Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression.

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.

The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation.

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.

Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis.

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.

Current status of exercise and its impact on quality of life in patients undergoing peritoneal dialysis in the post-COVID-19 period.

OBJECTIVES: The aims of this study were to investigate the current status and the influence factors of exercise, and to explore the impact of exercise on the quality of life (QoL) in peritoneal dialysis (PD) patients in the post-COVID-19 period. MATERIALS AND METHODS: Those PD patients who were followed up between September 2020 and August 2021 were enrolled. The collected data included demographic information, clinical data, exercise data, and QoL. RESULTS: In total, 339 PD patients were included in this cross-sectional study. The mean age was 44.0 ± 13.0 years, with a median PD duration of 6.7 (1.7 - 41.9) months. The primary renal disease was glomerulonephritis (68.4%). 277 (81.7%) PD patients performed exercise, with median exercise time 5.0 (3.5 - 7.8) hours per week. The main type of exercise was slow walking. Pain (odds ratio (OR) = 0.311, p = 0.002) and lower hemoglobin level (OR = 1.016, p = 0.033) were independent risk factors for exercise. Moreover, male sex (B = 2.803, p < 0.001) was an independent protective factor, while advanced age (B = -0.097, p < 0.001), higher body mass index (B = -0.154, p < 0.001), and pain (B = -0.643, p = 0.023) were independent risk factors for exercise intensity. After adjustment for other confounders, exercise (B = 5.787, p = 0.037) was an independent protective factor for total score of QoL in PD patients. CONCLUSION: In the current study, 81.7% of PD patients performed exercise in the post-COVID-19 period. Pain and anemia were independent risk factors for exercise in PD patients. Advanced age, female sex, higher body mass index, and pain were independently associated with lower exercise capacity in PD patients. PD patients undergoing exercise had better QoL.

Relationship Between Peritoneal Protein Clearance and Hemoglobin in Peritoneal Dialysis Patients: A Prospective Cohort Study.

OBJECTIVE: The relationship between higher peritoneal protein clearance (PPCl) and hemoglobin (Hb) levels in peritoneal dialysis (PD) patients is unknown. We explored this relationship and interaction on all-cause mortality in this prospective cohort study with a large number of PD patients. METHODS: We enrolled prevalent PD patients in a single PD center. Demographic characteristics and clinical and biochemical data were collected. The total amount of protein loss in the dialysate and PPCl corrected for serum albumin were calculated. The primary study endpoint was all-cause mortality. We examined the relationship between PPCl, Hb, and all-cause mortality in the Cox regression model. RESULTS: We included a total of 487 PD patients (58.3% males, mean age 49.5 ± 14.9 years). The median PD duration at enrollment was 30.1 (15.8-48.3) months. Mean Hb level was 11.1 ± 1.9 g/dL, and 221 (45.3%) patients had Hb levels <11 g/dL. Patients with Hb < 11 g/dL had lower serum albumin, lower residual renal creatinine clearance, and higher PPCl. In a multilinear regression model, PPCl (ß = -0.12, P = .015) had an independent negative linear association with Hb levels. In the logistic regression model, higher PPCl was independently associated with lower Hb (<11 g/dL) (odds ratio = 1.02; 95% confidence interval [CI]: 1.01-1.03). In the overall cohort, after adjusting for confounders in the Cox regression model, decrease in Hb level was independently associated with increased risk (hazard ratio: 0.86, 95% CI: 0.77-0.95) of all-cause mortality. Interaction-effect test showed that PPCl influenced the relationship between Hb level and all-cause mortality (P = .011). After adjusting for confounders, lower Hb level was independently associated with a higher risk (hazard ratio: 0.85, 95% CI: 0.74-0.97) of all-cause mortality only in patients with PPCl ≥59.5 mL/day and not in patients with lower PPCl. CONCLUSIONS: Higher PPCl was an independent predictive factor of lower Hb levels in PD patients. Therefore, PPCl influenced the relationship between Hb level and all-cause mortality in PD patients.

Mitochondrial DNA copy number in peripheral blood of IgA nephropathy: a cross-sectional study.

