Doubling Of Serum Creatinine Research Articles

A retrospective observational population-based study to assess the prevalence and burden of illness of type 2 diabetes with an estimated glomerular filtration rate < 90 mL/min/1.73 m2 in Ontario, Canada.

AimTo better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 in Ontario, Canada.Materials and MethodsWe used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m2 and adverse cardiovascular co‐morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes.ResultsWhile the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5‐year period (2011‐2012 to 2015‐2016), the prevalence of eGFR < 90 mL/min/1.73 m2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2‐year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes.ConclusionsThis real‐world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m2, and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes‐related complications.

Association between serum potassium levels and adverse outcomes in chronic kidney disease: the Fukushima CKD cohort study.

Serum potassium disorders, commonly observed in chronic kidney disease (CKD), are reportedly associated with higher mortality, but their impact on renal outcomes is still controversial. The present study used the longitudinal data of the Fukushima CKD cohort study to investigate the relationships between hypokalemia and hyperkalemia and adverse outcomes such as renal outcomes and all-cause mortality in Japanese patients with non-dialysis-dependent CKD. The study involved 1330 CKD patients followed-up for 2.8years. The primary endpoint of the present study was a kidney event, defined as a combination of doubling of baseline serum creatinine and end-stage kidney disease. Hyperkalemia (≥ 5.0mmol/L) was noted in 10.6% and hypokalemia (< 4.0mmol/L) in 16.4% of the study population. Significant U-shaped associations were observed between potassium levels and both kidney events and all-cause mortality on univariate Cox regression analyses. After adjustment for covariates, both hypokalemia and hyperkalemia were significantly associated with an increased risk of kidney events, with the lowest risk at a serum potassium of 4.0-4.4mmol/L. Compared with a reference level of 4.0-4.4mmol/L, the adjusted hazard ratio for kidney events was 2.49 (1.33-4.66) for serum potassium < 4.0mmol/L, 1.72 (1.00-2.96) for 4.5-4.9mmol/L, and 2.16 (1.15-4.06) for ≥ 5.0mmol/L. There was no significant association between serum potassium levels and mortality after multivariate adjustment. Hypokalemia and hyperkalemia were associated with an increased risk of CKD progression, but not with mortality in Japanese patients with non-dialysis-dependent CKD.

Comparative Effectiveness of SGLT2i Versus DPP4i on Cardiovascular, Kidney and Hyperkalemia Outcomes in Individuals from Routine Clinical Practice: Observational Cohort Study

Background: While clinical trials have demonstrated efficacy for SGLT2 inhibitors (SGLT2i) on preventing cardiovascular and kidney damage, few high-quality studies have expanded to routine-care settings of low-risk patients. Previous observational studies were limited by immortal time bias or did not adjust for laboratory measurements. Methods: We compared clinical outcomes of adults who started SGLT2i or DPP4i therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HHF). Secondary outcomes included major adverse cardiovascular events (MACE), all-cause mortality, atrial fibrillation, hyperkalemia and kidney disease progression (composite kidney failure and doubling of serum creatinine). Propensity score weighted Cox regression was used to estimate hazard ratios and balance 56 covariates. Results: We included 16,537 individuals (5526 SGLT2i; 11,011 DPP4i users), followed for median 1.9 years. Median age was 64 years (36% women), median estimated glomerular filtration rate 87 ml/min/1.73m2 and 31% had albuminuria. After weighting, patients starting SGLT2i therapy were at lower risk for the composite of CV death/HHF (HR 0.65; 95% CI 0.47-0.89) and hyperkalemia (HR 0.41; 95% CI 0.20-0.83) compared with DPP4i, without an increase in hypokalemia (HR 0.98; 95% CI 0.72-1.34). The adjusted HRs (95% CI) were 0.82 (0.64-1.06) for MACE, 0.74 (0.52-1.06) for all-cause mortality, 0.95 (0.68-1.33) for atrial fibrillation and 0.54 (0.27-1.08) for kidney disease progression. Conclusions: SGLT2i use compared with DPP4i was associated with a reduction in cardiovascular and kidney outcomes similar in magnitude to trials, as well as a lower risk of hyperkalemia. Funding: Research reported in this publication was supported by the Swedish Research Council (#2019-01059), the Swedish Heart and Lung Foundation and the Westman Foundation. ELF acknowledges support by a Rubicon Grant of the Netherlands Organization for Scientific Research (NWO). Declaration of Interests: JC acknowledges consultancy for Baxter and AstraZeneca, and grant support to Karolinska Institutet from AstraZeneca, Viforpharma and Astellas, all outside the submitted work. CMC has received consultation, advisory board membership or research funding from the Ontario Ministry of Health, Sanofi, Johnson & Johnson, Pfizer, Leo Pharma, Astellas, Janssen, Amgen, Boehringer-Ingelheim and Baxter, all outside the submitted work. None of the other authors declare relevant financial interests that would represent a conflict of interest. MJJ is responsible for research programs that have received unrestricted funding from Gambro, Baxter, Commonwealth Serum Laboratories (CSL), Amgen, Eli Lilly, and Merck; has served on advisory boards and steering committees sponsored by Akebia, Baxter, Boehringer Ingelheim, CSL, Janssen, and Vifor; and spoken at scientific meetings sponsored by Janssen, Amgen, and Roche, with any consultancy, honoraria, or travel support paid to her institution. Ethics Approval Statement: The study utilized only de-identified data and thus was deemed not to require informed consent, being approved by the regional ethical review boards and the Swedish National Board of Welfare.

