Renal Disease in HIV: Practical Aspects for Nephrologists

Patients with HIV represents a unique and often seemingly daunting challenge for nephrologists, as these patients often have many multi-system issues, and are on a mix of medications that are not well known or often prescribed by non-infectious disease specialists. HIV is a risk factor for acute kidney injury (AKI)/ chronic kidney disease (CKD), and there is a wide spectrum of renal disease that occurs in these patients, including those directly caused by the virus, and medication toxicities. Once the renal disease is advanced, these patients can also provoke difficult decisions regarding the issues of kidney biopsy, dialysis, and transplant. The nephrologist requires a working knowledge of the current state of overall HIV management, so that they can help with the prevention and treatment of acute and chronic kidney disease, within the multi-disciplinary HIV team

Conjunctive Therapy of Cisplatin With the OCT2 Inhibitor Cimetidine: Influence on Antitumor Efficacy and Systemic Clearance

The organic cation transporter 2 (OCT2) regulates uptake of cisplatin in proximal tubules and inhibition of OCT2 protects against severe cisplatin-induced nephrotoxicity. However, it remains uncertain whether potent OCT2 inhibitors such as cimetidine can influence the antitumor properties and/or disposition of cisplatin. Using an array of preclinical assays, we found that cimetidine had no effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with high OCT2 mRNA levels (IGROV-1). Moreover, the antitumor efficacy of cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100 mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg×2) revealed that cimetidine did not alter exposure to unbound cisplatin, a marker of antitumor efficacy (4.37 vs 4.38 μg×h/mL; P = 0.86). These results support the future clinical exploration of OCT2 inhibitors as specific modifiers of cisplatin-induced nephrotoxicity