aDepartment of Medicine, Division of Nephrology, Mount Sinai School of Medicine, New York, New York, USA
bDepartment of Infectious Diseases, Mount Sinai School of Medicine, New York, New York, USA.
Received 8 March, 2007
Revised 14 June, 2007
Accepted 20 June, 2007
Kidney disease is an important complication of HIV, particularly in minority populations. We describe the burden of chronic kidney disease among 1239 adults followed at an urban AIDS center, with an estimated prevalence of 15.5% (n = 192). Independent predictors of kidney disease included older age, black race, hepatitis C virus exposure, and lower CD4 cell count. These data suggest that chronic kidney disease remains a common complication of HIV infection in the era of antiretroviral therapy.
Kidney disease is an important complication of HIV infection in the era of antiretroviral therapy (ART) . Between 1999 and 2003, more than 4000 new cases of end-stage renal disease (ESRD) were attributed to HIV in the United States, over 90% in black individuals . With improved survival and a rising prevalence of HIV in minority populations, the prevalence of HIV-related ESRD is expected to increase . Previous studies of earlier chronic kidney disease (CKD) focused on more advanced disease, and often enrolled patients before the widespread use of ART [4–6]. Although ART improves the course of HIV-associated nephropathy [3,7–10], it may increase the risk of co-morbid CKD or nephrotoxicity . More recently, the EuroSIDA Study Group observed a low prevalence of CKD in a predominantly white, ART-treated cohort . The authors acknowledged that their results may not be generalizable to minority populations, and noted that proteinuria assessment may have identified additional cases of CKD . We sought to describe the prevalence of CKD, defined by decreased kidney function or proteinuria, in a large HIV clinic population with a high proportion of minority patients.
The Mount Sinai AIDS Center is a Designated AIDS Center serving East Harlem, New York. Cross-sectional data were abstracted for all active adult patients, including age, sex, self-reported race, serum creatinine, urinalysis, hepatitis C virus (HCV) antibody, hepatitis B virus surface antigen, CD4 cell count, and HIV viral load. Additional data were abstracted for patients with CKD, including history of diabetes or hypertension, ART regimen, and antihypertensive agents. The Mount Sinai Institutional Review Board approved this study.
To exclude spurious results or acute renal failure, any creatinine level deviating by 0.3 mg/dl or more from previous values was excluded, and the last stable value was used. Urinalyses with possible infection (leukocyte esterase ≥ 1+ or positive culture) or hematuria ≥ 2+ were also excluded. The glomerular filtration rate (GFR) was calculated using the four-variable Modification of Diet in Renal Disease equation. Because of a significant racial admixture, all GFR estimates assumed black race. Proteinuria was defined as urine protein of 100 mg/dl or greater. CKD was defined by proteinuria or GFR less than 60 ml/min per 1.73 m2, based on expert guidelines .
Data were analysed using STATA version 9 (College Station, Texas, USA). Inter-group comparisons were performed using chi-square or analysis of variance and unpaired t-tests, as appropriate. Factors associated with CKD (P < 0.1), as well as potential interactions, were tested for inclusion in a multivariate logistic regression model. Black race was included as a dichotomous variable. A P value of less than 0.05 was considered significant.
A total of 1241 adults had viral load testing within 12 months and were considered active patients. After excluding two men (aged 20 and 41 years) without creatinine data, 1239 patients were included (Table 1). One-third of patients were over the age of 50 years, and nearly 90% were black or Hispanic. One-quarter of patients had a CD4 cell count below 200 cells/μl, and approximately half had a detectable viral load.
Fifty-one patients (4.1%) had ESRD, including seven transplant recipients. Urine was available for 934 (79%) of the remaining patients. Ninety-eight patients had urine protein of 1+ or greater, including 68 with a GFR of 60 ml/min per 1.73 m2 or greater (stage 1–2). Thirty patients with proteinuria and 43 patients without proteinuria had a GFR less than 60 ml/min per 1.73 m2 (stage 3–5). Overall, 192 patients (15.5%) had chronic or end-stage kidney disease.
Patients with CKD were older, more likely to be black, and more likely to have HCV (Table 1). The mean CD4 cell count was lower among patients with CKD, with no difference in the proportion with CD4 cell counts below 200 cells/μl. In adjusted analyses, older age, black race, HCV and lower CD4 cell count were independently associated with CKD. In contrast to previous studies, virological suppression was more common among patients with CKD.
