Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C-Based Estimated GFR Equations Among Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.

Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults.

OBJECTVIES: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method. RESULTS: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries. CONCLUSIONS: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

Tenofovir disoproxil fumarate associated nephrotoxicity: a retrospective cohort study at two referral hospitals in Namibia.

INTRODUCTION: The incidence and risk factors of tenofovir disoproxil fumarate (TDF)-related renal impairment (RI) in Namibia are unknown where TDF-containing ART regimens are used as the first line for HIV. METHODOLOGY: A retrospective cohort study among HIV-infected patients at two intermediate hospitals. A decline in estimated glomerular filtration rate (eGFR) was significant if it was ≥25% and included a change to a lower eGFR stage. New-onset RI was defined as an eGFR <50 mL/min/1.73m2 . RESULTS: 10 387 patients were included: 11.4% (n = 1182) experienced the decline in eGFR. Of these, 0.6% (n = 62) migrated to eGFR stages IV and V. The incidence was 4.5 (95% CI: 4.3-4.8) per 100 patient years. RI developed in 400 patients for an incidence rate of 2.4 (95% CI: 2.2-2.6) cases per 100 patient years. Risk factors with effect sizes >2.0, for decline-in-eGFR were baseline eGFR >60 (aHR = 15.6); hyperfiltration (aHR = 5.0); and pregnancy (aHR = 2.4); while for RI, they were hyperfiltration (aHR = 4.1) and pregnancy (aHR = 29). CONCLUSION: The incidence of decline-in-eGFR was higher than in other sub-SSA countries, but not RI. A high baseline eGFR had the greatest risk for the decline, and hyperfiltration for the RI.

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function. STUDY DESIGN: Genome-wide association study (GWAS) and Mendelian randomization. SETTING & PARTICIPANTS: UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries. EXPOSURE: Coffee consumption. OUTCOMES: Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m2), and albuminuria. ANALYTICAL APPROACH: GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen. RESULTS: 2,126 SNPs were associated with coffee consumption (P<5×10-8), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (ß=0.022; P=1.6×10-6) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10-15). LIMITATIONS: Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations. CONCLUSIONS: This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.

A higher ratio of refined grain to whole grain is associated with a greater likelihood of chronic kidney disease: a population-based study.

A growing number of studies suggest that diet and renal function are related. However, little is known about the link between both whole grain (WG) and refined grain (RG) consumption and kidney function parameters. Thus, we investigated the association of WG and RG with urinary albumin to creatinine ratio (ACR) and prevalent chronic kidney disease (CKD). Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation. Survey design and sample weights were taken into consideration for statistical analyses. Finally, we included 16 325 participants from NHANES, 6·9 % of whom had prevalent CKD. In models adjusted for age, sex, race, fasting blood glucose, blood pressure, adiposity, hypertension and diabetes status, mean eGFR significantly increased across increasing quartiles of WG (Q1: 88·2 v. Q4: 95·4 ml/min per 1·73 m2, P<0·001), whereas it significantly decreased across increasing quartiles of RG (Q1: 97·2 v. Q4: 88·4 ml/min per 1·73 m2, P<0·001). Furthermore, serum uric acid levels and ACR significantly decreased across quartiles of WG (both P<0·001). In multivariable-adjusted logistic regression models, the likelihood of prevalent CKD was 21 % lower in the highest WG quartile compared with the lowest one. In conclusion, our results shed light on the beneficial impact of WG on kidney function and CKD, whereas RG is adversely associated with eGFR.

Dietary fibre intake in relation to the risk of incident chronic kidney disease.

