Adverse Renal Outcomes In Patients Research Articles

Association of triglyceride glucose index with the risk of acute kidney injury in patients with coronary revascularization: a cohort study

BackgroundThe triglyceride glucose (TyG) index is a novel and reliable alternative marker for insulin resistance. Previous studies have shown that TyG index is closely associated with cardiovascular outcomes in cardiovascular diseases and coronary revascularization. However, the relationship between TyG index and renal outcomes of coronary revascularization is unclear. The purpose of this study was to investigate the correlation between TyG index and the risk of acute kidney injury (AKI) in patients with coronary revascularization.MethodsA retrospective cohort study was conducted to select eligible patients with coronary revascularization admitted to ICU in the medical information mart for intensive care IV (MIMIC-IV). According to the TyG index quartile, these patients were divided into four groups (Q1-Q4). The primary endpoint was the incidence of AKI, and secondary endpoints included 28-day mortality and the rate of renal replacement therapy (RRT) use in the AKI population. Multivariate Cox regression analysis and restricted cubic splines (RCS) were used to analyze TyG index association with AKI risk. Kaplan-Meier survival analysis was performed to assess the incidence of endpoints in the four groups.ResultsIn this study, 790 patients who underwent coronary revascularization surgery were included, and the incidence of AKI was 30.13%. Kaplan-Meier analysis showed that patients with a high TyG index had a significantly increased incidence of AKI (Log-rank P = 0.0045). Multivariate Cox regression analysis showed that whether TyG index was a continuous variable (HR 1.42, 95% CI 1.06–1.92, P = 0.018) or a categorical variable (Q4: HR 1.89, 95% CI 1.12–3.17, P = 0.017), and there was an independent association between TyG index and AKI in patients with coronary revascularization. The RCS curve showed a linear relationship between higher TyG index and AKI in this particular population (P = 0.078). In addition, Kaplan-Meier analysis showed a significantly increased risk of RRT application in a subset of AKI patients based on quartiles of TyG index (P = 0.029).ConclusionTyG index was significantly associated with increased risk of AKI and adverse renal outcomes in patients with coronary revascularization. This finding suggests that the TyG index may be useful in identifying people at high risk for AKI and poor renal outcomes in patients with coronary revascularization.

#1829 Intravenous contrast exposure in stable CKD 4 and 5 patients and adverse renal outcomes: a propensity-score matched study

