Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts.

Autor: Beara-Lasic L; Nephrology Division, Department of Medicine and Pediatrics, New York University Langone Health and New York University School of Medicine, New York, NY, USA. lada.bearalasic@nyumc.org.; Rare Kidney Stone Consortium, Rochester, USA. lada.bearalasic@nyumc.org., Cogal A; Rare Kidney Stone Consortium, Rochester, USA.; Division of Nephrology, Department of Medicine and Pediatrics, Mayo Clinic, Rochester, MN, USA., Mara K; Rare Kidney Stone Consortium, Rochester, USA.; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Enders F; Rare Kidney Stone Consortium, Rochester, USA.; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Mehta RA; Rare Kidney Stone Consortium, Rochester, USA.; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Haskic Z; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Furth SL; Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman, School of Medicine, Philadelphia, PA, USA., Trachtman H; Nephrology Division, Department of Medicine and Pediatrics, New York University Langone Health and New York University School of Medicine, New York, NY, USA., Scheinman SJ; Geisinger Commonwealth School of Medicine, Scranton, PA, USA., Milliner DS; Rare Kidney Stone Consortium, Rochester, USA.; Division of Nephrology, Department of Medicine and Pediatrics, Mayo Clinic, Rochester, MN, USA., Goldfarb DS; Nephrology Division, Department of Medicine and Pediatrics, New York University Langone Health and New York University School of Medicine, New York, NY, USA.; Rare Kidney Stone Consortium, Rochester, USA., Harris PC; Rare Kidney Stone Consortium, Rochester, USA.; Division of Nephrology, Department of Medicine and Pediatrics, Mayo Clinic, Rochester, MN, USA., Lieske JC; Rare Kidney Stone Consortium, Rochester, USA.; Division of Nephrology, Department of Medicine and Pediatrics, Mayo Clinic, Rochester, MN, USA.
Jazyk: angličtina
Zdroj: Pediatric nephrology (Berlin, Germany) [Pediatr Nephrol] 2020 Apr; Vol. 35 (4), pp. 633-640. Date of Electronic Publication: 2019 Mar 10.
DOI: 10.1007/s00467-019-04210-0
Abstrakt: Background: Dent disease type 1 (DD1) is a rare X-linked disorder caused mainly by CLCN5 mutations. Patients may present with nephrotic-range proteinuria leading to erroneous diagnosis of focal segmental glomerulosclerosis (FSGS) and unnecessary immunosuppressive treatments.
Methods: The following cohorts were screened for CLCN5 mutations: Chronic Kidney Disease in Children (CKiD; n = 112); Multicenter FSGS-Clinical Trial (FSGS-CT) (n = 96), and Novel Therapies for Resistant FSGS Trial (FONT) (n = 30). Urinary α 1 -microglobulin (α 1 M), albumin (A), total protein (TP), and creatinine (Cr) were assessed from CKiD subjects (n = 104); DD1 patients (n = 14); and DD1 carriers (DC; n = 8). TP/Cr, α 1 M/Cr, α 1 M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC.
Results: No CLCN5 mutations were detected. TP/Cr was lower in DC and CKiD with tubulointerstitial disease than in DD1 and CKiD with glomerular disease (p < 0.002). α 1 M/Cr was higher in DD1 than in CKiD and DC (p < 0.001). A/TP was lower in DD1, DC, and CKiD with tubulointerstitial disease and higher in CKiD with glomerular disease (p < 0.001). Thresholds for A/TP of ≤ 0.21 and α 1 M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease.
Conclusions: CLCN5 mutations were not seen in screened CKiD/FSGS cohorts. In our study, a cutoff of TP/Cr > 600 mg/g (> 68 mg/mmol) and A/TP of < 0.3 had a high sensitivity and specificity to distinguish DD1 from both CKiD glomerular and tubulointerstitial cohorts. α 1 M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.
Databáze: MEDLINE
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