脊髄性筋萎縮症患者における腎機能障害：縦断的コホート研究

BackgroundSpinal muscular atrophy (SMA) is caused by loss-of-function of the survival motor neuron 1 (SMN1) gene and deficiency of the ubiquitously expressed SMN protein. Genetic therapies can partially rescue motor units and improve prognosis of SMA, but effects of SMN shortage in other tissues has not been studied in detail.MethodsWe longitudinally assessed renal function in a cohort of patients with SMA before and after the start of genetic therapies.ResultsWe enrolled 263 patients with SMA types 1c-4. Median age was 33 years (IQR: 22-49). Fifty (19%) patients had serum cystatin C based eGFR rates <90 ml/min/1.73m², indicating increased risk of developing chronic kidney failure, 9 (3.5%) patients had eGFR compatible with chronic kidney failure (eGFR <60 ml/min/1.73m²) and 2 patients showed end-stage renal failure based on eGFR <15 ml/min/1.73m². Symptoms of tubular dysfunction (abnormal low serum potassium levels (<3.8 mmol/L) and proteinuria) were present in 134 (51.7%) and 53 patients (22%), respectively. Forty-two (16%) patients had a history of kidney stones or nephrocalcinosis. Treatment with nusinersen or risdiplam resulted in reduction of the number of patients with hypokalaemia, but not of those with proteinuria. Cystatin C eGFR continued to decline during treatment.ConclusionsPatients with SMA are at risk of impaired renal clearance, which does not improve after treatment with SMN2-splicing modifying therapies. Tubular function may improve partially following the start of treatment. These data indicate that SMN protein deficiency affects kidneys and that this will probably cause health problems in later life.