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



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.


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 α1-microglobulin (α1M), 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, α1M/Cr, α1M/TP, and A/TP from the CKiD cohort were compared with DD1 and DC.


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). α1M/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 α1M/Cr of ≥ 120 mg/g (> 13.6 mg/mmol) creatinine were good screens for Dent disease.


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. α1M/Cr ≥ 120 mg/g (> 13.6 mg/mmol) had the highest sensitivity and specificity when differentiating DD1 and studied CKiD populations.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


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We thank Alicia Meek for her assistance in data collection.


This study was supported by Rare Kidney Stone Consortium grant U54KD083908, a part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research, the National Center for Advancing Translational Sciences (NCATS).

This consortium is funded through a collaboration between the NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases.

The study sponsor had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

The Chronic Kidney Disease in Children Cohort Study (CKiD) was conducted by the CKiD Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01DK-082194, U01-DK-66116). The data and samples from the CKiD study reported here were supplied by the NIDDK Central Repositories. This manuscript does not necessarily reflect the opinions or views of the CKiD study, the NIDDK Central Repositories, or the NIDDK.

The Multicenter FSGS-Clinical Trial (FSGS-CT) and Novel Therapies for Resistant FSGS Trial (FONT) was conducted by the FSGS-CT and FONT investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data and samples from the FSGS-CT and FONT reported here were supplied by the NIDDK Central Repositories. This manuscript does not necessarily reflect the opinions or views of the FSGS-CT and FONT study, the NIDDK Central Repositories, or the NIDDK.

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Correspondence to Lada Beara-Lasic.

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This study was approved by the Mayo Clinic Institutional Review Board. Ancillary studies were approved and biospecimens were obtained from CKiD, FSGS-CT, and FONT studies.

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The authors declare that they have no conflicts of interest.

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Beara-Lasic, L., Cogal, A., Mara, K. et al. Prevalence of low molecular weight proteinuria and Dent disease 1 CLCN5 mutations in proteinuric cohorts. Pediatr Nephrol 35, 633–640 (2020).

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  • Dent disease
  • FSGS
  • CLCN5
  • Proteinuria
  • Low molecular weight proteinuria
  • α1-Microglobulin