A novel drug response score more accurately predicts renoprotective drug effects than existing renal risk scores.

Background:Risk factor-based equations are used to predict risk of kidney disease progression in patients with type 2 diabetes order to guide treatment decisions. It is, however, unknown whether these models can also be used to predict the effects of drugs on clinical outcomes.Methods:The previously developed Parameter Response Efficacy (PRE) score, which integrates multiple short-term drug effects, was first compared with the existing risk scores, Kidney Failure Risk Equation (KFRE) and The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) renal risk score, in its performance to predict end-stage renal disease (ESRD; KFRE) and doubling of serum creatinine or ESRD (ADVANCE). Second, changes in the risk scores were compared after 6 months’ treatment to predict the long-term effects of losartan on these renal outcomes in patients with type 2 diabetes and chronic kidney disease.Results:The KFRE, ADVANCE and PRE scores showed similarly good performance in predicting renal risk. However, for prediction of the effect of losartan, the KFRE risk score predicted a relative risk change in the occurrence of ESRD of 3.1% [95% confidence interval (CI) −5 to 12], whereas the observed risk change was −28.8% (95% CI −42.0 to −11.5). For the composite endpoint of doubling of serum creatinine or ESRD, the ADVANCE score predicted a risk change of −12.4% (95% CI −17 to −7), which underestimated the observed risk change −21.8% (95% CI −34 to −6). The PRE score predicted renal risk changes that were close to the observed risk changes with losartan treatment [−24.0% (95% CI −30 to −17) and −22.6% (95% CI −23 to −16) for ESRD and the composite renal outcome, respectively].Conclusion:A drug response score such as the PRE score may assist in improving clinical decision making and implement precision medicine strategies.

The effects of dipeptidyl peptidase-4 inhibitors on kidney outcomes.

