In 2007, the worldwide prevalence of human immunodeficiency virus (HIV) infection was 33 million, with 2.7 million incident cases and 2 million deaths.1 The global burden of CKD in the HIV population is difficult to estimate, but proteinuria is relatively common and is associated with increased rates of death, hospitalization, and AIDS-defining illness.2 Proteinuria, in turn, often predicts the onset of HIV-associated nephropathy (HIVAN) which, untreated, almost always progresses to ESRD. On the other hand, ESRD in HIV-infected patients is no longer a death sentence, and outcomes are favorable for both dialysis and kidney transplantation. In this issue of Advances in Chronic Kidney Disease, a group of internationally renowned thought leaders presents the latest synthesis of the epidemiology, biochemistry, genetics, and pharmacotherapy of HIV and kidney disease for the benefit of the practicing nephrologist.
Broadly speaking, the widespread use of highly active antiretroviral therapy (HAART) during the last 10 to 15 years has transformed HIV from a fatal diagnosis to a chronic disease. As patients infected with HIV live longer and accumulate more comorbidity, their care may become increasingly fragmented among a number of specialists. Nephrologists, who often play the role of primary care physician for their CKD and ESRD patients, should have a basic working knowledge of HIV. Dr Gallant provides a primer for the generalist caring for HIV-infected patients, including principles of diagnosis, prescription of HAART, and prophylaxis against opportunistic infections.
Both HIV infection and the adverse effects of its treatment have been linked to CKD. Microalbuminuria may be the earliest manifestation of HIV-associated kidney disease, including HIVAN, and portends a worse prognosis. Expert guidelines recommend screening for proteinuria in all patients at the time of HIV diagnosis,3 but such testing could be especially useful for ESRD planning in high-risk populations. Drs Winston, Estrella, and Fine paint the epidemiological landscape of HIV and CKD, from urine protein analysis in patients with normal kidney function to prognostic stratification in those at risk for ESRD.
Among the many kidney diseases identified in HIV-infected patients, HIVAN is one of the most aggressive and, unfortunately, one of the most common. Patients with HIVAN usually present with high-grade proteinuria and collapsing glomerulopathy and often progress to ESRD in the space of weeks. Drs Kaufman, Collins, and Klotman discuss the molecular pathogenesis of HIVAN, including podocyte proliferation and dedifferentiation resulting from expression of the HIV genes nef and vpr. Drs Núñez, Saran, and Freedman expand on the genetic basis of HIVAN, especially the role of the host susceptibility gene MYH9 and its possible interactions with other genetic and environmental factors. Finally, Dr Atta illustrates the clinical diagnosis and natural history of HIVAN, and Dr Kalayjian weighs the evidence for and against treatment with HAART, glucocorticoids, and angiotensin-converting enzyme inhibitors.
HIVAN is probably the best known example of HIV-associated kidney disease, but a wide spectrum of pathology is possible and indeed frequent. Paradoxically, although HAART is used to treat HIVAN, the treatment itself can cause kidney damage, including proximal tubular dysfunction, acute tubular necrosis, and nephrolithiasis, as discussed by Drs Jao and Wyatt. In addition, HIV is linked to disorders such as thrombotic microangiopathy and glomerulonephritis associated with immune complex deposition and hepatitis C coinfection; these phenomena are explored by Drs Rachakonda and Kimmel.
Many patients with HIV and CKD progress to ESRD. Although solid organ transplantation was initially avoided in HIV-positive patients, graft and patient survival are excellent in kidney transplant recipients whose disease is controlled with HAART. Drs Reese, Blumberg, and Bloom discuss the risks and benefits of kidney transplantation in the HIV population, including allograft rejection, opportunistic infection, malignancy, drug interactions, and organ allocation policy. Drs Novak and Szczech review the diagnosis and management of HIV-infected patients with ESRD, comprising both dialysis and transplantation, with discussions of anemia, bone and mineral disease, infection control, and access complications.
In January 2010, patients infected with HIV can expect to live longer and better than ever before in the history of the disease, largely because of improvements in HAART. As therapy for HIV continues to evolve, the face of CKD and ESRD in this disease continues to change, and the nephrologist is increasingly challenged to stay abreast of current developments. We hope that this issue of Advances in Chronic Kidney Disease provides timely and useful information for those who care for patients with HIV and kidney disease.
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