Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction &gt; 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c &lt;7%.

Proteinuria and serum creatinine after 12 months of treatment for lupus nephritis as predictors of long-term renal outcome: a case–control study

Background Lupus nephritis (LN) is a major source of morbidity and mortality in patients with systemic lupus erythematosus (SLE), with 10–25% of patients progressing to end-stage renal disease (ESRD). Objective This study aims to elucidate the predictive capabilities of 24-h proteinuria (24PTU) and serum creatinine (sCr) after 12 months of treatment with respect to long-term renal outcomes in LN in a single-center cohort of LN patients. Methods A retrospective analysis was performed on 214 patients diagnosed with LN followed in our center. Values of 24PTU and sCr were assessed at baseline and after 3, 6 and 12 months, and after 5 years and/or the last evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months or longer. End-stage renal disease (ESRD) was defined as the need for permanent dialysis. Receiver operating characteristics curves (ROC) were used to test the best cut-off value of 24PTU and sCr at 12 months who predict bad long-term renal outcomes. Results The mean follow-up period was 11.2 ± 7.2 years. The best cut-off values for 24PTU and sCr as predictor of CKD were, respectively, 0.9 g/24 h and 0.9 mg/dL. ROC curve for 24PTU had a slightly lower performance than ROC curve for sCr as predictor for CKD (PTU AUC = 0.68; sCr AUC = 0.70), but sensitivity and specificity were better for 24PTU (24PTU: sensitivity = 63.5%, specificity = 71.2%; sCr: sensitivity = 54.8%, specificity = 75.3%). When the outcome was ESRD the best cut-off points were 0.9 g/24hs and 1.3 mg/dL for 24PTU and sCr, respectively, and the curve performance was better for 24PTU (PTU AUC = 0.72; sCr AUC = 0.61). Conclusions In this ethnically diverse population with LN followed for a long time (> 10 years), levels of 24PTU > 0.9/day at 12 months was a good predictor of bad long-term renal outcome. The serum creatinine > 0.9 mg/dL and > 1.3 mg/dL at 12 months were also good predictors of CKD and ESRD, respectively. Patients with 24PTU < 0.9 g/day and sCr < 1.3 mg/dL at 12 months are not likely to develop ESRD because of the high negative predictive values (NPV) (93.2% and 82%). 24PTU and sCr are relevant as components for a treat-to-target strategy for LN treatment, since their high NPV corroborates their importance as good predictors of long-term renal outcome.

Urine β2-Microglobulin and Retinol-Binding Protein and Renal Disease Progression in IgA Nephropathy

Background: Tubulointerstitial involvement has been reported to have a decisive influence on the progression of IgA nephropathy (IgAN). High levels of urine β2-microglobulin (β2-MG) and retinol-binding protein (RBP) were observed in patients with IgAN with tubulointerstitial lesions. However, their roles in disease progression remain unclear. This study aimed to evaluate the associations of urine β2-MG and RBP with the progression of IgAN.Methods: We retrospectively investigated a cohort of 2,153 patients with IgAN. Clinical and pathological features, outcomes, and urine β2-MG, and RBP at the time of biopsy were collected. The associations, of urine β2-MG and RBP with the composite renal outcome, defined as a decline in estimated glomerular filtration rate (eGFR) of ≥50% from baseline or end-stage renal disease (ESRD), were examined using restricted cubic splines and the Cox proportional hazards models.Results: During a median follow-up of 20.40 months, 140 (6.50%) patients reached the composite renal outcomes. Restricted cubic splines showed that patients with higher urinary β2-MG and RBP levels had worse renal outcomes. The Cox regression analysis revealed that urine β2-MG and RBP were associated with a risk of the composite renal outcome in the multivariate adjusted model [+1 SD for log β2-MG, hazard ratio (HR) = 1.462, 95% CI: 1.136–1.882, p = 0.003; +1 SD for log RBP, HR = 1.972, 95% CI: 1.486–2.617, p = 0.001]. The associations were detectable within patients with baseline eGFR &lt;90 ml/min/1.73 m2 (+1 SD for log β2-MG, HR = 1.657, 95% CI: 1.260–2.180, p &lt; 0.001; +1 SD for log RBP, HR = 1.618, 95% CI: 1.199–2.183, p = 0.002), but not among patients with eGFR ≥90 ml/min/1.73 m2.Conclusion: Higher levels of urine β2-MG and RBP were independent risk factors for renal disease progression in IgAN.