Complete clinical data were available for 129 out of 141 patients with pre-end stage CKD (92%). Seventy-seven (55%) had hypertension and 26 (20%) had diabetes. Only 26% were taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. More than 84% were on ART, including nucleoside/nucleotide reverse transcriptase inhibitors (82%), protease inhibitors (54%), non-nucleoside reverse transcriptase inhibitors (28%), and enfurvitide (2%). Forty-one patients were on trimethoprim, which may interfere with tubular creatinine secretion . Most of these patients had proteinuria (n = 31) or GFR below 30 ml/min per 1.73 m2 (n = 4). No patients with CKD were prescribed other nephrotoxic antimicrobial agents.
Fifteen per cent of patients in this urban HIV population met the current diagnostic criteria for CKD. These data support the projected rise in the prevalence of ESRD  and highlight the need for increased awareness of CKD, particularly in minority populations. Patients with HIV and CKD are at risk of ESRD, acute renal failure, and medication toxicity, and may be at an increased risk of cardiovascular disease . Early recognition facilitates the diagnosis and treatment of reversible causes, the anticipation of complications, and preparation for dialysis or transplantation in patients with progressive disease.
Factors associated with CKD in our population included previously reported risk factors such as older age, black race, HCV, and lower CD4 cell count [4,8]. In contrast to previous studies, virological suppression was more likely among patients with CKD. It is possible that patients with reduced GFR achieve higher blood levels of renally eliminated ART, or that improved survival with virological suppression allows the development of late complications.
Although our population is representative of many urban HIV populations, the high prevalence of CKD may not be generalizable to populations with few minority patients . Nonetheless, these data probably underestimate the burden of CKD in our population. The conservative assumption of black race in GFR calculations would overestimate GFR in non-black individuals, and lower levels of proteinuria were excluded to improve specificity. The inclusion of these patients would increase the prevalence of CKD to more than 35%.
The current study demonstrates a high prevalence of CKD among HIV-infected minority patients with access to ART and specialized HIV care. More than one-third of the patients identified had proteinuria and preserved kidney function, representing an opportunity to prevent or delay progression. Future studies should identify factors associated with kidney disease progression in this high-risk population.
Sponsorship: This work was partly supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant PO1 DK56492-05.
1. Gupta SK, Eustace JA, Winston JA, Boydstun II, Ahuja TS, Rodriguez RA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005; 40:1559–1585.
2. US Renal Data System (USRDS). USRDS 2005 Annual Data Report: atlas of end-stage renal disease in the United States. Bethesda, MD, USA: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2005.
3. Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. HAART and the epidemic of HIV+ end stage renal disease. J Am Soc Nephrol 2005; 16:2412–2420.
4. Szczech LA, Gange SJ, Van der Horst C, Bartlett JA, Young M, Cohen MH, et al. Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 2002; 61:195–202.
5. Gupta SK, Mamlin BW, Johnson CS, Dollins MD, Topf JM, Dube MP. Prevalence of proteinuria and the development of chronic kidney disease in HIV-infected patients. Clin Nephrol 2004; 61:1–6.
6. Krawczyk CS, Holmberg SD, Moorman AC, Gardner LI, McGwin G, HIV Outpatient Study Group. Factors associated with chronic renal failure in HIV-infected ambulatory patients. AIDS 2004; 18:2171–2178.
7. Atta MG, Gallant JE, Rahman MH, Nagajothi N, Racusen LC, Scheel PJ, Fine DM. Antiretroviral therapy in the treatment of HIV-associated nephropathy. Nephrol Dial Transplant 2006; 21:2809–2813.
8. Szczech LA, Gupta SK, Habash R, Guasch A, Kalayjian R, Appel R, et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int 2004; 66:1145–1152.
9. Lucas GM, Eustace JA, Sozio S, Mentari EK, Appiah KA, Moore RD. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS 2004; 18:541–546.
10. Cosgrove CJ, Abu-Alfa AK, Perazella MA. Observations on HIV-associated renal disease in the era of highly active antiretroviral therapy. Am J Med Sci 2002; 323:102–106.
11. Wyatt CM, Klotman PE. Antiretroviral therapy and the kidney: balancing benefit and risk in patients with HIV infection. Expert Opin Drug Saf 2006; 5:275–287.
12. Mocroft A, Kirk O, Gatell J, Reiss P, Gargalianos P, Zilmer K, et al, EuroSIDA Study Group. Chronic renal failure among HIV-1-infected patients. AIDS 2007; 21:1119–1127.
© 2007 Lippincott Williams & Wilkins, Inc.