Robert A. Mactier

How to measure renal function in clinical practice.

The reliable measurement of renal excretory function is of great importance in clinical practice and in research. The introduction of routine reporting of estimated glomerular filtration rate and a new definition of chronic kidney disease has renewed interest in methods of measuring renal function. Coupled with this is the fact that several countries are moving towards population screening for renal impairment to try to reduce the associated increased cardiovascular risk. Accurate measurement is methodologically difficult so surrogate measures such as serum creatinine levels and prediction formulas (based on factors such as the patients age, sex, and serum creatinine level) are more commonly used in routine practice. We describe routine and more specialised methods of assessing renal function and discuss estimated glomerular filtration rate. The kidney has several interlinked functions (box). These depend on glomerular filtration rate, the unit measure of kidney function. Glomerular filtration rate can be defined as the volume of plasma cleared of an ideal substance per unit of time (usually expressed as ml/min). The ideal substance is one that is freely filtered at the glomerulus and neither secreted nor reabsorbed by the renal tubules. Creatinine is the closest to an ideal endogenous substance for measuring glomerular filtration rate.w1 Plasma creatinine is almost exclusively a product of the metabolism of creatine and phosphocreatine in skeletal muscle, although ingestion of meat may also contribute slightly.w2 w3 In patients with stable renal function, serum creatinine levels are usually constant, with variability daily of about only 8%.w4 w5 Creatinine is freely filtered at the glomerulus and is not reabsorbed, but up to 15% is actively secreted by the tubules.w6 In advanced renal failure, excretion of creatinine through the gastrointestinal tract increases.w7 Measuring the creatinine clearance using serum creatinine level and a timed urine collection gives an …

Clinical practice guidelines for peritoneal access.

Faculdade de Enfermagem, Nutricao e Fisioterapia,1 Pontificia Universidade Catolica do Rio Grande do Sul, Brazil; Department of Nephrology,2 Serdang Hospital, Jalan Puchong, Kajang, Selangor, Malaysia; Sheffield Kidney Institute,3 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Nephrology,4 Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia; Renal Services,5 Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom; Nephrology,6 Sri Ramachandra University, Chennai, India; Dialysis Unit,7 Dianet Dialysis Centers and Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Encapsulating Peritoneal Sclerosis in the New Millennium: A National Cohort Study

BACKGROUND AND OBJECTIVES The study aim was to establish the incidence and characterize all encapsulating peritoneal sclerosis (EPS) cases in patients treated by peritoneal dialysis (PD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The patient cohort, which started PD from January 1, 2000, to December 31, 2007, was identified from the Scottish Renal Registry (n = 1238). Possible EPS cases were identified by the ten adult Scottish renal units. Patient records were examined to ensure cases met diagnostic criteria. RESULTS Forty-six cases were identified; 19 had their first PD exposure after January 1, 2000. The rate was 1.5%, an incidence of 4.9 per 1000 person-years. The incidence increased with PD duration, with rates of 0, 0.6, 2.0, 3.5, 8.1, 8.8 and 5% at <1, 1 to 2, >2 to 3, >3 to 4, >4 to 5, >5 to 6 and >6 yr PD exposure, respectively. The median PD duration of EPS cases was 5.1 yr (interquartile range [IQR] 3.4 to 6.1 yr). At diagnosis, 12 (26%) were on PD and 33 (72%) were diagnosed <2 yr after PD stopped. The cases had a median of 3.3 episodes of peritonitis (range 0 to 20, IQR 1 to 4.5). Thirty (65%) had used 3.86% dextrose dialysate and 45 (98%) had used Extraneal. The mortality was 42% at 1 yr postdiagnosis with a median survival of 149 d (IQR 61 to 408 d). CONCLUSIONS The incidence reported in this study may be used to inform patients of the minimum risk of developing EPS on PD.

Peritoneal dialysis-associated peritonitis rates and outcomes in a national cohort are not improving in the post-millennium (2000-2007).

