Continuous Peritoneal Research Articles

Chronic peritoneal dialysis in the tenth decade of life

In this retrospective study we present our experience with chronic peritoneal dialysis in nine patients with ESRD in their 10th decade of life (> or =90 years) at the Toronto Western Hospital. A family member or a private nurse assisted all patients in dialysis procedure. The co-morbid illnesses, survival, hospitalizations and complications related or unrelated to peritoneal dialysis were reviewed. Four patients started dialysis before and five after their 90th birthday, their mean age was 90.61+/-4.04 years. All patients had three or more co-morbid illnesses at the start of dialysis. Total duration of PD treatment was 210 patient months with a median duration of 25 months (range 4-68 months). Of the nine patients, four died after a mean follow up of 38.5 months on dialysis. Of the remaining five, one was transferred to hemodialysis after remaining for 10 months on peritoneal dialysis and the other four are continuing on PD for a mean duration of 9.25 months. Peritonitis (1/13.4 patient months) and exit site infection (1/100.5 patient months) responded to treatment. Hospitalization rate was one admission per 2.5 patient years. Most often, the cause of hospitalization was unrelated to PD, e.g., cardiovascular events, pneumonia and peripheral vascular disease etc. Patient survival at 1, 3 and 5 years was 88%, 58% and 24% respectively. The technique survival was 69%, 47% and 23% at 1, 3 and 5 years respectively. We conclude that continuous peritoneal dialysis is a safe and suitable treatment even in nonagenarians (> or =90 years) ESRD patients.

Analysis of factors associated with outcome in patients with malignant peritoneal mesothelioma undergoing surgical debulking and intraperitoneal chemotherapy.

Malignant mesothelioma (MM) arising in the peritoneal cavity is a rare neoplasm characterized by peritoneal progression and for which there are limited therapeutic options. We evaluated the peritoneal progression-free and overall survival (PFS and OS, respectively) for patients with peritoneal MM after surgical resection and regional chemotherapy. Forty-nine patients (28 males, 21 females; median age, 47 years; range, 16 to 76 years) with MM underwent laparotomy, tumor resection, continuous hyperthermic peritoneal perfusion with cisplatin (median dose 250 mg/m2), and a single postoperative intraperitoneal dwell of fluorouracil and paclitaxel (n = 35) on protocols approved by the Institutional Review Board. Standard techniques for actuarial analyses of potential prognostic variables (Kaplan-Meier method with two-tailed log-rank test and Cox proportional hazards model) were performed. At a median potential follow-up of 28.3 months, median actuarial PFS is 17 months and actuarial OS is 92 months. Factors associated with improved PFS and OS by the Cox proportional hazards model were a history of previous debulking surgery, absence of deep tissue invasion, minimal residual disease after surgical resection (OS only), and age younger than 60 years (OS only). Surgical resection and regional chemotherapy for MM results in durable PFS and OS. Favorable outcome is associated with age, tumor biology (selection of patients with a history of previous debulking), lack of invasive tumor growth, and minimal residual disease after tumor resection.

High Peritoneal Clearance of Small Molecules Did Not Provide Low Serum β2–Microglobulin Concentrations in Peritoneal Dialysis Patients

