Risk factors associated with End Stage Renal Disease (ESRD) in HIV positive patients in the US Veterans Association (VA) cohort
Simon Collins, HIV i-Base
An analysis of the risks associated with end stage renal disease (ESRD), defined as need for dialysis or transplant, in HIV positive patients who receive care from the Veterans Association (VA) in the US was published in the May 2012 edition of the American Journal of Kidney Diseases. 
This provides additional useful information to the VA analysis of the impact of ART on markers of renal dysfunction published in AIDS (and reviewed above). 
The current study was a retrospective review of >22,100 patients without ESRD who received care between 1996 and 2004. Data was retrieved for the following parameters: hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin <3.5 mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and eGFR. The researchers were particularly interested in association between ESRD and proteinuria and eGFR.
Over a median individual follow-up of 69 months, the review identified 366 cases of ESRD with an incidence of 3/1000 patient years (PY).
In multivariate analysis, traditional cormorbidities that were associated with ESRD (Hazard Ratio: 95%CI) were hypertension (HR 1.9; 1.5-2.4), diabetes (HR 1.7; 1.3-2.2), cardiovascular disease (HR 2.2; 1.7-2.7), hepatitis C virus coinfection (HR 1.9; 1.5-2.4), and hypoalbuminemia (HR 2.1; 1.8-2.5).
Although the study reported that CD4 count <200 cells/mm3 (HR 1.5; 1.2-2.0; compared to CD4 >350) and HIV viral load =30,000 copies/mL (HR 2.0; 1.5-2.8) were associated with ESRD, when adjusted for competing risk of death before ESRD, both these HIV related factors became non-significant.
Patients who developed ESRD were more likely to have had proteinuria or eGFR <60 at baseline compared as well as other cormorbidities with an exponential association relating to both factors: ranging from 6.6 /1,000 PY (urine protein excretion of 30-100 mg/dL and eGFR >60) to 193/1,000 PY (urine protein excretion =300 mg/dL and eGFR <30).
Similar to HIV negative studies, black patients were at 3-fold higher risk of ESRD than white patients (85% of cases were black vs 14% white).
When stratified by race, the adjusted hazard ratios for ESRD for each risk factor were similar between the white and black race groups, with the exception of diabetes (HR 4.5; 2.3-9.0 vs 1.6; 1.2-2.1) white vs in black individuals respectively, (p for interaction=0.002).
The study was not designed to look at the long-term effects of ART or individual drugs and kidney function. A similar proportion of patient with and without ESRD used ART
The researchers concluded that staging patients with CKD jointly by eGFR and proteinuria resulted in strong risk stratification for ESRD in HIV positive patients and that this could be used broadly in clinical practice.
Event rates of ESRD were reported as comparable to those of myocardial infarction reported in the D:A:D study , although it is notable that ESRD in D:A:D in considerably lower (with <100 ESRD compared to >900 MI’s). This appears to be accounted for by race as similar proportions of patients without ESRD were black and white (42% vs 36% respectively), but 85% of patients with ESRD were black compared to 13% who were white.
The study also discussed a limitation from not having biopsy results to distinguish HIVAN from other pathologies.
The potential to use combined proteinuria and eGFR to stage risk of ESRD in HIV positive patients warrants further study. Given the VA is an almost exclusively male cohort, this finding needs to be looked at in mixed populations.
- Jotwani V et al. Risk factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors: VA Study/risk factors. American Journal of Kidney Diseases American Journal of Kidney Diseases. Volume 59, Issue 5 , Pages 628-635, May 2012; DOI: 10.1053/j.ajkd.2011.10.050.
- Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.