Mitochondrial DNA (mtDNA) copy number (CN) is a biomarker of mitochondrial function and has been reported associated with kidney disease. However, its association with IgA nephropathy (IgAN), the most common cause of glomerulonephritis (GN), has not been evaluated. We included 664 patients with biopsy-proven IgAN and measured mtDNA-CN in peripheral blood by multiplexed real-time quantitative polymerase chain reaction (RT-qPCR). We examined the associations between mtDNA-CN and clinical variables and found that patients with higher mtDNA-CN had higher estimated glomerular filtration rate (eGFR) (r = 0.1009, p = .0092) and lower serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) (r=-0.1101, -0.1023, -0.07806, respectively, all p values <.05). In terms of pathological injury, mtDNA-CN was higher in patients with less mesangial hypercellularity (p = .0385, M0 vs. M1 score by Oxford classification). Multivariable logistic regression analyses also showed that mtDNA-CN was lower for patients with moderate to severe renal impairment (defined as eGFR < 60 mL/min/1.73 m2) vs. mild renal impairment, with the odds ratio of 0.757 (95% confidence interval: 0.579-0.990, p = .042). In conclusion, mtDNA-CN was correlated with better renal function and less pathological injury in patients with IgAN, proposing that systemic mitochondrial dysfunction may be involved in or reflect the development of IgAN.

Association between serum chloride levels with mortality in incident peritoneal dialysis patients.

BACKGROUND AND AIMS: Lower serum chloride (Cl) levels have been associated with excess mortality in pre-dialysis chronic kidney disease patients. However, the relationship between serum Cl levels and clinical outcomes in continuous ambulatory peritoneal dialysis (CAPD) patients is unclear. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 1656 eligible incident patients undergoing CAPD from 2006 to 2013, and followed until December 2018. Cox regression analyses were used to examine the association between baseline and time-varying serum Cl levels and mortality. During a median follow-up of 46 months, 503 patients (30.4%) died. In analyses of baseline serum Cl, the adjusted hazard ratios (HR) for tertile 1 (<100.0 mmol/L), tertile 2 (100.0-103.0 mmol/L) versus tertile 3 (>103.0 mmol/L) were 2.34 [95% confidence interval (CI) 1.43-3.82] and 1.73 (95% CI 1.24-2.42) for all-cause mortality, 2.86 (95% CI 1.47-5.56) and 1.90 (95% CI 1.19-3.02) for cardiovascular disease (CVD) mortality, respectively. And a linear relationship was observed between serum Cl and mortality. Further, the inverse association between serum Cl and CVD mortality was particularly accentuated in the patients who were ≥50 years or with a history of diabetes. Similarly, lower time-varying serum Cl levels were also associated with a significant increased risk of all-cause and CVD death. CONCLUSION: Lower serum Cl levels predicted higher risk of all-cause and CVD mortality in CAPD patients.

Incidence and Risk Factors Associated with Technique Failure in the First Year of Peritoneal Dialysis: A Single Center Retrospective Cohort Study in Southern China.

BACKGROUND: Technique failure is more likely to occur during the first 12 months after peritoneal dialysis (PD) initiation, which is a great challenge encountered in PD patients. The aim of this study was to investigate the incidence and risk factors associated with technique failure within the first year of PD patients in Southern China. METHODS: Incident PD patients who were followed up for at least one year at The First Affiliated Hospital of Sun Yat-sen University from January 1, 2006 to December 31, 2015 were included. Technique failure was defined as transferring to hemodialysis (HD) for more than 30 days or death within the first year after start of PD. A competitive risk regression analysis was used to explore the incidence and risk factors of the technique failure. RESULTS: Overall, 2,290 incident PD patients were included in this study, with a mean age of 48.2 ± 15.7 years, 40.9% female and 25.2% with diabetes. A total of 173 patients (7.5%) had technique failure during the first year of PD. Among them, the patient death account for 62.4% (n = 108) and transferring to HD account for 37.6% (n = 65). The main reasons for death were cardiovascular diseases (n = 32, 29.6%), infection (n = 15, 13.8%) and for conversion to HD were mechanical cause (n = 28, 43.1%), infection cause (n = 22, 33.8%). The risk factors for the technique failure included advanced age (HR 2.78, 95%CI 1.82-4.30), low body mass index (BMI < 18.5 kg/m2: HR 1.77, 95%CI 1.17-2.67), history of congestive heart failure (HR 2.81, 95%CI 1.58-4.98), or time on HD before PD ≤ 3 months (HR 1.49, 95%CI 1.05-2.10), peritonitis (HR 2.02, 95%CI 1.36-3.01);while higher serum albumin (HR 0.93, 95%CI 0.89-0.96) and using employee medical insurance to pay expenses (HR 0.47, 95%CI 0.32-0.69) were associated with reduced risk. CONCLUSIONS: Advanced age, poor nutritional status, history of HD or congestive heart failure, and peritonitis are related factors that increase the risk of technique failure in the first year of PD, while patients' type of medical insurance may also have an influence on early technique failure.

