Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

Gut permeability, circulating bacterial fragments and measures of congestion in peritoneal dialysis.

Background: Limited data exist on the association between gut permeability, circulating bacterial fragment and volume overload in peritoneal dialysis (PD) patients. We measured circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels, and evaluate their association with the clinical outcomes in PD patients. Methods: This was a single-center prospective study on 108 consecutive incident PD patients. Plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technique and patient survival, secondary outcomes were hospitalization data. Results: There was no significant correlation between plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA)-2ß index, which represents insulin resistance, positively correlated with plasma bacterial DNA (r = 0.421, P < .001) and calprotectin levels (r = 0.362, P = .003), while serum NT-proBNP level correlated with the severity of volume overload and residual renal function. Serum NT-proBNP level was associated with technique survival even after adjusting for confounding factors [adjusted hazard ratio (aHR) 1.030, 95% confidence interval 1.009-1.051]. NT-proBNP level was also associated with patient survival by univariate analysis, but the association became insignificant after adjusting for confounding factors (aHR 1.010, P = .073). Similarly, NT-proBNP correlated with the number of hospitalizations and duration of hospitalization by univariate analysis, but the association became insignificant after adjusting for confounding factors. Conclusion: There was no correlation between markers of gut permeability, circulating bacterial fragments and measures of congestion in PD patients. Bacterial fragments levels and gut permeability are both associated with insulin resistance. Serum NT-proBNP level is associated with the severity of volume overload and technique survival. Further studies are required to delineate the mechanism of high circulating bacterial fragment levels in PD patients.

Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease.

BACKGROUND: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases. METHOD: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months. RESULTS: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance. CONCLUSION: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.

Dietary Micronutrient Intake and Its Relationship with the Malnutrition-Inflammation-Frailty Complex in Patients Undergoing Peritoneal Dialysis.

BACKGROUND: The relationship between dietary patterns and the malnutrition-inflammation-frailty complex in patients undergoing peritoneal dialysis (PD) is currently unknown. Our objective was to measure dietary nutrient intake and evaluate its association with malnutrition, inflammation, and frailty. METHODS: We prospectively recruited adult PD patients. We assessed their dietary nutrient intake using a food frequency questionnaire. Frailty, malnutrition, and inflammation were evaluated by validated Frailty Score (FQ), Subjective Global Assessment (SGA), and Malnutrition-Inflammation Score (MIS). RESULTS: A total of 209 patients were recruited for the study. Among them, 89 patients (42.6%) had an insufficient protein intake, and 104 patients (49.8%) had an insufficient energy intake. Additionally, 127 subjects were identified as frail, characterized by being older (61.9 ± 9.5 vs. 55.6 ± 12.8, p < 0.001), malnourished (SGA: 21.0 ± 2.7 vs. 22.7 ± 3.1, p < 0.001), and having a high inflammation burden (MIS: 10.55 ± 3.72 vs. 7.18 ± 3.61, p < 0.001). There was a significant correlation between dietary zinc intake and body mass index (r = 0.31, p < 0.001), SGA (r = 0.22, p = 0.01), and MIS (r = -0.22, p = 0.01). In the multivariate model, a higher dietary zinc intake predicted a higher SGA (beta 0.03, p = 0.003) and lower FQ (beta -0.38, p < 0.001) and MIS (beta -0.14, p < 0.001), indicating a better nutrition, less frail and inflamed state. A higher dietary zinc intake was also associated with a lower odds of being frail (adjusted odds ratio 0.96, p = 0.009). CONCLUSION: Dietary inadequacy and micronutrient deficiency are common among the PD population. Dietary zinc intake is independently associated with an improved nutrition, physical condition, and reduced inflammatory state.

Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients.

Rationale & Objective: The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among patients receiving PD. Study Design: A pharmacokinetics study in a single center. Patients recruited received 1 week of apixaban at 2.5 mg twice a day to reach steady state. Serial blood samples were then taken before and after the last dose for pharmacokinetics analysis of apixaban. Setting & Participants: Ten stable PD patients with atrial fibrillation in an outpatient setting. Analytical Approach/Outcomes: Pharmacokinetic parameters including the area under the concentration-time curve from time 0 to 12 hours after the last dose of apixaban (AUC0-12), peak concentration, trough level, time to peak apixaban concentration, half-life, and drug clearance were analyzed. Results: There was a wide variation in the range of apixaban concentration across the 10 patients. The AUC0-12 for the PD group was significantly higher than those reported previously for hemodialysis patients or healthy individuals. Three patients had a supratherapeutic peak concentration whereas 2 patients had a supratherapeutic trough level as compared with the pharmacokinetic parameter in healthy individuals taking equivalent therapeutic dosage. Limitations: Small sample size with short study duration limits the ability to ascertain the true bleeding risk and to detect any clinical outcomes. Results may be limited to Asian populations only. Conclusions: A proportion of PD patients had supratherapeutic levels even when the reduced dosage 2.5 mg twice a day was used. Given the large interindividual variation in the drug level, therapeutic drug monitoring should be done if available. Otherwise, one should start the drug at reduced doses with caution and with more frequent clinical monitoring for any signs of bleeding.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