The purpose of this study was primarily to evaluate the association of total fibre intake with the risk of incident chronic kidney disease (CKD). We also evaluated the association of dietary fibre from fruits, vegetables, cereals and legumes with the incidence of CKD in a population-based prospective study. We followed up 1630 participants of the Tehran Lipid and Glucose Study for 6·1 years, who were initially free of CKD. Baseline diet was assessed by a valid and reliable FFQ. Estimated glomerular filtration rate (eGFR) was calculated, using the Modification of Diet in Renal Disease Study equation, and CKD was defined as eGFR <60 ml/min per 1·73 m2. OR using multivariable logistic regression was reported for the association of incident CKD with tertiles of dietary fibre intake. After adjustment for age, sex, smoking, total energy intake, physical activity, diabetes and using angiotensin-converting-enzyme inhibitor, the OR for subjects in the highest compared with the lowest tertile of total fibre intake was 0·47 (95 % CI 0·27, 0·86). In addition, for every 5 g/d increase in total fibre intake, the risk of incident CKD decreased by 11 %. After adjusting for potential confounders, OR for participants in the highest compared with the lowest tertile of fibre from vegetables was 0·63 (95 % CI 0·43, 0·93) and from legumes it was 0·68 (95 % CI 0·47, 0·98). We observed inverse associations between total fibre intake and risk of incident CKD, which demonstrate that high fibre intake, mainly from legumes and vegetables, may reduce the occurrence of CKD.

Effect of long-term low-dose folic acid supplementation on degree of total homocysteine-lowering: major effect modifiers.

We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 µmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 µmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60-<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status.

Vitamin D status in renal transplant recipients living in a low-latitude city: association with body fat, cardiovascular risk factors, estimated glomerular filtration rate and proteinuria.

Recent evidence suggests that vitamin D deficiency is associated with CVD, impaired kidney function and proteinuria. To date, no study has evaluated these associations in renal transplant recipients (RTR) adjusting for body adiposity assessed by a 'gold standard' method. This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum 25-hydroxyvitamin D (25(OH)D) concentration was used to define vitamin D status as follows: 10 % (n 19) had vitamin D deficiency (30 ng/ml). Percentage of body fat (DXA) was significantly associated with vitamin D deficiency independently of age, sex and eGFR. Lower 25(OH)D was associated with higher odds of the metabolic syndrome and dyslipidaemia after adjustment for age, sex and eGFR, but not after additional adjustment for body fat. Hypertension and diabetes were not related to 25(OH)D. Lower serum 25(OH)D was associated with increasing proteinuria and decreasing eGFR even after adjustments for age, sex and percentage of body fat. This study suggests that in RTR of a low-latitude city hypovitaminosis D is common, and is associated with excessive body fat, decreased eGFR and increased proteinuria.

Consumption of whole grains, fruit and vegetables is not associated with indices of renal function in the population-based longitudinal Doetinchem study.

Emerging evidence suggests that diet and renal function are related. Little is known, however, about the association of consumption of whole grains, fruit and vegetables with urinary albumin:creatinine ratio (ACR) and changes in estimated glomerular filtration rate (eGFR). We investigated this in a population-based cohort aged 26-65 years. Data were from 3787 participants from the Doetinchem cohort study, who were examined ≥3 times, 5 years apart. Consumption of food groups was assessed at each round with a validated FFQ. GFR was estimated at each round from routinely measured cystatin C and creatinine using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation. ACR was measured at the last round. Generalised estimated equation models were performed to examine associations with changes in eGFR. Linear regression was used to examine associations with ACR. Adjustments were made for covariates related to lifestyle, biological factors and diet. Mean baseline eGFR was 104·5 (sd 13·7) and mean annual decline was -0·95 (sd 0·67) ml/min per 1·73 m2 over a 15-year follow-up. A trend was observed towards slightly less annual decline in eGFR among those with higher consumption of whole grains (P=0·06). This association, however, was attenuated and no longer significant in multivariate models (P=0·29). Consumption of fruit and vegetables was not associated with changes in eGFR and urinary ACR. In conclusion, consumption of whole grains, fruit and vegetables is not associated with changes in eGFR and mean ACR. As this was the first longitudinal study into this association in the general population, and as results are only partially in line with related studies, further research is recommended.

Impact of low-carbohydrate diet on renal function: a meta-analysis of over 1000 individuals from nine randomised controlled trials.

