Jernej Pajek

Short-term effects of bicarbonate/lactate-buffered and conventional lactate-buffered dialysis solutions on peritoneal ultrafiltration: a comparative crossover study

BACKGROUND This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. METHODS Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. RESULTS Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 +/- 602 ml and 881 +/- 633 ml with P (P < 0.001) and this lower daily UF of 443 ml (95% CI 275-610 ml) with P was associated with a similarly lower daily total fluid removal of 394 ml (95% CI 210-577 ml), as urine volume did not differ between D and P. The decrement in UF with the P solution was reversible. There were no significant differences in other peritoneal membrane indices (D/P creatinine, D/D0 glucose, 4-h UF at PET, weekly creatinine clearance, weekly urea Kt/V) or blood pressure and body weight between the solutions whereas calculated peritoneal fluid absorption rate was significantly higher with the P than with the D solution. CONCLUSION This study shows that the daily UF with the P solution may be lower than with the D solution. The mechanism for this short-term and reversible effect that conceivably reflects differences in biocompatibility is not clear although our results implicate that the peritoneal fluid absorption rate may differ between the two solutions.

Cell-free DNA in the peritoneal effluent of peritoneal dialysis solutions.

The beneficial effects of novel peritoneal dialysis solutions low in glucose degradation products regarding peritoneal cell apoptosis and necrosis are well established in vitro, however in vivo data is lacking. Cell‐free DNA quantification is a possible method to determine cell damage through apoptosis and necrosis in vivo. We performed a prospective, cross‐over study on 26 stable continuous ambulatory peritoneal dialysis (CAPD) patients, treating each patient for 3 months in a randomized order with a conventional, lactate‐buffered, acidic solution (solution D) and a novel, bicarbonate/lactate‐buffered neutral solution (solution P). The timed overnight peritoneal effluent was sampled for cell‐free DNA quantification using a fluorometric assay. The effluent samples of eighteen patients were finally available for DNA quantification. The concentration range of cell‐free DNA in the peritoneal effluents was 1.8–9.5 µg/L. The coefficient of intrapatient variation in overnight effluent cell‐free DNA appearance was 15.6 ± 12.4%. Cell‐free DNA peritoneal appearance using solutions D and P was 14.9 ± 6.8 µg and 11.8 ± 3.4 µg, respectively (P = 0.02), with the average difference of 3.1 µg (95% CI, 0.7–5.6 µg). Our results show that cell‐free DNA is present in the overnight peritoneal effluent of stable CAPD patients. A significant decrease in the cell‐free DNA appearance with solution P was found; however, before accepting this as an indicator of a more biocompatible profile causing less peritoneal membrane cell necrosis and apoptosis, confirmatory data on larger patient samples are needed. Our results indicate the potential future role of cell‐free DNA in the diagnosis and prognosis of therapy‐related peritoneal membrane degeneration.

Serum with phospholipase A2 receptor autoantibodies interferes with podocyte adhesion to collagen.

The majority of sera from patients with primary membranous nephropathy have autoantibodies against the M‐type phospholipase A2 receptor (PLA2R) which is expressed on human podocytes. The rabbit variant of PLA2R attaches to collagen type IV via the fibronectin type II domain, which is also present in the human variant of PLA2R.

Influence of Renin‐Angiotensin‐Aldosterone System‐Blocking Drugs on Peritoneal Membrane in Peritoneal Dialysis Patients

Therapy with renin‐angiotensin‐aldosterone system (RAAS)‐blocking drugs prevents the development of fibrosis and angiogenesis in animal models and humans. In our study we have evaluated the systemic effect of RAAS blockade and the effect on peritoneal growth factors, cytokine production and membrane transport characteristics in patients on peritoneal dialysis. Thirty‐seven peritoneal dialysis (PD) patients were enrolled in our cross‐sectional study. Aldosterone and angiotensin II concentrations were measured in serum to determine the RAAS activity. The inflammatory and profibrotic activity was evaluated by measuring the concentration of C‐reactive protein (CRP), serum albumin, and peritoneal concentration of interleukin‐6 (IL‐6), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor‐1 (PAI‐1), transforming growth factor‐β (TGF‐β) and cancer antigen‐125 (CA‐125). The transport characteristics of the peritoneal membrane were analyzed with a peritoneal equilibration test (PET). Results were compared between the group with RAAS‐blocking drugs (RAAS group) and the group without them (non‐RAAS group). Mean serum aldosterone concentration was significantly lower in patients treated with ARB‐blocking drugs (P = 0.001) and serum angiotensin II concentration was lower in patients treated with ACE inhibitors (P = 0.009). RAAS blockade resulted in lower peritoneal PAI‐1 levels (748.1 to 1222.7 ng/L; P = 0.07) without any influence on CRP, peritoneal concentrations of IL‐6, VEGF, TGF‐β and CA‐125, or alteration in peritoneal membrane characteristics tested by PET. RAAS‐blocking drugs could be effective in preventing peritoneal fibrosis due to possible reduction of peritoneal PAI‐1 concentrations that have already been etiologically linked with fibrin deposition in the pathogenesis of encapsulating peritoneal sclerosis.

