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Periodontal disease is a chronic inflammatory disorder and being so it has been associated with accelerated atherosclerosis and malnutrition. Cardiovascular diseases are the leading cause of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Annual Data Report, 2010]. A recent scientific statement released by the American Heart Association [Lockhart et al.: Circulation 2012;125:2520-2544] claims that, even though evidence exists to believe that periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction, there is little evidence that those interventions prevent atherosclerotic vascular disease or modify the outcomes. In this review, we discuss the periodontal findings and their association with an increased prevalence of inflammatory markers and cardiovascular mortality in ESRD patients and CKD.

Background: We analyzed a large number of demographic and biochemical variables to identify predictors of hospitalization in subjects on peritoneal dialysis (PD)., Methods: All patients initiated on PD at our center from January 1990 through December 1999 were included. The following variables at the initiation of PD were included: demographics, clinical data, nutritional and adequacy parameters, transport characteristics, and various co-morbidities. Co-morbidities were graded for severity using a modified version of the Index of Coexistent Disease. Variables included during the course of PD consisted of weighted time average of a number of laboratory, adequacy, and nutritional parameters along with the number of peritonitis episodes per year. Stepwise linear regression was used following a univariate screening procedure to identify independent predictors of the outcome of hospitalization days per month on PD., Results: The subject population consisted of 191 subjects (105 men, 86 women; 180 Caucasians, 10 African-American, 1 Asian). The mean age was 61 +/- 13 (SD) years and mean duration of follow-up was 21 +/- 18 months. The baseline variable analysis revealed that the presence of partner to perform PD predicted increased hospitalization (p < 0.0001). Additionally, the presence and severity of peripheral vascular disease and residual renal Kt/V at baseline (negative association) predicted increased hospitalization. In the analyses of ongoing variables, stepwise linear regression solely identified weighted time average albumin as a strong negative predictor of hospitalization (p < 0.0001)., Conclusion: A comprehensive analysis of a large number of variables revealed that serum albumin during the course of PD (negative association) and the need for partner to perform PD strongly predicted increased hospitalization in PD subjects., (2007 S. Karger AG, Basel)

Automated peritoneal dialysis (APD) use has increased considerably in the last decade, and its growth has been mainly driven by patient preference and development of new, simpler cyclers. Careful management of the APD prescription can result in adequate solute and fluid removal in vast majority of patients, even anuric and large patients. So far, there are no convincing data that peritonitis rates, decline in residual renal function, protein losses, patient and technique survival, are different for APD and continuous ambulatory peritoneal dialysis (CAPD). APD has the major advantage of allowing positive changes in the life-style of end stage renal disease patients.

Malnutrition, inflammation and atherosclerosis are prevalent in end stage renal disease and constitute the Malnutrition-Inflammation-Atherosclerosis Syndrome. The syndrome is associated with high cardiovascular mortality and accounts for most of the premature deaths in peritoneal dialysis patients. Presence of elevated C-reactive protein levels correlates with malnutrition, decreased fluid removal and mortality in these patients. Early recognition of the syndrome is important to identify high risk patients. Nutritional support, changes in dialysis and drug therapy may decrease the cardiovascular morbidity and mortality.

Selection of the initial dialysis modality is crucial in the treatment of end-stage renal disease (ESRD) patients. Several patient- and physician-related factors play important roles in the decision between peritoneal dialysis (PD) and hemodialysis (HD). Although HD is the most common dialysis modality in the United States, in some studies PD has shown a survival advantage over HD, at least in the first 2 years of dialysis treatment, especially in non-diabetic patients and in young patients with diabetes. Other advantages accrue to early PD use in many patients. An integrated care approach with "healthy start" and PD as the initial renal replacement therapy, followed by timely transfer to HD once complications arise, may improve the long-term survival of ESRD patients.

Peritoneal dialysis (PD)-associated peritonitis contributes significantly to morbidity and modalityfailure. The number of patients on PD is declining in Western countries, and peritonitis is a potential deterrent to the therapy. Here, we present a clinically significant decline in the rate of peritonitis at a single center over a 28-year period, with current rates significantly lower than the national average, and we review several factors that have contributed to those outcomes. Peritonitis and duration of follow-up have been recorded for all patients followed in our program since 1977. Introduction of important technological changes into the program were also recorded. All peritonitis rates are expressed as episodes/patient-year or episodes/n patient-months. Data are summarized for each calendar year since 1977. We followed 682 patients for a total follow-up duration of 15,435 patient-months. Glass bottles were changed to plastic bags in 1978. Straight connecting tubes were replaced by Y-sets in 1988. The presternal dialysis catheter was introduced in 1991 and has been the primary PD access since 1995. The peritonitis rate in 1977 was 5.8 episodes/patient-year, and that rate has progressively declined over the past 27 years to 0.35 episodes/patient-year in 2004. Technical improvements that contributed to the decline in overall peritonitis rates have been adopted nationwide. The largest improvement occurred with the switch from glass bottles to plastic bags, and to the closed-system Y-set that incorporated the flush-before-fill principle. Advances in catheter technology have also played a key role. Quality improvement in the program and long years of experience in overall care of PD patients are significant factors that cannot be measured quantitatively. Improvements have been made to exit-site care protocols, to exit-site evaluation and diagnosis, and to treatment strategies. Patient education and training in catheter care remain the important factor in a PD program. Many factors have contributed to the reduction of PD-associated peritonitis rates at our center Improved connectology, catheter care, and patient education play key roles in the reduction of peritonitis.

