Mohan Biyani

Targeted therapies in diabetic nephropathy: an update.

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Various pathways in addition to the renin-angiotensinogen system have been implicated in the pathogenesis of diabetic nephropathy. Strategies to interrupt these pathophysiological pathways are a key to the development of new targeted therapies to prevent progression of diabetic nephropathy and are on the horizon. The various pharmacological drugs tried include aliskiren, a direct renin inhibitor blocking the first step in the renin pathway, and pentoxifylline and mammalian target of rapamycin inhibitors, which have antiinflammatory properties and have shown some promising results in management of diabetic nephropathy. Others include endothelin antagonists and vitamin D analogs which have been shown to decrease urinary albumin excretion. Inhibitors of advanced glycation and oxidative stress and plasminogen activator inhibitor-1 have proved useful in animal models of diabetic nephropathy. Others include ruboxistaurin, which blocks protein kinase C overexpression. Such targeted therapies would halt and might even reverse progression of diabetic nephropathy.

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.

Cystatin C and Residual Renal Function in Patients on Peritoneal Dialysis

mated GFR of 46 12 mL/min/1.73 m, which is almost half of the value reported in Dr Fukuda’s study (84 44 mL/min/1.73 m), and with a usual salt intake, as witnessed by the daily sodium excretion (approximately 160 mmol/d, versus 110 mmol/d in Dr Fukuda’s study). These data are compatible with a greater extracellular volume expansion in our patients that likely overcomes any other determinant of blood pressure sodium sensitivity. In addition, while Dr Fukuda studied untreated patients, all patients in our study, as usually seen in clinical practice, were on RAS inhibitors at baseline; this may have further blunted the potential class-specific effect of the drug shift on night-day blood pressure ratio. Therefore, while we agree that the point made by Dr Fukuda is intriguing, we believe that the independent role of RAS inhibition in restoring the circadian BP rhythm deserves further investigation.

A high serum vancomycin level is associated with lower relapse rates in coagulase-negative staphylococcal peritonitis.

Food and Drug Administration (FDA), Center for Drug Evaluation and research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical method Validation. rockville, MD: FDA; 2001. 9. Walker PC, Kaufmann rE, Massoud N. Compatibility of cefazolin and gentamicin in peritoneal dialysis solutions. Drug Intell clin Pharm 1986; 20:697–700. 10. Halstead DC, Guzzo J, Giardina JA, Geshan AE. In vitro bactericidal activities of gentamicin, cefazolin, and imipenem in peritoneal dialysis fluids. antimicrob agents chemother 1989; 33:1553–6. 11. Nahata MC, Ahalt PA. Stability of cefazolin sodium in peritoneal dialysis solutions. am J hosp Pharm 1991; 48:291–2. 12. British Pharmacopoeia Commission. British Pharmacopoeia 2012. London, UK: The Stationary Office; 2012. doi:10.3747/pdi.2013.00013

Characteristics and Outcomes of Exit Sites of Buried Peritoneal Dialysis Catheters: A Cohort Study

Buried peritoneal dialysis (PD) catheters are placed months before dialysis is needed and the exit site is created when the catheter is dissected out at the initiation of dialysis. In contrast, the exit site of an unburied catheter is created by the surgeon at the time of insertion. We reviewed all patients who initiated PD at our center over a 2-year period. At each clinic visit, exit sites were subjectively classified into standard predefined groups. Outcomes of interest were the frequency of perfect exit sites at 2, 6, and 12 months and rate of exit-site infections (ESIs) at 90 days. One hundred and seventy-seven patients initiated PD during the period of interest, and 169, 157, and 144 remained on PD at 2, 6, and 12 months, respectively. Ninety-three patients had buried catheters, and 76 patients had unburied catheters. Both groups had similar frequency of perfect appearance of exit sites at 2, 6, and 12 months (37/93 vs 41/76 at 2 months; 54/87 vs 43/70 at 6 months; 50/ 81 vs 35/ 63 at 12 months in buried and unburied groups, respectively). More patients with buried catheters had ESIs in the first 3 months (7/93 vs 1/76, p = 0.059). We conclude that exit sites of buried PD catheters do not differ qualitatively from those of unburied catheters. The trend towards more ESIs with buried catheters suggests that there may be clinical consequences of the tissue trauma at time of exteriorization.

