Development of Proteinuria or Elevated Serum Creatinine and Mortality in HIV-Infected Women

Centers for Disease Control and Prevention, Mailstop E-45 Division of HIV/AIDS, 1600 Clifton Road NE, Atlanta, GA 30333, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 02/2003; 32(2):203-9. DOI: 10.1097/00126334-200302010-00013
Source: PubMed


Data on the incidence and prognostic significance of renal dysfunction in HIV disease are limited.
To determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women.
The incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women.
Women from the general community or HIV care clinics in four urban locations in the United States.
Creatinine of >or=1.4 mg/dL, proteinuria 2 or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%).
At baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9-3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2.7%), p<.0001) in HIV-infected women with, compared with those without these renal abnormalities.
Proteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons.

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    • "urine protein >0.5 g/day) predicts both cardiovascular events and CKD progression [43]. The associations of elevated albumin and protein excretion with future risks of developing renal failure, cardiovascular events and death have also been confirmed in studies in HIV positive patients [44-47], and thus, urine albumin and protein excretion should be assessed and taken into account in cardiovascular and CKD risk reduction strategies. "
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    ABSTRACT: Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI). Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR. In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.
    BMC Nephrology 08/2012; 13(1):85. DOI:10.1186/1471-2369-13-85 · 1.69 Impact Factor
    • "The causes of renal disease in HIV-infected patients are multifactorial and include HIV infection itself, co-infections, co-morbidities, and their treatments.4 AIDS-related kidney disease has become a relatively common cause of end-stage renal disease (ESRD) requiring renal replacement therapy, and kidney disease may be associated with progression to AIDS and death.56 "
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    ABSTRACT: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria. This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1. Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively. Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs.
    Journal of the Nigeria Medical Association 07/2011; 52(3):182-5. DOI:10.4103/0300-1652.86133
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    • "Renal disease independently predicts progression to AIDS and overall mortality in US urban women not receiving cART [4,5]. In this study of urban American women enrolled in the Women's Interagency HIV Study (WIHS) cohort, Szczech et al showed that dipstick proteinuria, but not inverse creatinine, was significantly associated with the development of a new AIDS-defining illness [5]. "
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    ABSTRACT: The World Health Organization (WHO) has recently recommended that antiretrovirals be initiated in all individuals with CD4 counts of less than 350 cells/mm3. For countries with resources too limited to expand care to all such patients, it would be of value to able to identify and target populations at highest risk of HIV progression. Renal disease has been identified as a risk factor for disease progression or death in some populations. Times to meeting combination antiretroviral therapy (cART) initiation criteria (developing either a CD4 count < 200 cells/mm3 or WHO stage 3 or 4 disease) and overall mortality were evaluated in cART-naïve, HIV-infected Kenyan adults with CD4 cell counts ≥200/mm3 and with WHO stage 1 or 2 disease. Cox proportional hazard regression models were used to evaluate the associations between renal function and these endpoints. We analyzed data of 7383 subjects with a median follow-up time of 59 (interquartile range, 27-97) weeks. In Cox regression analyses adjusted for age, sex, WHO disease stage, CD4 cell count and haemoglobin, estimated creatinine clearance (CrCl) < 60 mL/min was significantly associated with shorter times to meeting cART initiation criteria (HR 1.34; 95% CI, 1.23-1.52) and overall mortality (HR 1.73; 95% CI, 1.19-2.51) compared with CrCl ≥60 mL/min. Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 was associated with shorter times to meeting cART initiation criteria (HR 1.39; 95% CI, 1.22-1.58), but not with overall mortality. CrCl and eGFR remained associated with shorter times to cART initiation criteria, but neither was associated with mortality, in weight-adjusted analyses. In this large natural history study, reduced renal function was strongly associated with faster HIV disease progression in adult Kenyans not initially meeting cART initiation criteria. As such, renal function measurement in resource-limited settings may be an inexpensive method to identify those most in need of cART to prevent progression to AIDS. The initial association between reduced CrCl, but not reduced eGFR, and greater mortality was explained by the low weights in this population.
    Journal of the International AIDS Society 06/2011; 14(1):31. DOI:10.1186/1758-2652-14-31 · 5.09 Impact Factor
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