Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

To review the role of Na, K-ATPase inhibitors in the pathogenesis of essential hypertension and hypertension associated with end-stage renal disease.

MEDLINE search, 1966 to 1997.

There is a suggestive physiologic and epidemiologic relationship between Na, K-ATPase inhibition and hypertension. However, clearance data cannot support the hypothesis that differential metabolism of this family of compounds explains the improved hypertensive control seen in patients on peritoneal dialysis compared to those on hemodialysis.

As a result of the complex methodologies involved, it is unclear whether Na, K-ATPase inhibitors playa significant role in the hypertension of endstage renal disease in general and peritoneal dialysis in particular.

To elucidate mechanisms of ultrafiltration failure (UFF) in patients on continuous ambulatory peritoneal dialysis (CAPD).

Retrospective analysis of patients with UFF during CAPD compared with cross-sectionally selected controls.

University peritoneal dialysis center.

Thirteen patients with UFF during CAPD necessitating change to hemodialysis (n = 6) or continuous cycling peritoneal dialysis (n = 1), or causing greatly increased need for high glucose-containing solutes, were compared with 18 CAPD patients without such problems.

Fisher's exact test, Student's independent t-test, univariate and multivariate correlation analyses.

Data were collected prior to analyses.

Systolic blood pressure and total cholesterol and triglyceride levels were higher in the UFF patients than in the controls (p = 0.006, p = 0.028, p = 0.013). Betablockers were used by 12 of the UFF patients, but only 2/ 18 controls (p < 0.0001). There was no intergroup difference in number of women, patient age or weight, incidence of diabetes or previous peritonitis, duration of PD, serum levels of albumin, creatinine, iron, or ferritin, or dosage of erythropoietin. Correlation was found between the daily amount of glucose instilled into the abdomen and serum triglycerides (r = +0.72, p < 0.001), total choles terol (r = +0.56, p = 0.008), and HbA1C(r =-0.41, p =0.039). Many patients were high absorbers of dialysis glucose.

The study indicates that beta-blockers may cause UFF, and that glucose and lipid metabolism differed between these patients and controls without UFF.

To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-α (TNFα) mRNA level, and TNFα secretion by peritoneal macrophages (PMΦ).

Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis -free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate(TB)and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pC02 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-Ioaded PMΦ exposed to different dialysis solutions or Hank's balanced salt solution. TNFα levels were measured by ELISA in the supernatant of lipopolysaccharide (LPS) stimulated PMΦ after their incubation in different solutions for 15 and 30 minutes. TNFα mRNA was measured by reverse transcriptase polymerase chain reaction (RT PCR) of total RNA extracted from LPS-stimulated PMΦ after their incubation in different solutions for 30 minutes. β-actin mRNA was used as the control.

Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFα secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFα secretion. Accordingly, TNFα mRNA level in PMΦ was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFα secretion by PMΦ was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFα mRNA levels could not be detected with TB or TBL even at high dextrose concentrations.

In contrast to Dianeal, both bicarbonate based solutions caused only a mild drop in pHi of PMΦ. We postulate this effect to be responsible for the improved capacity of PMΦ to secrete TNFα when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMΦ. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMΦ function.

To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations.

A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders.

Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed.

In nonselected CAPD patients, treatment with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily be reversed with an immediate adjustment of the treatment. After 3 months, stable plasma Ca and PTH levels could be maintained using only monthly investigations. In patients with hypercalcemia and elevated PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied a considerable risk for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca concentration of 1.25 or 1.35 mmol/L.

Most CAPD patients can be treated effectively and safely with a reduced dialysate Ca concentration of 1.35 or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L should not be used. A small fraction of patients with persistent hypocalcemia need treatment with high dialysate Ca, such as 1.75 mmol/L.

To determine the level of bacterial contamination associated with touch contact of a connector set during peritoneal dialysis (PD).

The experiment utilized a laboratory-based simulation of a bag exchange procedure. Deliberatetouch contamination of the connector set spike was followed by quantitative recovery of micro-organisms from the connector and, in some cases, the dialysis bag.

Patients undergoing PD were used as the “test” group. Departmental secretarial and laboratory staff served as the comparative control group.

The patients were voluntary subjects from a PD outpatients unit and were tested in their own homes.

The numbers of micro-organisms contaminating a connector set and entering the dialysis bag during a touch-contamination event were determined. Additionally we identified hand hygiene and, in particular, the care taken to dry the hands after washing as being highly relevant to microbial touch-contamination levels. Patient hand disinfection, as practised in most PD units, effectively reduced touch contamination to low levels.

Touch contamination of a connector set with unprepared hands led to fewer than 100 micro-organisms translocating from fingers to the spike. If the hands were washed but not dried before touch contact was made, up to 4500 micro-organisms trans located to the connector set spike. Air-towel drying of washed hands before touch contact reduced the translocating numbers by 95% -99%. Hand disinfection, as routinely practiced by PD patients, reduced the bacterial numbers reaching the peritoneal cavity after touch contamination to <5. The range of micro-organisms isolated from the fingers of PD patients using hand disinfectants on a regular basis showed considerably more diversity than the control group.