To summarize evidence from randomized controlled trials (RCTs) concerning the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on kidney outcomes in patients with type 2 diabetes mellitus (T2DM). The Medline, EMBASE and Cochrane databases were searched for RCTs comparing DPP-4 inhibitors with a placebo, active comparator or standard care, with at least 500 person-years follow-up in patients with T2DM and with reporting of kidney outcomes. Treatment effects were summarized using random-effects meta-analysis. Ten trials including 47 955 patients (mean estimated glomerular filtration rate [eGFR] 71 mL/min/1.73m2 , mean follow-up 10 762 patient-years per trial) were eligible for inclusion. DPP-4 inhibitors were compared with placebo (five trials), active comparator (three trials), and standard care (two trials). Overall, treatment with DPP-4 inhibitors was associated with a greater decline in eGFR than treatment with the comparators (weighted mean difference -1.12 mL/min/1.73m2 , 95% confidence interval [CI] -1.61, -0.62; high-certainty evidence). There were no detectable effects of DPP-4 inhibitors on rates of doubling serum creatinine (risk ratio [RR] 1.10, 95% CI 0.90, 1.34; high-certainty evidence), end-stage kidney disease (RR 0.97, 95% CI 0.77, 1.23; high-certainty evidence), death from kidney causes (RR 1.81, 95% CI 0.67, 4.93; low-certainty evidence), or all-cause mortality (RR 1.01, 95% CI 0.95, 1.09; high-certainty evidence). DPP-4 inhibitors significantly reduced the risks of the surrogate kidney outcome of new albuminuria (RR 0.88, 95% CI 0.8, 0.98; moderate-certainty evidence) and worsening albuminuria (RR 0.88, 95% CI 0.82, 0.94; moderate-certainty evidence). There was no difference in the safety outcome of acute kidney injury (RR 1.04, 95% CI 0.57, 1.87; high-certainty evidence). Dipeptidyl peptidase-4 inhibitors are associated with a greater decline in eGFR, despite reducing the development and progression of albuminuria, and have no clear effect on other key kidney outcomes.

Relationship between decline in estimated or measured glomerular filtration rate and 16-year postrenal transplant outcome.

BackgroundGlomerular filtration rate (GFR) decline ≥30% over 2 years can substitute for the conventional ‘doubling of serum creatinine’ to predict end-stage renal disease in patients with native kidneys. While chronic kidney disease trajectory is less predictable in transplanted patients, recent data have suggested that similar GFR decline might be an acceptable surrogate for long-term transplant outcome. We sought (i) to confirm the prognostic value of an early GFR decline in kidney transplant recipients and (ii) to determine whether using direct measurement of GFR with inulin improves the performance of this surrogate.MethodsWe retrospectively analysed all recipients transplanted between 1989 and 2000 in our centre, with inulin-measured and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated GFR at 1 and 5 years post-transplant, and evaluated the performance [time-dependent area under the receiver operating characteristic curve (ROC AUC) and subdistribution hazard ratio (sdHR) with competing risk model] of GFR change to predict graft failure and all-cause mortality.ResultsOut of 417 kidney transplant recipients, 116 patients had lost their graft and 77 had died 16 years after transplantation. While being significantly associated with graft failure [sdHR = 2.37 (95% confidence interval 1.47–3.83)], CKD-EPI-GFR decline ≥30% failed to appropriately predict long-term graft survival (C-statistics of 0.63). Concordance between inulin-GFR and CKD-EPI-GFR to detect similar GFR change was only 53%. Inulin-GFR change was, however, not a better predictor (C-statistics of 0.59). Comparable results were observed for mortality.ConclusionsOur data suggest that early GFR decline is a poor surrogate for long-term transplant outcome, even when change in GFR is directly measured by a reference method.

Pharmacological Actions of Indoxyl Sulfate and AST-120 That Should Be Recognized for the Strategic Treatment of Patients with Chronic Kidney Disease.

Although there are many uremic substances in the body, the most studied and well-known molecule that predominantly binds to plasma proteins is indoxyl sulfate (IS). Many research groups have reported IS to have toxic effects on the kidney and cardiovascular system. It is difficult to remove IS with regular hemodialysis or hemodiafiltration. On the other hand, AST-120 has the capacity to bind to indole, which is a precursor of IS in the intestinal tract and excrete it in feces. IS production in the liver is efficiently suppressed by AST-120 administration. However, large-scale clinical studies have not shown that AST-120 suppresses hard endpoints such as doubling serum creatinine, end-stage renal disease, and death. In patients with accelerated chronic kidney disease (CKD) progression, AST-120 is expected to suppress those hard renal endpoints, but only when compliance to treatment is high. It is necessary to validate the renal protective effect of AST-120, as expected from the basic study on IS, including more patients with slowly progressive CKD in a large-scale clinical study in the future.