Therapeutic Response and Long-Term Renal Outcomes in Childhood Idiopathic Steroid-Resistant Nephrotic Syndrome: A Single-Center Study

<b><i>Purpose:</i></b> We aimed to evaluate therapeutic response and long-term renal outcomes of childhood idiopathic steroid-resistant nephrotic syndrome (iSRNS). <b><i>Methods:</i></b> We retrospectively reviewed treatment regimens, especially calcineurin inhibitor (CNI), pathologic diagnoses, and long-term renal outcomes of iSRNS patients for 30 years. <b><i>Results:</i></b> Of 516 patients with idiopathic NS, 52 (10.1%) had iSRNS. Renal biopsies from 48 patients showed minimal change disease (MCD) in 23 (47.9%), focal segmental glomerulosclerosis in 24 (50.0%), and mesangioproliferative glomerulonephritis in 1 (2.1%). The median follow-up period was 66.5 (range, 4–275) months, and 90.4% of them were treated with a CNI. CNI induced remission in 70.2% within 50.4 ± 43.5 days. Of the patients with MCD and focal segmental glomerular sclerosis (FSGS), 86.4% (19/22) and 45.0% (9/20) (<i>p =</i> 0.005) responded to CNI, respectively. Mean time until remission after using CNI was longer with FSGS (90.4 ± 54.0 days) than with MCD (29.6 ± 26.3 days) (<i>p =</i> 0.010). CNI-responsive patients with FSGS or MCD showed preserved renal function, and CNI nonresponsive MCD patients also showed preserved renal function during follow-up. However, end-stage renal disease (ESRD) progressed in 8 out of 11 patients with FSGS nonresponsive to the CNI for an average of 44.9 ± 18.4 months after diagnosis. <b><i>Conclusion:</i></b> Different response rates and times for remission were achieved with the CNI according to the pathology of iSRNS. All MCD patients regardless of CNI response and all CNI-responsive patients with FSGS showed excellent renal outcomes, while almost all FSGS patients nonresponsive to CNI eventually progressed to ESRD.

The incidence, mortality and renal outcomes of acute kidney injury in patients with suspected infection at the emergency department

Background Acute kidney injury (AKI) is a major health problem associated with considerable mortality and morbidity. Studies on clinical outcomes and mortality of AKI in the emergency department are scarce. The aim of this study is to assess incidence, mortality and renal outcomes after AKI in patients with suspected infection at the emergency department. Methods We used data from the SPACE-cohort (SePsis in the ACutely ill patients in the Emergency department), which included consecutive patients that presented to the emergency department of the internal medicine with suspected infection. Hazard ratios (HR) were assessed using Cox regression to investigate the association between AKI, 30-days mortality and renal function decline up to 1 year after AKI. Survival in patients with and without AKI was assessed using Kaplan-Meier analyses. Results Of the 3105 patients in the SPACE-cohort, we included 1716 patients who fulfilled the inclusion criteria. Of these patients, 10.8% had an AKI episode. Mortality was 12.4% for the AKI group and 4.2% for the non-AKI patients. The adjusted HR for all-cause mortality at 30-days in AKI patients was 2.8 (95% CI 1.7–4.8). Moreover, the cumulative incidence of renal function decline was 69.8% for AKI patients and 39.3% for non-AKI patients. Patients with an episode of AKI had higher risk of developing renal function decline (adjusted HR 3.3, 95% CI 2.4–4.5) at one year after initial AKI-episode at the emergency department. Conclusion Acute kidney injury is common in patients with suspected infection in the emergency department and is significantly associated with 30-days mortality and renal function decline one year after AKI.