Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Abstract

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.

Clinical Pharmacology in HIV Therapy

“…The use of atazanavir in conjunction with ritonavir as a booster has the potential of increasing the risk for the development of granulomatous interstitial nephritis (53)(54)(55). Similar to pharmacoenhancers, these agents are not recommended in those undergoing organ transplantations because of the significant drug-drug interactions with calcineurin inhibitors and mammalian target of rapamycin inhibitors (5,56). Likewise, awareness of other potential drug interactions with these agents is critical in predicating safety and efficacy of other concomitantly administered drugs.…”

“…From the kidney standpoint, many of these agents are secreted or cleared by the kidney, requiring dose adjustments in those with compromised kidney function, and they have drug-drug interactions that may increase the effect of adverse reactions, particularly in HIV-1-positive individuals undergoing organ transplantation (4,5). Likewise and equally important, some of these agents have been shown to be directly nephrotoxic, inducing a variety of kidney disorders ranging from AKI, acute interstitial nephritis, kidney stones, crystalline nephropathy, and CKD to proximal and distal tubular kidney dysfunction (1,(6)(7)(8)(9)(10)(11).…”

Early safety of tenofovir alafenamide in patients with a history of tubulopathy on tenofovir disoproxil fumarate: a randomized controlled clinical trial

“…Reported risk factors for PRT include older age, white ethnicity, immunodeficiency, more prolonged exposure to TDF and co‐exposure to didanosine or ritonavir‐ and cobicistat‐boosted agents . The pathological hallmark of TDF‐associated PRT is acute tubular injury (ATI), with prominent mitochondrial dysmorphia . Although kidney function generally improves upon TDF discontinuation, some 20–30% of patients may be left with residual renal impairment .…”

Nephrology in South Africa: Not Yet <b><i>ubuntu</i></b>

“…This is on a background of a now well-established genetic predisposition to CKD in people of African ancestry. The strongest link has been associated with APOL1 and its predisposition to hypertension and focal segmental glomerulosclerosis (either idiopathic or HIV related) [12]. …”

“…Renal involvement occurs due to HIV itself or/and due to the opportunistic infections frequently accompanying HIV infection (as well as the drugs used in treatment). There is also an increasing prevalence of non-communicable diseases (obesity, hypertension, and diabetes) as people are living longer on antiretroviral therapy [12]. …”