Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

CAPD in Dammam Central Hospital, Saudi Arabia: A Five-Year Experience

Thirty-one patients with end-stage renal disease (ESRD) were offered continuous ambulatory peritoneal dialysis (CAPD) at the Dammam Central Hospital, Dammam, Saudi Arabia over a period of five years. The group included 21 women and 10 men with a mean age of 41.3 &#x00B1; 17.2 years. The main indication for CAPD was poor or failed vascular access (51.4&#x0025;). Peritonitis remained the major complication with an overall incidence of 0.62 episode per patient year. <i> Staphylococcus epidermidis </i> was the main causative organism. Therapy with CAPD lasted a mean of 26 &#x00B1; 7.4 months. Our results, showing good technique survival and low peritonitis rate, suggest that CAPD should be promoted to become a full arm of the integrated care of ESRD in Saudi Arabia

Cross-Sectional Assessment of Achievement of Therapeutic Goals in a Canadian Multidisciplinary Clinic for Patients With Advanced Chronic Kidney Disease

Background: The implementation of advanced chronic kidney disease (CKD) multidisciplinary clinics has now demonstrated their effectiveness in delaying and even avoiding dialysis for patients with CKD. However, very little has been documented on the management and achievement of targets for a number of parameters in this context. Objective: Our goal was to assess our multidisciplinary clinic therapy performance in relation to the targets for hypertension, anemia, and calcium phosphate assessment. Methods Design and setting: A cross-sectional descriptive study was conducted with a cohort including all patients followed up in our multidisciplinary clinic in July 2014. Measurements: Comorbidity, laboratory, and clinical data were collected and compared with the recommendations of scientific organizations. Results: The cohort included 128 patients, 37.5% of whom were women. Mean follow-up time was 26.6 ± 25.1 months and mean estimated glomerular filtration rate (eGFR) was 14.0 ± 4.7 mL/min/1.73 m 2 . A total of 24.2% of patients with diabetes achieved blood pressure targets of <130/80 mm Hg, while 56.5% of patients without diabetes achieved targets of <140/90 mm Hg. Hemoglobin of patients treated with erythropoiesis-stimulating agents was 100 to 110 g/L in 36.2% of the patients, below 100 for 39.7% of them, and above 110 for 24.1%, whereas 67.2% were within the acceptable limits of 95 to 115 g/L. In addition, 63.4% of patients had a serum phosphate of <1.5 mmol/L, and 90.9% of patients had total serum calcium <2.5 mmol/L. Limitations: Our study is a single center study with the majority of our patients being Caucasian. This limits the generalizability of our findings. Conclusion: The control rates of various parameters were satisfactory given the difficult clinical context, but could be optimized. We publish these data in the hope that they are helpful to others engaged in quality improvement in their own programs or more generally