Adverse Renal Outcomes Research Articles

Differential effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes according to renal function: a dose-response meta-analysis involving 10 randomized clinical trials and 71 553 individuals.

The main target of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the sodium-glucose cotransporters 2, is found in the kidneys, and their activity is reduced in patients with chronic kidney disease (CKD). How the efficacy of SGLT2i may vary in patients with different levels of renal impairment has not been fully elucidated. We searched the PubMed databases for relevant studies published through May 25, 2022. Randomized control trials comparing SGLT2i with placebo and reporting cardiovascular or renal outcomes were included. The primary outcome was the composite of major adverse cardiovascular events (MACE), which were defined as cardiovascular death (CV death), nonfatal myocardial infarction (MI), and nonfatal ischemic stroke. Secondary outcomes included the components of MACE, all-cause mortality, hospitalization for heart failure (HHF), the composite of CV death and HHF, and composite renal outcomes. Linear meta-regression analysis was used to assess the effects of estimated glomerular filtration rate (eGFR) on the risks associated with SGLT2i treatment vs placebo for all outcomes. Nonlinear meta-regression analysis was also performed for MACE to investigate the combined influence of reduced drug efficacy in CKD but possible greater risk reduction in a population with higher risk at baseline. Further analyses were performed by including additional study-level covariates, including the prevalence of diabetes mellitus (DM), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). Risk ratios for MACE, CV death, nonfatal MI, HHF, and composite renal outcomes associated with SGLT2i treatment were not significantly related to baseline eGFR values. A positive association was observed between eGFR values and the risk of stroke with SGLT2i use (regression coefficient β = .0109, 95% confidence interval [CI] 0.0029-0.0188). A similar positive association was observed between eGFR values and the composite outcome of CV death and HHF (β = .0025, 95% CI 0.0000-0.0051). The results of the meta-regression analyses, including the additional covariates of DM, HF, and ASCVD, were consistent with the results of the primary analyses for most outcomes. The protective effects of SGLT2i for reducing most adverse cardiovascular and renal outcomes persisted in patients with variable degrees of renal impairment. The observed benefits such as preventing CV death, HF worsening, or stroke may be greater for patients with more severe CKD. Considering the cardiovascular and renal benefits associated with SGLT2i treatment, patients with CKD should be treated aggressively to improve outcomes. CRD42021273500.

Association of Reversal of Renin Suppression With Long-Term Renal Outcome in Medically Treated Primary Aldosteronism.

Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/mL per hour; otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/mL per hour) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/mL per hour). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (-0.46 [95% CI, -0.63 to -0.28] mL/min per 1.73 m2 per year) than those with suppressed posttreatment renin (-1.41 [95% CI, -1.56 to -1.27] mL/min per 1.73 m2 per year; difference, 0.96 [95% CI, 0.72-1.20] mL/min per 1.73 m2 per year). Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

The association between intraoperative cardiopulmonary bypass power and complications after cardiac surgery.

Low cardiac power (product of flow and pressure) has been shown to be associated with mortality in patients with cardiogenic shock after acute myocardial infarction, but has not been studied in cardiac surgical patients. This study's hypothesis was that cardiac power during cardiopulmonary bypass for cardiac surgery would have a greater association with adverse events than either flow or MAP (mean arterial pressure) alone. We undertook a retrospective observational study using patient data from February 2015 to March 2022 undergoing cardiac surgery at Fiona Stanley Hospital in Perth Australia. Excluded were patient age less than 18years old, patients undergoing thoracic transplantation, ventricular assist devices, off pump cardiac surgery and aortic surgery. The primary outcome was a composite outcome of 30-days mortality, stroke or new-onset renal insufficiency. Overall, 1984 cardiac surgeries were included in the analysis. Neither duration nor area below thresholds tested for power, MAP or flow was associated with the primary composite outcome. However, we found that an area below MAP thresholds 35-50mmHg was associated with new renal insufficiency (adjusted odds ratio 1.17 [95% CI 1.02 to 1.35] for patients spending 10min at 10mmHg below 50mmHg MAP compared to those who did not). This study suggests that MAP during cardiopulmonary bypass, but not power or flow, was an independent risk factor for adverse renal outcomes for cardiac surgical patients.