Hand care prior to bag exchange has a major effect on touch-contamination levels. Accidental touch contact of connecting devices by unprepared hands using a PD-bag exchange procedure leads to the translocation of 500 micro-organisms or fewer to the connector device. If the hands are wet at the time of contact the number translocating can be as high as 4500. Hand drying with an air towel before touch contact reduces the numbers translocating by 95% -99%. Hand disinfection procedures carried out prior to bag exchange minimizes touch-contamination levels.

To analyze pathogenetic associations, clinical features, management, and outcome of ascites following discontinuation of continuous peritoneal dialysis (CPD).

Retrospective analysis of symptomatic ascites, defined as ascites requiring at least one therapeutic paracentesis, developing in patients who discontinued CPD.

Dialysis unit of one tertiary care center.

Twelve patients with 13 episodes of symptomatic ascites diagnosed soon after (a few days to 2 months) discontinuation of CPD.

Diagnostic tests to characterize the pathogenesis of ascites; management of ascites by hemodialysis or CPD.

Evolution of clinical features and nutritional parameters, survival.

Ascites was infectious in 3 episodes (nontuberculous mycobacterial peritonitis) and noninfectious in the remaining 10 episodes. Serum-to-ascites albumin concentration gradient (AG) was 6.3 ± 1.5 g/L in infectious ascites and 17.3 ± 2.7 g/L (>11 g/L in every episode) in noninfectious ascites. Infectious ascites was managed with hemodialysis, prolonged courses of antimicrobial agents, and repeated paracentesis. Paracentesis ceased after 3 9 months. The patients were alive after 52 ± 19 months. Seven episodes of noninfectious ascites were managed by hemodialysis and repeated paracentesis. Five patients died within 6 months from cardiac causes or sepsis. The remaining 2 patients died after 14 and 16 months from cardiac causes. Three episodes of noninfectious ascites in 2 patients were treated by restarting CPD within 2 -5 months. Patients were alive at 16.9 ± 13.2 months. They were asymptomatic and achieved fluid control. On the same CPD schedule, peritoneal clearances of urea and creatinine and normalized protein nitrogen appearance were unchanged between the initial and restarted CPD. Serum albumin was 33.3 ± 2.5 g/L at the end of the first CPD period, 23.6 ± 2.5 g/L soon after restarting CPD, and 31.3 ± 5.5 g/L 4 months after restarting CPD.

Noninfectious ascites after discontinuation of CPD is often characterized by an AG > 11 g/L, suggesting portal hypertension. Restarting CPD in noninfectious ascites may be associated with improvement in ascites symptomatology and nutritional parameters and with satisfactory survival.

We report our experience with maintenance peritoneal dialysis (PD) in small children.

This is a retrospective analysis of the patient records of all children under the age of 5 years treated with continuous peritoneal dialysis (CPD) between 1986 and 1994 in Finland.

Treatment was started and the patients were seen at the outpatient clinic at the Hospital for Children and Adolescents, University of Helsinki, every 3 months. Between these visits, they had controls at their local hospital every 2 -4 weeks.

The most common primary renal disease in these 34 patients was congenital nephrotic syndrome of the Finnish type (27 patients). Others were: congenital nephrotic syndrome (3 patients), polycystic kidney disease (1), urethral valve (1), neuroblastoma (1), and renal dysplasia (1).

Mean age at onset was 1.6 years and median treatment time 9.3 months. Time spent in hospital decreased from 270 days/year in the 1980s to 150 days/year in the 1990s. Two children died (5.9%). The peritonitis rate on continuous cyclic peritoneal dialysis was 1:11.5 patient-months. Hernias were diagnosed in 29% of the patients. After 3 months half of the patients were on antihypertensive medication. Pulmonary edema was diagnosed once in 12 patients and twice in 2 patients. During the first 6 months on PD the mean height standard deviation score (hSDS) increased from -2.13 to -1.66 (p < 0.0001). The 6-month change in hSDS before initiation and 6 months after the start of CPD increased from -0.12 ± 0.68 to +0.59 ± 0.64 (p = 0.0008).

Our results indicate that peritoneal dialysis is feasible and safe in small children. Mortality was low and growth was good. The major challenges presented by CPD therapy were maintenance of optimal nutrition, avoidance of peritonitis, and control of volemia.

Peritonitis is considered an acceptable and controllable risk in patients undergoing chronic peritoneal dialysis (PD). In contrast, peritonitis due to visceralleakage represents a true “abdominal catastrophe” because of striking morbidity and mortality. To delineate the incidence, causes, and outcomes of catastrophic peritonitis, we compared patients who developed peritonitis due to documented visceral leakage with patients who developed peritonitis due to enteric organisms without evidence of visceral leakage.

Retrospective chart review.

PD Unit located in tertiary care referral center.

230 patients treated by PD between January 1988 and June 1996.