Epoetin Responsiveness in Peritoneal Dialysis Patients: A Multi-center Slovenian Study

Abstract:  The objective of our study was to assess the influence of residual renal function and other factors on epoetin requirements in chronic peritoneal dialysis patients. Fifty‐one stable patients (mean age ± SD: 52 ± 13 years; 20 women) without recent bleeding, bone marrow disease or malignancy were recruited in four Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal equilibration test results and relevant clinical and laboratory parameters were recorded. The epoetin resistance index was expressed as a weekly epoetin dose/body weight/hemoglobin concentration. Twenty‐four percent of the patients did not need epoetin treatment, the rest were treated with epoetin‐beta in a dose of 70 ± 56 U/kg per week s.c.; the hemoglobin concentration was 124 ± 15 g/L. Ferritin >100 µg/L and transferrin saturation >20% fulfilled 63% of patients whose epoetin resistance index was not significantly lower (0.43 ± 0.5 U/kg per week per g/L vs 0.6 ± 0.72 U/kg per week per g/L, P = 0.502). No difference was found between diabetic and non‐diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, was associated with increased epoetin resistance index (0.56 ± 0.59 vs 0.3 ± 0.4 U/kg per week per g/L, P = 0.038). No correlation between epoetin resistance index and residual glomerular filtration rate was found (r = −0.2, P = 0.173). A multiple linear regression analysis showed C‐reactive protein, intact parathormone level, female sex and treatment with angiotensin system antagonists to be the independent predictors influencing epoetin resistance index. Our results show that systemic inflammation, secondary hyperparathyroidism and angiotensin system antagonist treatment are the most important modifiable parameters affecting epoetin requirements in stable peritoneal dialysis patients.

Impact of Dialysis Duration and Glucose Absorption on Nutritional Indices in Stable Continuous Ambulatory Peritoneal Dialysis Patients

OBJECTIVE The presence of comorbidity is a risk factor for both poor nutrition and poor outcome in continuous ambulatory peritoneal dialysis (CAPD) patients. In CAPD specifically, peritoneal glucose load is associated with a possible suppression of appetite, contributing to protein malnutrition. This study sought to explore the factors associated with malnutrition indices in stable peritoneal dialysis patients without significant comorbidity, and to assess the impact of peritoneal glucose absorption on nutrition parameters. DESIGN This was a cross-sectional observational study. SETTING This study took place in the peritoneal dialysis department of a university hospital, and involved outpatients. PATIENTS There were 23 stable, comorbidity-free CAPD patients (9 women), aged 54 +/- 12 years, with a CAPD duration of 28 +/- 25 months (values are mean +/- SD unless otherwise noted). METHODS Nutritional status was evaluated by means of anthropometric and serum measurements. A peritoneal equilibration test was performed, and daily glucose absorption was measured. Lean body mass (LBM) was assessed through creatinine kinetics. RESULTS A significant impact of CAPD duration was found. Patients in the upper quartile of CAPD duration had worse nutritional parameters compared with the rest of the group: their mid-upper-arm surface area and fat surface area were lower (65 +/- 9 cm(2) vs. 78 +/- 6.2 cm(2) and 16 +/- 5.3 cm(2) vs. 26 +/- 9.5 cm(2), respectively, P < .05), their albumin concentration was lower (36 +/- 0.5 g/L vs. 42 +/- 4 g/L, P < .05), and their cholesterol and triglycerides were lower (3.5 +/- 0.5 vs. 5.2 +/- 1 mmol/L and 1.3 +/- 0.6 vs. 2.3 +/- 1.1 mmol/L, respectively, P < .05). No significant correlations between peritoneal glucose absorption and these indices were found. CONCLUSION The duration of dialysis treatment, but not peritoneal glucose absorption, is a predictor of malnutrition in stable, comorbidity-free CAPD patients.

Original paper BIAS OF JUDGING IN MEN’S ARTISTIC GYMNASTICS AT THE EUROPEAN CHAMPIONSHIP 2011

The purpose of this study was to establish the validity (unbiasedness) and reliability of E-panel judges officiating execution of exercises in men’s artistic gymnastics at the European Championship 2011 (EC 2011) in Berlin. Overall bias was established in terms of average over-scoring or under-scoring of each judge compared to the final E score of a judges’ E panel. National bias was expressed as average over-scoring of gymnasts of the same nationality as the judge’s. Both types of bias were mostly small (within the +/0.1 point range), but statistically significant and also substantial (over 0.2 point) in some cases. Compared to other competitions, it seems that bias is becoming smaller over time and is also smaller in competitions of higher importance. Analysis of possible consequences of bias showed that overall bias may influence both scores and ranks of competitors, while national bias may be especially problematic in the qualification round, where it may prevent some competitors from qualifying for apparatus finals.

