Reduction In eGFR Research Articles

Quality of life in older adults with chronic kidney disease and transient changes in renal function: Findings from the Oxford Renal cohort.

BackgroundQuality of life (QoL) is an important measure of disease burden and general health perception. The relationship between early chronic kidney disease (CKD) and QoL remains poorly understood. The Oxford Renal Study (OxRen) cohort comprises 1063 adults aged ≥60 years from UK primary care practices screened for early CKD, grouped according to existing or screen-detected CKD diagnoses, or biochemistry results indicative of reduced renal function (referred to as transient estimated glomerular filtration rate (eGFR) reduction).ObjectivesThis study aimed to compare QoL in participants known to have CKD at recruitment to those identified as having CKD through a screening programme.MethodsHealth profile data and multi-attribute utility scores were reported for two generic questionnaires: 5-level EuroQol-5 Dimension (EQ-5D-5L) and ICEpop CAPability measure for Adults (ICECAP-A). QoL was compared between patients with existing and screen-detected CKD; those with transient eGFR reduction served as the reference group in univariable and multivariable linear regression.ResultsMean and standard deviation utility scores were not significantly different between the subgroups for EQ-5D-5L (screen-detected:0.785±0.156, n = 480, transient:0.779±0.157, n = 261, existing CKD:0.763±0.171, n = 322, p = 0.216) or ICECAP-A (screen-detected:0.909±0.094, transient:0.904±0.110, existing CKD:0.894±0.115, p = 0.200). Age, smoking status, and number of comorbidities were identified as independent predictors of QoL in this cohort.ConclusionQoL of participants with existing CKD diagnoses was not significantly different from those with screen-detected CKD or transient eGFR reduction and was similar to UK mean scores for the same age, suggesting that patient burden of early CKD is minor. Moreover, CKD-related comorbidities contribute more significantly to disease burden in earlier stages of CKD than renal function per se. Larger prospective studies are required to define the relationship between QoL and CKD progression more precisely. These data also confirm the essentially asymptomatic nature of CKD, implying that routine screening or case finding are required to diagnose it.

Incidence of chronic renal injury in patients undergoing autologous stem cell transplant therapy.

Haemopoietic stem cell transplant (HSCT) is a well-established treatment option for many haematologic immunologic and oncologic diseases, allowing the safe administration of high-dose chemotherapy. Increased risk of acute renal injury is associated with HSCT; however, the risk of chronic kidney injury in autologous HSCT remains unclear. This cohort study investigates the incidence of chronic renal injury and its predisposing factors in a single-centre population of 139 patients who underwent autologous HSCT. Estimated glomerular filtration rate (eGFR) was measured at baseline and at 3, 6, 12 and 24 months following autologous stem cell reinfusion and used as a marker of renal dysfunction. A significant reduction in mean eGFR of patients was observed from baseline (80.62 ± 2.97 mL/min) to 24 months (71.54 ± 4.14 mL/min), independent of primary diagnosis (P= 0.0019). At baseline, 12% of the cohort had stage 3 or worse chronic renal injury and this increased to 38% by 24 months. By univariate analysis, age at baseline greater than the mean of 58 years and the occurrence of acute kidney injury during the peritransplant period emerged as predictive factors for the development of chronic kidney disease at 24 months. The current results indicate there is an increased incidence of chronic renal injury in patients who have undergone autologous peripheral blood haemopoietic stem cell transplantation therapy and this injury is potentiated by the autologous stem cell transplant procedure.

Baseline cardiovascular risk in subjects with type 2 diabetes and chronic kidney disease from the FLOW trial