Although early reports demonstrated that serum beta(2)-microglobulin (s-beta(2)m) concentrations in patients on peritoneal dialysis (PD) were lower than those in patients on hemodialysis (HD), more recent studies demonstrated lower s-beta(2)m concentrations in HD patients treated mainly with high-flux synthetic membranes. We therefore compared s-beta(2)m concentrations between patients on PD and on HD, and also analyzed the relationship between s-beta(2)m concentrations and other parameters in patients on PD. We investigated 24 patients who had been undergoing PD [11 on continuous ambulatory peritoneal dialysis, 13 on continuous cycling peritoneal dialysis] for 4.3 +/- 2.7 years, and 24 patients who had been undergoing HD with high-flux synthetic membranes for 6.1 +/- 3.2 years. Concentrations of s-beta(2)m in the PD patients were compared to concentrations in the HD patients. In patients on PD, we also analyzed the relationship between s-beta(2)m concentration and other parameters, including residual renal function, total weekly Kt/V urea, total weekly creatinine clearance (CCr), and dialysis schedules. We found no significant difference in s-beta(2)m concentrations between the PD and HD patients (33.6 +/- 10.4 mg/L vs 30.3 +/- 10.5 mg/L respectively). Concentrations of s-beta(2)m in PD patients rose with PD duration and were significantly inversely correlated with residual renal function (r = -0.71, p < 0.0001). Unexpectedly, concentrations of s-beta(2)m in anuric PD patients rose as peritoneal CCr increased. And most of the patients with high s-beta(2)m levels fell into the high or high-average transport categories according to a peritoneal equilibration test. Concentrations of s-beta(2)m in patients on PD did not differ significantly from concentrations in HD patients who were using high-flux synthetic membranes. The contribution of residual renal function to removal of beta(2)m was more important than the contribution of peritoneal clearance. High peritoneal clearance of small molecules did not result in low s-beta(2)m concentrations, especially in anuric patients with accelerated peritoneal permeability.

Continuous peritoneal dialysis-associated peritonitis: a review and current concepts.

The percentage of end-stage renal disease (ESRD) patients in the United States maintained on continuous peritoneal dialysis (CPD) therapy is decreasing. Complications from CPD therapy, including peritonitis, may be the reason for the decline. Improvements in CPD technology and a better understanding of the risk factors that predispose patients to the development of peritonitis have been responsible for a decline in the rate of peritonitis. Yet peritonitis remains a significant cause of patient morbidity and mortality and the overall outcome of peritonitis is not acceptable. Factors that have limited our ability to lessen the impact of peritonitis include a lack of data on dosing antibiotics in patients on continuous cycling peritoneal dialysis (CCPD) therapy, a lack of knowledge concerning the biology of bacterial biofilm, and the development of resistance to the current prophylactic antibiotic protocols. Further studies are needed concerning the optimal management of the peritoneal catheter and whether it is feasible to resume CPD therapy after catheter removal.

Sudden blindness caused by anterior ischemic optic neuropathy in 5 children on continuous peritoneal dialysis

The authors report the occurrence of sudden blindness in 5 children (mean age, 32 months; range, 11 to 60) during continuous peritoneal dialysis regimen. All children presented with loss of light perception, visual fixation and ocular pursuit, and bilateral mydriasis unreactive to bright light. Fundoscopic examination found signs of anterior ischemic optic neuropathy with disc swelling, edema, and hemorrhages. Whereas 1 patient was dehydrated, the 4 other patients appeared well and not dehydrated. Nevertheless, blood pressure was below the normal range in all of them. Therefore, hypovolemia is highly suspected to have been the cause of ischemic optic neuropathy in all cases. Treatment consisted of steroids (4 patients), anticoagulation or antiagregation drugs (3 patients), plasma or macromolecules infusions (2 patients), vasodilatators (2 patients), and transient dialysis interruption (1 patient). One child with hepatic cirrhosis died 4 days later of acute liver insufficiency owing to ischemic hepatic necrosis. The other children had only partial improvement of vision during the following months. Because the prognosis of ischemic optic neuropathy is very poor, diagnosis and treatment of chronic hypovolemia in children on continuous peritoneal dialysis is essential to prevent such a devastating complication.

Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis

Accurate measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are essential for the proper assessment of renal osteodystrophy. The first-generation immunometric PTH assay (1st PTH-IMA) not only detects the intact hormone, but also additional PTH fragments truncated at the amino N-terminally truncated PTH-derived fragments [ntPTH(1-84)]. A second-generation immunometric PTH assay (2nd PTH-IMA) recognizes only PTH(1-84) and possibly PTH fragments that are truncated at the carboxyl-terminus but not PTH(7-84). Whether estimates of the ratio between PTH(1-84) and ntPTH(1-84) fragments are a better predictor of bone turnover remains controversial. Thirty-three patients aged 12.8 +/- 4.4 years treated with continuous cycling peritoneal dialysis (CCPD) for 13 +/- 9 months underwent iliac crest bone biopsy. PTH levels were measured by two newly developed first-generation and second-generation PTH-IMA. The ntPTH(1-84) fragments were calculated by subtracting PTH values determined using the 2nd PTH-IMA from values obtained using 1st PTH-IMA that detects both PTH(1-84) and relatively large ntPTH(1-84). Determinations of PTH levels by both assays were highly correlated (r = 0.89, P < 0.001). The relationships between first-generation and second-generation PTH-IMA and bone formation were similar (r = 0.67, P < 0.0001 and r = 0.64, P < 0.0001, respectively). When patients were grouped according to the presence or absence of secondary hyperparathyroidism, the ratio PTH(1-84) to ntPTH(1-84) did not differ between groups. PTH concentrations determined by either the first- or the second-generation PTH-IMA were found to be better predictors of bone formation than the PTH(1-84) to ntPTH(1-84) fragments ratio.

Bone density measurements in pediatric patients with renal osteodystrophy.

Peripheral quantitative computed tomography (pQCT) can selectively measure the densities of cortical and trabecular bone, but there is limited information about its use in patients with renal osteodystrophy. Thus pQCT (Norland XCT-2000, Stratec, Pforzheim, Germany) was performed at the ultradistal radius in 21 patients aged 16+/-3.6 (SD) years on continuous cycling peritoneal dialysis. Trabecular bone density (TBD) was higher in patients, 206+/-16 mg/cm(3), than in controls, 182.7+/-24.8 mg/cm(3) ( P<0.0001), whereas cortical bone density (CBD) was lower in patients, 946.5+/-147.5 mg/cm(3), than in controls, 1,153+/-25.4 mg/cm(3) ( P<0.001). TBD was inversely correlated with age ( r=-0.59, P=0.05), height ( r=-0.59, P<0.01), and weight ( r=-0.51, P<0.05). In contrast, CBD was positively correlated with age ( r=0.53, P<0.05), height ( r=0.56, P<0.05), and weight ( r=0.53, P<0.05). CBD was inversely related to serum alkaline phosphatase ( r=-0.71, P<0.001) and parathyroid hormone levels ( r=-0.50, P<0.05). In patients with adynamic bone, TBD was less, 192+/-9 mg/cm(3), than in those with high-turnover lesions, 215+/-13 mg/cm(3), P<0.001. CBD, however, was lower in patients with high-turnover lesions, 900+/-151 mg/cm(3), than in those with low turnover, 1,022+/-111 mg/cm(3), P<0.05. Compared with controls, in patients with high-turnover lesions, CBD was lower ( P<0.0001) and TBD higher ( P<0.0001). These findings suggest that pQCT may be an additional tool in the assessment of renal osteodystrophy.

Recovery of Renal Function and the Discontinuation of Dialysis in Patients Treated with Continuous Peritoneal Dialysis