Effects of Keluoxin capsule combined with losartan potassium on diabetic kidney disease: study protocol for a randomized double-blind placebo-controlled multicenter clinical trial

BackgroundDiabetic kidney disease (DKD) is one of the most important microvascular complications of diabetes, and its prevalence has increased dramatically in the past few decades. DKD is responsible for considerable morbidity and mortality of patients with diabetes. Keluoxin capsule (KLX) is a Chinese patent medicine that has been used in the clinic to control DKD for years. Previous studies have shown that KLX appears to reduce proteinuria, but the study protocols as well as the primary outcome need to be improved. Thus, we aim to evaluate whether losartan potassium combined with KLX is more effective than losartan potassium in DKD treatment and to provide validated evidence for the application of KLX in the treatment of DKD.MethodsWe will conduct a randomized double-blind placebo-controlled multicenter clinical trial. A total of 252 participants diagnosed with DKD recruited from 18 institutions will be randomly allocated to either a losartan potassium plus KLX (n = 126) or a losartan potassium plus placebo group (n = 126). The participants will be administered KLX or placebo in addition to losartan potassium for 24 weeks. The primary outcome measure will be the decline in estimated glomerular filtration rate (eGFR) (ml/min/1.73 m2/year) from baseline within 24 weeks, and the secondary outcomes will be the incidence of serum creatinine doubling, the incidence of end-stage renal disease (ESRD), the proportion of subjects with a progressive decline in eGFR > 30%, the percent change in 24 h urinary total protein (UTP), the change in the urinary albumin/creatinine ratio (UACR), and the total effective rate of the traditional Chinese medicine (TCM) syndrome scale scores. Comparison of the differences in the variables between groups will be performed according to the data revealed by independent t tests, chi-squared tests, Fisher’s exact tests, or Wilcoxon’s tests. All statistical tests will be two-sided, and significance will be considered for p values < 0.05.DiscussionThis study will be the first randomized clinical trial to evaluate the efficacy and safety of KLX versus the placebo for the treatment of patients with DKD. The outcome of this trial will provide a basis for prescribing KLX to patients with DKD.Trial registrationChinese Clinical Trial Registry (www.chictr.org.cn) ChiCTR1900021113. Registered on January 29, 2019.

Comparison of Circulating Biomarkers in Predicting Diabetic Kidney Disease Progression With Autoantibodies to Erythropoietin Receptor

IntroductionSeveral circulating markers, including autoantibodies to erythropoietin receptor (anti-EPOR antibodies), have been identified as useful biomarkers in predicting diabetic kidney disease progression. However, a direct comparison of their utility is lacking. We aimed to validate and to compare the prognostic value of anti-EPOR antibodies with that of other known biomarkers, using the ADVANCE trial and its long-term follow-up, ADVANCE-ON, cohorts.MethodsIn this nested case-control study from the ADVANCE trial cohort, we included 165 case participants who had the composite kidney outcome (renal replacement therapy, renal death, or doubling of serum creatinine to ≥200 μmol/l) and 330 matched controls. We compared the associations of baseline plasma levels of anti-EPOR antibodies, tumor necrosis factor receptor (TNFR)-1 and -2, and bone morphogenetic protein (BMP)-7 with kidney outcomes.ResultsCases had higher baseline plasma levels of anti-EPOR antibodies than controls (median 1.7 vs. 0.6 enzyme-linked immunosorbent assay unit, P < 0.001). Higher levels of anti-EPOR antibodies were associated with an increased risk of kidney outcome (odds ratio 2.16 [95% confidence interval 1.51, 3.08], per 1 SD of log-transformed levels) after adjusting for conventional markers. Elevated circulating TNFR1 and TNFR2 levels, and lower BMP-7 levels at baseline, were associated with poor kidney outcome (odds ratios 2.06 [1.29, 3.30], 1.66 [1.13, 2.43], and 0.45 [0.32, 0.65], respectively). The addition of anti-EPOR antibodies into the model improved the prediction of kidney outcome, regardless of other biomarkers.ConclusionAnti-EPOR antibodies provide a promising biomarker, as with TNFR1, TNFR2, and BMP-7, in predicting kidney disease progression in people with type 2 diabetes mellitus.

Cumulative iodinated contrast exposure for computed tomography during acute kidney injury and major adverse kidney events.