Effect of Mean Platelet Volume to Platelet Count Ratio on Mortality in Peritoneal Dialysis.

Background and Aims: Mean platelet volume to platelet count ratio (MPV/PC) has been found to be an independent risk factor for mortality in various diseases, including cardiovascular disease, cancer, and hemodialysis. We aimed to evaluate the association between MPV/PC and all-cause and cardiovascular (CV) mortality in peritoneal dialysis (PD) patients. Methods and Results: We conducted a retrospective cohort study at a single center and enrolled 1473 PD patients who were catheterized at our PD center from January 1, 2006, to December 31, 2013. All patients were divided into four groups according to the quartiles of baseline MPV/PC levels and followed up until December 31, 2018. A total of 453 patients died, and 221 deaths were caused by cardiovascular disease during a median follow-up time of 48.0 (21.9-82.2) months. There was a significant interaction by age of association between MPV/PC level and all-cause mortality (P = 0.009), and multivariate Cox regression analysis showed that higher MPV/PC level was related to a decreased risk of all-cause and CV mortality in PD patients aged < 60 years (HR = 0.62, 95%CI = 0.40 - 0.96, P = 0.032; HR = 0.49, 95%CI = 0.26 - 0.93, P = 0.029, respectively), rather than in patients aged ≥ 60 years (HR = 1.37, 95%CI = 0.84 - 2.22, P = 0.208; HR = 1.50, 95%CI = 0.77 - 2.92, P = 0.237, respectively). Conclusion: Our results indicated that low MPV/PC level was an independent risk factor for all-cause and CV mortality in PD patients aged less than 60 years.

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis.

BACKGROUND AND AIMS: Previous studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients. METHODS AND RESULTS: In this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6-71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06-1.93, P = 0.019), 1.54 (95%CI = 1.01-2.35, P = 0.046), respectively. CONCLUSION: Higher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.

Abnormal iron status is associated with an increased risk of mortality in patients on peritoneal dialysis.

BACKGROUND AND AIMS: Iron deficiency is prevalent, but there is limited data about the relationship between iron status and poor outcomes in chronic kidney disease patients undergoing peritoneal dialysis (PD). We aimed to investigate the association between iron status and mortality in PD patients. METHODS AND RESULTS: This retrospective study was conducted on incident PD patients from January 2006 to December 2016 and followed up until December 2018. Patients were categorized into four groups according to baseline serum transferrin saturation (percent) and ferritin levels (ng/ml): reference (20-30%, 100-500 ng/ml), absolute iron deficiency (<20%, <100 ng/ml), function iron deficiency (FID) (<20%, >100 ng/ml), and high iron (>30%, >500 ng/ml). Among the 1173 patients, 77.5% had iron deficiency. During a median follow-up period of 43.7 months, compared with the reference group, the FID group was associated with increased risk for all-cause [adjusted hazard ratio (aHR) 1.87, 95% confidence interval (95% CI) 1.05-3.31, P = 0.032], but not cardiovascular (CV) mortality. Additionally, the high iron group had a more than four-fold increased risk of both all-cause and CV mortality [aHR 4.32 (95% CI 1.90-9.81), P < 0.001; aHR 4.41 (95% CI 1.47-13.27), P = 0.008; respectively]. CONCLUSION: FID and high iron predict worse prognosis of patients on PD.