The association of normal-range serum phosphorus with immunoglobulin A nephropathy progression: a retrospective cohort study.

The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73-1.04mmol/L; second tertile: 1.04-1.21mmol/L; third tertile: 1.21-1.60mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. During a median 16month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953-1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522-92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019-87.165, P = 0.048). Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy.

#6517 CLINICOHISTOLOGICAL CHARACTERISTICS, THERAPEUTIC APPROACH AND RENAL OUTCOME IN PATIENTS WITH C3 GLOMERULOPATHY: A SINGLE-CENTER EXPERIENCE

Abstract Background and Aims C3 glomerulopathy has been identified as a distinct disease in the last decade but it has already been associated with a high burden of end stage renal disease (ESRD). Due to the rarity and heterogeneity of the disease, data regarding the prognosis and optimal treatment are still lacking. We aimed to describe the clinical and histological phenotype of patients with C3 glomerulopathy followed at our center, the treatment regimens applied and their long-term renal outcome. Method We conducted a retrospective medical chart review of 19 patients with C3 glomerulopathy followed at our center and we reported clinical, histological and therapeutic parameters as well as their long-term renal outcome. Results Median age of patients at the time of diagnosis was 23 years (IQR 28), median proteinuria 2.6 g/d (IQR 2.8) and median eGFR 63ml/min (IQR 63). 26% of patients (5/19) presented with an eGFR <30ml/min. Low serum C3 levels were reported in 11/19 patients (58%). Α monoclonal paraprotein was detected in three patients and pathogenous mutations of CFH/CFI genes in 4 out of 10 patients who underwent genetic testing. 41% of patients (7/17) were treated with RAAS inhibitors only, while 59% (10/17) received immunosuppressive treatment. Immunosuppressive treatment consisted of different combinations of steroids with mycophenolic acid, cyclophosphamide, cyclosporine or rituximab and steroid monotherapy in one patient. Treatment data were not available for two patients. There was a significant difference in baseline proteinuria between patients treated with RAAS inhibitors only (median 1.5g/d, IQR 1.14) and those who were treated with immunosuppressants (median 3.95g/d, IQR 4.8) (p = 0.003). Remission (complete or partial) was achieved by 43% of patients at 6 months and by 50% at 12 months. Median follow up time was 45 months (IQR 66). Eight patients (42%) reached ESRD in a median time of 58.5 months (IQR 62.5) while other three patients (16%) ended up with a GFR decline >30%. Among patients with adverse renal outcome (ESRD, GFR decline >30%), 54.5% (6/11) had baseline proteinuria >3g/d, 73% (8/11) had low serum C3 and 54.5% (6/11) had interstitial fibrosis/tubular atrophy >25%, while the median percentage of glomerulosclerosis was 33% (IQR 58). On the contrary, in the group of patients with favorable renal outcome, baseline proteinuria >3g/d was reported in only 25% (2/8), low serum C3 in 37.5% (3/8), interstitial fibrosis/tubular atrophy >25% in 25% (2/8), while median glomerulosclerosis was only 8% (IQR 15). Attainment of complete remission was associated with favorable renal outcome (p = 0.001). Five of eight patients who reached ESRD underwent kidney transplantation from a living related donor. All of them received basiliximab, mycophenolic acid, tacrolimus and steroids. Recurrence of C3 glomerulopathy was reported in four of these patients and eculizumab was given in two of them. Graft loss due to disease recurrence was observed in one patient. Conclusion The present case series of patients with C3 glomerulopathy highlights the great heterogeneity in the clinical phenotype, therapeutic approach and renal prognosis of the disease. It also underscores the importance of attainment of complete remission regarding the long-term renal survival. Large studies are needed in order to better define clinical and histological predictors of adverse renal outcome as well as the optimal treatment regimens.