Abstract Background and Aims Previous studies of intravenous (IV) contrast administration in patients with CKD have focused on the association between contrast exposure and AKI. Here we explore the association of IV contrast administration for CT imaging with a broader range of adverse renal outcomes in patients with advanced CKD (stages 4 and 5). Method Data covering nephrology care in the West of Scotland were obtained from the Strathclyde Electronic Renal Patient Record. We included adult patients with an incident CT scan and an eGFR < 30 mL/min/1.73 m2 between April 2008 and May 2020. Patients with AKI were excluded. Structured query language (SQL) was used to analyse CT scan reports and identify whether IV contrast had been administered or not. Patient demographics (age, sex, Scottish index of multiple deprivation), co-morbidities, laboratory tests (including eGFR slope for 6 months preceding the study calculated by linear regression, eGFR at time of CT, C-reactive protein, urine protein:creatinine ratio), anthropometric measurements (blood pressure, body mass index), and medications were collected. The primary outcome was a composite renal outcome (AKI, sustained eGFR drop, renal replacement therapy [RRT], and renal death). Secondary outcomes included individual components of the composite outcome and all-cause death. AKI was defined as a 25% creatinine rise from index creatinine between days 7 and 14 post CT. Sustained eGFR drop was defined as two consecutive eGFR < 15 mL/min/1.73 m2 more than 4 weeks apart. Renal death was defined as death from acute kidney injury, chronic kidney disease or end stage renal disease without dialysis. A propensity-score matched dataset was created using a 1:2 ratio with no replacement. Multivariable logistic, proportional hazards and Fine-Gray (competing risks) regressions were used to identify independent correlates of the primary and secondary outcomes. Missing data were multiply imputed using the “mice: Multivariate Imputation by Chained Equations” package on R studio. Results 9226 patients with an eGFR < 30 mL/min/1.73 m2 underwent an incident CT scan during the study period. Among 6371 patients meeting the inclusion criteria (3067 (48.1%) men; mean [SD] age 72.8 [13.8] years; mean [SD] eGFR 20.4 [6.9] ml/min/1.73 m2), 875 had received IV contrast. A propensity-score matched dataset was generated consisting of 875 patients who had a contrast CT and 1750 patients with non-contrast CT. On multivariable analysis, contrast administration was associated with a higher risk of AKI (HR 1.49, 95% CI 1.06-2.10, p = 0.02) but not with the composite renal outcome (HR 0.89, 95% CI 0.66-1.20, p = 0.45). Contrast administration did not change the risk of a sustained eGFR drop (HR 0.88, 95% CI 0.54-1.43, p = 0.60), RRT (HR 0.85, 95% CI 0.61-1.20, p = 0.36), or all-cause death (HR 0.95, 95% CI 0.76-1.19, p = 0.65). We did not identify an effect of contrast administration on the time to composite renal outcome, RRT, or all-cause death by Cox regression (HR 0.92, 95% CI 0.70-1.22, p = 0.56; HR 0.88, 95% CI 0.64-1.23, p = 0.46; and HR 1.07, 95% CI 0.94-1.20, p = 0.30, respectively). On Fine-Gray regression, we did not identify an impact of contrast administration on the risk of RRT (HR 0.84, 95% CI 0.63-1.12, p = 0.24) or death (HR 1.07, 95% CI 0.95-1.20, p = 0.27). In subgroup analysis in patients with an index eGFR < 20 mL/min/1.73 m2, contrast administration was not associated with the composite renal outcome (HR 0.79, 95% CI 0.51-1.22, p = 0.28), RRT (HR 0.85, 95% CI 0.52-1.39, p = 0.51), AKI (HR 1.28, 95% CI 0.66-2.45, p = 0.46), or death (HR 0.94, 95% CI 0.64-1.39, p = 0.76). Conclusion In a stable population with advanced CKD, we identified an association between IV contrast administration and the risk of AKI, but this did not translate in adverse long-term renal outcomes. These findings suggest that increases in serum creatinine post-IV contrast in patients with stable CKD are not clinically significant.

Trajectories of atherosclerotic cardiovascular disease risk scores as a predictor for incident chronic kidney disease

BackgroundThe relationship between atherosclerosis and renal function is well established. Atherosclerotic cardiovascular disease (ASCVD) risk scores reflect atherosclerotic burden, which changes over time. We investigated the association between ASCVD risk trajectories and incident chronic kidney disease (CKD) using data from a large community-based Korean cohort with up to 16 years of follow-up.MethodsWe analyzed data from 5032 participants without CKD from the baseline survey of the Korean Genome and Epidemiology Study Ansan-Ansung cohort. Participants were categorized into stable or increasing ASCVD risk groups based on the revised ASCVD risk pooled cohort equation over a median period of exposure of 5.8 years. Incident CKD was defined as two consecutive events of an estimated glomerular filtration rate < 60 mL/min/1.73 m2.ResultsDuring a median 9.9 years of event accrual period, 449 (8.92%) new-onset CKD cases were identified. Multiple Cox proportional regression analyses showed that the hazard ratio (95% confidence interval) for incident CKD in the increasing group, compared to the stable group, was 2.13 (1.74–2.62) in the unadjusted model and 1.35 (1.02–1.78) in the fully-adjusted model. Significant relationships were maintained in subgroups of individuals in their 50s, without diabetes mellitus or hypertension. The prevalence of proteinuria was consistently higher in the increasing group than that in the stable group.ConclusionsAn increasing trend in ASCVD risk scores independently predicted adverse renal outcomes in patients without diabetes mellitus or hypertension. Continuous monitoring of ASCVD risk is not only important for predicting cardiovascular disease but also for predicting CKD.

Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14–2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

Geriatric Nutritional Risk Index as a Prognostic Factor for Renal Progression in Patients with Type 2 Diabetes Mellitus.