To determine if contrast-enhanced CT imaging performed in patients during their episode of AKI contributes to major adverse kidney events (MAKE). A propensity score-matched analysis of 1127 patients with AKI defined by KDIGO criteria was done. Their mean age was 63 ± 16years with 56% males. A total of 419 cases exposed to CT contrast peri-AKI were matched with 798 non-exposed controls for 14 covariates including comorbidities, acute illnesses, and initial AKI severity; outcomes including MAKE and renal recovery in hospital were compared using bivariate analysis and logistic regression. MAKE was a composite of mortality, renal replacement therapy, and doubling of serum creatinine on discharge over baseline; renal recovery was classified as early versus late based on a 7-day timeline from AKI onset to nadir creatinine or cessation of renal replacement therapyin survivors. Sixty-two patients received cumulatively > 100mL of CT contrast, 143 patients had > 50-100mL, and 214 patients had 50mL or less; MAKE occurred in 34%, 17%, and 21%, respectively, as compared with 20% in non-exposed controls (p = 0.008 for patients with > 100mL contrast versus none). More contrast-exposed patients experienced late renal recovery (27% versus 20%) and longer hospital days (median 10 versus 8) than non-exposed patients (all p < 0.01). On multivariate analysis, cumulative CT contrast > 100mL was independently associated with MAKE (odds ratio 2.39 versus non-contrast, adjusted for all confounders, p = 0.005); cumulative CT contrast under 100mL was not associated with MAKE. High cumulative volume of CT contrast administered to patients with AKI is associated with worse short-term renal outcomes and delayed renal recovery. • Cumulative intravenous iodinated contrast for CT imaging of more than 100mL, during an episode of acute kidney injury, was independently associated with worse renal outcomes and less renal recovery. • These adverse outcomes including renal replacement therapy were not more frequent in similar patients who received cumulatively 100mL or less of CT contrast, compared with non-exposed patients. • More patients with CT contrast exposure during acute kidney injury experienced delayed renal recovery.

Perioperative use of renin-angiotensin system inhibitors and short-term outcomes in patients undergoing cardiac surgery

Abstract Background Controversy exists about whether preoperative angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) therapy is associated with adverse outcomes after cardiac surgery. Current guidelines stated that it is uncertain about the safety of the preoperative administration of this medications because of the potential deleterious consequences of perioperative hypotension Purpose To determine the effect of preoperative therapy with ACEi or ARB on short-term outcome after cardiac surgery. Methods Single-center prospective cohort between January 2018 and December 2019. Patients were eligible if they were submitted to elective on-pump cardiac surgery and aged ≥18 years. Patients were divided into two groups according to previous use of ACEi or ARB. All preoperative demographic, clinical, and intraoperative surgical variables were collected prospectively. Outcomes of interests were intensive care unit (ICU) mortality, incidence and duration (hours) of postoperative shock (defined as the need for intravenous vasopressors or inopressors), postoperative acute kidney injury (AKI), defined as a doubling of serum creatinine, duration of mechanical ventilation (hours) and length of stay in the ICU (days). A multivariate regression was performed for categorical outcomes and Kruskal-Wallis test for non-parametric continuous variables. Results 353 patients were evaluated in the period, 182 (51.6%) of male sex, with a mean age of 54.5 (±14.7) and STS mortality and EURO scores of 1.93 (±1.81) and 1.89 (±1.9), respectively. Coronary artery bypass grafting was the common procedure, 168 (47.6%). After multivariate regression, use of ACEi or ARB preoperatively was associated with postoperative shock: RR: 2.03, CI 1.25–3.30, p=0.004; incidence of AKI: RR: 2.84, CI 1.01–7.98, increased length of ICU stay: 4 (3–6) vs 3 (2–5), p=0.03; and increased duration of shock: 10 (0–39) vs 0 (0–24), p&amp;lt;0.01. There was no association with the duration of mechanical ventilation: 10.5 (6–20) vs 11.0 (5–18), p=0.31 or ICU mortality: 14 (7.3%) vs 16 (10.0%), p=0,44. Conclusions The use of preoperative ACEi or ARBs was associated with increased incidence and duration of postoperative shock, incidence of acute kidney injury, and durations of mechanical ventilation and ICU stay. Funding Acknowledgement Type of funding source: None

Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.

Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease.

SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio>300mg/g, and estimated glomerular filtration rate of 30 to<90mL/min/1.73m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

SGLT2 Inhibition for CKD and Cardiovascular Disease in Type 2 Diabetes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Diabetes is the most frequent cause of chronic kidney disease (CKD), leading to nearly half of all cases of kidney failure requiring replacement therapy. The principal cause of death among patients with diabetes and CKD is cardiovascular disease (CVD). Sodium/glucose cotransporter 2 (SGLT2) inhibitors were developed to lower blood glucose levels by inhibiting glucose reabsorption in the proximal tubule. In clinical trials designed to demonstrate the CVD safety of SGLT2 inhibitors in type 2 diabetes mellitus (T2DM), consistent reductions in risks for secondary kidney disease end points (albuminuria and a composite of serum creatinine doubling or 40% estimated glomerular filtration rate decline, kidney failure, or death), along with reductions in CVD events, were observed. In patients with CKD, the kidney and CVD benefits of canagliflozin were established by the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial in patients with T2DM, urinary albumin-creatinine ratio >300 mg/g, and estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2. To clarify and support the role of SGLT2 inhibitors for treatment of T2DM and CKD, the National Kidney Foundation convened a scientific workshop with an international panel of more than 80 experts. They discussed the current state of knowledge and unanswered questions in order to propose therapeutic approaches and delineate future research. SGLT2 inhibitors improve glomerular hemodynamic function and are thought to ameliorate other local and systemic mechanisms involved in the pathogenesis of CKD and CVD. SGLT2 inhibitors should be used when possible by people with T2DM to reduce risks for CKD and CVD in alignment with the clinical trial entry criteria. Important risks of SGLT2 inhibitors include euglycemic ketoacidosis, genital mycotic infections, and volume depletion. Careful consideration should be given to the balance of benefits and harms of SGLT2 inhibitors and risk mitigation strategies. Effective implementation strategies are needed to achieve widespread use of these life-saving medications.

Adult-onset minimal change disease: the significance of histological chronic changes for clinical presentation and outcome.

Data on pathologic features with prognostic utility in adults with minimal change disease (MCD) are limited. We assessed the relationship between histologic chronic changes and clinical presentation and outcomes. The consecutive records of 79 patients with MCD and minimum of 6months follow-up were retrospectively reviewed. Kidney survival was the primary endpoint (doubling serum creatinine or dialysis initiation). Secondary endpoints were time to remission and relapse. Total chronicity score was the sum of glomerulosclerosis (0-3), interstitial fibrosis (0-3), tubular atrophy (0-3), and arteriolosclerosis (0/1). The median renal chronicity score was 1; 77% had minimal (0-1), 18% mild (2-4), and 5% moderate (5-7) chronicity. Fifty percent had a null score; they were younger, had higher eGFR, similar proteinuria, better renal survival, and lower mortality. Mean kidney survival time was 5.7 (95% CI 5.2-6.2) years; 89% reached a form of remission at a median of 8weeks; 31% relapsed at a mean of 26months. Chronic changes severity predicted both relapses and kidney survival, each one-point increase in score raised with 27% the risk of relapse and with 31% the risk of dialysis initiation. Acute kidney injury (AKI) was present in 42% of the patients; they had more often mesangial proliferation, interstitial inflammation, tubular atrophy, arteriosclerosis, podocyte villous hypertrophy, and higher chronicity score. Standardized grading of chronicity was a predictor of kidney survival and disease relapse and was related to AKI. Older patients with severe nephrotic syndrome and with increased chronicity score could represent a high-risk category.

Relationship between blood pressure and kidney diseases in large randomized controlled trials: secondary analyses using SPRINT and ACCORD-BP trials.

