Brendan B. McCormick

The Effect of Pentoxifylline on Proteinuria in Diabetic Kidney Disease: A Meta-analysis

BACKGROUND Pentoxifylline is a potential therapeutic agent for diabetic kidney disease because it has anti-inflammatory, antifibrotic, and hemorheological properties. STUDY DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING, POPULATION, & INTERVENTION Adult patients with diabetic kidney disease who received oral pentoxifylline. SELECTION CRITERIA FOR STUDIES We searched bibliographic databases for trials involving pentoxifylline that reported proteinuria, glomerular filtration rate, or blood pressure. OUTCOMES The primary outcome measure was the effect of pentoxifylline on proteinuria stratified by whether pentoxifylline was compared with renin-angiotensin system blockade. RESULTS 10 studies including a total of 476 participants with a median duration of 6 months were identified. Pentoxifylline significantly decreased proteinuria (weighted mean difference, -278 mg/d of protein; 95% confidence interval [CI], -398 to -159; P < 0.001) compared with placebo or usual care. Compared with captopril, the decrease in proteinuria with pentoxifylline was similar (weighted mean difference, 0 mg/d of protein; 95% CI, -17 to 18; P = 0.9). Secondary analysis showed that patients with microalbuminuria had a nonsignificant decrease in protein excretion (weighted mean difference, -87 mg/d; 95% CI, -201 to 27; P = 0.1), whereas those with overt proteinuria (protein > 300 mg/d) had a significant decrease (weighted mean difference, -502 mg/d; 95% CI, -805 to -198; P = 0.001). No significant changes in systolic or diastolic blood pressure or glomerular filtration rate were found. LIMITATIONS Quality scores of studies were low, and there was significant heterogeneity. CONCLUSIONS Available evidence suggests that pentoxifylline may decrease proteinuria in patients with diabetic nephropathy. To confirm these findings, large high-quality studies are required.

Severe Hypocalcemia Following Denosumab Injection in a Hemodialysis Patient

Denosumab is a human monoclonal antibody directed against RANKL (receptor activator of NF-κB ligand) and is a novel treatment for postmenopausal osteoporosis, although its safety and efficacy in end-stage renal disease is unclear. We report the case of a 61-year-old female hemodialysis patient who developed severe hypocalcemia (total serum calcium, 5.37 mg/dL [1.34 mmol/L]) after receiving a single subcutaneous injection of denosumab. We review this medications mechanism of action and the very limited data regarding its use in stage 5 chronic kidney disease. We advise against the use of denosumab in those treated with hemodialysis due to the risk of severe hypocalcemia and lack of evidence supporting its efficacy in treating osteoporosis in this population.

CLINICAL PRACTICE GUIDELINES AND RECOMMENDATIONS ON PERITONEAL DIALYSIS ADEQUACY 2011

Division of Nephrology,1 University of Western Ontario, London, Ontario; Division of Nephrology,2 University of Toronto, Toronto, Ontario; Division of Nephrology,3 McMaster University, Hamilton, Ontario; Division of Nephrology and Transplant Immunology,4 University of Alberta, Edmonton, Alberta; Division of Nephrology,5 Dalhousie University, Halifax, Nova Scotia; Division of Nephrology,6 University of Ottawa, Ottawa, Ontario; Division of Nephrology,7 University of British Columbia, Vancouver, British Columbia, Canada

Complications and catheter survival with prolonged embedding of peritoneal dialysis catheters

BACKGROUND Our centre uses a modification of the Moncrief technique of embedding peritoneal dialysis (PD) catheters. We undertook this study to test the hypothesis that catheter survival on PD is a function of the time a catheter is left embedded prior to use. METHODS Data were retrospectively abstracted from review of patient records of those who received a first PD catheter over a 5-year period. Patients were divided into tertiles based on the number of days between insertion of the catheter and exteriorization to create three equal groups representing early (group 1, 11-47 days), mid (group 2, 48-133 days) and late (group 3, 134-2041 days) exteriorization strategies. RESULTS 435 embedded PD catheters were inserted, 349 were exteriorized and total observation period was 5624 patient-months. Time to catheter loss was shortest in group 1 and longest in group 2 (P = 0.04). The overall rate of primary catheter failure was 6% and was significantly different in the three groups (6.9% in group 1, 1.7% in group 2 and 9.4% in group 3, P = 0.04). The time to first episode of peritonitis was longest in group 3 and shortest in group 1 (group 1 versus group 3, P = 0.009; group 2 versus group 3, P = 0.03). Adjusted peritonitis rates, however, were not different between the three groups. CONCLUSIONS Mechanical complications and catheter loss are associated with the length of time a catheter is embedded. We recommend insertion 6 weeks to 5 months ahead of the need for PD to maximize catheter survival.

Effect of Neutral-pH, Low–Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES Neutral-pH, low-glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. RESULTS Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =-110; 95% confidence interval, -312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). CONCLUSIONS The use of neutral-pH, low-glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low-glucose degradation products solutions on hard clinical outcomes.

Canadian Society of Nephrology Commentary on the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guidelines relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant.