Previous studies have shown that patients with end-stage renal disease (ESRD) treated with continuous peritoneal dialysis (CPD) have better preservation of endogenous renal function than patients treated with hemodialysis (HD). We wondered if this better preservation of endogenous renal function seen with CPD patients translates into the improved likelihood of recovery of endogenous renal function in those patients with potentially reversible causes of renal failure. To evaluate this question, we reviewed the records of all 1200 patients that completed CPD training at a large, freestanding peritoneal dialysis center in New Haven, Connecticut, between 1979 and 1999, and the records of all patients completing CPD training in New England between 1993 and 1998. In New Haven, about half the new patients with ESRD were started on CPD compared to only 15% in New England. We then compared the chances of recovery of renal function in these two cohorts of CPD patients to the chances of recovery of renal function in two groups of HD patients. The first group consisted of all patients that started on HD in New England between 1993 and 1998. The second group consisted of all patients that started HD in our HD unit in New Haven, Connecticut, between 1993 and 1999. The data on the New England patients were provided by the ESRD Network of New England. All patients entered into the present study had to have been on dialysis for a minimum of 3 months, as in the United States Renal Data System database, and had to have recovered sufficient renal function to be able to be maintained off dialysis for a minimum of 30 days. 29 of 1,200 CPD patients (2.4%) trained in New Haven recovered sufficient renal function to permit the discontinuation of dialysis for a minimum of 30 days. In comparison, only 305 of 19,032 patients (1.6%) managed with HD in New England (p < 0.05 compared to New Haven CPD patients) and 3 of 430 patients (0.7%) in our HD center (p < 0.05 compared to New Haven CPD patients) recovered sufficient glomerular filtration rate (GFR) to allow the discontinuation of dialysis for at least 30 days. If only those CPD patients that initiated dialysis between 1993 and 1999 in New Haven were analyzed, 15 of 369 (4.1%) recovered sufficient GFR to allow discontinuation of dialysis for at least 30 days (p < 0.025 compared to both groups of HD patients). Of the 2,924 patients completing CPD training in New England, 60 (2.1%) recovered renal function; this percentage is not significantly different from the percent of HD patients in New England recovering renal function. Although the present study is a retrospective study and the actual criteria for selection of CPD and HD therapy are not controlled for, the data raise the question of whether there may be a therapeutic advantage to treating newly diagnosed ESRD patients, that have a potentially reversible cause of renal failure, with CPD.

Pharmacokinetic study of docetaxel in intraoperative hyperthermic i.p. chemotherapy for ovarian cancer

The purpose of this study was to evaluate the pharmacokinetics and toxicity of docetaxel in continuous hyperthermic perfusion peritoneal chemotherapy (CHPPC) after cytoreductive surgery for peritoneal involvement of gynecological malignancies, mainly ovarian cancer. Eighteen patients, with a mean age of 64 years (range 51-80), underwent cytoreductive surgery and subsequent CHPPC with 75 mg/m2 docetaxel at 41-43 degrees C. One patient was treated twice. In eight cases, peritoneal fluid and blood samples were obtained for pharmacokinetic analysis. Death occurred in two heavily pretreated elderly patients with a high volume i.p. tumor recurrence, probably reflecting poor patient selection (mortality rate 10.5%). Other complications, mainly minor, were recorded after 63% of the procedures. Hematological docetaxel-induced toxicity was limited, while the incidence of wound complications was relatively high and probably caused by the direct exposure of the wound to docetaxel during CHPPC. The maximal i.p. versus plasma concentration ratio ranged from 17 to 95 (average 45), while the i.p. versus systemic exposure ratio varied between 105 and 555 (average 207). We conclude that the use of docetaxel in CHPPC following cytoreductive surgery seems feasible and results in a high i.p. versus systemic exposure ratio. The AUC for the peritoneal cavity is on average 13-27 times higher after i.p. administration of 75 mg/m2 during CHPPC than the AUC achieved in the systemic compartment after i.v. administration of the recommended dose of 100 mg/m2, while docetaxel-induced systemic toxicity is highly limited.

Fecal incontinence secondary to CAPD

A 74-year-old patient who has developed fecal incontinence following continuous ambulatory peritoneal dialysis (CAPD) is presented. Incontinence was caused by elevated intra-abdominal pressure during peritoneal dialysis, which correlated with the volume of dialysate and position of the patient. The lowest pressure was found in the recumbent position. A change of dialysis schedule to continuous cycler peritoneal dialysis (CCPD) with “dry day” resulted in a disappearance of the symptoms. Am J Kidney Dis 41:E2. © 2003 by the National Kidney Foundation, Inc.