Hypertension is a risk factor for acute kidney injury. In this study, we aimed to identify the optimal blood pressure (BP) targets for CKD and non-CKD patients. We analyzed the data of the Systolic Blood Pressure Intervention Trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) to determine the nonlinear relationship between BP and renal disease development using the Generalized Additive Model (GAM). Optimal systolic BP/diastolic BP (SBP/DBP) with lowest renal risk were estimated using GAM. Logistic regression was employed to find odds ratios (ORs) of adverse renal outcomes by three BP groups (high/medium/low). Both study trials have demonstrated a "U"-shaped relationship between BP and renal outcomes. For non-CKD patients in SPRINT trial, risk of 30% reduction in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 2.31, 95% CI = 1.51-3.53). For non-CKD patients in ACCORD trial, risk of doubling of serum creatinine (SCr) or >20 mL/min decrease in eGFR among intensive group patients with DBP ≤ 70 mmHg was significantly higher than the group with DBP between 71 and 85 mmHg (OR = 1.49, 95% CI = 1.12-1.99). For CKD patients in SPRINT trial, there are no significant differences in renal outcomes by different SBP/DBP levels. Our analysis of both SPRINT and ACCORD datasets demonstrated that lower-than-optimal DBP may lead to poor renal outcomes in non-CKD patients. Healthcare providers should be cautious of too low DBP level in intensive BP management due to poor renal outcomes for non-CKD patients.

EFFECT OF ARTERIAL CATHETER ON VASOPRESSOR USE IN PATIENTS WITH SHOCK: A PROPENSITY SCORE MATCHING ANALYSIS ON A MULTI-CENTER RETROSPECTIVE COHORT

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Intra-arterial catheters (IAC) placement is common in the intensive care unit (ICU), with studies showing more than third of ICU admissions will have one placed. However, the benefit of IAC is questionable, with comparable reading from non-invasive, less costly blood pressure measurements, as well as risk of complications such as infections, limb ischemia, and pseudoaneurysm. With that, there is a call for studies to define their role and type of patient to best benefit from them. We conducted a retrospective cohort study to determine the correlation between IAC placement and days alive and vasopressor free in adults admitted to the ICU on vasopressors METHODS: We used the eICU Collaborative Research Database, a freely available multi-center database for critical care research, which consists more than two hundred thousand patient encounters admitted to 335 ICUs in the United States in 2014 and 2015. Patients were included if vasopressors were started within 10 hours prior to admission or within 24 hours of ICU admission. IAC placement was defined as a minimum of five invasive blood pressure readings on the day of admission. The primary outcome was days alive and free of vasopressors at day 7. Secondary outcomes were inpatient mortality, total duration of vasopressor therapy, and acute kidney injury defined as doubling of serum creatinine or need for renal replacement therapy. A nearest neighbor 1:1 propensity score (PS) matching was conducted to find the best control for each treated unit, with the PS (probability of receiving IAC) estimated from a logistic regression from the following matching variables: age, severity of illness, full therapy status, and type of hospital. Sensitivity analysis included trying various matching methods, matching cut-off criteria, PS modeling options on the matched cohort, and a logistic regression estimating the outcomes on the unmatched cohort. RESULTS: A total of 17,218 ICU admissions were included in the cohort, in which 9,442 (54.8%) had IAC. After matching, IAC was associated with similar hours alive and free of vasopressors (Median difference -1.35 hours, CI: -3.15, 0.08, p = NS), unchanged mortality (OR 0.95, CI: 0.89 – 1.01, p = NS), and similar time on vasopressors (1.08 days vs. 1.07 days, p = NS) but associated with increased risk of renal dysfunction (OR 1.36, CI 1.22 – 1.51, p < 0.01). The results from sensitivity analysis were consistent with the primary analysis. CONCLUSIONS: IAC use in patients admitted to the ICU on vasopressors is not associated with a difference in time alive and free of vasopressors or increased risk of death but is associated with new renal dysfunction. CLINICAL IMPLICATIONS: The routine use of IAC in patients with shock should be studied prospectively DISCLOSURES: No relevant relationships by Sura Alqaisi, source=Web Response No relevant relationships by Andrew Barros, source=Web Response No relevant relationships by Hyunjoon Lee, source=Web Response no disclosure on file for Susana Margare; No relevant relationships by Susan McLean, source=Web Response No relevant relationships by Hieu Nguyen, source=Web Response No relevant relationships by Priscilla Rivera, source=Web Response No relevant relationships by Saira Samani, source=Web Response

Predictors of Doubling of Serum Creatinine at the Time of Biopsy in a Lupus Nephritis Cohort

Predictors of Doubling of Serum Creatinine at the Time of Biopsy in a Lupus Nephritis Cohort

Early Change in Albuminuria with Canagliflozin Predicts Kidney and Cardiovascular Outcomes: A PostHoc Analysis from the CREDENCE Trial.