Abstract Background Patients with chronic kidney disease and type 2 diabetes (T2D) have a high risk of progression to kidney failure as well as cardiovascular (CV) events. It is established that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and reduce body weight. Some CV outcomes trials have shown that GLP-1RAs reduce CV risk in people with T2D at high CV risk; for example, the SUSTAIN 6 trial demonstrated that the GLP-1RA semaglutide significantly lowered the rate of major CV events (CV death, non-fatal myocardial infarction and non-fatal stroke) versus placebo. Some trials have also indicated that GLP-1RAs reduce albuminuria and estimated glomerular filtration rate (eGFR) decline. Based on these previous results indicating potential kidney-protective effects, the FLOW trial (NCT03819153) is evaluating once-weekly, subcutaneous semaglutide 1.0 mg versus placebo on kidney- and CV-related outcomes in participants with T2D. We describe the baseline characteristics and the calculated CV risk of this patient population using the atherosclerotic CV disease (ASCVD) and second manifestations of arterial disease (SMART) risk calculators. Methods FLOW is an ongoing, multicentre, randomised, double-blind, parallel-group, event-driven, phase 3b trial, with participants randomised 1:1 to semaglutide or placebo, each in addition to standard of care. Recruitment is complete and 3,535 participants with T2D, an eGFR ≥25–≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio ≥100–≤5,000 mg/g have been enrolled. The primary endpoint is time to first occurrence of a kidney composite that includes ≥50% persistent eGFR reduction, kidney failure (persistent eGFR <15 mL/min/1.73 m2 or initiation of chronic dialysis or kidney transplantation), and kidney-related death, or CV death. Key secondary outcomes include time to first occurrence of CV death, myocardial infarction or stroke. Results The baseline clinical characteristics and demographics are shown (Table 1). Median age was 68 years, 30% were female, mean diabetes duration was 17 years, and 98% had a history of hypertension. Overall, 52% of participants had a previous CV event. The calculated 10-year risk for ASCVD events in those without prior ASCVD was 31% in males and 18% in females, and in those with previous CV events was 37–56% in males and 35–53% in females depending on the type of CV disease reported in the calculator (Table 2). Conclusions The FLOW trial has completed enrolment. Based on the ASCVD and SMART risk calculators, the enrolled population has a substantial risk for adverse CV outcomes. Event ascertainment is ongoing, and the FLOW trial will provide evidence for the potential of semaglutide to improve kidney and CV outcomes in the T2D population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk

S1209 Longer Time to Recovery From Acute Kidney Injury Is Associated with Increased Major Adverse Kidney Events in Patients With Cirrhosis

Introduction: In patients with cirrhosis, non-recovery from acute kidney injury (AKI) is associated with major adverse kidney events (MAKE). However, in patients with AKI recovery, little is known about how the timing of recovery affects the risk of MAKE. Thus, we aimed to examine the association between timing of recovery and risk of MAKE in patients with AKI recovery. Methods: Hospitalized patients with cirrhosis and AKI in the Cerner Health Facts database from 1/2009-09/2017 were assessed for AKI recovery and were followed for 180 days for outcomes. The timing of AKI recovery [return of serum creatinine (sCr) < 0.3mg/dL of baseline] from AKI onset was grouped into 0-2, 3-7, 8-14, and >14 days. The primary outcome was MAKE at 90-180 days. Per consensus definition, MAKE was defined as the composite outcome of >25% decline in estimated glomerular filtration rate (eGFR) compared with baseline with CKD stage >3 or progression of CKD (defined as >50% reduction in eGFR compared with baseline) or new hemodialysis. Competing risk multivariable modeling (death/transplant as competing risk) was performed to determine the independent association between timing of recovery and risk of MAKE. Results: Out of 6,250 eligible patients, 4,655 (75%) achieved AKI recovery. The median age was 60 years [interquartile range (IQR) 25, 70], 71% White and 60% male. The most common etiologies of cirrhosis were non-alcoholic steatohepatitis (38%), alcohol (27%), and hepatitis C (17%), and the median (IQR) MELD-Na score was 23 (16, 28). 60% had ascites and the median baseline sCr was 1.00 (0.70, 1.44) mg/dL. The characteristics of patients who recovered 0-2 (n=2,791, 60%), 3-7 (n=1,455, 31%), , 8-14 (n=255, 5%), and >14 days (n=184, 4%) after AKI are shown in Table. The incidence of MAKE was 12%, 16%, 22%, and 25% for 0-2, 3-7, 8-14, and >14 days recovery groups, respectively. On adjusted multivariable competing risk analysis, compared to 0-2 days, recovery at 3-7, 8-14, and >14 days was independently associated with an increased risk for MAKE: sHR 1.48 (95% CI 1.03-2.14, p=0.036), sHR 2.92 (95% CI 1.11-4.31, p=0.023), and sHR 2.60 (95% CI 1.37-4.96, p=0.004), respectively. Conclusion: In patients with cirrhosis who recover from AKI, longer time to recovery is associated with an increased risk of major adverse kidney events. Interventions to hasten recovery from AKI should be considered in patients with cirrhosis who develop AKI. Table 1. - Comparison of Patient and Clinical Demographics Between AKI Recovery Groups Variable 0-2 Days N=2,791 3-8 Days N=1,455 8-14 days N=225 >14 days N=184 P-value Age 60 (52, 69) 62 (53, 71) 62 (55, 71) 60 (50, 68) < 0.001 Race, white 71 71 68 68 0.069 Sex, male 61 59 60 59 0.925 Etiology of cirrhosis Hepatitis C Alcohol NASH Other Unknown etiology 17 29 37 5 12 18 24 40 6 12 17 19 47 6 11 21 27 34 6 12 0.635 0.001 0.006 0.518 0.966 Ascites 56 66 68 73 < 0.001 Hepatic encephalopathy 25 27 31 32 0.054 Diabetes 50 55 64 54 < 0.001 Hypertension 57 60 63 9 0.044 Baseline creatinine, mg/dL 0.94 (0.70, 1.44) 1.00 (0.74, 1.42) 1.10 (0.80, 1.74) 1.07 (0.76, 1.82) < 0.001 MELD-Na at time of AKI 20 (14, 26) 24 (19, 29) 26 (21, 30) 26 (23, 31) < 0.001 Stage of AKI at diagnosis 1/2/3 87/10/3 69/20/11 61/21/18 63/14/13 < 0.001 Peak AKI stage 1/2/3 75/13/12 48/27/25 20/31/49 16/21/63 < 0.001 Infection 25 30 41 35 < 0.001 Required ICU care 24 28 37 33 < 0.001 Mechanical ventilation use 12 14 24 12 < 0.001 Vasopressor use 14 17 24 23 < 0.001 Continuous variables shown as median interquartile range (IQR); categorical variables presented as %.

