METHODS: MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision.
RESULTS: This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min-1 (95% confidence interval [CI], -29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min-1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction.
CONCLUSION: Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters.
METHODS: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included individuals aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to less than 45 mL/min per 1·73 m2, or with an eGFR of 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110.
FINDINGS: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and then followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroups of eGFR included 2282 (34·5%) participants with an eGFR of less than 30 mL/min per 1·73 m2, 2928 (44·3%) with an eGFR of 30 to less than 45 mL/min per 1·73 m2, and 1399 (21·2%) with an eGFR 45 mL/min per 1·73 m2 or higher. Prespecified subgroups of uACR included 1328 (20·1%) with a uACR of less than 30 mg/g, 1864 (28·2%) with a uACR of 30 to 300 mg/g, and 3417 (51·7%) with a uACR of more than 300 mg/g. Overall, allocation to empagliflozin caused an acute 2·12 mL/min per 1·73 m2 (95% CI 1·83-2·41) reduction in eGFR, equivalent to a 6% (5-6) dip in the first 2 months. After this, it halved the chronic slope from -2·75 to -1·37 mL/min per 1·73 m2 per year (relative difference 50%, 95% CI 42-58). The absolute and relative benefits of empagliflozin on the magnitude of the chronic slope varied significantly depending on diabetes status and baseline levels of eGFR and uACR. In particular, the absolute difference in chronic slopes was lower in patients with lower baseline uACR, but because this group progressed more slowly than those with higher uACR, this translated to a larger relative difference in chronic slopes in this group (86% [36-136] reduction in the chronic slope among those with baseline uACR <30 mg/g compared with a 29% [19-38] reduction for those with baseline uACR ≥2000 mg/g; ptrend<0·0001).
INTERPRETATION: Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor.
FUNDING: Boehringer Ingelheim and Eli Lilly.
AIMS: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations.
METHODS: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke.
RESULTS: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month).
CONCLUSION: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.
MATERIALS AND METHODS: This is a cross-sectional study of patients referred for 99mTc-DTPA scan at the Nuclear Medicine Centre of International Islamic University Malaysia. The record was taken from patients visiting the centre from January 2016 to December 2019.
RESULTS: The mean measured GFR by 99mTc-DTPA scan was 42.2 ± 20.38 ml/min. These were lower than that estimated by CG, MDRD, and CKD-EPI equations. CKD-EPI had the highest correlation of 0.72, least bias (mean bias of 11.08 ± 23.08) and was more precise (r2 = 0.4) as compared to MDRD and CG. In patients < 65 years old, CKD-EPI had the highest correlation; however, MDRD had the least bias and highest accuracy. In terms of BMI, CKD-EPI had the least bias and highest accuracy for BMI >30 and with the highest correlation for all classes of BMI.
CONCLUSION: CKD-EPI has the best estimation of GFR taking into account the effect of BMI and age. A further study can be done to determine the correlation of estimated GFR equations with different ethnicity in Malaysia.
MATERIALS AND METHODS: The CKD-CHECK (CKD-CHECK EGFR Chart in Kidney disease) is a toolkit that was developed to auto-generate patients' eGFR trend using a line graph, displaying the trend visually over a year. It identifies patients with rapid CKD progression, triggers the doctors to order appropriate tests (proteinuria quantification or renal imaging) and helps in decision making (continued monitoring at primary care level or referral to nephrologist). The toolkit was piloted among medical officers practising in a hospital-based primary care clinic treating patients with eGFR<60ml/min/1.73m2 using an interventional before-after study design from February to May 2022. In the preintervention period, the CKD patients were managed based on standard practice. The doctors then used the CKDCHECK toolkit on the same group of CKD patients during the intervention period. The feasibility and acceptability of the toolkit was assessed at the end of the study period using the Acceptability of Intervention Measure (AIM) and Feasibility of Intervention Measure (FIM) questionnaires. All patients' clinical data and referral rate were collected retrospectively through medical files and electronic data systems. Comparison between the pre- and post-intervention group were analysed using paired t-test and McNemar test, with statistical significance p value of <0.05.
RESULTS: A total of 25 medical officers used the toolkit on 60 CKD patients. The medical officers found the CKD-CHECK toolkit to be highly acceptable and feasible in primary care setting. The baseline characteristics of the patients were a mean age of 72 years old, predominantly females and Chinese ethnicity. Majority of the CKD patients had diabetes mellitus, hypertension and dyslipidemia. The numbers of CKD rapid progressors was similar (26.7% in the preintervention group vs 33.3% in the post-intervention group). There were no significant differences in terms of proteinuria assessment and ultrasound kidney for CKD rapid progressors before and after the intervention. However, a significant number of CKD rapid progressors were referred to nephrologists after the use of CKD-CHECK toolkit (p=0.016).
CONCLUSIONS: CKD-CHECK toolkit is acceptable and feasible to be used in primary care. Preliminary findings show that the CKD-CHECK toolkit improved the primary care doctor's referral of rapid CKD progressors to nephrologists.
METHODS: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110.
FINDINGS: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62-0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1).
INTERPRETATION: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease.
FUNDING: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.
Objective: To assess the periodontal status of pre-dialysis CKD patients in Hospital Universiti Sains Malaysia.
Methods: A total of 46 pre-dialysis CKD patients who attended the nephrology clinic at Hospital Universiti Sains Malaysia were enrolled in this study. Periodontal examination was performed using the periodontal probing depth (PPD), clinical attachment loss (CAL) and plaque index.
Results: The majority of the CKD patients were Malay (95.7%) and 80.4% were males. The mean age of the patients was 58.5 years. Using PPD measurement, 37 (74.0%) of the patients had mild periodontitis, 9 (20.0%) had moderate periodontitis and 3 (6.0%) had no periodontitis. Based on CAL measurement, 12 (26%) patients had mild periodontitis, 29 (63.0%) had moderate periodontitis and 5 (11%) had severe periodontitis. The mean (standard deviation [SD]) value of mild and moderate-to-severe periodontitis by PPD measurement were 4.26 (0.26) and 5.24 (0.36), respectively. The mean of mild and moderate-to-severe periodontitis by CAL measurement were 2.66 (0.62) and 4.98 (0.73), respectively. There was no correlation between the periodontal parameters and estimated glomerular filtration rate (PPD: r = -0.160, P = 0.914; CAL: r = -0.135, P = 0.372; plaque index: r = 0.005, P = 0.974).
Conclusion: This study revealed a greater prevalence and severity of chronic periodontitis among CKD patients. Thus, the periodontal health of CKD patients' needs to be screened and monitored.