Organization and Structures for Detection and Monitoring of CKD Across World Countries and Regions: Observational Data From a Global Survey.

RATIONALE & OBJECTIVE: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We report the current global status of CKD detection programs. STUDY DESIGN: A multinational cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders, including nephrologist leaders, policymakers, and patient advocates from 167 countries, participating in the International Society of Nephrology (ISN) survey from June to September 2022. OUTCOME: Structures for the detection and monitoring of CKD, including CKD surveillance systems in the form of registries, community-based detection programs, case-finding practices, and availability of measurement tools for risk identification. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Of all participating countries, 19% (n=31) reported CKD registries, and 25% (n=40) reported implementing CKD detection programs as part of their national policies. There were variations in CKD detection program, with 50% (n=20) using a reactive approach (managing cases as identified) and 50% (n=20) actively pursuing case-finding in at-risk populations. Routine case-finding for CKD in high-risk populations was widespread, particularly for diabetes (n=152; 91%) and hypertension (n=148; 89%). Access to diagnostic tools, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) was limited, especially in low-income (LICs) and lower-middle-income (LMICs) countries, at primary (eGFR: LICs 22%, LMICs 39%, UACR: LICs 28%, LMICs 39%) and secondary/tertiary health care levels (eGFR: LICs 39%, LMICs 73%, UACR: LICs 44%, LMICs 70%), potentially hindering CKD detection. LIMITATIONS: A lack of detailed data prevented an in-depth analysis. CONCLUSIONS: This comprehensive survey highlights a global heterogeneity in the organization and structures (surveillance systems and detection programs and tools) for early identification of CKD. Ongoing efforts should be geared toward bridging such disparities to optimally prevent the onset and progression of CKD and its complications. PLAIN-LANGUAGE SUMMARY: Early detection and management of chronic kidney disease (CKD) is crucial to prevent progression to kidney failure. A multinational survey across 167 countries revealed disparities in CKD detection programs. Only 19% reported CKD registries, and 25% implemented detection programs as part of their national policy. Half used a reactive approach while others actively pursued case-finding in at-risk populations. Routine case-finding was common for individuals with diabetes and hypertension. However, limited access to gold standard tools such as estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), especially in low-income and lower-middle income countries, may hinder CKD detection. A global effort to bridge these disparities is needed to optimally prevent the onset and progression of CKD and its complications.

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.

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.

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.

ISPD Catheter-related Infection Recommendations: 2023 Update.

Peritoneal dialysis (PD) catheter-related infections are important risk factors for catheter loss and peritonitis. The 2023 updated recommendations have revised and clarified definitions and classifications of exit site infection and tunnel infection. A new target for the overall exit site infection rate should be no more than 0.40 episodes per year at risk. The recommendation about topical antibiotic cream or ointment to catheter exit site has been downgraded. New recommendations include clarified suggestion of exit site dressing cover and updated antibiotic treatment duration with emphasis on early clinical monitoring to ascertain duration of therapy. In addition to catheter removal and reinsertion, other catheter interventions including external cuff removal or shaving, and exit site relocation are suggested.

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.

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.

Relationship between gut microbiota and nutritional status in patients on peritoneal dialysis.

Malnutrition is a common complication in the dialysis population, both hemodialysis and peritoneal dialysis (PD). We report our exploratory study on the characteristics of intestinal microbiota and nutritional status in PD patients. The nutritional status of our PD patients were evaluated, and their feces were collected for 16S rRNA gene V3-V4 regions amplification and high-throughput sequencing. The characteristics and differences of microbiota between the well-nourished (W) and malnourished (M) groups were compared. We studied the genera and the operational taxonomic units (OTUs) within the genus of our patients, initially comparing the malnourished and the well- nourished groups and later on reanalyzing the whole group using these OTUs. At the OTU level, 6 bacteria were significantly correlated with the serum albumin level. The abundances of 2 OTUs (OTU208 Lachnospiraceae_incertae_sedi and OTU4 Bacteroides) were more in W group. Meanwhile, 4 OTUs (OTU225 Akkermansia, OTU87 Megasphaera, OTU31 Peptostreptococcaceae_incertae_sedi and OTU168 Clostridium_sensu_strictu) displayed higher abundance among individuals in M group. Notably, the OTU168 Clostridium_sensu_stricto was the only bacteria that significantly correlated with serum albumin (r = - 0.356, P = 0.05), pre-albumin (r = - 0.399, P = 0.02), and SGA (r = 0.458, P = 0.01). The higher the OTU168 Clostridium_sensu_strictu, the lower serum albumin and pre-albumin and a higher score of SGA signifying a worse nutritional status. Our preliminary findings suggested a relationship between the nutrition status and microbiota in PD patients. Our results provide a basis for further exploration of the interactions between malnutrition and intestinal flora in PD patients with potential interventions using probiotics and prebiotics.

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.

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.

Kidney Organ Allocation System: How to Be Fair.

Transplantation is a life-saving medical intervention that unfortunately is constrained by scarcity of available organs. An ideal system for allocating organs should seek to achieve the greatest good for the greatest number of people. It also must be fair and not disadvantage certain populations. However, policies aimed at reducing disparities also must be balanced with considerations of utility (graft outcomes), cost, efficiency, and any adverse effects on organ utilization. Here, we discuss the ethical challenges of creating a fair and equitable organ allocation system, focusing on the principles governing deceased donor kidney transplant waitlists around the world. The kidney organ allocation systems in the United States, Australia, and Hong Kong are used as illustrations.

Introducing Incentives and Reducing Disincentives in Enhancing Deceased Organ Donation and Transplantation.

Despite the effectiveness of solid organ transplantation, progress to close the gap between donor organs and demand remains slow. An organ shortage increases the waiting time for transplant and involves significant costs including patient morbidity and mortality. Against the background of a low deceased organ donation rate, this article discusses the option of introducing incentives and removing disincentives to deceased organ donation. Perspectives from ethics, general public opinion, and the health care profession are examined to ensure a comprehensive appraisal and illustrate different facets of opinion on this complex area. Special cultural and psychosocial considerations in Asia, including the family based consent model, are discussed.

Controversies in Living Kidney Donation.

The most precious gift that can be given is, arguably, a living organ to a person in need of replacement because of failure of that organ. Kidney transplantation remains the best modality of renal replacement therapy and there is an ever-increasing demand for organ donation. The inability of cadaveric organ donation to meet the needs of the increasing numbers of patients on global waiting lists highlights the important needs for alternate sources for kidneys such as those from living kidney donation. However, living donor kidney transplantation has been a focus of intense debate, with ethical concerns and controversies emanating from operating on an individual who does not need, and is put at a small but quantifiable risk from, the surgical intervention. Furthermore, health care systems across the world also are funded with different levels of national and individual affordability, leading to health inequalities for the sick and risks of exploitation for the poor, especially through commercialization of transplantation. This article highlights some of these contemporary ethical concerns and controversies in living organ donation.