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Background and Aims Cardiovascular disease (CVD) is the main cause of death in chronic kidney patient. Increase pulse pressure (PP) is associated with adverse cardiovascular outcomes and is an independent risk factor of progression of chronic kidney disease. In this study we aim to identify the risk factors associated with increased PP in a population with severely decreased glomerular filtration rate. Method This was a prospective analysis conducted in an outpatient nephropathy clinic between 2005-2018, enrolling 692 patients with stage 4 CKD. Patients were divided into two groups according to their pulse pressure. Group 1 mean PP< 50 mmHg, Group2 mean PP >50 mmHg. Based on the calcium/magnesium ratio (rCaMg), the subjects were also divided into 4 risk groups according to the following criteria: 75th percentile (rCaMg: > 8.6; n=165) - G4. We used descriptive analysis, Student's t test, Univariate logistics regression analysis and CHAID analysis to determine the relationship between variables and PP. Results Total of 682 patients, with mean age 70 (SD 12.5), female 54%. An independent t-test was conducted to compare groups. There was a significant difference in mean hemoglobin level (p=0.005), calcium (p=0.029), phosphorus (p=0.017), magnesium (p Phosphorus OR 1.906 (CI 1.338-2.715) p After adjusting for confounding variables only sex OR 0.613 (CI 0.420-0.896) p=0.012 and rCa/Mg groups: G1 OR 7.392 (CI 4.362-12.527) p CHAID analysis identified rCa/Mg G2, G3, G4 (82.4%) as the more likely significant predictor to PP> 50 mmHg (p Conclusion These results suggest increased calcium/magnesium rate and male gender were associated with increased pulse pressure in a population with stage 4 CKD. Further studies are needed to understand this relationship.

Background and Aims Survival analysis is a cornerstone in medical research. For this purpose Kaplan-Meier is the most widely used statistical test, but the presence of competing risks violates the fundamental assumption that the censoring mechanism is independent of survival time. This leads to overestimation of the cumulative probability of cause-specific failure. Cumulative incidence estimate and competing risks analysis are preferred. The purpose of this study was to compare different survival analysis methods: Kaplan-Meier and cumulative incidence function estimates in a cohort of Peritoneal Dialysis (PD) patients. Method The survival of 115 incident patients on PD in a university hospital was evaluated after establishing 2 cohorts: patients starting renal replacement therapy with PD (PD first; n=85) and patients switching to PD on the first 6 months of dialysis (PD transfer; n=30). Kaplan-Meier, cumulative incidence function, cause-specific and subdistribution hazards were performed. The event of interest was death and the competing risk events were transfer to hemodialysis and renal transplantation. Results Besides higher residual renal function (RRF) and kt/V in the PD first group, there were no other significant differences between groups. There were 22 deaths. PD first group had a better survival with both Kaplan-Meier (log-rank test, p=0.013) and cumulative incidence function (p=0.021) approaches. The Cox regression model showed, as protecting variables, higher albumin (HR=0.174; CI95% 0.054-0.562), higher RRF (HR=0.785; CI95% 0.666-0.925) and PD first (HR=0.350; CI95% 0.132-0.927). Higher Charlson Index predicted worse outcome (HR=1.459; CI95% 1.159-1.835). PD as first dialysis therapy was associated with 65.0 % lower risk of death comparing with PD transfer. The subdistribution multivariable model found higher Charlson Index (HR=1.389; CI95% 1.118-1.725) and lower RRF (HR=0.798; CI95% 0.680-0.936) were statistically associated with death, but not PD transfer or albumin. This result differs from the obtained using the cause-specific hazard model. Analyzing the competing events, patients submitted to renal transplantation had a lower Charlson Index. Conclusion The probability of death was overestimated by the Kaplan-Meier method. The bias of Kaplan-Meier is especially great when the hazard of the competing risks is large. This study consisted on a statistical critical analysis of a real medical example, broader clinical conclusions related with “PD first initiative” should be cautious in this context. It is primordial to recognize the presence of competing risks in studies with multiple outcomes, as in Peritoneal Dialysis studies, to estimate cumulative incidence and yield more accurate results. This study shows how different conclusions are attained with different statistical methodology and its relevance in clinical context.

Background and Aims Peritoneal protein loss (PPL) in peritoneal effluent is a well-recognised detrimental result of peritoneal dialysis treatment since its inception. Hydrostatic convection is a major drive for peritoneal protein transport; therefore venous congestion may have a role in peritoneal protein loss (Krediet RT et al Perit Dial Int. 2019 ). The aim of this study was to explore the importance of overhydration on the magnitude of peritoneal protein clearance in incident PD patients. Method A total of 97 adult incident PD patients were included. A standard peritoneal equilibration test, 24-hour urine and dialysate collection, and multifrequency bioimpedance analysis were performed. Independent-samples t test and Pearson correlation coefficient were performed to evaluate relevant clinical associations and linear multivariable regression was done. Results Statistically significant univariable relationships for 24h PPL were found for continuous ambulatory PD technique (CAPD) and, with a correlation coefficient >0.20, for age, pulse pressure, 4-hour dialysate/plasma creatinine and extracellular water/total body water. On multivariable analysis, type of PD technique (β=0.327, p=0.011), 4-hour dialysate/plasma creatinine (β=0.247, p=0.037), and extracellular water/total body water (β=0.304, p=0.016) were significant independent predictors of peritoneal protein loss. Conclusion Overhydration revealed the most important connection with peritoneal protein loss. Mortality has been associated with PPL in some studies, but not others. This could be a result of this relationship, as volume overload has been strongly related with lower survival.

Background and Aims Peritoneal Dialysis (PD) is currently the first option as renal replacement therapy to many patients, for several reasons, as personal flexibility, volemic management in cardiorenal patients, poor vascular access to dialysis, among others. Mechanical complications can be a drawback in these patients, which may occur during or after catheter placement. Abdominal wall hernias and dialysate leaks are relatively common and highly related to chronically increased intraperitoneal pressure. In this setting CT peritoneography is the technique of choice as it allows differentiation between a true hernia or a wall leakage. Method We describe a case of a 69-year-old man, with a personal history of polycystic kidney disease, colonic diverticulosis and hypertension, which opted for PD. The patient later developed a mechanical complication for which a proper diagnostic approach, namely through specific imaging, and surgical planning were essential. Results After 15 months without complications, it was detected a bulging in the periumbilical area, exacerbated by orthostatism. Changes in dialytic prescription included lower dialytic volumes during orthostatic period, with some improvements. The limitation of volumes and difficulty of drainage were limiting dialytic prescription and insufficient kt/V. An ultrasound (figure 1) and CT peritoneography (figure 2) were performed, revealing an hernial sac with peritoneal liquid leak, without any intestinal loop, approachable by minimally invasive surgery and local anesthesia. Mini-laparotomy was performed, hernial sac was removed, without peritoneum aperture, with only a 4-day pause on PD technique. Conclusion CT peritoneography allowed the differentiation between this true hernia and a wall leakage, by providing accurate anatomical detail, allowing proper planning of surgical intervention. In this case, the patient had additional predisposing factors, namely polycystic kidney disease. Moreover, only a short pause on PD was necessary. Although some limitations exist, such as the use of iodinated contrast material and ionizating radiations, CT peritoneography is currently the gold standard for the evaluation of mechanical complications in PD; in addition to those mentioned, it is also useful for complications related to the catheter (kinking, entrapment, malposition), intrabdominal adhesions or loculated fluid collections.

Background and Aims Cardiovascular disease (CVD) is the most life-threatening complication in chronic kidney disease (CKD) patients. In addition to traditional risk factors, most patients with CKD display abnormal mineral metabolism with underlying hormonal dysregulation, defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). CKD-MBD involves changes in mineral ion homeostasis, bone quality and turnover, cardiovascular and soft tissue calcifications, which highly contribute for cardiovascular complications. Vascular calcification (VC) is associated with significant morbidity and mortality and a strong predictor of cardiovascular risk in CKD patients. Early preventive measures, including new diagnostic/prognostic tools, are required to reduce the development and progression of VC, left ventricular hypertrophy and arterial stiffness, which are crucial for the prevention of CVD outcomes in CKD patients. Gla-rich protein (GRP) is a vitamin K-dependent protein with a dual capacity to function as an inhibitor of pathological calcification and anti-inflammatory agent in the cardiovascular system, whose clinical utility is unknown. Our aim with this study was to evaluate the potential of GRP as a new marker for CKD-MBD and vascular calcification, in type 2 diabetic patients with chronic kidney disease (CKD) stages 2-4. Method In an observational prospective study including all eligible type 2 diabetic patients with CKD stages 2-4 (n=80) followed in outpatient nephrology consultation from 2010 to 2017, we explored correlations between levels of GRP in serum with mineral metabolism and inflammation markers, CKD developmental stage, vascular calcification and pulse pressure (PP). Vascular calcification score (VCS) was evaluated using the plain x-ray of the hands and pelvis (Adragão score), and increased cardiovascular risk was considered for VCS≥3. Measurements of GRP in serum were performed using a recently developed sandwich ELISA assay. Descriptive statistics, ANOVA and post hoc analysis with Scheffe test were used for analysis. Forward stepwise logistic regression (likelihood ratio) analysis was applied to identify predictive factors for VCS and PP, and ROC curves were used to assess the sensitivity and specificity of GRP in relation to these exposure factors. Results Spearman’s correlation analysis revealed the strong positive correlation between levels of serum GRP and eGFR (r=0.863, p Conclusion Reduced levels of GRP were associated with higher levels of vascular calcification promoters such as P, FGF-23 and CaxP, and with lower levels of the VC inhibitor α-Klotho, indicating a correlation between GRP and the dysregulation of phosphate metabolism characteristic of CKD-MBD. In addition, this pilot cohort study indicates that GRP levels might be a significant clinical predictor of vascular calcifications in diabetic patients with CKD. Funding This research was funded by the Portuguese Society of Nephrology (SPN) through project funding 2016, by the Portuguese national funds from FCT - Foundation for Science and Technology through the transitional provision DL57/2016/CP1361/CT0006 and project UID/Multi/04326/2019. Acknowledgments To SPN by the attribution of the Jacinto Simões award (2018) financed by Fresenius medical care.