#6663 PRIMARY SJöGREN SYNDROME WITH BIOPSY PROVEN RENAL INVOLVEMENT: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease, characterized by inflammation and destruction of the exocrine glands and the involvement of multiple organs. A wide variety of kidney manifestations associated with pSS have been described. The prevalence of kidney involvement is not clear. Our aim was to describe the renal involvement of patients with pSS diagnosed by kidney biopsy (KB). We also analyzed the clinical manifestations, laboratory and immunological characteristics, clinical outcomes and treatments received in patients with pSS referred to a specialized kidney centre. Method Observational, retrospective study of adult patients (age > 18 years) diagnosed with pSS (EULAR criteria) referred and treated at a kidney referral centre (Fundació Puigvert) in Barcelona, Spain. We collected data from the clinical records registry including demographic variables, laboratory parameters, biopsy results and adverse outcomes, defined by the need of renal replacement therapy (RTT) and/or death. Absolute frequencies, percentages, means and standard deviations were used for statistical analysis. Multivariate analysis was performed as appropriate in SPSS V28.0 Results A total of 27 patients with pSS underwent KB from January 1994 to July 2022; all patients were female, with a median age of 58.4 years (SD ±12.4); 85% were Caucasian. The mean baseline glomerular filtration rate (eGFR) was 65.9 mL/min (SD ±16) (before nephrologist referral), with 8 of 27 patients (29.6%) having eGFR less than 60 mL/min at baseline. The main indication for nephrological evaluation was acute kidney injury (AKI) (63%), followed by the presence of non-nephrotic proteinuria with dysmorphic haematuria (29.6%). The most common finding in KB was acute interstitial nephritis (AIN) (55.6%), as an isolated AIN kidney lesion in twelve patients (44.4%). Mild interstitial nephritis was noted in the context of a predominant glomerular lesion in three other patients (one membranoproliferative glomerulonephritis, one IgA nephropathy and one AA amyloidosis). Nine patients (33.3%) had glomerular lesion (see Table 1). In 18.5% of patients, the diagnosis of pSS was made after the renal biopsy. The percentage of patients receiving ACEI/ARB was 77.8%. A total of 25 patients received some type of immunosuppression (IS). Corticosteroids being the most frequently used (77.8%), followed by the combination IS treatment (44%) and rituximab (33.3%). At the time of the KB, the mean eGFR was 46.3 mL/min (SD ±24), compared to eFGR of 45.2 mL/min (SD ±22) one-year after KB. During follow-up, seven patients (25.9%) required RRT and three (11.1%) died from non-renal causes, mainly by infections associated with immunosuppression. Factors associated with adverse renal outcomes were AKI (p = 0.01), baseline eGFR CKD-EPI less than 60 mL/min (p = 0.005), presence of anti-Ro60 antibodies (p = 0.046), use of plasmapheresis (p = 0.013), use of cyclophosphamide (p = 0.013) and the presence of tubulointerstitial atrophy with glomerular sclerosis on kidney biopsy (p = 0.010). Conclusion Our study included a larger cohort than previously reported before in a single centre. In our cohort of patients with pSS who were evaluated by KB, AIN was the leading cause of renal involvement, as has been seen in other studies. The presence of eGFR below 60 mil/min at baseline and the finding of chronicity in the KB are associated with an adverse outcome, as well as is the presence of AKI. Early referral to nephrologist may be important for prognosis, and KB is necessary for accurate diagnosis of kidney involvement to allow targeted treatment.

