Renal phenotype in Bardet-Biedl syndrome: a combined defect of urinary concentration and dilution is associated with defective urinary AQP2 and UMOD excretion
| Autor: | Enrica Zona, Francesca Simonelli, Luca Rinaldi, Ilaria Raiola, Giovanna Capolongo, Miriam Zacchia, Alessandra F. Perna, Orson W. Moe, Giovambattista Capasso, Valentina Di Iorio, Enza Zacchia, Diego Ingrosso, Francesco Trepiccione |
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| Přispěvatelé: | Zacchia, Miriam, Zacchia, Enza, Zona, Enrica, Capolongo, Giovanna, Raiola, Ilaria, Rinaldi, Luca, Trepiccione, Francesco, Ingrosso, Diego, Perna, Alessandra, Di Iorio, Valentina, Simonelli, Francesca, Moe, Orson W, Capasso, Giovambattista |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Tamm–Horsfall protein Adolescent Physiology Urinary system 030232 urology & nephrology Renal function urologic and male genital diseases Kidney BBS Hyposthenuria UMOD Pathogenesis Kidney Concentrating Ability 03 medical and health sciences Young Adult 0302 clinical medicine Bardet–Biedl syndrome Internal medicine Uromodulin medicine Humans Child Bardet-Biedl Syndrome Aquaporin 2 biology Translational Physiology AQP2 Middle Aged medicine.disease Phenotype 030104 developmental biology Endocrinology medicine.anatomical_structure Child Preschool biology.protein Female Glomerular Filtration Rate |
| Zdroj: | American journal of physiology. Renal physiology. 311(4) |
| ISSN: | 1522-1466 |
| Popis: | 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. The renal phenotype in BardetBiedl 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. |
| Databáze: | OpenAIRE |
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