Risk of death in dialysis patients taking cisapride

AbstractBackgroundCisapride is a prokinetic agent that is useful to relieve gastrointestinal symptoms that often occur in dialysis patients. However, sudden death has been reported and alarmed the use of cisapride in dialysis patients. This study was performed to identify whether the use of cisapride increases the risk of death.MethodsWe retrospectively analyzed all records of dialysis patients followed during the period November 1997 to March 2000. Cisapride dosage and risk factors associated with increased risk of sudden death such as cardiovascular disease, hypokalemia, and possible interacting drugs were recorded.ResultsOf 364 dialysis patients, 85 had been prescribed with cisapride (group A) whereas 279 had not (group B). Group A patients were older, with more female patients and longer duration of dialysis. There was no significant difference in mortality or causes of death between the two groups after adjusting for the baseline demographic differences. For group A, eight patients (9.41%) died while still on cisapride and 19 (22.4%) died after cisapride had been stopped. The causes of death were peritonitis (n = 2), infection (n = 2), ischemic heart disease (n = 1), malignancy (n = 1), sudden death (n = 1), and unknown (n = 1). Low serum albumin (p=0.013) and hypokalemia (p=0.066) were potential predictors of death while taking cisapride, but the presence of diabetes mellitus, maximum dosage of cisapride, and underlying cardiovascular disease were not. There was no drug interaction leading to cisapride toxicity.ConclusionsPatients who were given cisapride were older, more often women, and had a longer duration of dialysis. Low serum albumin and hypokalemia were significant predictors of death in patients given cisapride. Although no excessive risk of death was documented, the use of cisapride in dialysis patients should still be cautious and potential drug interactions and electrolyte disturbances should be avoided

Detection of microalbuminuria in non-insulin dependent diabetes mellitus (NIDDM) patients without overt proteinuria by a semiquantitative albumin-creatinine urine strips

AbstractMicroalbuminuria is the hallmark of the reversible stage of incipient diabetic nephropathy. A cost- effective and convenient bedside screening test is essential to detect this phase. We used Clinitek 50® which is a semiquantitative strip test to check spot urine sample from 81 patients with albustix one plus or less. The incidence of Clinitek 50® microalbuminuria was 17%, 18.2% and 75% in 47, 22 and 12 patients with albustix negative, trace or one plus respectively. Nineteen and 13 of the 21 Clinitek 50® positive patients were checked for spot urine DCA 2000® and two 12-hour urine collection for immunoassay respectively. Around 60% of these samples fell into the microalbuminuria range and 40% into the overt albuminuria range by either technique. There was no false positive of Clinitek 50®. The lowest range of microalbuminuria detected by Clinitek 50® was 27 μg/minute (38 mg/day). We concluded that Clinitek 50® is a useful screening test as it is nonexpensive, easily operated and has a sensitivity close to the lower range of microalbuminuria

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

The in vivo mechanism of actions of mycophenolate mofetil: insights from murine models of allograft rejection,endotoxemia, ischemia reperfusion injury and lupus nephritis

published_or_final_versionabstracttocMedicineMasterDoctor of Medicin

Therapeutic potential of rapamycin in renal parenchymal diseases: insights from murine models of lupusnephritis, adriamycin nephropathy and renal ischemia reperfusioninjury

published_or_final_versionMedicineDoctoralDoctor of Philosoph