Efficacy and safety of empagliflozin in people with type 2 diabetes during Ramadan fasting

Background and aimsTo explore efficacy and safety of empagliflozin in people with type2 diabetes during Ramadan fasting MethodsPeople with type2 diabetes (T2DM) who were taking empagliflozin and sulphonylurea with or without a metformin and dipeptidyl peptidase inhibitors (DPP4) recruited a month before Ramadan. Glycated hemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR) were recorded pre- and post-Ramadan. A predesigned diary was given to the participants to keep track of their T2DM status during Ramadan. The proportion of the people who had hypoglycaemia, or any adverse event related to the study drug was assessed after-Ramadan. ResultsA total of 116 participants completed the study. Symptomatic episodes of hypoglycaemia were more common among people who used sulphonylurea (i.e., 8.6%). Genitourinary infections and volume depletion events were recorded more in people on empagliflozin i.e., (6.9% and 5.17%, respectively). A significant reduction in body mass index (BMI), and HbA1c was noted among people on empagliflozin post Ramadan. A significant reduction in eGFR was noted only in people who were taking empagliflozin in combination with metformin. ConclusionEmpagliflozin was found to be safe and effective in fasting people with T2DM. Further large-scale studies are needed to validate our findings.

Estimation of Glomerular Filtration Rate Using Serum Cystatin C as an Early Predictor of Renal Insufficiency in Overweight/ Obese Children and Adolescents with Non-alcoholic Fatty Liver Disease

Background: NAFLD is a clinical spectrum ranging from steatosis (fatty infiltration) to steatosis with inflammation, necrosis, fibrosis and cirrhosis resembling alcoholic hepatitis in the absence of alcoholic abuse. The aim of this work was to determine early renal functional alterations in overweight / obese children and adolescents with NAFLD, as assessed by estimated glomerular filtration rate using cystatin C, and to evaluate its relation to the degree and various clinic-laboratory parameters of NAFLD.&#x0D; Methods: This case control research included 60 overweight and obese children and adolescent. The Cases were classified into two equal groups: group 1: overweight or obese children and adolescents with NAFLD and group 2: overweight or obese children and adolescents without NAFLD. Twenty healthy age-and-sex matched children with BMI less than the 85th percentile for age and sex were chosen as controls.&#x0D; Results: There was significantly positive correlation among serum cystatin C and weight, BMI, Waist/Hip ratio, ALT, AST, cholesterol, Hip circumference, Fasting plasma insulin and Insulin resistance. There was significantly negative correlation among serum cystatin C and eGFR. There were significant negative correlations between eGFR and weight z score, BMI z score, hip circumference, waist/hip ratio, ALT, AST, cholesterol, fasting plasma insulin, insulin resistance and cystatin C.&#x0D; Conclusions: Serum Cystatin C correlated significantly to the degree of hepatic steatosis. Values of eGFR were significantly lower in NAFLD patients compared to those without NAFLD and controls. The reduction in eGFR was correlated significantly with the degree of hepatic steatosis. There was a statistically significant negative correlation between serum cystatin C and eGFR. Levels of eGFR were significantly correlated with weight, BMI, W/H ratio, ALT, AST, cholesterol and insulin resistance.

