TY - JOUR
T1 - Glomerular pathology in dent disease and its association with kidney function
AU - Wang, Xiangling
AU - Anglani, Franca
AU - Beara-Lasic, Lada
AU - Mehta, Anila J.
AU - Vaughan, Lisa E.
AU - Hernandez, Loren Herrera
AU - Cogal, Andrea
AU - Scheinman, Steven J.
AU - Ariceta, Gema
AU - Isom, Robert
AU - Copelovitch, Lawrence
AU - Enders, Felicity T.
AU - Prete, Dorella Del
AU - Vezzoli, Giuseppe
AU - Paglialonga, Fabio
AU - Harris, Peter C.
AU - Lieske, John C.
N1 - Publisher Copyright:
© 2016 by the American Society of Nephrology.
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%619% 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%619% 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.
KW - Biopsy
KW - Dent disease
KW - Disease Progression
KW - Glomerular filtration rate
KW - Glomerulosclerosis
KW - Glomerulosclerosis, Focal Segmental
KW - Humans
KW - Inflammation
KW - Interstitial fibrosis
KW - Kidney
KW - Kidney Glomerulus
KW - Male
KW - Molecular Weight
KW - Podocyte
KW - Podocytes
KW - Proteinuria
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U2 - 10.2215/CJN.03710416
DO - 10.2215/CJN.03710416
M3 - Article
C2 - 27697782
AN - SCOPUS:85021747955
SN - 1555-9041
VL - 11
SP - 2168
EP - 2176
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 12
ER -