Racial variations in erythropoietic response to epoetin alfa in chronic kidney disease and the impact of smoking.

BACKGROUND: Of the known risk factors for chronic kidney disease (CKD), race represents one that is non-modifiable, while smoking is another that is modifiable. Moreover, smoking tends to increase red blood cell mass, which is frequently diminished in CKD. No studies have examined the interplay of race with smoking on anaemia management in patients with CKD. METHODS: We examined the effects of smoking on anaemia management in CKD and its variation across race in a previously conducted study of CKD patients (n = 1312) initiated on weekly epoetin alfa and followed for 16 weeks. Smoking status was classified as current vs non-smoker. Race was classified as African-American vs non-African-American. Changes in estimated glomerular filtration rate, urinary albumin excretion, and erythropoietic response to weekly epoetin alfa were examined. RESULTS: Overall, African-Americans had lower baseline Hb than non-African-Americans. African-American non-smokers did not mount an erythropoetic response comparable to other non-smokers by final Hb (mean 11.29 g/dl vs 11.64 g/dl, P<0.001) or week 16 Hb (mean 11.61 g/dl vs 11.86 g/dl, P = 0.02). However, African-American smokers had a more significant erythropoietic response than their non-smoking counterparts and were comparable to their smoking non-African-American counterparts. There was no effect of smoking on renal function or urinary protein excretion over the course of the study. CONCLUSION: African-American non-smokers exhibit a diminished response to standard epoetin alfa dosing than non-smokers in other races. However, African-American smokers with CKD exhibit a response to epoetin alfa comparable to patients of other races. These findings may have implications for African-Americans who have CKD-related anaemia.

Characterization of hepatic cytochrome p4503A activity in patients with end-stage renal disease.

BACKGROUND: The cytochrome p450 (CYP) oxidative enzyme system, located primarily in the liver and small intestine, is responsible for metabolism and detoxification of numerous endogenous and exogenous substances. The most abundant CYP enzyme, CYP3A, is known to be involved in the metabolism of more than 200 commonly used medications. In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however, direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end-stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug-drug interactions. METHODS: We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls. Hepatic CYP3A phenotype was characterized with the erythromycin breath test, and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days). RESULTS: The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P <.05); however, enzyme induction capacity after rifampin administration was similar between groups (P =.70). CONCLUSION: The findings suggested that one mechanism by which patients with end-stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A enzyme pathway.