Early nutritional intervention is thought to play a major role in the preservation of renal function and the overall wellbeing in the renal patient. In preparation for renal replacement therapy (RRT), a consultation with the renal nutritionist to establish a diet consistent with the existing diagnosis may increase the likelihood of reducing cardiovascular risk factors, preventing malnutrition and anemia, and slowing the progression of renal disease, all of which can contribute to positive patient outcomes. In a 1999 United States Renal Data System survey of 3,468 new dialysis patients, 46% indicated that they had not consulted with a dietitian before the initiation of dialysis. To help with establishing education programs, determine staffing guidelines, and planning future endeavors, the National Kidney Foundation Council on Renal Nutrition conducted a survey of their 1,748 members. The survey was designed to assess the current demographic profile and clinical practice elements of practicing renal dietitians. Surveys were distributed as a section of the 1999-2000 winter issue of the CRN Quarterly Newsletter, with 353 of the members responding. Information collected pertained to patient care settings, number of facilities covered, patient age, patient treatment modalities, dietitian contact hours required to effectively educate pre-end-stage renal disease patients on a low-protein diet and to ensure optimal nutrition status for the chronic kidney disease patients. The dietitians of this cohort had practiced dietetics for 14.5 +/- 8.6 years and renal nutrition for 9.15 +/- 6.9 years. The survey data showed a discrepancy between what the clinical practices were in 1999 and what the current recommendations are, based on the Kidney Disease Outcomes Quality Initiatives (K/DOQI) Clinical Practice Guidelines.

The purpose of this study was to examine the impact of low levels of residual renal function (RRF) on nutritional status in end-stage renal disease patients starting peritoneal dialysis (PD) at baseline and after a year on dialysis. We conducted a single center retrospective analysis of 116 patients who started long-term PD in a university teaching hospital from 1989 to 1998 and were followed for 1 year. Patients were divided into four equal groups according to their initial renal Kt/V(urea) (L/week) levels at the start of PD and followed for 1 year. There were no interventions. The relationship between dialysis adequacy (renal and total Kt/V(urea)) and nutritional status was studied at baseline and at 1 year. Baseline data for patients who survived were compared with the baseline data of those who died and with their own 1 year data. At baseline, the mean serum albumin (3.31 g/dl, p < 0.0001) and lean body mass (47.20% body weight, p < 0.04) of group 1 were significantly lower than in groups 2, 3, and 4. Levels of normalized protein equivalent of nitrogen appearance (nPNA) were significantly lower in group 1 than in groups 3 and 4 (p < 0.005). Although group 1 patients showed trends toward improvement in nutritional parameters, they never caught up with the other groups. At the end of 1 year, the lower total Kt/V(urea) in group 1, with the lowest RRF, was associated with the lowest mean values for nutritional status and the highest death rate. Comparison of baseline and 1 year data of survivors showed that nutritional status improved or remained stable in groups 3 and 4, who exceeded the minimum recommended adequacy targets as per Dialysis Outcome Quality Initiative criteria (mean 12 month total Kt/V(urea) 2.18 and 2.58, respectively). Comparison of baseline data of survivors and those who died showed that patients who died had lower mean values for serum albumin, nPNA, lean body mass, and body weight across all groups. Low RRF at the start of dialysis is associated with poor nutritional status. Also, patients who start dialysis with low RRF and poor nutritional status do not have significantly improved nutritional status even after 1 year on dialysis.

In the early 1960s, peritoneal dialysis (PD) was introduced as a form of long-term maintenance therapy in patients with end-stage renal disease (ESRD). We have come a long way since. Increasing understanding of peritoneal kinetic behavior, its innovative manipulation to meet patient needs, critical monitoring of clinical outcomes, and parallel development in technology have all contributed to the worldwide success of the therapy over the past four decades. In this article we review the evolution of the various PD modalities in the context of these factors.

