indinavir-sulfate and Kidney-Calculi

Drug-induced renal calculi represent 1-2% of all renal calculi. They include two categories: those resulting from the urinary crystallisation of a highly excreted, poorly soluble drug or metabolite, and those due to the metabolic effects of a drug. Indinavir, used in HIV-infected patients, sulfonamides, especially sulfadiazine, and triamterene, which is less prescribed today, are the most frequent. Besides these drugs, about twenty other molecules, among them silicate-containing drugs and some antibiotics have been reported in patients receiving high doses or long-term treatments. Calculi analysis by physical methods such as infrared spectroscopy or x-ray diffraction can demonstrate the presence of the drug or its metabolites inside the calculi. In those calculi due to the metabolic effects of a drug, diagnosis relies on both stone analysis and clinical inquiry. Incidence of such calculi is probably underestimated, especially those due to calcium/vitamin D supplements or carbonic anhydrase inhibitors. Drug-induced calculi occur more often during high-dose or long term treatments, but there are also patient-related risk factors in relation to urine pH, urine output and other parameters, which can provide a basis for preventive treatment of such calculi. A better knowledge of these lithogenic complications of treatments and of solubility characteristics of drugs should reduce the incidence of drug-induced nephrolithiasis, especially in patients with identified risk factors.

Topics: HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi

Topics: Abdominal Abscess; Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Associated Nephropathy; Erectile Dysfunction; Humans; Indinavir; Kidney; Kidney Calculi; Lymphoma; Male; Male Urogenital Diseases; Middle Aged; Prostatic Diseases; Prostatitis; Sarcoma, Kaposi; Testicular Diseases; Urination Disorders

To report a case of severe and recurrent crystalluria resulting from the use of indinavir and to review the literature describing this adverse effect.. A 26-year-old HIV-positive white woman had recurrent episodes of left-sided flank pain accompanied by dilation of the left renal collecting system while undergoing treatment with a triple-drug regimen including indinavir 1200 mg every 12 hours (full dosage). Typical indinavir crystalluria was observed, with no evidence of stones. Acute episodes were treated with intravenous fluids, diclofenac, and ciprofloxacin. Crystalluria and clinical symptoms eventually resolved with withdrawal of indinavir and substitution with a different protease inhibitor. Renal function remained normal.. A wide spectrum of disorders of the urinary tract can occur in subjects taking indinavir, with potentially severe complications caused by crystalluria and stones. Indinavir is excreted in the urine; the low solubility of those crystals is the critical factor accounting for the risk of stone formation. An elevated pH with a reduced excretion of citric acid contributes to the low urinary solubility of indinavir. Pharmacokinetic interactions with other drugs, leading to elevated plasma concentrations of indinavir, and dehydration could also increase the risk of stone formation. The impact on renal function can be unfavorable over the long-term period. Cornerstones of treatment and prevention are increased fluid intake and possibly urinary acidification. Emergency drainage may be required for patients with severe obstruction. Reducing the dosage of indinavir has been proposed, but this carries the risk of viral mutations with development of resistance.. Treatment with indinavir can result in crystalluria with potentially severe obstruction. All patients taking indinavir, not only those with documented crystalluria or renal effects from the drug, should greatly increase their fluid intake and have renal function checked at baseline and then monitored regularly. Urinalysis also should be performed regularly for appropriate monitoring and prevention.

Topics: Adult; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Urologic Diseases

There is some evidence of retroviral infection in ALS. A randomized, double-blind, placebo-controlled trial of indinavir in ALS was performed to assess safety and efficacy trends. Nephrolithiasis and gastrointestinal side effects were frequent with indinavir treatment. Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.