Automated Peritoneal Dialysis Symposium: Host Defenses in APD

The incidence of peritonitis in peritoneal dialysis (PD) has further decreased after the introduction of automated peritoneal dialysis (APD) into clinical routine. Technical advances such as a reduction in the number of connections, more motivated patients, and improved host defense mechanisms in APD have been described. We found that the long daytime interval without dialysate exchanges leads to a higher absolute number of peritoneal macrophages which are capable of an improved first‐line host defense. This is demonstrated by a higher release of cytokines of peritoneal macrophages after stimulation with lipopolysaccharides. The dry “day” in nightly intermittent PD seems to have no relevant additional positive effects on peritoneal host defense compared to continuous cyclic peritoneal dialysis. The regeneration of peritoneal cell populations induced by intervals without PD remains relevant even in times when more “biocompatible” PD solutions become available.

Peritoneal dialysis in the developing world: the Mexican scenario.

In the developing countries it is not possible to determine the total amount of money spent in the treatment of chronic diseases, and the practice of renal replacement therapies faces many obstacles. In Mexico, the introduction of continuous ambulatory peritoneal dialysis and continuous cycling peritoneal dialysis (CCPD) achieved very good results. Unfortunately, renal disease still affected as much as 95% of chronic renal failure patients and it became a disaster with an annual mortality rate higher than 60%. This was known as the Mexican Model which failed in establishing peritoneal dialysis as the only procedure for treating patients. In order to avoid a similar scenario with the 2 replacement therapies, we created the Official Norm for hemodialysis, and now we are experimenting with an increase from 5% to 20% of hemodialysis patients who are receiving therapy, principally in private units that attend Social Security patients. In addition, the government has established a Council for Transplantation that acts as a regulatory board. In other words, we are in the process of making chronic renal diseases a priority within the National Program.

Nutrition Indices in Obese Continuous Peritoneal Dialysis Patients with Inadequate and Adequate Urea Clearance

To test whether better nutrition is associated more with adequate urea clearance than with inadequate urea clearance in obese patients on continuous peritoneal dialysis (CPD). Retrospective analysis of clearance and nutrition indices in obese CPD patients. Only obese patients were analyzed. Obesity was defined as a ratio of actual weight to desired weight (W/DW) > or = 1.2. The dose of dialysis was considered adequate at weekly Kt/V urea > or = 2.0. Small solute clearances and nutrition indices were compared between patients with weekly Kt/V urea < 2.0 and patients with weekly Kt/V urea > or = 2.0 at the first clearance study. Four university-affiliated and two private dialysis units in Canada and the United States. A total of 270 CPD patients with W/DW > or = 1.2 at the first clearance study. Among the 270 obese CPD patients, 157 (58.1%) were underdialyzed (weekly Kt/V urea 1.66 +/- 0.22) and 113 (41.9%) had adequate dialysis (weekly Kt/V urea 2.51 +/- 0.47) at the first clearance study. Creatinine clearance values also differed between the underdialyzed and adequately dialyzed obese groups (55.6 +/- 15.2 vs 87.6 +/- 29.8 L/1.73 m2 weekly, respectively, p < 0.001). The underdialyzed group contained fewer women (39.5% vs 60.2%, p < 0.001) and more patients with anuria (35.0% vs 8.8%, p < 0.001), and had higher serum urea (20.7 +/- 6.9 vs 18.2 +/- 5.3 mmol/L, p = 0.001) and serum creatinine (974 +/- 283 vs 734 +/- 275 micromol/L, p < 0.001), marginally lower serum albumin (35.8 +/- 5.2 vs 37.2 +/- 6.4 g/L, p = 0.082), lower urea nitrogen excretion (5778 +/- 2290 vs 7085 +/- 2238 mg/24 hr, p < 0.001) and indices derived from urea nitrogen excretion (protein nitrogen appearance and normalized protein nitrogen appearance), and lower creatinine excretion (1034 +/- 349 vs 1217 +/- 432 mg/24 hr, p < 0.001) and indices derived from creatinine excretion (lean body mass normalized to actual or desired weight) than the adequately dialyzed group. Nutrition indices derived from urea nitrogen and creatinine excretion are worse in underdialyzed than in adequately dialyzed obese CPD patients. This finding may have clinical importance, despite the mathematical coupling between small solute clearances and excretion rates in cross-sectional studies, because of evidence from other studies that small solute excretion rate in cross-sectional studies is a robust Independent predictor of outcome in CPD.

