Nephrolithiasis is not a classic or well-documented symptom of spinal muscular atrophy (SMA). Nonetheless, anecdotal reports from physicians, patients, and caregivers suggest that patients with SMA may suffer from kidney stones more frequently than an otherwise healthy population of children/young adults.
Kidney stones that develop in patients with SMA are not likely due to mutations that are responsible for other SMA pathology (e.g. SMN1 mutations). While SMN protein levels in kidney are reduced among patients with SMA compared to age-matched controls1, the kidney is considered one of the tissues that is relatively spared in SMA.2 More likely, SMA patients who develop kidney stones likely do so as a secondary consequence of their disease. In other words, relative immobility, reduced fluid intake, and obesity may increase the risk of developing nephrolithiasis.
Decreased fluid intake is a known risk factor for kidney stones in healthy adults3,4,5 and children as evidenced by decreased urinary volume.6 Swallowing difficulties, decreased tendency to voice feelings of thirst, and mobility challenges that make self-hydration difficult could theoretically contribute to dehydration and lower urinary volume. In patients with spinal cord injury, prolonged immobility can predispose to hypercalciuria, which is a cause of urinary tract stones.7 Indeed, immobility may result in hypercalcemia among adolescent boys with polyneuropathy8 and/or prolonged immobilization.9 At least one case report documents hypercalcemia, hypercalciuria and nephrocalcinosis in a child with SMA Type 2.10 The authors theorized that hypercalcemia with hypercalciuria observed in this case reflects altered bone turnover secondary to reduced muscular activity.10 Apart from SMA, children with nephrolithiasis in general are more likely to have metabolic abnormalities.11
Patients with SMA at increased fast mass and struggle with issues of overweight and obesity.12 Recent research suggests obesity may play a role in the development of nephrolithiasis.12 Obesity is associated with lower urine pH, increased urinary oxalate, uric acid, sodium, and phosphate excretion.12,13 Insulin resistance, which is more common in people with obesity and is also frequently seen in patients with SMA, can alter tubular sodium hydrogen exchange, increase the production of ammonia, and contribute to an acidic urine.12,13
No documented reason suggests the management of kidney stones is different in patients with SMA than in other children and adolescents. It is prudent to ask patients and caregivers about symptoms of nephrolithiasis including flank/abdominal pain, dysuria and urgency, and gross hematuria.14 Nausea and vomiting is a presenting symptom in 1 out of 10 patients.14 Initial laboratory workup includes urinalysis and urine culture if infection is suspected. CT is more sensitive for renal stone detection than ultrasound15, though ultrasound may be preferable to avoid radiation exposure.16
Acute management includes intravenous fluid administration, adequate pain control, treatment for urinary tract infection when present, and medical expulsive therapy.17 Medical expulsive therapy is the use of antispasmodics to facilitate the passage of the stone (e.g. alpha adrenergic drugs, calcium channel blockers).17,18
1. Burlet P, Huber C, Bertrandy S, et al. The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy. Hum Mol Genet. Nov 1998;7(12):1927-1933.
2. Shababi M, Lorson CL, Rudnik-Schöneborn SS. Spinal muscular atrophy: a motor neuron disorder or a multi-organ disease? Journal of Anatomy. 2014;224(1):15-28.
3. Curhan GC, Willett WC, Knight EL, et al. Dietary factors and the risk of incident kidney stones in younger women: Nurses’ Health Study II. Arch Intern Med. Apr 26 2004;164(8):885-891.
4. Curhan GC, Willett WC, Rimm EB, et al. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med. Mar 25 1993;328(12):833-838.
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9. Dibble JB, Penney MD. Analysis of the components of the hypercalcaemia in a 14-year-old boy following prolonged immobilisation. Acta Paediatr Scand. Mar 1983;72(2):207-210.
10. Khawaja K, Houlsby WT, Watson S, et al. Hypercalcaemia in infancy; a presenting feature of spinal muscular atrophy. Arch Dis Child. Apr 2004;89(4):384-385.
11. Sas DJ, Hulsey TC, Shatat IF, et al. Increasing incidence of kidney stones in children evaluated in the emergency department. J Pediatr. Jul 2010;157(1):132-137.
12. Sproule DM, Montes J, Montgomery M, et al. Increased fat mass and high incidence of overweight despite low body mass index in patients with spinal muscular atrophy. Neuromuscul Disord. Jun 2009;19(6):391-396.
13. Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. J Nephrol. Feb 2017;30(1):1-10.
14. Gearhart JP, Herzberg GZ, Jeffs RD. Childhood urolithiasis: experiences and advances. Pediatrics. Apr 1991;87(4):445-450.
15. Roberson NP, Dillman JR, O’Hara SM, et al. Comparison of ultrasound versus computed tomography for the detection of kidney stones in the pediatric population: a clinical effectiveness study. Pediatr Radiol. Jul 2018;48(7):962-972.
16. Colleran GC, Callahan MJ, Paltiel HJ, et al. Imaging in the diagnosis of pediatric urolithiasis. Pediatr Radiol. Jan 2017;47(1):5-16.
17. Frassetto L, Kohlstadt I. Treatment and prevention of kidney stones: an update. Am Fam Physician. Dec 1 2011;84(11):1234-1242.
18. Tian D, Li N, Huang W, et al. The efficacy and safety of adrenergic alpha-antagonists in treatment of distal ureteral stones in pediatric patients: A systematic review and meta-analysis. J Pediatr Surg. Feb 2017;52(2):360-365.