Predictive Factors of Renal Function Decline in Patients with Type 2 Diabetes Treated with Canagliflozin in the Real-Wecan Study.

The Real-WECAN study evaluated the real-life effectiveness and safety of canagliflozin 100 mg daily (initiated in SGLT-2 inhibitors naïve patients) and canagliflozin 300 mg daily (switching from canagliflozin 100 mg or other SGLT-2 inhibitors) in individuals with type 2 diabetes. The objectives of this sub-analysis were to estimate the eGFR slope over the follow-up period and to identify predictive factors of eGFR decline in a multiple linear regression analysis. A total of 583 patients (279 on canagliflozin 100 mg and 304 on canagliflozin 300 mg) were included, with median follow-up at 13 months. The patients had a mean age of 60.4 years, HbA1c of 7.76%, BMI of 34.7 kg/m2, eGFR below 60 mL/min/1.73 m2 8.6%, and urine albumin-to-creatinine ratio (UACR) above 30 mg/g 22.8%. eGFR decreased by −1.9 mL/min/1.73 m2 (p < 0.0001) by the end of the study. The mean eGFR slope during the maintenance phase was −0.16 mL/min/1.73 m2 per year. There were no significant differences between both doses of canagliflozin in the eGFR reduction or in the eGFR slope. The best predictive multivariate model of eGFR decline after canagliflozin therapy included age, hypertension, combined hyperlipidemia, heart failure, eGFR and severely increased albuminuria. All these variables except hypertension were independently associated with the outcome. In conclusion, in this real-world study, individuals with older age, combined hyperlipidemia, heart failure, higher eGFR and UACR > 300 mg/g showed a greater decline in their eGFR after canagliflozin treatment.

On-Clamp vs. Off-Clamp Robot-Assisted Partial Nephrectomy for cT2 Renal Tumors: Retrospective Propensity-Score-Matched Multicenter Outcome Analysis.

Simple SummaryRobot-assisted partial nephrectomy is a viable option to treat tumors >7 cm. In this setting, however, the risk of postoperative renal function deterioration is higher because of the prolonged warm ischemia times (>20 min) that are required in two-thirds of cases, if an on-clamp approach is used. On the contrary, an off-clamp robotic partial nephrectomy is associated with shorter operation times and significantly improves the probabilities of achieving favorable perioperative outcomes.We compared perioperative outcomes after on-clamp versus off-clamp robot-assisted partial nephrectomy (RAPN) for >7 cm renal masses. A multicenter dataset was queried for patients who had undergone RAPN for a cT2cN0cM0 kidney tumor from July 2007 to February 2022. The Trifecta achievement (negative surgical margins, no severe complications, and ≤ 30% postoperative estimated glomerular filtration rate (eGFR) reduction) was considered a surrogate of surgical quality. Overall, 316 cases were included in the analysis, and 58% achieved the Trifecta. A propensity-score-matched analysis generated two cohorts of 89 patients homogeneous for age, ASA score, preoperative eGFR, and RENAL score (all p > 0.21). Compared to the on-clamp approach, OT was significantly shorter in the off-clamp group (80 vs. 190 min; p < 0.001), the incidence of sRFD was lower (22% vs. 40%; p = 0.01), and the Trifecta rate higher (66% vs. 46%; p = 0.01). In a crude analysis, >20 min of hilar clamping was associated with a significantly higher risk of sRFD (OR: 2.30; 95%CI: 1.13–4.64; p = 0.02) and with reduced probabilities of achieving the Trifecta (OR: 0.46; 95%CI: 0.27–0.79; p = 0.004). Purely off-clamp RAPN seems to be a safe and viable option to treat cT2 renal masses and may outperform the on-clamp approach regarding perioperative surgical outcomes.

