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.

Estimation of risk for major bleeding in native kidney biopsies in patients with multiple risk factors.

BACKGROUND AND AIMS: Individuals undergoing kidney biopsy are increasingly older and may have concurrent illnesses that cause deranged hematological and renal parameters that are associated with post-biopsy bleeding. We aimed to develop a clinical risk model to quantify bleeding risks in high-risk individuals with multiple risk factors. METHODS: Single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 2 mg/dL (176 µmol/L) and had ultrasound-guided percutaneous native kidney biopsies between June 2011 and July 2015 in our tertiary referral center. The primary outcome was major bleeding, defined as need for red cell transfusion, radiological or surgical intervention, or if bleeding led to death within 7 days after kidney biopsy. RESULTS: Among 184 native kidney biopsies with serum creatinine ≥ 2 mg/dL, median age was 54.1 years and eGFR was 18.8 ml/min/1.73 m2. Major bleeding occurred in 19 biopsies (10.3%). Multivariate analysis accounting for age, weight, hemoglobin, platelet, prothrombin time and urea found that higher hemoglobin (adjusted OR 0.51, 95% CI 0.33-0.79, p = 0.003) and platelet (adjusted OR 0.99, 95% CI 0.98-0.99, p = 0.01) were independently associated with reduced major bleeding. A risk model that included (1) age ≥ 62 years old, (2) hemoglobin < 10 g/dL and (3) platelets ≤ 216 × 109/L as categorical variables predicted major bleeding post-biopsy. CONCLUSION: We developed a risk model that included multiple risk factors to quantify bleeding risks in native kidney biopsies with renal impairment.

A Descriptive Evaluation of Health Literacy and Determinants of COVID-19 Vaccine Acceptance among Patients with IgA Nephropathy with High Vaccine Uptake.

Aims: Shared decision-making regarding COVID-19 vaccination in IgA nephropathy involves the ability to handle health information regarding potential benefits and risk of flare, but few studies have evaluated health literacy in the context of vaccination. We aimed to evaluate the health literacy and COVID-19 vaccination uptake and acceptance in IgA nephropathy. Methods: Single-center cross-sectional study of 126 consecutive patients with IgA nephropathy. Health literacy was assessed using the HLS-EU-47 questionnaire. Determinants of vaccine acceptance such as contextual influences, individual and group influences, and vaccine-specific issues were adapted from the World Health Organization framework. Results: Forty-eight patients (38.1%) with IgAN nephropathy completed the survey between June and August 2021. The participants' median age was 40.5 (31.6, 52.8) years with median disease duration of 2.8 (1.3, 4.3) years. The median general health literacy index was 31.74 (29.88, 35.82) with significantly greater difficulty in the competency of appraising health information and in the domain of disease prevention (p < 0.001). Forty-five patients (93.8%) received at least one dose of COVID-19 vaccine between January and August 2021. Among the 3 unvaccinated patients, 2 intended to receive the vaccination while and 1 did not intend to get vaccinated. There was a high level of trust and belief that their government and healthcare providers had their best interests at heart and that the healthcare providers were honest about the vaccine's risk and benefits, although 31.2% did not understand how the vaccine works and 22.9% believed that there were other ways to prevent infection. Most thought there was adequate safety information, were confident in the system for tracking adverse events and had no issues with access to the vaccine. Conclusion: Participants with IgA nephropathy had high health literacy scores and low vaccine hesitancy. The determinants for vaccine acceptance can potentially guide efforts to optimize vaccination coverage.

Changes in metabolic parameters and adverse kidney and cardiovascular events during glomerulonephritis and renal vasculitis treatment in patients with and without diabetes mellitus.