#4482 PREGNANCY AND RENAL OUTCOMES IN WOMEN WITH CHRONIC KIDNEY DISEASE: A POPULATION STUDY

Abstract Background and Aims Women with CKD stages 3-5 are at higher risk of adverse pregnancy outcomes, including preterm delivery and low birthweight and progression of kidney disease. However, data describing outcomes of women with less severe kidney disease are limited, and few compare with women normal renal function. Furthermore, most studies report cohorts recruited from specialist clinics and may not be representative. This study aimed to describe pregnancy outcomes in a UK population cohort according to pre-conception eGFR <90 ml/min/1.73 m2 compared with women with eGFR ≥90 ml/min/1.73 m2. Method Routinely collected pregnancy data from three NHS Trust hospitals in Kent (UK) between 2010 and 2020 were extracted with Research Ethics Committee approval (19/LO/1242 and 18/SC/0158). Local laboratory and clinical data were linked to identify women with eGFR measured within two years of conception. Women without preconception creatinine were excluded from analysis. Baseline characteristics were described and comparisons between eGFR and adverse pregnancy and renal outcomes were tested. Results A total of 14,243 pregnancies with confirmed pre-pregnancy creatinine were included, of which 1,405/14,243 (9.9%) had CKD stages 1-4 (stage 1: 221/14,243 (1.6%), stage 2: 1,170/14,243 (8.2%), stage 3: 12/14,243 (0.1%), stage 4: 2/14,243 (0.01%) (Table 1). Women with pre-pregnancy eGFR 60-89 ml/min/1.73 m2 (stage 2) were significantly older at conception than women without CKD (eGFR ≥90 ml/min/1.73 m2) but there were no significant differences in live birth rates, small for gestational age, gestation at delivery, and preterm birth. In pregnancies with CKD (1,405, stages 1-4), pre-pregnancy eGFR was weakly correlated with birthweight (rs = 0.05, p = 0.05), and gestational age (rs = 0.06, p = 0.05). Conclusion To our knowledge, this is the largest population cohort to describe pregnancy outcomes between women with eGFR 60-89 ml/min/1.73 m2 compared with eGFR ≥90 ml/min/1.73 m2. Women with eGFR 60-89 ml/min/1.73 m2 did not have worse renal or pregnancy outcomes compared to eGFR ≥90 ml/min/1.73 m2. Limitations include lack of proteinuria data and details of structural CKD (Class 1 CKD), and only one eGFR measurement prior to pregnancy may have led to some women with temporary reduction in function being included in the cohort. Overall, the findings suggest that women with eGFR 60-89 ml/min/1.73 m2 should not be discouraged from pregnancy.

#3015 EFFECT OF DAPAGLIFLOZIN ON ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES AND CKD

Abstract Background and Aims Albuminuria in patients with diabetes presents a higher risk for adverse renal and cardiovascular (CV) outcomes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors demonstrate improved albuminuria and reduces the risk of end-stage renal disease in patients with chronic kidney disease. The study aim was the impact of the SGLT2 inhibitor dapagliflozin on urine albumin-to-creatinine ratio (UACR) and GFR decline. Method In the single center trial, total 132 participants with CKD and type 2 diabetes (T2D) were randomly assigned to dapagliflozin (n = 78) 10 mg once daily or placebo (n = 54). Kidney inclusion criteria were eGFR 30-60ml/min/1.73 m2 and any UACR. The primary end point was a composite of sustained decline in eGFR ≥50%, end-stage renal disease, or kidney or cardiovascular death. Percentage treatment difference was estimated by geometric mean ratio for the overall cohort and by eGFR and UACR subgroups. Progression/regression of UACR were assessed. Hazard ratios, 95% confidence intervals (CI), and p-values were estimated by Cox proportional hazards model. Results Median baseline eGFR was 42.3ml/min/1.73 m2, with 5% at <30ml/min/1.73 m2. At baseline, median UACR was 103 mg/g, and 1/4 of patients had normoalbuminuria, 2/4 had micro, and 1/4 had macroalbuminuria. Median follow up was 18 months. The UACR difference for dapagliflozin vs placebo was -25.1% (95% CI -27.5, -23.2; p<0.001). Reductions were similar across eGFRs. In UACR 30-299mg/g and ≥300mg/g, reductions were significant in dapagliflozin (p<0.001). Progression risk was lower and regression risk higher in dapagliflozin vs placebo (p<0.001). Conclusion Dapagliflozin significantly slowed long-term eGFR decline in patients with CKD with T2D compared with placebo, and significantly reduced UACR and had favorable effects on UACR progression and regression.