Severe Peritonitis in Patients Treated With Peritoneal Dialysis: A Case Series Study

Severe peritonitis causing death and/or technique termination (catheter explanted) is one of the most devastating complications of peritoneal dialysis (PD). The aim of this case series study was to reveal the predictors of risk and clinical characteristics of these cases. We included 38 patients with either peritonitis causing death (18 patients, 47%) or catheter removal (20 patients, 53%) in the period 1996–2006. Their last clinical, laboratory and peritoneal equilibration test data before the peritonitis episode and hospitalization data after the start of peritonitis were reviewed. Their median (range) age was 66 (25–85) years, 61% were male, and the median PD duration was 60 (1–144) months. Baseline C‐reactive protein (17.5 ± 19.1 mg/L) was substantially higher than in contemporary stable controls from our unit (3.5 ± 4.2 mg/L, P = 0.002). For 14 patients (37%), this was their first episode, with a significantly lower mortality of 14% as opposed to 47% across the whole group (P = 0.002). Almost half the patients (42%) had a causative abdominal condition identified, such as diverticulitis or cholecystitis. Clinical and laboratory data at presentation were variable and not different according to survival. Non‐surviving cases had a significantly larger proportion of fast transporters (83 vs. 45%, P = 0.03), a significantly lower estimate of daily protein intake (0.72 vs. 0.88 g/kg/day, P = 0.007), and a significantly higher proportion of non‐Gram‐positive causative microorganisms (72 vs. 40%, P = 0.019). The patients with severe peritonitis were characterized as older with a longer PD duration, and a higher baseline C‐reactive protein. Fast peritoneal transport, lower normalized protein catabolic rate, and non‐Gram‐positive causative bacteria were associated with mortality.

Integrative Examination of Motor Abilities in Dialysis Patients and Selection of Tests for a Standardized Physical Function Assessment

To reduce the need for a large number of executed physical function tests we examined inter‐relations and determined predictive power for daily physical activity of the following tests: 6‐min walk, 10 repetition sit‐to‐stand, time up‐and‐go, Storke balance, handgrip strength, upper limb tapping and sitting forward bend tests. In 90 dialysis and 140 healthy control subjects we found high correlations between all tests, especially those engaging lower extremities. Sit‐to‐stand, forward bend and handgrip strength were selected for the test battery and composite motor performance score. Sit‐to‐stand test was superior in terms of sensitivity to uremia effects and association with daily physical function in adjusted analyses. There was no incremental value in calculating the composite performance score. We propose to standardize the physical function assessment of dialysis patients for cross‐sectional and longitudinal observations with three simple, cheap, well‐accessible and easily performed test tools: sit‐to‐stand test, handgrip strength and Human Activity Profile questionnaire.

Six-Minute Walk Test in Renal Failure Patients: Representative Results, Performance Analysis and Perceived Dyspnea Predictors.

Objectives Six-minute walk test in dialysis population hasn’t been consistently evaluated for the isolated impact of renal failure and other predictive factors. We measured six-minute walk distance in patients representative for low level of comorbidity and searched for potentially modifiable predictive factors of performance and dyspnea. Methods This was a cross-sectional study with hemodialysis patients (N = 90) and control subjects (N = 140). Main outcome measures: six-minute walk test distance and dyspnea severity using the 10-item Borg scale. Results Median distance decreased from 600m below the 6th decade to 420m in the 8th decade of age. Dialysis dependence predicted 101.5m shorter distance in the adjusted model that explained 70% of variability in results. Adjusted for significant covariates of age, height and spontaneous gait speed, fat mass (but not lean body mass) and serum total iron binding capacity were significantly associated with distance (95% CI for B coefficients -4.6 to –1.4 m/kg and 0.1 to 5 m/μmol/l, respectively). Serum total iron binding capacity as an explanatory variable was superior to C-reactive protein and albumin. Dialysis dependence, odds ratio (OR) 2.97 (1.11–7.94), spontaneous gait speed, OR 0.08 (0.02–0.41), rate-pressure product, OR 1.15 (1.08–1.23) and hemoglobin, OR 0.95 (0.92–0.98) predicted dyspnea in the adjusted model. Conclusions Renal failure without the confounding effect of comorbidity is a significant negative predictor of performance at six-minute walk test and perceived level of dyspnea. Body fat mass and serum total iron binding capacity are the main potentially modifiable predictors of performance, total iron binding capacity being superior to C-reactive protein and albumin. Although hemoglobin is not associated with test performance, it negatively predicts perceived shortness of breath.