Uric acid to high-density lipoprotein cholesterol ratio predicts cardiovascular mortality in patients on peritoneal dialysis.

BACKGROUND AND AIMS: Serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) disorders are both considered as risk factors of cardiovascular mortality. The predictive value of UA to HDL-C ratio (UHR) has been validated in diabetes. However, association of UHR with cardiovascular (CV) mortality is undetermined in peritoneal dialysis (PD) patients. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 1953 eligible incident patients who commenced PD treatment on our hospital from January 1, 2006 to December 31, 2015, and followed up until December 31, 2019. Of the participants, 14.9% were older than 65 years (mean age 47.3 ± 15.2 years), 24.6% were diabetics, and 59.4% were male. Patients were categorized into quartiles according to baseline UHR level. Multivariate Cox Proportional Regression analysis was applied to explore the association of UHR with mortality. Overall, 567 patients died during a median follow-up period of 61.3 months, of which 274 (48.3%) were attributed to CV death. The mean baseline UHR was 16.4 ± 6.7%. Compared to quartile 2 UHR, hazard ratios (HRs) for the highest quartile UHR were 1.35 (95% confidence interval [CI] 1.06-1.78; P = 0.017) and 1.46 (95% CI 1.00-2.12; P = 0.047) for all-cause and CV mortality, respectively. Subgroup analysis showed that association of UHR with CV mortality was remarkable among PD patients with age ≥65 years, malnutrition (albumin <35 g/L), diabetes, and CVD history. CONCLUSIONS: An elevated UHR predicted increased risk of all-cause and CV mortality in PD patients.

Elevated Serum Trimethylamine N-Oxide Levels Are Associated with Mortality in Male Patients on Peritoneal Dialysis.

BACKGROUND: Elevated levels of serum trimethylamine N-oxide (TMAO) have been previously linked to adverse cardiovascular (CV) and all-cause mortality in hemodialysis patients. However, the clinical significance of serum TMAO levels in patients treated with peritoneal dialysis (PD) is unclear. METHODS: A total of 1,032 PD patients with stored serum samples at baseline were enrolled in this prospective study. Serum concentrations of TMAO were quantified by ultra-performance liquid chromatography-tandem mass spectrometry. Cox proportional hazards and competing-risk regression models were performed to examine the association of TMAO levels with all-cause and CV mortality. RESULTS: The median level of serum TMAO in our study population was 34.5 (interquartile range (IQR), 19.8-61.0) µM. During a median follow-up of 63.7 months (IQR, 43.9-87.2), 245 (24%) patients died, with 129 (53%) deaths resulting from CV disease. In the entire cohort, we observed an association between elevated serum TMAO levels and all-cause mortality (adjusted subdistributional hazard ratio [SHR], 1.22; 95% confidence interval [95% CI], 1.01-1.48; p = 0.039) but not CV mortality. Further analysis revealed such association differed by sex; the elevation of serum TMAO levels was independently associated with increased risk of both all-cause (SHR, 1.37; 95% CI, 1.07-1.76; p = 0.013) and CV mortality (SHR, 1.41; 95% CI, 1.02-1.94; p = 0.038) in men but not in women. CONCLUSIONS: Higher serum TMAO levels were independently associated with all-cause and CV mortality in male patients treated with PD.

Identification of susceptibility locus shared by IgA nephropathy and inflammatory bowel disease in a Chinese Han population.

