Cost-effectiveness of sodium zirconium cyclosilicate for advanced chronic kidney patients in Singapore.

INTRODUCTION: Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin-angiotensin-aldosterone system inhibitors (RAASi). This study evaluated the cost-effectiveness of a newly developed anti-HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. METHODS: We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non-fatal events. Effectiveness data was derived from ZS-004 and ZS-005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality-adjusted life years (QALYs) of each HK treatment, and the incremental cost-effectiveness ratio of SZC. RESULTS: SZC demonstrated cost-effectiveness with an incremental cost-effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness-to-pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost-effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. CONCLUSION: This study establishes the cost-effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation.

Rapid point-of-care test for diagnosis of peritonitis in peritoneal dialysis patients.

BACKGROUND: Periplex® is a rapid point-of-care test based on the detection of interleukin-6 (IL-6) or matrix metalloproteinase-8 (MMP-8) to diagnose peritonitis in peritoneal dialysis (PD) patients. METHODS: This single-centre study was conducted in Singapore General Hospital from 2019 to 2022. The study recruited PD patients suspected of having peritonitis. Periplex was performed at the presentation and recovery of peritonitis. Primary outcomes were sensitivity and specificity of Periplex at presentation. The positive and negative predictive values of tests were also performed. RESULTS: A total of 120 patients were included in the study. The mean age was 60.9 ± 14.9 years, 53% were male, 79% were Chinese and 47.5% had diabetes mellitus. Periplex was positive in all patients with peritonitis (n = 114); sensitivity of 100%; 95% confidence interval (CI): 100-100%. Periplex was falsely positive in three patients with non-infective eosinophilic peritonitis, resulting in a low specificity of 50%; 95% CI: 41.1-59.0%. Periplex had a positive predictive value of 97.4% and a negative predictive value of 100%. During recovery from peritonitis, Periplex had high specificity (93.6%) and negative predictive value (98.7%) to indicate the resolution of infection. MMP-8 was more sensitive than IL-6 in detecting peritonitis. Periplex was positive in all patients with peritonitis regardless of the types of PD solutions used. CONCLUSIONS: Periplex had high sensitivity, and positive and negative predictive values in the diagnosis of peritonitis can be considered as a screening tool for peritonitis. Given its high specificity and negative predictive value, it may also be used to document the resolution of peritonitis.

Results from a cross-specialty consensus on optimal management of patients with chronic kidney disease (CKD): from screening to complications.

BACKGROUND: Chronic kidney disease (CKD) affects around 10% of the global population and has been estimated to affect around 50% of individuals with type 2 diabetes and 50% of those with heart failure. The guideline-recommended approach is to manage with disease-modifying therapies, but real-world data suggest that prescribing rates do not reflect this in practice. OBJECTIVE: To develop a cross-specialty consensus on optimal management of the patient with CKD using a modified Delphi method. DESIGN: An international steering group of experts specialising in internal medicine, endocrinology/diabetology, nephrology and primary care medicine developed 42 statements on aspects of CKD management including identification and screening, risk factors, holistic management, guidelines, cross-specialty alignment and education. Consensus was determined by agreement using an online survey. PARTICIPANTS: The survey was distributed to cardiologists, nephrologists, endocrinologists and primary care physicians across 11 countries. MAIN OUTCOMES AND MEASURES: The threshold for consensus agreement was established a priori by the steering group at 75%. Stopping criteria were defined as a target of 25 responses from each country (N=275), and a 4-week survey period. RESULTS: 274 responses were received in December 2022, 25 responses from Argentina, Australia, Brazil, Guatemala, Mexico, Singapore, South Korea, Taiwan, Thailand, Turkey and 24 responses from Egypt. 53 responses were received from cardiologists, 52 from nephrologists, 55 from endocrinologists and 114 from primary care physicians. 37 statements attained very high agreement (≥90%) and 5 attained high agreement (≥75% and <90%). Strong alignment between roles was seen across the statements, and different levels of experience (2-5 years or 5+ years), some variation was observed between countries. CONCLUSIONS: There is a high degree of consensus regarding aspects of CKD management among healthcare professionals from 11 countries. Based on these strong levels of agreement, the steering group derived 12 key recommendations focused on diagnosis and management of CKD.

Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools.

INTRODUCTION: Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed. METHODS AND ANALYSIS: This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease. ETHICS AND DISSEMINATION: Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023433906.

Comparative effectiveness of first-line antihypertensive drug classes on the maintenance of estimated glomerular filtration rate (eGFR) in real world primary care.

Renin-angiotensin system inhibitors (RASi), particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), are commonly used in the treatment of hypertension and are recommended for kidney protection. Uncertainty remains about the effectiveness of RASi being used as first-line antihypertensive therapy on eGFR maintenance compared to its alternatives, especially for those with no or early-stage chronic kidney disease (CKD). We conducted a retrospective cohort study of 19,499 individuals (mean age 64.1, 43.5% males) from primary care in Singapore with 4.5 median follow-up years. The study cohort included newly diagnosed individuals with hypertension (whose eGFR was mainly in CKD stages G1-G2) and initiated on ACEIs, ARBs, beta-blockers (BBs), calcium channel blockers (CCBs) or diuretics (Ds) as first-line antihypertensive monotherapy. We compared the estimated glomerular filtration rate (eGFR) curve before/after the drug initiation over time of patients under different drug classes and analyzed the time to declining to a more advanced stage CKD. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounding factors. Two key findings were observed. First, after initiating antihypertensive drugs, the eGFR almost maintained the same as the baseline in the first follow-up year, compared with dropping 3 mL/min/1.73 m2 per year before drug initiation. Second, ARBs were observed to be slightly inferior to ACEIs (HR = 1.14, 95% CI = (1.04, 1.23)) and other antihypertensive agents (HR = 1.10, 95% CI = (1.01, 1.20)) in delaying eGFR decline to a more advanced CKD stage in the study population. Our results showed that initiating antihypertensive agents can significantly maintain eGFR for those newly diagnosed patients with hypertension. However, RASi may not be superior to other antihypertensive agents in maintaining eGFR levels for non-CKD or early stages CKD patients.