♦ Background: Peritoneal dialysis (PD)–related peritonitis remains the leading cause of technique failure and a significant cause of morbidity among PD patients. Rates in the literature vary, reflecting differences in study design and in populations. The objective of the present study was to determine peritonitis incidence and outcomes in Scotland and to compare them with national guidelines. ♦ Methods: All 10 adult renal units in Scotland prospectively collect data relating to peritonitis for all PD patients in Scotland. Complete audit data between 1 January 2000 and 31 December 2007 were analyzed for the study. ♦ Results: The 1918 peritonitis episodes in 38 106 PD treatment months yielded a national rate of 1 episode every 19.9 months. The UK Renal Association standard was met every year, but is not consistently improving. The median peritonitis-free survival was 526 days (95% confidence interval: 463 to 589 days). The spectrum of causative organisms reflected those in previous reports, with a culture-negative rate of 19.4%. Nationally, the cure rate was 74.6%, the refractory rate was 22.6%, and the death rate was 2.8%. Outcome varied by organism. Recurrences represented 9.3% of episodes, and technique failure occurred in 14.9%. The peritonitis rate was higher for continuous ambulatory PD patients than for automated PD patients (1 episode every 17.6 months vs 1 episode every 22.3 months, p < 0.001, relative risk: 1.27). There were significant differences between renal units. ♦ Conclusions: This large national PD cohort met targets for peritonitis rates every year during the 8 years covered by the present report, but showed no consistent trend for improvement. Peritonitis remains the main cause of technique failure in Scotland. Peritonitis rates varied widely between the units, which suggests that we should look to the units and countries with lower peritonitis rates to see if we can adopt successful elements of their practice before resigning ourselves to our ongoing peritonitis burden.

Peritoneal Cavity Lymphatics

Intraperitoneal fluid is absorbed continuously by convective flow into the peritoneal cavity lymphatics [1, 2]. The importance of lymphatic absorption from the peritoneal cavity in the pathophysiology of ascites is well established [3–16] and the considerable absorptive capacity of the peritoneal cavity lymphatics has been exploited clinically to perform intraperitoneal blood transfusions in the fetus and in children [17–21]. Nevertheless, until recently, studies of the kinetics of peritoneal dialysis ‘ascites’ have neglected the role of the peritoneal cavity lymphatics and have focused only on fluid and solute exchange between the peritoneal microcirculation and the hypertonic dialysis solution instilled into the peritoneal cavity [22–34]. Recent investigations, however, have demonstrated a significant contribution of lymphatic absorption to loss of ultrafiltration and solute clearances after long-dwell peritoneal dialysis exchanges [35–39].

A prospective observational study of catheter-related bacteraemia and thrombosis in a haemodialysis cohort: univariate and multivariate analyses of risk association

BACKGROUND Central venous catheterization is a fundamental component in delivering haemodialysis yet is associated with significantly higher complication rates than other methods of vascular access. In this study, we report results of univariate and multivariate analyses designed to identify and quantify independent risk association for catheterization type, clinical variables and laboratory variables with regard to the development of catheter-related bacteraemia (CRB) and catheter failure due to poor haemodialysis flow. METHODS A 2-year prospective study of all incident haemodialysis vascular access catheter insertions was conducted. Laboratory and clinical variables were recorded at catheter insertion, and the clinical course was followed up to the point of catheter removal. CRB and catheter failure due to poor flow were recorded as outcome events. Univariate and multivariate analyses were used to test for association between clinical and laboratory variables and outcome. RESULTS Forty-four thousand five hundred seventy-six catheter days were accumulated over the study period. Multivariate analysis demonstrated an independent association between non-tunnelled catheterization procedures and adverse outcomes compared with tunnelled central venous catheter insertions. Elevated modified Charlson comorbidity score was independently associated with the development of CRBc. Elevated C-reactive protein and low haemodialysis blood pump flow were independently associated with catheter failure due to poor flow. CONCLUSIONS The data demonstrate that tunnelled central venous catheter insertions have an association with lower complication rates than non-tunnelled central venous catheter insertions that is independent of whether patients have acute or chronic renal failure, or high levels of comorbidity.

Pharmacological reduction of lymphatic absorption from the peritoneal cavity increases net ultrafiltration and solute clearances in peritoneal dialysis

Lymphatic drainage from the peritoneal cavity occurs mainly via the subdiaphragmatic stomata and significantly reduces net ultrafiltration and solute clearances during long-dwell peritoneal dialysis. Intraperitoneal cholinergic drugs constrict these stomata and may reduce peritoneal cavity lymphatic absorption. We evaluated ultrafiltration kinetics, solute transport, and lymphatic drainage during single hypertonic exchanges in rats using 2.5% dextrose dialysis solution with and without added neostigmine. Net ultrafiltration was enhanced in the neostigmine group (p less than 0.01) by a reduction in cumulative lymphatic absorption (p less than 0.01) and without an increase in total transcapillary ultrafiltration during the dwell time. Likewise solute clearances were significantly augmented with neostigmine primarily due to the increase in dialysate drain volume (p less than 0.01) since dialysate/serum solute ratios were unchanged. Pharmacological manipulation of peritoneal lymphatic absorption provides an alternative means of increasing the efficiency of long-dwell peritoneal dialysis without altering peritoneal transport of solutes and water.

