Adrian Fine

Sleep complaints are common in a dialysis unit

Sleep disturbance among uremic patients is reported to be high, but data on the actual prevalence, clinical significance, and causative factors is limited. A sleep questionnaire was distributed to an entire hemodialysis unit of 64 patients. Of the 54 patients who completed the survey, 83.3% had sleep-wake complaints. Disturbed sleep was reported by 28 patients (51.8%), and causes were secondary to delayed sleep onset in 25 patients (46.3%), frequent awakening in 19 patients (35.2%), restless legs syndrome (RLS) in 18 patients (33.3%), and generalized restlessness in six patients (11.1%). Daytime sleepiness was the most frequent complaint, reported by 36 patients (66.7%), and RLS was the second most frequent specific complaint, reported by 31 patients (57.4%). Symptoms of sleep apnea were described by seven patients (13.0%). Male gender, age more than 60 years, RLS, and caffeine intake were associated with more sleep-wake complaints (P = 0.009, P = 0.002, P = 0.028, and P = 0.008, respectively). Urea and creatinine levels were higher in patients with RLS (P = 0.04 and P = 0.08, respectively); otherwise, no other metabolic or demographic variable was associated with specific sleep disorders or disturbance. Sleep problems are very common in dialysis patients and likely contribute to the impaired quality of life experienced by many of these patients.

Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy: A Randomized Controlled Trial

CONTEXT Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B(6), and vitamin B(12)) has been shown to lower the plasma concentration of homocysteine. OBJECTIVE To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized, double-blind, placebo-controlled trial (Diabetic Intervention with Vitamins to Improve Nephropathy [DIVINe]) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy. INTERVENTION Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B(6) (25 mg/d), and vitamin B(12) (1 mg/d), or matching placebo. MAIN OUTCOME MEASURES Change in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes were dialysis and a composite of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured. RESULTS The mean (SD) follow-up during the trial was 31.9 (14.4) months. At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m(2) in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m(2) in the placebo group (mean difference, -5.8; 95% confidence interval [CI], -10.6 to -1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04). Plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) micromol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) micromol/L in the placebo group (mean difference, -4.8; 95% CI, -6.1 to -3.7; P < .001, in favor of B vitamins). CONCLUSION Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN41332305.

Prediction of early death in end-stage renal disease patients starting dialysis

Demand for dialysis for patients with end-stage renal disease is growing, as is the comorbidity of dialysis patients. Accurate prediction of those destined to die quickly despite dialysis could be useful to patients, providers, and society in making decisions about starting dialysis. To determine whether age and comorbidity accurately predict death within 6 months of first dialysis for end-stage renal disease, a prospective cohort study of 822 patients starting dialysis at one of 11 Canadian centers was performed. Patient characteristics were recorded at first dialysis. Follow-up continued until death or study end (at least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients died within 6 months. Although an existing scoring system predicted prognosis, adverse scores greater than 9 were found in only 9.7% of those who died; only 52% of those who scored higher than 9 died within 6 months. No score cutoff point combined high true-positive and low false-positive rates for predicting early death. Age, severity of heart failure or peripheral vascular disease, arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic factors identified in multivariate models. However, the best fit discriminant and logistic models were also unable to accurately predict death within 6 months. Clinicians were very accurate in assigning patients to prognostic groups up to a 50% risk of death by 6 months, above which they tended to overestimate risk. However, clinicians were only marginally better than the predictive models in determining whether a given high-risk patient would die. The inability of a scoring system or clinical intuition to accurately predict death soon after starting dialysis for end-stage renal disease suggests that limiting access to dialysis on the basis of likely short survival may be inappropriate in Canada.

Severe hyperphosphatemia following phosphate administration for bowel preparation in patients with renal failure: Two cases and a review of the literature

Two cases of severe hyperphosphatemia following phosphate bowel preparation are described and a review of the literature is presented. Impairment of renal function appears to be a risk factor in those patients without primary bowel pathology. One of our patients died, and the mortality rate combining our cases with all other reported cases is 33%. Repeated doses of phosphate bowel preparations/purgatives can be dangerous in patients with renal impairment.

A multicenter study of noncompliance with continuous ambulatory peritoneal dialysis exchanges in US and Canadian patients

Recent evidence suggested that noncompliance (NC) with continuous ambulatory peritoneal dialysis (CAPD) exchanges may be more common in US than in Canadian dialysis centers. This issue was investigated using a questionnaire-based method in 656 CAPD patients at 14 centers in the United States and Canada. NC was defined as missing more than one exchange per week or more than two exchanges per month. Patients were ensured of the confidentiality of their individual results. Mean patient age was 56 +/- 16 years, 52% were women, and 39% had diabetes. The overall admitted rate of NC was 13%, with a rate of 18% in the United States and 7% in Canada (P < 0.001). NC was more common in younger patients (P < 0.0001), those without diabetes (P < 0.001), and employed patients (P < 0.05). It was also more common in black and Hispanic than in Asian and white patients (P < 0.001). NC was more common in patients prescribed more than four exchanges daily (P < 0.0001) but was not affected by dwell volume. On multiple regression analysis, the independent predictors of NC, in order of importance, were being prescribed more than four exchanges per day, black race, being employed, younger age, and not having diabetes. Being treated in a US unit did not quite achieve significance as a multivariate independent predictor. These findings suggest that NC is not uncommon in CAPD patients and is more frequent in US than in Canadian patients. However, country of residence is less powerful as a predictor of NC than a variety of other demographic and prescription factors.

