Discontinuation of RAAS Inhibition in Children with Advanced CKD

Background and objectives Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study. Design, setting, participants,& measurements In this study, 69 children with CKD(67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73m(2)) who discontinued RAASi during prospective follow-up were included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during a median of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling. Results Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declined more rapidly after discontinuation of RAASi (23.9 ml/min per 1.73m2 per year; 95% confidence interval, 25.1 to 22.6) compared with the slope during RAASi treatment (21.5 ml/min per 1.73 m(2) per year; 95% confidence interval, 22.4 to 20.6; P=0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued. Conclusions Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD

URINARY EPIDERMAL GROWTH FACTOR (UEGF) IMPROVES PREDICTION OF CHRONIC KIDNEY DISEASE (CKD) PROGRESSION IN CHILDREN

WOS: 000443998400035

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease

Caliskan, Salim/0000-0002-3316-8032; Canpolat, Nur/0000-0002-3420-9756; Cakar, Nilgun/0000-0002-1853-0101; Ozcakar, Zeynep/0000-0002-6376-9189; Holle, Johannes/0000-0001-8032-4096; Shroff, Rukshana/0000-0001-8501-1072; DUZOVA, ALI/0000-0002-4365-2995WOS: 000503390100012PubMed: 31428929Background Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. Methods Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m(2). Results the median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 mu mol/l (8.7) and 17.0 mu mol/l (21.6), respectively. in a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. Conclusions Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.European Renal Association-European Dialysis and Transplant Association; Kuratorium fur Dialyse und Nierentransplantation (KfH) Foundation for Preventive Medicine; German Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [01EO0802]; Pfizer Deutschland GmbHThis study was made possible by grants from the European Renal Association-European Dialysis and Transplant Association (www.era-edta.org), th e Kuratorium fur Dialyse und Nierentransplantation (KfH) Foundation for Preventive Medicine, the German Federal Ministry of Education and Research (reference no. 01EO0802), and Pfizer Deutschland GmbH. the entire study was solely initiated and performed by the investigators of the 4C study group. the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Findings from 4C-T Study demonstrate an increased cardiovascular burden in girls with end stage kidney disease and kidney transplantation see

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre-and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum followup time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz + 0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m(2) per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m(2) per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure.German Federal Ministry of Education and Research [01EO0802]; European Renal Association -European Dialysis and Transplant Association; Roche Organ Transplant Research Foundation [365520785]This study was made possible by grants from the German Federal Ministry of Education and Research (#01EO0802), the European Renal Association -European Dialysis and Transplant Association (www.eraedta.org), and Roche Organ Transplant Research Foundation (#365520785). Several coauthors are members of the European Rare Kidney Disease Reference Network (ERKNet). This study has been presented as an abstract at the TTS (The Transplantation Society) 2020 Virtual Congress on September 14, 2020

Transplantation

BACKGROUND: Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. METHODS: We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. RESULTS: A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P  =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. CONCLUSIONS: IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk

Stricter blood pressure control is associated with lower left ventricular mass in children after kidney transplantation: a longitudinal analysis of the 4C-T study

BACKGROUND: We assessed the effect of blood pressure control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH). METHODS: Ninety-six patients (64 males) ≥9 months post–kidney transplantation from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease—Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic blood pressure exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively. RESULTS: At baseline, LVMI was 49.7±12.7g/m2.16 with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of −5.24g/m2.16 (P=0.007). A similar tendency was seen for cumulative SBP≤50th (β=−3.70 g/m2.16; P=0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic blood pressure, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic blood pressure ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03–1.07). CONCLUSIONS: Continuous exposure to blood pressure below the 60th pct led to regression of LVMI and LVH. Our data suggest stricter blood pressure control, which needs to be substantiated in a randomized controlled trial

Discontinuation of RAAS Inhibition in Children with Advanced CKD

Background and objectives Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study

URINARY EPIDERMAL GROWTH FACTOR (UEGF) IMPROVES PREDICTION OF CHRONIC KIDNEY DISEASE (CKD) PROGRESSION IN CHILDREN

WOS: 00044399840003