Trimethylamine-N-oxide (TMAO) and clinical outcomes in patients with end-stage kidney disease receiving peritoneal dialysis

Background: Trimethylamine-N-oxide (TMAO) is a gut bacteria-derived metabolite of l-carnitine and choline. A high concentration of TMAO has been proven to relate to cardiovascular disease (CVD), all-cause mortality and chronic kidney disease progression. We aimed to investigate the relation between the value of serum TMAO and outcomes for peritoneal dialysis (PD) patients. Methods: This is a prospective cohort study with data retrospectively analysed. All incident PD patients were enrolled and followed up. Log-rank test, competing risk survival analysis and COX regression were performed to test the effect of serum TMAO on developing first-episode peritonitis, all-cause and CVD mortality. Results: A wide distribution of serum TMAO concentration was observed in 513 PD patients, with a median level of 72.3 (43.7, 124.7) µmol/L. Patients with lower TMAO concentration were more likely to be without diabetes and hypertension. Patients with lower TMAO concentration showed better residual kidney function and solute clearance at baseline. Participants in the higher three TMAO quartiles showed an increased risk for first-episode peritonitis ( p = 0.039). By competing risk survival analysis, after adjusting for age, sex, diabetes mellitus, CVD, body mass index, albumin, high-sensitive C-reactive protein, potassium, phosphorus, residual kidney function, normalised protein equivalent of total nitrogen appearance and calendar year of catheter implantation, patients in the higher three TMAO quartiles had a statistically or marginally higher risk for first-episode peritonitis compared with patients in the lowest quartile, with hazard ratio (HR) 1.65 (1.05, 2.58), 1.46 (0.92, 2.31) and 1.66 (1.05, 2.61), respectively. In the COX model, patients in the third quartile TMAO group had significantly higher CVD mortality risk compared with the lowest quartile group, as HR 2.27 (1.02, 5.05) after adjusting for various factors. As for all-cause mortality, TMAO did not show any associated effects. Conclusions: Serum TMAO concentration is associated with the risk of first-episode peritonitis and CVD mortality in PD patients. No obvious association between serum TMAO and all-cause mortality was observed.

Association of blood pressure after peritoneal dialysis initiation with the decline rate of residual kidney function in newly-initiated peritoneal dialysis patients

Background Lower blood pressure (BP) levels are linked to a slower decline of kidney function in patients with chronic kidney disease (CKD) without kidney replacement therapy. However, there are limited data on this relation in peritoneal dialysis (PD) patients. Here we evaluated the association of BP levels with the decline of residual kidney function (RKF) in a retrospective cohort study. Methods We enrolled 228 patients whose PD was initiated between 1998 and 2014. RKF was measured as the average of creatinine and urea clearance in 24-hr urine collections. We calculated the annual decline rate of RKF by determining the regression line for individual patients. RKF is thought to decline exponentially, and thus we also calculated the annual decline rate of logarithmic scale of RKF (log RKF). We categorized the patients’ BP levels at 3 months after PD initiation (BP3M) into four groups (Optimal, Normal & High normal, Grade 1 hypertension, Grade 2 & 3 hypertension) according to the 2018 European Society of Cardiology and European Society of Hypertension Guidelines for the management of arterial hypertension. Results The unadjusted, age- and sex-adjusted, and multivariable-adjusted decline rate of RKF and log RKF decreased significantly with higher BP3M levels (P for trend <0.01). Compared to those of the Optimal group, the multivariable-adjusted odds ratios (95% confidence interval) for the faster side of the median decline rate of RKF and log RKF were 4.04 (1.24–13.2) and 5.50 (1.58–19.2) in the Grade 2 and 3 hypertension group, respectively (p<0.05). Conclusions Higher BP levels after PD initiation are associated with a faster decline in RKF among PD patients.

Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis

Background and objectives. Residual native kidney function confers health benefits in dialysis patients. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes. This study assessed whether lower plasma concentrations of uremic solutes were associated with residual kidney function in pediatric patients on peritoneal dialysis. Design, setting, participants, and measurements. Samples were analyzed from 29 pediatric peritoneal dialysis patients including 13 without residual kidney function and 10 with residual kidney function. Metabolomic analysis by untargeted mass spectrometry compared plasma solute levels in patients with and without residual kidney function. Dialytic and residual clearances of selected solutes were also measured by assays employing chemical standards. Results. Metabolomic analysis showed that plasma levels of 256 uremic solutes in patients with residual kidney function averaged 64 (51-81 IQR) percent of the values in patients without residual kidney function who had similar total Kt/Vurea. The plasma levels were significantly lower for 59 of the 256 solutes in the patients with residual kidney function and significantly higher for none. Assays employing chemical standards showed that residual kidney function provides a higher portion of the total clearance for non-urea solutes than it does for urea. Conclusions. Concentrations of many uremic solutes are lower in peritoneal dialysis patients with residual kidney function than in those without residual kidney function receiving similar treatment as assessed by Kt/Vurea.

MO790PREDICTORS OF ERYTHROPOIETIN HIPORESPONSIVENESS IN PREVALENT PATIENTS ON PERITONEAL DIALYSIS: A CROSS-SECTIONAL STUDY

Background and Aims Anemia resistant to recombinant human erythropoietin (EPO) is a risk factor for mortality in dialyzed patients with chronic kidney disease. Identifying the causes of hyporesponsiveness may help overcome this resistance. The aim of this study was to investigate the risk factors of EPO hyporesponsiveness in a prevalent population of patients on peritoneal dialysis (PD). Method Cross-sectional study involving 50 prevalent DP patients. To evaluate the dose–response effect of EPO therapy, we used the erythropoietin resistance index (ERI), calculated as the average weekly weight-adjusted dose of EPO (U/Kg per week) divided by the average hemoglobin level (g/dL), over a 3-month period. Patients were classified in two groups according to ERI: ERI ≤ 10 and ERI &gt; 10. We compared clinical, analytical and demographic data among groups. Body composition and fluid volume were evaluated by bioimpedance using the body composition monitor (BCM). Logist regression analysis was performed to identify predictors of EPO hyporesponsiveness. Statistical analysis was executed using SPSS (Version 23 for Mac OSX). Results The average age of 50 prevalent DP patients was 52.04 ± 15.98 years, 29 (58%) were male, 29 (58%) were diabetic and 31 (64%) were treated with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Average hemoglobin level (Hb) was 10.99 ± 0.81g/dL and average ERI was 7.64 ± 7.25. Eleven patients (22%) had hyporesponsiveness to EPO therapy (ERI&gt;10). There was no age, gender, cause of chronic kidney disease or PD modality difference among groups. There was also no difference in the use of ACEIs or ARBs. Hyporesponsive patients had lower body mass index (BMI) (22.94 ± 2.89 vs 26.74 ± 4.53Kg/m2, p=0.01) and lower lean tissue index (LTI) (9.96 ± 1.94 vs 16.23 ± 18.51Kg/m2, p=0.02), but not fat tissue index (FTI). Weekly creatinine clearance (peritoneal plus urinary), but not Kt/V, was also significantly lower in this group (68.76 ± 37.29 vs 87.84 ± 35.35L/1.73m2, p=0.028). Hyporesponsive patients had lower urine volume (0.73 ± 0.63 vs 1.39 ± 0.67L, p=0.005) and residual kidney function (3.43 ± 3.04 vs 6.13 ± 3.69mL/min/1.73m2, p=0.044). The proportion of patients with fluid overload, defined as overhydration (OH)/extracellular water (ECW) &gt; 15%, was significantly higher in this group (p=0.04). No difference was observed in albumin, c-reactive protein, serum iron, serum ferritin, transferrin saturation index or parathormone among groups. In a logist regression analysis, BMI [(OR) 0.56 (CI: 0.364-0.849)] and LTI [(OR) 0.315 (CI: 0.130-0.767)] were predictors of hyporesponsiveness to EPO therapy. Conclusion Lower BMI and lower LTI were predictors of resistance to EPO therapy in our study. Body composition, fluid status and residual kidney function seem to be the main factors influencing the response to EPO therapy in prevalent patients on PD, emphasizing the importance of strategies oriented to preserve residual kidney function in these patients.