The aim of this study was to evaluate whether the geriatric nutritional risk index (GNRI) is associated with chronic kidney disease (CKD) progression in patients with type 2 diabetes mellitus (DM). In total, 1100 patients with type 2 DM with a follow-up duration > 1 year were included in this longitudinal study. The risk of CKD progression was assessed according to GNRI quartiles. Patients in the lowest GNRI quartile exhibited a significantly lower estimated glomerular filtration rate (eGFR), compared with those in quartile four. Moreover, these patients had poorer glycemic control and lower hemoglobin levels, body mass index, and albumin levels. Additionally, they exhibited a greater annual decline in eGFR. Multivariate logistic regression analysis showed that old age (>60 years), baseline eGFR, the presence of proteinuria, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and low GNRI were significantly associated with CKD progression. GNRI may serve as a valuable predictive tool for identifying the risk of adverse renal outcomes in patients with type 2 DM. It may potentially serve as a more feasible measure for assessing the nutritional status of these patients, as well as for predicting their clinical outcomes.

Impact of components of metabolic syndrome on the risk of adverse renal outcomes in patients with atrial fibrillation: a nationwide cohort study.

The renal effect of metabolic syndrome components is unclear in patients with atrial fibrillation. This study aimed to investigate the association between metabolic syndrome components and incident end-stage renal disease among patients with atrial fibrillation. A total of 202,434 atrial fibrillation patients without prevalent end-stage renal disease were identified from the National Health Insurance Service database between 2009 and 2016. We defined the metabolic score range from 0 to 5 points such that a patient received every 1 point if the patient met each component listed in the diagnostic criteria of metabolic syndrome. The population was divided into 6 groups: MS0-MS5 for a metabolic score of 0-5, respectively. Multivariate Cox regression analysis was used to estimate the risks of end-stage renal disease. There were 12,747, 31,059, 40,361, 48,068, 46,630, and 23,569 patients for MS0-MS5, respectively. Compared with MS0, MS5 had a higher CHA2DS2-VASc score (3.8 vs. 1.0) (P < .001). During a median follow-up of 3.5 years, compared with MS0, MS1-MS5 were associated with a gradually increasing incidence of end-stage renal disease, in relation to an increase in the metabolic score, (log-rank P < .001). After multivariate adjustment, a higher metabolic score was associated with a greater risk of incident end-stage renal disease: adjusted hazard ratio [95% confidence interval] = 1.60 [0.78-3.48], 2.08 [1.01-4.31], 2.94 [1.43-6.06], 3.71 [1.80-7.66], and 4.82 [2.29-10.15], for MS1-MS5, respectively. Metabolic syndrome components additively impacts the risk of incident end-stage renal disease among patients with atrial fibrillation.

APOL1 and the risk of adverse renal outcomes in patients of African ancestry with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) disproportionately affects individuals of African ancestry (AA) compared to European ancestry (EA). In the general population, high risk (HR) variants in the apolipoprotein L1 (APOL1) gene increase the risk of renal and hypertensive disorders in individuals of AA. Since SLE is characterized by an interferon signature and APOL1 expression is driven by interferon, we examined the hypothesis that APOL1 HR genotypes predominantly drive higher rates of renal and hypertensive-related comorbidities observed in SLE patients of AA versus those of EA. We performed a retrospective cohort study in patients with SLE of EA and AA using a genetic biobank linked to de-identified electronic health records. APOL1 HR genotypes were defined as G1/G1, G2/G2, or G1/G2 and low risk (LR) genotypes as 1 or 0 copies of the G1 and G2 alleles. To identify renal and hypertensive-related disorders that differed in prevalence by ancestry, we used a phenome-wide association approach. We then used logistic regression to compare the prevalence of renal and hypertensive-related disorders in EA and AA patients, both including and excluding patients with the APOL1 HR genotype. In a sensitivity analysis, we examined the association of end stage renal disease secondary to lupus nephritis (LN-related ESRD) with ancestry and the APOL1 genotype. We studied 784 patients with SLE; 195 (24.9%) were of AA, of whom 27 (13.8%) had APOL1 HR genotypes. Eighteen renal and hypertensive-related phenotypes were more common in AA than EA patients (p-value ≤ 1.4E-4). All phenotypes remained significantly different after exclusion of patients with APOL1 HR genotypes, and most point odds ratios (ORs) decreased only slightly. Even among ORs with the greatest decrease, risk for AA patients without the APOL1 HR genotype remained significantly elevated compared to EA patients. In the sensitivity analysis, LN-related ESRD was more prevalent in SLE patients of AA versus EA and AA patients with the APOL1 HR genotype versus LR (p-value < .05 for both). The higher prevalence of renal and hypertensive disorders in SLE patients of AA compared to those of EA is not fully explained by the presence of APOL1 high risk variants.

