Background:

Proteinuria is routinely measured for assessment of renal allograft status, but its diagnostic value for transplant pathology and herewith-related prognostic value remain unclear.

Methods:

We included 1518 renal allograft recipients in this observational cohort study, divided into a test and validation population. All renal allograft biopsies (N=2274; 1555 clinically indicated biopsies in both cohorts, and 719 protocol-specified biopsies at 3, 12, and 24 months post-transplantation in the validation cohort) with concomitant data on 24h proteinuria were included in the analyses. Biopsies were rescored according to the updated Banff classification and histology data were integrated with data on donor-specific HLA antibodies. Patients were followed for at least 7 years after transplantation.

Results:

At time of clinically indicated biopsies, proteinuria was <0.3 in 49.8%, 0.3-1.0 in 30.0%, 1.0-3.0 in 16.3%, and >3.0 g/24h in 3.9% of cases. Compared with <0.3 g/24h, the hazard ratio for graft failure was 1.14 (95% CI 0.81-1.60; P=.50) for proteinuria 0.3-1.0, 2.17 (1.49-3.18; P<.001) for 1.0-3.0 g/24h, and 3.01 (1.75-5.18; P<.001) for >3.0 g/24h, independent of glomerular filtration rate and of renal allograft histology. This association was confirmed in the validation cohort and at protocol-specified time points. Against a 27.3% likelihood of graft loss by 5 years after a clinically indicated biopsy, specificity of proteinuria >1.0 g/24h for graft failure was 86.1% (83.5%-88.4%), and sensitivity was 31.7% (27.0%-36.7%). The independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The specificity of 24h proteinuria >1.0 g/24h for these intragraft injury processes was 85.0% (82.6%-87.2%), with a sensitivity of 31.7% (27.1%-36.5%).

Conclusions:

Detection of proteinuria >1.0 g/24h after kidney transplantation should prompt investigation to identify the underlying specific intragraft disease process. Proteinuria should be considered a clinical end point in kidney transplantation and is the benchmark against which novel non-invasive biomarkers of kidney graft injury and prognosis are to be compared.

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