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.

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.

Background: We previously reported a very high incidence of calciphylaxis, mainly in peritoneal dialysis (PD) patients. Although we identified several risk factors for the condition, including PD, we were unable to identify why our particular unit had such a high frequency of the condition and a reliable treatment.Objectives: To assess the apparent changing frequency of the condition and the response to therapy, and to attempt to determine putative factors that might explain our uniquely high incidence of calciphylaxis.Methods: A prospective clinical record was kept on all patients that developed calciphylaxis in our center [both PD and hemodialysis (HD) units] between 1998 and 2006.Results: Of the 59 patients that developed calciphylaxis, 54 were on PD, 4 were on HD, and 1 was in predialysis. In the PD population, the mean yearly incidence from 1998 to 2003 was 4.5/100 patient-years, falling to 1.3/100 patient-years in 2004-2006. The percent of patients not taking calcium salts fell during this time period. Conversion to HD led to marked early improvement. A marked discrepancy between the levels of ionized calcium (routinely used in our center) and corrected serum calcium was found, with most cases of hypercalcemia (corrected) being missed by using ionized values.Conclusions: The incidence of calciphylaxis is falling dramatically. This may be related partially to reduction in usage of calcium salts. Conversion to HD is beneficial. Our uniquely high incidence of calciphylaxis may be related to our use of ionized calcium levels to monitor these patients.

to diabetes mellitus and hypertension. The operation was uneventful and the kidney functioned well. The serum creatinine declined from 14.5mg/dl pre-operatively to 1.36mg/dl on day 22 post-transplantation. The patient received immunosuppressive therapy with prednisolone, tacrolimus and mycophenolate mofetil. Twenty-seven days after transplantation, the patient presented to our emergency department with general oedema and abdominal distension. The serum creatinine concentration was 1.4mg/dl, and the ultrasound scan of the abdomen showed a large amount of ascites. Diagnostic paracentesis was performed and 2 l of fluid were drained. The ascitic fluid was milky in gross appearance with the triglycerides content at 188.2mg/dl, which was compatible with chyle [5]. The other biochemical analysis revealed cell count at 90WBCs/mm with all lymphocytes and was sterile for aerobic, anaerobic and tuberculous cultures. The creatinine concentration of ascites was 1.61mg/dl, vs a urinary creatinine concentration of 20.6mg/dl, which excludes the possibility of the fluid being of urinary origin. The lymphoscintigraphy revealed transient flush of lymphatic flow in the right lower quadrant area, abnormality of lymphatic circulation and disturbance in the lower abdomen. An abdominal magnetic resaonance imaging (MRI) on day 9 after the diagnosis of chyloperitoneum showed neither enlarged lymph node nor abnormal peritoneal fluid collection, although there was localized fluid over the anterior aspect of the transplanted kidney, which was suspected to be a lymphocele. Dietary intervention with high protein, low fat and medium-chain triglyceride was implemented and maintained for 2 months, and the patient’s symptoms did not worsen. A repeat abdominal ultrasonographic examination revealed the disappearance of lymphocele on day 65 post-transplantation. During the 15 months follow-up, the patient was free from ascites and the transplanted kidney worked well. Post-operative chylous ascites is a rare complication that is caused either by surgical interruption of lymphatic channels or by the fenestration of lymphoceles to the peritoneum. The diagnostic tools are limited to prevent further graft damage by nephrotoxic contrast. Lymphoscintigraphy and 3D MRI may be helpful in demonstrating abnormality of lymph vasculature, especially in renal transplantation. Dietary intervention, during and after chyloperitoneum, is recommended according to our experience. The rapid recovery of chylous ascites may mean that the injury to the lymphatic system is less severe in transplanted procedure.

to a monoclonal IgM have been previously described in patients known to have Waldenstrom’s macroglobulinaemia. These falsely elevated results occurred with an enzymatic assay (Roche Diagnostics) and were confirmed to be normal using high performance liquid chromatography (HPLC) [1]. Fortunately, this appears to be an uncommon problem, although possibly under-recognized. The mechanism remains unknown, although its occurrence with a number of different assays implies that there may be more than one. The previous report in the literature referred to an aqueous test method [1]. Our patients’ serum was tested with similar methods without any resulting interference. As clinicians who see patients frequently for elevated serum creatinine values, nephrologists must be aware of the limitations of this test. Pseudohypercreatininaemia secondary to a monoclonal protein should be considered in patients with an isolated creatinine elevation, particularly when associated with a normal urea, or an elevated total protein. Measuring the serum creatinine using a completely different method may prevent other unnecessary tests or procedures.

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.