Genome-wide association studies (GWAS) had discovered several genetic risk loci for IgA nephropathy (IgAN), where the susceptibility genes of CARD9 and HORMAD2 for IgAN were also implicated in inflammatory bowel disease (IBD), suggesting a shared genetic etiology of these two diseases. The aim of this study is to explore the common susceptibility loci between IgAN and IBD and provide evidences to elucidate the shared pathogenesis between these two autoimmune diseases. Nineteen single-nucleotide polymorphisms (SNPs) associated with IBD in Asian populations were selected through the National Human Genome Research Institute (NHGRI) GWAS Catalog, and 2078 IgAN patients and 2085 healthy individuals of Chinese Han ancestry were included in the two-stage case-control association study. Serum levels of complement factor B (CFB) and complement split product C3a were detected by enzyme-linked immunosorbent assay (ELISA). One significant shared association at rs4151657 (OR = 1.28, 95%CI = 1.13-1.45, P = 1.42 × 10-4) was discovered between these two diseases, which implicated CFB as a susceptibility gene for IgAN. Genotype-phenotype correlation analysis found significant association of the rs4151657-C allele with decreased serum C3 levels. In addition, the rs4151657-C allele was also associated with higher CFB levels and C3a levels, which suggested a certain degree of systemic complement activation in IgAN patients with the rs4151657-CT or CC genotypes. Our study identified one risk locus (CFB) shared by IgAN and IBD, and genetic variants of CFB may affect complement activation and associate with the predisposition to IgAN.

Higher Eosinophils Predict Death-Censored Technique Failure in Peritoneal Dialysis Patients.

INTRODUCTION: Eosinophilia (eosinophil fraction of leukocytes >5%), an indicative parameter for bioincompatibility in various circumstances, is well established in hemodialysis. However, change in eosinophil count (EOC) and its association with death-censored technique failure among peritoneal dialysis (PD) patients remain unclear. METHODS: We compared eosinophils before and after PD initiation among 1,432 eligible continuous ambulatory PD patients regularly followed up in our PD center during 2007-2018. Risk factors of early-stage eosinophilia were examined by the logistic regression test. The relationship of early-stage eosinophilia and EOC with death-censored technique failure was examined using the Cox proportional hazards model for overall patients and for men and women separately. RESULTS: After PD initiation, the EOC and percentage of patients with eosinophilia were significantly increased compared with baseline. Being male (odds ratio [OR]: 2.26; 95% confidence interval [CI]: 1.55-3.31; p < 0.001) and higher EOC at baseline (100 cells/µL increase, OR: 1.62; 95% CI: 1.45-1.82; p < 0.001) were risk factors of early-stage eosinophilia after PD initiation. During follow-up, 204 death-censored technique failures were recorded. In fully adjusted models, each with 100 cells/µL increase in EOC, the adjusted hazard ratios (HRs) of technique failure were 1.11 (95% CI: 1.03-1.20; p = 0.009) in the whole cohort, 1.29 (95% CI: 1.10-1.51; p = 0.002) in women, and 1.07 (95% CI: 0.97-1.17; p = 0.196) in men. Eosinophilia was significantly associated with the risk of technique failure for women (HR: 2.24; 95% CI: 1.07-4.70; p = 0.033), which was especially significant for women aged <55 years (HR: 7.61; 95% CI: 1.88-30.90; p = 0.005). CONCLUSION: EOC was increased significantly after PD initiation, and increased numbers of eosinophils were associated with higher death-censored technique failure in PD patients, especially women.

Serum Sodium Modifies the Association of Systolic Blood Pressure with Mortality in Peritoneal Dialysis Patients.

