Capacity for the management of kidney failure in the International Society of Nephrology Oceania and South East Asia (OSEA) region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

The International Society of Nephrology (ISN) region of Oceania and South East Asia (OSEA) is a mix of high- and low-income countries, with diversity in population demographics and densities. Three iterations of the ISN-Global Kidney Health Atlas (GKHA) have been conducted, aiming to deliver in-depth assessments of global kidney care across the spectrum from early detection of CKD to treatment of kidney failure. This paper reports the findings of the latest ISN-GKHA in relation to kidney-care capacity in the OSEA region. Among the 30 countries and territories in OSEA, 19 (63%) participated in the ISN-GKHA, representing over 97% of the region's population. The overall prevalence of treated kidney failure in the OSEA region was 1203 per million population (pmp), 45% higher than the global median of 823 pmp. In contrast, kidney replacement therapy (KRT) in the OSEA region was less available than the global median (chronic hemodialysis, 89% OSEA region vs. 98% globally; peritoneal dialysis, 72% vs. 79%; kidney transplantation, 61% vs. 70%). Only 56% of countries could provide access to dialysis to at least half of people with incident kidney failure, lower than the global median of 74% of countries with available dialysis services. Inequalities in access to KRT were present across the OSEA region, with widespread availability and low out-of-pocket costs in high-income countries and limited availability, often coupled with large out-of-pocket costs, in middle- and low-income countries. Workforce limitations were observed across the OSEA region, especially in lower-middle-income countries. Extensive collaborative work within the OSEA region and globally will help close the noted gaps in kidney-care provision.

Chronic kidney disease and the global public health agenda: an international consensus.

Early detection is a key strategy to prevent kidney disease, its progression and related complications, but numerous studies show that awareness of kidney disease at the population level is low. Therefore, increasing knowledge and implementing sustainable solutions for early detection of kidney disease are public health priorities. Economic and epidemiological data underscore why kidney disease should be placed on the global public health agenda - kidney disease prevalence is increasing globally and it is now the seventh leading risk factor for mortality worldwide. Moreover, demographic trends, the obesity epidemic and the sequelae of climate change are all likely to increase kidney disease prevalence further, with serious implications for survival, quality of life and health care spending worldwide. Importantly, the burden of kidney disease is highest among historically disadvantaged populations that often have limited access to optimal kidney disease therapies, which greatly contributes to current socioeconomic disparities in health outcomes. This joint statement from the International Society of Nephrology, European Renal Association and American Society of Nephrology, supported by three other regional nephrology societies, advocates for the inclusion of kidney disease in the current WHO statement on major non-communicable disease drivers of premature mortality.

Precision Medicine in Erythropoietin Deficiency and Treatment Resistance: A Novel Approach to Management of Anaemia in Chronic Kidney Disease.

The study of anaemia is a well-developed discipline where the concepts of precision medicine have, in part, been researched extensively. This review discusses the treatment of erythropoietin (EPO) deficiency anaemia and resistance in cases of chronic kidney disease (CKD). Traditionally, erythropoietin-stimulating agents (ESAs) and iron supplementation have been used to manage anaemia in cases of CKD. However, these treatments pose potential risks, including cardiovascular and thromboembolic events. Newer treatments have emerged to address these risks, such as slow-release and low-dosage intravenous iron, oral iron supplementation, and erythropoietin-iron combination therapy. Another novel approach is the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This review highlights the need for precision medicine targeting the genetic components of EPO deficiency anaemia in CKD and discusses individual variability in genes such as the erythropoietin gene (EPO), the interleukin-ß gene (IL-ß), and the hypoxia-inducible factor gene (HIF). Pharmacogenetic testing aims to provide targeted therapies and interventions that are tailored to the specific characteristics of an individual, thus optimising treatment outcomes and minimising resistance and adverse effects. This article concludes by suggesting that receptor modification has the potential to revolutionise the treatment outcomes of patients with erythropoietin deficiency anaemia through the integration of the mentioned approach.

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.

Current Insights on Dyslipidaemia Management for Prevention of Atherosclerotic Cardiovascular Disease: A Malaysian Perspective.

