CYP2C9 genotype and pharmacodynamic responses to losartan in patients with primary and secondary kidney diseases.

BACKGROUND: Losartan is used for anti-proteinuric as well as blood pressure effects in chronic kidney disease (CKD). It is metabolized by cytochrome P450 (CYP) 2C9 to active E-3174. Single nucleotide polymorphisms in CYP2C9 that reduce catalytic activity could reduce clinical benefits. AIM: The study aims were to determine whether CYP2C9 variant alleles (*2 and *3) altered urinary protein excretion, glomerular filtration rate, and blood pressure in Caucasian patients prescribed losartan. METHODS: Differences between baseline and 6-month follow-up outcomes were compared by CYP2C9 genotypes in 59 patients using unpaired t test or Mann-Whitney U test. RESULTS: Primary renal disease patients had a trend toward less favorable antiproteinuric response (-31.7 +/- 156 vs. -125 +/- 323%; p = 0.123) when carrying variant alleles. Patients with secondary renal diseases had less favorable diastolic blood pressure (9.8 +/- 16.0 vs. -3.2 +/- 10.6 mmHg; p = 0.043) and systolic blood pressure (16.2 +/- 27.1 vs. -5.5 +/- 17.5 mmHg; p = 0.044) with CYP2C9 variants. CONCLUSION: These preliminary results suggest a possible influence of CYP2C9 genotype on proteinuria and blood pressure in Caucasian CKD patients treated with losartan.

Reengineering clinical operations in a medical practice to optimize the management of anemia of chronic kidney disease.

OBJECTIVES: To describe the clinic design, clinical evaluations, and treatment approaches used in a multidisciplinary clinic for management of anemia of chronic kidney disease (CKD), and to evaluate several selected clinical outcomes associated with this approach to anemia management. SETTING: University-affiliated, division of nephrology, outpatient multidisciplinary model CKD clinic headed by a clinical pharmacist. PATIENTS: One hundred sixty-six patients with anemia of CKD who were referred by nephrologists and primary care providers to the multidisciplinary clinic from March 1, 2002-July 31, 2004. MEASUREMENTS AND MAIN RESULTS: Patients received darbepoetin alfa dosed on an every-other-week basis. If patients were already receiving once-weekly recombinant human erythropoietin (r-HuEPO), the darbepoetin alfa dose was calculated by using the darbepoetin alfa package insert conversion table. If patients were naïve to previous erythropoietic therapy, the darbepoetin alfa dose was either 60 microg or 0.7 microg/kg. The dose and frequency of darbepoetin alfa and oral iron supplements were adjusted to achieve the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) targets for hemoglobin levels and iron measures. The primary outcome analyzed was the proportion of patients with at least 30 days of treatment who achieved a target hemoglobin level of 11.0 g/dl or greater. Of 128 patients who received at least 30 days of treatment, 100 (78%) attained the hemoglobin level (mean +/- SD 11.7 +/- 7 g/dl). Ninety-nine of 128 patients were originally naïve to erythropoietic therapy; 77 (78%) of these 99 patients achieved the hemoglobin target in a mean +/- SD of 7.9 +/- 7.5 weeks. These data contrast with the data of 29 patients seen in the year previous to the reengineered clinic process, whereby only 12 (41%) of these comparable patients reached hemoglobin target with r-HuEPO therapy. Of the 77 previously erythropoietic-naïve patients, 82% were receiving darbepoetin alfa every other week, 14% every 3 weeks, and 4% every 4 weeks at the time the hemoglobin target was achieved. Oral iron administration significantly increased the chance of achieving the K/DOQI targets for hemoglobin and iron. CONCLUSION: Redefining roles and practices of members of a clinical practice and reengineering processes for anemia management were effective in achieving and maintaining target hemoglobin and iron levels.

Lanthanum carbonate.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of lanthanum carbonate, a phosphate binder for chronic kidney disease (CKD). DATA SOURCES: Information was selected from PubMed (1965-October 2005). All studies presented as scientific posters and abstracts from nephrology meetings from 1999 to 2005 were also included. STUDY SELECTION AND DATA EXTRACTION: All published articles regarding lanthanum carbonate were included. In addition, abstracts and presentations from scientific meeting symposia were also considered for inclusion. DATA SYNTHESIS: Lanthanum carbonate has been recently approved as non-calcium-based therapy for phosphate reduction in patients with stage 5 CKD requiring dialysis. The recommended dose is 250-500 mg with meals, for a maximum of 1500 mg daily. Clinical studies have shown short- and long-term safety with lanthanum carbonate administration. Adverse effects were primarily gastrointestinal in nature. Clinical trials have also shown reductions in serum phosphorus to target concentrations, reductions in associated calcium-phosphorus product, and minimal effects on serum calcium and parathyroid hormone concentrations. CONCLUSIONS: Lanthanum carbonate is an effective phosphate-binding agent without significant risk of hypercalcemia or worsening metabolic acidosis. Lanthanum carbonate is a safe and effective drug for reduction of elevated serum phosphorus levels associated with stage 5 CKD. The role of lanthanum carbonate relative to other phosphate-binding drugs, such as calcium salts and sevelamer, remains to be determined.