#5551 THE TROPONIN LEVEL AND ITS INFLUENCE ON RENAL AND CARDIOVASCULAR EFFECTS IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Cardiovascular (CV) morbidity and mortality are highly prevalent in renal transplant recipients (RTRs). As such, assessments of CV status using troponin concentrations could help to identify patients at risk for death or CV events and as a predictor for deterioration of graft function. The aim of the study was to investigate the biomarker troponin for the prediction of adverse renal and cardiovascular outcomes in stable RTRs. Method 305 stable RTRs with a median age of 53 years, (60.6% male) transplanted between 1994 and 2018 were enrolled in the study. General characteristics are shown in Table 1. At baseline, troponin, NT-pro BNP, carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) were measured. Troponin was measured during a routine baseline visit in stable RTR without cardiac symptoms. The median troponin concentration (11 ng/l) was used as cut-off. Patients were divided into two groups high (≥11 ng/l) and low (<11 ng/l) troponin and followed for 54 months. During this time CV events (stroke, myocardial infarction, peripheral artery thrombosis) death, graft loss and deterioration of renal graft function (increasing creatinine ≥30%) or proteinuria (urine protein creatinine ratio UPCR ≥500 mg/g) were monitored. Results At baseline, significant differences were observed between groups in terms of creatinine, eGFR, troponin, UPCR, PP, and PWV. In the group with baseline troponin ≥11ng/l, more patients had coronary artery disease/peripheral obliterans artery disease (CAD/POAD), heart failure (HF), and diabetes. Baseline troponin correlated only weakly with age (R = 0.47), cfPWV (R = 0.41), eGFR (R = −0.52). During follow-up, patients with high troponin experienced more frequently an increase in creatinine ≥30% (32.9% vs 13%), doubling creatinine (11.2% vs 3.1%), an increase in UPCR (22.4% vs 9.2%), graft loss (16.1% vs 1,8%), death (13.3% vs 0%), and CV events (6.3% vs 4.9%). Conclusion 1. Age, arterial stiffness, and eGFR only have a weakly impact on troponin in stable RTR. 2. Higher troponin is associated with poor outcomes and might be useful not only for the identification of patients with high-risk CV events but also for the deterioration of allograft function.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery.

Postoperative acute kidney injury (AKI) is a prevalent condition and associated with increased morbidity and mortality following cardiac surgery. This study aimed to investigate the association of underweight and obesity with adverse postoperative renal outcomes in infants and young children undergoing congenital heart surgery. This retrospective cohort study included patients aged from 1month to 5years who underwent congenital heart surgery with cardiopulmonary bypass at the Second Xiangya Hospital of Central South University from January 2016 to March 2022. On the basis of the percentile of body mass index (BMI) for age and sex, eligible participants were divided into three nutritional groups: normal bodyweight, underweight (BMI P5), and obesity (BMI P95). Primary outcomes included postoperative AKI and major adverse kidney events within 30days (MAKE30). Multivariable logistic regression was performed to determine the association of underweight and obesity with postoperative outcomes. The same analyses were reproduced for classifying patients using weight-for-height instead of BMI. A total of 2,079 eligible patients were included in the analysis, including 1,341 (65%) patients in the normal bodyweight group, 683 (33%) patients in the underweight group, and 55 (2.6%) patients in the obesity group. Postoperative AKI (16% vs. 26% vs. 38%; P < 0.001) and MAKE30 (2.5% vs. 6.4% vs. 9.1%; P < 0.001) were more likely to occur in the underweight and obesity groups. After adjusting for potential confounders, underweight (OR1.39; 95% CI 1.08-1.79; P = 0.008) and obesity (OR 3.85; 95% CI 1.97-7.50; P < 0.001) were found to be associated with an increased risk of postoperative AKI. In addition, both underweight (OR 1.89; 95% CI 1.14-3.14; P = 0.014) and obesity (OR 3.14; 95% CI 1.08-9.09; P = 0.035) were independently associated with MAKE30. Similar results were also found when weight-for-height was used instead of BMI. Conclusion: In infants and young children undergoing congenital heart surgery, underweight and obesity are independently associated with postoperative AKI and MAKE30. These results may help assess prognosis in underweight and obese patients, and will guide future quality improvement efforts. What is Known: • Postoperative acute kidney injury (AKI) is prevalent and associated with increased morbidity and mortality following pediatric cardiac surgery. • Major adverse kidney events within 30days (MAKE30) have been recommended as a patient-centered endpoint for evaluating AKI clinical trajectories. A growing concern arises for underweight and obesity in children with congenital heart disease. What is New: • Prevalence of underweight and obesity among infants and young children undergoing congenital heart surgery was 33% and 2.6%, respectively. • Both underweight and obesity were independently associated with postoperative AKI and MAKE30 following congenital heart surgery.

