Prognostic Significance of Creeping Proteinuria in the First Year After Transplantation.

BACKGROUND: Proteinuria changes have a prognostic significance in proteinuric nephropathies. Proteinuria has been related to kidney transplant outcomes, but there are no information about the impact of increasing proteinuria during the first year on long-term graft and patient survival. METHODS: Retrospective cohort study of 591 kidney transplants to analyze the effect on long-term prognosis of: proteinuria at 3 (n = 591) and 12 (n = 583) months (no proteinuria: 150-299 mg/24 hours, 300-999 mg/24 hours, and ≥1 g/24 hours), and changes in proteinuria during the first year in such patients with proteinuria at 3 months (reduction ≥50% of proteinuria from 3 to 12 months, variation <50%, and increase ≥50% or "creeping proteinuria") (n = 283). RESULTS: Higher levels of proteinuria, at both 3 and 12 months, were progressively related to lower graft survival (P < 0.0001). Proteinuria at 12 months was related to mortality (P = 0.026). Creeping proteinuria, which was present in 35 patients (12.4%), was related to graft failure (P < 0.0001) and mortality (P = 0.030), even at lower levels of proteinuria at 3 months. De novo HLA antibody development was the only factor related to creeping proteinuria (hazard ratio, 2.946; 95% confidence interval, 1.158-7.491; P = 0.023). CONCLUSIONS: Creeping proteinuria during the first year was associated with long-term graft failure and mortality and could be considered as a surrogate of kidney disease progression in the renal transplant population, as it is in proteinuric nephropathies. It could also be viewed as an expression of immunological damage.

Prognostic significance and diagnosis of proteinuria in renal transplantation.

Proteinuria is considered one of the most important prognostic markers of chronic kidney disease progression in native kidneys. In renal-transplanted population, proteinuria presents a high prevalence because early stages and its presence, in higher or lower degrees, have been related to the lower graft survival and a higher risk of death, mainly because of cardiovascular diseases, in renal transplantation. Although there is a good correlation between higher degree proteinuria and histologic findings, histology is not very useful in the study of lower degree proteinuria. In that case, the knowledge of different types of proteins present in urine could be useful to know which type of damage underlies on the graft. Proteomics and different laboratory techniques could be helpful to identify damage markers on different conditions, especially on tubulointerstitial damage, that should have a subtle clinical presentation. Diagnosis of proteinuria in renal transplantation follows the same criteria of general population, actually, and in the last years, some authors have tried to achieve the usefulness of different diagnostic methods such as protein/creatinine ratio or albumin/creatinine ratio in the renal-transplanted population in comparison with 24-hour collected urine diagnostic techniques. Nevertheless, there are no studies about the limit to be considered as "normal" in this population, which shows a reduced nephron mass and a higher risk of developing proteinuria. Recent literature about the prognostic significance of lower degrees of proteinuria on graft and patient survival in this population could be the proof that new studies are needed to establish the normal threshold of proteinuria to be considered in kidney transplantation.