Renal outcomes of rivaroxaban compared with warfarin in Asian patients with nonvalvular atrial fibrillation: A nationwide population-based cohort study.

Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians. To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients. Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m2 at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population. We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA2DS2-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m2, rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001). Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

Serum triglycerides level is independently associated with renal outcomes in patients with non-dialysis chronic kidney disease: Results from KNOW-CKD study.

To investigate whether high serum triglycerides (TG) level is associated with adverse renal outcomes in patients with non-dialysis chronic kidney disease (CKD), a total of 2,158 subjects from a prospective cohort study (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) were divided into the quartile by serum TG level. The primary outcomes were composite renal events, which is defined as a composite of decline of kidney function (the first occurrence of > 50% decline of estimated glomerular filtration rate or doubling of serum creatinine from the baseline) or onset of end-stage renal disease (initiation of dialysis or kidney transplantation). During the median follow-up of 6.940 years, the cumulative incidence of composite renal event was significantly differed by serum TG level in Kaplan-Meier curve analysis (P < 0.001, by Log-rank test). Cox regression analysis demonstrated that, compared to that of the 1st quartile, the risk of composite renal event was significantly higher in the 4th quartile (adjusted hazard ratio 1.433, 95% confidence interval 1.046 to 1.964). The association between high serum TG level and adverse renal outcome remained consistent in the cause-specific hazard model. Subgroup analyses revealed that the association is modified by age, estimated glomerular filtration rate, and spot urine albumin-to-creatinine ratio. In conclusion, high serum TG level is independently associated with adverse renal outcomes in patients with non-dialysis CKD. Interventional studies are warranted to determine whether lowering serum TG levels may alter the natural course of CKD.

Urinary Angiotensinogen and Progression of Chronic Kidney Disease: Results from KNOW-CKD Study

The prognostic value of urinary angiotensinogen (UAGT) in patients with chronic kidney disease (CKD) has not been completely evaluated, although the association of UAGT with renal outcomes has been suggested in specific subsets of CKD. In the present study, to investigate the association of UAGT with renal outcomes in patients with non-dialysis CKD irrespective of the primary cause, a total of 1688 subjects from the Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were prospectively analyzed. The subjects were divided into the quintile by UAGT to urine creatinine ratio (UAGT/Cr) level. The primary outcomes of interest were composite renal event, which included decline in kidney function and onset of end-stage renal disease during follow-up periods. The median follow-up duration was 6.257 years. Cox regression model analysis unveiled that the risk of composite renal event was significantly higher in the fifth quintile (adjusted hazard ratio 1.528, 95% confidence interval 1.156 to 2.021) compared to that of the first quartile. The association between high UAGT/Cr level and adverse renal outcome remained consistent in sensitivity analyses, including the analysis of the cause-specific hazard model. Subgroup analyses revealed that the association of UAGT level with renal outcomes is modified by certain clinical contexts, such as BMI and albuminuria. In conclusion, high UAGT level is associated with adverse renal outcomes in patients with non-dialysis CKD. Further studies are warranted to elaborate and expand the predictive role of UAGT as a biomarker for renal outcomes in CKD.

Prognostic value of chronicity grading on renal outcomes in patients with IgA nephropathy.

