Infection with HIV associated with increased risk of dialysis and end-stage kidney disease

HIV infection increases the risk of kidney disease requiring renal replacement therapy or dialysis, according to Danish research published in the online edition of Nephrology Dialysis Transplantation. The investigators compared the incidence of disease needing replacement therapy and end-state renal disease between people living with HIV and matched HIV-negative controls from the general population.

Infection with HIV was associated with a fivefold increase in the risk of requiring acute renal replacement treatment and a fourfold increase in the risk of end-stage renal disease. High blood pressure (hypertension) and injecting drug use were risk factors for renal replacement therapy. However, neither tenofovir (Viread, also in the combination pills Truvada, Eviplera and Atripla) nor atazanavir (Reyataz) were associated with disease requiring dialysis.

Kidney disease is now an important cause of serious illness and death in people living with HIV. The reasons are unclear, but appear to include traditional risk factors, the damage caused by HIV and the side-effects of some antiretroviral drugs, especially tenofovir and atazanavir.

Investigators in Denmark wanted to see if HIV increased the risk of kidney disease requiring acute or chronic renal replacement therapy or dialysis.

They therefore compared the incidence of these outcomes between 5300 people living with HIV who received care after 1995 and 53,000 age- and sex-matched HIV-negative controls in the general Danish population.

Over three-quarters (79%) of patients were white, 13% were African and 46% were gay men. They had a high prevalence of traditional risk factors for kidney disease: 11% of patients had a history of injecting drug use, 7% had hepattis C virus (HCV) co-infection and 3% had diabetes.

A total of 68 people required acute renal replacement therapy during 43,000 person-years of follow-up, an incidence rate of 16 per 10,000 person-years. Incidence was highest during the first year after diagnosis with HIV (IR = 24.8 per 10,000 person-years vs subsequent years IRR = 15.4 per 10,000 person-years).

Among the controls there were 182 cases during 534,000 person-years, an incidence rate of 3.4 per 10,000 person-years.

The investigators therefore calculated that incidence was fivefold higher among people living with HIV than the control population. This finding remained robust in sensitivity analyses including only people diagnosed after 1995 (fivefold higher incidence) and non-injecting drug users and non-Africans (3.5-fold increase in incidence).

Of the 68 people with HIV requiring acute renal replacement therapy, 19 (28%) developed end-stage kidney disease and required chronic renal replacement therapy, an incidence rate of 4.4 per 10,0000 person-years. None of these patients underwent kidney transplantation.

A total of 66 control patients (36%) experienced disease progression, an incidence of 1.2 per 10,000 person-years. This meant that the rate of disease progression was 3.6 higher among the people with HIV.

For the people with HIV, the risk factors for disease requiring acute therapy included older age, use of HIV therapy, injecting drug use and an AIDS diagnosis.

Factors associated with chronic renal replacement therapy were hypertension (IRR = 19; 95% CI, 6.2-56.0) and impaired kidney function at baseline (eGFR below 60ml/min pr. 1.73m²; IRR = 7.8; 95% CI, 1.2-50.0).

Neither tenofovir nor atazanavir were associated with disease requiring acute renal replacement therapy.

The investigators believe their findings have important clinical implications, demonstrating that HIV is associated with an increased risk of renal disease requiring acute and chronic replacement therapy. “Important risk factors are, an AIDS-defining illness, being IDU and having hypertensive disease,” conclude the authors. “In a setting with regular monitoring of renal function, treatment with tenofovir or atazanavir or their combination does not seem to increase the risk of severe and irreversible renal disease.”