INTRODUCTION: High serum sodium is associated with increased blood pressure (BP) in dialysis patients, which is a risk factor for cardiovascular (CV) disease. However, the interaction between serum sodium and BP and their association with clinical outcomes in peritoneal dialysis (PD) patients is uncertain. METHODS: We analyzed a retrospective cohort of 1,656 incident PD patients from January 2006 to December 2013, who were followed up until December 2018. Cox proportional hazards regression models were used to evaluate the association of serum sodium and BP with all-cause and CV mortality. A priori interaction between serum sodium and systolic BP (SBP) was explored, and a subgroup analysis was performed by stratifying SBP into the following 3 groups: <110, 110-130, and >130 mm Hg. RESULTS: Mean baseline serum sodium was 140.2 ± 3.6 mmol/L, mean SBP was 137 ± 20 mm Hg, and diastolic BP was 85 ± 14 mm Hg. During a median (range) follow-up time of 46.5 (2.6-154.3) months, 507 patients died, 252 of whom died due to CV disease. SBP did not predict all-cause and CV mortality when BP was assessed as a continuous variable. However, SBP >130 or <110 mm Hg was associated with higher risk of all-cause and CV mortality compared with SBP of 110-130 mm Hg. There was a significant interaction between baseline serum sodium and SBP for all-cause mortality (p for interaction = 0.016). In subgroup analysis, among those with SBP >130 mm Hg, the risk of all-cause mortality was elevated in those with serum sodium ≥140 mmol/L (adjusted hazard ratio [aHR] 1.45 [95% confidence interval (CI): 1.07-1.98]), but not for those with serum sodium <140 mmol/L (aHR 1.27 [95% CI: 0.89-1.82]). Conversely, among those with SBP <110 mm Hg, those with serum sodium <140 mmol/L had an elevated risk of mortality (aHR 1.99 [95% CI: 1.31-3.02]), but not those with serum sodium ≥140 mmol/L (aHR 1.15 [95% CI: 0.74-1.79]) (p for interaction = 0.028). CONCLUSION: The association of BP with mortality was modified by serum sodium levels in PD patients. Further studies are needed to evaluate whether individualized BP control based on serum sodium levels contributes to improve patient outcomes.

The predictive study of the relation between elevated low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and mortality in peritoneal dialysis.

BACKGROUND: The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio constitutes a strong risk predictor of cardiovascular events. However, the association between this ratio and cardiovascular death in peritoneal dialysis (PD) patients is uncertain. The study aimed to investigate whether a high LDL-C/HDL-C ratio could predict both cardiovascular and all-cause mortalities in patients on PD. METHODS: A total of 1616 incident patients on PD included from January 1, 2006 to December 31, 2013 were followed up with until 31 December 2018 in this single-center prospective cohort study. Participants were divided into three categories according to LDL-C/HDL-C ratio tertile. The primary endpoint was cardiovascular mortality; the secondary endpoint was all-cause mortality. RESULTS: The mean age of the study cohort was 47.5 years and the mean body mass index (BMI) was 21.6 kg/m2. During a median follow-up period of 47.6 months, 492 patients died, including 246 (50.0%) due to cardiovascular disease (CVD). A multivariate analysis revealed that the highest LDL-C/HDL-C ratio tertile was significantly associated with increased CVD mortality [hazard ratio (HR): 1.69, 95% CI: 1.24-2.29; P = 0.001] and all-cause mortality (HR: 1.46, 95% CI: 1.18-1.81; P = 0.001) relative to the lowest tertile. After adjusting for covariates, the HRs of cardiovascular and all-cause mortalities were 1.84 (95% CI: 1.25-2.71; P = 0.002) and 1.35 (95% CI: 1.03-1.77; P = 0.032). Subgroup analysis showed that the risk of CVD death rose with a higher LDL-C/HDL-C ratio among PD patients who were female, younger than 65 years old, without being malnourished (BMI ≥ 18.5 kg/m2 or albumin ≥35 g/L), and with a history of diabetes or CVD, respectively. CONCLUSIONS: A high LDL-C/HDL-C ratio is an independent risk factor for both cardiovascular and all-cause mortalities among PD patients.

Age Difference in the Association between Hyponatremia and Infection-Related Mortality in Peritoneal Dialysis Patients.

OBJECTIVES: This study aimed to examine the association of serum sodium with infection-related mortality and its age difference among continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: A total of 1,656 CAPD patients from January 2006 to December 2013 were included in this study. All patients were followed up until December 2018. Hyponatremia was defined as serum sodium <135 mmol/L. Cox proportional hazards regression model was used to investigate the relationship between baseline serum sodium levels and infection-related mortality. RESULTS: Participants were aged 47.5 ± 15.3 years, 666 (40.2%) patients were female. Glomerulonephritis was the main cause of end-stage renal disease (61.1%). After a median of 46 months of follow-up, 507 patients died. Among the deaths, 252 (49.7%) died from cardiovascular diseases, 105 (20.7%) from infections, and 150 (29.6%) from other causes. The overall infection-related mortality was 14.8 events per 1,000 patients-year, which was higher in patients aged ≥50 years than those younger than 50 years (28.3 vs. 5.3 events per 1,000 patients-year). In the entire cohort, hyponatremia at was not associated with infection-related (hazards ratios [HR] 1.66, 95% CI 0.91-3.02) and all-cause mortality (HR 1.14, 95% CI 0.83-1.57) after adjusting for potential confounders. There was a significant interaction by age of association of serum sodium with infection-related (p = 0.002) and all-cause (p = 0.0002) death. Age-stratified analysis showed that compared with control group, hyponatremia was independently related to increased risks of infection-related death, but not all-cause mortality in patients aged ≥50 years, with HR of 2.32 (95% CI 1.25-4.32) and 1.33 (95% CI 0.95-1.87), respectively. CONCLUSIONS: Hyponatremia was associated with increased risk of infection-related mortality in CAPD patients aged ≥50 years.

