Chronic kidney disease in propionic acidemia

Abstract

Purpose: Propionic acidemia (PA) is a severe metabolic disorder characterized by multiorgan pathology, including renal disease. The prevalence of chronic kidney disease (CKD) in PA patients and factors associated with CKD in PA are not known.

Methods: Thirty-one subjects diagnosed with PA underwent laboratory and clinical evaluations through a dedicated natural history study at the National Institutes of Health (ClinicalTrials.gov identifier: NCT02890342).

Results: Cross-sectional analysis of the creatinine-based estimated glomerular filtration rate (eGFR) in subjects with native kidneys revealed an age-dependent decline in renal function (P < 0.002). Among adults with PA, 4/8 (50%) had eGFR <60 mL/min/1.73 m². There was a significant discrepancy between eGFRs calculated using estimating equations based on serum creatinine compared with serum cystatin C (P < 0.0001). The tubular injury marker, plasma lipocalin-2, and plasma uric acid were strongly associated with CKD (P < 0.0001). The measured 24-hour creatinine excretion was below normal, even after adjusting for age, height, and sex.

Conclusion: CKD is common in adults with PA and is associated with age. The poor predictive performance of standard eGFR estimating equations, likely due to reduced creatine synthesis in kidney and liver, could delay the recognition of CKD and management of ensuing complications in this population.

Keywords: GFR; chronic kidney disease; creatinine; cystatin C; propionic acidemia.

Figure 1.. Significant discrepancy between the creatinine and cystatin C GFR estimates and select laboratory parameters associated with declining eGFR.

A. Cross-sectional analysis of creatinine eGFR in non-transplanted patients suggested an age-dependent trend of renal function decline (P value <0.002, r = −0.536). G2, G3 and G4–5 denotes levels of renal function based on eGFR. B. Cystatin C eGFR in non-transplanted patients suggested the eGFR was reduced in early childhood, with progressive decline in some subjects in the late teen-age or early adult years; 25/30 subjects (82%) had eGFR <90 mL/min/1.73 m² (chronic kidney disease stages 2–4). C. Creatinine (Cr eGFR) and cystatin C eGFRs (CysC eGFR) showed significant disagreement (P value <0.0001). D. Linear regression of creatinine eGFR and cystatin C eGFR in non-transplanted patients demonstrated that the intercept of the creatinine eGFR was significantly different from cystatin C eGFR (P value < 0.0001, denoted by the # sign). E. Plasma lipocalin-2, a biomarker of tubular injury, was associated with the cystatin C eGFR (P value <0.0001, r = − 0.717). F. Plasma uric acid, a factor that can be associated with CKD, rises with decreasing cystatin C eGFR (P value <0.0001, r = −0.718). Dotted lines in Figures 1A, 1B, 1E, and 1F represent 95% prediction bands.