Urinary Long Non-Coding RNA Levels as Biomarkers of Lupus Nephritis.

BACKGROUND: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. METHOD: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. RESULTS: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). CONCLUSIONS: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.

Impact of Weight Gain on the Subsequent Survival of New Peritoneal Dialysis Patients.

Introduction: Obesity at the initiation of dialysis was reported to adversely affect the clinical outcome of peritoneal dialysis (PD) patients, and weight gain is common after started on PD. However, there are few studies on the prognostic implications of weight gain after PD. Methods: We reviewed the change in body weight of 954 consecutive patients during the first 2 years of PD in a single Hong Kong center. Their subsequent clinical outcomes, including patient and technique survival rates, hospitalization, and peritonitis rates, were analyzed. Results: The mean age was 60.3 ± 12.2 years; 535 patients (56.1%) were men, and 504 (52.8%) had diabetes. From 1995-1999 to 2015-2019, the percentage of body weight gain during the first 2 years of PD was 1.0 ± 7.9%, 1.6 ± 7.1%, 1.6 ± 7.2%, 3.9 ± 9.5%, and 4.0 ± 10.3% for each 5-year period, respectively (p for linearity <0.0001). The subsequent 5-year patient survival rates were 29.9%, 43.3%, 40.5%, 43.6%, and 43.3% for patients with weight loss >5%, weight loss 2-5%, weight change with ±2%, weight gain 2-5%, and weight gain >5% during the first 2 years on PD, respectively (log-rank test, p = 0.035). With multivariable Cox regression model to adjust for clinical confounders, weight loss >5% during the first 2 years of PD was associated with a worse patient survival rate subsequently (adjusted hazard ratio 4.118, 95% confidence interval 1.040-16.313, p = 0.044), while weight gain was not associated with subsequent patient survival. Weight change during the first 2 years of PD does not appear to affect subsequent technique survival, hospitalization, decline in residual renal function, or peritonitis rate. Discussion and Conclusions: Weight gain is common during the first 2 years of PD, but weight gain does not appear to have any significant impact on the subsequent outcome. In contrast, weight loss >5% was significantly associated with worse patient survival subsequently.

Plasma vaspin levels and clinical outcome in incident peritoneal dialysis patients.

BACKGROUND: Vaspin is an adipokine that regulates glucose and lipid metabolism. Plasma vaspin level is increased in chronic kidney disease but decreased in hemodialysis patients. However, plasma vaspin level in peritoneal dialysis (PD) patients, as well as its prognostic role, has not been studied. METHODS: We recruited 146 incident PD patients. Their baseline plasma vaspin levels, body anthropometry, the profile of insulin resistance, bioimpedance spectroscopy parameters, dialysis adequacy, and nutritional indices were measured. They were followed for up to 5 years for survival analysis. RESULTS: The average age was 58.4 ± 11.8 years; 96 patients (65.8%) were men, and 90 (61.6%) had diabetes. The median vaspin level was 0.18 ng/dL (interquartile range [IQR] 0.11 to 0.30 ng/dL). Plasma vaspin level did not have a significant correlation with adipose tissue mass or baseline insulin level. However, plasma vaspin level had a modest correlation with the change in insulin resistance, as represented by the HOMA-IR index, in non-diabetic patients (r = -0.358, p = 0.048). Although the plasma vaspin level quartile did not have a significant association with patient survival in the entire cohort, it had a significant interaction with diabetic status (p < 0.001). In nondiabetic patients, plasma vaspin level quartile was an independent predictor of patient survival after adjusting for confounding clinical factors (adjusted hazard ratio 2.038, 95% confidence interval 1.191-3.487, p = 0.009), while the result for diabetic patients was not significant. CONCLUSIONS: Plasma vaspin level quartile had a significant association with patient survival in non-diabetic PD patients. Baseline plasma vaspin level also had a modest inverse correlation with the subsequent change in the severity of insulin resistance, but the exact biological role of vaspin deserves further studies.