Long-term prognosis of primary focal segmental glomerulosclerosis in children

Objective: To investigate risk factors for the long-term prognosis of primary focal segmental glomerulosclerosis (FSGS) and associated with renal prognosis in children. Methods: A retrospective study was conducted by collecting clinical data including general information, clinical features and renal pathological findings of 124 children with primary FSGS in Department of Pediatrics of Jinling Hospital from January 2003 to December 2019. The cumulative renal survival rate was calculated by Kaplan-Meier survival analysis. The risk factors related to renal prognosis were identified by Cox regression risk model analysis and receiver operating characteristic (ROC) curve. Results: Among 124 children, 94 were males (75.8%) and 30 were females (24.2%). The children were 16 (14, 17) years of age at the time of kidney biopsies. There were 102 cases (82.3%) aged from 13 to 18 years. The period of follow-up was 64.8 (32.1, 86.0) months. There were 49 cases (39.5%) with nonspecific variant, 33 cases (26.6%) with tip variant, 22 cases (17.7%) with collapsing variant, 14 cases (11.3%) with cellular variant and 6 cases (4.8%) with periportal variant. The data of Kaplan-Meier survival analysis showed that cumulative renal survival rates of end-stage kidney disease (ESKD) or ≥50% decline in estimated glomerular filtration rate (eGFR) from baseline at the year of 5, 10 and 15 after renal biopsies were 66.9%, 51.4% and 21.0% respectively. Multivariate Cox regression analysis showed that hypertension, glomerular segmental sclerosis ratio, moderate to severe chronic tubulointerstitial lesions were independent risk factors for progressing to ESKD or ≥50% reduction in eGFR from baseline in pediatric FSGS (HR=5.28, 1.03, 7.81, 95%CI 2.77-10.05, 1.01-1.04, 4.08-14.98, all P<0.01). ROC curve analysis showed glomerular segmental sclerosis ratio (AUC=0.734, P<0.05, optimal cut-off value=25.4%, sensitivity=50.0%, specificity=88.6%), moderate and severe chronic renal tubulointerstitial lesions (AUC=0.724, P<0.05, sensitivity=46.3%, specificity=98.6%) had good efficacy in evaluating renal outcomes of FSGS. Conclusions: The long-term prognosis of FSGS in children is poor. The risk factors of poor prognosis in children with FSGS are hypertension, moderate to severe chronic renal tubulointerstitial lesions and glomerular segmental sclerosis (≥25.4%).

Perioperative Management and Outcomes of Hip Fracture Patients with Advanced Chronic Kidney Disease.

To explore clinical characteristics, perioperative management and outcomes of Hip Fracture patients with advanced Chronic Kidney Disease (HF-aCKD) compared to the general Hip Fracture population without aCKD (HF-G) within a large volume tertiary hospital in Western Australia. Retrospective chart review of patients admitted with hip fracture (HF) to a single large volume tertiary hospital registered on Australian and New Zealand Hip Fracture Registry (ANZHFR). We compared baseline demographic and clinical frailty scale (CFS) of HF-aCKD (n = 74), defined as eGFR < 30mls/min/1.73m2, with HF-G (n = 452) and determined their outcomes at 120days. We identified 74 (6.97%) HF patients with aCKD. General demographics were similar in HF-aCKD and HF-G populations. 120-days mortality for HF-aCKD was double that of HF-G population (34% vs 17%, P = .001). For dialysis patients, 120-days mortality was triple that of HF-G population (57%). Except for the fit category of HF-aCKD group, higher CFS was associated with higher 120-days mortality in both groups. Of all HF-aCKD patients, 96% had operative intervention and 48% received blood transfusion. There were no new starts to dialysis peri-operatively. Each point reduction in eGFR below 12mL/min/1.73m2 was associated with 3% increased probability of death in hospital. 120-days mortality was double in HF-aCKD and triple in HF-dialysis that of the HF-G within our institution. Clinical frailty scale can be useful in predicting mortality after HF in frail aCKD patients. High rate of blood transfusions was observed in HF-aCKD group. Further studies with larger HF-aCKD numbers are required to explore these associations in detail.