Topics: Amyotrophic Lateral Sclerosis; Central Nervous System; Double-Blind Method; Female; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Male; Middle Aged; Neuroprotective Agents; Pilot Projects; Placebos; Riluzole; Treatment Failure

There is no standard treatment of HIV-infected patients who fail protease inhibitor (PI)-containing antiretroviral therapy. This open-label, noncomparative 24-week study with a 24-week extension evaluated the efficacy, safety, and tolerability of twice-daily indinavir/ritonavir 800/200 mg plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) in this population. Presented here are the results of the 24-week study. Patients were HIV-infected adults who had prior viral RNA (vRNA) suppression (<400 copies/mL), subsequent failure (> or =400 and < or =100,000 copies/mL) on antiretroviral therapy, and at least one new NRTI available for treatment. The proportions of patients achieving plasma vRNA <400 and <50 copies/mL were analyzed with data as observed (DAO) and intention-to-treat (ITT) models using generalized estimating equations (GEE) or counting noncompleters as failures (NC = F). Mean changes from baseline in vRNA and CD4 cell count were evaluated using DAO and an ITT mixed-model approach. Sixty-three patients (87% male) with a mean age of 42 years and mean baseline vRNA and CD4 cell counts of 3.8 log(10) copies/mL and 360 cells/mm(3), respectively, were enrolled. The proportion (95% confidence interval) of patients achieving vRNA <400 and <50 copies/mL at week 24 were 76% (61%, 87%) and 50% (35%, 65%) for DAO, 64% (50%, 75%) and 43% (30%, 56%) for GEE, and 56% (43%, 68%) and 37% (25%, 50%) for NC = F, respectively. At Week 24, baseline vRNA decreased by >1.0 log(10) copies/mL and CD4 cell counts increased by approximately 90 cells/mm(3). Three patients (5%) experienced serious drug-related adverse events. Seven patients (11%) discontinued treatment due to clinical or laboratory adverse events. In this study, the enhanced, twice-daily regimen of indinavir/ritonavir 800/200 mg plus 2 NRTIs provided suppression of HIV in many patients who had failed a PI-containing regimen and was generally well tolerated.

Topics: Acidosis; Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Hyperbilirubinemia; Hypercholesterolemia; Hyperglycemia; Hypertriglyceridemia; Indinavir; Kidney Calculi; Male; Middle Aged; Ritonavir; RNA, Viral; Treatment Failure

Antiretroviral regimens containing HIV protease inhibitors suppress viremia in HIV-infected patients, but the durability of this effect is not known.. To describe the 3-year follow-up of patients randomly assigned to receive indinavir, zidovudine, and lamivudine in an ongoing clinical trial.. Open-label extension of a randomized, double-blind study.. Four clinical research units.. 33 HIV-infected, zidovudine-experienced patients with serum HIV RNA levels of at least 20,000 copies/mL and CD4 counts ranging from 50 to 400 cells/mm3.. Indinavir, zidovudine, and lamivudine.. Safety assessments, HIV RNA levels, CD4 cell counts, and genotypic analyses.. After 3 years of follow-up, 21 of 31 contributing patients (68% [95% CI, 49% to 83%]) had serum viral load levels less than 500 copies/mL. Twenty of 31 (65% [CI, 45% to 80%]) had levels less than 50 copies/mL. The median increase in CD4 count from baseline was 230 cells/mm3 (interquartile range, 150 to 316 cells/mm3). Nephrolithiasis occurred in 12 of 33 patients (36%).. A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia in two thirds of patients for at least 3 years.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Genotype; HIV; HIV Infections; Humans; Indinavir; Kidney Calculi; Lamivudine; Male; Middle Aged; RNA, Viral; Viral Load; Viremia; Zidovudine

Indinavir was approved by the Food and Drug Administration in 1996 as a human immunodeficiency type 1 protease inhibitor to treat human immunodeficiency virus infection. Prompted by the high number of patients receiving indinavir who present with renal colic at our institution, we performed a detailed investigation of the true frequency of urolithiasis during indinavir treatment.. We evaluated 105 patients with a mean age of 38.1 years who were treated with indinavir from 1996 to 1997. Before indinavir treatment was initiated all patients underwent renal ultrasonography, urinalysis, and determination of serum sodium, potassium, calcium, uric acid and creatinine. It was recommended that all patients drink 2 l of fluids daily, and all remained under continuous surveillance.. Metabolic evaluation and ultrasonography showed no abnormality in any case. A stone episode occurred in 13 men (12.4%) as renal colic during observation. Colic recurred in 1 patient after 2 and 5 months, and in 1 after 2 months. Median duration of indinavir treatment until an acute stone episode was 21.5 weeks (range 6 to 50). A total of 12 stones passed spontaneously. Three patients underwent ureteroscopic calculous removal and 1 was treated with extracorporeal shock wave lithotripsy.. Despite adequate patient information and compliance the rate of nephrolithiasis during indinavir therapy was 12.4%.