All episodes of PD-related peritonitis occurring over an 8-year period. Hospital course of all patients with or without renal failure who were treated at University Hospitals of Cleveland for ischemic bowel disease, cholecystitis, viscus perforation, or diverticulitis.

Anatomically documented visceral injury caused 32.5% of episodes of enteric bacterial peritonitis in 72 patients between January 1988 and June 1996. The overall incidence of this “abdominal catastrophe” was 11.3%, or 26 of a total of 230 patients treated by PD. Of the 26 patients, 50% died, 30.7% survived but switched permanently to hemodialysis, and only 19.2% remained on, or returned to, PD. Compared to renal failure patients treated by hemodialysis or transplantation and to nonrenal failure patients, the incidence of abdominal catastrophe was 20 -60 times greater in patients treated by PD.

Evidence for injury of an abdominal organ should be sought in all patients treated by PD who develop peritonitis with enteric organisms. Surgical intervention is definitive for diagnosis, and if performed early may reduce morbidity and mortality.

To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD).

Endothelin-1 mRNA level in peripheral blood monocytes and plasma ET -1 level were studied in 30 HD patients, 15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20 normal healthy controls. Hemodialysis patients were dialyzed three times per week with a bicarbonate dialysate. Different types of dialyzer membrane, viz., cellulose triacetate, cuprophane, poly-sulfone, polyacrylonitrile, and ethylenevinylalcohol were used in 8,6,6,5, and 5 patients, respectively. Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to 2.5%.

Higher levels of ET -1 mRNA in monocytes were observed in HD patients than in CAPD patients (p < 0.01), chronic renal failure patients (p < 0.01), or normal healthy controls (p < 0.001). The level of ET -1 mRNA in monocytes at the end of HD was not significantly higher than that at the start of HD. ln addition, these mRNA levels in HD patients showed littledifference with different types of dialysis membrane. Plasma ET -1 level in HD patients (10.2 ± 2.4 pg/mL) was also higher than that in CAPD patients (7.8 ± 1.6 pg/mL, p < 0.01), in chronic renal failure patients (4.8 ± 1.2 pg/mL, p < 0.01), or in normal controls (2.6 ± 0.8 pg/mL, p < 0.001).

Dialysis itself did not significantly affect ET -1 mRNA levels in monocytes. Chronic stimulation of peripheral blood monocytes may be associated with higher levels of ET -1 mRNA and plasma ET -1 in HD patients than in CAPD patients.

To evaluate the safety, efficacy, and biocompatibility of icodextrin and glucose-containing dialysis fluid during continuous cycling peritoneal dialysis (CCPD), patients were treated for 2 years with either icodextrin or glucose-containing dialysis fluid for their daytime dwell (14 -15 hours). Prior to entry into the study, all patients used a standard glucose solution (Dianeal 1.36%,2.27%, or 3.86%, Baxter, Utrecht, The Netherlands).

Open, randomized, prospective, two-center study.

University hospital and teaching hospital.

Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18, those with peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a follow-up period of 12 months or longer in December 1996.

Serum icodextrin metabolites: one to five glucose units (G1–G5), a high molecular weight fraction (G > 10), and total carbohydrate level, as well as a biochemical profile were determined every 3 months in combination with all other study variables.

In icodextrin-treated patients, serum disaccharide (maltose) concentrations increased from 0.05 ± 0.01 (mean±SEM) at baseline, to an average concentration in the follow-up visits of 1.14 ± 0.13 mg/mL (p < 0.001). All icodextrin metabolites increased significantly from baseline, as illustrated by the serum total carbohydrate minus glucose levels: from 0.42 ± 0.05 mg/mL to an average concentration in the follow-up visits of 5.04 ± 0.49 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 ± 0.7 mmol/L to an average concentration in the follow-up visits of 135.4 ± 0.8 mmol/L (p < 0.05). However, after 12 months the serum sodium concentration increased nonsignificantly (NS) from base line to 136.6 ± 0.9 mmol/L, after an initial decrease. Serum osmolality increased significantly from baseline in icodextrin users at 9 and 12 months, but did not differ significantly from glucose users in any visit. In icodextrintreated patients, the calculated serum osmolal gap increased significantly from 4.1 ± 1.4 mOsm/kg to an average of 11.8 ± 1.7 mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in millimoles/liter equaled the increase in osmolal gap. Body weight increased in icodextrin users (71.9 ± 2.7 kg to 77.8 ± 3.0 kg; NS). Clinical adverse effects did not accompany these findings. Residual renal function remained stable during follow-up.

The serum icodextrin metabolite levels in the present study increased markedly and were the same as those found previously in continuous ambulatory peritoneal dialysis patients treated with icodextrin, despite thelonger dwell time for CCPDpatients (14 -16 hr versus 8 -12 hr). The initial decrease in serum sodium concentration was followed by an increase to a concentration not different from baseline at 12 months. The pathophysiology of this finding is speculated. Calculated osmolal gap in icodextrin patients increased significantly (p < 0.01) at every follow-up visit, and could be explained by the serum icodextrin metabolite increase. We encountered no clinical side effects of the observed levels of icodextrin metabolites.