That decade, 1975 to 1984, saw many important events in the history of PD, including (1) the beginnings of CAPD; (2) the performance in Canada of CAPD with solutions in bags; (3) the First International Peritoneal Dialysis Symposium, in Mexico, preceding all the symposia and congresses to follow; (4) the approval of solutions in bags and CAPD Medicare reimbursement in the USA; (5) the start of the NIH CAPD Registry, probably setting the groundwork for the USRDS; (6) the First Annual CAPD Conference, beginning 23 years of consecutive conferences; (7) the start of the Peritoneal Dialysis Bulletin, which later became Peritoneal Dialysis International; and (8) the formation of the ISPD. One hopes those caring for patients on chronic PD will remember the ideas and hopes of this period and build on them into the distant future. In my opinion, the new ideas, the clinical and laboratory studies, and the experiences shared during this exciting time not only advanced PD and its results, but also had a positive impact on our understanding of uremia and improved the quality of care and results obtained with all renal replacement therapies.

Background: Because the prevalence of end-stage renal disease (ESRD) has progressively increased in both the United States and Canada, patients with ESRD are likely to constitute progressively larger proportions of nephrology practices., Methods: We mailed a questionnaire to US and Canadian nephrology program directors to determine methods used in dialysis training; 53% of US and 73% of Canadian programs responded., Results: Training programs in the United States enrolled a larger median number of fellows and had a lower median faculty-fellow ratio compared with programs in Canada. However, the availability of faculty in providing training in the care of patients undergoing maintenance hemodialysis (MHD) or chronic peritoneal dialysis (CPD) was similar in both countries. There were wide variations in availability of patients in both the United States and Canada. US training programs offered trainees significantly lower numbers of MHD and CPD patients; 29% of US training programs had less than five CPD patients per fellow. Similarly, there were wide variations in the amount of time trainees spent providing care to MHD and CPD patients; in 14% of US training programs, fellows spent less than 5% of their time receiving training for patients undergoing CPD. Only a small proportion of training programs had faculty resources or ensured training for fellows in the placement of percutaneous tunneled venous hemodialysis catheters or peritoneal dialysis catheters., Conclusions: To conclude, there are wide variations in dialysis training in both the United States and Canada. This survey raises concerns that many US training programs either do not have an appropriate number of CPD patients or do not allocate appropriate time to ensure the preparedness of fellows in providing independent care for patients with ESRD undergoing CPD., (Copyright 2002 by the National Kidney Foundation, Inc.)

Background: In general, there is a good correlation between the specific gravity and osmolality of a urine sample. In certain clinical conditions, such as uncontrolled diabetes mellitus, nephrotic syndrome, after the administration of intravenous radiocontrast material or saline diuresis, dependence upon specific gravity for determining the concentrating ability will result in over- or underestimation., Methods: We studied the relationship between specific gravity and osmolality in vitro with simulated urines of varying composition. Urine samples from patients with different clinical conditions were also analyzed., Results: The in vitro curves for sodium chloride, urea, creatinine, glucose, contrast dye, and albumin were plotted (specific gravity versus osmolality). We found a linear correlation between the specific gravity and osmolality of the 6 substances that were studied and for their combinations. The urine samples obtained from patients with different clinical conditions documented that reliance on specific gravity could over- or underestimate the urine osmolality., Conclusions: We concluded that in those clinical conditions, urine osmolality should always be determined and it should not be estimated based on specific gravity.

High transporters are defined based on the peritoneal equilibration test. Peritoneal transport rate changes over time, inflammation and angiogenesis affecting the total pore area. Factors influencing the neovascularization process are described. High transporters have distinctive clinical and laboratory features. The incidence of high transporters varies among different populations. Unfortunately, high transporters have the worst clinical outcomes. Mechanisms proposed to explain the adverse prognosis--including hypoalbuminemia, chronic fluid overload, malnutrition, and chronic inflammation--are discussed. We suggest dividing baseline high transporters into two groups: "sick" and "healthy" high transporters. The two types of high transporters have different baseline characteristics and different clinical outcomes. Hopefully, further studies will better define the appearance of the two groups of high transporters.

The role of peritoneal dialysis (PD) as a modality in renal replacement therapy has been well established. In this article we review various aspects in the evolution of PD, with special emphasis on adequacy. Until the late 1950s PD was still considered as a last resort in the treatment of terminal uremia. The introduction of a chronic indwelling catheter made chronic PD possible. The concept of continuous ambulatory peritoneal dialysis (CAPD), proposed in 1975, had a major impact on the way PD was performed later. The value of determining the adequacy, using urea clearance normalized to total body water (Kt/V) or creatinine clearance normalized to body surface area, was clearly highlighted by the Canada-USA (CANUSA) study. Introduction of standardized peritoneal equilibration tests has been very helpful in enhancing the efficiency of PD. In 1995 the National Kidney Foundation-Dialysis Outcomes Quality Initiatives (NKF-DOQI) established guidelines to improve patient survival and outcome on dialysis. These guidelines established minimum criteria for PD adequacy. Compliance and malnutrition remain important factors determining the efficacy of PD. The "healthy start" concept emphasizes an early start of dialysis in patients with end-stage renal disease (ESRD). The quest for an ideal PD modality has recently led to renewed interest in the idea of continuous flow peritoneal dialysis (CFPD). PD continues to grow and at the same time faces many challenges. Its role as a renal replacement therapy is likely to evolve further in the years to come.