Topics: Adult; Aged; Anti-HIV Agents; Female; HIV Seropositivity; Humans; Incidence; Indinavir; Kidney Calculi; Male; Middle Aged; Prospective Studies

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

Indinavir is a protease inhibitor used in the therapy of HIV-1+ patients. It causes indinavir stone formation. It has been shown to precipitate in the loop of Henle (LH) at plasma concentrations (conc[P]) of approximately 8 mg/L. Those experiments were performed at room temperature. Given the influence of temperature on crystallization in general, and solubility of indinavir in particular, we repeated the experiments under physiological (body) temperature conditions.. Test solutions contained indinavir concentrations of 100-750 mg/L at ionic strengths varying from 0 to 800 mM simulating conditions in the proximal tubule and the LH. Solutions were titrated with base (NaOH) to find the pH value where nucleation is initiated. Experiments were conducted at room temperature (20 degrees C) and repeated under constantly monitored (body) temperature (37 degrees C).. Experiments at 20 degrees C confirmed our previous results. At 37 degrees C, the relationship between pH and indinavir concentration remained inversely proportional. Again, the LH was confirmed as the most likely localization of crystallization. However, at 37 degrees C precipitation occurred at a lower urinary concentration (100 versus 125 mg/L) and within a lower pH range (6.67-7.26 versus 7.23-7.44). This lower urinary concentration corresponds to a lower conc[P] [critical value (CV)] of 6.41 mg/L, as compared with 8.01 mg/L at 20 degrees C.. The CV is even lower at 37 degrees C than previously assumed. Plasma peak concentration above the CV of 6.4 mg/L will induce crystallization in the LH and should be avoided.

Topics: Anti-HIV Agents; Body Temperature; Crystallization; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Calculi; Loop of Henle

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

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

Topics: Anti-HIV Agents; Drug Therapy, Combination; Follow-Up Studies; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Lamivudine; Risk Factors; Zidovudine

Topics: Crystallization; HIV Protease Inhibitors; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Calculi; Male; Reproducibility of Results; Sensitivity and Specificity; Urinalysis

Topics: Atrophy; Child, Preschool; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Kidney Cortex

Protease inhibitors together with reverse transcriptase inhibitors are used in antiretroviral treatment. Indinavir, precipitating in renal tubules, quite often can cause nephrolithiasis. The case of a HIV infected patient with renal colic probably caused by indinavir, diagnostic and therapeutic options in such cases are described in the paper.

Topics: Adult; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Kidney Calculi; Male

Indinavir is a protease inhibitor used in the treatment of HIV with a lithogenic capacity as a urological side effect. The pathogenesis, diagnosis and treatment of indinavir urolithiasis are briefly reviewed.. A 37-year-old male, seropositive for HIV on treatment with indinavir, lamiduvine and zidovudine, consulted for colicky left lumbar pain, nausea, vomiting and dark urine for the past three days.. Patient evaluation showed a nonfunctioning left kidney and ureterohydronephrosis of unknown origin. URS showed a yellowish, friable material with a mucinous appearance that occupied the entire lumen of the ureter. Fragmentation was achieved with the lithotriptor probe. Six months later the patient had fully recovered and was asymptomatic.. The incidence of protease inhibitor-induced urolithiasis is increasing. This condition should be distinguished from uric acid calculi whose treatment will aggravate the indinavir urolithiasis.

