CHARACTERIZATION OF THE BRAZPD II COHORT AND DESCRIPTION OF TRENDS IN PERITONEAL DIALYSIS OUTCOME ACROSS TIME PERIODS

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Peritoneal dialysis in acute kidney injury: trends in the outcome across time periods

Peritoneal dialysis (PD) should be considered a suitable method of renal replacement therapy in acute kidney injury (AKI) patients. This study is the largest cohort providing patient characteristics, clinical practice, patterns and their relationship to outcomes in a developing country. Its objective was to describe the main determinants of patient and technique survival, including trends over time of PD treatment in AKI patients. This was a Brazilian prospective cohort study in which all adult AKI patients on PD were studied from January/2004 to January/2014. For comparison purposes, patients were divided into 2 groups according to the year of treatment: 2004-2008 and 2009-2014. Patient survival and technique failure (TF) were analyzed using the competing risk model of Fine and Gray. A total of 301 patients were included, 51 were transferred to hemodialysis (16.9%) during the study period. The main cause of TF was mechanical complication (47%) followed by peritonitis (41.2%). There was change in TF during the study period: compared to 2004-2008, patients treated at 2009-2014 had relative risk (RR) reduction of 0.86 (95% CI 0.77-0.96) and three independent risk factors were identified: period of treatment at 2009 and 2014, sepsis and age>65 years. There were 180 deaths (59.8%) during the study. Death was the leading cause of dropout (77.9% of all cases) mainly by sepsis (58.3%), followed cardiovascular disease (36.1%). The overall patient survival was 41% at 30 days. Patient survival improved along study periods: compared to 2004-2008, patients treated at 2009-2014 had a RR reduction of 0.87 (95% CI 0.79-0.98). The independent risk factors for mortality were sepsis, age>70 years, ATN-ISS > 0.65 and positive fluid balance. As conclusion, we observed an improvement in patient survival and TF along the years even after correction for several confounders and using a competing risk approach.

Low serum potassium levels increase the infectious-caused mortality in peritoneal dialysis patients: a propensity-matched score study

Background and ObjectivesHypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.Design, Setting, Participants and MeasurementsThis is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.ResultsThere was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K < 3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).ConclusionsHypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Systemic lupus erythematous and clinical outcomes in peritoneal dialysis

Background: The prevalence of systemic lupus erythematous (SLE) patients requiring renal replacement therapy (RRT) is increasing but data on clinical outcomes are scarce. Interestingly, data on technique failure and peritoneal-dialysis (PD)-related infections are rarer, despite SLE patients being considered at high risk for infections. The aim of our study is to compare clinical outcomes of SLE patients on PD in a large PD cohort. Methods: We conducted a nationwide prospective observational study from the BRAZPD II cohort. For this study we identified all patients on PD for greater than 90 days. Within that subset, all those with SLE as primary renal disease were matched with PD patients without SLE for comparison of clinical outcomes, namely: patient mortality, technique survival and time to first peritonitis, then were analyzed taking into account the presence of competing risks. Results: Out of a total of 9907 patients, we identified 102 SLE patients incident in PD and with more than 90 days on PD. After matching the groups consisted of 92 patients with SLE and 340 matched controls. Mean age was 46.9 +/- 16.8 years, 77.3% were females and 58.1% were Caucasians. After adjustments SLE sub-hazard distribution ratio for mortality was 1.06 (CI 95% 0.55-2.05), for technique failure was 1.01 (CI 95% 0.54-1.91) and for time to first peritonitis episode was 1.40 (CI 95% 0.92-2.11). The probability for occurrence of competing risks in all three outcomes was similar between groups. Conclusion: PD therapy was shown to be a safe and equally successful therapy for SLE patients compared to matched non-SLE patients.

Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH)

Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Automated peritoneal dialysis is associated with better survival rates compared to continuous ambulatory peritoneal dialysis: a propensity score matching analysis

The impact of peritoneal dialysis modality on patient survival and peritonitis rates is not fully understood, and no large-scale randomized clinical trial (RCT) is available. In the absence of a RCT, the use of an advanced matching procedure to reduce selection bias in large cohort studies may be the best approach. The aim of this study is to compare automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) according to peritonitis risk, technique failure and patient survival in a large nation-wide PD cohort. This is a prospective cohort study that included all incident PD patients with at least 90 days of PD recruited in the BRAZPD study. All patients who were treated exclusively with either APD or CAPD were matched for 15 different covariates using a propensity score calculated with the nearest neighbor method. Clinical outcomes analyzed were overall mortality, technique failure and time to first peritonitis. For all analysis we also adjusted the curves for the presence of competing risks with the Fine and Gray analysis. After the matching procedure, 2,890 patients were included in the analysis (1,445 in each group). Baseline characteristics were similar for all covariates including: age, diabetes, BMI, Center-experience, coronary artery disease, cancer, literacy, hypertension, race, previous HD, gender, pre-dialysis care, family income, peripheral artery disease and year of starting PD. Mortality rate was higher in CAPD patients (SHR1.44 CI95%1.21-1.71) compared to APD, but no difference was observed for technique failure (SHR0.83 CI95%0.69-1.02) nor for time till the first peritonitis episode (SHR0.96 CI95%0.93-1.11). In the first large PD cohort study with groups balanced for several covariates using propensity score matching, PD modality was not associated with differences in neither time to first peritonitis nor in technique failure. Nevertheless, patient survival was significantly better in APD patients.