Peritoneal Dialysis Catheter Insertion Strategies and Maintenance Of Catheter Function

It has been more than 40 years since permanent peritoneal dialysis (PD) access with the Tenckhoff catheter was first described, and despite much experimentation with catheter design and insertion techniques, access to timely and skilled PD catheter insertion remains a barrier to more widespread PD use in many centers. This article reviews different insertion techniques with a focus on both mechanical outcomes as well as logistic advantages associated with the embedded catheter and percutaneous techniques. Maintenance of catheter function is discussed with a focus on an organized and evidence-based approach to preventing and treating mechanical catheter problems.

Peritoneal phosphate clearance is influenced by peritoneal dialysis modality, independent of peritoneal transport characteristics.

BACKGROUND AND OBJECTIVES Hyperphosphatemia is an independent risk factor for mortality in ESRD, but factors regulating phosphate clearance on peritoneal dialysis (PD) are incompletely understood. The objective of this study was to test the hypothesis that peritoneal phosphate clearance is better with continuous ambulatory PD (CAPD) as compared with continuous cyclic PD (CCPD) after adjusting for membrane transport status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this cross-sectional and retrospective study, measurements of peritoneal phosphate clearance of 129 prevalent PD patients were reviewed. Patients were divided according to membrane transport status (high, high average, low average-low categories) and PD modality (CAPD or CCPD). RESULTS Among high transporters, peritoneal phosphate clearances were comparable in both modalities. However, treatment with CAPD was associated with increased peritoneal phosphate clearance compared with CCPD among high-average transporters (42.4 +/- 11.4 versus 36.4 +/- 8.3 L/wk/1.73 m(2), P = 0.01), and low-average-low transporters (35.6 +/- 5.9 versus 28.9 +/- 11 L/wk/1.73 m(2), P = 0.034). On multivariate linear regression, PD modality, membrane transport category, and peritoneal creatinine clearance, but not Kt/V urea, were independently associated with peritoneal phosphate clearance. CONCLUSIONS Peritoneal phosphate clearance is determined by PD modality and membrane transport category, suggesting that PD regimes with longer dwell times may help control hyperphosphatemia in lower transporters.

Fluoroscopic Manipulation of Peritoneal Dialysis Catheters: Outcomes and Factors Associated with Successful Manipulation

BACKGROUND AND OBJECTIVES Mechanical failure of the peritoneal dialysis (PD) catheter is an important cause of technique failure. Fluoroscopic guidewire manipulation may be undertaken in an attempt to correct the failure. The purpose of this study was to determine the efficacy of fluoroscopic manipulation of previously embedded PD catheters, the factors associated with successful manipulation, and the complication rate associated with manipulation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A single-center, retrospective review of 70 consecutive PD patients undergoing fluoroscopic manipulation for mechanical failure of their PD catheter from June 2006 to February 2011 was undertaken. Logistic regression models were developed to determine the variables associated with successful manipulation. RESULTS Of the 70 manipulations, 44 were successful (62.9%). In univariate analysis, catheters located in the pelvis compared with those in the upper abdomen (73.5% versus 42.9%, P=0.01) and catheters that were previously functional compared with those that failed at exteriorization (75.0% versus 46.7%, P=0.04) were more likely to be successfully manipulated. Time embedded, previous hemodialysis, and number of intra-abdominal surgeries were not correlated with likelihood of successful manipulation. In multivariate analysis, catheters located in the pelvis (P=0.01) and those with secondary failure (P=0.01) were more likely to successfully manipulated. Two of the patients developed peritonitis (2.9%), neither requiring cessation of PD. CONCLUSIONS Fluoroscopic manipulation is an effective and safe therapy for failed PD catheters that are unresponsive to conservative treatment. Properly positioned catheters and those that were previously functional are more likely to be successfully manipulated.

Peritoneal dialysis catheter implantation by nephrologists is associated with higher rates of peritoneal dialysis utilization: a population-based study

BACKGROUND The likelihood of peritoneal dialysis (PD) utilization following a PD catheter insertion attempt is poorly described. We explored the risk factors for PD nonuse, focusing on the method of PD catheter implantation. METHODS This population-based retrospective cohort study employed Ontario administrative health data to identify 3886 predialysis adults who had an incident PD catheter implantation between 2002 and 2010. The impact of the method of catheter implantation including open-surgical (open, n = 1884), surgical-laparoscopic (laparoscopic, n = 1154), nephrology-percutaneous (nephrology, n = 498) and radiology-percutaneous (radiology, n = 350) on rates of PD utilization (defined as four consecutive weeks of PD) was examined. RESULTS Eighty-three percent of study patients received PD. After adjustment, relative to patients with openly inserted catheters, PD utilization was greater for those with nephrology-inserted catheters [adjusted hazard ratio (aHR) 1.59, 95% confidence interval (CI) 1.29-1.95] and similar for radiology-inserted catheters [aHR 1.16, 95% CI 0.94-1.43] or laparoscopic-inserted catheters [aHR 0.97 (95% CI 0.86-1.09)]. Among PD nonusers, death occurred in 10% of the open group, 6% of the laparoscopic group, 27% of the radiology group and in fewer than 3% of the nephrology group. Sixty-nine percent received hemodialysis in the open group, 63% in the laparoscopic group, 61% in the radiology group and 88% in the nephrology group. Those remaining predialysis comprised 12% of the open group, 22% of the laparoscopic group, 11% of the radiology group and <3% of the nephrology group. CONCLUSIONS Nephrology insertion resulted in lower overall rates of PD nonuse, particularly due to death or remaining predialysis. Greater use may be related to insertion timing, technique or greater commitment on the part of nephrologists to the success of PD.