Background: The decline of residual renal function (RRF) on dialysis has been reported to be slower in peritoneal dialysis (PD) then hemodialysis (HD). However, some clinicians have questioned whether this reported difference might not be caused by selection bias. In particular, if continuous ambulatory PD (CAPD) delivers only marginally adequate therapy as some clinicians speculate, then perhaps those patients on CAPD with low glomerular filtration rate (GFR) are purposefully switched to HD. If true, transferring CAPD patients with low GFR to HD could create a selection bias that very well may account for the differences in GFR between PD and HD. This is particularly problematic if one then censors patients at the time of transfer from PD to HD from analysis (that is, patients are no longer followed in the study once they have switched treatment modalities). When this occurs, the data are said to be informatively censored, a term used by statisticians to describe any kind of systematic bias associated with censored or incomplete data. In particular, informative censoring occurs when patients who die or transfer to another modality very early have an associated lower starting GFR or higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship differs between PD and HD but is ignored in the analysis, then the results of such analysis may be biased., Methods: This article analyzes the decline in GFR among 141 incident dialysis patients (39 HD and 102 PD) undergoing either HD or PD at the University of Missouri-Columbia. The decline in GFR was modeled as a nonlinear function of time, taking into account the possibility that missing values of GFR may be associated with patient dropout (death, transfer to another modality, or transplantation). To safeguard against this possibility, we utilized a conditional nonlinear mixed-effects model. The model was used to fit and compare each patient's GFR data to time adjusting for the patient's treatment modality (HD vs. PD), cause of dropout (death, transfer, transplant, lost to follow-up/study ended), and time to dropout. The model allowed a comparison of the starting GFR and the rate of decline in GFR between PD and HD adjusting for these three factors., Results and Conclusions: The results of our analysis suggest that such informative censoring is independent of treatment modality and that even after correcting for dropout caused by death or transfer to another modality, patients starting on PD have a lower rate of decline in GFR (that is, better preservation of GFR) than patients starting on HD.

Background: We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane., Methods: Seventy-two male Sprague-Dawley rats weighing 85 to 110 g were divided into two groups and seven subgroups. Group I consisted of rats on iron-deficient chow, and group II consisted of rats on normal chow. Both groups contained dialysis control subgroups (N = 12: IA, IID), dialyzed with Dianeal solution, and tissue control subgroups (N = 6: IE, IIN), in which rats were not dialyzed and catheters were not implanted. Study group I contained the following study subgroups (N = 12): (B) rats dialyzed with Dianeal solution containing 2 mg/L of iron dextran and (C) rats dialyzed with Dianeal solution containing 1 mg/L of iron dextran. Group IID was dialyzed with Dianeal solution containing 2 mg/dL of iron dextran. Study duration was 12 weeks with peritoneal equilibration tests (PETs) performed at baseline, 6 weeks, and 12 weeks. Prior to baseline, rats were placed on iron-deficient chow or normal chow for three weeks. Dialysis was performed with three 25 mL volume exchanges per day. Hematocrit (Hct), serum iron (Fe), and total iron binding capacity (TIBC) were determined for each study interval. After the final PET, the animals were sacrificed, and the peritoneal membrane was evaluated by gross inspection and light microscopy., Results: Rats on an iron-deficient diet developed severe iron-deficiency anemia after three weeks of the diet (Hct 27; Fe 21 to 23; TIBC 799 to 806). After 12 weeks, the rats remained anemic in groups A (Hct 34 +/- 0.9; Fe 16 +/- 2; TIBC 998 +/- 27) and IE (Hct 38 +/- 2.7), whereas the rats corrected anemia in group B (Hct 45.8 +/- 1.8; Fe 115 +/- 15; TIBC 546 +/- 77). The results were not significantly different from those of group IID (Hct 47.1 +/- 1.6; Fe 94 +/- 19; TIBC 516 +/- 46). In group C, Hct (44.8 +/- 2.1) and Fe (94 +/- 19) did not differ significantly from group IID, but TIBC (734 +/- 76) remained significantly higher than that in the group IID. Peritoneal iron deposits were not detected. The morphometric analysis of the submesothelial space did not reveal any difference in thickness between dialysis groups. PETs were not significantly different among groups., Conclusions: Intraperitoneal iron dextran supplementation in concentrations of 2 mg/L of dialysis solution is nontoxic to the peritoneum and effective in correcting iron deficiency in rats maintained on an iron-deficient diet. Iron dextran in concentration of 1 mg/L of dialysis solution may be sufficient for correcting a lesser degree of iron deficiency.