We aimed to clarify the effect of low-carbohydrate diet (LCD) on renal function in overweight and obese individuals without chronic kidney disease (CKD). Literature searches were performed using EMBASE, MEDLINE and Cochrane Library until December 2015. We selected articles that reported human studies from their inception until December 2015 in English using the following searching terms: 'Low carbohydrate diet' AND ('Clinical trial' OR 'Clinical study' OR 'Clinical investigation' OR 'Observational study' OR 'Cohort study'). We compared the effects of LCD on renal function, defined as change in estimated glomerular filtration rate (eGFR), assessed in randomised-controlled trials. We calculated the mean change in eGFR and the mean change in standard deviations by eGFR or creatinine clearance, and compared the mean change in eGFR and standard deviations in LCD with those in the control diet using fixed-effects models. We selected nine randomised controlled trials including 1687 participants (861 were fed LCD and 826 were fed the control diet). The mean change in eGFR in the LCD group was -4·7 to 24·0 ml/min per 1·73 m2 and that in the control diet group was -4·1 to 10·8 ml/min per 1·73 m2. The mean change in eGFR in the LCD group was greater than that in the control diet (0·13 ml/min per 1·73 m2; 95 % CI 0·00, 0·26). In the present meta-analysis, we identified that the increase in eGFR was greater in LCD compared with the control diet in overweight and obese individuals without CKD.

Oxidative stress and nitric oxide are increased in obese children and correlate with cardiometabolic risk and renal function.

Oxidative stress and nitric oxide (NO) appear to represent important links between obesity and cardiovascular, metabolic and/or renal disease. We investigated whether oxidative stress and NO production/metabolism are increased in overweight and obese prepubertal children and correlate with cardiometabolic risk and renal function. We performed a cross-sectional evaluation of 313 children aged 8-9 years. Anthropometrics, 24-h ambulatory blood pressure, pulse wave velocity (PWV), insulin resistance (homoeostasis model assessment index (HOMA-IR)), inflammatory/metabolic biomarkers, estimated glomerular filtration rate (eGFR), plasma total antioxidant status (TAS), plasma and urinary isoprostanes (P-Isop, U-Isop), urinary hydrogen peroxide (U-H2O2), and plasma and urinary nitrates and nitrites (P-NOx, U-NOx) were compared among normal weight, overweight and obese groups, according to WHO BMI z-score reference. U-Isop were increased in the obese group, whereas U-NOx were increased in both overweight and obese children. U-Isop were positively correlated with U-H2O2, myeloperoxidase (MPO), high-sensitivity C-reactive protein, HOMA-IR and TAG. TAS correlated negatively with U-Isop and MPO and positively with PWV. HOMA-IR and U-H2O2 were associated with higher U-Isop, independently of BMI and eGFR, and total cholesterol and U-H2O2 were associated with U-NOx, independently of BMI, eGFR values and P-NOx concentration. In overweight and obese children, eGFR decreased across P-NOx tertiles (median: 139·3 (25th, 75th percentile 128·0, 146·5), 128·0 (25th, 75th percentile 121·5, 140·4), 129·5 (25th, 75th percentile 119·4, 138·3), P for linear trend=0·003). We conclude that oxidant status and NO are increased in relation to fat accumulation and, even in young children, they translate into higher values of cardiometabolic risk markers and affect renal function.

Reduction in sodium intake is independently associated with improved blood pressure control in people with chronic kidney disease in primary care.