Calciphylaxis presenting with calf pain and plaques in four continuous ambulatory peritoneal dialysis patients and in one predialysis patient

Calciphylaxis is a rare disease associated with hemodialysis or transplantation, high parathyroid hormone values, and increased serum calcium x phosphate (Ca x P) product. Only four patients on continuous ambulatory peritoneal dialysis have been reported with this condition. We report five cases presenting within a 2-year period with severe calf pain and tenderness with extensive nonulcerating large, hard, and tender subcutaneous plaques in the calves. Calcium deposition was confirmed radiologically and by bone scanning. Four patients were on continuous ambulatory peritoneal dialysis, and the other was not yet on dialysis. High serum Ca x P product was found in three of these patients at onset of the condition. Two patients had normal parathyroid hormone levels at onset. Calcium salts and/or calcitriol had been taken prior to onset in three patients. When presenting in this fashion, the diagnosis can be easily made by the uniqueness of the physical findings in the legs. Our observation suggests that the condition should no longer be considered rare and is not confined to hemodialysis patients. Furthermore, it can occur in predialysis patients.

Atheroma Progression in Chronic Kidney Disease

BACKGROUND AND OBJECTIVES Cardiovascular events are 10 to 100 times more frequent in chronic kidney disease (CKD). We tested the hypothesis that the rate of atherosclerotic plaque growth is faster in severe versus moderate CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a prospective cohort study in 318 prevalent CKD patients with initial creatinine clearance (CCr) between 20 and 50 ml/min/1.73 m(2). Baseline clinical and laboratory data were obtained on all patients. Plaque area was determined every 6 mo using bilateral carotid ultrasonography. Plaque area distribution was normalized using a cube root transformation. Unadjusted and adjusted associations between CCr quintiles and rate of change in the transformed plaque area were assessed using multiple linear regression. RESULTS The rate of plaque progression appeared lower in patients with the lowest CCr. Median rate of plaque growth was 0.4 mm(2)/yr in the lowest quintile of CCr (< 23 ml/min/1.73 m(2)) versus 5.0 mm(2)/yr in the highest quintile (> 43 ml/min/1.73 m(2)). This association remained significant after adjustment for potential confounders. A secondary analysis using quintiles of Modification of Diet in Renal Disease (MDRD) GFR confirmed the absence of increased plaque growth at low GFR, although a reduced rate of growth in the lowest quintile of MDRD GFR was not observed. CONCLUSION We did not observe accelerated plaque growth at low levels of renal function. We suggest that mechanisms other than plaque growth are responsible for the observed excess of cardiovascular disease in CKD patients.

Digoxin‐rifampin interaction

Digoxin doses required to maintain therapeutic serum concentrations rose substantially in two patients dependent on dialysis with the commencement of rifampin therapy. When rifampin was discontinued, doses fell to requirements before rifampin. Serum digoxin concentration may fall to ineffective levels with rifampin therapy and rise to potentially toxic levels when rifampin is discontinued.

Modest Reduction of Serum Albumin in Continuous Ambulatory Peritoneal Dialysis Patients Is Common and of No Apparent Clinical Consequence

It is commonly assumed that a reduction in serum albumin is a reliable sign of nutritional inadequacy affecting prognosis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied prospectively 19 patients starting CAPD and monitored them for a minimum of 15 months. Serum albumin, changes in dry weight, morbid events, and, where possible, protein catabolic rates (PCR) and urea nitrogen appearance (UNA) were determined. A modest reduction in serum albumin (25 to 33 g/L [2.5 to 3.3 g/dL]) was found in the majority of patients 3 months after starting CAPD, which persisted for 12 months. Most of these patients gained weight and were not hospitalized in that period. PCR and UNA values showed adequate nutrition. Two patients developed serious medical problems leading to clinical malnutrition and serum albumin rapidly falling below 20 g/L. A modest reduction in serum albumin (25 to 33 g/L) is common in healthy CAPD patients and, if stable, does not indicate a poor prognosis or nutritional inadequacy.

Troponin I testing in dialysis patients presenting to the emergency room: does troponin I predict the 30-day outcome?

Background: Troponins are often measured in acutely ill chronic dialysis patients admitted to the emergency room, irrespective of their clinical presentation. The significance of an elevated troponin level in this setting is unclear. Methods: We identified all chronic dialysis patients presenting over 1 year to a tertiary care hospital emergency room who also had at least one cardiac troponin I (cTnI) level determination. We evaluated presenting complaints, risk factors for cardiac disease, cTnI levels, and major cardiac events (MCE; occurrence of cardiovascular death, myocardial infarction, de novo heart failure, or coronary revascularization) within 30 days by chart review in 149 patients (79 on hemodialysis, 70 on peritoneal dialysis). Results: Chest pain was documented in only 29% of the patients. Twenty-two patients (15%) experienced an MCE. The incidence of an MCE was the same in patients with and without chest pain. A cTnI level >0.1 ng/l was a significant predictor of an MCE (odds ratio 15.2, 95% confidence interval CI 5.26, 43.6). The likelihood ratios for MCEs were 0.32 (CI 0.16, 0.63) for a cTnI level <0.1 ng/l, 0.72 (CI 0.09, 5.5) for cTnI concentrations 0.1–0.3 ng/l, 7.8 (CI 4.2, 15) for a cTnI level >0.3, and 11.7 (CI 4.4, 31) for a cTnI concentration >2.0 ng/l. Conclusion: In acutely ill chronic dialysis patients presenting to a hospital emergency room, an elevated cTnI level indicates an increased 30-day cardiac risk, regardless of their clinical presentation.