METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation.
RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05).
CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
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.
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.
BACKGROUND: AVFs are preferred for haemodialysis access but are limited by high rates of early failure.
METHODS: A post hoc analysis of 353 participants from ANZ and Malaysia included in the FAVOURED randomised-controlled trial undergoing de novo AVF surgery was performed. Composite AVF failure (thrombosis, abandonment, cannulation failure) and its individual components were compared between ANZ (n = 209) and Malaysian (n = 144) participants using logistic regression adjusted for patient- and potentially modifiable clinical factors.
RESULTS: Participants' mean age was 55 ± 14.3 years and 64% were male. Compared with ANZ participants, Malaysian participants were younger with lower body mass index, higher prevalence of diabetes mellitus and lower prevalence of cardiovascular disease. AVF failure was less frequent in the Malaysian cohort (38% vs 54%; adjusted odds ratio (OR) 0.53, 95% confidence interval (CI) 0.31-0.93). This difference was driven by lower odds of cannulation failure (29% vs 47%, OR 0.45, 95% CI 0.25-0.80), while the odds of AVF thrombosis (17% vs 20%, OR 1.24, 95% CI 0.62-2.48) and abandonment (25% vs 23%, OR 1.17, 95% CI 0.62-2.16) were similar.
CONCLUSIONS: The risk of AVF failure was significantly lower in Malaysia compared to ANZ and driven by a lower risk of cannulation failure. Differences in practice patterns, including patient selection, surgical techniques, anaesthesia or cannulation techniques may account for regional outcome differences and warrant further investigation.
METHOD AND ANALYSIS: We conducted a retrospective cohort analysis of all patients with OHVIRA at our institution, Sabah Women and Children's Hospital, Malaysia, between the 2013 and 2022. Data were collected by reviewing patients' medical notes.
RESULTS: There were a total of 18 patients diagnosed with OHVIRA from 2013 to 2022, aged 10-41 years old. Nine patients (50%) presented during adolescence. Most (88.9%) came with symptoms such as abdominal pain, urinary symptoms, abnormal uterine bleeding, foul-smelling vaginal discharge, and primary infertility, whereas only 2 patients (11.1%) were asymptomatic and diagnosed incidentally. Acute abdomen was more common in the adolescent group (P = .015). No significant difference was found on the side of the renal anomaly.
CONCLUSION: Presenting symptoms vary and are often mimicked other gynecologic or surgical conditions, making the diagnosis difficult and delayed. Some patients were incidentally diagnosed while being managed for other problems, and it was not uncommon to have unnecessary surgery before the correct diagnosis was made. We suggest that all female patients with abdominal and pelvic complaints should be screened for renal anomaly during pelvic scan to improve diagnostic rates.
AIM: We want to demonstrate that the antioxidant properties of Swietenia macrophylla ethanol extract nanoparticles can prevent kidney cell damage brought on by streptozotocin (STZ) in the current investigation.
METHODS: This study employs high-energy ball milling to produce nanoparticles from S. macrophylla extract. Additionally, dynamic light scattering (DLS) is utilized to characterize the nanoparticle sizes of the S. macrophylla ethanol extract. Five groups, each consisting of 8 rats, were formed from 40 rats. Control rats received distilled water, the diabetic rats were administered STZ injections, while S. macrophylla rats were given S. macrophylla extract nanoparticles orally and STZ injection. After the trial, blood from a rat was drawn intracardially to check the levels of blood urea nitrogen (BUN) and creatinine. The levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were then assessed in kidney tissue samples. Histological alterations were evaluated in kidney section samples.
RESULTS: A DLS analysis estimated the size of the S. macrophylla ethanol extract nanoparticles to be about 91.50 ± 23.06 nm. BUN and creatinine levels were significantly raised after STZ treatment. STZ significantly decreased SOD and GPx levels in kidney tissue while raising MDA levels (p < 0.05). Swietenia macrophylla ethanol extract nanoparticle caused the decreased levels of BUN and creatinine in blood to normal levels (p < 0.05), indicating that S. macrophylla ethanol extract prevented the STZ-induced kidney cell damage. Additionally, S. macrophylla nanoparticles significantly raise GPx and SOD levels in kidney tissue while lowering MDA levels (p < 0.05). These actions are thought to have prevented kidney histological alterations (degeneration and necrosis) in diabetic rats.