Intrarenal and Urinary Glycogen Synthase Kinase-3 Beta Levels in Diabetic and Nondiabetic Chronic Kidney Disease.

BACKGROUND: Renal glycogen synthase kinase-3 beta (GSK3ß) overactivity has been associated with a diverse range of kidney diseases. GSK3ß activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3ß levels in DKD and nondiabetic chronic kidney disease (CKD). METHODS: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3ß levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. RESULTS: DKD group had higher intrarenal and urinary GSK3ß levels than nondiabetic CKD (p < 0.0001 for both), but their urinary GSK3ß mRNA levels were similar. Urinary p-GSK3ß level is statistically significantly correlated with the baseline estimated glomerular filtration rate (eGFR), but urinary GSK3ß level by ELISA, its mRNA level, the p-GSK3ß level, or the p-GSK3ß/GSK3ß ratio had no association with dialysis-free survival or the slope of eGFR decline. In contrast, the intrarenal pY216-GSK3ß/total GSK3ß ratio significantly correlated with the slope of eGFR decline (r = -0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors. CONCLUSION: Intrarenal and urinary GSK3ß levels were increased in DKD. The intrarenal pY216-GSK3ß/total GSK3ß ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3ß in kidney diseases deserve further studies.

Omentin-1 Levels and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients. Study Design: Retrospective analysis of prospective cohort. Setting & Participants: 152 incident PD patients. Predictors: Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression. Outcomes: Patient survival, technique survival, hospital admission, and duration of stay. Analytical Approach: Time-to-event survival analyses; linear regression for hospitalization. Results: The mean age was 58.4 ± 11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival (P = 0.92) or technique survival (P = 0.83) but had a modest correlation with a lower number of hospital admissions (P = 0.07) and shorter duration of hospital stay (P = 0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (ß, -0.13; 95% CI, -0.26 to -0.002; P = 0.05) and shorter hospitalization duration (ß, -0.20; 95% CI, -0.38 to -0.02; P = 0.03). Limitations: Observational study with baseline measures only. Conclusions: Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients.

Epidemiology and Outcomes of Hypernatraemia in Patients with COVID-19-A Territory-Wide Study in Hong Kong.

BACKGROUND: Dysnatraemias are commonly reported in COVID-19. However, the clinical epidemiology of hypernatraemia and its impact on clinical outcomes in relation to different variants of SARS-CoV-2, especially the prevailing Omicron variant, remain unclear. METHODS: This was a territory-wide retrospective study to investigate the clinical epidemiology and outcomes of COVID-19 patients with hypernatraemia at presentation during the period from 1 January 2020 to 31 March 2022. The primary outcome was 30-day mortality. Key secondary outcomes included rates of hospitalization and ICU admission, and costs of hospitalization. RESULTS: In this study, 53,415 adult COVID-19 patients were included for analysis. Hypernatraemia was observed in 2688 (5.0%) patients at presentation, of which most cases (99.2%) occurred during the local "5th wave" dominated by the Omicron BA.2 variant. Risk factors for hypernatraemia at presentation included age, institutionalization, congestive heart failure, dementia, higher SARS-CoV-2 Ct value, white cell count, C-reactive protein and lower eGFR and albumin levels (p < 0.001 for all). Patients with hypernatraemia showed significantly higher 30-day mortality (32.0% vs. 5.7%, p < 0.001) and longer lengths of stay (12.9 ± 10.9 vs. 11.5 ± 12.1 days, p < 0.001) compared with those with normonatraemia. Multivariate analysis revealed hypernatraemia at presentation as an independent predictor for 30-day mortality (aHR 1.32, 95% CI 1.14-1.53, p < 0.001) and prolonged hospital stays (OR 1.55, 95% CI 1.17-2.05, p = 0.002). CONCLUSIONS: Hypernatraemia is common among COVID-19 patients, especially among institutionalized older adults with cognitive impairment and other comorbidities during large-scale outbreaks during the Omicron era. Hypernatraemia is associated with unfavourable outcomes and increased healthcare utilization.

From MIA to FIFA: The vicious matrix of frailty, inflammation, fluid overload and atherosclerosis in peritoneal dialysis.