Tuberculosis and diabetes: increased hospitalisations and mortality associated with renal impairment.

Diabetes mellitus (DM) triples a person's risk of active tuberculosis (TB) and is associated with increased mortality. It is unclear whether diabetes status and/or the associated renal dysfunction is associated with poor TB outcomes in New Zealand, which has high diabetes screening. To characterise the population of TB-DM and TB-alone to assess the effect of diabetes status and renal function on hospitalisation and mortality. Clinical records from all adult patients diagnosed with TB in Auckland over a 6-year period (2010-2015) were reviewed. Baseline demographics, clinical presentation and microbiological data were assessed to compare the rates of hospitalisation and mortality between those with TB-DM and TB-alone. Statistical significance was defined as P < 0.05. A total of 701 patients was identified with TB; 120 (17%) had an unknown diabetes status and were excluded, and 135 had co-existing diabetes. The TB-DM and TB-alone groups had similar distribution of TB site and proportions of Mycobacterium tuberculosis culture positivity. Univariate analysis showed TB-DM patients had statistically significantly higher proportions of acute hospitalisation and mortality. Multivariate logistic regression showed only a reduced estimated glomerular filtration rate (eGFR) accounted for the higher rates of hospitalisation, with the odds of hospitalisation increasing by 2% for every unit decrease in eGFR. The odds of mortality increased by 6% for every year increase in age, and the odds of mortality increased by 3% for every unit reduction in eGFR. Diabetes is associated with higher TB hospitalisation and mortality; however, this is likely mediated by increased age and chronic kidney disease.

Comparison between outcomes of IgA nephropathy with nephrotic-range proteinuria and nephrotic syndrome: do podocytes play a role?

Background Nephrotic syndrome (NS) and nephrotic-range proteinuria (NRP) are uncommon in IgA nephropathy (IgAN), and their clinicopathology and prognosis have not been discussed. Podocytes may play an important role in both clinical phenotypes. Methods We investigated 119 biopsy-proven IgAN patients with proteinuria over 2 g/d. The patients were divided into three groups according to proteinuria level: the overt proteinuria (OP) group, NS group, and NRP group. In addition, according to the severity of foot process effacement (FPE), the patients were divided into three groups: the segmental FPE (SFPE) group, moderate FPE (MFPE) group, and diffuse FPE (DFPE) group. The outcome was survival from a combined event defined by a doubling of the baseline serum creatinine and a 50% reduction in eGFR or ESRD. Results Compared with the NRP group, patients in the NS group had more severe microscopic hematuria, presented with more severe endocapillary hypercellularity and had a higher percentage of DFPE. The Kaplan–Meier curve showed that MFPE patients had a better outcome in the NRP group <50% of tubular atrophy/interstitial fibrosis. In the multivariate model, the NRP group (HR = 17.098, 95% CI = 3.835–76.224) was associated with an increased risk of the combined event, while MFPE (HR = 0.260, 95% CI = 0.078–0.864; p = 0.028) was associated with a reduced risk of the combined event. After the addition of renin-angiotensin system inhibitors (RASi), the incidence of the combined event in the MFPE group (HR = 0.179, 95% CI = 0.047–0.689; p = 0.012) was further reduced. Conclusions NS presented more active lesions and more severe FPE in IgAN. NRP was an independent risk factor for progression to the renal endpoint, while MFPE indicated a better prognosis in NRP without obvious chronic renal lesions, which may benefit from RASi.

Dose-Response Analysis of the Tubular and Glomerular Effects of Chronic Exposure to Environmental Cadmium.