End-stage renal disease (ESRD) patients frequently have multiple comorbidities, and cardiovascular disease remains the leading cause of death in these patients. The objectives of the present study were (1) to characterize the number and severity of cardiovascular comorbidities at the start of peritoneal dialysis (PD), and (2) to determine the impact of these comorbidities on mortality. We retrospectively studied all ESRD patients starting peritoneal dialysis at our center between 1990 and 1999. The baseline cardiovascular comorbid factors were categorized as ischemic heart disease, congestive heart failure, arrhythmia, peripheral vascular disease, and cerebrovascular disease. The severity of each factor was scored from 0 to 3. The number of comorbidities and the total cardiovascular comorbidity severity scores were determined for each patient. Cardiovascular deaths included those attributed to sudden death, cardiac disease, cerebrovascular disease, and complications of peripheral vascular disease. Of the 191 patients, 105 were men, and 105 (55%) had diabetes mellitus. The mean age was 60.8 +/- 13.3 years and the mean time on PD was 18.8 +/- 16.3 months. As the number of cardiovascular comorbidities increased, the proportion of patients who died of cardiovascular causes increased eighteen-fold. At each level of cardiovascular comorbidity, diabetic patients starting dialysis were younger, and their survival time was shorter as compared with non diabetic patients. Baseline comorbidity determination is important, as comorbidities are prognostic harbingers of eventual complications.

Objective: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD)., Design: Thirty-three male Sprague-Dawley rats weighing between 275-300 g were divided into five groups: group C (n = 6), control rats implanted with a catheter but not dialyzed; group D (n = 5), diabetic rats implanted with a catheter but not dialyzed; group G (n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H (n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics., Results: The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G (p < 0.001), group C and group H (p = 0.001), and group C and group I (p < 0.05). Significant differences were also found between group G and group D (p < 0.05), and between group G and group I (p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to-plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 +/- 0.01 vs 0.35 +/- 0.01, p < 0.05; D/P urea: 0.87 +/- 0.03 vs 0.97 +/- 0.02, p < 0.05)., Conclusions: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Until 1996, no guidelines existed for the initiation of dialysis in patients with progressive renal failure. The publication of the National Kidney Foundation-Dialysis Outcome Quality Initiative guidelines has generated a debate on the management of advanced renal failure and the role of low-protein diets (LPDs). We performed a review of the literature to identify articles on the initiation of dialysis and LPDs, particularly those since 1996. Delayed referral of patients is widespread in both the United States and Europe, and almost 25% of patients are started on dialysis at a glomerular filtration rate (GFR) of <5 mL/min/1.73 m2. There is a high prevalence of malnutrition at the time of first dialysis, which progressively improves upon initiation of dialysis. There is no evidence regarding the efficacy or safety of LPDs in nondiabetic patients younger than 70 years old [approximately 40% of U.S. incident end-stage renal disease (ESRD) patients] and in diabetics with GFR <25 mL/min/1.73 m2 (>40% of incident U.S. ESRD). In nondiabetics who are younger than 70 years old, adherence to LPD for four to five years can be estimated to result in a delay in dialysis by 6 to 11 months. However, suboptimal energy intake is widespread in advanced renal failure, which declines further upon institution of LPD. Even nutritionally sound patients develop subclinical nutritional decline despite intense counseling. There are no data on the efficacy or safety of LPD in subgroups that constitute approximately 80% of incident ESRD patients. Concerns still exist regarding their nutritional safety in the remainder. Initiation of dialysis results in improved nutritional status and should be considered in a timely fashion.

Background: Residual renal function (RRF) plays an important role in dialysis patients. Studies in patients on maintenance dialysis suggest that RRF is better preserved in patients receiving peritoneal dialysis (PD) vis-à-vis those receiving hemodialysis (HD). We speculated that regardless of the patient's type of therapy, the estimate obtained for the rate of decline in glomerular filtration rate (GFR) may be biased because of informative censoring associated with patient dropout. Informative censoring occurs when patients who die or transfer to another modality very early have associated with them a lower starting GFR or a higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship is ignored in the analysis, then the estimate obtained of the rate of decline in GFR may be biased., Methods: In an attempt to determine if there is a relationship between patient dropout and the decline in GFR, we reanalyzed the CANUSA data by modeling GFR as a nonlinear function of time with the rate of decline being exponential., Results: This article highlights the significance of "informative censoring" when studying the decline of RRF on dialysis. The results show that for the CANUSA cohort, the mean initial GFR was significantly lower, and the rate of decline was significantly higher for patients who died or transferred to HD than for patients who were randomly censored or received a transplant. It is important to emphasize that the impact of informative censoring on previous analyses of the decline of RRF between PD versus HD is presently unclear. If bias caused by informative censoring is the same regardless of what therapy a patient is on, then conclusions from previous studies comparing the decline in GFR between PD and HD would still be valid. However, if the magnitude of the bias differs according to therapy, then additional adjustments would be needed to fairly compare the decline in GFR between PD and HD. Because this analysis is restricted to patients on PD, it would be scientifically incorrect to interpret previous studies solely on the basis of the results from this analysis., Conclusion: In any longitudinal study designed to estimate trends in an outcome measured over time, it is important that the analysis of the data takes into account any effect patient dropout may have on the estimated trend. This analysis demonstrates that among PD patients, both the starting GFR and the rate of decline in GFR are associated with patient dropout. Consequently, future studies aimed at estimating the rate of decline in GFR among PD patients should also account for any dependencies between dropout and GFR. Similarly, data analyzing for apparent differences in the rate of decline of GFR between PD and HD should also adjust for possible informative censoring.

