Nelson Kopyt

Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

BACKGROUND Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. STUDY DESIGN Prospective randomized clinical trial, post hoc analyses. SETTING & PARTICIPANTS 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. INTERVENTION Randomized; pravastatin, 40 mg/d, or usual care. OUTCOMES & MEASUREMENTS Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. RESULTS Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. LIMITATIONS Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. CONCLUSIONS In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

A prospective cohort study of mineral metabolism after kidney transplantation

Background Kidney transplantation corrects or improves many complications of chronic kidney disease, but its impact on disordered mineral metabolism is incompletely understood. Methods We performed a multicenter, prospective, observational cohort study of 246 kidney transplant recipients in the United States to investigate the evolution of mineral metabolism from pretransplant through the first year after transplantation. Participants were enrolled into 2 strata defined by their pretransplant levels of parathyroid hormone (PTH), low PTH (>65 to ⩽300 pg/mL; n = 112), and high PTH (>300 pg/mL; n = 134) and underwent repeated, longitudinal testing for mineral metabolites. Results The prevalence of posttransplant, persistent hyperparathyroidism (PTH >65 pg/mL) was 89.5%, 86.8%, 83.1%, and 86.2%, at months 3, 6, 9, and 12, respectively, among participants who remained untreated with cinacalcet, vitamin D sterols, or parathyroidectomy. The results did not differ across the low and high PTH strata, and rates of persistent hyperparathyroidism remained higher than 40% when defined using a higher PTH threshold greater than 130 pg/mL. Rates of hypercalcemia peaked at 48% at week 8 in the high PTH stratum and then steadily decreased through month 12. Rates of hypophosphatemia (<2.5 mg/dL) peaked at week 2 and then progressively decreased through month 12. Levels of intact fibroblast growth factor 23 decreased rapidly during the first 3 months after transplantation in both PTH strata and remained less than 40 pg/mL thereafter. Conclusions Persistent hyperparathyroidism is common after kidney transplantation. Further studies should determine if persistent hyperparathyroidism or its treatment influences long-term posttransplantation clinical outcomes.

Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia

Hyponatremia is the most common electrolyte disorder in clinical practice. Its incidence increases with age and it is associated with increased morbidity and mortality. Recently, the vaptans, antagonists of the arginine vasopressin pathway, have shown promise for safe treatment of hyponatremia. Here we evaluated the efficacy, safety, and tolerability of oral lixivaptan, a selective vasopressin V2-receptor antagonist, for treatment of nonhospitalized individuals with euvolemic hyponatremia (sodium less than 135 mmol/l) in a multicenter, randomized, double-blind, placebo-controlled, phase III study. About half of the 206 patients were elderly in a chronic care setting. Of these patients, 52 were given a placebo and 154 were given 25-100 mg per day lixivaptan, titrated based on the daily serum sodium measurements. Compared with placebo (0.8 mmol/l), the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 (primary efficacy endpoint) with lixivaptan treatment. A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium (39.4%) by day 7 relative to placebo (12.2%). Overall, lixivaptan was considered safe and well-tolerated. Thus, oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia.

Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism

BACKGROUND Treatment with cinacalcet improves the control of secondary hyperparathyroidism (SHPT) and the achievement of calcium and phosphorus targets. Most data come from subjects receiving cinacalcet after several years of dialysis treatment. We therefore compared the efficacy of treatment with cinacalcet and low doses of active vitamin D to flexible doses of active vitamin D alone for the management of SHPT in patients recently initiating haemodialysis. METHODS This open-label trial randomized subjects (n = 309) with parathyroid hormone (PTH) >300 pg/mL on dialysis for 3-12 months to either cinacalcet with low-dose active vitamin D, if prescribed (cinacalcet); or usual care without cinacalcet (control). Randomized subjects were stratified by PTH at screening (300-450, >450-600, >600 pg/mL) and by the use of active vitamin D at enrolment. Treatment duration was 12 months, with primary efficacy endpoint (mean PTH reduction ≥ 30% from baseline) assessed at 6 months. RESULTS The mean [standard deviation (SD)] haemodialysis vintage at enrolment was 7.2 (2.7) months; 53% of subjects were not receiving active vitamin D at enrolment. There was a significant difference in the achievement of the primary endpoint (≥ 30% PTH reduction at 6 months) between cinacalcet-treated subjects and controls in both the entire cohort (63 versus 38%; n = 304; P < 0.0001) and the subgroup of subjects not receiving active vitamin D at enrolment (70 versus 44%; n = 161; P < 0.01). Hypocalcaemia and gastrointestinal adverse events were more commonly observed in cinacalcet-treated subjects. CONCLUSIONS These results indicate that cinacalcet with low-dose active vitamin D, if prescribed, provides a more effective treatment approach than usual care without cinacalcet for SHPT in incident haemodialysis patients, even in relatively treatment-naive patients.

Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid-lowering component of ALLHAT

Background/Aims: The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). Methods: Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. Results: Through Year 6, total cholesterol declined in pravastatin (–20.7%) and usual-care groups (–11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory “as-treated” analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 – 0.85), p < 0.001) and lower CHD (HR = 0.84 (0.73 – 0.97), p = 0.01), but not combined cardiovascular disease (HR = 0.95 (0.88 – 1.04), p = 0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. Conclusions: In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory “as-treated” analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.

A Comparison of the Safety and Efficacy of HX575 (Epoetin Alfa Proposed Biosimilar) with Epoetin Alfa in Patients with End-Stage Renal Disease

Background: HX575 (biosimilar epoetin alfa) was approved in Europe in 2007 for the treatment of chronic kidney disease (CKD)-related anemia. This study assessed the clinical equivalence of HX575 with the US-licensed reference epoetin alfa (Epogen®/Procrit®, Amgen/Janssen) following subcutaneous (SC) administration in dialysis patients with CKD-related anemia. Methods: This randomized, double-blind, parallel-group, multicenter study (NCT01693029) was conducted at 49 US clinical sites. Eligible patients were aged ≥18 years, had end-stage renal disease, were on hemodialysis or peritoneal dialysis for ≥6 months (or ≥12 months in the case of a failed kidney transplant), and were receiving treatment with stable SC doses of epoetin alfa. Eligible patients also had mean hemoglobin (Hb) concentration between 9.0 and 11.5 g/dL during the screening period. The primary endpoint was the mean absolute change in Hb concentration between the screening/baseline period (week-4 to week-1) and the evaluation period (weeks 21 to 28). Results: Hb values at the end of the evaluation period and the Hb change from baseline to evaluation period were similar between treatment groups. The estimated difference between groups in mean absolute change in Hb concentration was –0.093 g/dL, with 90% CI (–0.23 to 0.04) entirely within the pre-specified equivalence limits (–0.5 to 0.5 g/dL). The safety profile of each medicine was similar and as expected in dialysis patients, and neither method of treatment led to the development of neutralizing, clinically relevant antibodies. Conclusions: SC HX575 in dialysis patients with renal anemia was therapeutically equivalent to the reference medicine in terms of maintaining stable Hb levels and safety.

A case of suppurative peritonitis by a commensal oral organism, Kingella denitrificans, in an adult peritoneal dialysis patient.

In conclusion, we report 6 patients with asymptomatic peritoneal leukocytosis and sterile effluent post-exteriorization of buried PD catheters. The pathophysiology of this phenomenon is not clear. We recommend that persistent cloudy effluent post-exteriorization of a buried PD catheter be empirically treated for PD peritonitis, but if patients are asymptomatic and cultures return negative, then our data suggest that antibiotics may safely be stopped.