RT Journal Article
SR Electronic
T1 Impaired kidney structure and function in spinal muscular atrophy
JF Neurology Genetics
JO Neurol Genet
FD Lippincott Williams & Wilkins
SP e353
DO 10.1212/NXG.0000000000000353
VO 5
IS 5
A1 Nery, Flávia C.
A1 Siranosian, Jennifer J.
A1 Rosales, Ivy
A1 Deguise, Marc-Olivier
A1 Sharma, Amita
A1 Muhtaseb, Abdurrahman W.
A1 Nwe, Pann
A1 Johnstone, Alec J.
A1 Zhang, Ren
A1 Fatouraei, Maryam
A1 Huemer, Natassja
A1 Alves, Christiano R.R.
A1 Kothary, Rashmi
A1 Swoboda, Kathryn J.
YR 2019
UL http://ng.neurology.org/content/5/5/e353.abstract
AB Objective To determine changes in serum profiles and kidney tissues from patients with spinal muscular atrophy (SMA) type 1 compared with age- and sex-matched controls.Methods In this cohort study, we investigated renal structure and function in infants and children with SMA type 1 in comparison with age- and sex-matched controls.Results Patients with SMA had alterations in serum creatinine, cystatin C, sodium, glucose, and calcium concentrations, granular casts and crystals in urine, and nephrocalcinosis and fibrosis. Nephrotoxicity and polycystic kidney disease PCR arrays revealed multiple differentially expressed genes, and immunoblot analysis showed decreased calcium-sensing receptors and calbindin and increased insulin-like growth factor–binding proteins in kidneys from patients with SMA.Conclusions These findings demonstrate that patients with SMA type 1, in the absence of disease-modifying therapies, frequently manifest impaired renal function as a primary or secondary consequence of their disease. This study provides new insights into systemic contributions to SMA disease pathogenesis and the need to identify coadjuvant therapies.ASO=antisense oligonucleotide; CaSR=calcium-sensing receptor; CALB1=calbindin 1; IGF=insulin-like growth factor; IGFBP=insulin-like growth factor–binding proteins; SMA=spinal muscular atrophy; SMN=survival motor neuron