Dyslipidaemia is highly prevalent in the Malaysian population and is one of the main risk factors for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) is recognised as the primary target of lipid-lowering therapy to reduce the disease burden of ASCVD. Framingham General CV Risk Score has been validated in the Malaysian population for CV risk assessment. The Clinical Practice Guidelines (CPG) on the management of dyslipidaemia were last updated in 2017. Since its publication, several newer randomised clinical trials have been conducted with their results published in research articles and compared in meta-analysis. This underscores a need to update the previous guidelines to ensure good quality care and treatment for the patients. This review summarises the benefits of achieving LDL-C levels lower than the currently recommended target of < 1.8mmol/L without any safety concerns. In most high and very high-risk individuals, statins are the first line of therapy for dyslipidaemia management. However, certain high-risk individuals are not able to achieve the LDL-C goal as recommended in the guideline even with high-intensity statin therapy. In such individuals, lower LDL-C levels can be achieved by combining the statins with non-statin agents such as ezetimibe and PCSK9 inhibitors. Emerging non-statin lipid-lowering therapies and challenges in dyslipidaemia management are discussed in this article. The review also summarises the recent updates on local and international guidelines for dyslipidaemia management.

Urinary Tract Infection Prevention and Treatment.

Urinary tract infections are the most common bacterial infections encountered by health care professionals. In women, the lifetime incidence of urinary tract infections may be up to 40% to 50%, of whom a further 40% may have recurrent infections. Urinary tract infections are associated with significant morbidity and potential mortality-they may be complicated by frequent recurrences, kidney damage, sepsis, and preterm birth, as well as collateral damage of antimicrobial use, which includes Clostridium difficile colitis and selection of drug-resistant organisms. There are personal costs such as reduced quality of life in patients affected by recurrent urinary tract infections, and societal impacts resulting from absenteeism and health care costs. In this review, we discuss the definitions and classifications, pathogenesis, and current principles of management and prevention of urinary tract infections. Semin Nephrol 43:x-xx © 2023 Elsevier Inc. All rights reserved.

Effectiveness of a Nutritional Mobile Application for Management of Hyperphosphatemia in Patients on Hemodialysis: A Multicenter Open-Label Randomized Clinical Trial.

This study aims to determine the effectiveness of a phosphate mobile app (PMA), MyKidneyDiet-Phosphate Tracker ©2019, on hemodialysis (HD) patients with hyperphosphatemia. A multicenter, open-label, randomized controlled trial design allowed randomization of patients with hyperphosphatemia to either the usual care group (UG; receiving a single dietitian-led session with an education booklet) or the PMA group (PG). Thirty-three patients in each intervention group completed the 12-week study. Post-intervention, serum phosphorus levels were reduced in both groups (PG: −0.25 ± 0.42 mmol/L, p = 0.001; UG: −0.23 ± 0.33 mmol/L, p < 0.001) without any treatment difference (p > 0.05). Patients in both groups increased their phosphate knowledge (PG: 2.18 ± 3.40, p = 0.001; UG: 2.50 ± 4.50, p = 0.003), without any treatment difference (p > 0.05). Dietary phosphorus intake of both groups was reduced (PG: −188.1 ± 161.3 mg/d, p < 0.001; UG: −266.0 ± 193.3 mg/d, p < 0.001), without any treatment difference (p > 0.05). The serum calcium levels of patients in the UG group increased significantly (0.09 ± 0.20 mmol/L, p = 0.013) but not for the PG group (−0.03 ± 0.13 mmol/L, p = 0.386), and the treatment difference was significant (p = 0.007). As per phosphate binder adherence, both groups reported a significant increase in Morisky Medication Adherence Scale scores (PG: 1.1 ± 1.2, p < 0.001; UGa: 0.8 ± 1.5, p = 0.007), without any treatment difference (p > 0.05). HD patients with hyperphosphatemia using the PMA achieved reductions in serum phosphorus levels and dietary phosphorus intakes along with improved phosphate knowledge and phosphate binder adherence that were not significantly different from a one-off dietitian intervention. However, binder dose adjustment with meal phosphate content facilitated by the PMA allowed stability of corrected calcium levels, which was not attained by UC patients whose binder dose was fixed.

Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.

A Mobile App for Triangulating Strategies in Phosphate Education Targeting Patients with Chronic Kidney Disease in Malaysia: Development, Validation, and Patient Acceptance.