Topics: Adult; HIV Protease Inhibitors; HIV Seropositivity; Humans; Indinavir; Kidney Calculi; Male

A HIV-1 patient database was scanned in March 1998, and 750 patients were identified who had received HAART including indinavir. Of these, 28 cases had nephrolithiasis; and 85 asymptomatic indinavir-treated patients were randomly selected as controls. The characteristics of cases and controls were compared by analysis of variance for quantitative parameters and by Fisher's exact test for classes.. We observed a significant increase in the incidence of nephrolithiasis in patients co-infected with HIV-1 and either hepatitis C virus (HCV) (HCV RNA-positive) or hepatitis B virus (HBV) (HBs antigen-positive) (odds ratio and 95% confidence intervals: 2.8 and 1.1-7.7), whereas no significant differences were demonstrated between cases and controls with regard to age (42.4 +/- 8.0 versus 39.8 +/- 9.8 years), sex (male patients 70.4 versus 74.1%), duration of HIV-1 infection (8.6 +/- 3.1 versus 7.7 +/- 4.0 years), duration of indinavir treatment (16.1 +/- 5.8 versus 14.1 +/- 5.4 months), AST increase > or = 1.25 of normal (29.6 versus 25.9%), or ALT increase > or = 1.25 of normal (33.3 versus 22.4%). In co-infected patients, ALT increase (> or = 1.25 of normal), but not AST increase, at the time of indinavir initiation was statistically related to the occurrence of nephrolithiasis.. We found a significant increase of nephrolithiasis incidence in patients co-infected with HIV-1 and HCV or HBV, which suggests that underlying multifactorial hepatic damage may limit liver catabolism of indinavir, and consequently increase its renal excretion and the risk of nephrolithiasis. Caution is therefore advised when initiating indinavir treatment in HIV patients with evidence of HBV or HCV infection.

Topics: Adult; Anti-HIV Agents; Case-Control Studies; Databases, Factual; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis C; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Incidence; Indinavir; Kidney Calculi; Male; Middle Aged; Reverse Transcriptase Inhibitors

Indinavir is a protease inhibitor used for treating HIV-1. The drug is lithogenic and was thought to cause a 3% incidence of kidney stones. We evaluated a cohort of patients positive for HIV on indinavir to determine the incidence of indinavir nephrolithiasis and identify risk factors for indinavir stone formation.. Our cohort study of the prevalence of indinavir nephrolithiasis included 155 patients with HIV for 5,732 patient-weeks. The same cohort was then used for a retrospective chart review to assess patient age, weight, duration of drug use, time to stone formation, CD4 count, creatinine, alanine transaminase, and urinary pH and specific gravity as risk factors for stone formation.. We estimated the cumulative incidence of indinavir stone formation by the Kaplan-Meier product limit estimator method. At 78 weeks 43.2% of patients had stones (95% confidence interval [CI] 0.292 to 0.543). Increasing age was the only variable that was a statistically significant predictor of indinavair urolithiasis (relative risk 0.955, 95% CI 0.918 to 0.993, p = 0.0159). The mean duration plus or minus standard deviation of indinavir use was statistically the same in each group (42.5 +/- 27. 2 and 40.3 +/- 27.1 weeks in those without and with stones, respectively) despite the observed mean time to stone formation of 23.0 +/- 19.8 weeks.. The clinical prevalence of indinavir nephrolithiasis is much greater than initially reported. Nephrolithiasis during indinavir use does not appear to induce patients to withdraw from the drug.

Topics: Adult; Age Factors; Cohort Studies; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Kidney Calculi; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Risk Factors