High transporters on chronic peritoneal dialysis are challenged by increased protein losses, high glucose absorption with associated metabolic abnormalities, and poor ultrafiltration. Furthermore, the relative risk of mortality and technique failure is higher in high transporters than in patients of other transport types. An approach for satisfactory management of such patients on peritoneal dialysis (PD) has not been clearly demonstrated.

Tidal peritoneal dialysis (TPD) was introduced in 1990 in the hopes of improving dialysis efficiency. Studies comparing low dialysate flow rates show that tidal peritoneal dialysis has no clearance advantage over intermittent peritoneal dialysis (IPD). With high dialysate flow rates, TPD may be superior or similar to IPD in efficacy, but it is expensive because of the high volumes of dialysis solution used. However, it provides better fluid flow mechanics and more comfort to the patient owing to fewer alarms and less pain during inflow and outflow.

Objective: To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD)., Study Design: Thirty-three male Sprague-Dawley rats weighing between 275 - 300 g were divided into 5 groups: group C (n = 6), control rats with catheter but not dialyzed; group D (n = 5), diabetic rats with catheter but not dialyzed; group G (n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H (n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics., Results: The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I (p < 0.001, p = 0.001, and p< 0.05 respectively). Significant differences were also found between group G and groups D and I (p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40+/-0.01 vs 0.35+/-0.01, p < 0.05); and between groups C and H for D/P urea (0.87+/-0.03 vs 0.97+/-0.02, p < 0.05)., Conclusions: These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.

A vital conceptual difference between intermittent and continuous dialysis therapies is the difference in the relationship between Kt/V urea and dietary protein intake. For a given level of protein intake the intermittent therapies require a higher Kt/V urea due to the reasons mentioned above. The recently released adequacy guidelines by DOQI for intermittent and continuous therapies are based on these assumptions. The link between adequacy targets and patient survival is well documented for an intermittent therapy like HD. For a continuous therapy like CAPD however, the evidence linking improved peritoneal clearance to better survival is not as direct. However, present consensus allows one to extrapolate results based on HD. The concept of earlier and healthier initiation of dialysis is gaining hold and incremental dialysis forms an integral aspect of the whole concept. Tools like urea kinetic modeling give us valuable insight in making mathematical projections about the timing as well as dosing of dialysis. Daily home hemodialysis is still an underutilized modality despite offering best survival figures. Hopefully, with increasing availability of better and simpler machines its use will increase. Still several questions remain unanswered. Despite availability of data in hemodialysis patients suggesting that an increased dialysis prescription leads to a better survival, optimal dialysis dose is yet to be defined. Concerns regarding methodology of such studies and conclusions thereof has been raised. Other issues relating to design of the studies, variation in dialysis delivery, use of uncontrolled historical standards and lack of patient randomization etc also need to be considered when designing such trials. Hopefully an ongoing prospective randomized trial, namely the HEMO study, looking at two precisely defined and carefully maintained dialysis prescriptions will provide some insight into adequacy of dialysis dose and survival. In diabetic patients, the relationship between outcome and dialysis dose needs to be better defined. Data relating adequacy of dialysis to outcome in a pediatric population is not available. In dialysis therapy, the Risk/Dose (R/D) function does not bear a linear relationship. This together with a lack of proof equating peritoneal to renal clearance lends some uncertainty to the validity of the recommendation that there is a linear and constant decrease in RR for std (Kt/V) [equivalent standardized Kt/V calculated from average predialysis BUN for any frequency and/or combination of intermittent and continuous dialysis ref] up to 2.3 as reported in the CANUSA study. Due to the complex nature of this problem it may be prudent to undertake a multi-center trial with std (Kt/V) prospectively randomized to either 2.0 or 2.4. This would provide a reliable database to evaluate the R/D function over this critical range of normalized peritoneal urea clearance. Likewise in PD, the postulated linearity between dialysis dose and outcome needs to be studied in a prospective randomized manner. The amount of dialysis dose required for malnourished patients, diabetic and pediatric patients needs to be better defined. The role of aggressive dialysis in reversing malnutrition needs to be studied and studies need to be done to identify the most scientific use of V in malnourished patients. Justification of a healthy start/incremental dialysis based on outcome measures needs to be established and it's cost effectiveness validated by clinical trials. Again, a prospective randomized controlled trial comparing incremental dialysis with dietary protein restriction in patients with GFR < or = 10.5 ml/min/1.73 m2 with properly defined outcome measures like morbidity, mortality, decline of GFR and quality of life needs to be conducted. Comparisons of incremental hemodialysis and incremental peritoneal dialysis need to be made especially with regard to technique survival and preservation of residual renal function (RRF). (ABSTR