Summary of the 5th Edition of the Renal Association Clinical Practice Guidelines (2009-2012)

Robert Mactier, Simon Davies, Chris Dudley, Paul Harden, Colin Jones, Suren Kanagasundaram, Andrew Lewington, Donald Richardson, Maarten Taal, Peter Andrews Richard Baker, Cormac Breen, Neill Duncan, Ken Farrington, Richard Fluck, Colin Geddes, David Goldsmith, Nic Hoenich, Stephen Holt, Alan Jardine, Sarah Jenkins, Mick Kumwenda, Elizabeth Lindley, Mark MacGregor, Ashraf Mikhail, Edward Sharples, Badi Shrestha, Rajesh Shrivastava, Simon Steddon, Graham Warwick, Martin Wilkie, Graham Woodrow, Mark Wright

A Randomized, Single-Blind, Crossover Trial of Recovery Time in High-Flux Hemodialysis and Hemodiafiltration

Background The choice between hemodiafiltration (HDF) or high-flux hemodialysis (HD) to treat end-stage kidney disease remains a matter of debate. The duration of recovery time after treatment has been associated with mortality, affects quality of life, and may therefore be important in informing patient choice. We aimed to establish whether recovery time is influenced by treatment with HDF or HD. Study Design Randomized patient-blinded crossover trial. Settings & Participants 100 patients with end-stage kidney disease were enrolled from 2 satellite dialysis units in Glasgow, United Kingdom. Intervention 8 weeks of HD followed by 8 weeks of online postdilution HDF or vice versa. Outcomes Posttreatment recovery time, symptomatic hypotension events, dialysis circuit clotting events, and biochemical parameters. Measurements Patient-reported recovery time in minutes, incidence of adverse events during treatments, hematology and biochemistry results, quality-of-life questionnaire. Results There was no overall difference in recovery time between treatments (medians for HDF vs HD of 47.5 [IQR, 0-240] vs 30 [IQR, 0-210] minutes, respectively; P = 0.9). During HDF treatment, there were significant increases in rates of symptomatic hypotension (8.0% in HDF vs 5.3% in HD; relative risk [RR], 1.52; 95% CI, 1.2-1.9; P < 0.001) and intradialytic tendency to clotting (1.8% in HDF vs 0.7% in HD; RR, 2.7; 95% CI, 1.5-5.0; P = 0.002). Serum albumin level was significantly lower during HDF (3.2 vs 3.3 g/dL; P < 0.001). Health-related quality-of-life scores were equivalent. Limitations Single center; mean achieved HDF convection volume, 20.6 L. Conclusions Patients blinded to whether they were receiving HD or HDF in a randomized controlled crossover study reported similar posttreatment recovery times and health-related quality-of-life scores.

Role of Lymphatics in Peritoneal Dialysis

There is a renewed interest in understanding the precise role of lymphatics in the ultrafiltration kinetics during peritoneal dialysis. In the normal state, lymphatics draining the peritoneal cavity are the principal means of removal of intraperitoneal isosmotic fluid and macromolecules. During a hypertonic peritoneal dialysis exchange, after peak intraperitoneal volume is achieved, fluid removal proceeds at an almost linear rate, causing intraperitoneal fluid volume to reduce. The isosmotic fluid removal from the peritoneal cavity could occur through the microcirculatory capillaries or through the lymphatic capillaries draining the peritoneal cavity. Animal and human studies suggest that this fluid loss occurs primarily through lymphatics. The two indirect methods of lymph flow measurements, plasma appearance and peritoneal disappearance of tracer colloid, show conflicting results. Although direct measurement of lymph flow rates through cannulation of mediastinal lymph vessels in animals suggests a significant flow through the lymph channels in response to intraperitoneal fluid instillation, lymph flow modification at the lymph node level may prevent use of this technique to assess the precise role played by lymphatics in fluid kinetics during peritoneal dialysis. By analogy with ascites and by extrapolation from previous studies of drain volumes after infusion of isotonic and hypertonic solutions, the average daily lymph absorption rate during CAPD may be predicted to be at least 1 liter per day.