BACKGROUND: Cardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increasingly diagnosed in older individuals who may have diabetes mellitus (DM). We evaluated the impact of DM on metabolic profile, renal and cardiovascular outcomes during treatment and follow-up of individuals with glomerulonephritis. METHODS: We performed a retrospective cohort study of 601 consecutive adults with biopsy-proven glomerulonephritis for factors associated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were excluded. RESULTS: The median patient age was 49.8 years (36.7-60.9 years) with estimated glomerular filtration rate of 56.7 mL/min/1.73 m2 (27.7-93.2 mL/min/1.73 m2). DM was present in 25.4%. The most frequent diagnoses were minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) (29.5%), lupus nephritis (21.3%), immunoglobulin A (IgA) nephropathy (19.1%), and membranous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 individuals with lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, MCD/FSGS, membranous nephropathy, and IgA nephropathy, 52 (10.2%) developed kidney failure at a median 16.4 months (IQR, 2.3-32.2 months), while 29 (5.7%) had cardiovascular-related hospitalizations at 12.9 months (IQR, 4.8-31.8 months) and 31 (6.1%) died at 13.5 months (IQR, 2.5-42.9 months) after diagnosis. Cox regression analysis found that baseline DM was independently associated with kidney failure (adjusted hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.06-4.05, p = 0.03) and cardiovascular-related hospitalization (adjusted HR, 2.69; 95% CI, 1.21-5.98, p = 0.02) but not with mortality. CONCLUSION: DM was strongly associated with kidney failure and hospitalization for cardiovascular events in patients with biopsy-proven glomerulonephritis.

Health Literacy in Glomerulonephritis and Renal Vasculitis Attending Nephrology Clinics.

Aims: Glomerulonephritis is one of the leading causes of progressive chronic kidney disease worldwide and treatment requires shared decision-making to improve self-care and plan immunosuppressant therapy. However, information on health literacy (HL) in patients with glomerulonephritis is scanty. We aimed to assess HL in our multiethnic population with glomerulonephritis. Methods: Single-center cross-sectional study of patients with glomerulonephritis receiving induction immunosuppressants at the ambulatory nephrology clinic and who completed the anonymized self-administered HLS-EU-47 questionnaire. The standardized HL index and domain item mean scores were compared with participant sociodemographic characteristics. Results: Among 65 patients who attend the clinics over a month, 27 agreed to participate in the survey. After excluding responses with significant missing information, we included 23 participants (16 Chinese, 4 Malay, 2 Indian, and 1 other ethnicity) in the analysis. The median age was 39 (interquartile range 27, 60 years). The median general HL index was 26.2 (19.8, 29.8). The item mean scores were 2.64 (2.43, 2.77), 2.45 (2.09, 2.72), 2.33 (2.17, 2.58), and 2.50 (2.25, 2.75) for the domains of accessing, understanding, appraising, and applying health-care-related information, respectively. Male patients had significantly higher HL indices and higher scores for accessing and appraising health information, while higher personal income was significantly associated with higher score for applying health knowledge. Conclusion: Patients with glomerulonephritis had lowest HL in the domain of appraising health information. Further research on targeted interventions to improve the HL in appraising treatment options and vaccinations in patients with glomerulonephritis is required.

Clinical course of Immunoglobulin A nephropathy with crescents in a multi-ethnic Southeast Asian cohort.

AIM: Clinical presentation and course of Immunoglobulin A nephropathy vary by ethnicity and geography and significance of extracapillary proliferation or crescents (IgAN-C) in Southeast Asia is not well described. We aimed to describe the clinical course of IgAN-C in Singapore. METHODS: Retrospective cohort study of adult biopsy-proven IgAN diagnosed between February 2011 and October 2016 in 2 hospital-based nephrology units. Outcome was chronic kidney disease (CKD) progression, defined as reduction in eGFR ≥50% or end stage renal failure (ESRF). RESULTS: One hundred and forty-five patients were studied. Among individuals with IgAN-C (n = 44, 30%), 38 patients had cellular or fibrocellular crescents in 1 to 25% of the glomeruli and 6 had crescents in >25%. Median eGFR was 54 (33, 83) mL/min/1.73 m2 . Compared to IgAN without crescents, IgAN-C had greater proteinuria (median 2.9 [1.4, 5.4] g/g vs 1.9 [1.1, 3.6] g/g, P = .03) and more had endocapillary hypercellularity (96% vs 39%, P < .001). IgAN-C were also more likely to receive immunosuppressants (66% vs 43%, P = .01) such as prednisolone (63% vs 38%, P = .006) and cyclophosphamide (12% vs 2%, P = .03). Median follow up was 27 (12, 46) months. IgAN-C were more likely to achieve proteinuria reduction ≥50% at 6 months (66% vs 44%, P = .03). CKD progression within 12 months was not different among those with and without crescents (13% vs 10% respectively, P = .73). However, immunosuppressant treatment of IgAN-C was associated with reduced ESRF (0 vs 20%, P = .03). CONCLUSION: Immunosuppressants may attenuate the risk of ESRF in IgAN-C.

