What is the best management approach for a patient with central core disease and impaired renal function, as indicated by low creatinine levels?

Management of Central Core Disease with Low Creatinine

In patients with central core disease presenting with low creatinine, the low creatinine reflects reduced muscle mass from the underlying myopathy rather than impaired renal function, and you should use cystatin C-based eGFR or measured GFR to accurately assess kidney function while focusing management on monitoring for malignant hyperthermia risk and addressing any progressive muscle weakness. 1, 2

Understanding the Clinical Context

Central core disease is a congenital myopathy characterized by muscle weakness, atrophy, and importantly, reduced muscle mass that directly decreases creatinine generation. 3, 4 The disease shows wide clinical variation—some patients remain asymptomatic while others develop moderate weakness, though severe progression is rare. 4

The critical pitfall: Low serum creatinine in this population falsely suggests normal or even supranormal kidney function when calculating standard creatinine-based eGFR, potentially masking significant renal impairment if present. 2, 5 Since approximately 75% of creatinine originates from skeletal muscle catabolism, the muscle wasting inherent to central core disease substantially reduces creatinine production independent of kidney function. 5

Accurate Assessment of Kidney Function

Primary Approach

• Use cystatin C-based eGFR (eGFRcys) or combined creatinine-cystatin C eGFR (eGFRcr-cys) as these methods provide GFR assessment independent of muscle mass, avoiding the confounding effect of sarcopenia from the myopathy. 1, 5
• The 2024 KDIGO guidelines specifically recommend eGFRcr-cys in muscle-wasting diseases, noting that both eGFRcr and eGFRcys show large bias in these conditions when used alone. 1

When Greater Accuracy is Needed

• Measure GFR using plasma or urinary clearance of an exogenous filtration marker (mGFR) if treatment decisions depend critically on the GFR level, such as for nephrotoxic drug dosing or transplant evaluation. 1
• This is particularly important because the standard eGFR equations may remain inaccurate even with cystatin C in the setting of severe muscle wasting. 1

What NOT to Do

• Never rely on serum creatinine alone or standard creatinine-based eGFR to assess kidney function in central core disease patients. 2, 5
• The K/DOQI guidelines explicitly state that serum creatinine should not be used alone to assess kidney function in conditions affecting muscle mass. 5

Nutritional and Muscle Mass Assessment

Calculate Creatinine Index

• Measure 24-hour urinary creatinine excretion to calculate the creatinine index, which assesses creatinine production, dietary skeletal muscle protein intake, and total muscle mass. 1, 2, 6
• The formula: Creatinine index (mg/24h) = dialysate creatinine + urine creatinine + change in body creatinine pool + creatinine degradation. 1
• This helps distinguish whether low creatinine reflects the baseline myopathy versus superimposed malnutrition or disease progression. 6

Assess for Protein-Energy Malnutrition

• Evaluate serum albumin, prealbumin, and cholesterol as additional nutritional markers beyond creatinine. 2, 6, 5
• Low creatinine index correlates with mortality independent of cause, so declining values warrant aggressive nutritional intervention. 6, 5

Disease-Specific Management Priorities

Malignant Hyperthermia Surveillance

• All patients with central core disease should be considered at risk for malignant hyperthermia unless in-vitro contracture testing proves otherwise. 4
• This takes precedence over the low creatinine issue and requires documentation in the medical record for any surgical procedures. 4

Monitor for Cardiac Complications

• Screen for mitral valve prolapse and cardiac arrhythmias, which occur in a subset of central core disease patients. 4
• These may require separate management but don't directly relate to the low creatinine. 4

Musculoskeletal Deformities

• Address kyphoscoliosis, hip dislocation, foot deformities, and joint contractures as they arise, though these don't typically alter disease natural history. 4
• Surgical correction may be needed for functional impairment. 4

Monitoring Strategy

• Track creatinine index over time rather than serum creatinine alone, as declining values indicate worsening muscle mass or nutritional status and correlate with increased mortality risk. 6, 5
• Reassess cystatin C-based eGFR at least annually, more frequently if other risk factors for kidney disease emerge. 6
• Changes in serum creatinine should be interpreted relative to the patient's baseline, not population normal ranges. 6

Common Pitfalls to Avoid

1. Misinterpreting "normal" creatinine as normal kidney function—the muscle wasting makes standard interpretation invalid. 2, 5
2. Using creatinine-based equations for drug dosing—this will lead to underdosing of renally cleared medications if kidney function is actually impaired. 1
3. Attributing low creatinine solely to the myopathy without assessing for superimposed malnutrition—both require evaluation. 2, 6
4. Failing to document malignant hyperthermia risk—this is the most critical safety issue in central core disease. 4