Readability, Understandability, and Actionability of Online Cardiovascular Risk Assessment Tools and Patient Educational Material: A Systematic Review.

Introduction: Individuals with kidney diseases have increased risk of cardiovascular disease and death. Online cardiovascular risk assessment tools can educate patients on risks and modifiable factors. Since patients have variable health literacy, we evaluated the readability, understandability, and actionability of publicly available online cardiovascular risk assessment tools. Methods: We systematically searched, reviewed, characterized, and assessed English-language cardiovascular risk assessment tools online for readability (Flesch-Kincaid Grade Level [FKGL] score), understandability, and actionability (Patient Education Materials Assessment Tool for printable materials [PEMAT-P]). Results: After screening 969 websites, 69 websites employing 76 risk tools were included. The most frequently used tools were the Framingham Risk Score (n = 13) and the Atherosclerotic Cardiovascular Disease score (n = 12). Most tools were intended for the general population and estimated the 10-year incident cardiovascular risk. Patient education was provided in the form of targets for blood pressure (n = 17), lipids (n = 15), or glucose (n = 5); and advice regarding diet (n = 18), exercise (n = 19), and smoking cessation (n = 20). The median FKGL, PEMAT understandability, and actionability scores were 6.2 (4.7, 8.5), 84.6% (76.9%, 89.2%), and 60% (40%, 60%), respectively. Conclusion: The online cardiovascular risk tools were generally easy to read and understand, but only a third provided education on risk modification. Judicious selection of an online cardiovascular risk assessment tool may help patients in self-management.

Impact of focal segmental glomerulosclerosis over the past decade.

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

Development and validation of a novel nomogram to predict diabetic kidney disease in patients with type 2 diabetic mellitus and proteinuric kidney disease.

PURPOSE: Differentiating between diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) in patients with Type 2 diabetes mellitus (T2DM) is important due to implications on treatment and prognosis. Clinical methods to accurately distinguish DKD from NDKD are lacking. We aimed to develop and validate a novel nomogram to predict DKD in patients with T2DM and proteinuric kidney disease to guide decision for kidney biopsy. METHODS: A hundred and two patients with Type 2 Diabetes Mellitus (T2DM) who underwent kidney biopsy from 1st January 2007 to 31st December 2016 were analysed. Univariate and multivariate analyses were performed to identify predictive variables and construct a nomogram. The discriminative ability of the nomogram was assessed by calculating the area under the receiver operating characteristic curve (AUROC), while calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration plot. Internal validation of the nomogram was assessed using bootstrap resampling. RESULTS: Duration of T2DM, HbA1c, absence of hematuria, presence of diabetic retinopathy and absence of positive systemic biomarkers were found to be independent predictors of DKD in multivariate analysis and were represented as a nomogram. The nomogram showed excellent discrimination, with a bootstrap-corrected C statistic of 0.886 (95% CI 0.815-0.956). Both the calibration curve and the Hosmer-Lemeshow goodness-of-fit test (p = 0.242) showed high degree of agreement between the prediction and actual outcome, with the bootstrap bias-corrected curve similarly indicating excellent calibration. CONCLUSIONS: A novel nomogram incorporating 5 clinical parameters is useful in predicting DKD in type 2 diabetes mellitus patients with proteinuric kidney disease.

Non-steroidal anti-inflammatory drugs in chronic kidney disease and risk of acute adverse kidney events according to route of administration.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration. METHODS: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days. RESULTS: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs. CONCLUSION: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.

Validation of the kidney failure risk equation in predicting the risk of progression to kidney failure in a multi-ethnic Singapore chronic kidney disease cohort.

INTRODUCTION: The Kidney Failure Risk Equation (KFRE) was developed to predict the risk of progression to end-stage kidney disease (ESKD). Although the KFRE has been validated in multinational cohorts, the Southeast Asian population was under-represented. This study aimed to validate the KFRE in a multi-ethnic Singapore chronic kidney disease (CKD) cohort. METHODS: Stage 3-5 CKD patients referred to the renal medicine department at Singapore General Hospital in 2009 were included. The primary outcome (time to ESKD) was traced until 30 June 2017. The eight- and four-variable KFRE (non-North America) models using age, gender, estimated glomerular filtration rate, urine albumin-creatinine ratio, serum albumin, phosphate, bicarbonate and calcium were validated in our cohort. Cox regression, likelihood ratio (Χ2), adequacy index, Harrell's C-index and calibration curves were calculated to assess the predictive performance, discrimination and calibration of these models on the cohort. RESULTS: A total of 1,128 patients were included. During the study period, 252 (22.3%) patients reached ESKD at a median time to ESKD of 84.8 (range 0.1-104.7) months. Both the eight- and four-variable KFRE models showed excellent predictive performance and discrimination (eight-variable: C-index 0.872, 95% confidence interval [CI] 0.850-0.894, adequacy index 97.3%; four-variable: C-index 0.874, 95% CI 0.852-0.896, adequacy index 97.9%). There was no incremental improvement in the prediction ability of the eight-variable model over the four-variable model in this cohort. CONCLUSION: The KFRE was validated in a multi-ethnic Singapore CKD cohort. This risk score may help to identify patients requiring early renal care.