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

To investigate if intraperitoneal and systemic interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) are related to each other and to peritoneal solute transport rate (PSTR).

Longitudinal study in retrospectively selected patients.

Peritoneal dialysis (PD) unit of a university-based hospital.

31 PD patients on treatment with conventional glucose-based solutions participated in a longitudinal study. IL-6 and sIL-6R were measured in plasma and overnight effluent, both at baseline and after 12 ± 2 months on PD. C-reactive protein (CRP) and serum albumin were used as surrogate markers of inflammation. PSTR of small solutes was evaluated using the dialysate-to-plasma ratio (D/P) of creatinine after a 4-hour dwell; PSTR of large solutes was evaluated using the 24-hour D/P ratio of albumin.

D/P creat increased over time (0.67 ± 0.15 vs 0.80 ± 0.11, p < 0.0001) and correlated to D/P albumin only at the baseline evaluation. Patients with plasma IL-6 ≥median had higher (p < 0.005) D/P creat at baseline [0.74 (0.62 – 0.87)] compared to patients with IL-6 < median [0.57 (0.47 – 0.66)]. Dialysate IL-6 at baseline was also higher (p < 0.05) in patients with plasma IL-6 ≥median [24.7 (16.5 – 38.5) pg/mL] compared to patients with IL-6 < median [14.1 (10 – 25.7) pg/mL]. Neither CRP nor albumin changed over time on PD, although they were closely linked to plasma IL-6 levels. A strong positive correlation was found between D/P creat and dialysate IL-6 (rho = 0.77, p < 0.0001) at baseline, but not at 1 year. In contrast, there was a significant correlation between D/P creat and dialysate sIL-6R (rho = 0.39, p < 0.05) at 1 year, but not at baseline. At 1 year, 17 patients with increasing PSTR had higher increases in dialysate IL-6 (28 ± 26 vs –21 ± 78 pg/mL, p < 0.05) and levels of dialysate sIL-6R (693 ± 392 vs 394 ± 274 pg/mL, p = 0.05) compared to patients with stable PSTR (n = 11). Patients who had peritonitis presented higher baseline serum IL-6 concentration (6.8 ± 1.0 pg/mL) compared with patients without peritonitis (4.0 ± 0.6 pg/mL, p < 0.05). Finally, both at baseline and after 1 year, there were significant correlations between plasma and dialysate IL-6 (rho = 0.46, p < 0.05, and rho = 0.40, p < 0.05) respectively.

These findings indicate that, (1) intraperitoneal and systemic inflammation increase in PD patients during the first year of therapy; (2) intraperitoneal and systemic inflammation may be interrelated and the IL-6 system may be the link; (3) the IL-6 system (both intraperitoneal and systemic) is associated with PSTR, particularly in the early phase of PD treatment, in which small and large solute transport are linked. Signs of a transition between acute and chronic inflammation were observed in the follow-up evaluation. Inflammation may, at least in part, be responsible for the development of a high PSTR, and this could be one reason for the high mortality in patients with high PSTR.

The correction of anemia by recombinant human erythropoietin (rHuEPO) improves quality of life and prolongs life in end-stage renal failure. rHuEPO requirements for an individual are determined by a range of factors, including iron deficiency and inflammation. Single nucleotide polymorphisms in the promoter sequence of several proinflammatory cytokines have been shown, in different fields of medicine, to influence the cytokine response to different stimuli, with effects on clinical outcome.

The angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and polymorphisms in the promoter regions of the genes for tumor necrosis factor alpha (-308 A/G), interleukin-6 (-174 G/C), and interferon gamma were examined for their association with rHuEPO requirements in 112 patients on continuous ambulatory peritoneal dialysis (CAPD). Genomic DNA was extracted from peripheral blood leukocytes and genotyping performed with ARMS-PCR methodology, with sequence-specific primers. We examined rHuEPO requirements and C-reactive protein at baseline and during a 6-month study period.

