Is proteinuria reversible, after withdrawal of mammalian target of rapamycin inhibitors?

Conversion to mammalian target of rapamycin inhibitors (mTORi) is an ever more frequent practice in renal transplant recipients, even if it is not always satisfactory, needing to be suspended for various reasons in certain patients. We analyzed the evolution of proteinuria as a marker of kidney damage after withdrawal of mTORi for any reason in order to assess conversion failure risk. Among 1633 renal transplant patients with 185 converted to mTORi, we considered the 52 (28%) who withdrew as result of intolerance or a bad evolution after at least 3 months use (median: 142 days after conversion). Four groups were defined according to the evolution of proteinuria: group 1 (G1), stable after conversion; group 2 (G2), increased with complete recovery (<1 g); group 3 (G3), increased with partial recovery (>1 g); or group 4 (G4), increased without recovery. The evolution according to the groups was: G1 (57.1%), G2 (17.2%), G3 (5.7%), and G4 (20%). There were no differences between the good (G1 and G2) and the bad evolution groups (G3 and G4) in proteinuria at the time of conversion (838 ± 641 vs 532 ± 404 mg/d) or renal function (1.95 ± 0.47 vs 1.90 ± 0.4 mg/dL). Six months after withdrawal, proteinuria was stable in G1 and G2 but worse in G3 and G4 (781 ± 643 vs 4479 ± 3235 mg/d); the same observation was noted for renal failure (2.1 ± 0.71 vs 2.8 ± 1.57 mg/dL). Among about 75% of patients in whom mTORi was withdrawn, no injury remained in the medium term whereas among the other 25%, there was a residual injury.

Early prediction of new-onset diabetes mellitus by fifth-day fasting plasma glucose, pulse pressure, and proteinuria.

Renal transplant recipients are at high risk of cardiovascular disease (CVD). New-onset diabetes mellitus after transplantation (NODAT) contributes to the risk of CVD, reducing graft and patient survival. To improve outcome of kidney transplant recipients, it is of great interest to identify those patients who will develop NODAT. The aim of our study was to explore the predictive value of fifth-day fasting plasma glucose (FPG), third-month proteinuria, and pulse pressure (PP) for NODAT development. We analyzed 282 non-previously-diabetic kidney transplants in our center. Fifth-day FPG, PP, and third-month 24-hour proteinuria were collected. NODAT was defined at month 12 according to the "consensus guidelines": symptoms of diabetes plus casual glucose concentrations ≥ 200 mg/dL or FPG ≥ 126 mg/dL. Some 46 patients (16.3%) developed NODAT at month 12. Fifth-day FPG (133 ± 35 vs 108 ± 16 mg/dL, P < .001) and PP (57 ± 17 vs 49 ± 15 mm Hg, P = .007) were significantly higher in patients at risk for NODAT, but there was no difference in third-month proteinuria (652 ± 959 vs 472 ± 1336 mg, P = .390). A multivariate regression model showed an increased risk for NODAT associated with recipient age, body mass index, smoking habit, and a fifth-day FPG ≥ 126 mg/dL (relative risk 4.784, 95% confidence interval 2.121-10.788, P = .0002). The negative predictive value of a fifth-day FPG ≥ 126 mg/dL for predicting 1-year NODAT was 89.4%. Fifth-day FPG was independently related to NODAT development. The detection of a fifth-day FPG ≥ 126 mg/dL increases the risk of suffering NODAT more than 4 times. Fifth-day FPG < 126 mg/dL allows us to identify a transplant population with a low risk (near 10%) for NODAT.