Decreasing sodium intake has been associated with improvements in blood pressure (BP) and proteinuria, two important risk factors for CVD and chronic kidney disease (CKD) progression. We aimed to investigate the role of sodium intake by examining the effect of changes in sodium intake over 1 year on BP and proteinuria in people with early stage CKD. From thirty-two general practices, 1607 patients with previous estimated glomerular filtration rate of 59-30 ml/min per 1.73 m² and mean age of 72.9 (sd 9.0) years were recruited. Clinical assessment, urine and serum biochemistry testing were performed at baseline and after 1 year. Sodium intake was estimated from early morning urine specimens using an equation validated for this study population. We found that compared with people who increased their sodium intake from ≤ 100 to >100 mmol/d over 1 year, people who decreased their intake from >100 to ≤ 100 mmol/d evidenced a greater decrease in all BP variables (Δmean arterial pressure (ΔMAP) = -7.44 (SD 10.1) v. -0.23 (SD 10.4) mmHg; P<0.001) as well as in pulse wave velocity (ΔPWV = -0.47 (SD 1.3) v. 0.08 (SD 1.88) m/s; P<0.05). Albuminuria improved only in albuminuric patients who decreased their sodium intake. BP improved in people who maintained low sodium intake at both times and in those with persistent high intake, but the number of anti-hypertensive increased only in the higher sodium intake group, and PWV improved only in participants with lower sodium intake. Decreasing sodium intake was an independent determinant of ΔMAP. Although more evidence is needed, our results support the benefits of reducing and maintaining sodium intake below 100 mmol/d (2.3-2.4 g/d) in people with early stages of CKD.

Total Joint Arthroplasty in Patients with Chronic Renal Disease: Is It Worth the Risk?

26-27% of patients with end stage hip and knee arthritis requiring TJR have chronic renal disease. A multi-center, prospective clinical registry was queried for TJA's from 2006 to 2012, and 74,300 cases were analyzed. Renal impairment was quantified using estimated glomerular filtration rate (eGFR) to stratify each patient by stage of CRD (1-5). There was a significantly greater rate of overall complications in patients with moderate to severe CRD (6.1% vs. 7.6%, P<0.001). In those with CRD (Stage 3-5), mortality was twice as high (0.26% vs. 0.48%, P<0.001). Patients with Stage 4 and 5 CRD had a 213% increased risk of any complication (OR 2.13, 95% CI: 1.73-2.62). Surgeons may use these findings to discuss the risk-benefit ratio of elective TJR in patients with CRD.

Effect of exercise on renal function in diabetic nephropathy-a systematic review and meta-analysis.

Diabetic nephropathy causes cardiovascular complications among individuals with diabetes which results in decreased kidney function and overall physical decline. The objective of this systematic review was to determine effects of exercise on various renal function parameters amond individuals with type 2 diabetes and nephropathy. It was registered with PROSPERO (CRD42020198754). Total 6 databases (PubMed/Medline, Scopus, Web of Science, CINAHL, ProQuest, and Cochrane) were searched. Among 1734 records, only four randomized controlled trials were included. The review included a total of 203 participants (103 in the intervention group and 100 in the control/standard group) with type 2 diabetic nephropathy or stage 2,3, or 4 of chronic kidney disease. The meta-analysis showed no effects of exercise on serum creatinine, serum cystatin c and varied eGFR equations. However, exercise decreased urinary albumin to creatinine ratio, urinary protein to creatinine ratio, serum urea nitrogen, creatinine clearance, and urinary protein excretion while increasing urea clearance. Limited evidence on the reno-protective role of exercise demands future research in this direction.

Calf Circumference as an Indicator for Cystatin C Testing in Hospitalized Elderly Male Patients for Detecting Hidden Renal Impairment.

Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.

Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in bridge-to-transplant patients supported with centrifugal-flow left ventricular assist devices.

BACKGROUND: The safety and tolerability of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with end-stage heart failure supported with left-ventricular-assist-devices (LVADs), irrespective of diabetes mellitus, is not known. METHODS: A retrospective analysis of 31 outpatients implanted with LVADs as bridge-to-transplant (BTT) was conducted. Patients with biventricular support, aged under 18 years, who were discharged from the index hospitalisation, or were prescribed SGLT2i prior to their first outpatient clinic were excluded. Patient demographics, laboratory studies, pump haemodynamic and adverse event data was collected. RESULTS: Sixteen (51.6%) of 31 patients were prescribed SGLT2i over median 101.5 days (37.5-190.8). No patients discontinued SGLT2i use or reported attributable adverse symptoms. No significant differences between patients prescribed SGLT2i compared to those SGLT2i-naïve were seen in: [1] renal function; [2] weight; [3] mean arterial pressure. There were numerically lower infection-related (n = 4 vs 7, HR 0.32 (0.08-1.28), p = 0.11) and haemocompatibility-related (n = 3 vs 4, HR 0.52 (0.09-2.83), p = 0.45) adverse events in the SGLT2i group, albeit non-significant. CONCLUSIONS: We found SGLT2i to be safe and well-tolerated in the BTT LVAD cohort with no significant difference in rates of infection or haemocompatibility-related adverse events with SGLT2i use. Larger studies will inform further beneficial effects of SGLT2i prescription in this cohort.