We found no significant effect of proinflammatory cytokine polymorphisms on rHuEPO responsiveness. However, throughout the study, we observed that there was a significantly higher rHuEPO requirement in the II and ID ACE genotypes compared with the DD group, which remained an independent association following multivariate analysis.

ACE insertion/deletion polymorphism may determine rHuEPO responsiveness in CAPD patients and should be considered in relative rHuEPO resistance.

Insertion of percutaneous endoscopic gastrostomies (PEG) in patients on chronic peritoneal dialysis (PD) has been reported to be contraindicated due to an increased risk of morbidity and mortality. However, no systematic survey on this topic has yet been published.

Retrospective multicenter study.

23 pediatric dialysis units associated with the working group Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN).

A structured questionnaire on clinical details of PD patients who had undergone PEG insertion or open gastrostomy (OG) since 1994 was distributed to all pediatric dialysis units of the APN.

27 PD patients (20 males) from 12 centers in whom PEG insertion was performed after Tenckhoff catheter introduction were evaluated. Age at intervention ranged from 0.25 to 10.9 years (median 1.3 years). Most patients were malnourished, with standard deviation score (SDS) for body weight between –4.2 and –0.6 (median -2.2). Major complications were early peritonitis <7 days after PEG in 10/27 (37%) patients, episodes of fungal peritonitis in 7/27 (26%) patients, 4 cessations of PD and change to hemodialysis, and 2 associated deaths. However, in 14 patients, no such problems were encountered and, in 4 patients, early peritonitis effectively treated with intraperitoneal antibiotics was the only major complication. Thus, in 18/27 (67%) patients, PD was successfully reinitiated shortly after PEG insertion. Among all participating centers, only two OG procedures were reported during the study period, illustrating a clear preference for the PEG over the OG procedure among members of the APN.

PEG insertion following PD initiation carries a high risk for fungal peritonitis and potential PD failure; however, complication rates in this largest reported series were lower than previously described. Antibiotic and anti-fungal prophylaxis, withholding PD for 2 – 3 days, and gastrostomy placement by an experienced endoscopy team are suggested precautions for lowering the risk of associated complications. When gastrostomy placement does not occur prior to or at the time of initiating PD, the risks and benefits of percutaneous versus open placement must be carefully weighed.

The frequency of low-turnover bone disease (LTBD) in patients with chronic kidney disease (CKD) has increased in past years. This change is important because LTBD is associated with bone pain, growth delay, and higher risk for bone fractures and extraosseous calcifications. LTBD is a histological diagnosis. However, serum markers such as parathyroid hormone (PTH) and calcium levels offer a noninvasive alternative for diagnosing these patients.

To describe the prevalence of LTBD in pediatric patients with renal failure undergoing some form of renal replacement therapy, using serum calcium and intact PTH levels as serum markers.

In this cross-sectional study, 41 children with CKD undergoing dialysis treatment (31 on continuous ambulatory peritoneal dialysis and 10 on hemodialysis) were included. There were no inclusion restrictions with respect to gender, cause of CKD, or dialysis modality. The children were studied as outpatients. The demographic data, CKD course, time on dialysis, phosphate-binding agents, and calcitriol prescription were registered, as well as weight, height, Z-score for height, linear growth rate, and Z-score for body mass index. Serum calcium, phosphorus, aluminum, PTH, alkaline phosphatase, osteocalcin, glucose, creatinine, urea, cholesterol, and triglycerides were measured.

There were 20 (48.8%) children with both PTH <150 pg/mL and corrected total calcium >10 mg/dL who were classified as having LTBD[(+)]; the remaining 21 (51.2%) children were classified as having no LTBD[(–)]. The LTBD(+) patients were younger (11.2 ± 2.7 vs 13.2 ± 2.4 years, p < 0.01) but they had no differences regarding Z-scores for height. Linear growth in 6 months was less than expected in both groups (-0.15 ± 0.23 cm/month), but the difference between expected and observed growth was higher in the LTBD(+) group (-0.24 ± 0.14 vs –0.07 ± 0.28 cm/mo, p < 0.03). LTBD(+) patients also had lower serum creatinine (8.69± 2.75 vs 11.19 ± 3.17 mg/dL, p < 0.01), higher serum aluminum levels [median (range) 38.4 (9 – 106) vs 28.1 (9 – 62) μg/L, p < 0.05], and lower systolic blood pressure (112.0 ± 10.3 vs 125.0 ±12.9 mmHg, p < 0.015) and diastolic blood pressure (76.0 ± 9.7 vs 84.5 ± 8.2 mmHg, p < 0.017). A significant correlation was found between PTH and alkaline phosphatase (r = 0.68, p < 0.001), but not between PTH and aluminum.