Risk-stratified approach to anti-viral prophylaxis against cytomegalovirus disease in glomerulonephritis and renal vasculitis treated with potent immunosuppressants.

Aim: Cytomegalovirus (CMV) reactivation and disease in immunocompromised individuals is associated with significant morbidity and mortality. Preventive measures such as anti-viral prophylaxis or surveillance and pre-emptive therapy effectively reduced CMV disease in solid organ transplant but have not been evaluated among patients with glomerulonephritis at-risk for CMV disease after immunosuppressive therapy. We evaluated the utility and outcomes of a risk-stratified approach to anti-viral prophylaxis for adults with glomerulonephritis treated with potent immunosuppressants. Methods: Single-center retrospective cohort study of adults with glomerulonephritis and renal vasculitis prescribed methylprednisolone, cyclophosphamide or rituximab in a tertiary referral centre. A risk-stratified approach to CMV anti-viral prophylaxis was implemented in March 2015. We compared the incidence of CMV disease in the pre-implementation (January 2008-December 2014) and post-implementation (June 2015-June 2017) groups. Results: We studied 119 individuals: 85 in the pre-implementation group and 34 in the post-implementation group. The post-implementation group had worse kidney function, greater proteinuria, higher prednisolone dose and more received intravenous methylprednisolone and plasma exchanges but CMV disease within 6 months was similar to the pre-implementation group (2.9% vs. 3.5%, p = 1.00). Among individuals in the post-implementation group who satisfied criteria to receive anti-viral prophylaxis (n = 21), CMV disease was more frequent in the group not given prophylaxis compared to those given prophylaxis as recommended (8.3% versus 0%, p = 1.00). Adverse events related to anti-viral prophylaxis occurred in 40%. Conclusion: This study provided pilot data for future randomized controlled trials to evaluate CMV preventive strategies in selected high-risk patients with glomerulonephritis or renal vasculitis.

Desmopressin for the prevention of bleeding in percutaneous kidney biopsy: efficacy and hyponatremia.

BACKGROUND: Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment. METHOD: This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding. RESULTS: 240 native kidney and 196 allograft biopsies were performed. Median age was 51 (IQR 42.3, 60) years and eGFR was 21.9 (12.9, 30.1) ml/min/1.73 m2. Although patients prescribed desmopressin prophylaxis (n = 226) had higher serum creatinine [279 (201, 392) vs. 187 (160, 241), p < 0.001], bleeding (15.0% vs. 13.3%, p = 0.60) was not significantly different with and without desmopressin. Severe hyponatremia occurred in 30 biopsies (6.9%) with nadir serum sodium level of 122 (119, 124) mmol/L at 3 (2, 5) days after biopsy, more frequently among those with desmopressin prophylaxis (10.7% vs. 3.0%, p = 0.002). Multi-variate analysis found that pre-biopsy serum sodium level [adjusted OR 0.80 (95% CI 0.72, 0.90), p < 0.001] and desmopressin prophylaxis [adjusted OR 4.02 (95% CI 1.58, 10.21), p = 0.003] were independently associated with severe hyponatremia after kidney biopsy. CONCLUSION: Pre-biopsy desmopressin was associated with severe hyponatremia in individuals with renal impairment; hence, susceptible patients given desmopressin should be closely monitored.

New-onset diabetes mellitus among patients with glomerular diseases.

