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Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case-control study.

ABSTRACT: INTRODUCTION:Children with chronic kidney disease (CKD) risk progressing to end-stage kidney disease (ESKD). The majority of CKD causes in children are related to congenital anomalies of the kidney and urinary tract, which may be treated by urologic care. OBJECTIVE:To examine the association of ESKD with urologic care in children with CKD. STUDY DESIGN:This was a nested case-control study within the Chronic Kidney Disease in Children (CKiD) prospective cohort study that included children aged 1-16 years with non-glomerular causes of CKD. The primary exposure was prior urologic referral with or without surgical intervention. Incidence density sampling matched each case of ESKD to up to three controls on duration of time from CKD onset, sex, race, age at baseline visit, and history of low birth weight. Conditional logistic regression analysis was performed to estimate rate ratios (RRs) for the incidence of ESKD. RESULTS:Sixty-six cases of ESKD were matched to 153 controls. Median age at baseline study visit was 12 years; 67% were male, and 7% were black. Median follow-up time from CKD onset was 14.9 years. Seventy percent received urologic care, including 100% of obstructive uropathy and 96% of reflux nephropathy diagnoses. Cases had worse renal function at their baseline visit and were less likely to have received prior urologic care. After adjusting for income, education, and insurance status, urology referral with surgery was associated with 50% lower risk of ESKD (RR 0.50 [95% confidence interval [CI] 0.26-0.997), compared to no prior urologic care (Figure). After excluding obstructive uropathy and reflux nephropathy diagnoses, which were highly correlated with urologic surgery, the association was attenuated (RR 0.72, 95% CI 0.24-2.18). DISCUSSION:In this study, urologic care was commonly but not uniformly provided to children with non-glomerular causes of CKD. Underlying specific diagnoses play an important role in both the risk of ESKD and potential benefits of urologic surgery. CONCLUSION:Within the CKiD cohort, children with non-glomerular causes of CKD often received urologic care. Urology referral with surgery was associated with lower risk of ESKD compared to no prior urologic care but depended on specific underlying diagnoses.

SUBMITTER: Chu DI

PROVIDER: S-EPMC6588473 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case-control study.

Chu D I DI Abraham A G AG Tasian G E GE Denburg M R MR Ross M E ME Zderic S A SA Furth S L SL

Journal of pediatric urology 20190316 3

<h4>Introduction</h4>Children with chronic kidney disease (CKD) risk progressing to end-stage kidney disease (ESKD). The majority of CKD causes in children are related to congenital anomalies of the kidney and urinary tract, which may be treated by urologic care.<h4>Objective</h4>To examine the association of ESKD with urologic care in children with CKD.<h4>Study design</h4>This was a nested case-control study within the Chronic Kidney Disease in Children (CKiD) prospective cohort study that inc ...[more]

PMID: 30962011

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Project description:Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression.Prospective multicenter observational cohort study.496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study.Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia.Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR).398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally.Small number of events in glomerular patients and use of internal cross-validation.Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.

Project description:Rationale & objectiveChronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.Study designObservational study.Participants702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsPlasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).OutcomesNeurocognitive tests of intelligence, academic achievement, and executive functions.Analytical approachLinear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.ResultsAt baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β = 2.3 [1.0, 3.6]), Variability (β=1.4 [0.4, -2.4]), and Hit Reaction Time (β = 1.3 [0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (P < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).LimitationsThe study does not assess the cumulative effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.ConclusionsIn children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.

Project description:BACKGROUND AND OBJECTIVES:We investigated the incidence of ESKD after surgical management of kidney cancer in the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy resulting from kidney cancer across Australia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:All newly diagnosed cases of kidney cancer in the Australian state of Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using international classification of disease-10-coded hospital administrative data. Incidence rate and 3-year cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data. RESULTS:The incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated with increased ESKD risk were age?65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists classification ?3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and postoperative length of hospitalization ?6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to 0.6 per 100,000 per year. CONCLUSIONS:In Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_09_28_CJASNPodcast_18_1_.mp3.

Project description:BackgroundAnemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25--the key hormone of iron-metabolism--on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.Methods249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003-2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.ResultsPatients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).ConclusionsWe found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define "high risk" populations in CKD.

Project description:BackgroundAcute kidney injury (AKI) and chronic kidney disease (CKD) are common syndromes associated with significant morbidity, mortality and cost. The extent to which repeated AKI episodes may cumulatively affect the rate of progression of all-cause CKD has not previously been investigated. In this study, we explored the hypothesis that repeated episodes of AKI increase the rate of renal functional deterioration loss in patients recruited to a large, all-cause CKD cohort.MethodsPatients from the Salford Kidney Study (SKS) were considered. Application of KDIGO criteria to all available laboratory measurements of renal function identified episodes of AKI. A competing risks model was specified for four survival events: Stage 1 AKI; stage 2 or 3 AKI; dialysis initiation or transplant before AKI event; death before AKI event. The model was adjusted for patient age, gender, smoking status, alcohol intake, diabetic status, cardiovascular co-morbidities, and primary renal disease. Analyses were performed for patients' first, second, and third or more AKI episodes.ResultsA total of 48,338 creatinine measurements were available for 2287 patients (median 13 measures per patient [IQR 6-26]). There was a median age of 66.8years, median eGFR of 28.4 and 31.6% had type 1 or 2 diabetes. Six hundred and forty three (28.1%) patients suffered one or more AKI events; 1000 AKI events (58% AKI 1) in total were observed over a median follow-up of 2.6 years [IQR 1.1-3.2]. In patients who suffered an AKI, a second AKI was more likely to be a stage 2 or 3 AKI than stage 1 [HR 2.04, p 0.01]. AKI events were associated with progression to RRT, with multiple episodes of AKI progressively increasing likelihood of progression to RRT [HR 14.4 after 1 episode of AKI, HR 28.4 after 2 episodes of AKI]. However, suffering one or more AKI events was not associated with an increased risk of mortality.ConclusionsAKI events are associated with more rapid CKD deterioration as hypothesised, and also with a greater severity of subsequent AKI. However, our study did not find an association of AKI with increased mortality risk in this CKD cohort.

Dataset Information

Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case-control study.

Publications

Urologic care and progression to end-stage kidney disease: a Chronic Kidney Disease in Children (CKiD) nested case-control study.

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