We retrospectively analyzed data on the excretion of cadmium (ECd), β2-microglobulin (Eβ2M) and N-acetyl-β-D-glucosaminidase (ENAG), which were recorded for 734 participants in a study conducted in low- and high-exposure areas of Thailand. Increased Eβ2M and ENAG were used to assess tubular integrity, while a reduction in the estimated glomerular filtration rate (eGFR) was a criterion for glomerular dysfunction. ECd, Eβ2M and ENAG were normalized to creatinine clearance (Ccr) as ECd/Ccr, Eβ2M/Ccr and ENAG/Ccr to correct for interindividual variation in the number of surviving nephrons and to eliminate the variation in the excretion of creatinine (Ecr). For a comparison, these parameters were also normalized to Ecr as ECd/Ecr, Eβ2M/Ecr and ENAG/Ecr. According to the covariance analysis, a Cd-dose-dependent reduction in eGFR was statistically significant only when Ecd was normalized to Ccr as ECd/Ccr (F = 11.2, p < 0.001). There was a 23-fold increase in the risk of eGFR ≤ 60 mL/min/1.73 m2 in those with the highest ECd/Ccr range (p = 0.002). In addition, doubling of ECd/Ccr was associated with lower eGFR (β = −0.300, p < 0.001), and higher ENAG/Ccr (β = 0.455, p < 0.001) and Eβ2M/Ccr (β = 0.540, p < 0.001). In contrast, a covariance analysis showed a non-statistically significant relationship between ECd/Ecr and eGFR (F = 1.08, p = 0.165), while the risk of low eGFR was increased by 6.9-fold only among those with the highest ECd/Ecr range. Doubling of ECd/Ecr was associated with lower eGFR and higher ENAG/Ecr and Eβ2M/Ecr, with the β coefficients being smaller than in the Ccr-normalized dataset. Thus, normalization of Cd excretion to Ccr unravels the adverse effect of Cd on GFR and provides a more accurate evaluation of the severity of the tubulo-glomerular effect of Cd.

Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial.

In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk. In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes. Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001). Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease.

Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa≥ 1+ and the kappa-lambda codominant (KL) group by a difference< 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria< 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P= 0.04) in the LD group, but no other significant difference in histopathologic features. In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.

Kidney function and prescribed dose in middle-aged and older patients starting selective serotonin reuptake inhibitors.

PurposeTo avoid adverse drug reactions, dose reductions are recommended when prescribing selective serotonin reuptake inhibitors (SSRIs) to patients with impaired kidney function. The extent of this practice in routine clinical care is however unknown. We aimed to evaluate the starting and maintenance SSRI doses prescribed to patients stratified by levels of kidney function in real‐world practice.MethodsUsing data from the Stockholm CREAtinine Measurements (SCREAM) project, we identified 101 409 new users of antidepressants (including 52 286 SSRI users) in the region of Stockholm during 2006–2019, who were ≥50 years of age and had a recent creatinine test taken in order to estimate glomerular filtration rate (eGFR). SSRI dose reduction was defined as a prescribed SSRI dose of ≤0.5 defined daily doses, according to current recommendations. We examined the associations between eGFR and reductions in initial dose and maintenance dose of SSRIs using logistic regression models.ResultsOverall, reductions in initial and maintenance dose were observed among 54.1% and 34.1% of new SSRI users. Nevertheless, about 40% of individuals with an eGFR <30 ml/min/1.73 m2 were prescribed an SSRI without dose reduction. After adjusting for age and other covariates, lower eGFR was associated with moderately higher odds of dose reduction, for both initial and maintenance dose. Compared to individuals with an eGFR of 90–104 ml/min/1.73 m2, the adjusted odds ratios for those with an eGFR <30 ml/min/1.73 m2 were 1.18 (95% CI: 1.03, 1.36) for initial dose reduction, and 1.49 (1.29, 1.72) for maintenance dose reduction. Stratified analyses showed stronger associations between lower eGFR and SSRI dose reduction among individuals aged 50–64 years and in those receiving prescriptions from psychiatric care.ConclusionsLower kidney function was moderately associated with a reduced SSRI dose, independently of age. Prescribing SSRIs to middle‐aged and older patients should not only consider patients' age but also their kidney function.

Effects of elevated serum urate on cardiometabolic and kidney function markers in a randomised clinical trial of inosine supplementation