Hyperphosphatemia afflicts end-stage chronic kidney disease (CKD) patients, contributing to comorbidities and mortality. Management strategies are dialysis, phosphate binder, and limiting dietary phosphate intake, but treatment barriers are poor patient compliance and low health literacy arising from low self-efficacy and lack of educational resources. This study describes developing and validating a phosphate mobile application (PMA). The PMA development based on the seven-stage Precaution Adoption Process Model prioritized titrating dietary phosphate intake with phosphate binder dose supported by educational videography. Experts (n = 13) first evaluated the PMA for knowledge-based accuracy, mobile heuristics, and clinical value. Adult HD patients validated the improved PMA using the seven-point mHealth App Usability Questionnaire (MAUQ). Patient feedback (n = 139) indicated agreement for ease of use (69.2%), interface and satisfaction (69.0%), and usefulness (70.1%), while 72.7% said they would recommend this PMA. The expectation confirmation for 25 PMA features ranged from 92.1% (lifestyle) up to 100.0% (language option); and the utilization rate of each feature varied from 21.6% (goal setting and feature-based log) to 91.4% (information on dietary phosphate and phosphate binder). The Conclusions: MyKidneyDiet-Phosphate Tracker PMA was acceptable to adult Malaysian HD patients as part of clinical phosphate management in low-resource settings.

First Successful Kidney Transplantation After Hematopoeitic Stem Cell Transplantation in Malaysia.

Promising outcomes of kidney transplantation following hematopoeitic stem cell transplantation has been reported. Data from some centers have demonstrated stable graft function without long term immunosuppression. We present our experience with the first successful case in Malaysia. This is a 21-year-old man who had acute myeloid leukemia, received stem cell transplant from his younger brother 8 years prior, underwent kidney transplantation from the same donor, and had an excellent 1-year graft function post-transplant. As the post-transplant genetic analysis revealed full chimerism, his immunosuppression regimen can be tapered to minimal doses safely. The concept of immunotolerance is now widely studied and could potentially be the curative strategy for patients who develop end stage kidney disease after hematopoeitic stem cell transplantation.

Current clinical practice in adapted automated peritoneal dialysis (aAPD)-A prospective, non-interventional study.

Adapted automated peritoneal dialysis (aAPD), comprising a sequence of dwells with different durations and fill volumes, has been shown to enhance both ultrafiltration and solute clearance compared to standard peritoneal dialysis with constant time and volume dwells. The aim of this non-interventional study was to describe the different prescription patterns used in aAPD in clinical practice and to observe outcomes characterizing volume status, dialysis efficiency, and residual renal function over 1 year. Prevalent and incident, adult aAPD patients were recruited during routine clinic visits, and aAPD prescription, volume status, residual renal function and laboratory data were documented at baseline and every quarter thereafter for 1 year. Treatments were prescribed according to the nephrologist's medical judgement in accordance with each center's clinical routine. Of 180 recruited patients, 160 were analyzed. 27 different aAPD prescription patterns were identified. 79 patients (49.4%) received 2 small, short dwells followed by 3 long, large dwells. During follow-up, volume status changed only marginally, with visit mean values ranging between 1.59 (95% confidence interval: 1.19; 1.99) and 1.97 (1.33; 2.61) L. Urine output and creatinine clearance decreased significantly, accompanied by reductions in ultrafiltration and Kt/V. 25 patients (15.6%) received a renal transplant and 15 (9.4%) were changed to hemodialysis. Options for individualization offered by aAPD are actually used in practice for optimized treatment. Changes observed in renal function and dialysis efficiency measures reflect the natural course of chronic kidney disease. No safety events were observed during the study period.

Anemia Management in Peritoneal Dialysis: Perspectives From the Asia Pacific Region.

Anemia is an important complication in patients with chronic kidney disease. Peritoneal dialysis (PD) is one of the most common modalities of kidney replacement therapy for patients with end-stage kidney disease. PD is particularly prevalent in the Asian Pacific region. Among the different countries and regions, including mainland China, Hong Kong, Japan, Malaysia, Singapore, South Korea, and Thailand, PD accounts for 2.8% to 74.6% of the dialysis population. In addition, 82% to 96% of the PD populations from these countries and regions are receiving erythropoiesis-stimulating agents (ESAs). Asian Pacific countries and regions follow the latest KDIGO (Kidney Disease: Improving Global Outcomes) guidelines for the initiation of treatment of anemia in PD patients. The types of ESAs commonly used include shorter-acting (epoetin alfa and beta) and longer-acting agents, including darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. The most commonly used ESAs in Mainland China, Malaysia, Singapore, and Thailand are the shorter-acting agents, whereas in Hong Kong, Japan, and South Korea, longer-acting ESAs are most common. Oral iron therapy is still the most commonly used iron supplement. The route and dosage of iron administration in PD patients requires more research studies. With the introduction of oral hypoxia-inducible factor prolyl hydroxylase inhibitors into clinical use, the landscape of treatment of anemia in the PD population in the Asia Pacific region may change in the coming years.