CONCLUSION: According to these results, the anti-oxidative stress properties of S. macrophylla nanoparticles make them potentially effective nephroprotective therapies for STZ-induced kidney cell damage.
METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.
RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.
MATERIALS AND METHODS: We conducted a prospective, multicentre study in seven hospitals in West Malaysia. All the adults admitted in March 2017 fulfilling Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI were included.
RESULTS: Of the 34,204 patients screened, 2,457 developed AKI (7.18%), 13.1% of which occurred in intensive care unit (ICU). There were 60.2% males with a mean age of 57.8 (±17.5) years. The most common comorbidities were hypertension (55.0%), diabetes (46.6%), ischaemic heart disease (15.1%) and chronic kidney disease (12.0%). The commonest causes of AKI were sepsis (41.7%), pre-renal (24.2%) and cardiorenal syndrome (10.8%). Nephrotoxin exposure was reported in 31%. At diagnosis, the proportion of AKI stages 1, 2 and 3 were 79.1%, 9.7%, 11.2%, respectively. Referral to nephrologists was reported in 16.5%. Dialysis was required in 176 (7.2%) patients and 55.6% were performed in the ICU. Acidosis (46.2%), uraemia (31.6%) and electrolyte disturbance (11.1%) were the commonest indications. Continuous renal replacement therapy (CRRT) was required in 14%. The average length of hospital stay was 9.5 days. In-hospital mortality was 16.4%. Among survivors, full and partial renal recovery was seen in 74.7% and 16.4% respectively while 8.9% failed to recover. After a mean follow-up of 13.7 months, 593 (30.2%) of survivors died and 38 (1.9%) initiated chronic dialysis. Mortality was highest among those with malignancies (Hazard Ratio, HR 2.14), chronic liver disease (HR 2.13), neurological disease (HR 1.56) and cardiovascular disease (HR 1.17).
CONCLUSION: AKI is common in hospitalised patients and is with associated high mortality during and after hospitalisation.
METHODS: This is a retrospective, single-centre study comprising 105 living kidney donor candidates from the year 2007 to 2020. By comparing against 51-Chromium ethylenediamine-tetraacetic acid (51Cr-EDTA), we analysed creatinine clearance for correlation, bias, precision and accuracy.
RESULTS: The study group had a mean age of 45.68 ± 10.97 years with a mean serum creatinine of 64.43 ± 17.68 µmol/L and a urine volume of 2.06 ± 0.83 L. Mean measured GFR from 51Cr-EDTA was 124.37 ± 26.83 ml/min/1.73m2 whereas mean creatinine clearance was 132.35 ± 38.18 ml/min/1.73m2. Creatinine clearance overestimated 51Cr-EDTA significantly with a correlation coefficient of 0.48 (p
AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1.
MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells.
RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment.
CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.
OBJECTIVE: To examine the feasibility of TV-NOSE in live donor nephrectomy.
MATERIALS AND METHODS: 53 patients received LDN surgery at our hospital from September 2017 to December 2021. Retrospectively, living donor nephrectomy with TV-NOSE was compared to three different surgical procedures with standard specimen extraction.
RESULTS: 53 donor patients were included: 15 open (OLDN), 12 retroperitoneoscopic living donor nephrectomy (RPLDN), 10 transperitoneal living donor nephrectomy (TPLDN), and 16 standard laparoscopic living donor nephrectomy with transvaginal extraction (SLLDN TV-NOSE). SLLDN TVNOSE's longer operating time (p<0.0041) did not affect graft function. SLLDN TV-NOSE and RPLDN had shorter lengths of stay and better VAS trends than open LDN and TPLDN (p<0.05). SLLDN TV-NOSE donors reported acceptable surgical outcomes and unchanged sexual function. All patients had similar discharge creatinine levels, with 1-year transplant survival of 98% and just 1 graft loss in the TPLDN group.
CONCLUSION: SLLDN TV-NOSE is equivalent to RPLDN and better than open LDN and TPLDN in terms of duration of stay, VAS score, surgical outcomes, and sexual function. TVNOSE is a safe surgical procedure with an acceptable donor complication. TV-NOSE may be safely conducted in both developed and developing countries with proper patient selection.