Glomerular Pathology in Dent Disease and Its Association with Kidney Function

X. Wang, F. Anglani, Lada Beara-Lasic, A. J. Mehta, Lisa E Vaughan, Loren Herrera Hernandez, Andrea Cogal, Steven J. Scheinman, Gema Ariceta, Robert Isom, Lawrence Copelovitch, Felicity T Enders, D. Del Prete, G. Vezzoli, F. Paglialonga, Peter C. Harris, John C Lieske, Investigators of the Rare Kidney Stone Consortium

Research output: Contribution to journalArticle

Abstract

BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2 and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%+/-19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline. CONCLUSIONS: These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.
Original languageEnglish
Pages (from-to)2168-2176
Number of pages9
JournalClinical journal of the American Society of Nephrology : CJASN
Volume11
Issue number12
Publication statusPublished - 2016

Fingerprint

Dent Disease
Pathology
Kidney
Foot
Biopsy
Proteinuria
Focal Segmental Glomerulosclerosis
Podocytes
Clinical Pathology
Disease Progression
Fibrosis
Molecular Weight
Steroids
Urine
Inflammation

Keywords

  • Dent disease
  • Disease Progression
  • Glomerulosclerosis, Focal Segmental
  • Humans
  • Inflammation
  • Kidney Glomerulus
  • Male
  • Molecular Weight
  • Podocytes
  • biopsy
  • glomerular filtration rate
  • glomerulosclerosis
  • interstitial fibrosis
  • kidney
  • podocyte
  • proteinuria

Cite this

Wang, X., Anglani, F., Beara-Lasic, L., Mehta, A. J., Vaughan, L. E., Herrera Hernandez, L., ... Consortium, I. O. T. R. K. S. (2016). Glomerular Pathology in Dent Disease and Its Association with Kidney Function. Clinical journal of the American Society of Nephrology : CJASN, 11(12), 2168-2176.

Glomerular Pathology in Dent Disease and Its Association with Kidney Function. / Wang, X.; Anglani, F.; Beara-Lasic, Lada; Mehta, A. J.; Vaughan, Lisa E; Herrera Hernandez, Loren; Cogal, Andrea; Scheinman, Steven J.; Ariceta, Gema; Isom, Robert; Copelovitch, Lawrence; Enders, Felicity T; Del Prete, D.; Vezzoli, G.; Paglialonga, F.; Harris, Peter C.; Lieske, John C; Consortium, Investigators of the Rare Kidney Stone.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 11, No. 12, 2016, p. 2168-2176.

Research output: Contribution to journalArticle

Wang, X, Anglani, F, Beara-Lasic, L, Mehta, AJ, Vaughan, LE, Herrera Hernandez, L, Cogal, A, Scheinman, SJ, Ariceta, G, Isom, R, Copelovitch, L, Enders, FT, Del Prete, D, Vezzoli, G, Paglialonga, F, Harris, PC, Lieske, JC & Consortium, IOTRKS 2016, 'Glomerular Pathology in Dent Disease and Its Association with Kidney Function', Clinical journal of the American Society of Nephrology : CJASN, vol. 11, no. 12, pp. 2168-2176.
Wang X, Anglani F, Beara-Lasic L, Mehta AJ, Vaughan LE, Herrera Hernandez L et al. Glomerular Pathology in Dent Disease and Its Association with Kidney Function. Clinical journal of the American Society of Nephrology : CJASN. 2016;11(12):2168-2176.
Wang, X. ; Anglani, F. ; Beara-Lasic, Lada ; Mehta, A. J. ; Vaughan, Lisa E ; Herrera Hernandez, Loren ; Cogal, Andrea ; Scheinman, Steven J. ; Ariceta, Gema ; Isom, Robert ; Copelovitch, Lawrence ; Enders, Felicity T ; Del Prete, D. ; Vezzoli, G. ; Paglialonga, F. ; Harris, Peter C. ; Lieske, John C ; Consortium, Investigators of the Rare Kidney Stone. / Glomerular Pathology in Dent Disease and Its Association with Kidney Function. In: Clinical journal of the American Society of Nephrology : CJASN. 2016 ; Vol. 11, No. 12. pp. 2168-2176.
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T1 - Glomerular Pathology in Dent Disease and Its Association with Kidney Function

AU - Wang, X.

AU - Anglani, F.

AU - Beara-Lasic, Lada

AU - Mehta, A. J.

AU - Vaughan, Lisa E

AU - Herrera Hernandez, Loren

AU - Cogal, Andrea

AU - Scheinman, Steven J.

AU - Ariceta, Gema

AU - Isom, Robert

AU - Copelovitch, Lawrence

AU - Enders, Felicity T

AU - Del Prete, D.

AU - Vezzoli, G.

AU - Paglialonga, F.

AU - Harris, Peter C.

AU - Lieske, John C

AU - Consortium, Investigators of the Rare Kidney Stone

N1 - LR: 20170220; CI: Copyright (c) 2016; JID: 101271570; OTO: NOTNLM; PMCR: 2017/12/07; 2016/04/01 [received]; 2016/08/16 [accepted]; ppublish M1 - Journal Article

PY - 2016

Y1 - 2016

N2 - BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2 and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%+/-19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline. CONCLUSIONS: These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.

AB - BACKGROUND AND OBJECTIVES: Dent disease is a rare X-linked disorder characterized by low molecular weight proteinuria and often considered a renal tubular disease. However, glomerulosclerosis was recently reported in several patients. Thus, Dent disease renal histopathologic features were characterized and assessed, and their association with kidney function was assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Clinical renal pathology reports and slides (where available) were collected from 30 boys and men in eight countries who had undergone clinical renal biopsy between 1995 and 2014. RESULTS: Median (25th, 75th percentiles) age at biopsy was 7.5 (5, 19) years with an eGFR of 69 (44, 94) ml/min per 1.73 m2 and a 24-hour urine protein of 2000 (1325, 2936) mg. A repeat biopsy for steroid-resistant proteinuria was performed in 13% (four of 30) of the patients. Prominent histologic findings included focal global glomerulosclerosis in 83% (25 of 30; affecting 16%+/-19% glomeruli), mild segmental foot process effacement in 57% (13 of 23), focal interstitial fibrosis in 60% (18 of 30), interstitial lymphocytic infiltration in 53% (16 of 30), and tubular damage in 70% (21 of 30). Higher percentages of globally sclerotic glomeruli, foot process effacement, and interstitial inflammation were associated with lower eGFR at biopsy, whereas foot process effacement was associated with steeper annual eGFR decline. CONCLUSIONS: These associations suggest a potential role for glomerular pathology, specifically involving the podocyte, in disease progression, which deserves further study. Furthermore, Dent disease should be suspected in boys and men who have unexplained proteinuria with focal global glomerulosclerosis and segmental foot process effacement on renal biopsy.

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KW - Disease Progression

KW - Glomerulosclerosis, Focal Segmental

KW - Humans

KW - Inflammation

KW - Kidney Glomerulus

KW - Male

KW - Molecular Weight

KW - Podocytes

KW - biopsy

KW - glomerular filtration rate

KW - glomerulosclerosis

KW - interstitial fibrosis

KW - kidney

KW - podocyte

KW - proteinuria

M3 - Article

VL - 11

SP - 2168

EP - 2176

JO - Clinical journal of the American Society of Nephrology : CJASN

JF - Clinical journal of the American Society of Nephrology : CJASN

SN - 1555-9041

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ER -