The LTBD(+) biochemical profile was found in 48.8% of the children and was associated with impaired linear growth. Aluminum contamination, evidenced by higher serum aluminum levels, may have had a pathogenic role in these disorders. Higher systolic and diastolic blood pressure levels may be related to higher serum PTH levels.

This study was undertaken to investigate the effect of long-term blood pressure (BP) reduction, achieved with salt restriction and strict volume control, on frequency and regression of left ventricular hypertrophy (LVH) in long-term peritoneal dialysis (PD) patients.

56 patients who had been treated for more than 2 years under our care were enrolled. After echocardiographic (Echo) evaluation, 46 patients were included in the follow-up study. In our unit, we aim to keep patients’ BP below 130/85 mmHg and cardiothoracic index below 0.50. To reach these targets, moderate salt restriction is advised, and if necessary, hypertonic PD solutions are used. Echo was performed at the beginning of the study (after a mean period of 36 months on PD) and at the end of the prospective follow-up period (24 months later).

At the time of the first Echo, LVH was detected in only 8 (21%) patients. Residual urine volume was significantly decreased compared to data taken when they first started PD (658 ± 795 vs 236 ± 307 mL/day). Mean left ventricular mass index (LVMI) was 107 ± 26.5 g/m². LVMI was significantly decreased at the end of the follow-up in patients who had LVH at baseline. No LVH developed in patients who had normal LVMI at baseline.

Our results indicate that control of hypertension is possible when extracellular fluid volume is kept under control using hypertonic PD solutions in case of recruitment in addition to salt restriction in long-term PD patients. Sustained normovolemia is associated with low incidence and regression of LVH.

The aim of this prospective study was to collect long-term experience in incident peritoneal dialysis (PD) patients treated with pure bicarbonate-buffered PD fluids.

The metabolic parameters acidosis, acid–base status, adequacy, fluid balance, nutritional markers, calcium, phosphorus, parathyroid hormone (PTH), and general laboratory work and medication were compared between incident PD patients in two groups: one treated with a 34 mmol/L bicarbonate-buffered PD fluid (BIC), the other with a 35 mmol/L lactate-buffered PD fluid (LAC). The observation period included 5 visits from 1 month (visit 1) until 12 months (visit 5) after the start of dialysis treatment. For the descriptive analysis, means and standard deviations were calculated. Student's t-test and linear mixed models were used to compare the two treatment groups.

36 patients were followed for 12 months, 18 in the BIC group and 18 in the LAC group. Statistically significant differences between the groups (at the end of study) were found. In BIC group, venous plasma bicarbonate was 27.4 ± 2.3 mmol/L, base excess 0.8 ± 2.2 mmol/L, and pH 7.31 ± 0.05; in LAC group, venous bicarbonate was 25.9 ± 2.4 mmol/L, base excess –0.6 ± 2.1 mmol/L, and pH 7.30 ± 0.04. No patient from the BIC group needed oral bicarbonate, in contrast to 4 patients in the LAC group. Whereas peritoneal urea and creatinine clearances did not differ between the groups, there was better renal solute clearance in the BIC group, accompanied by better-preserved diuresis at 12 months (1333 ± 935 mL with BIC vs 839 ± 556 mL with LAC). The reverse was true for ultrafiltration.

Pure bicarbonate-buffered PD solutions were superior in correcting metabolic acidosis and they allowed omission of oral bicarbonate. The minor ultrafiltration with bicarbonate-buffered PD solutions was counterbalanced by better-preserved residual renal function with these solutions.