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

Indinavir sulfate is an effective protease inhibitor of the human immunodeficiency virus type 1. Use is associated with a significant incidence of crystallization and stone formation in the urinary tract, and these calculi are not visible on plain radiographs. Previously all urinary stones, including uric acid and matrix, were believed to be radiodense on computerized tomography (CT). We conducted a retrospective study to evaluate the radiographic appearance of indinavir calculi.. Retrospective chart review of 36 patients taking indinavir sulfate and presenting with renal colic was performed with attention to presentation, urinalysis, radiographic evaluation and management. Specifically, imaging characteristics on CT were addressed.. All patients complained of ipsilateral flank pain and 35 had nausea and/or vomiting. Of 30 patients with dysuria or urgency the majority had hematuria, and most had pyuria and/or proteinuria. No stones were visualized on abdominal radiography. Diagnosis was confirmed on 1 of 13 excretory urograms and 4 of 11 renal ultrasounds. None of 12 CT scans was diagnostic of renal lithiasis.. Indinavir sulfate is a protease inhibitor with poor solubility and significant urinary excretion. Crystallization and stone formation are demonstrated in as many as 20% of patients taking the medication. Most patients present with flank pain, nausea or vomiting and hematuria. Previously CT was thought to identify all urinary calculi with clarity but it cannot reliably confirm the presence of indinavir calculi.

Topics: Adult; Aged; Algorithms; Anti-HIV Agents; Crystallization; Female; Humans; Indinavir; Kidney Calculi; Male; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed

Topics: Abdominal Pain; Acquired Immunodeficiency Syndrome; Adult; Crystallization; Humans; Indinavir; Kidney; Kidney Calculi; Male; Radiography

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: Adult; Anti-HIV Agents; HIV Infections; Humans; Indinavir; Kidney Calculi; Male; Radiography

The crystallization of indinavir in synthetic urine at different pH values and indinavir concentrations was kinetically studied. It was found that precipitation time notably decreases at urinary pH values above 6.0. The effects of some products as potential crystallization inhibitors were studied. Some natural saponins such as escin and glycyrrhizic acid provoked a notable increase in the precipitation time of indinavir, this pointing out their possible use to prevent renal tubular solid deposition.

Topics: Chemical Precipitation; Crystallization; HIV Protease Inhibitors; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Calculi

We analyzed the influence of temperature, humidity, and atmospheric pressure on the 1-year incidence of nephrolithiasis among human immunodeficiency virus type 1-infected patients treated with indinavir. One hundred three patients (13.6%) developed 326 episodes of nephrolithiasis. Eighty-two patients (79.6%) had more than one episode (range, two to seven episodes). The overall incidence ranged from 0 to 10.2 episodes per 100 patients exposed per month. There was a significant correlation between temperature and the overall incidence of nephrolithiasis and the incidence of recurrences but not with the incidence of first episodes. Nephrolithiasis was not related to humidity or atmospheric pressure. Our data support the standard recommendation of drinking at least 1.5 L of water daily to prevent nephrolithiasis in most patients treated with indinavir irrespective of meteorologic factors. However, the risk of nephrolithiasis is higher for a certain subgroup of patients when the environment is hot irrespective of adequate water intake.

Topics: Atmospheric Pressure; HIV Infections; HIV Protease Inhibitors; Humans; Humidity; Incidence; Indinavir; Kidney Calculi; Prospective Studies; Temperature

(1) Nephrolithiasis is found in 4-13% of patients treated with indinavir, an HIV protease inhibitor. Most of these stones are composed of indinavir. (2) Outcome is often favourable, with simple passage of the stone, but endoscopic or surgical treatment is sometimes required. (3) Crystalluria seems to be more frequent, but is often asymptomatic. (4) Prevention is based on fluid intake of at least 1.5 litres a day. Indinavir withdrawal may be necessary.

Topics: HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Treatment Outcome

Topics: Hemophilia A; Hemorrhage; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Thrombocytopenia

Topics: Adult; Anti-HIV Agents; Humans; Indinavir; Kidney Calculi; Male

Topics: Acute Kidney Injury; Anuria; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Male; Middle Aged

Topics: Anti-HIV Agents; Chromatography, High Pressure Liquid; Crystallization; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Mass Spectrometry

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

To determine whether the protease inhibitor indinavir sulfate, which is extremely insoluble at physiologic pH levels and which is known to be associated with nephrolithiasis, is associated with crystalluria at a usual therapeutic dose.. Freshly voided urine from 27 male human immunodeficiency virus patients being treated with indinavir at a dose of 800 mg, tid, in an outpatient setting and from 20 healthy subjects undergoing routine physical examination was subjected to dipstick urinalysis and microscopic examination of urinary sediments.. Three (11%) of 27 patients treated with indinavir developed highly characteristic crystalluria during the course of therapy. No such crystals were observed in the urine of the 20 healthy subjects.. Indinavir crystalluria was identified in asymptomatic patients treated with usual therapeutic doses of the drug. Screening urines of patients taking indinavir may be useful in identifying patients at risk for developing nephrotoxicity.