Cardiovascular disease (CVD) is a major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Two decades ago, the common co-existence of malnutrition and systemic inflammation PD patients with atherosclerosis and CVD led to the proposed terminology of 'malnutrition-inflammation-atherosclerosis (MIA) syndrome'. Although the importance of malnutrition is well accepted, frailty represents a more comprehensive assessment of the physical and functional capability of the patient and encompasses the contributions of sarcopenia (a key component of malnutrition), obesity, cardiopulmonary as well as neuropsychiatric impairment. In recent years, it is also increasingly recognized that fluid overload is not only the consequence but also play an important role in the pathogenesis of CVD. Moreover, fluid overload is closely linked with the systemic inflammatory status, presumably by gut oedema, gastrointestinal epithelial barrier dysfunction and leakage of bacterial fragments to the systemic circulation. There are now a wealth of published evidence to show intricate relations between frailty, inflammation, fluid overload and atherosclerotic disease in patients with chronic kidney disease (CKD) and those on PD, a phenomenon that we propose the term 'FIFA complex'. In this system, frailty and atherosclerotic disease may be regarded as two patient-oriented outcomes, while inflammation and fluid overload are two inter-connected pathogenic processes. However, there remain limited data on how the treatment of one component affect the others. It is also important to define how treatment of fluid overload affect the systemic inflammatory status and to develop effective anti-inflammatory strategies that could alleviate atherosclerotic disease and frailty.

Circulating and Adipose Tissue Adiponectin Level and Outcomes in Incident Peritoneal Dialysis Patients.

Rationale & Objective: Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients. Study Design: Retrospective analysis of a prospective observational study. Setting & Participants: 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls. Predictors: Plasma adiponectin level and its adipose tissue mRNA expression. Outcomes: Body build and composition, patient and technique survival. Analytical Approach: Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis. Results: The median plasma adiponectin level was 31.98 µg/mL (IQR, 16.81-49.49 µg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression (r = 0.40, P < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride (r = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P < 0.001 for all), as well as serum insulin level (r = -0.24, P = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival. Limitations: Observational study, single center, single baseline measurement. Conclusions: Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD.

Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy Study.

Rationale & Objective: Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. Study Design: Observational cohort. Setting & Participants: 118 consecutive patients with biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls. Predictors: Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting. Outcomes: Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months. Analytical Approach: Correlation and time to event analysis. Results: Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level (r = 0.562, P < 0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P = 0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P = 0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline (r = 0.238, P = 0.01) but did not predict dialysis-free survival. Limitations: Small sample size; lack of serial measurement. Conclusions: Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use.

Predictors and prognostic significance of persistent fluid overload: A longitudinal study in Chinese peritoneal dialysis patients.

BACKGROUND: Cross-sectional studies showed that fluid overload (FO) measured by bioimpedance spectroscopy (BIS) predicted adverse outcomes in patients on peritoneal dialysis (PD). We aimed to describe the longitudinal change in volume status in Chinese PD patients and determine its relation with clinical outcomes. METHODS: We performed a single-centre, retrospective analysis of all PD patients who underwent repeated BIS from 2010 to 2015. FO was defined by relative hydration index (RHI; volume of overhydration adjusted by extracellular water >7%). Variability of volume status (VVS) was denoted by the standard deviation of all RHI. The association of time-averaged RHI and VVS on patient and technique survival was explored by a competing risk model. RESULTS: A total of 269 patients were followed for a median of 47.1 months. Mean time-averaged RHI was 17.6 ± 10.2%. Multivariable mixed linear regression revealed that RHI was significantly associated with diabetes, time-varying systolic blood pressure, and inversely with time-varying albumin level, lean tissue index and fat tissue index (p <0.0001 for all). Time-averaged RHI independently predicted patient survival (subdistribution hazard ratio (SHR) 1.05, 95% CI 1.03-1.07, p <0.0001) and technique survival (SHR 1.04, 95% CI 1.02-1.06, p <0.0001), whereas VVS did not. The mortality risk for patients with persistent FO was consistently higher than the corresponding risk estimated from baseline FO of the same extent. CONCLUSIONS: Persistent FO was a strong predictor of patient and technique failure. Repeated bioimpedance measurements to monitor volume status may provide additional prognostic information in PD patients.

SGLT2 inhibitors reduce adverse kidney and cardiovascular events in patients with advanced diabetic kidney disease: A population-based propensity score-matched cohort study.