BASELINE CARDIAC BIOMARKER ANALYSIS FROM THE BASEL POSTPARTUM HYPERTENSION REGISTRY

Objective: Postpartum hypertension (PPHT) is defined by elevated blood pressure measurements after birth of more than 140 mmHg systolic and more than 90 mmHg diastolic, that persist or develop directly after pregnancy and is associated with adverse cardiovascular and renal outcome. Aim of the current analysis was the evaluation of different prognostic cardiac and stress related biomarkers like cardiac troponin T (cTnT), N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) in the setting of PPHT. Design and method: Enrollment for the prospective observational Basel Postpartum Hypertension Registry began in June 2020 at the University Hospital Basel. Women with preexisting hypertension, hypertensive disorders of pregnancy (HDP), and de novo postpartum hypertension were enrolled and followed up in structured management program. Clinical history and lab values were collected out of the electronic health records. Additional blood samples were stored for further evaluation. The present analysis contains biomarker analysis of a subset of 58 out of 288 patients using blood samples taken within one week of giving birth. Serum samples were analyzed for detectable levels of cTnT, NT-proBNP and GDF-15 at the department for Laboratory Medicine at University Hospital Basel using electrochemiluminescence immunoassay Elecsys on the Cobas e 801 platform (Roche Diagnostics, Rotkreuz, Switzerland). Results: Mean age of the patients from whom we measured biomarkers at baseline was 34±4.7. Mean troponin was 8.5 ng/l ±2.2 with normal cuttoffs for this age group being 14ng/l and sex specific cutoffs at 9ng/l. NT-proBNP was 229.86ng/l ±80.4, with 125ng/l being the normal cut off in an acute disease setting. Mean GDF-15 was 1895.8ng/l ±323.5 with correlating normal values in healthy populations in the same age range being 564 ± 223 ng/l. Conclusions: This first biomarker analysis shows a trend of elevated NT-proBNP and GDF-15 which are associated with cardiovascular disease or stress. Cardiac troponin T was not elevated in most of the patients, but in a subset of 13 patients. Further analysis and long term outcome correlations remains to be established and may be part of the follow-up analyses of the Basel PPHT cohort.

Atherosclerotic renovascular disease: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and the Working Group Hypertension and the Kidney of the European Society of Hypertension (ESH).

Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health problem with clinical presentations relevant to many medical specialties and carries a high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension or rapid loss of kidney function). This clinical practice document, prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH), summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision making and everyday management of patients with this condition.

Long-term effects of contrast media exposure on renal failure progression: a retrospective cohort study