Individual patient variability with the application of the kidney failure risk equation in advanced chronic kidney disease.

The Kidney Failure Risk Equation (KFRE) predicts the need for dialysis or transplantation using age, sex, estimated glomerular filtration rate (eGFR), and urine albumin to creatinine ratio (ACR). The eGFR and ACR have known biological and analytical variability. We examined the effect of biological and analytical variability of eGFR and ACR on the 2-year KFRE predicted kidney failure probabilities using single measure and the average of repeat measures of simulated eGFR and ACR. Previously reported values for coefficient of variation (CV) for ACR and eGFR were used to calculate day to day variability. Variation was also examined with outpatient laboratory data from patients with an eGFR between 15 and 50 mL/min/1.72 m2. A web application was developed to calculate and model day to day variation in risk. The biological and analytical variability related to ACR and eGFR lead to variation in the predicted probability of kidney failure. A male patient age 50, ACR 30 mg/mmol and eGFR 25, had a day to day variation in risk of 7% (KFRE point estimate: 17%, variability range 14% to 21%). The addition of inter laboratory variation due to different instrumentation increased the variability to 9% (KFRE point estimate 17%, variability range 13% to 22%). Averaging of repeated measures of eGFR and ACR significantly decreased the variability (KFRE point estimate 17%, variability range 15% to 19%). These findings were consistent when using outpatient laboratory data which showed that most patients had a KFRE 2-year risk variability of ≤ 5% (79% of patients). Approximately 13% of patients had variability from 5–10% and 8% had variability > 10%. The mean age (SD) of this cohort was 64 (15) years, 36% were females, the mean (SD) eGFR was 32 (10) ml/min/1.73m2 and median (IQR) ACR was 22.7 (110). Biological and analytical variation intrinsic to the eGFR and ACR may lead to a substantial degree of variability that decreases with repeat measures. Use of a web application may help physicians and patients understand individual patient’s risk variability and communicate risk (https://mccudden.shinyapps.io/kfre_app/). The web application allows the user to alter age, gender, eGFR, ACR, CV (for both eGFR and ACR) as well as units of measurements for ACR (g/mol versus mg/g).

Can economic incentives increase the use of home dialysis

There are advantages to home dialysis for patients, and kidney care programs, but use remains low in most countries. Health-care policy-makers have many levers to increase use of home dialysis, one of them being economic incentives. These include how health-care funding is provided to kidney care programs and dialysis facilities; how physicians are remunerated for care of home dialysis patients; and financial incentives-or removal of disincentives-for home dialysis patients. This report is based on a comprehensive literature review summarizing the impact of economic incentives for home dialysis and a workshop that brought together an international group of policy-makers, health economists and home dialysis experts to discuss how economic incentives (or removal of economic disincentives) might be used to increase the use of home dialysis. The results of the literature review and the consensus of workshop participants were that financial incentives to dialysis facilities for home dialysis (for instance, through activity-based funding), particularly in for-profit systems, could lead to a small increase in use of home dialysis. The evidence was less clear on the impact of economic incentives for nephrologists, and participants felt this was less important than a nephrologist workforce in support of home dialysis. Workshop participants felt that patient-borne costs experienced by home dialysis patients were unjust and inequitable, though participants noted that there was no evidence that decreasing patient-borne costs would increase use of home dialysis, even among low-income patients. The use of financial incentives for home dialysis-whether directed at dialysis facilities, nephrologists or patients-is only one part of a high-performing system that seeks to increase use of home dialysis.