Low protein diets have been used for a long time in the conservative management of chronic renal failure as they have a beneficial effect in preventing the appearance of symptoms. However, with the exception of the beneficial effect on hyperphosphatemia of the very low protein diets supplemented with ketoacids, they have no proven effects on the other aspects of the uremic syndrome. Moreover, the weight of the evidence suggests that the effect of these diets on preservation of GFR, if any, in patients with nondiabetic renal disease is small and of little clinical relevance. There is very little evidence in the literature of its role in patients with diabetes. The nutritional safety of these diets is still suspect. Patients with chronic renal failure have low energy intakes, which is further reduced when these diets are prescribed. Metabolic studies predict that these patients would be in negative nitrogen balance and in fact, even nutritionally sound, nondiabetic patients enrolled in the Modification of Diet in Renal Disease Study developed subclinical signs of malnutrition. It is possible that the nutritional decline may have been more pronounced on longer duration of follow-up. Finally, these diets are difficult to follow, leading to issues of compliance and exert a great toll on the time of the dietitians. Hence, we conclude that low protein diets are not necessary in chronic renal failure.

A severely burned patient receiving neutral phosphate supplement developed renal tubular alkalosis. This phenomenon is compared with the results of experimental observations on animals, reported in the literature. The physiologic mechanism, including the possible role of parathyroid hormone, is illustrated.

The traditional approach of initiating dialysis when the patient begins to manifest uremic symptoms may result in the development of significant malnutrition with detrimental effects on subsequent morbidity and mortality. The recently issued Dialysis Outcome Quality Initiative guidelines suggest that dialysis be initiated when the Kt/V from residual renal function decreases to less than 2.0. We have used the urea kinetic model to show how dialytic dose can be titrated to compensate for declining renal function while maintaining a constant total dose of delivered therapy (Kt/V = 2.0). For hemodialysis (HD), we show that initiating dialysis with once-weekly therapy may be a viable option only for a few months, being replaced by twice-weekly and subsequently with the more typical regimen of thrice-weekly HD. We recommend that the patient be directly initiated with twice-weekly HD to minimize wide swings in the serum concentrations of small-molecular-weight solutes. With continuous ambulatory peritoneal dialysis (CAPD), a hypothetical average-sized patient with high-average transport can be maintained for approximately 8 months with a single 2.5-L nocturnal exchange and from 8 to 17 months with two nocturnal exchanges of 2.5 L each. The use of nocturnal exchanges allows more normal daytime activities and is less intrusive on patient lifestyle. We have shown that both HD and CAPD regimens can be successfully adjusted to achieve a constant total Kt/V of 2.0 for 5 or more years, although CAPD may provide a smoother transition from no dialysis to a complete 10-L regimen.

Calcium channel blocker given intraperitoneally (i.p.) in rats was reported to increase urea D/P ratio without protein loss. Chlorpromazine (CP) given i.p. in humans was reported to increase ultrafiltration (UF) and urea clearance. We studied the effects of i.p. Diltiazem (DZ) (15 mg/kg) and i.p. chlorpromazine (0.25 mg/L dialysate)--given alone or in combination--on urea D/P ratio, dialysate protein (Dpro), glucose concentration (Dg), UF, and drainage volume (Vd). Six male Sprague-Dawley rats were studied. The rats underwent 21 consecutive 30-minute exchanges with 15 mL of 1.5% of Dianeal solution (Baxter Healthcare Inc., Deerfield, Illinois, U.S.A.). DZ or CP was added to the dialysis solution during exchanges 4-6 and 10-12. During exchange 16-18 both DZ and CP were added to the dialysis solution. Exchanges 1-3, 7-9, 13-15, and 19-21 were control exchanges performed with 1.5% Dianeal solution alone. The mean weight of the rats was 541.6 +/- 44 g. The animals' blood pressure remained stable during the study period. An increase in D/Purea ratio was observed with DZ, with CP, and with the two drugs in combination, without increase in dialysate protein loss. An increase in UF with a decrease in D/D0 was observed with DZ, with CP, and with the two drugs in combination, suggesting a mechanism other than osmotic gradient--such as increased blood flow or decreased surface tension.

Patients initiating dialysis therapy must make a choice between hemodialysis (HD) and peritoneal dialysis (PD). Controversy persists over the relative merits of each modality in the treatment of end-stage renal disease (ESRD). Issues relating to survival, morbidity, economics, and patient characteristics will all determine the final choice of therapy. Non medical factors are the most important determinant of dialysis modality selection. In the United States, HD has been the more commonly used modality, while PD is underrepresented. This disparity arises from multiple factors including reactions (sometimes incorrect) to the healthcare financing structure, physician biases, and changing demographic patterns in the ESRD population. We discuss these issues and present collected evidence showing that increased use of PD may have substantial overall benefit.