BACKGROUND Some investigators have recommended the convenient practice of administering vancomycin doses during the last hour of the hemodialysis treatment. Accepting that a greater amount of vancomycin is lost to dialysis with this recent approach, the objective of this study is to determine the pharmacokinetics of vancomycin and assess the adequacy of this dosing regimen in maintaining therapeutic predialysis concentrations. METHODS A sampling of 22 consecutive patients administered intradialytic vancomycin, 1 g, intravenously (IV) and maintenance doses of 500 mg during the last hour of high-flux dialysis sessions was studied. A population-modeling program and Bayesian pharmacokinetic analysis were used to identify all global and unique pharmacokinetic parameters of interest based on measured vancomycin predialysis concentrations. RESULTS For the 22 patients studied, this regimen achieved the targeted predialysis concentration range of 5 to 20 microg/mL for 96% of levels, whereas more narrowly within 5 to 15 microg/mL for 86% of levels. Average amount of vancomycin removed during a standardized 3- to 4-hour dialytic session ranged from 30% +/- 7% to 38% +/- 8%. Average elimination half-life of vancomycin on hemodialysis treatment was 5.4 hours (interquartile range, 5.0 to 5.9 hours). Patients showed an average predialysis plasma concentration of 11 +/- 3 microg/mL for the first 7 days of therapy. CONCLUSION Our results indicate that intradialytic dosing with vancomycin using a 1-g IV load and 500 mg IV with subsequent high-flux dialysis sessions conveniently maintains adequate predialysis plasma concentrations. The lack of drug accumulation with this regimen provides convincing support for a limited blood sampling approach to plasma concentration determinations.

Background: For many dialysis patients, survival is no different than with certain cancers. Yet, it appears that most nephrologists do not give detailed information about survival prior to obtaining informed consent for chronic dialysis. There are no published data on whether patients wish to be so informed.Objective: To assess whether patients would want voluntary disclosure by their physician of their survival should they need dialysis, and if so, why?Method. A questionnaire was completed by 100 general nephrology patients during their first visit to a nephrologist.Results: The vast majority of patients (97 %) would want to be given life-expectancy information, and for the physician to do so without having to be prompted. Furthermore, the majority of patients would want as much information as possible, both good and bad.Conclusions: Virtually all patients want, and therefore should receive from their physician, prognostic information about dialysis to facilitate informed decision-making. This is in accordance with current practice guidelines.

Objectives To analyze clinical outcomes of Staphylococcus epidermidis peritoneal dialysis peritonitis before and after an interventional switch from a vancomycin/tobramycin to a cefazolin/tobramycin regimen for empiric treatment. To examine risk factors associated with clinical failure. Design A retrospective study. Setting A peritoneal dialysis program within a university-affiliated tertiary-care hospital. Patients 93 episodes of S. epidermidis peritonitis over a 6-year period. Interventions Clinical responses were compared between treatments using chi-square or Fisher's exact test. Univariate and multivariate analyses were used to identify significant risk factors for clinical failure. Measurements and Main Results There was no difference in the overall response rates observed with vancomycin (40/49; 81.6%) and cefazolin (23/29; 79.3%) regimens for episodes of S. epidermidis peritonitis. Furthermore, the presence of methicillin resistance in 63 of 93 cases (67.7%) had no influence on clinical outcome, with response rates of 83.9% (26/31) and 82.4% (14/17) for empiric vancomycin and cefazolin regimens, respectively. Tobramycin therapy of less than 2 days was an independent risk factor for clinical failure in multivariate logistic regression analysis (odds ratio 4.44, 95% confidence interval 1.28 – 15.48; p = 0.02). Conclusions Empiric treatment with intraperitoneal cefazolin was as effective as vancomycin for S. epidermidis peritonitis despite a high prevalence of methicillin resistance. Tobramycin therapy of less than 2 days was strongly associated with treatment failure.

No scientific data exist to support inpatient peritoneal dialysis catheter insertion (PDCI). There is also no evidence to support that regular flushing of PDCs prior to PD training decreases the incidence of malfunction. Literature on these subjects is lacking. A brief, informal telephone survey that we performed across Canadian tertiary-care university hospitals prior to initiation of this study suggested that surgical PDCI in this country is generally performed as an inpatient procedure, and that there is no consensus on whether or on how often peritoneal catheter flushing is necessary prior to daily use. As in most Canadian hospital centers, at our institution, hospital bed resources have become increasingly scarce, and in August 1999, the hospital administration demanded that PDCI be performed on an outpatient basis because the three hospital beds traditionally reserved for inpatient PDCI could no longer be secured. This study was therefore performed to compare the outcomes of inpatient versus outpatient PDCI. The Moncrief PDC (1–3), which is generally inserted several months before use, does not get flushed prior to exteriorization and yet is reported to be highly functional. We therefore hypothesized that regular catheter flushing may not be necessary and this practice, previously performed weekly, was abandoned in August 1999, with initiation of outpatient PDCI.