Volume overload is common in diabetic patients on continuous ambulatory peritoneal dialysis (PD), especially when the patient's residual renal function decreases with time on PD. Due to the higher dietary salt and fluid intake, diabetic PD patients tend to use more hyper-tonic glucose solution to remove excess fluid, which in turn may lead to increased membrane permeability. In the present study, we investigated the effect of negotiated care on fluid status in diabetic PD patients.

All diabetic PD patients who had been on PD for at least 3 months by the end of year 2002 in the First Hospital of Peking University were included in the present study. A primary nurse was assigned to each patient and intensive patient education was implemented, focusing on the importance of dietary salt and fluid restriction, the detrimental effect of using more hypertonic glucose solution, and the consequence of fluid overload. Decisions on dialysis prescriptions were made after extensive discussion among the primary nurse, nephrologists, patients, and patients’ families. A patient support group was also involved when it was necessary. All the patients were followed for 1 year and fluid status, compliance to dietary restriction, and dialysis prescription were evaluated before the start and at the end of the study.

There were 30 diabetic PD patients (age 65.4 ± 10.3 years; on PD for 24.5 ± 19.9 months, range 3 – 66 months) included in the study when it was started. During the 1 year of follow-up, 4 patients died of diabetic complications, 3 patients were transferred to hemodialysis due to resistant peritonitis, and 2 patients were transplanted. By the end of follow-up, 21 patients remained on PD, among whom 15 had improved fluid status, 4 did not change, and 2 had worsened fluid status as assessed by clinical and bio-impedance evaluation. Patient compliance to dietary salt and fluid restriction had increased from 19.5% to 76.2%. During the follow-up, 8 patients were anuric at the beginning of the study and the remaining 22 patients had declining residual renal function. Only 4 patients increased their use of hypertonic solution including 2.5% (3 patients) and 4.25% (1 patient) glucose, whereas 5 patients decreased their use of 2.5% dialysis solution. By the end of follow-up, only 1 of the 21 patients was using 4.25% glucose solution and all the patients had good blood glucose control.

Our results suggest that negotiated care can be successfully used in diabetic PD patients. It helps to minimize the use of hypertonic glucose solution and improves patient compliance to dietary restriction of salt and fluid intake, and thus improves their fluid status.

In experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose peritonitis based on dialysate white blood cell counts. To study the value of serum markers for the presence of peritonitis, alpha-2-macroglobulin (α2M) and albumin were measured in rats with and without peritonitis after chronic exposure to dialysis solutions. To further investigate the time course of these markers in relation to the severity of peritonitis, nondialyzed rats were challenged with increasing numbers of bacteria and followed for 28 days.

In the first study, α2M and albumin were measured in rats exposed to glucose/lactate-based dialysis fluid before sacrifice. A comparison was made between animals with peritonitis, as judged from the presence of extensive infiltrates after sacrifice (gold standard) and/or clinical signs of peritonitis, or absence of peritonitis and infiltrates. In the second study, rats were intraperitoneally (IP) injected with 3 different concentrations of Staphylococcus aureus, and serum α2M and albumin were measured at various time points.

In the first study, serum α2M was higher and serum albumin was lower in animals with peritonitis compared to animals without peritonitis (both p < 0.05). In the second study, induction of α2M was clearly dependent on the inoculum concentration. Peak values of α2M were found at days 1 and 3. At all time points after inoculation, α2M was higher in all injected groups compared to the control group. Serum albumin values decreased in the highest inoculum group and remained decreased until 28 days after IP injection. Despite a low sensitivity, serum α2M >40 mg/L and albumin <32 g/L had a specificity of 100% for peritonitis.

Measurement of α2M and albumin once per month is an additional tool in the diagnosis of silent peritonitis in the chronic peritoneal exposure model in the rat. Levels of α2M >40 mg/L and albumin <32 g/L are strong indicators for peritonitis. However, normal values do not exclude infectious peritonitis.