Evidence-based medicine: an update on treatments for peritoneal dialysis-related peritonitis

Peritonitis continues to be a major complication of peritoneal dialysis (PD), and adequate treatment is crucial for a favorable outcome. There is no consensus regarding the optimal therapeutic regimen, and few prospective controlled studies have been published. The objective of this manuscript is to review the results of PD peritonitis treatment reported in narrative reviews, systematic reviews, and proportional meta-analyses. Two narrative reviews, the only existing systematic review and its update published between 1991 and 2014 were included. In addition, we reported the results of a proportional meta-analysis published by our group. Results from systematic reviews of randomized control trials (RCT) and quasi-RCT were not able to identify any optimal antimicrobial treatment, but glycopeptide regimens were more likely to achieve a complete cure than a first generation cephalosporin. Compared to urokinase, simultaneous catheter removal and replacement resulted in better outcomes. Continuous and intermittent IP antibiotic use had similar outcomes. Intraperitoneal antibiotics were superior to intravenous antibiotics in reducing treatment failure. In the proportional meta-analysis of RCTs and the case series, the resolution rate (86%) of ceftazidime plus glycopeptide as initial treatment was significantly higher than first generation cephalosporin plus aminoglycosides (66%) and glycopeptides plus aminoglycosides (75%). Other comparisons of regimens used for either initial treatment or treatment of gram-positive rods or gram-negative rods did not show statistically significant differences. The superiority of a combination of a glycopeptide and a third generation cephalosporin was also reported by a narrative review study published in 1991, which reported an 88% resolution rate.

Percutaneous endoscopic gastrostomy in children on peritoneal dialysis

OBJECTIVE: 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. DESIGN: Retrospective multicenter study. SETTING: 23 pediatric dialysis units associated with the working group Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN). DATA SOURCE: 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. RESULTS: 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. CONCLUSION: 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 antifungal 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.

Clinical Validation of a Peritoneal Dialysis Prescription Model in the PatientOnLine Software

Peritoneal transport characteristics and residual renal function require regular control and subsequent adjustment of the peritoneal dialysis (PD) prescription. Prescription models shall facilitate the prediction of the outcome of such adaptations for a given patient. In the present study, the prescription model implemented in the PatientOnLine software was validated in patients requiring a prescription change. This multicenter, international prospective cohort study with the aim to validate a PD prescription model included patients treated with continuous ambulatory peritoneal dialysis. Patients were examined with the peritoneal function test (PFT) to determine the outcome of their current prescription and the necessity for a prescription change. For these patients, a new prescription was modeled using the PatientOnLine software (Fresenius Medical Care, Bad Homburg, Germany). Two to four weeks after implementation of the new PD regimen, a second PFT was performed. The validation of the prescription model included 54 patients. Predicted and measured peritoneal Kt/V were 1.52 ± 0.31 and 1.66 ± 0.35, and total (peritoneal + renal) Kt/V values were 1.96 ± 0.48 and 2.06 ± 0.44, respectively. Predicted and measured peritoneal creatinine clearances were 42.9 ± 8.6 and 43.0 ± 8.8 L/1.73 m2/week and total creatinine clearances were 65.3 ± 26.0 and 63.3 ± 21.8 L/1.73 m2/week, respectively. The analysis revealed a Pearson's correlation coefficient for peritoneal Kt/V of 0.911 and Lin's concordance coefficient of 0.829. The value of both coefficients was 0.853 for peritoneal creatinine clearance. Predicted and measured daily net ultrafiltration was 0.77 ± 0.49 and 1.16 ± 0.63 L/24 h, respectively. Pearson's correlation and Lin's concordance coefficient were 0.518 and 0.402, respectively. Predicted and measured peritoneal glucose absorption was 125.8 ± 38.8 and 79.9 ± 30.7 g/24 h, respectively, and Pearson's correlation and Lin's concordance coefficient were 0.914 and 0.477, respectively. With good predictability of peritoneal Kt/V and creatinine clearance, the present model provides support for individual dialysis prescription in clinical practice. Peritoneal glucose absorption and ultrafiltration are less predictable and are likely to be influenced by additional clinical factors to be taken into consideration.

A peritoneal dialysis patient with fatal culture-negative peritonitis

Culture-negative peritoneal inflammation accounts for between 5 and 20% of cases of peritonitis in peritoneal dialysis patients. Diagnostic yields may be enhanced considerably by reculturing dialysate effluents using appropriate collection methods and optimal laboratory techniques (including prolonged low-temperature and anaerobic incubations). In patients with persistent culture-negative peritonitis, consideration should be given to the possibilities of unusual or fastidious microorganisms (especially fungi and mycobacteria) and non-infective causes (especially drug reactions, malignancy, visceral inflammation and retroperitoneal inflammation). In this paper, an illustrative case of persistent culture-negative peritonitis is presented followed by a discussion of the investigative approach to such patients, with particular emphasis on differential diagnosis and the limitations of currently available tests.