Renal phenotype in bardet-biedl syndrome

A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion

Miriam Zacchia, Enza Zacchia, Enrica Zona, Giovanna Capolongo, Ilaria Raiola, Luca Rinaldi, Francesco Trepiccione, Diego Ingrosso, Alessandra Perna, Valentina Di Iorio, Francesca Simonelli, Orson W. Moe, Giovambattista Capasso

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate 60 ml·min-1·1.73 m-2. Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling.

Original languageEnglish (US)
Pages (from-to)F686-F694
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number4
DOIs
StatePublished - 2016

Fingerprint

Bardet-Biedl Syndrome
Phenotype
Kidney
Aquaporin 2
Urine
Water
Osmolar Concentration
Extremities
Uromodulin
Vasopressin Receptors
Glomerular Filtration Rate
Renal Insufficiency
Albumins
Creatinine
Endothelial Cells

Keywords

  • AQP2
  • BBS
  • Hyposthenuria
  • UMOD

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Renal phenotype in bardet-biedl syndrome : A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion. / Zacchia, Miriam; Zacchia, Enza; Zona, Enrica; Capolongo, Giovanna; Raiola, Ilaria; Rinaldi, Luca; Trepiccione, Francesco; Ingrosso, Diego; Perna, Alessandra; Iorio, Valentina Di; Simonelli, Francesca; Moe, Orson W.; Capasso, Giovambattista.

In: American Journal of Physiology - Renal Physiology, Vol. 311, No. 4, 2016, p. F686-F694.

Research output: Contribution to journalArticle

Zacchia, M, Zacchia, E, Zona, E, Capolongo, G, Raiola, I, Rinaldi, L, Trepiccione, F, Ingrosso, D, Perna, A, Iorio, VD, Simonelli, F, Moe, OW & Capasso, G 2016, 'Renal phenotype in bardet-biedl syndrome: A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion', American Journal of Physiology - Renal Physiology, vol. 311, no. 4, pp. F686-F694. https://doi.org/10.1152/ajprenal.00224.2016
Zacchia, Miriam ; Zacchia, Enza ; Zona, Enrica ; Capolongo, Giovanna ; Raiola, Ilaria ; Rinaldi, Luca ; Trepiccione, Francesco ; Ingrosso, Diego ; Perna, Alessandra ; Iorio, Valentina Di ; Simonelli, Francesca ; Moe, Orson W. ; Capasso, Giovambattista. / Renal phenotype in bardet-biedl syndrome : A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion. In: American Journal of Physiology - Renal Physiology. 2016 ; Vol. 311, No. 4. pp. F686-F694.
@article{a3c6e385edf0475a97724995b02e44a6,
title = "Renal phenotype in bardet-biedl syndrome: A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion",
abstract = "The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12{\%}) showed an estimated glomerular filtration rate 60 ml·min-1·1.73 m-2. Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling.",
keywords = "AQP2, BBS, Hyposthenuria, UMOD",
author = "Miriam Zacchia and Enza Zacchia and Enrica Zona and Giovanna Capolongo and Ilaria Raiola and Luca Rinaldi and Francesco Trepiccione and Diego Ingrosso and Alessandra Perna and Iorio, {Valentina Di} and Francesca Simonelli and Moe, {Orson W.} and Giovambattista Capasso",
year = "2016",
doi = "10.1152/ajprenal.00224.2016",
language = "English (US)",
volume = "311",
pages = "F686--F694",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Renal phenotype in bardet-biedl syndrome

T2 - A combined defect of urinary concentration and dilution is associated with defective urinary aqp2 and umod excretion

AU - Zacchia, Miriam

AU - Zacchia, Enza

AU - Zona, Enrica

AU - Capolongo, Giovanna

AU - Raiola, Ilaria

AU - Rinaldi, Luca

AU - Trepiccione, Francesco

AU - Ingrosso, Diego

AU - Perna, Alessandra

AU - Iorio, Valentina Di

AU - Simonelli, Francesca

AU - Moe, Orson W.

AU - Capasso, Giovambattista

PY - 2016

Y1 - 2016

N2 - The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate 60 ml·min-1·1.73 m-2. Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling.

AB - The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate 60 ml·min-1·1.73 m-2. Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling.

KW - AQP2

KW - BBS

KW - Hyposthenuria

KW - UMOD

UR - http://www.scopus.com/inward/record.url?scp=84989953464&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989953464&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00224.2016

DO - 10.1152/ajprenal.00224.2016

M3 - Article

VL - 311

SP - F686-F694

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4

ER -