Hyperhomocysteinemia in children on renal replacement therapy.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hcy) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hcy levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hcy, red blood cell (RBC) folate, and serum vitamin B(12) levels were measured. The plasma Hcy levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hcy level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation ( r=-0.49) between plasma Hcy levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 micro g/ml) and normalization of the plasma Hcy levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hcy level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hcy level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hcy concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hcy concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hcy levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hcy levels and should be added to the medical treatment of all children with impaired renal function.

Nephrectomy and peritoneal dialysis eliminates circulating renin and controls uraemia in the rat.

The aim of the present study was to develop a rat model for in vivo studies of the local effects of the renin-angiotensin system (RAS) following elimination of circulating renin. Sprague Dawley rats were bilaterally nephrectomised and had a peritoneal dialysis catheter implanted. The rats were maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose dialysis solution. The peritoneal catheter and an automated system for dialysate exchange were made in our laboratory. A sham nephrectomised control group of rats was also dialysed. Nephrectomised and sham-operated rats remained active and in good general condition during peritoneal dialysis. At 48 hours, in nephrectomised, dialysed rats, peritoneal urea clearance was 4.14+/-0.52 ml/hour, plasma urea was 40.0+/-7.7 mmol/L, plasma creatinine was 0.423+/- 0.070 mmol/L and plasma renin was below the limit of detection. In conclusion, it was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal dialysis for 48 hours, pending elimination of renin from the circulation. The nephrectomised dialysed rat model should be useful for investigation of the physiological effects of the circulating versus the local RAS.

Lack of efficacy of prophylactic continuous hyperthermic peritoneal perfusion on subsequent peritoneal recurrence and survival in patients with advanced gastric cancer

Background. Peritoneal recurrence is a major cause of death in advanced gastric cancer. Although many kinds of chemotherapy intended to prevent peritoneal recurrence of gastric cancer have been evaluated, few have been successful. Few studies have assessed the clinical significance of continuous hyperthermic peritoneal perfusion in peritoneal recurrence. Methods. From 1992 to 1999, a total of 124 patients with advanced gastric cancer with tumors invading deeper than the serosa but with no peritoneal metastasis underwent potentially curative gastrectomy and were enrolled in this study. Prophylactic continuous hyperthermic peritoneal perfusion (P-CHPP) was performed in 45 patients younger than 65 years old and without comorbidity who gave informed consent. Seventy-nine patients who did not meet the inclusion criteria represented the control group. After reconstruction of the alimentary tract, P-CHPP was carried out for 40 minutes with 150 mg cisplatin, 15 mg mitomycin C, and 150 mg etoposide in 5 to 6 L physiologic saline maintained at 42°C to 43°C. The surgical results, recurrent pattern, and postoperative morbidity were assessed by univariate and multivariate analysis. Results. When compared with patients not undergoing P-CHPP, patients treated by P-CHPP had higher incidences of respiratory failure (73% vs 19%; P <.0001) and renal failure (7% vs 0%; P <.03). Neither 5-year survival (49% vs 56%) nor the patterns of recurrence (peritoneal, hematogenous, and lymphatic) were affected by P-CHPP. Conclusions. P-CHPP by our methods had no efficacy as prophylactic treatment for peritoneal recurrence induced by gastric cancer. New therapeutic strategies, such as chemosensitivity assessment, are necessary to obtain good therapeutic results with CHPP. (Surgery 2002;131:521-8.)

