ESPN 50th Annual Meeting

ESPN 2017


 
Evidence for bone and mineral metabolism alterations in children with Autosomal Dominant Polycystic Kidney Disease
STEPHANIE DE RECHTER 1 JUSTINE BACCHETTA 2 NATHALIE GODEFROID 3 LAURENCE DUBOURG 2 PIERRE COCHAT 2 JULIE MAQUET 4 ANN RAES 5 JEAN DE SCHEPPER 6 PIETER VERMEERSCH 7 MARIA VAN DYCK 1 ELENA LEVTCHENKO 1 PATRICK D’HAESE 8 PIETER EVENEPOEL 9 DJALILA MEKAHLI 1

1- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITALS LEUVEN, LEUVEN, BELGIUM
2- CENTRE DE RéFéRENCE DES MALADIES RéNALES RARES, HôPITAL FEMME MèRE ENFANT, HOSPICES CIVILS DE LYON, BRON, FRANCE
3- DEPARTMENT OF PEDIATRIC NEPHROLOGY, CLINIQUES UNIVERSITAIRES SAINT-LUC, BRUSSELS, BELGIUM
4- DEPARTMENT OF PEDIATRIC NEPHROLOGY, CHC, LIèGE, BELGIUM
5- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITALS GHENT, GHENT, BELGIUM
6- DEPARTMENT OF PEDIATRIC ENDOCRINOLOGY, DEPARTMENT OF PEDIATRICS, BRUSSELS UNIVERSITY HOSPITAL, BRUSSELS, BELGIUM
7- LABORATORY MEDICINE, UNIVERSITY HOSPITALS LEUVEN, LEUVEN, BELGIUM
8- LABORATORY OF PATHOPHYSIOLOGY, UNIVERSITY OF ANTWERP, ANTWERP, BELGIUM
9- DEPARTMENT OF INTERNAL MEDICINE, DIVISION OF NEPHROLOGY, UNIVERSITY HOSPITALS LEUVEN, LEUVEN, BELGIUM
 
Introduction:

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of renal failure. Data from adult ADPKD population show increased fibroblast growth factor 23 (FGF23) levels, resulting in low maximum rates of tubular phosphate reabsorption to GFR (TmP/GFR) and hypophosphatemia. TmP/GFR was however higher than would be expected from the circulating FGF23 level, unrevealing FGF23 resistance, with Klotho deficiency as most probable culprit. As it is unknown whether the same holds true in pediatric ADPKD patients, we prospectively assessed bone metabolism and renal phosphate handling in ADPKD children compared to healthy controls.

Material and methods:

Anthropometric data, medical personal/familial history and drug intake were collected at enrollment from all patients and healthy controls. A specific questionnaire on bone health, including previous fractures or bone deformities was performed. Blood and spot urine samples were collected from all participants. In a subgroup, a X-ray of the left hand and a dual-energy X-ray-absorption (DXA) were performed.

Results:

We included 92 children with ADPKD and normal renal function (52 males, mean ± SD age: 10.2 ± 5.0 years) and 22 healthy controls (10 males, mean ± SD age: 10.3 ± 4.1). Patients had significantly lower serum phosphate levels compared to healthy controls. Low TmP/GFR was observed in 24% of patients. Serum FGF23, PTH, calcitriol and Klotho levels did not differ between patients and healthy controls. Remarkably, ADPKD patients showed depressed bone alkaline phosphatase levels, suggesting low bone formation.

Conclusions:

This is the first report highlighting bone formation anomalies in early ADPKD stages. We demonstrated hypophosphatemia in combination with renal phosphate leak in ADPKD children with normal eGFR with an inappropriately high FGF23 and normal Klotho levels. Further studies are required to elucidate the underlying pathophysiology and to investigate potential clinical consequences.