Many studies have shown that chronic changes are strong predictors of renal outcomes in various kidney diseases, including IgA nephropathy. The Mayo Clinic/Renal Pathology Society suggested a glomerulonephritis reporting system with a proposal for standardized grading of chronic changes. The purpose of this study was to predict renal outcomes in patients with IgA nephropathy using chronicity grading in comparison to the Oxford classification which did not include global sclerosis. A total of 4,151 patients with IgA nephropathy were enrolled from the Korean GlomeruloNephritis Study Group registry. Chronicity grading was categorized into minimal, mild, moderate, and severe according to the extent of chronic changes. The Oxford T and S scores were considered as chronic lesions. Three prediction models were constructed: the Oxford classification model (Oxford S plus T), chronicity grading model A (chronicity grading), and chronicity grading model B (chronicity grading plus Oxford S). Using these three prediction models, the primary renal outcome (end-stage renal disease) was evaluated using Cox regression analysis and prediction performance. During the median follow-up of 6.1 (2.7–9.9) years, 304 (7.3%) patients progressed to end-stage renal disease with a cumulative incidence rate of 1.02 events per 100 person-years. In a fully adjusted multivariable model, chronicity grading was independently associated with the primary renal outcome in both models A and B. Compared to the Oxford model, both models A and B showed improvements in model fit, but not in discrimination (ΔC 0.001; 95% CI, −0.010 to 0.013 and ΔC 0.002; 95% CI, −0.005 to 0.008, respectively). Model B demonstrated improvements in integrated discrimination improvement (0.01; 95% CI, 0–0.03) and continuous net reclassification improvement (0.49; 95% CI, 0.02–0.72). The severity of chronicity grading is closely related to adverse renal outcomes in patients with IgA nephropathy, and chronicity grading could provide additional information in clinical practice alongside the Oxford classification.

Urinary mRNA Signatures as Predictors of Renal Function Decline in Patients With Biopsy-Proven Diabetic Kidney Disease.

The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs—LYZ, C3, FKBP5, and G6PC—reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85–32.87, p < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD.

Predictive association of pulmonary hypertension with risks of adverse renal outcomes in type 2 diabetes

Abstract Background Diabetic kidney disease is a major diabetic complication which contributes to the end-stage renal disease and renal deaths in diabetic patients. The aim of our study was to investigate the role of pulmonary hypertension (PHT) in the development of adverse renal outcomes in patients with type 2 diabetes (T2DM). Methods A total of 1479 diabetic patients (mean age 67±13 years; women, 44.7%) were recruited. Pulmonary artery systolic pressure (PASP) was estimated by transthoracic echocardiography at baseline. Adverse renal outcomes were defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy, kidney transplantation or renal deaths. Cox regression hazard model was used to assess the association between PHT and incident adverse renal outcomes. Results Patients were divided into three groups based on their baseline PASP: no PHT (n=1204, 75.1%), mild PHT (321, 20.0%) and significant PHT (78, 4.9%). A total of 474 adverse renal outcomes occurred during a median follow-up of 53 months, Kaplan-Meier survival curve showed that patients with significant PHT had highest risk of adverse renal outcomes. Multivariate cox regression demonstrated both mild PHT (HR=1.66, 95% CI 1.33, 2.06, P&amp;lt;0.001) and significant PHT (HR=2.09, 95% CI 1.45, 3.02, P&amp;lt;0.001) were independently associated with the incident adverse renal outcomes. Conclusion The presence of PHT was associated with adverse renal outcomes in patients with T2DM. Funding Acknowledgement Type of funding sources: None.

Renal outcomes and prognostic factors in patients with type-2 diabetes and chronic kidney disease confirmed by renal biopsy.