Effects of CYP3A5 Polymorphism on Rapid Progression of Chronic Kidney Disease: A Prospective, Multicentre Study.

Personalised medicine is potentially useful to delay the progression of chronic kidney disease (CKD). The aim of this study was to determine the effects of CYP3A5 polymorphism in rapid CKD progression. This multicentre, observational, prospective cohort study was performed among adult CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, who had ≥4 outpatient, non-emergency eGFR values during the three-year study period. The blood samples collected were analysed for CYP3A5*3 polymorphism. Rapid CKD progression was defined as eGFR decline of >5 mL/min/1.73 m2/year. Multiple logistic regression was then performed to identify the factors associated with rapid CKD progression. A total of 124 subjects consented to participate. The distribution of the genotypes adhered to the Hardy-Weinberg equilibrium (X2 = 0.237, p = 0.626). After adjusting for potential confounding factors via multiple logistic regression, the factors associated with rapid CKD progression were CYP3A5*3/*3 polymorphism (adjusted Odds Ratio [aOR] 4.190, 95% confidence interval [CI]: 1.268, 13.852), adjustments to antihypertensives, young age, dyslipidaemia, smoking and use of traditional/complementary medicine. CKD patients should be monitored closely for possible factors associated with rapid CKD progression to optimise clinical outcomes. The CYP3A5*3/*3 genotype could potentially be screened among CKD patients to offer more individualised management among these patients.

Factors associated with the frequency of antihypertensive drug adjustments in chronic kidney disease patients: a multicentre, 2-year retrospective study.

Background Optimum antihypertensive drug effect in chronic kidney disease is important to mitigate disease progression. As frequent adjustments to antihypertensive drugs might lead to problems that may affect their effectiveness, the modifiable factors leading to frequent adjustments of antihypertensive drugs should be identified and addressed. Objective This study aims to identify the factors associated with frequent adjustments to antihypertensive drugs among chronic kidney disease patients receiving routine nephrology care. Setting Nephrology clinics at two Malaysian tertiary hospitals. Method This multi-centre, retrospective cohort study included adult patients under chronic kidney disease clinic follow-up. Demographic data, clinical information, laboratory data and medication characteristics from 2018 to 2020 were collected. Multiple logistic regression was used to identify the factors associated with frequent adjustments to antihypertensive drugs (≥ 1 per year). Main outcome measure Frequent adjustments to antihypertensive drugs. Results From 671 patients included in the study, 219 (32.6%) had frequent adjustments to antihypertensive drugs. Frequent adjustment to antihypertensive drugs was more likely to occur with follow-ups in multiple institutions (adjusted Odds Ratio [aOR] 1.244, 95% confidence interval [CI] 1.012, 1.530), use of traditional/complementary medicine (aOR 2.058, 95% CI 1.058, 4.001), poor medication adherence (aOR 1.563, 95% CI 1.037, 2.357), change in estimated glomerular filtration rate (aOR 0.970, 95% CI 0.951, 0.990), and albuminuria categories A2 (aOR 2.173, 95% CI 1.311, 3.603) and A3 (aOR 2.117, 95% CI 1.349, 3.322), after controlling for confounding factors. Conclusion This work highlights the importance of close monitoring of patients requiring initial adjustments to antihypertensive drugs. Antihypertensive drug adjustments may indicate events that could contribute to poorer outcomes in the future.

Clinical effectiveness of a Malaysian-manufactured CAPD product: A randomised trial.

