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Achieving remission of proteinuria in childhood CKD.

ABSTRACT: A multidrug treatment strategy that targets urinary proteins with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) up-titrated to the respective maximum tolerated dose combined with intensified blood pressure (BP) control has been found to prevent renal function loss in adults with proteinuric nephropathies. Herein, we investigated the effects of this treatment protocol in the pediatric patient population.From May 2002 to September 2014 we included in this observational, longitudinal, cohort study 20 consecutive children with chronic nephropathies and 24-h proteinuria of >200 mg who had received ramipril and losartan up-titrated to the respective maximum approved and tolerated doses [mean (?standard deviation) dose:2.48?(1.37) mg/m2 and 0.61 (0.46) mg/kg daily, respectively]. The primary efficacy endpoint was a >50 % reduction in 24-h proteinuria to <200 mg (remission). Secondary outcomes included changes in proteinuria, serum albumin, BP, and glomerular filtration rate (GFR).Mean (± standard deviation) patient age at inclusion was 13.8?±?2.8 years, and the median [interquartile range (IQR)] serum creatinine level and proteinuria were 0.7 (0.6-1.0) mg/dl and 690 (379-1270) mg/24 h or 435 (252-711) mg/m2/24 h, respectively. Proteinuria significantly decreased by month 6 of follow-up, and serum albumin levels increased over a median follow-up period of 78 (IQR 39-105) months. In the nine children who achieved remission, proteinuria reduction persisted throughout the whole follow-up without rebounds. The GFR improved in those children who achieved remission and worsened in those who did not. The mean GFR slopes differed significantly between these two groups (p?

SUBMITTER: Ruggenenti P

PROVIDER: S-EPMC5915370 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Achieving remission of proteinuria in childhood CKD.

Ruggenenti Piero P Cravedi Paolo P Chianca Antonietta A Caruso MariaRosa M Remuzzi Giuseppe G

Pediatric nephrology (Berlin, Germany) 20161004 2

<h4>Background</h4>A multidrug treatment strategy that targets urinary proteins with an angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) up-titrated to the respective maximum tolerated dose combined with intensified blood pressure (BP) control has been found to prevent renal function loss in adults with proteinuric nephropathies. Herein, we investigated the effects of this treatment protocol in the pediatric patient population.<h4>Methods</h4>From May 2002 to ...[more]

PMID: 27704256

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Project description:Background and objectivesProteinuria is used as an indicator of FSGS disease activity, but its use as a clinical trial end point is not universally accepted. The goal of this study was to refine proteinuria definitions associated with long-term kidney survival.Design, setting, participants, & measurementsData on 466 patients with primary FSGS with proteinuria (urine protein-to-creatinine ratio >1 g/g) were analyzed from five independent cohorts. Proteinuria by months 1, 4, and 8 after study baseline was categorized by conventional definitions of complete (<0.3 g/g) and partial remission (<3.5 g/g and 50% reduction in proteinuria). Novel remission definitions were explored using receiver operating curves. Kaplan-Meier methods were used to estimate the associations of proteinuria with progression to ESRD or a 50% loss in kidney function. Propensity score-adjusted Cox proportional hazards models were used to adjust for baseline proteinuria, eGFR, and therapy.ResultsIn the initial derivation cohort, conventional partial remission was not associated with kidney survival. A novel definition of partial remission (40% proteinuria reduction and proteinuria<1.5 g/g) on the basis of receiver operating curve analyses of 89 patients was identified (Sensitivity=0.70; Specificity=0.77). In the validation cohort analyses, complete remission was associated with better prognosis (6 out of 41 patients progressed to kidney failure; 6.6 per 100 patient-years) as was the novel partial remission (13 out of 71 progressed; 8.5 per 100 patient-years), compared with those with no response (51 out of 116 progressed; 20.1 per 100 patient-years). Conventional partial remission at month 8, but not month 4, was also associated with better response (19 out of 85 patients progressed; risk=10.4 per 100 patient-years). Propensity score-adjusted analyses showed the novel partial remission was associated with less progression at months 4 and 8 (month 4: hazard ratio, 0.50; P=0.01; month 8: hazard ratio, 0.30; P=0.002).ConclusionsReaching either a complete or partial remission using a novel or conventional definition was associated with better long-term outcomes in patients with FSGS.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_02_20_CJASNPodcast_18_3_T.mp3.

Project description:BackgroundsData on how lifestyle changes due to the coronavirus disease 2019 (COVID-19) pandemic have influenced the clinical features of kidney disease patients remain scarce.MethodsThis study retrospectively analyzed clinical variables in patients with stage G1-G4 chronic kidney disease (CKD) with complete or incomplete remission of proteinuria, who were managed in a nephrology outpatient clinic of a university hospital in Tokyo. The clinical variables during the COVID-19 pandemic (term 1, June-July 2020) were compared to those one year before the pandemic (term 0, June-July 2019). The urinary protein excretion (UPE) was used as the primary outcome measure.ResultsThis study included 325 patients with stage G1-G4 CKD (mean age 58.5 years old, 37.5% female, 80.6% on renin-angiotensin aldosterone system inhibitors [RAASis], 12.0% on maintenance dose immunosuppression therapy) evaluated at term 0. The UPE at terms 0 and 1 was 247 (92-624) and 203 (84-508) mg/day [median (25th-75th percentile)], respectively; the value in term 1 was 18% lower than that in term 0 (p<0.001), with no marked difference in body weight, blood pressure, protein intake or urinary salt excretion. In multivariable analyses, incomplete remission of proteinuria in term 0 (odds ratio [OR] = 2.70, p = <0.001), RAASi use (OR = 2.09, p = 0.02) and decreased urinary salt excretion in term 1 vs. term 0 (OR = 1.94, p = 0.002) were identified as independent variables associated with reduced UPE in term 1 vs. term 0. No significant interactions between the variables were observed.ConclusionIn kidney disease patients receiving standard medical care from nephrologists, the UPE after the emergency declaration in relation to the COVID-19 pandemic was lower than before the declaration. The UPE reduction may be associated with reduced dietary salt intake during the pandemic in patients treated with RAASi for insufficient control of proteinuria. Our results support the current proposal to continue therapeutic approaches to these patients, which involve RAASi therapy along with optimizing dietary habits, even while dealing with the COVID-19 pandemic.

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Achieving remission of proteinuria in childhood CKD.

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Achieving remission of proteinuria in childhood CKD.

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