A Population-Specific Formula Predicting Creatinine Excretion in Continuous Peritoneal Dialysis

The Cockroft-Gault formula was shown to systematically overestimate the decline in creatinine excretion with age in continuous peritoneal dialysis (CPD) patients and is, therefore, not suitable for studying creatinine excretion. The purpose of the present study was to develop and test a population-specific formula predicting average creatinine excretion in CPD. Creatinine excretion in urine plus dialysate was measured in 925 CPD patients. Forty patients were excluded because of evidence of noncompliance. The remaining 885 subjects were randomly grouped into a derivation group (n = 432) and a validation group (n = 453). Stepwise multiple linear regression models were used to predict creatinine excretion in the derivation group. The candidate variables, chosen because they were previously shown to be predictors of creatinine excretion in CPD, included weight (W), age (A), gender (G), diabetes (D), and interaction terms between these four variables. Estimates of creatinine excretion from the best-fit regression formula (CrExcr1) and from the Cockroft-Gault formula (CrExcr2) were compared to creatinine excretion (CrExcr) in the validation group. The best-fit regression model in the derivation group included all four candidate variables (W, A, G, D), but no interaction terms. This model was as follows: CrExcr1 = 302.150 - 4.380A + 171.234G - 39.041D + 11.730W (r2 = 0.477, p < 0.001). In the validation set, CrExcr = -15.795 + 0.988CrExcr1 (r2 = 0.447, p < 0.001), and CrExcr = -303.823 + 0.732CrExcr2 (r2 = 0.340, p < 0.001). When the differences between measured and predicted creatinine excretion did not take into account the sign of each individual difference, CrExcr - CrExcr1 = 201 +/- 156 mg/24 hours, and CrExcr - CrExcr2 = 235 +/- 174 mg/24 hr (p < 0.001) in the validation group. When the sign of the difference was taken into account, CrExcr - CrExcr1 = -28 +/- 149 mg/24 hr, and CrExcr - CrExcr2 = 63 +/- 295 mg/24 hr (p < 0.001). A population-specific formula predicting creatinine excretion in CPD was derived. This formula has greater accuracy than the Cockroft-Gault formula and can be used in studies of creatinine excretion in CPD.

Chronic Fatigue in Long-Term Peritoneal Dialysis Patients

Objective: Fatigue is a common symptom in long-term dialysis patients. This study investigated possible clinical factors which may cause the development of fatigue in patients receiving peritoneal dialysis (PD). We also investigated the relationship between total solute clearance (TSC) and fatigue symptoms in PD patients. Design: A cross-sectional study design was used to compare the clinical characteristics among groups of PD patients classified by different degrees of fatigue. The relationship among dialysis adequacy (including Kt/V_urea and weekly creatinine clearance; C_cr), clinical characteristics and fatigue symptoms were also assessed. Setting: The PD unit of a major university teaching hospital in Taipei, Taiwan. Patients: Consecutive patients who had received PD for a minimum duration of 4 months were recruited for participation in the study. Patients were excluded if they had a history of ischemic heart disease, severe heart failure (NYHA function III or IV), malignant neoplasm, active infection, major psychiatric problems, chronic obstructive pulmonary disease, or disturbed consciousness. Finally, a total of 64 patients, 31 of whom were receiving continuous ambulatory peritoneal dialysis and 33 who were receiving continuous cycling-assisted peritoneal dialysis, were enrolled in the study. Methods: Fatigue was evaluated using a specially designed questionnaire that includes fourteen items. Patients were divided into three groups according to their fatigue scores (FS): mild (FS, 0–3), moderate (FS, 4–8), and severe (FS, 9–14) fatigue. The demographic data, dialysis variables, and clinical parameters of patients were compared among these groups. The relationship between fatigue and TSC was also examined. Results: The FS were correlated with serum intact parathyroid hormone (iPTH) level and total cholesterol concentration (p < 0.05). A linear correlation was also noted between serum iPTH level and total cholesterol level. When the patients were divided into an adequate- and an inadequate-dialysis group according to values of TSC, Kt/V_urea as well as weekly creatinine clearance, a significant correlation was found between weekly C_cr and FS. Conclusion: This study has demonstrated that dialysis adequacy plays a key role in the development chronic fatigue. In addition, weekly C_cr was better correlated with fatigue than Kt/V_urea.