BACKGROUND: We compared the clinical effectiveness of a new peritoneal dialysis (PD) product with polyvinyl chloride-containing tubing (Stay Safe Link®, SSL) with the plastic-free alternative (Stay Safe®, STS) in patients on continuous ambulatory peritoneal dialysis (CAPD). METHOD: A multicentre, parallel, randomised, controlled, open-label, non-inferiority trial was conducted. Adult patients receiving CAPD were randomised in a 1:1 ratio to SSL or STS. The primary outcome was the rate of peritonitis after 1 year of follow-up. RESULTS: A total of 472 subjects were randomised (SSL, n = 233; STS, n = 239). One subject in each group was excluded from the analysis as they withdrew consent before the first dialysis dose. Four hundred and seventy subjects (SSL, n = 232; STS, n = 238) were included in the modified intention-to-treat analysis. Non-inferiority between two groups was established as no significant difference was found in peritonitis rate (incident rate ratio: 0.91, 95% CI: 0.65-1.28). No significant difference was detected in weekly Kt/V (p = 0.58) and creatinine clearance (p = 0.55). However, the average ultrafiltration volume was significantly lower in SSL, with a mean difference of 93 ml (p < 0.01). SSL also demonstrated a 2.57-times higher risk of device defect than STS (95% CI: 1.77-3.75). CONCLUSION: SSL was non-inferior in peritonitis rate compared to plastic-free STS over 1 year in patients requiring CAPD. There was no difference in the delivered dialysis dose, but there was a higher rate of device defects with SSL.

Muscle Status Response to Oral Nutritional Supplementation in Hemodialysis Patients With Protein Energy Wasting: A Multi-Center Randomized, Open Label-Controlled Trial.

Background: Muscle wasting, observed in patients with end-stage kidney disease and protein energy wasting (PEW), is associated with increased mortality for those on hemodialysis (HD). Oral nutritional supplementation (ONS) and nutrition counseling (NC) are treatment options for PEW but research targeting muscle status, as an outcome metric, is limited. Aim: We compared the effects of combined treatment (ONS + NC) vs. NC alone on muscle status and nutritional parameters in HD patients with PEW. Methods: This multi-center randomized, open label-controlled trial, registered under ClinicalTrials.gov (Identifier no. NCT04789031), recruited 56 HD patients identified with PEW using the International Society of Renal Nutrition and Metabolism criteria. Patients were randomly allocated to intervention (ONS + NC, n = 29) and control (NC, n = 27) groups. The ONS + NC received commercial renal-specific ONS providing 475 kcal and 21.7 g of protein daily for 6 months. Both groups also received standard NC during the study period. Differences in quadriceps muscle status assessed using ultrasound (US) imaging, arm muscle area and circumference, bio-impedance spectroscopy (BIS), and handgrip strength (HGS) methods were analyzed using the generalized linear model for repeated measures. Results: Muscle indices as per US metrics indicated significance (p < 0.001) for group × time interaction only in the ONS + NC group, with increases by 8.3 and 7.7% for quadriceps muscle thickness and 4.5% for cross-sectional area (all p < 0.05). This effect was not observed for arm muscle area and circumference, BIS metrics and HGS in both the groups. ONS + NC compared to NC demonstrated increased dry weight (p = 0.039), mid-thigh girth (p = 0.004), serum prealbumin (p = 0.005), normalized protein catabolic rate (p = 0.025), and dietary intakes (p < 0.001), along with lower malnutrition-inflammation score (MIS) (p = 0.041). At the end of the study, lesser patients in the ONS + NC group were diagnosed with PEW (24.1%, p = 0.008) as they had achieved dietary adequacy with ONS provision. Conclusion: Combination of ONS with NC was effective in treating PEW and contributed to a gain in the muscle status as assessed by the US, suggesting that the treatment for PEW requires nutritional optimization via ONS.

Clinical and genetic markers of erythropoietin deficiency anemia in chronic kidney disease (predialysis) patients.

Aim: To determine the clinical and genetic markers associated with erythropoietin deficiency anemia in predialysis individuals. Materials & methods: Patients were categorized into cases and control group. Demographic characteristics and clinical parameters were obtained from medical record review and serum EPO and ferritin were obtained with ELISA. HIF-1α (rs2057482), IL-1ß (rs1143627) and EPO (rs1617640) gene polymorphism were genotyped. Results: Female gender, glomerular filtration rate, treatment with hematinics, anticoagulant and diuretic were strong predictors of EPO-deficient anemia in predialysis chronic kidney disease patients. Genetic polymorphism in the HIF-1α recessive model was associated with non-EPO-deficiency, followed by EPO recessive allele associated with low-serum erythropoietin and IL-1ß recessive model with low hemoglobin level. Conclusion: EPO-deficiency anemia can be diagnosed more conveniently in the presence of biomarkers.