Assessment of metabolites in urine in post-kidney transplant patients: insights into allograft function and creatinine clearance.

Abstract

Introduction: The suboptimal function of transplanted kidney can lead to imbalances in processes controlled by the kidneys, necessitating long-term monitoring of the graft's function and viability. Given the kidneys' high metabolic activity, a metabolomics approach is well-suited for tracking changes in post-transplant patients and holds significant potential for monitoring graft function.

Objectives: Examination of the response of urinary creatinine levels to (i) serum creatinine levels and (ii) allograft function during periods of impaired kidney function in post-transplant patients.

Methods: We analyzed morning and 24-h urine samples from 55 patients who underwent primary kidney transplantation and were uniformly treated with immunosuppressants, with an average follow-up of 50 months post-surgery. We assessed the relative levels of urinary metabolites detectable by NMR spectroscopy and investigated correlations between these metabolite levels and renal function.

Results: We observed rather unexpected independence of urinary creatinine levels on levels of serum creatinine as well as on allograft function expressed by eGFR (estimated glomerular filtration rate). This observation allowed a very good agreement of outcomes from raw and creatinine-normalized data, consistent for both morning urine samples and 24-h urine collections. The urinary levels of citrate and acetone were detected to be sensitive to allograft function, and the urinary levels of metabolites in combination showed promising prediction for kidney function, on the level of p-value: for 24 h pooled urine: 4.6 × 10^-12 and morning urine: 5.36 × 10^-9. We discussed the data also in the light of metabolic changes in blood plasma.

Conclusion: We support the opinion of critical assessment of renal creatinine clearance when judging the filtration function of the allograft. As the next, urinary metabolomics can serve as an easily available supplement to prediction for allograft function in patients after kidney transplantation.