The Risk of Adverse Events in Patients With Polycystic Kidney Disease With Advanced Chronic Kidney Disease

Background: Polycystic kidney disease (PKD) leads to progressive chronic kidney disease (CKD) with a subsequent risk of adverse events such as cardiac disease, infections, end-stage kidney disease (ESKD), and mortality. Objectives: To determine the risks of CKD-related adverse outcomes in patients with PKD compared with patients without PKD. Setting: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT) was a prospective pan-Canadian cohort study from 2008-2013 involving 28 facilities with adjudicated outcomes. Patients: Adult CKD patients (estimated glomerular filtration rate [eGFR] = 15-45 mL/min/1.73 m2) under the care of a nephrologist. Measurements: Polycystic kidney disease as identified by the treating physician. Methods: Patients with PKD (PKD) and non-PKD were propensity score (PS) matched (1:4) using demographics, comorbidities, and laboratory values. We used conditional Cox proportional hazards models to examine the risk of cardiac disease (defined as coronary artery disease or congestive heart failure), infection, ESKD, or all-cause mortality in patients with PKD compared with no PKD. Results: Among a total of 2370 patients, 105 with PKD were matched with 416 without PKD with a baseline mean age and eGFR of 62.6 years and 27.8 mL/min, respectively. During 1680 person-years of follow time (median follow-up: 3.8 years), there were a total of 43 cardiac, 83 ESKD, 117 infectious, and 39 all-cause mortality events. PKD was associated with a higher risk of cardiac events (9.5% vs 7.9%, hazard ratio [HR] = 1.46, 95% confidence interval [CI] = 1.04-2.04) and ESKD (25.7% vs 13.5%, HR = 2.00, 95% CI = 1.33-3.01), and with similar risks for infection (21.9% vs 22.6%, HR = 1.16, 95% CI = 0.75-1.82) or all-cause mortality (6.7% vs 7.7%, HR = 0.87, 95% CI = 0.40-1.91) compared with non-PKD. There were no differences in the types of infections (urinary, respiratory, hematologic, or other) between the 2 groups (P = .585). Conclusions: Patients with PKD with advanced CKD are at a potentially higher risk of ESKD and cardiac events compared with patients without PKD. These findings, if confirmed in larger cohorts, suggest that monitoring and treatment for adverse outcomes in patients with PKD, especially related to cardiac disease, may be beneficial.

Successful Treatment of PD Peritonitis Due to Morganella morganii Resistant to Third-Generation Cephalosporins – A Case Report

Morganella morganii is a rare cause of peritonitis in patients on peritoneal dialysis (PD). Most of the reported cases have resorted to a switch to hemodialysis. We herein report a case of peritonitis due to M. morganii resistant to third-generation cephalosporins, which was treated successfully with intraperitoneal (IP) tobramycin followed by oral ciprofloxacin. Early microbiologic diagnosis is essential in the treatment of peritonitis from rare microorganisms such as Morganella morganii, and appropriate antibiotic therapy is the key to avoiding catheter loss and subsequent switch to hemodialysis.

Asymptomatic peritoneal leukocytosis after exteriorization of buried peritoneal dialysis catheters: a case series.

2. Diaz-Buxo JA, Turner MW, Nelms M. Fluoroscopic manipulation of Tenckhoff catheters: outcome analysis. Clin Nephrol 1997; 47:384–8. 3. Amerling R, Vande Maele D, Spicak H, Lo AY, White P, Beaton H, et al. Laparoscopic salvage of malfunctioning peritoneal catheters. Surg Endosc 1997; 11:249–52. 4. Lee M, Donovan JF. Laparoscopic omentectomy for salvage of peritoneal dialysis catheters. J Endourol 2002; 16:241–4. 5. Barone GW, Johnson DD, Webb JW. A practical approach to laparoscopic surgery for malfunctioning peritoneal dialysis catheters. J Laparoendosc Adv Surg Tech A 1998; 8:19–23. 6. Takara Y, Ishibashi Y, Fujishiro M, Fujita T. Endoscopic treatment of obstructed peritoneal catheter. Kidney Int 2011; 80:679. 7. Di Paolo N, Sacchi G. Atlas of peritoneal histology. Perit Dial Int 2000; 20:S5–96. doi: 10.3747/pdi.2012.00288