Aim:To evaluate the renal outcomes and prognostic factors among patients with type-2 diabetes (T2D) and biopsy-confirmed diabetic nephropathy (DN), non-diabetic renal disease (NDRD) and DN mixed with NDRD (MIX).Design and Methods:Patients with both T2D and chronic kidney disease (CKD) who underwent renal biopsy between January 2014 and December 2016 were recruited in this prospective observational study. Participants were divided into DN group, NDRD group, or MIX group according to the baseline pathological diagnosis. The primary endpoint was a composite renal event of end-stage renal disease (ESRD) or ⩾ 40% reduction in estimated glomerular filtration rate (eGFR).Results:Among the 292 participants included, 153 (52.4%) belonged to the DN group, 30 (10.3%) belonged to the NDRD group, and 109 (37.3%) belonged to the MIX group. During the median follow-up of 27 months, the adverse renal events occurred in 132 (44.2%) patients. Compared with NDRD group, the multiple adjusted hazard ratios (HRs) for renal events in patients with DN and MIX groups were 3.900 (95% confidence interval [CI]: 1.103–13.788) and 2.691 (95% CI: 0.662–10.936), respectively. Baseline lower eGFR (HR: 1.159, 95% CI: 1.060–1.266), severe proteinuria (HR: 2.047, 95% CI: 1.227–3.416), lower hemoglobin (HR: 1.170, 95% CI: 1.008–1.267), and a family history of diabetes (HR: 1.138, 95% CI: 1.008–2.285) were independent predictors for adverse renal outcomes in patients with DN.Conclusion:In patients with T2D and CKD, pure DN and MIX group displayed a worse renal prognosis than NDRD group. Worse renal function, severe proteinuria, lower hemoglobin, and a family history of diabetes may be associated with adverse renal outcomes in patients with DN.

The association of echocardiographic parameters on renal outcomes in chronic kidney disease

Background Patients with chronic kidney disease (CKD) often have structural abnormalities of the heart due to pressure and volume overload. The aim of this study was to evaluate associations between echocardiographic parameters and renal outcomes (estimated glomerular filtration rate [eGFR] slope and progression to dialysis) in patients with stage 3–5 CKD. Methods This longitudinal study enrolled 419 patients. Changes in renal function were assessed using the eGFR slope. Rapid renal progression was defined as an eGFR slope < −3 mL/min/1.73 m2/year, and the renal endpoint was defined as commencing dialysis. Results Increased left atrial diameter (LAD), ratio of left ventricular mass to body surface area (LVM/BSA), ratio of LVM to height2.7 (LVM/ht2.7), and ratio of observed to predicted LVM (o/p LVM) were associated with eGFR slope in an adjusted model, but left ventricular ejection fraction (LVEF) was not. Furthermore, LAD ≥ 4.7 cm, LVM/BSA > 115 g/m2 in males and > 95 g/m2 in females, and LVM/ht2.7 > 48 g/ht2.7 in males and > 44 g/ht2.7 in females were correlated with progression to dialysis, but o/p LVM and LVEF were not. The maximum change in χ2 change to predict renal outcomes was observed for LAD, followed by LVM/BSA and LVM/ht2.7. Conclusions A large LAD and increased LVM, regardless of how it was measured (LVM/BSA, LVM/ht2.7 and o/p LVM), were correlated with adverse renal outcomes in patients with CKD stage 3–5. LAD had superior prognostic value to LVM and LVEF.

Intra-individual variability of eGFR trajectories in early diabetic kidney disease and lack of performance of prognostic biomarkers

Studies reporting on biomarkers aiming to predict adverse renal outcomes in patients with type 2 diabetes and kidney disease (DKD) conventionally define a surrogate endpoint either as a percentage of decrease of eGFR (e.g. ≥ 30%) or an absolute decline (e.g. ≥ 5 ml/min/year). The application of those study results in clinical practise however relies on the assumption of a linear and intra-individually stable progression of DKD. We studied 860 patients of the PROVALID study and 178 of an independent population with a relatively preserved eGFR at baseline and at least 5 years of follow up. Individuals with a detrimental prognosis were identified using various thresholds of a percentage or absolute decline of eGFR after each year of follow up. Next, we determined how many of the patients met the same criteria at other points in time. Interindividual eGFR decline was highly variable but in addition intra-individual eGFR trajectories also were frequently non-linear. For example, of all subjects reaching an endpoint defined as a decrease of eGFR by ≥ 30% between baseline and 3 years of follow up, only 60.3 and 45.2% lost at least the same amount between baseline and year 4 or 5. The results were similar when only patients on stable medication or subpopulations based on baseline eGFR or albuminuria status were analyzed or an eGFR decline of ≥ 5 ml/min/1.73m2/year was used. Identification of reliable biomarkers predicting adverse prognosis is a strong clinical need given the large interindividual variability of DKD progression. However, it is conceptually challenging in early DKD because of non-linear intra-individual eGFR trajectories. As a result, the performance of a prognostic biomarker may be accurate after a specific time of follow-up in a single population only.

