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Background: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction.

Methods: To assess kidney function during prolonged critical illness we enrolled 38 mechanically ventilated patients with expected length of stay of >72h near admission to ICU in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modelling. We simultaneously measured muscle mass by ultrasound of rectus femoris to assess the confounding effect on serum creatinine generation.

Results: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min/1.73m2/day (95% confidence interval 1-2). By ICU discharge the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min/1.73m2 (95% credible interval 24-42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average 2-fold greater than the iohexol gold-standard, posterior mean difference 59 ml/min/1.73m2 (95% credible interval 49-69). The posterior mean for eGFR cystatin C suggested a 22 ml/min/1.73m2 (95% credible interval 13-31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95%CI 1-3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R=0.61 (95% confidence interval, 0.50-0.72).

Conclusions: eGFR creatinine systematically over-estimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function as it appeared unaffected by the muscle loss of prolonged critical illness.