BackgroundWith the constant need for technique improvement for ensuring correct diagnoses and precise treatment, imaging examinations that use contrast media have become unavoidable and indispensable. However, the long-term effects of contrast media on renal function remain unclear in populations with advanced renal failure. This study aimed to examine the relationship between contrast media exposure and long-term trends in renal function in patients with renal failure.MethodsThis retrospective cohort study included patients with a definitive diagnosis of chronic kidney disease who visited medical institutions in Japan between April 2012 and December 2020. The cohort was divided into contrast agent therapy and non-contrast agent therapy groups. The assessment indices were the number of contrast exposures and renal function decline. Renal function decline was calculated based on observed chronic kidney disease stage trends and glomerular filtration rate correspondence tables sourced from various guidelines. A stratified analysis focusing on changes in renal function while accounting for the acceleration of chronic kidney disease progression was also performed.ResultsAfter adjusting for patient background with propensity score matching, 333 patients each were included in both groups. The observation period was 5.3 ± 2.1 and 4.9 ± 2.2 years per case in the contrast-enhanced and non-contrast-enhanced groups, respectively. The baseline estimated glomerular filtration rate at the beginning of the observation period was 55.2 ± 17.8 mL/min/1.73 m2 in the contrast-enhanced groups (P = 0.65). Although only slightly different in both groups, the glomerular filtration rate change was 1.1 ± 3.3 mL/min/1.73 m2/year in the contrast agent therapy group and tended to be higher with contrast media exposure. Stratified analysis showed that the annual glomerular filtration rate changes in patients with more contrast media exposures and altered renal function were 7.9 ± 7.1 mL/min/1.73 m2/year and 4.7 ± 3.6 mL/min/1.73 m2/year in the contrast agent therapy and non-contrast agent therapy groups, respectively (1.69 times, P < 0.05).ConclusionWe were able to identify a clinical trend of successful measures for preventing adverse renal outcomes associated with contrast media exposure. However, increased frequency of contrast media exposure has a long-term effect on renal function in patients with altered it. Appropriate treatment choices related to contrast media may control chronic kidney disease.

Non-insulin-based insulin resistance indices for predicting all-cause mortality and renal outcomes in patients with stage 1-4 chronic kidney disease: another paradox.

Non-insulin-based insulin resistance (IR) indices serve as the indicators of metabolic syndrome (MetS) but have limited value for predicting clinical outcomes. Whether the obesity paradox affects the predictive value of these indicators in patients with chronic kidney disease (CKD) remains unknown. We investigated whether MetS and non-insulin-based IR indices can predict all-cause mortality and renal outcomes in a prospective observational study with stage 1-4 CKD Asians (N = 2,457). These IR indices were associated with MetS. A Cox regression model including body mass index (BMI) revealed an association between MetS and renal outcomes. Among the IR indices, only high triglyceride-glucose (TyG) index was associated with adverse renal outcomes: the hazard ratio of Q4 quartile of the TyG index was 1.38 (1.12-1.70). All-cause mortality was marginally associated with MetS but not high IR indices. Low TyG and TyG-BMI indices as well as low BMI and triglyceride were paradoxically associated with increased risks of clinical outcomes. The triglyceride-to-high-density lipoprotein cholesterol ratio and metabolic score for IR indices were not associated with clinical outcomes. In conclusion, MetS and TyG index predict renal outcome and obesity paradox affects the prediction of IR indices in patients with stage 1-4 CKD.

O029 Adverse renal outcomes following endovascular or open repair of infra-renal and supra-renal abdominal aortic aneurysms: a systematic review and meta-analysis

Abstract Introduction This study aims to quantify the risk of permanent renal dialysis for AAA repair, with comparison between endovascular (EVAR) and open repair (OAR) techniques for suprarenal (SR) and infrarenal (IR) AAA. Methods Systematic review, meta-analysis and meta-regression of post-operative, permanent dialysis outcomes were performed, following PRISMA guidance (Prospero registration: CRD42021272422). Database searches were conducted on MEDLINE, Embase, CENTRAL using ProQuest Dialog. We included data published after 2011, reporting primary elective AAA repair, for a minimum of 100 patients with &amp;gt;75% of operations undertaken after January 1, 2000. Results Seventy-nine studies (IR AAAs: 54877 EVAR &amp; 7145; SR AAAs: 4241 EVAR &amp; 1723 OAR) were included (n=67986). Overall, low rates of permanent dialysis were reported: 0.35% of IR-EVAR, 0.68% IR-OAR, 0.82% SR-EVAR, and 0.59% SR-OAR. No significant difference in the risk of permanent dialysis for endovascular and open repair was observed (EVAR vs. OAR: odds ratio (OR) 0.52 95% CI[.06, 4.78], for IR, 2.14 [.46, 10.05], for SR). A lower risk of permanent dialysis was observed for IR vs. SR EVAR (OR .05 [0, .46]). Meta-regression indicated that post-operative permanent dialysis decreased over time as determined by study midpoint for IR-EVAR and IR-OAR. For IR-OAR, increased dialysis rates were significantly associated with study participants’ ages. Conclusion The rate of permanent dialysis &amp;lt;1% for all modalities of SR and IR AAA repair. For EVAR, the risk of dialysis was higher for SR compared to IR AAA. The likelihood of permanent dialysis has decreased with modern practice yet increases among older patients.