Natriuretic peptide as a predictor of adverse renal outcomes in patients with acute kidney injury

Abstract Background Since cardiorenal syndrome has been increasingly recognised as the intense interaction between the heart and the kidneys, we hypothesised that in patients with acute kidney injury (AKI), a biomarker of cardiovascular stress and heart failure (HF), N-terminal pro-brain natriuretic peptide (NT-proBNP), can predict adverse renal outcomes. Purpose The purpose of this study was to investigate the ability of NT-proBNP to predict need for dialysis and dialysis dependence in patients with AKI. Methods We analysed the association between baseline NT-proBNP measured before renal consultation, and need for dialysis and dialysis dependence, using a cohort of 1,052 AKI patients admitted to the Cleveland Clinic between 2011 and 2016. AKI was defined as acute increase in serum creatinine (Cr) of at least 0.3 mg/dL or 50% from baseline. Dialysis dependence was defined as patients still need dialysis within 72 hours of discharge. Results Mean age was 65.8±13.6 years, 57% were male, 45.4% had chronic HF and 28.2% had chronic kidney disease (CKD). There was no significant difference in chronic HF, CKD, or baseline Cr between AKI patients with and without dialysis. Median NT-proBNP was 6,484.50 pg/mL (interquartile range 2,200.75–15,717.50 pg/mL). We observed that 43.1% had dialysis (among them 67.8% became dialysis dependence). After adjustment for age, gender, hypertension, and baseline Cr, higher NT-proBNP levels were associated with greater likelihood of needing dialysis [quartile (Q) 4 vs. 1, Odd ratio (OR) 1.98, 95% confidence interval (CI) 1.38–2.85, P&amp;lt;0.001] and dialysis dependence (Q 4 vs. 1, OR 2.63, 95% CI 1.41–4.9, P=0.002) (Figure 1). Conclusion Elevated NT-proBNP was independently associated with need for dialysis and dialysis dependence in patients with AKI. Figure 1 Funding Acknowledgement Type of funding source: None

Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data

IntroductionThe Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study showed that compared with placebo, canagliflozin 100 mg significantly reduced the risk of major cardiovascular events and adverse renal outcomes in patients with diabetic kidney disease (DKD). We developed a simulation model that can be used to estimate the long-term health and economic consequences of DKD treatment interventions for patients matching the CREDENCE study population.MethodsThe CREDENCE Economic Model of DKD (CREDEM-DKD) was developed using patient-level data from CREDENCE (which recruited patients with estimated glomerular filtration rate 30 to < 90 mL/min/1.73 m2, urinary albumin to creatinine ratio > 300–5000 mg/g, and taking the maximum tolerated dose of a renin–angiotensin–aldosterone system inhibitor). Risk prediction equations were fit for start of maintenance dialysis, doubling of serum creatinine, hospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. A micro-simulation model was constructed using these risk equations combined with user-definable kidney transplant event risks. Internal validation was performed by loading the model to replicate the CREDENCE study and comparing predictions with trial Kaplan–Meier estimate curves. External validation was performed by loading the model to replicate a subgroup of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program with patient characteristics that would have qualified for inclusion in CREDENCE.ResultsRisk prediction equations generally fit well and exhibited good concordance, especially for the placebo arm. In the canagliflozin arm, modest underprediction was observed for myocardial infarction, along with overprediction of dialysis, doubling of serum creatinine, and all-cause mortality. Discrimination was strong (0.85) for the renal outcomes, but weaker for the macrovascular outcomes and all-cause mortality (0.60–0.68). The model performed well in internal and external validation exercises.ConclusionCREDEM-DKD is an important new tool in the evaluation of treatment interventions in the DKD population.Trial RegistrationClinicalTrials.gov identifier, NCT02065791.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00923-w) contains supplementary material, which is available to authorized users.