Background and Aims The report of peritoneal protein loss should be related with a timely collection (24-hour measurement or 4-hour PET assessment) or concentration. Standardized and reproducible estimation of peritoneal protein transport is obtained during PET. The 24-hour measurements estimate the real amount of PPL, but may be affected by other factors unrelated to the prognosis of PD patients, as inconsistencies in collection and management of the samples. Overall, PET protein loss quantification may be a more specific marker of peritoneal large-pore dysfunction and is seemingly more convenient than 24-hour measurements. The aim of this study was to compare the results of both sampling methods. Method A total of 144 adult incident PD patients were included. A standard peritoneal equilibration test, 24-hour urine and dialysate collection, and multifrequency bioimpedance analysis were performed. Independent-samples t test and Pearson correlation coefficient were performed to evaluate relevant clinical associations. Results Statistically significant univariable relationships for 24h PPL were found for continuous ambulatory PD technique (CAPD) and, with a correlation coefficient >0.20, for pulse pressure, 4-hour dialysate/plasma creatinine and extracellular water/total body water. Studying 240 min PPL, only with 4-hour dialysate/plasma creatinine, creatinine clearance and bicarbonate levels were statistically significant. In both samples there was no significant association with age, gender, type of effluent (biocompatible solutions or lactate plus bicarbonate comparing with bicarbonate), comorbidity Charlson Index, or presence of diabetes. Correlation between 240 min PPL and 24h PPL ensues, but it is not strong (p Conclusion The weak correlation between 24h and 240 minutes show that these two measurements should not be considered equivalent. Measurements of a 24h sample might be more close to patients’ clinical status and prognosis, despite more frequent sampling errors. PET protein loss quantification should be regarded as a marker of peritoneal large-pore dysfunction.

Background and Aims Cardiovascular disease (CVD) is the main cause of death in chronic kidney patient. The interaction between calcium and magnesium and mineral metabolism have been identified as risk markers for CVD. The main objective was to identify the variables associated with cardiovascular and other causes of mortality in a group of patients with stage 4 of chronic kidney disease (CKD). Method This was a prospective analysis conducted in an outpatient nephropathy clinic between 2005-2018, enrolling 692 patients with stage 4 CKD. Based on the calcium/magnesium ratio (rCaMg) the subjects were divided into 4 risk groups according to the following criteria: 75th percentile (rCaMg: > 8.6; n=165) - G4. Descriptive statistics, ANOVA, chi-square and Log Rank test were used for comparison between groups. Bonferroni test was used as a post-hoc test. Kaplan-Meier analysis was used to evaluate mortality. The Kaplan-Meier method for measuring patient survival rate was applied and a comparison between the four percentiles was based on the log rank test The multinomial regression models were used to assess predictive factors for cardiovascular mortality. CHAID analysis was used to assign patients to risk groups. Results The mean age was 70 years, 53.5% women, with an eGFR of 19.9 ml/min (sd 8.1). Differences among groups were evaluated with the use of an analysis of variance (ANOVA) model. Age (p 8.6) were older (p Survival at 84 months was progressively shorter with higher rCaMg (G- 1=81.4%, G-2:70.7, G- 3=60.5%, G- 4=28.4%. log Rank =xxx, p=0.004) Multinomial regression analysis showed that Phosphorus; ORa: 1.946 (CI 1.194-3.169), p=0.007, rCaMg; ORa: 1.106 (CI 1.071-1.261) p=0.031, Age: ORa; 1.032 (CI 1.007-1.058) p=0.013, Pulse pressure: ORa; 1.033 (CI 1.007-1.060) p=0.011 were linked to increased cardiovascular mortality. CHAID analysis identified that in 43.7% of patients with P> 4.1 mg/dl, 15.5% were associated with cardiovascular mortality (p Conclusion The calcium/magnesium ratio was shown to be a strong predictor of cardiovascular mortality in patients with stage 4 chronic kidney disease. After CHAID analysis the phosphorus level was assumed to be strongest predictor of cardiovascular mortality in this group of patients.