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Published on: June 23, 2015
Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease
Katherine M Dell1, Matthew Matheson2, Erum A Hartung3
1Center for Pediatric Nephrology, Cleveland Clinic Children's, Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
Insights
Autosomal recessive polycystic kidney disease (ARPKD) shows slow GFR decline and less proteinuria compared to controls. Standard measures may not fully capture disease progression in ARPKD, necessitating new biomarkers.
Area of Science:
- Pediatric Nephrology
- Genetics and Rare Diseases
- Chronic Kidney Disease
Background:
- Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder affecting kidney development.
- Understanding the natural history of ARPKD is crucial for managing pediatric kidney disease.
- Limited data exists on key clinical markers like GFR decline, hypertension, and proteinuria in ARPKD patients.
Purpose of the Study:
- To characterize glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in children with ARPKD.
- To compare these parameters in ARPKD patients against two control groups with congenital kidney diseases.
- To evaluate the utility of standard clinical markers in assessing ARPKD progression.
Main Methods:
- Analysis of data from the Chronic Kidney Disease in Children cohort.
- Inclusion of 22 ARPKD subjects and 44 subjects in each of two control groups (aplastic/hypoplastic/dysplastic disorders and obstructive uropathies).
- Assessment of GFR decline via iohexol clearance, HTN via blood pressures, and proteinuria via urine protein:creatinine ratio; statistical comparison using Wilcoxon rank sum test.
Main Results:
- Annualized GFR decline in ARPKD was -1.4 mL/min/1.73 m(2), with faster decline in those aged ≥10 years, but overall GFR decline did not significantly differ from controls.
- Hypertension and left ventricular hypertrophy rates were similar between ARPKD and control groups.
- ARPKD subjects showed significantly higher use of ≥3 blood pressure medications (32% vs 0%) and ACE inhibitors (82% vs 27-36%), and significantly less proteinuria (0.1 vs 0.6).
Conclusions:
- This study provides key insights into GFR decline, HTN, and proteinuria in a well-defined ARPKD cohort.
- The observed slow GFR decline and minimal proteinuria in ARPKD suggest standard markers may be insufficient for evaluating treatment efficacy.
- There is a clear need for novel biomarkers to better monitor kidney disease progression in autosomal recessive polycystic kidney disease.
Objective:
To define glomerular filtration rate (GFR) decline, hypertension (HTN), and proteinuria in subjects with autosomal recessive polycystic kidney disease (ARPKD) and compare with 2 congenital kidney disease control groups in the Chronic Kidney Disease in Children cohort.
Study Design:
GFR decline (iohexol clearance), rates of HTN (ambulatory/casual blood pressures), antihypertensive medication usage, left ventricular hypertrophy, and proteinuria were analyzed in subjects with ARPKD (n = 22) and 2 control groups: aplastic/hypoplastic/dysplastic disorders (n = 44) and obstructive uropathies (n = 44). Differences between study groups were examined with the Wilcoxon rank sum test.
Results:
Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age ≥ 10 years (-11.5%). However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. There were no significant differences in rates of HTN or left ventricular hypertrophy, but subjects with ARPKD had a greater percent on ≥ 3 blood pressure medications (32% vs 0%, P < .0001), more angiotensin-converting enzyme inhibitor use (82% vs 27% vs 36%, P < .0005), and less proteinuria (urine protein: creatinine = 0.1 vs 0.6, P < .005).
Conclusions:
This study reports rates of GFR decline, HTN, and proteinuria in a small but well-phenotyped ARPKD cohort. The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers.
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