African American HIV Patients Experience More Aggressive Kidney Disease Progression

By Liz Highleyman

Several previous studies have shown that HIV positive African Americans have a higher risk of end-stage renal disease (ESRD), or kidney failure, compared with their white counterparts. This racial disparity is also apparent in the HIV negative general population.

Blacks have been shown to be particularly prone to a form of kidney disease known as HIV-associated nephropathy (HIVAN), which involves damage to the glomeruli, structures in the kidneys that filter blood.

As previously reported, Gregory Lucas and colleagues from Johns Hopkins University in Baltimore found that nearly 1% of HIV positive African Americans required renal replacement therapy (kidney dialysis or transplant) annually. This rate was similar in the HAART and pre-HAART eras. "While new cases of CKD [chronic kidney disease] decreased, the prevalence of CKD increased in the HAART era," the authors noted, "primarily because survival in those with HIV-associated CKD has improved."

In a new study, published in the June 1, 2008 Journal of Infectious Diseases, Lucas and his team looked at racial differences in the incidence and progression of HIV-related kidney disease that underlie the observed disparities in ESRD between African Americans and whites.
The researchers measured CKD incidence, glomerular filtration rate (GFR) slope, and progression to ESRD in 3332 African American and 927 white HIV positive participants in the John Hopkins HIV Clinical Cohort. The mean follow-up period was 4.5 years.

Results

• Of 4185 subjects without kidney disease at enrollment, 210 developed incident (new-onset) CKD (11.2 cases per 1000 person-years).

• Among the 284 study participants with pre-existing or incident CKD during follow-up, 100 (35%) subsequently developed ESRD.

• 99 African American with CKD progressed to ESRD, compared with just 1 white patient (39% vs 3%; P < 0.001).

• African American subjects had a slightly higher risk of developing incident CKD -- about twice as likely -- compared with white patients (hazard ratio [HR] 1.9).

• Having an AIDS diagnosis was the strongest predictor of new-onset CKD.

• However, once CKD developed, African Americans progressed to ESRD "markedly faster" -- nearly 18 times as fast -- compared with white patients (HR 17.7).

• At CKD diagnosis, African Americans had significantly higher serum creatinine and urinary protein excretion, and significantly lower GFR, serum albumin, and serum hemoglobin, compared with whites.

• African Americans experienced a 6-fold more rapid decline in GFR after CKD diagnosis.

• Progression to ESRD was significantly faster in African Americans than in white patients with CKD, irrespective of the presence of HIVAN (which was only observed in blacks).

• Among African American patients with available kidney biopsies, 63% of those with HIVAN progressed to ESRD, compared with 46% of those with non-HIV-associated nephropathy.

• In addition to race, younger age, baseline GFR, annual GFR slope, serum albumin concentration, degree of proteinuria, and non-use of kidney medications were significantly associated with progression to ESRD (though a multivariate analysis could not be performed because only 1 white patient developed ESRD).

• While the incidence of CKD declined in successive calendar periods, the risk of progression to ESRD was similar during the pre-HAART and HAART eras and was not associated with type of antiretroviral therapy.

In conclusion, the study authors wrote, "The results of this study suggest that African American-white disparities in HIV-related ESRD are explained predominantly by a more aggressive natural disease history in African Americans and less by racial differences in CKD incidence."

In their discussion, the investigators stated that their findings support the incorporation of kidney function screening into routine HIV care, as well as use of angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker drugs to reduce the risk of progression to ESRD in patients with HIV-related CKD.

They also said their findings "suggest that initiation of HAART be considered earlier during HIV disease than is suggested by current treatment guidelines. This point may be particularly applicable to HIV-infected African Americans, who, compared with whites, tend to start therapy later during the course of the disease and are at substantially higher risk of progressing to ESRD."

Results from the large SMART study, they added, showed that CD4 cell-guided structured treatment interruption was associated with a higher risk of fatal and non-fatal kidney disease (as well as heart and liver disease) compared with continuous therapy.

The latest U.S. treatment guidelines recommend that all individuals with HIVAN should start combination antiretroviral therapy, regardless of CD4 cell count, as HAART has been shown to improve kidney function in such patients.

However, Lucas and colleagues emphasized that African American patients with non-HIVAN histopathology also had a significantly higher risk of progression to ESRD compared with whites, suggesting that "a substantial racial difference in CKD progression exists independent of HIVAN."

Editorial

In an accompanying editorial, Christina Wyatt from Mount Sinai School of Medicine noted that as far back as 1984, New York City physicians described an aggressive form of kidney disease -- later recognized as HIVAN -- affecting 12% of AIDS patients at their hospital, all of whom were African Americans or Haitian immigrants. Today, African Americans account for nearly 90% of new ESRD cases due to HIVAN in the U.S.

Wyatt added that other studies, including a recent analysis of U.S. veterans, also observed a much higher rate of incident ESRD in African Americans with HIV, even though the baseline prevalence of decreased kidney function was similar across racial groups.

She further noted that given this racial disparity among HIV patients in the U.S., "[t]he potential implications for sub-Saharan Africa are even more staggering, particularly in light of the limited infrastructure for identification and management of kidney disease and ESRD."

"In light of the potential for an epidemic of HIV-related kidney disease and ESRD in disadvantaged minority populations and in Africa, the international medical community should work to develop simple, inexpensive, and reliable methods to detect and manage early kidney disease in these vulnerable populations," she concluded.

7/22/08

References

GM Lucas, B Lau, MG Atta, and others. Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races. Journal of Infectious Disease 197(11): 1548-1557. June 1, 2008.
(Abstract)

CM Wyatt. HIV and the Kidney: a spotlight on racial disparities. Journal of Infectious Disease 197(11): 1490-1492. June 1, 2008.