Prasugrel-Based De-Escalation in Patients With Acute Coronary Syndrome According to Renal Function.

Background: Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI). Objectives: This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function. Methods: We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up. Results: Prasugrel de-escalation was beneficial regardless of baseline renal function (P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) (P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) (P for interaction = 0.119). Conclusions: In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function.

People with diabetes and hypovitaminosis C fail to conserve urinary vitamin C.

Background: Hypovitaminosis C has negative health consequences. People with diabetes and hypovitaminosis C may fail to conserve vitamin C in the urine, thereby displaying evidence of inappropriate renal leak of vitamin C. This study describes the relationship between plasma and urinary vitamin C in diabetes, with a focus on the clinical characteristics of participants with renal leak. Methods: Retrospective analysis of paired, non-fasting plasma and urine vitamin C, and also clinical characteristics, from participants with either type 1 or type 2 diabetes, recruited from a secondary care diabetes clinic. Plasma vitamin C thresholds for renal leak have been defined previously as 38.1 µmol/L for men and 43.2 µmol/L for women. Results: Statistically significant differences in clinical characteristics were seen between those with; i) renal leak (N = 77) and; ii) hypovitaminosis C but no renal leak (N = 13) and; iii) normal plasma vitamin C levels (n = 34). Compared to participants with adequate plasma vitamin C levels, participants with renal leak tended to have type 2 (rather than type 1) diabetes, a lower eGFR and a higher HbA1c. Conclusion: In the diabetes population studied, renal leak of vitamin C was common. In some participants, it may have contributed to hypovitaminosis C.

The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.

BACKGROUND: The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. METHODS: Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. RESULTS: We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. CONCLUSIONS: This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.

Changes in Kidney and Liver Volumes in Patients With Autosomal Dominant Polycystic Kidney Disease Before and After Dialysis Initiation.

Objective: To examine the changes in total kidney volume (TKV) and total liver volume (TLV) before and after dialysis initiation in patients with autosomal dominant polycystic kidney disease. Patients and Methods: This was a retrospective, single-center cohort study to investigate the changes in TKV and TLV before and after dialysis initiation, along with influencing factors, using linear mixed models. We enrolled 95 patients with autosomal dominant polycystic kidney disease (85 receiving hemodialysis [HD] and 10 receiving peritoneal dialysis [PD]) who began receiving dialysis at Toranomon Hospital from January 1, 2008, to December 31, 2020. Results: The least squares mean TKV ratio (TKV at each time point/TKV at dialysis initiation) was 63.8% (95% confidence interval [CI], 54.7%-72.9%) at 6 years before dialysis initiation and 95.5% (95% CI, 82.9%-108.2%) at 6 years after dialysis initiation (P<.001). A multivariate linear mixed model analysis revealed that dialysis style (HD or PD) had the strongest effect on changes in TKV (P=.002). The least squares mean TLV ratio was 98.2% (95% CI, 88.4%-108.0%) at 6 years before dialysis initiation and 95.7% (95% CI, 85.2%-106.2%) at 6 years after dialysis initiation (P=.01). Although PD did not have significant effects on changes in TLV (P=.27), the changes in TLV were greater in patients on PD than in those on HD. Conclusion: The TKV increased until dialysis initiation and generally decreased after dialysis initiation. The TLV continued to increase even after dialysis initiation, however, changes in the TLV significantly decreased after dialysis initiation. The increases in TKV and TLV were greater in patients on PD than in those on HD.