BACKGROUND: There were limited data on the efficacy and safety profile on use of sodium-glucose co-transporter 2 receptor (SGLT2) inhibitors in diabetic patients with advanced chronic kidney disease (CKD). We aimed to evaluate the efficacy, in terms of improvement in glycemic profile, kidney function, prevention of adverse kidney and cardiovascular events, and the safety profile of SGLT2 inhibitors in a group of diabetic patients at CKD stage 3B-5 from a real-world population-based cohort. METHODS: We performed a retrospective observational cohort study of type 2 diabetic patients at CKD stage 3B-5 who received SGLT2 inhibitors as compared to control from 1 January 2015 through 31 December 2021. Propensity score assignment by logistic regression and matching with control by the nearest score at 1:3 ratio was done. All patients were followed for 1 year. Outcomes were kidney-related adverse events and major adverse cardiovascular events (MACE), change in estimated glomerular filtration rate (eGFR), glycemic control, and side effects profiling. RESULTS: We analyzed 1,450 SGLT2 inhibitor users. They had significantly lower rates of kidney-related adverse events (7.7 % versus 24.1 %, p < 0.001) and MACE (9.6 % versus 15.1 %, p < 0.001) as compared to control group. Their eGFR also significantly improved (0.4 ± 9.3 versus -5.5 ± 10.6 ml/min/1.73 m2, p < 0.001). These patients also had a greater reduction in HbA1c (-0.40 ± 1.13 versus -0.04 ± 1.47 %, p < 0.001), and insulin requirement (-8.8 ± 35.2 versus 4.1 ± 19.4 units/day, p < 0.001). After adjusting for confounders, SGLT2 inhibitors protected against kidney-related adverse events (odds ratio [OR] 0.48, 95 % confidence interval [CI] 0.33 - 0.71, p < 0.001) and MACE (OR 0.47, 95 % CI 0.37 - 0.60, p < 0.001). Apart from a marginally higher rate of fungal urinary tract infection (0.08 ± 0.66 versus 0.03 ± 0.23 episodes per year, p < 0.001), SGLT2 inhibitor use was not associated with other side effects. CONCLUSIONS: SGLT2 inhibitor improved kidney function, glycemic profile, and reduced adverse kidney-related and cardiovascular events in diabetic patients with advanced CKD.

Nutritional Assessments by Bioimpedance Technique in Dialysis Patients.

Bioelectrical impedance analysis (BIA) has been extensively applied in nutritional assessments on the general population, and it is recommended in establishing the diagnosis of malnutrition and sarcopenia. The bioimpedance technique has become a promising modality through which to measure the whole-body composition in dialysis patients, where the presence of subclinical volume overload and sarcopenic obesity may be overlooked by assessing body weight alone. In the past two decades, bioimpedance devices have evolved from applying a single frequency to a range of frequencies (bioimpedance spectroscopy, BIS), in which the latter is incorporated with a three-compartment model that allows for the simultaneous measurement of the volume of overhydration, adipose tissue mass (ATM), and lean tissue mass (LTM). However, clinicians should be aware of common potential limitations, such as the adoption of population-specific prediction equations in some BIA devices. Inherent prediction error does exist in the bioimpedance technique, but the extent to which this error becomes clinically significant remains to be determined. Importantly, reduction in LTM has been associated with increased risk of frailty, hospitalization, and mortality in dialysis patients, whereas the prognostic value of ATM remains debatable. Further studies are needed to determine whether modifications of bioimpedance-derived body composition parameters through nutrition intervention can result in clinical benefits.

Excessive risk and poor outcome of hospital-acquired peritoneal dialysis-related peritonitis.

Background: Peritoneal dialysis (PD) is a home-based renal replacement therapy. Since hospital staff are not often familiar with PD and its complications, PD patients may have an excess risk of developing PD-related peritonitis during hospital admission for unrelated reasons, and the outcome may be affected. Methods: We reviewed 371 episodes of hospital-acquired PD peritonitis in our center from 2000 to 2019. Their clinical characteristics and outcomes were compared with 825 episodes that required hospital admission and 1964 episodes that were treated as outpatient. Results: Hospitalized PD patients had a significantly higher risk of developing peritonitis than outpatients [incident rate ratio 4.41 (95% confidence interval 3.95-4.91]. Hospital-acquired peritonitis episodes were more commonly culture negative. Bacterial isolates from the hospital-acquired episodes were more likely resistant to ceftazidime (P < .0001) than the other groups. The primary response rate, complete cure rate and overall mortality of the hospital-acquired episodes were 66.6%, 62.0%, and 23.2%, respectively, all worse than episodes that developed outside the hospital (P < .0001 for all). Conclusion: PD patients admitted to the hospital had a 4-fold increase in the risk of developing peritonitis. Hospital-acquired peritonitis episodes were more likely culture negative and resistant to antibiotics. They also had a lower primary response rate, a lower complete cure rate and higher mortality than episodes that developed outside the hospital.

Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis.

BACKGROUND: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. METHODS: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. RESULTS: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57-3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08-2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80-13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13-12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006-0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02-0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35-50.5, p = 0.02). CONCLUSION: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.