Glomerular Hyperfiltration and Renal Progression in Children with Autosomal Dominant Polycystic Kidney Disease

University of Colorado Denver, Division of Renal Diseases and Hypertension, Aurora, CO 80045, USA.
Clinical Journal of the American Society of Nephrology (Impact Factor: 5.25). 09/2011; 6(10):2439-43. DOI: 10.2215/CJN.01010211
Source: PubMed

ABSTRACT The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children.
One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance ≥140 ml/min per 1.73 m(2).
Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm(3)/year) over 5 years compared with those without GH at baseline (β = -4.3 ± 7.7 cm(3)/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = -5.0 ± 0.8 ml/min per 1.73 m(2) per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m(2) per year), P < 0.0001.
This study revealed that occurrence of GH in ADPKD children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
    Journal of the American Society of Nephrology 06/2014; 25(11). DOI:10.1681/ASN.2013111184 · 9.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypertension is more common in adults with type 1 diabetes mellitus (T1DM) than the general population. The aim of this study was to detect the pre-hypertensive stage in children with T1D and to evaluate its correlation with diabetic nephropathy compared to non-diabetic children. This was a prospective cross-sectional study in an out-patient clinic of a university hospital. A total of 62 which consists of 36 males and 26 females patients with stable T1D with a median age of 13 year and 42 age - sex-matched healthy children were entered in the study between September 2008 and February 2011. Three readings of blood pressure were recorded. Fasting blood sample was drawn for hemoglobin A1C (HbA1C), creatinine and a 24 h urine aliquot was collected to measure microalbumin, creatinine and volume to estimate glomerular filtration rate (eGFR). From 62 children with T1DM, 25.8% were in pre-hypertensive stage, 4.8% Stage 1, and 1.6% Stage 2. In controls, 1 (2.4%) out of 42 children was in pre-hypertensive stage (P < 0.0001). Abnormal blood pressures were correlated with eGFR and the duration of disease (P < 0.05), but there were not associated with microalbominuria or HbA1C level. There was a higher rate of early stage of high normal blood pressure in children with T1DM compared with the healthy controls and this abnormality was only correlated with puberty stage and glomerular filtration rate.
    International journal of preventive medicine 03/2014; 5(Suppl 1):S44-S49.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the development of chronic kidney disease (CKD) after high nephrotoxic medication exposure-associated acute kidney injury (NTMx-AKI) in hospitalized children.
    Journal of Pediatrics 06/2014; 165(3). DOI:10.1016/j.jpeds.2014.04.058 · 3.74 Impact Factor