Plasma fibrinogen and mortality in patients undergoing peritoneal dialysis: a prospective cohort study.

BACKGROUND: Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. METHODS: This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. RESULTS: The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72-1.95, P = 0.51), 1.47 (95% CI, 0.93-2.33, P = 0.10), and 1.78 (95% CI, 1.15-2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86-1.68, P = 0.28), 1.29 (95% CI, 0.93-1.78, P = 0.13), and 1.53 (95% CI, 1.12-2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. CONCLUSIONS: An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

Roles of peritoneal clearance and residual kidney removal in control of uric acid in patients on peritoneal dialysis.

BACKGROUND: There have been few systematic studies regarding clearance of uric acid (UA) in patients undergoing peritoneal dialysis (PD). This study investigated peritoneal UA removal and its influencing factors in patients undergoing PD. METHODS: This cross-sectional study enrolled patients who underwent peritoneal equilibration test and assessment of Kt/V from April 1, 2018 to August 31, 2019. Demographic data and clinical and laboratory parameters were collected, including UA levels in dialysate, blood, and urine. RESULTS: In total, 180 prevalent patients undergoing PD (52.8% men) were included. Compared with the normal serum UA (SUA) group, the hyperuricemia group showed significantly lower peritoneal UA clearance (39.1 ± 6.2 vs. 42.0 ± 8.0 L/week/1.73m2; P = 0.008). Furthermore, higher transporters (high or high-average) exhibited greater peritoneal UA clearance, compared with lower transporters (low or low-average) (42.0 ± 7.0 vs. 36.4 ± 5.6 L/week/1.73 m2; P < 0.001). Among widely used solute removal indicators, peritoneal creatinine clearance showed the best performance for prediction of higher peritoneal UA clearance in receiver operating characteristic curve analysis [area under curve (AUC) 0.96; 95% confidence interval [CI], 0.93-0.99]. Peritoneal UA clearance was independently associated with continuous SUA [standardized coefficient (ß), - 0.32; 95% CI, - 6.42 to - 0.75] and hyperuricemia [odds ratio (OR), 0.86; 95% CI, 0.76-0.98] status, only in patients with lower (≤2.74 mL/min/1.73 m2) measured glomerular filtration rate (mGFR). In those patients with lower mGFR, lower albumin level (ß - 0.24; 95%CI - 7.26 to - 0.99), lower body mass index (ß - 0.29; 95%CI - 0.98 to - 0.24), higher transporter status (ß 0.24; 95%CI 0.72-5.88) and greater dialysis dose (ß 0.24; 95%CI 0.26-3.12) were independently associated with continuous peritoneal UA clearance. Furthermore, each 1 kg/m2 decrease in body mass index (OR 0.79; 95% CI 0.63-0.99), each 1 g/dL decrease in albumin level (OR 0.08; 95%CI 0.01-0.47), and each 0.1% increase in average glucose concentration in dialysate (OR 1.56; 95%CI 1.11-2.19) were associated with greater peritoneal UA clearance (> 39.8 L/week/1.73m2). CONCLUSIONS: For patients undergoing PD who exhibited worse residual kidney function, peritoneal clearance dominated in SUA balance. Increasing dialysis dose or average glucose concentration may aid in controlling hyperuricemia in lower transporters.