Beyond the Amount: The Selectivity of Proteinuria and Risk of Graft Failure in Kidney Transplant Recipients

Patients with nonselective proteinuria generally have a worse prognosis than those with selective proteinuria. However, this has never been studied in kidney transplant recipients (KTRs). This study aimed to evaluate the association between proteinuria selectivity and graft failure among KTRs.

We used data from KTRs with a functioning graft ≥1 year after transplantation who enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study and had urinary albumin excretion ≥30 mg/24-h and urinary protein excretion >150 mg/24-h. The selectivity of proteinuria was based on the clearance ratio of IgG to albumin (≤0.10 = highly selective; >0.10 = moderate/nonselective). Multivariable Cox regression analyses were performed to evaluate the association between proteinuria selectivity and graft failure.

A total of 335 KTRs (36% female, median 6 years after transplantation, mean estimated glomerular filtration rate [eGFR] 47 mL/min/1.73 m2) were included in the analyses. Of them, 107 (31.9%) had moderate/nonselective proteinuria. KTRs with moderate/nonselective proteinuria had lower eGFR, higher 24-h urinary protein excretion, and higher levels of tubular injury markers. During a median follow-up of 5.2 years after baseline measurement, 66 (19.7%) KTRs developed death-censored graft failure. Moderate/nonselective proteinuria was significantly associated with a higher risk of graft failure, independent of potential confounders, including eGFR and 24-h urinary protein excretion (adjusted hazard ratio [95% confidence interval] = 2.10 [1.12-3.94], p = 0.020).

The independent association between proteinuria selectivity and graft failure highlights the importance of evaluating proteinuria selectivity, in addition to urinary protein, in routine clinical care for KTRs.