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.
PATIENTS AND METHODS: We collected 1-year follow-up data from records of 98 diabetic KTRs on SGLT2I, 41 on GLP- 1RA and 70 on standard-of-care medicines. Patients were more than 3 months post-transplant with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min/1.73 m2 . Demographic data were similar except for a slightly lower HbA1c in the control group and higher albuminuria in SGLT2i group.
RESULTS: HbA1c dropped significantly by .4% in both SGLT2i and GLP-1RA compared to .05% in the control group. A significant decrease in BMI by .32 in SGLT2i and .34 in GLP-1RA was observed compared to an increase by .015 in control group. A tendency for better eGFR in study groups was observed but was non-significant except for the SGLT2i group with an eGFR above 90 (p = .0135). The usual dip in eGFR was observed in the SGLT2i group at 1-3 months. Albuminuria was significantly reduced in both study groups. Adverse events were minimal with comparable safety in all groups.
CONCLUSION: The use of SGLT2i and GLP-1RA appears to be effective and safe in diabetic KTRs with good outcomes. Randomized control trials are required to confirm these findings and establish guidelines.
MATERIALS AND METHODS: We performed a cross-sectional study involving 70 patients with biopsy-proven immunoglobulin A nephropathy with a stable estimated glomerular filtration rate and urinary albuminuria. Their demographic profiles were documented, and blood samples were taken for serum 25-hydroxyvitamin D, highly sensitive C-reactive protein, urine albuminuria and other routine blood tests.
RESULTS: We found nine patients (12.9%) had sufficient 25- hydroxyvitamin D [25(OH)D] levels of more than 30ng/mL and the rest of the patients; 61 (87.1%) had serum 25(OH)D levels below 30 ng/ml. Amongst those with low vitamin D, 38 (62.3%) had serum 25(OH)D between 15-30 ng/mL (insufficient), and the remaining 23 (37.7%) had serum 25(OH)D below 15 ng/ml (deficient). Their mean level of serum 25(OH)D was 19.92 ± 9.04 ng/mL with a serum creatinine of 106.23 ± 38.56 μmol/L and mean estimated glomerular filtration rate (eGFR) at 68.11± 27.65 mL/min/1.73 m2. There was no association between urinary albuminuria, highly sensitive C-reactive protein, estimated glomerular filtration rate or systolic blood pressure with serum 25(OH)D level.
CONCLUSION: Low vitamin D (insufficiency and deficiency) are indeed prevalent in stable immunoglobulin A nephropathy patients. We found no correlation between the vitamin D levels with albuminuria, renal function and highly sensitive C-reactive.
MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.
RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.
CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.
METHOD: Forty-one T2DM patients on follow-up at a community clinic were divided into normo-(NA), micro-(MIC), and macroalbuminuria (MAC) groups. Differential levels of miRNAs in 12 samples were determined using the pathway-focused (human fibrosis) miScript miRNA qPCR array and was validated in 33 samples, using the miScript custom qPCR array (CMIHS02742) (Qiagen GmbH, Hilden, Germany).
RESULTS: Trends of upregulation of 3 miRNAs in the serum, namely, miR-874-3p, miR-101-3p, and miR-145-5p of T2DM patients with MAC compared to those with NA. Statistically significant upregulation of miR-874-3p (p = 0.04) and miR-101-3p (p = 0.01) was seen in validation cohort. Significant negative correlations between the estimated glomerular filtration rate (eGFR) and miR-874-3p (p = 0.05), miR-101-3p (p = 0.03), and miR-145-5p (p = 0.05) as well as positive correlation between miR-874-3p and age (p = 0.03) were shown by Pearson's correlation coefficient analysis.
CONCLUSION: Upregulation of previously known miRNA, namely, miR-145-5p, and possibly novel ones, namely, miR-874-3p and miR-101-3p in the serum of T2DM patients, was found in this study. There was a significant correlation between the eGFR and these miRNAs. The findings of this study have provided encouraging evidence to further investigate the putative roles of these differentially expressed miRNAs in DKD.
MATERIALS AND METHODS: An e-mail invitation to participate in an online survey was sent to hospital laboratories in Malaysia (n=140). Questions regarding methods for measuring creatinine, equations for calculating eGFR, eGFR reporting, the terminology used in reporting urine albumin, types of samples and the cut-off values used for normal albuminuria.
RESULTS: A total of 42/140 (30%) laboratories answered the questionnaire. The prevalent method used for serum creatinine measurement was the Jaffé method (88.1%) traceable to isotope-dilution mass spectrometry. eGFR was reported along with serum creatinine by 61.9% of laboratories while 33.3% of laboratories report eGFR on request. The formula used for eGFR reporting was mainly MDRD (64.3%) and results were reported as exact numbers even when the eGFR was <60 ml/min/1.73m2. The term microalbumin is still used by 83.3% of laboratories. There is a large heterogeneity among the labs regarding the type of sample recommended for measuring urine albumin, reference interval and reporting units.