BACKGROUND C-reactive protein (CRP) levels are increased in 30 to 50% of dialysis patients and predict cardiovascular morbidity and mortality. It is usually considered that raised CRP levels reflect underlying atherosclerosis. However, many patients may have clinically apparent cardiovascular disease without raised CRP levels. This study was designed to assess both the risk factors for high CRP levels and the usefulness of the test as a marker of clinically apparent coronary artery disease (CAD), peripheral vascular disease (PVD) and the presence of ongoing infections/inflammatory disorders (INF-INFL) in peritoneal dialysis patients. METHODS A chart review of 190 prevalent peritoneal dialysis patients was performed. CRP, albumin, ferritin, erythropoietin (EPO) dose and resistance, Kt/V, and residual renal function values were obtained and a history or presence of cardiovascular disease (CAD, PVD) and presence of INF-INFL recorded. Data were analyzed by Chi-square, Spearman correlation and logistic regression. RESULTS A total of 31% of patients had a raised CRP. INF-INFL was highly predictive of raised CRP levels (OR 16.97; 95% CI 5.41 to 53.14, P=0.000), whereas CAD and PVD either singly or in combination had no such association. The sensitivity/specificity for CRP as a test for INF-INFL was 83/77%. For CAD and PVD, the sensitivities were less than 40% and specificities 70%. Increased CRP values were more common in females but not in diabetics. Weak linear correlations existed between CRP levels and albumin, ferritin and residual renal function (r=-0.212, 0.228 and -0.163 respectively, P < 0.02). By regression analysis, INF-INFL predicted high CRP levels, but CAD and PVD did not. The majority of patients (57%) with high CRP had no identifiable cause; 40% of these patients had subsequent or previous normal CRP values. High transport status predicted high CRP levels (OR 7.28; 95% CI 1.417 to 37.36, P=0.006). CONCLUSIONS The majority of elevated CRP levels in peritoneal dialysis patients occur without an obvious cause. Clinically apparent cardiovascular disease does not predict high CRP levels. CRP levels vary over time in the same patient, from normal to high or vice versa, for no obvious reason. Sources of inflammation other than CAD, PVD and clinically obvious INF-INFL in peritoneal dialysis patients remain to be identified.

BACKGROUND Calciphylaxis, historically considered rare, seems to be increasing in frequency. In our single center, 36 new cases have accumulated in seven years. The majority of these cases were non-ulcerating, which we believe to be early disease, in contradistinction to the vast majority of published cases that presented with ulcers. METHODS Prospective data were collected on all patients with calciphylaxis. As well, a case control study, with two controls per patient, was performed on patients presenting with non-ulcerating plaques. RESULTS The incidence of calciphylaxis in dialysis patients increased with a rate of 4.5/100 patient-years in the past three years. Eighty percent of cases presented with non-ulcerating subcutaneous plaques in the calves, easily confused with cellulitis. In those patients presenting with plaques only, the mortality rate was 33% at six months. Once ulceration develops, the mortality rate increased to above 80%. Bone scan was positive in 97% of patients. Steroid therapy appeared to be beneficial in some patients. Peritoneal dialysis, female sex and diabetes were risk factors. In the case control study of patients presenting with plaques only, serum phosphate (OR 2.6; 95% CI 1.05 to 6.45, P = 0.038) and Ca x P product (OR 1.46; 95% CI 1.02 to 20, P = 0.038) predicted the disease, as did being on calcium salts + vitamin D (OR 4.05; 95% CI 1.14 to 14.5, P = 0.03). CONCLUSIONS Calciphylaxis is no longer rare. It is usually nonulcerating and can be diagnosed clinically in all patients. These patients have a high mortality, especially once ulceration occurs. Calcium salts plus vitamin D, as well as serum Ca x P product and high serum P increase the chance of the diseases. Therefore, the disease may be preventable. Steroids may be of benefit to some patients.

The objective was to test antibiotic activity against Staphylococcus epidermidis and Pseudomonas aeruginosa in fresh dianeal fluid and spent dialysate from patients undergoing chronic ambulatory peritoneal dialysis. MICs and MBCs were measured and compared with those in standard broth. For S. epidermidis, there was some reduction in cefazolin and vancomycin activity in dialysis fluids. For P. aeruginosa, ciprofloxacin and tobramycin MICs increased significantly, and all isolates were tolerant to ceftazidime and piperacillin in dialysis fluids. Dialysis fluids can significantly impair antibiotic activity. The clinical implications warrant further study of antibiotic pharmacodynamics in the treatment of peritonitis.

Seasonal variation in blood pressure in patients undergoing hemodialysis in Europe has recently been described. If confirmed, this has important therapeutic, research, and epidemiological implications. All normotensive patients not administered antihypertensive drugs in our unit were studied. Predialysis blood pressures were measured before each dialysis treatment over two 2-month periods, January through February and July through August, in Winnipeg, Canada, a city with one of the most extreme seasonal temperature variations in North America. No difference in blood pressures was found between summer and winter (141 ± 5/75 ± 2 versus 140 ± 4/74 ± 2 mm Hg; P = not significant). Average daily temperatures were –16°C in winter and 23°C in summer. Interdialytic weight gain was the same in both groups. In conclusion, season has no effect on blood pressure in hemodialysis patients in a North American center. Reported seasonal changes in blood pressure in Europe may be related to nonclimatic factors.

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.

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9 kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year, and duration of hospitalization was 4.8 +/- 3.7 days per patient-year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.