HIV-Associated Kidney Disease

John G. Bartlett, MD


June 02, 2009

This Viewpoint synthesizes a recent review of HIV-related kidney disease by 6 experts on the topic.

Kidney Disease in Patients With HIV Infection and AIDS

Winston J, Deray G, Hawkins T, Szczech L, Wyatt C, Young B
Clin Infect Dis. 2008;47:1449-1457

Article Summary

HIV-associated nephropathy was first reported in 1984.[1] This complication has since become the third leading cause of end-stage renal disease (ESRD) in black individuals aged 20-64 years.[2] Highly active antiretroviral therapy (HAART) reduced the risk for ESRD by 40% to 60%; the 1-year survival for patients undergoing dialysis increased from 25% to 75%; and kidney transplantation became an option.

Risk Factors for Chronic Kidney Disease

  • Major indicators of renal damage are measurement of protein excretion (dipstick or quantitative measurements) and calculation of creatinine clearance or glomerular filtration rate (GFR). A sustained GFR < 60 mL/min is the criterion for chronic kidney disease (CKD).

  • Diabetes and hypertension are the most common causes of CKD in the general population; they increase the risk for CKD by 10-fold and account for 71% of all ESRD. Results of the Multicenter AIDS Cohort Study indicate that the prevalence of diabetes among men with HIV infection is 14%, which is 4-fold higher than for those without HIV.[3] The rate of hypertension in this population also shows a 3-fold increase compared with age-matched controls.[4]

  • Race: Young black men have an 11-fold increased risk for CKD.[5] Black patients with CKD experience a much more aggressive disease course compared with white patients, with an odds ratio of 18 for a rapid decrease in GFR.[6]

  • Age: The increasing age of patients with HIV infection also contributes to the rate of and risk for CKD.

Acute Renal Failure

  • Drugs: Many drugs that are taken for HIV infection are responsible for causing acute renal failure, including acyclovir, adefovir, aminoglycosides, amphotericin, beta lactams (interstitial nephritis), cidofovir, foscarnet, ganciclovir, pentamidine, sulfonamides, and trimethoprim.

  • Infections: 10% of patients in a large clinic experienced at least 1 episode of acute renal failure during a 2-year period, and half of these were attributed to infection, usually an AIDS-defining complication.[7]

Antiretroviral Agents and Kidney Disease

Several reports link antiretrovirals to kidney disease, but most indicate very low rates, with the exception of indinavir, a drug that is used infrequently at present. Other drugs associated with renal disease include abacavir, atazanavir, didanosine, efavirenz, enfuvirtide, lamivudine, ritonavir, and stavudine. The antiretroviral most associated with nephrotoxicity is tenofovir:

  • Tenofovir is structurally similar to adefovir and cidofovir; cidofovir has been reported to cause acute renal failure and adefovir has been implicated as well, with a dose that is 10 times higher than that used for hepatitis B virus. In both cases, there is a characteristic proximal renal tubule damage characterized by proteinuria, glycosuria, hypokalemia, and hypophosphatemia (Fanconi syndrome).

  • Rare cases of tenofovir-associated Fanconi syndrome have been reported.

  • Decreases in GFR: Many prospective clinical trials have shown no reduction in GFR for tenofovir recipients.[8] Others have shown very modest declines in GFR averaging 7-10 mL/min/year.[9,10,11,12] The susceptibility of black patients to renal toxicity has been reported to be either nil or rare.[13] Studies of tenofovir given with a protease inhibitor-boosted regimen have also shown rates of nephrotoxicity that are nil or less than 2%.[14,15,16]

Conclusions regarding tenofovir:

  • Combined data reveal rates of drug discontinuation related to renal dysfunction of 0% to 2% and no difference in severe renal disease compared with the alternative HIV drugs.

  • Decreases in GFR of up to 7-10 mL/min/year have been noted, although the GFR has generally remained in the normal range. However, if this reduction were sustained over a period of several years, it could lead to high rates of serious renal disease, although no such trends have been reported.

  • The authors recommend baseline renal screening and, for those with preexisting renal disease, dose adjustments with careful monitoring. An alternative regimen should be considered for patients with a GFR < 60 mL/min.

Treatment of CKD

  • The standard urine dipstick is adequate to screen for proteinuria; patients with diabetes should also be tested for microalbuminuria.

  • Renal biopsy should be strongly considered for unexplained renal disease on the basis of heavy proteinuria or decreased GFR because these represent the greatest risk for ESRD.

  • HIV-associated nephropathy: Kidney biopsy is usually indicated and antiretroviral therapy should be given regardless of CD4 count because HIV replication is the cause of this complication.

  • Patients with hypertension should receive angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers because these reduce protein excretion and slow the progression of ESRD. In the setting of diabetes, blood glucose control is critical for delaying diabetic nephropathy.