abscesses of the kidney.. Successful treatment of bilateral aspergillus abscesses of the kidneys with purely conservative antimycotic measures. This was largely due to stabilization of the immune status by supplementing antiretroviral treatment with the proteinase inhibitor indinavir.. The options now available for improving immune status in AIDS also improve the treatment chances in renal aspergillosis.

Topics: Abscess; Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Humans; Indinavir; Kidney Diseases; Tomography, X-Ray Computed

Topics: Adult; Anti-HIV Agents; HIV Infections; Humans; Indinavir; Kidney Calculi; Kidney Diseases; Male; Protease Inhibitors

Many sessions at the 5th Conference on Retroviruses and Opportunistic Infections dealt specifically with HIV infection and treatment in women. Highlights are presented from several sessions, including indinavir blood levels at various points in the menstrual cycle, abnormal kidney function associated with women taking indinavir, abnormal pap smears in women with high viral load, the relationship between viral load and the increased risk of death in women, and the impact of ddI crossing the placenta in pregnant women. Information is given on each presentation, including clinical trial results, side effects, and impacts on disease progression.

Topics: Anti-HIV Agents; Cervix Uteri; Chicago; Clinical Trials as Topic; Congresses as Topic; Didanosine; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Diseases; Male; Maternal-Fetal Exchange; Menstrual Cycle; Papanicolaou Test; Papillomavirus Infections; Pregnancy; Risk Factors; RNA, Viral; Tumor Virus Infections; Vaginal Smears; Viral Load

Topics: Acquired Immunodeficiency Syndrome; Antiviral Agents; Humans; Indinavir; Kidney Diseases; Male; Middle Aged

Topics: Adult; Anti-HIV Agents; Colic; Drug Therapy, Combination; Female; HIV Infections; Humans; Indinavir; Kidney Diseases; Zidovudine

Topics: Adult; Anti-HIV Agents; HIV Infections; Humans; Indinavir; Kidney Diseases; Kidney Function Tests; Male