Venous congestion assessment using the venous excess ultrasound score: strongest predictor of acute kidney injury in patients with acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: None. Background Elevated mean central venous pressure is associated with an increased risk of acute kidney injury (AKI) in critically ill patients with a broad spectrum of cardiovascular diseases. Nowadays, it is possible to perform a non-invasive assessment of systemic venous congestion using the Venous Excess Ultrasound Score (VExUS) which may enable early identification of patients with increased risk of adverse renal outcomes. Purpose This study aimed to evaluate the association between venous congestion assessed with VExUS and the incidence of AKI in patients with acute coronary syndrome (ACS). Methods Venous congestion assessment using VExUS was performed in consecutive patients with ACS. Linear regression analysis was used to determine the variables associated with the highest measured serum creatinine (sCr) during hospitalization and the admission sCr. In addition, a multivariable logistic regression analysis was performed for assessing the independent risk factors for AKI, which was defined according to the KDIGO criteria. Results A total of 77 patients hospitalized with ACS were prospectively enrolled in this study. Nineteen (25.6%) patients developed AKI. Baseline chronic kidney disease, Killip-Kimball &amp;gt;II on admission, GRACE score, admission NTproBNP values, and VExUS were significantly higher in the AKI-group than in the non-AKI group. Baseline chronic kidney disease, admission NT-proBNP values, and VExUS were independent risk factors associated with the highest measured sCr and the admission sCr. In multivariable logistic regression analysis, the risk of AKI was significantly associated with baseline chronic kidney disease, admission NT-proBNP values, and VExUS. Conclusion Baseline chronic kidney disease, admission NT-proBNP values, and VExUS were significant independent predictors of AKI in patients with ACS.

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.

Rituximab treatment of adults with primary focal segmental glomerulosclerosis

To evaluate the efficacy and safety of rituximab (RTX) in the treatment of primary focal segmental glomerulosclerosis (FSGS) in adults. The clinical data of patients with primary FSGS who received RTX treatment in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The selected patients received RTX twice or four times, with a single dose of 375 mg/m2, and the interval between two times of administration of RTX was 2–4 weeks. The treatment target is to achieve the clearance of B cells (peripheral blood B cell count < 5/μl). The primary outcome measures were remission and recurrence of renal disease, and the secondary outcome measures were adverse events and renal outcomes. A total of 14 FSGS patients were included, including 12 males, 9 with glucocorticoid-dependent or frequently relapsing nephrotic syndrome, and 3 with newly diagnosed nephrotic syndrome. After RTX treatment, 7 patients with glucocorticoid-dependent/recurrent nephrotic syndrome were completely relieved. At 6 months of follow-up, glucocorticoids were discontinued in all patients except 1 patient. The other 5 patients achieved partial remission (PR), of which 1 patient relapsed after PR, and 1 initial patient achieved complete remission. One patient progressed to end-stage renal disease (ESRD) after 4 months of follow-up. RTX in the treatment of adult glucocorticoid-dependent/relapsing FSGS can reduce the risk of recurrence and help to decline or discontinue the use of glucocorticoid and immunosuppressants.

Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials

ObjectivesTo evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. Study designWe extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. Main outcome measuresHazard ratios (HRs) were used to calculate summary statistics. ResultsIn this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76–1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54–1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74–0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56–0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69–1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40–1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12–1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06–1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41–2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48–6.56; p = 0.40) at baseline. ConclusionsIntensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome.