Background and Aims Chronic kidney disease (CKD) is a frequent complication of non-kidney solid organ transplant (NKSOT) and is related to increased morbidity and mortality. Identifying predisposing factors is crucial for an early approach and correct referral to Nephrology, a specialty with an important role in managing these patients. Method This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the department of nephrology during the period between January 2010 to December 2020. A total of 212 patients were analyzed. Patients transplanted before 2010 (101 patients), with combined transplantation with renal transplantation (9 patients), and those with no follow-up in external consultations (28 patients) were removed from the sample. A final population sample was obtained with 74 patients. Statistical analysis was performed between all the risk above factors (Figure 1) and the four dependent variables: advanced chronic kidney disease (ACKD), increased serum creatinine ≥50%, renal replacement therapy (RRT), and death in three different periods: pre-transplant period, peri-transplant period and post-transplant period. Results 74 patients were analyzed (7 heart transplant recipients, 34 liver transplant recipients, and 33 lung transplant recipients). • 45 patients presented an increase in Creatinine ≥50%. Receiving a lung transplant confers more risk versus a liver (HR 0.048 [95% CI] 0.012 to 0.192) or heart (HR 0.075 [95% CI] 0.01 to 0.5) transplant. It was significantly associated with pre-transplant obesity (p 0.003), peri-transplant mechanical ventilation (p < 0.001), peri-transplant (p 0.009) and post-transplant (p. 005) anticalcineurin overdose, peri-transplant (p. 0.046) and post-transplant nephrotoxics (0.03) and the number of hospital admissions (p. 0.002). Not having follow-up by Nephrology in the pre-transplant (p 0.027), peri-transplant (p. 0.045), and the longest time until external consultations (HR 1,032 [95% CI] 1,011 to 1,054) conferred more risk. • 24 patients developed ACKD. Receiving a lung transplant confers more risk versus a liver (HR 0.14 [95% CI] 0.045 to 0.463) or heart (HR 0.13 [95% CI] 0.015 to 1.28) transplant. Per-transplant mechanical ventilation (p. 0.03), peri-transplant (p. 0.024) and post-transplant (p. 0.038) anticalcineurin overdose, peri-transplant (p. 0.045) and post-transplant nephrotoxic antimicrobials (p. 0.04) and the number of hospital admissions (p 0.015) were significantly associated. The time to nephrology consultations after the transplant (p 0.035) conferred more risk. Mean ACKD-free survival was 93.29 months (95% CI 79.04-107.5), 121.5 months in heart transplantation recipients (95% CI of 86.70-155.297), 104 months in liver transplantation recipients (95% CI of 86.67-122.134) and 66.86 months in lung transplantation recipients (CI at 95% of 55.93 – 80.79) (Figure 2). • 8 patients required RRT. It was significantly associated with the active smoking habit in the pre-transplant period (p 0.02) and the overdose of calcineurin inhibitors in the peri-transplant period (p 0.045). • 21 patients died. It was significantly associated with the active smoking habit in the pre-transplant (p. 0.03) and the number of hospital admissions in the post-transplant (p 0.006). Conclusion Early follow-up by Nephrology is associated with a decrease in the deterioration of renal function and the development of advanced chronic kidney disease, by being able to act on the risk factors for each transplant recipient, such as an overdose of calcineurin inhibitors and nephrotoxicity, and allowing the identification of patients at higher risk, such as those requiring mechanical ventilation during peri-transplantation, patients with the highest number of hospital admissions, and lung transplant patients.
Background and Aims The relation between inflammation and cardiovascular disease is well established. Dialysis patients are at a higher risk of cardiovascular death, mostly attributed to cardiovascular disease. This study evaluated the potential benefits of citrate (CD) vs. acetate dialysate (AD) regarding the patients’ inflammatory status. Method Single-center, cross-over, prospective study, with a follow-up of a total of 24 dialysis sessions, 12 with each dialysate. Blood samples were taken on the twelfth dialysis session with each type of dialysate. Every patient acted as its own control. The pre-dialysis parameters analyzed were procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Results Pre-dialysis hsRCP [AD: 4,32 (1,27 – 12,16) vs. CD: 4,08 (0,98 – 8,65) mg/L, p = 0,031], PCT [AD: 0,44 (0,28 – 0,74) vs. CD: 0,38 (0,29 – 0,44) ng/mL, p = 0,037], and IL-6 [AD: 13,7 (7,85 – 29,03) vs. CD: 11,8 (5 – 27,13) pg/mL, p = 0,029] are significativly higher after twelve dialysis sessions with AD vs. CD. Conclusion Even in the medium term, the use of citrate instead of acetate as the dialysate acidifier, reduces the measured inflammatory parameters and could therefore be considered a more biocompatible dialysate option.
BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P < 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.
Background and Aims Unlike other high-cardiovascular-risk populations, the efficacy obtained from lipid-lowering therapy remains uncertain in dialysis-dependent chronic kidney disease (DD-CKD) patients. This is probably given to the exclusion in clinical trials of patients with very high LDL levels, their population's heterogeneity, accompanying cardiovascular morbidities, and the higher mortality risk explained partly by chronic inflammation. The latter has been associated with the accumulation of uremic toxins, membrane biocompatibility, and acetate-based dialysates, which promote inflammation. Different dialysate weak acidifying agents such as lactic, pyruvic, hydrochloric, or citric acids have surged as less-inflammatory alternatives to acetate. This study aims to evaluate the effects of the metabolism of acetate and citrate in the lipidic profile of DD-CKD patients. Method In a unicentric, cross-over, prospective study, we compared the lipidic profile by assessing the plasma levels of total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), high-density (HDL) and very low-density (VLDL) lipoprotein cholesterol, and lipoprotein (a) [Lp(a)] comparing the use of citrate (CD) vs. acetate (AD) as dialysate buffers, after twelve sessions with each one. Prealbumin was also measured to rule out malnutrition as a potential confounding factor. Prevalent (i.e., dialysis vintage ≥3 months) adult patients on maintenance hemodialysis were included. The dialysis prescription parameters and additional medical treatments remained unchanged during their sessions with both dialysates. Quantitative variables are reported with mean and standard deviation. Normal distribution was assessed with the Shapiro-Wilk test, and the comparisons were made with the Student's paired T-test or Wilcoxon's signed-rank test, accordingly. A two-sided p-value ≤0,05 was considered statistically significant. Results After twelve dialysis sessions with CD, compared to AD, there was a statistically significant decline in TG and HDL and an increase in LDL. There was also a notable but non-significant reduction in VLDL (Table 1). Conclusion There were noteworthy differences in the lipid profile that can only be attributed to the change of dialysis fluid, as we avoided inter-individual (with a cross-over design) and intra-individual (different inflammatory or nutritional profiles would not be expected with this short-term setting) variabilities. Further studies must elucidate if the short-term changes induced in the lipidic profile of DD-CKD patients by the dialysate's weak acid translate into clinical implications.
Background and Aims Dialysate composition is an essential feature of hemodialysis treatment. The use of acetate as the dialysate buffer and its calcium concentration are still topics of debate. Calcium transfer during dialysis sessions is related to short-term (hemodynamic tolerance and arrhythmias) and long-term effects (cardiovascular calcification and mortality). This study aims to identify the potential benefits derived from acetate-free dialysis by using citrate as a buffer in terms of calcium balance and CKD-MBD biomarkers. Method We performed a prospective crossover study that analyzed 24 dialysis sessions, 12 with each dialysate buffer, on every patient. Ionized calcium and CKD-MBD parameters were analyzed with each acidifier. Both dialysates had a calcium concentration of 1.5 mml/L. The remaining hemodialysis patients’ parameters were unchanged during the study period. Results No differences were found between pre-dialytical ionized calcium (iCa) (1,11 ± 0,12 vs. 1,08 ± 0,12 mmol/L) in both groups. However, we identified a significant iCa increase in the sessions were acetate dialysate was used, both in immediate (1,29 ± 0,07 mmol/L) and in 30-minutes post-dialytical blood analysis (1,22 ± 0,07 mmol/L). Whereas iCa levels remained stable during the immediate (1,07 ± 0,06 mmol/L) and 30-minutes post-dialytical analysis (1,08 ± 0,11 mmol/L) when using citrate. On the other hand, pre-dialysis albumin-corrected total calcium was higher with acetate (8,9 ± 0,6 vs. 8,31 ± 0,75 mg/dL, p = 0,003) and PTH was lower with acetate (169 vs. 267 pg/mL, p < 0,001). Conclusion Acetate-free dialysis using citrate as an acidifier stabilizes iCa levels during dialysis sessions while maintaining a neutral or negative effect in calcium balance. This analytical benefit may translate into better cardiovascular long-term outcomes.
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