The association between early changes in albuminuria and kidney and cardiovascular events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association occurs with sodium-glucose cotransporter 2 inhibition. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial enrolled 4401 patients with type 2 diabetes and CKD (urinary albumin-creatinine ratio [UACR] >300 mg/g). This post hoc analysis assessed canagliflozin's effect on albuminuria and how early change in albuminuria (baseline to week 26) is associated with the primary kidney outcome (ESKD, doubling of serum creatinine, or kidney death), major adverse cardiovascular events, and hospitalization for heart failure or cardiovascular death. Complete data for early change in albuminuria and other covariates were available for 3836 (87.2%) participants in the CREDENCE trial. Compared with placebo, canagliflozin lowered UACR by 31% (95% confidence interval [95% CI], 27% to 36%) at week 26, and significantly increased the likelihood of achieving a 30% reduction in UACR (odds ratio, 2.69; 95% CI, 2.35 to 3.07). Each 30% decrease in UACR over the first 26 weeks was independently associated with a lower hazard for the primary kidney outcome (hazard ratio [HR], 0.71; 95% CI, 0.67 to 0.76; P<0.001), major adverse cardiovascular events (HR, 0.92; 95% CI, 0.88 to 0.96; P<0.001), and hospitalization for heart failure or cardiovascular death (HR, 0.86; 95% CI, 0.81 to 0.90; P<0.001). Residual albuminuria levels at week 26 remained a strong independent risk factor for kidney and cardiovascular events, overall and in each treatment arm. In people with type 2 diabetes and CKD, use of canagliflozin results in early, sustained reductions in albuminuria, which were independently associated with long-term kidney and cardiovascular outcomes.

Long-term renal outcomes of IgA nephropathy presenting with different levels of proteinuria

Proteinuria is a strong prognostic factor in IgA nephropathy (IgAN). However, the risk threshold of proteinuria for kidney disease progression remains in debate. This study aimed to evaluate the risk of different levels of proteinuria on renal outcomes in Chinese patients with IgAN. Patients with biopsy-proven primary IgAN were recruited and divided into four groups based on their proteinuria levels: ≤ 0.30 g/d, 0.31-0.50g/d, 0.51-1.00g/d, and >1.00 g/d. The primary outcomes were composed by doubling of baseline serum creatinine (Scr) and end-stage renal disease (ESRD, defined as eGFR <15 mL/min/1.73m2, initiation of dialysis or transplantation). A total of 921 IgAN patients were enrolled in this study. During a median follow-up duration of 48 (34-62) months, higher risks of doubling of baseline Scr developed in patients with proteinuria 0.31-0.50g/d (HR=2.87, p=0.04), 0.51-1.00 g/d (HR=4.26, p=0.002), and >1.00g/d (HR=14.56, p<0.001), while increased risks for ESRD were observed in patients with proteinuria 0.51-1.00g/d (HR=3.00, p=0.02) and >1.00g/d (HR=13.03, p<0.001) in unadjusted Cox regression models. After adjusted for potential confounders, proteinuria 0.31-0.50 g/d (HR=3.70, p=0.04), 0.51-1.00 g/d (HR=3.67, p=0.02), and >1.00 g/d (HR=8.20, p<0.001) remained to be significantly associated with higher risks of doubling of Scr, while only those with proteinuria >1.00g/d (HR=6.04, p=0.001) exhibited a markedly increased risk of ESRD. Patients with proteinuria levels > 0.30g/d already have a higher risk of doubling of baseline Scr, suggesting the necessity of early intervention in patients presenting with minimal proteinuria.