Prospective study of urinalysis abnormalities in HIV-positive individuals treated with indinavir

Gagnon, Raymonde F.; Tecimer, Sandy N.; Watters, Andrew; Tsoukas, Christos

doi:10.1053/ajkd.2000.9791

Cited by 60 publications

(33 citation statements)

References 25 publications

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“…Our study shows statistical association between ARV drugs and CKD that needs to be documented further to identify nephrotoxic mechanisms. Tenofovir and indinavir have been shown to be related to nephrotoxicity in many studies (2,5,6,10,11,25). Some factors (hepatitis B or C and diabetes) traditionally reported as related to CKD in persons with or without HIV-1 infection were not found to be independently associated with the occurrence of CKD in our analysis (5,26,27).…”

Section: Discussionmentioning

confidence: 49%

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Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Flandre¹,

Puglièse²,

Cuzin³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients.Design, setting, participants, & measurements Patients were followed from seven large HIV reference centers in France that maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR Յ60 ml/min per 1.73 m 2 over Ն3 months. A Cox's model with delayed entry was used to search predictive factors of time to CKD.Results From 1993 to 2006, 349 out of 7378 patients were found to have CKD. Of these, 166 had hypertension, 33 had diabetes, and 26 were antiretroviral therapy-naïve. Occurrence of acute kidney injury (hazard ratio [HR] ϭ 2.40) and hypertension (HR ϭ 2.39) were strongly associated with an increased risk of CKD. Patients with a durable level of CD4 count Ͼ200 cells/mm 3 had a lower risk of CKD (HR ϭ 0.63). Recent exposure to indinavir (HR ϭ 2.03), totenofovir (HR ϭ 1.55), and abacavir (HR ϭ 1.37) were associated with an increased risk of CKD. Past exposure to tenofovir was also associated with an increased risk of CKD (HR ϭ 2.23), and a trend toward significance was observed for past exposure to indinavir (HR ϭ 1.28).Conclusions CKD was not rare in HIV-infected patients and occurs preferentially in HIV-infected patients exposed to certain ARVs, specifically abacavir, indinavir and tenofovir. This requires closer monitoring of renal function in patients exposed to one of these drugs.

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Section: Discussionmentioning

confidence: 49%

“…AKI and a decline in renal function have been reported in association with indinavir (2,6), atazanavir (7), and ritonavir (8,9). Proximal tubular dysfunction and acute tubular necrosis have been reported in patients starting tenofovir (10 -13) or didanosine (14), often precipitated by drug interactions (15).…”

Section: Introductionmentioning

confidence: 99%

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Flandre¹,

Puglièse²,

Cuzin³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…Indinavir has been associated with crystalluria, nephrolithiasis, and obstructive ARF (82)(83)(84)(85). Asymptomatic crystalluria occurs in up to two thirds of treated patients; pyuria, microscopic hematuria, and low-grade proteinuria are also seen.…”

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 99%

“…Indinavir is highly soluble in acidic urine (100 mg/ml at pH 3.5) but relatively insoluble in more alkaline urine (0.3 mg/ml at pH 5.0, 0.035 mg/ml at pH 6.0, and 0.02 mg/ml at pH 7.0), predisposing to the development of crystals at typical urine pH levels (90). Crystals of varying shapes have been described and are more common in urine with pH Ն6 (83,84,91). Urinary stones are composed primarily of indinavir monohydrate; calcium oxalate and phosphate as well as indinavir metabolites may also be present (83,92).…”

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 99%

Highly Active Antiretroviral Therapy and the Kidney

Berns

Kasbekar

2006

Clinical Journal of the American Society of Nephrology

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Highly active antiretroviral therapy has dramatically altered the treatment and life expectancy of individuals who are infected with HIV. More than 20 antiretroviral drugs and drug combinations now are available in the United States. Nephrologists need to have an understanding of the pharmacokinetics of antiretroviral medications and the proper dosing of these medications in patients with impaired kidney function. It is also important for nephrologists to be aware of drug-drug interactions that can occur between antiretroviral medications and other medications that they may prescribe, including immunosuppressive medications that are used for renal transplantation, as this becomes more common in HIV-infected patients. Adverse reactions that affect the kidneys and cause fluid-electrolyte complications occur with certain antiretroviral agents, although most are relatively free of nephrotoxicity. This article reviews the clinical pharmacology and dosing modifications of the newer antiretroviral medications in patients with reduced kidney function; important drug-drug interactions involving these medications, particularly with other medications that are likely to be prescribed by nephrologists; and renal toxicities of antiretroviral agents.

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“…A number of cofactors, such as African-American ethnicity, advanced immunodeficiency (CD4 cell count o200 cells/mL), detectable HIV plasma viral load (pVL)44000 copies/mL, hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection, high blood pressure (HBP) and diabetes mellitus (DM), have all been associated with nephropathy in HIV-infected subjects [14][15][16]. Highly active antiretroviral therapy (HAART) seems to improve the overall survival rate of patients with HIVAN and reduce the incidence of cases of HIV-related kidney damage [17,18], but some specific antiretroviral (ARV) drugs, such as indinavir [19,20] and tenofovir (TDF) [20][21][22][23][24][25][26][27][28][29][30], have been associated with increased risk of acute and chronic renal failure. HIV-infected patients may also be frequently exposed to nephrotoxic drugs, commonly used for treatment or prophylaxis of opportunistic infections, and this practice may result in overlapping renal toxicity between these agents and ARVs.…”

Section: Introductionmentioning

confidence: 99%

Comparison of glomerular filtration rate estimates vs. 24‐h creatinine clearance in HIV‐positive patients

Ravasi¹,

Lauriola²,

Tinelli

et al. 2009

HIV Medicine

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BackgroundGuidelines for kidney function monitoring and antiretroviral drug dosing are available and respectively refer to glomerular filtration rate and creatinine clearance (CrCl). ObjectiveThe aim of the study was to compare kidney function estimates vs. measured 24-h CrCl in HIVinfected subjects. MethodsA cross-sectional design was used, with comparison of Cockcroft-Gault (CG), original and simplified modification of diet in renal disease (MDRD) equations vs. measured 24-h CrCl. Subjects were HIVinfected, 18-70 years old, without pre-existing kidney disease. ResultsResults are presented as mean (AE standard deviation), unless otherwise stated. The study population consisted of 90 patients, of whom 71% were male, with a mean age of 45 years (AE 6.5 years). At the time of evaluation, the mean body mass index was 23 (AE 3.3); mean serum creatinine was 0.91 mg/dL (AE 0.2 mg/dL); and mean blood urea nitrogen (BUN) was 34.7 mg/dL (AE 10.6 mg/dL). Differences between paired methods were all significant (Po0.00001), except between CG and simplified MDRD (P 5 0.21; Pearson r 5 0.81). In univariate analysis, male gender, CD4 nadir, hepatitis B virus coinfection, BUN and current CD4 cell count showed a significant positive correlation (Po0.2) with the difference between measured 24-h CrCl and either CG or simplified MDRD estimates. In multivariate analysis, only BUN showed a significant positive correlation (Po0.05). ConclusionsEstimates were lower than the measurements of 24-h CrCl. Original MDRD estimates were lower than those with other equations. CG and simplified MDRD estimates showed a satisfactory correlation.

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Prospective study of urinalysis abnormalities in HIV-positive individuals treated with indinavir

Cited by 60 publications

References 25 publications

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Risk Factors of Chronic Kidney Disease in HIV-infected Patients

Highly Active Antiretroviral Therapy and the Kidney

Comparison of glomerular filtration rate estimates vs. 24‐h creatinine clearance in HIV‐positive patients

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