P0706THE EFFECT OF NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS ON RENAL OUTCOMES IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

Abstract Background and Aims Lifelong oral anticoagulation (either with warfarin or a non–vitamin K antagonist oral anticoagulant (NOACs)) is indicated for stroke prevention in most patients with atrial fibrillation (AF). NOACs has been recommended for thromboembolism prophylaxis of nonvalvular AF. However, studies on the impact of NOACs on renal outcomes has been inconclusive. Method This retrospective cohort study compared 3 NOACs: apixaban, dabigatran and rivaroxaban to warfarin for their effects on renal outcomes in patients with nonvalvular AF who had been using these medications for at least 2 years as of 2017-2018. The primary outcome was either the incidence of &amp;gt; 30% decline in estimated glomerular filtration rate (eGFR) or doubling of the serum creatinine levels compare to baseline values at 24 months, and the secondary outcome was the incident of primary outcomes in different baseline eGFR subgroups (&amp;gt; 60 vs &amp;lt; 60 ml/min/1.73 m2) and major bleeding as an adverse event. Results 90 patients were enrolled in each group, totaling to 360 patients. The incidence of &amp;gt; 30% decline in eGFR is significantly higher in rivaroxaban compared to warfarin (hazard ratio: 2.09; 95% confidence interval: 1.35 to 3.24; p = 0.001). After multivariate analysis (using age, stage of chronic kidney disease, eGFR, CHAD2VAS and HASBLED score), dabigatran was also shown to significantly increase the incidence of &amp;gt; 30% decline in eGFR. In subgroup analysis, rivaroxaban resulted in higher incidence of &amp;gt; 30% decline in eGFR, in eGFR &amp;lt; 60 ml/min/1.73 m2 subgroup and higher incidence of doubling of the serum creatinine level in eGFR &amp;gt; 60 ml/min/1.73 m2 subgroup. There was no occurrence of major bleeding. Conclusion NOACs, especially rivaroxaban, may increase adverse renal outcomes in patients with nonvalvular AF.

Impact of increased venous pressure on kidney function and mortality in cardiovascular patients with preserved ejection fraction

Background: Right but not left ventricular hemodynamic parameters have been found to be independently associated with adverse renal outcomes in patients with acute decompensated heart failure (HF).Aim: To investigate the hemodynamic profile of patients without acute decompensated heart failure and left ventricular ejection fraction >50% referred for elective left and right heart catheterization and to correlate left and right filling pressures, stroke volume and arterial blood pressure to renal function parameters. Subsequently, we tested the hypothesis that right ventricle and left ventricle hemodynamic parameters can predict all-cause mortality in our non-HF subjects.Methods: Between October 2009 and November 2010, 151 consecutive patients referred for elective left and right heart catheterization were studied and consequently followed up for a mean period of 8 years in order to identify all-cause mortality. Patient’s initial cohort was subdivided in two groups according to right atrial pressure. The RAPRLOW group (Right Atrium Pressure ≤ 9 mmHg) and the RAPRHIGH group (Right Atrium Pressure > 9mmHg)Results: No correlation between blood pressure, pulmonary capillary wedges pressure, cardiac index, stroke volume and stroke volume index (SVI), and parameters of kidney function was observed. However, a weak, although, significant correlation between right atrial pressure (RAP) and modification of diet in renal disease (MDRD) (r = –0.202; p = .014) could be detected. RAPRLOW patients had a statistically significant lower MDRD value of 16.6 mL/min/1.73 m2 than RAPRHIGH patients. Increased RAP (HR = 2.03; 95% [CI]: 1.05 to 3.9; p = .025) and age (HR = 1.08, 95% [CI] 1.04–1.12, p < .001) independently predicted all-cause mortality during follow up.Conclusions: Our study demonstrates that right ventricular preload affects renal function in patients with preserved systolic function and that neither aortic systolic pressure nor left ventricle pressure indices were related to estimated glomerular filtration rate. Furthermore, we demonstrate for the first time that an increased RAP is able to predict a worse prognosis in patients with preserved ejection fraction independently of well-established risk factors, such as blood pressure and SVI.