Impaired kidney structure and function in spinal muscular atrophy

Figures

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  Figure 1. Kidney histopathology in patients with SMA type 1 Sections from the kidneys of SMA cases show medullary calcifications (yellow arrows, H&E and PAS) along collecting ducts. Medullary interstitial fibrosis is also present (trichrome). Representative images were taken at 100× (indicated as 10× objective) and 400× magnifications. H&E = hematoxylin and eosin; PAS = periodic acid–Schiff; SMA = spinal muscular atrophy.

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  Figure 2. Medullary calcifications in patients with SMA type 1 The medullary calcifications (black arrows) are positive for von Kossa and Alizarin red stains. Immunohistochemical studies show CD3+ (brown) and CD68+ (blue) cells along calcifications black (arrows). Representative images were taken at 100× (indicated as 10× objective) and 400× magnifications. SMA = spinal muscular atrophy.

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  Figure 3. Changes in genes involved in calcium reabsorption in the kidney from SMA participants Volcano plots derived from (A) Nephrotoxicity RT2 Profiler PCR Array and (B) Polycystic Kidney Disease RT2 Profiler PCR Array in kidney samples from SMA and controls. Upregulated and downregulated genes are indicated in red and blue, respectively (n = 3–4). Unpaired 2-tailed Student t tests were used to compare groups. SMA = spinal muscular atrophy.

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  Figure 4. Increased IGFBPs in kidney from SMA participants (A) Representative immunohistochemistry (magnification 100×) and (B) quantification of staining intensity for CaSR and CALB1 in kidney samples from SMA and controls (n = 9–10). (C) Representative immunoblot and (D) quantification of protein content in kidney samples from SMA (n = 4) and controls (n = 4). Data are presented as mean SEM with dots as individual values. Unpaired 2-tailed Student t tests were used to compare groups. *p < 0.05; **p < 0.01; ****p < 0.0001. CALB1 = calbindin 1; CaSR = calcium-sensing receptor; IGF = insulin-like growth factor; IGFBP = insulin-like growth factor binding proteins; SMA = spinal muscular atrophy.