The risk of chronic and end-stage kidney disease among HIV-positive people of African ethnicity varies according to the region of origin and is highest among those of West African descent, according to UK research published in The Journal of Infectious Diseases. A low CD4 cell count and ongoing viral replication were also risk factors for serious kidney disease.
“This is, to our knowledge, the first study to directly compare the rate of kidney disease progression in different African populations,” comment the authors. “After adjusting for demographic and HIV-specific parameters, we observed marked regional differences among people from sub-Saharan Africa who were resident in Britain.”
The investigators believe that genetic factors are the key determinant in the risk of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) risk, and that their findings have implications for increasing HIV coverage in regions with the highest CKD/ESKD rates.
CKD is an important and increasing cause of serious illness and death in Africa. In black HIV-positive people, HIV-associated nephropathy (HIVAN) is the most severe form of kidney disease and the leading cause of ESKD. Antiretroviral therapy (ART) that suppresses viral load and increases CD4 cell count reduces the risk of HIVAN.
Previous research has shown that the risk of HIVAN is strongly associated with the APOL1 gene. Prevalence of this gene in sub-Saharan Africa is highest in West Africa, lower in Southern Saharan Africa and lowest in East Africa.
A large number of people of sub-Saharan African ancestry are receiving HIV care in the UK. Monitoring of kidney function is a key component of this care. Investigators from the UK Collaborative HIV Cohort (UKCHIC) undertook an observational study to determine the prevalence and risk factors of CKD and ESKD among adults of African descent enrolled in the cohort. They hypothesised that, consistent with the distribution of the APOL1 gene in Africa, rates of serious kidney disease would be highest among those of West Africa descent, intermediate in people of Southern African ancestry and lowest in those of East African ancestry. People of Caribbean origin, most of whom are of West African ancestry, were also included in the analysis.
A total of 7788 people were included in the analysis.
Mean age was approximately 36 years. The majority of African patients (58-68%) were female, whereas two-thirds of Caribbean patients were male.
Between a third and 53% of people were ART experienced. Median viral load ranged between region from 800 copies/ml and 8000 copies/ml. Median CD4 cell count was approximately 300 cells/mm3 among people of sub-Saharan African origin and 370 cells/mm3 among people of Caribbean ancestry.
There were significant differences in baseline kidney function according to region of origin. People of West African origin were less likely to have normal kidney function than people from other regions.
A total of 3% of people presented with or developed CKD (defined as two eGFR measurements < 60 mL/min/1.73m2 over more than three months) during follow-up whereas incidence of ESKD (defined as < 15 mL/min/1.73m2 over greater than three months) was 1%.
The probability of developing serious kidney disease was highest among people of West African origin, with 6% developing CKD and 2% ESKD during ten to 15 years of follow-up. People from Southern Africa had intermediate rates of CKD, with the lowest among people of East African origin. Rates of CKD among people of Caribbean origin were broadly similar to those observed in people of West African ancestry.
After controlling for demographic and HIV-related factors and using East African patients as a reference group, incidence of CKD/ESKD was highest among West Africans (IRR = 6.35; 95% CI, 2.53-15.96). Incidence was slightly lower among individuals of Caribbean origin (IRR = 5.26; 95% CI, 1.91-14.43) and lower still among people of Southern African ancestry (IRR = 3.14; 95% 1.26-7.84).
A higher CD4 cell count and viral suppression were associated with a reduced risk of serious kidney disease.
Tenofovir-containing ART was likewise associated with a lower risk of CKD/ESKD. Although tenofovir has been associated with kidney toxicities, the investigators note that research in Africa has previously shown that tenofovir treatment is associated with a reduced risk of kidney disease.
“We observed notably higher rates of CKD in West Africans and Caribbeans, 2 populations with shared ancestry, suggesting that genetic factors are likely to be important CKD risk factors in the setting of HIV,” conclude the investigators. “As immunovirological control was an important additional CKD risk factor and levels of HIV diagnosis, ART coverage, and viral suppression, especially in West Africa and the Caribbean, remain well below the 90-90-90 target set by UNAIDS, scale up of HIV diagnosis, treatment, and prevention programs in these regions should be prioritized.”
Jose S et al. Chronic kidney disease risk in African and Caribbean population with HIV. J Infect Dis, online edition, 2018. https://doi.org/10.1093/infdis/jiy397