Balancing toxicities

Research and years of experience in the care of the general nephrology patient have established that the likelihood of heart disease is greater than would be expected owing to the presence of kidney disease. Because of the growing rates of comorbidities, such as diabetes mellitus and hypertension, among those with HIV as well as the independent contribution of the virus itself to the risk of heart disease, a similar association is likely present among persons with HIV and kidney disease.

We need to help the HIV specialist make the best decision possible, given the information available, to balance these toxicities. The studies described are decidedly not sufficient to prove in a scientifically rigorous manner the link, the risk factors, and the mechanisms by which each of these medications is associated with its respective toxicity.

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The results are sufficiently consistent within each group, however, to assume that this risk is tangible. Appropriately, the burden of proof to suggest a safety risk need not be as steep, particularly when alternative therapies that might obviate the risk are available.

But there lies the true dilemma. Given the tremendous burden of cardiac disease seen among those patients without HIV but with kidney disease, a similar burden of heart disease among patients with HIV and kidney disease is not beyond the realm of possibility.

Therefore, there will exist a population of patients who may be at increased risk for a toxicity regardless of whether tenofovir or abacavir is chosen as one of their antiretroviral medications. Knowledge of the risks associated with the non-tenofovir regimens is essential to assist nephrologists in being a part of the decision-making team when a patient on tenofovir presents with abnormalities in creatinine.

For the nephrologist, knowing that a change in antiretroviral medication may offer similarly complex and serious toxicities as the current regimen could prompt a decision to pursue more evidence (such as through kidney biopsy) that the tenofovir is definitively the cause of the decline in kidney function (whether acute or chronic).

Regardless of whether this evidence is sought, the nephrologist can assist the infectious diseases clinician in estimating the likelihood of CVD in selected patients even when our experience with general nephrology patients is not directly applicable. 

Neither of the toxicities detailed in this article has been sufficiently described. However, both have been described well enough to establish that some degree of risk is likely present. Until more definitive studies have been completed, the careful balance of risks and benefits associated with switching therapy when one toxicity is present must take into consideration the likelihood that the patient has both cardiac and kidney disease.

If a patient has heart disease, how likely is it that he has kidney disease, and vice versa? In the setting where one disease is associated with a substantial likelihood of the second, perhaps we need more definitive proof of toxicity before we change a patient’s antiviral regimen.

Dr. Szczech is Associate Professor of Nephrology at Duke University School of Medicine in Durham, N.C., and a member of the Editorial Advisory Board for Renal & Urology News.