CONCLUSION: It is evident that the laboratory assessment of chronic kidney disease in Malaysia is not standardised. It is essential to provide a national framework for standardised reporting of eGFR and urine albumin. Recommendations developed by the MACB CKD Task Force, if adopted by all laboratories, will lead to a reduction in this variability.
METHODS: A population-based study was conducted on a total of 890 respondents who were representative of the adult population in Malaysia, i.e., aged ≥18 years old. Respondents were randomly selected using a stratified cluster method. The estimated glomerular filtration rate (eGFR) was estimated from calibrated serum creatinine using the CKD-EPI equation. CKD was defined as eGFR albuminuria if eGFR ≥60 ml/min/1.73m2.
RESULTS: Our study shows that the prevalence of CKD in Malaysia was 15.48% (95% CI: 12.30, 19.31) in 2018, an increase compared to the year 2011 when the prevalence of CKD was 9.07%. An estimated 3.85% had stage 1 CKD, 4.82% had stage 2 CKD, and 6.48% had stage 3 CKD, while 0.33% had stage 4-5 CKD. Hypertension (aOR 3.72), diabetes mellitus (aOR 3.32), increasing BMI (aOR 1.06), and increasing age (aOR 1.06) were significantly associated with CKD.
CONCLUSION: Our study has shown that CKD has become one of the leading public health issues in Malaysia. Thus, there is an urgent need to screen for CKD and prevent its progression, associated morbidity, and mortality at the national level.
Methods: A systematic search using predefined search terms in three scholarly databases, ScienceDirect, Google Scholar, and PubMed, was conducted. Original research articles published in the English language between 2012 and 2020 that reported renal outcomes associated with the use of non-insulin AD pharmacotherapy were eligible for inclusion. Review articles, meta-analysis studies, and conference proceedings were excluded. A study-specific data extraction form was designed to extract the author's name, country, publication year, study design, study population, objectives, key findings, and conclusions. A narrative review of the key findings that focused on renal outcomes and renal safety issues was conducted.
Results: Of the 18,872 results identified through the initial search, a total of 32 articles were included in this review. Of these, 18 of the included articles reported the renal outcomes of newer antidiabetic medications, eg, SGLT2 inhibitors and GLP-1 agonists. Eight studies focussed on the well-established antidiabetic medications, eg, metformin and sulphonylureas. The review reported three main types of the clinical impact of the prescribed AD on the renal outcomes: "renoprotective effects", "no additional risk" and "associated with a decline in renal parameters". Seventeen studies reported the renoprotective effects of AD, including SGLT2i studies (n=8), GLP1 studies (n=6), and DPP4i studies (n=3). The reported renoprotective effects included slowing down the GFR decline, improving albuminuria, and reducing renal adverse events. The "no additional risk" impact was reported in eight studies, including DPP4i studies (n=3), two SGLT2i studies (n=2), metformin studies (n=2), and one study involving pioglitazone. Furthermore, seven studies highlighted the "associated with a decline in renal parameters" effect. Of these, three involved SGLT2i, two with metformin, and one for each DPP4i and sulphonylurea.
Conclusion: More than half of the studies included in this review supported the renoprotective effects associated with the use of AD medications, particularly GLP-1A, SGLT2i, and some of the DPP4i. Further studies involving patients with various stages of chronic kidney disease (CKD) are required to compare AD medications' renal effects, particularly the newer agents.
METHODS: We studied 101 patients with pre-operative diabetes and albuminuria [defined as urine albumin:creatinine ratio (uACR) > 30 mg/g] who underwent bariatric surgery at an academic center from 2005 to 2014.
RESULTS: Fifty-seven patients (56%) were female with a mean age of 53 (± 11) years. The mean pre-operative BMI and glycated hemoglobin (HbA1c) were 43.1 (± 7.6) kg/m2 and 8.4 (± 1.8)%, respectively. The median pre-operative uACR was 80.0 (45.0-231.0) mg/g. Bariatric procedures included Roux-en-Y gastric bypass (n = 75, 74%) and sleeve gastrectomy (n = 26, 26%). The mean follow-up period was 61 (± 29) months. At last follow-up, the mean BMI was 33.8 (± 8.3) kg/m2. The overall glycemic control improved after bariatric surgery. At last follow-up, 73% had good glycemic control (HbA1c Albuminuria improved in 77% and resolved in 51% of patients at long-term.
CONCLUSIONS: Bariatric surgery has a significantly positive impact on albuminuria in patients with obesity and type 2 diabetes. Our data showed almost an 80% improvement in albuminuria at the short- and long-term period after bariatric surgery.
OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015.
SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure.
AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.