Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.
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.
- SourceAvailable from: Anna Caroli[Show abstract] [Hide abstract]
ABSTRACT: Background Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no eff ective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the eff ect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder. Methods We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in fi ve hospitals in Italy. Adult (>18 years) patients with estimated glomerular fi ltration rate (GFR) of 40 mL/min per 1·73 m² or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratifi ed by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modifi ed intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283. Findings Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased signifi cantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the diff erence was not signifi cant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related. Interpretation These fi ndings provide the background for large randomised controlled trials to test the protective eff ect of somatostatin analogues against renal function loss and progression to end-stage kidney disease.The Lancet 01/2013; · 39.21 Impact Factor
- [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.The Journal of pediatrics. 06/2014;
- [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.