Spinal Muscular Atrophy Reveals Hidden Kidney Impairment Risk

For patients with spinal muscular atrophy (SMA), routine kidney function monitoring is rarely a priority. However, emerging data suggest that renal impairment may be far more common than previously recognized. Standard creatinine-based assessments can miss kidney dysfunction in neuromuscular populations where muscle mass is profoundly reduced.

Recently, researchers from the University Medical Centre Utrecht in the Netherlands presented longitudinal data that challenged assumptions about kidney health in SMA. Read on for a quick look at what they found.

A Longitudinal Look at Renal Function

The study enrolled 263 patients with SMA types Ic-4 across a median age of 33 years (IQR: 22-49). Investigators measured glomerular filtration rates (eGFR) using cystatin C rather than creatinine—a critical methodological choice, given that nearly half the cohort (46.3%) had unmeasurably low creatinine levels due to severe muscle wasting.

What they found was significant. About one in five patients (19%) showed eGFR below 90 ml/min/1.73m², indicating increased risk for chronic kidney failure. Nine patients (3.5%) met criteria for moderate-to-severe chronic kidney disease with eGFR below 60 ml/min/1.73m², and two patients had progressed to end-stage renal failure.

Beyond Filtration: Signs of Tubular Dysfunction

Kidney impairment extended beyond reduced filtration. More than half the cohort (51.7%) had abnormally low serum potassium levels, and 22% showed proteinuria—both markers of tubular dysfunction. Additionally, 16% of patients reported a history of kidney stones or nephrocalcinosis, complications likely linked to reduced mobility, wheelchair dependence, and postural changes that affect urine flow.

The underlying biology may involve SMN protein itself. High concentrations of SMN are found in adult kidney tubules, where the protein appears essential for endocytosis and vesicle trafficking—discrete processes critical to tubular function.

eGFR Declines Faster Than Expected

Longitudinal follow-up revealed that eGFR declined progressively over time, irrespective of whether patients received genetic therapies like nusinersen or risdiplam (p<0.0001). The rate of decline varied by comorbidity status:

• Patients without diabetes or hypertension: average annual decline of 0.89 ml/min/1.73m²
• Patients with diabetes and/or hypertension: average annual decline of 1.45 ml/min/1.73m²

Both rates exceed the typical age-related decline of 1 ml/min/1.73m² per year seen in the general population, suggesting that SMA itself accelerates kidney aging. This raises the possibility that relatively young patients could face renal failure earlier than their peers.

Why Standard Screening Falls Short

Creatinine-based eGFR calculations assume normal muscle mass, making them unreliable in SMA. This study underscores the value of cystatin C, a biomarker unaffected by muscle wasting, for accurate kidney assessment in neuromuscular disease.

Although the findings are drawn from a single-center cohort and longitudinal follow-up periods varied, the data highlight an underrecognized clinical need. The mechanism driving progressive renal decline remains uncertain, but the association with age and comorbidities points toward the importance of cardiovascular risk management in SMA care.

Practice Implications: Monitoring Matters

The authors recommend routine cystatin C-based kidney monitoring for all patients with SMA, supplemented by urinalysis to detect early tubular dysfunction. Importantly, SMA severity does not appear to determine renal vulnerability—patients with type 3 SMA were among those with end-stage renal disease, despite typically milder phenotypes and near-normal life expectancy. This finding underscores that monitoring should extend across the full disease spectrum, not just severe cases.

For clinicians managing SMA, these findings suggest that kidney health deserves attention alongside neuromuscular and respiratory measures, particularly as patients age and comorbidities accumulate.

Reference:

Asselman FL, Meijvis SC, Wadman RI, et al. Impaired renal function in patients with spinal muscular atrophy: A longitudinal cohort study. J Neuromuscul Dis. Published online January 16, 2026. doi:10.1177/22143602251377240