Topics: Crystallization; HIV Infections; HIV Protease Inhibitors; Humans; Hydrogen-Ion Concentration; Indinavir; Kidney Calculi; Male; Risk Factors; Urine

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

Nephrolithiasis may be an important consequence of indinavir therapy; however little has been published on the variation in incidence between different populations of patients or the possible mechanisms of calculus formation.. To examine variation in the incidence of indinavir-associated nephrolithiasis (IAN) in HIV-positive patients in relation to hemophilia and hepatitis C virus (HCV) infection.. Clinical data were abstracted retrospectively from the medical records of all adult patients treated with indinavir from September 1995 to September 1997. Occurrence of first IAN, defined as flank pain and hematuria after initiation of therapy, was analyzed in relation to hemophilia status and HCV infection.. There were 17 episodes of IAN (22%) among 79 patients treated with indinavir. Of 10 patients with hemophilia, 50% developed IAN as compared with 17% of patients without hemophilia (P = 0.03). Median days to first IAN was 22 (range 7-110 days) for hemophiliacs and 156 (range 5-611 days) for those without hemophilia. Data for HCV status were available for 74 out of 79 patients: 10 out of 27 (37%) patients with HCV developed IAN compared with six out of 42 (14%) without HCV (P = 0.02).. Overall incidence of IAN was higher than that previously reported and was significantly greater in hemophiliacs than in non-hemophiliacs. HCV may be a contributing factor.

Topics: Adult; Anti-HIV Agents; Female; Hemophilia A; Hepatitis C; HIV Infections; HIV Protease Inhibitors; Humans; Incidence; Indinavir; Kidney Calculi; Male; Risk Factors

Topics: Acquired Immunodeficiency Syndrome; Adult; Female; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi

Topics: Anti-HIV Agents; Climate; Drinking; Florida; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi

Topics: Crystallization; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Urine

Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir.. To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir.. Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health.. Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms.. Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. Of 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging.. Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic.

Topics: Adult; Anti-HIV Agents; Chromatography, High Pressure Liquid; Female; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Male; Mass Spectrometry; Middle Aged; Pain; Risk Factors; Urination Disorders; Urine; Urologic Diseases

Two patients with oliguric acute renal failure (ARF) attributed to crystalluria and nephrolithiasis with obstructive uropathy caused by the human immunodeficiency virus protease inhibitor indinavir are described. In both patients, ARF resolved with administration of intravenous fluids. One patient required urologic intervention to relieve bilateral ureteral obstruction.

Topics: Acute Kidney Injury; Adult; Crystallization; Fluid Therapy; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Male

To report the association between the protease inhibitor indinavir and the development of urolithiasis.. Case reports of three adult patients infected with the human immunodeficiency virus who developed surgical renal stones while being treated with indinavir are presented.. Of the 3 patients requiring surgical intervention, stone analyses were available in 2. One stone revealed an inner core of an unidentifiable crystal surrounded by calcium oxalate, and another was found to have indinavir components as determined by thin-layer chromatography and gas chromatography-mass spectrometry. Metabolic evaluation of all 3 patients identified significant hypocitraturia as an isolated finding.. The widely used protease inhibitor indinavir is associated with the development of urolithiasis and may act as a nidus for heterogeneous nucleation leading to the development of mixed urinary stones. Surgical intervention may be necessary in some cases. Underlying metabolic abnormalities may contribute to the increased incidence of stone formation. Urologists and other health care providers should be aware of this association, as combined medical and surgical intervention may be necessary.

Topics: Adult; Female; HIV Protease Inhibitors; Humans; Indinavir; Kidney Calculi; Male; Middle Aged