Daily hemodialysis efficiency: an analysis of solute kinetics.

Increasing the frequency of hemodialysis increases its efficiency, which causes the popular dialysis yardstick, single-pool Kt/V, to underestimate the dose just as it overestimates the dose of less frequent dialysis. The frequency dependence of hemodialysis can be explained by examining solute kinetics. Several factors, including the logarithmic fall in solute concentration and solute disequilibrium within the patient, account for the improved efficiency of both daily hemodialysis and continuous peritoneal dialysis, but to fully explain the marked difference in clinical targets for dosing peritoneal versus hemodialysis, one must go outside the realm of urea kinetics. Solutes that dialyze easily, such as urea, but diffuse less readily within the patient, require a 2-compartment model to accurately predict their concentration profiles and to measure efficiency. When applied to appropriately selected solutes, the model can account for the difference in clinical targets and can explain the failure of other indices, such as middle molecule clearance, eKt/V, and EKR, to account for the differences. A cumulative toxic effect of these relatively secluded compounds might offer a better explanation of uremic toxicity and an objective rationale for increasing dialysis frequency and time. Simplified methods for measuring the dose of dialysis fail when the patient is treated more often than 3 times per week, but 2 new and independently derived methods that include parameters to account for the improved efficiency have been developed for measuring frequent dialysis. The new expressions of dose as a weekly analog of urea clearance are similar in magnitude and independent of frequency, giving present-day clinicians a choice of methods to compare 2 to 7 treatments per week. The kinetic behavior of solutes removed by dialysis and the new expressions of dose support the subjective improvement reported by patients, many of whom have embraced a transition to more frequent and prolonged hemodialysis.

Creatinine excretion in continuous peritoneal dialysis: A systematic error of the Cockroft-Gault formula

We investigated the hypothesis that the rate of loss of creatinine excretion with age in peritoneal dialysis (PD) patients differs from the rate predicted from the Cockroft-Gault formula (CrPred) by analyzing creatinine excretion data obtained from clearance studies of 925 patients on continuous ambulatory PD therapy with an age range of 12 to 91 years. Measured creatinine generation (CrMeas) is the sum of creatinine excretion in urine plus dialysate (CrExcr) plus an estimated metabolic degradation of creatinine. The effect of age on CrExcr and the differences CrExcr − CrPred and CrMeas − CrPred were analyzed by linear regression. In 373 women, CrExcr = W(16.9360 − 0.084A), r = −0.342, P < 0.001 (where W is weight in kilograms and A is age in years). The regression slope was one half of the slope in the Cockroft-Gault formula. CrExcr − CrPred = −413.91 + 4.78A, r = 0.300, P < 0.001. CrMeas − CrPred = −176.36 + 4.37A, r = 0.278, P < 0.001. In 552 men, CrExcr = W(21.079 − 0.108A), r = −0.338, P < 0.001. The regression slope was approximately one half of the slope in the Cockroft-Gault formula. CrExcr − CrPred = −493.25 + 6.28A, r = 0.267, P < 0.001. CrMeas − CrPred = −66.41 + 3.63A, r = 0.143, P = 0.001. The rate of loss of creatinine excretion with age is one half of the rate predicted by the Cockroft-Gault formula in both women and men on PD therapy. Therefore, the difference between excretion (or measured generation) of creatinine and creatinine generation predicted by the Cockroft-Gault formula is not constant, but increases with age. The Cockroft-Gault formula systematically overestimates the effect of age on creatinine excretion in PD patients and is not suitable for predicting creatinine excretion in these subjects. © 2001 by the National Kidney Foundation, Inc.