BACKGROUND: Glomerulonephritis commonly causes kidney failure. Immunosuppressant treatment may be diabetogenic, but data on hyperglycaemia in glomerulonephritis treated with usual clinical care are scant. AIM: To assess the epidemiology, risk factors and outcomes for new-onset diabetes among patients with glomerular disease (NODAG). METHODS: A single-centre retrospective cohort of nondiabetic adults diagnosed with glomerulonephritis between January 2011 and July 2015. Clinical, laboratory and pharmacotherapy data were retrieved from electronic medical records. Using modified American Diabetes Association criteria, the primary outcome of NODAG was present if fasting venous glucose was ≥7 mmol/L for at least two readings, HbA1c was ≥6.5% or if patient required antidiabetic medications. Secondary outcomes were end-stage renal disease, cardiovascular disease and death. RESULTS: NODAG occurred in 48 patients (10.7%); 22 required antidiabetic medication at median 6.2 (interquartile range 1.7, 20.0) months after glomerulonephritis diagnosis. Patients with NODAG had higher prebiopsy fasting glucose, greater proteinuria and lower fasting high-density lipoprotein cholesterol levels. Methylprednisolone and cyclophosphamide were more commonly used among patients with NODAG. In multivariate logistic regression, greater proteinuria (odds ratio 1.08 (95% confidence interval 1.01, 1.16), P = 0.02) and methylprednisolone use (odds ratio 4.02 (95% confidence interval 1.76, 9.18), P = 0.001) were significantly associated with NODAG, independent of the triglyceride/high-density lipoprotein cholesterol ratio as a surrogate measure of insulin resistance. Median follow up was 39.6 (26.9, 57.2) months. Secondary outcomes were not significantly different in patients with and without NODAG. CONCLUSION: Proteinuria and methylprednisolone were associated with incident diabetes among patients with glomerular disease treated with usual care. At-risk patients should be appropriately counselled and monitored for hyperglycaemia.

Long-term renal outcomes in multi-ethnic Southeast Asians with lupus nephritis: a retrospective cohort study.

BACKGROUND: Renal involvement is common among Asians with systemic lupus erythematosus and long-term renal outcomes have been described in homogeneous Caucasian and East Asian populations with lupus nephritis, but data are scarce for other ethnicities. AIM: To evaluate the incidence and risk factors for progressive chronic kidney disease (CKD) in multi-ethnic Southeast Asians with lupus nephritis. METHODS: This is a single-centre retrospective cohort study of adults with biopsy-proven lupus nephritis diagnosed between May 2001 and May 2009. Demographic and clinical data were retrieved from electronic medical records. Patients were excluded if baseline comorbid, renal function or pharmacotherapy data were incomplete or if they default follow-up within 3 months from time of diagnosis. Primary outcome was progressive CKD, defined by end-stage renal disease or persistent doubling of serum creatinine or reduction in eGFR ≥50% for ≥3 months from baseline. RESULTS: We studied 113 patients with newly diagnosed biopsy-proven lupus nephritis. Median age was 42 (interquartile range 29-52) years; the majority were Chinese (76%; Malay 13% and others 11%) and female (81%). Two-thirds had International Society of Nephrology and Renal Pathology Society Class III or IV nephritis; serum creatinine was 86 (67-125) µmol/L with heavy proteinuria (6.3 (2.5-12.2) g/g creatinine). Median follow-up was 110 (83-142) months. Remission (partial and complete) occurred in 96% at 3.1 (1.6-5.2) months after diagnosis. Among patients who achieved remission, 56% had disease relapse at 19.0 (6.0-40.2) months after remission. Patients with progressive CKD (n = 13, 11%) had lower baseline CKD Epidemiology Collaboration estimated glomerular filtration rate (37.3 (16.5-82.0) vs 79.4 (57.5-101.0) mL/min/1.73 m2 , P = 0.03) and higher chronicity index (5 (3-6) vs 3 (2-3), P = 0.04) than those who did not. Remission, early remission within 6 months, complete remission and non-relapse were less frequently associated with progressive CKD (P < 0.01). CONCLUSION: Multi-ethnic Southeast Asians with biopsy-proven lupus nephritis had high remission rates and low incidence of progressive CKD. Progressive CKD was associated with poorer baseline renal function, higher histological chronicity index, failure to achieve remission and occurrence of relapse.

Letter to the Editor: Time for cost-effectiveness studies for preventive strategies applied according to risk of cytomegalovirus-related morbidity and mortality in ANCA-associated vasculitis.

Gastrointestinal cytomegalovirus (CMV) disease in ANCA-associated vasculitis is associated with significant morbidity. Studies should be performed to identify the epidemiology and risk factors for CMV disease in AAV so that vulnerable patients may be risk-stratified for consideration of preventive strategies such as surveillance and pre-emptive therapy or anti-viral prophylaxis. Given the absence of evidence-based guidelines for prevention of CMV disease in patients with AAV receiving potent immunosuppressive therapy, further risk-benefit studies are required to ascertain if preventive strategies will reduce CMV-related morbidity and mortality in individuals with AAV.