In observational studies, serum urate positively associates with cardiometabolic and kidney diseases. We analyzed data from a randomised placebo-controlled trial to determine whether moderate hyperuricemia induced by inosine affects cardiometabolic and kidney function markers. One hundred and twenty post-menopausal women were recruited into a 6-month randomised, double-blind, placebo-controlled trial of inosine for bone health. Change from baseline in the following pre-specified endpoints was analyzed: body mass index; blood pressure; lipid profile; C-reactive protein; fasting glucose; insulin; HbA1c; serum creatinine; and estimated glomerular filtration rate (eGFR). Despite increases in serum urate levels (+ 0.17 mmol/L at week 6, P < 0.0001), no significant between-group differences were observed in cardiometabolic markers, with the exception of lower fasting glucose concentrations with inosine at week 19. In the inosine group, change in serum urate correlated with change in serum creatinine (r = 0.41, P = 0.0012). However, there was no between-group difference in serum creatinine values. Over the entire study period, there was no significant difference in eGFR (ANCOVA P = 0.13). Reduction in eGFR was greater in the inosine group at Week 13 (mean difference − 4.6 mL/min/1.73 m2, false detection rate P = 0.025), with no between-group difference in eGFR at other time points. These data indicate that increased serum urate does not negatively influence body mass index, blood pressure, lipid profile, or glycaemic control. Serum urate changes associated with inosine intake correlate with changes in serum creatinine, but this does not lead to clinically important reduction in kidney function over 6 months.Clinical trial registration number: Australia and New Zealand Clinical Trials Registry (ACTRN12617000940370), registered 30/06/2017.

Diverting ileostomy is a risk factor for renal impairment during CAPOX therapy.

Temporary ileostomy is sometimes created after colorectal surgery and may cause renal impairment. However, the impact of ileostomy on renal function during adjuvant chemotherapy for colorectal cancer (CRC) remains unknown. The aim of the present study was to examine the effects of ileostomy on renal function during adjuvant chemotherapy. We examined 184 patients who received adjuvant CAPOX therapy (capecitabine and oxaliplatin) for CRC with or without ileostomy between January 2011 and December 2020 at the University of Tokyo Hospital. Clinicopathological factors, including renal function, were retrospectively reviewed in association with temporary ileostomy. Factors associated with reductions in the estimated glomerular filtration rate (eGFR) during CAPOX therapy were analyzed. Eighteen patients (10%) underwent temporary ileostomy. The maximum decrease in eGFR during CAPOX therapy was significantly higher in patients with than in those without ileostomy (-16.1 vs. -5.6mL/min/1.73m2, p = 0.003). A multivariate analysis identified ileostomy as one of factors independently associated with reductions in eGFR during CAPOX therapy (p = 0.003). The cumulative number of readmission due to dehydration was also higher in patients with ileostomy (33% vs. 1%, p < 0.001). Ileostomy significantly reduced eGFR during adjuvant CAPOX therapy. Therefore, renal function needs to be monitored during CAPOX therapy, particularly in patients with ileostomy.

Identification of Major Risk Factors and Non-linear Effects to the Development of Left Ventricular Hypertrophy in Chronic Kidney Disease by Constructing and Validation of Nomograms

BackgroundLeft ventricular hypertrophy (LVH) is a common cardiovascular complication among chronic kidney disease (CKD) patients. The present study aimed to identify major independent risk factors and determine their contribution and relationship to LVH development.MethodsClinical and echocardiographic data of 2002 pre-dialytic CKD patients were retrospectively collected. Independent risk factors for LVH were identified using univariable and multivariable logistic regression. Nomograms together with restricted cubic splines method were employed to explore the effect size and possible non-linear relationship with regard to LVH. A simplified predictive model was constructed and its predictive ability was validated to demonstrate to which extent the identified risk factors accounted for LVH risk.ResultsMultivariable logistic regression identified age, body mass index (BMI), systolic blood pressure (SBP), eGFR and hemoglobin as independent influencing factors for LVH. Nomogram revealed BMI, SBP and hemoglobin concentration as the most important risk factors. Impaired renal function only showed obvious risk for LVH when eGFR declined below 30 ml/min/1.73 m2. Significant threshold effects existed for blood pressure and obesity that the risks for LVH doubled when SBP exceeded 160 mmHg or BMI exceeded 30 kg/m2. The predictive model constructed performed well on both the training and validation cohort using calibration curve, ROC curve and AUC value, with AUC above 0.80 for both the training cohort and the validation cohort.ConclusionsWith the help of nomogram model, we identified five independent factors that explain a large proportion of LVH risk in CKD patients. Among them, major contribution to LVH development was resulted from comorbidities and complications of CKD (hypertension, anemia, obesity) rather than eGFR reduction per se. Non-linear relationship and threshold relationship between eGFR, blood pressure, obesity and LVH risk were also identified.

Non-diabetic urine glucose in idiopathic membranous nephropathy

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-β-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.