Drs. Nicola Wearne and Charles Swanepoel

In a recent review published by the American Journal of Kidney Diseases, Swanepoel et al discuss the history and evolving knowledge of HIV-associated kidney disease in Africa. Corresponding author Dr. Charles Swanepoel (CS) and co-author Nicola Wearne (NW), from Groote Schuur Hospital and the University of Cape Town, South Africa, discuss their review with eAJKD Blog Editor Kenar D. Jhaveri (eAJKD).

eAJKD: In 1970s, the Congolese capital of Kinshasa experienced the first epidemic of HIV-1. Subsequently, Uganda then became the highest infected nation. What contributed to these epidemics?

CS: The epidemic is currently the highest in South Africa, but started in Cameroon before spreading to Uganda and other neighbouring countries. The prevalence of disease increased in countries afflicted by civil war and unrest; Uganda was an example a country with major oppression by the dictators. In such areas of unrest and associated poverty, the sex trade flourishes and prevalence of HIV/AIDS increases.

eAJKD: You recently published the largest series of kidney biopsies in HIV-positive patients. Please give us a short description of that study?

CS: The study, published in Nephrology Dialysis Transplantation, was the first to look at correlating renal histology with clinical findings and outcome. A histologic classification of HIVAN was derived from this. The study also showed that treatment unequivocally improved renal outcomes, regardless of the histologic findings. This was particularly interesting in those with glomerulonephritis without any histologic evidence of HIV infection, who also showed improved renal survival with treatment. Because of the denial by the South African government that the virus was the main culprit in the pathogenesis of the disease, we were not able to give any form of antiretroviral therapy until 2004.

eAJKD: In your review, you mention “fetal FSGS”. That terminology is not part of the FSGS Columbia classification. Can you please explain this term?

Figure 3 from Swanepoel et al

CS: Dr Maureen Duffield, our pathologist, has described this variant. She showed that in this variant, the glomerulus did not collapse but was replaced by a dense mesangial sclerotic core with no peripheral loops. There were very prominent hypertrophied and hyperplastic podocytes which resembled the early fetal development of the glomerulus, which is characterized by a prominent surface lining of epithelial cells. The finding of such glomeruli offers a poor prognosis. In our NDT series, the “fetal variant” had the worst prognosis even on anti-retrovirals. This variant also had the heaviest proteinuria (median = 1.52 g/mmol) and the most microcysts. In our series, we had shown that the collapsing variant, as previously demonstrated to be a poor responder to anti-retrovirals, did respond with a significant mortality benefit on medications.

eAJKD: Why was HIV called “slimmer’s disease”?

NW: Weight loss is a prominent sign of advanced AIDS. Before an infective agent was discovered as a cause of AIDS, those that became sick with loss of weight where described as having “slimmer’s disease.”

eAJKD: Given the high cost of dialysis for all patients in Africa, the GSH hospital in Cape Town developed a category of acceptance criteria that you describe in Box 3. Can you explain how this was derived?

CS: The burden of disease in South Africa has severely strained the healthcare system and the ability of the government to pay for necessary care. The categorization is a compromise between the Western Cape Health Department and the academic hospitals in the Western Cape. It is a means of ensuring access to an expensive form of treatment for selected patients. Category 1 patients will never be denied treatment. It ensures that there will be treatment for the young otherwise healthy patient. Category 2 and 3 are self-explanatory. You will note that anyone over the age of 60 will not be accepted for renal replacement therapy. The whole plan behind the categorization was to ensure that whoever came onto dialysis was ultimately transplantable.

eAJKD: If one looks at patients in the Western world with category 3 (age >60 y, BMI >35 kg/m², diabetes mellitus and age >50 y), the majority of our population would not be eligible for dialysis. It is very interesting to learn from your categorization how resource allocation due to monetary reasons can be applied.

CS: We are not proud of this categorization for care, and the process is a work in progress which will be evaluated from time to time. Thus far, this categorization has allowed more patients access to dialysis than previously.

eAJKD: Can you describe the South African experience of HIV to HIV transplants recently published in the New England Journal of Medicine?

NW: In order to utilize the big pool of HIV-positive donors that we find on routine evaluation, Dr. Muller designed a study to perform kidney transplants between HIV-positive donors and HIV-positive recipients. Dr. Muller has perfected the dosing of immunosuppression with the antiretroviral agents (ARVs). There are major interactions between these two groups or medication. To date, she has done 15 transplants and the program continues to recruit HIV-positive recipients from all over South Africa.

eAJKD: What is the role of steroids in the treatment of HIVAN?

NW: Currently, we are recruiting participants for a corticosteroid trial for the treatment of HIVAN. In vitro data has demonstrated up-regulation of many of the pro-inflammatory genes in renal tissue of patients with HIVAN. We have also demonstrated in our biopsy series a significant proportion of biopsies having an interstitial infiltrate. Hence, there appears to be a rational for the use of corticosteroids for the treatment of HIVAN. To date, we have seen no opportunistic infections associated with the use of steroids in the study. We will hopefully complete recruitment by the end of 2012.

To view the article, please visit AJKD.org.