Background: The presternal peritoneal catheter is composed of two silicone rubber tubes joined by a titanium connector at the time of implantation, and has an exit on the chest., Objective: Comparison of survival and complication rates of Swan neck abdominal catheters with those of the presternal catheter., Design: Nonrandomized study with prospective collection of data between August 1991 and October 1997., Setting: Tertiary referral center., Patients: In 57 patients, 58 presternal catheters and, in 81 patients, 86 abdominal catheters were implanted. Patients chose the type of catheter; however, obese individuals and those with ostomies and previous catheter problems were encouraged to opt for the presternal catheter. Others chose the presternal catheter in order to take tub baths or use a whirlpool., Main Outcome Measures: Life-table analyses of catheter survival censored for transplant, transfer, and death; reasons for catheter removal due to complications; and patient satisfaction., Results: Two-year survival probabilities were 0.95 and 0.75 for presternal and abdominal catheters, respectively. Nine abdominal catheters were removed due to exit/tunnel infections (including five with peritonitis), and four due to peritonitis. External cuff shaving in four presternal catheters has extended survival for more than 1 year. Four presternal catheters were removed due to peritonitis. No catheters in either group were lost due to leakage or obstruction. The peritonitis rate was 1 episode per 37.4 patient-months and 1/20.5 patient-months for presternal and abdominal catheters, respectively. These differences are not significant. Patient acceptance of the presternal catheters was excellent; in the latest period, from January to October 1997, presternal catheters were chosen by 15/24 patients., Conclusions: The trend to improved outcomes in presternal catheters continues to validate the rationale for presternal catheter design. Decreased frequency of exit/tunnel infection may be due to more effective immobilization on the chest, less trauma, and avoidance of submersion in stagnant water. No specific contraindications to use of the presternal catheter have been identified.

We (Perit Dial Int 17:426 and 497, 1997) and the Dialysis Outcomes Quality Initiative guidelines (Am J Kidney Dis 30:S69, 1997) have reported evidence that protein intake often is < 0.8 g/kg standard weight when renal weekly urea clearance (L) normalized to total body water (V, L) is less than 2.0, and that initiation of dialysis should be considered if nutritional status is decreasing. We have prospectively followed renal urea (C(urea)) and creatinine clearances (C(cr)) in 20 patients with chronic renal failure. Nine patients received dietary counseling, but we have previously shown this has minimal effects on protein intakes (Perit Dial Int 17:497, 1997). In 16 patients (group 1), glomerular filtration rate (GFR) estimated as (C(urea) + C(cr))/2 decreased from 14.6 +/- 1.5 (mean +/- SEM) to 9.8 +/- 0.9 (ml/min/1.73 m2 BSA) over a mean interval of 10.3 +/- 1.6 months; in the other 4 patients (group 2), mean GFR did not decrease and was initially 17.6 +/- 3.8 and 21.7 +/- 2.2 after 8.5 +/- 2.3 months. In group 1, Kt/V went from 2.5 +/- 0.3 to 1.7 +/- 0.2; in group 2, Kt/V went from 3.1 +/- 1.0 to 3.7 +/- 0.6. In group 1, protein intake as assessed from the normalized equivalent of protein nitrogen appearance calculated from urea nitrogen and protein losses in urine (nPNA; g/kg standard weight) went from 1.0 +/- 0.1 to 0.8 +/- 0.1. In group 2, mean nPNAs were 1.1 +/- 0.3 and 1.1 +/- 0.1. In all measurements with Kt/V less than 2.0 (n = 18), 10 (56%) were with nPNA less than 0.8. In all measurements of Kt/V > or = 2.0 (n = 22), only 3 (13.6%) were with an nPNA of less than 0.8. These percentage values were different (p < 0.0001) by chi-squared analysis. Changes in nPNA correlated directly (but insignificantly, probably because of a small n) with C(cr), GFR, and Kt/V. These prospective results provide additional evidence that protein intakes decrease to dangerously low levels (without intense dietary monitoring) in most patients when renal weekly Kt/V decreases to below 2.0, which is similar to findings in patients on continuous ambulatory peritoneal dialysis.

The objective of this study was to evaluate the association of peritoneal membrane transport with technique and patient survival. In the Canada-USA prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis (CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo after initiation of dialysis; patients were defined as high (H), high average (HA), low average (LA), and low (L) transporters. The Cox proportional hazards method evaluated the association of technique and patient survival with independent variables (demographic and clinical variables, nutrition, adequacy, and transport status). Among 606 patients evaluated by PET, there were 41 L, 192 LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72, and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P = 0.11). The 2-yr probabilities of both patient and technique survival were 86, 61, 52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA, and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33, and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22 for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P < 0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher peritoneal transport is associated with increased risk of either technique failure or death. The decreased drain volume, increased albumin loss, and decreased serum albumin concentration suggest volume overload and malnutrition as mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in H and HA transporters.