Quantitative assessment of serum free light chains in renal transplantation.

Plasma cell dyscrasias can cause renal disease. Sensitive methods have recently been introduced to quantify serum free light chains (sFLCs). Renal function may influence the variability of these methods, as shown in chronic kidney disease (CKD) patients, but this problem has not been widely addressed in renal transplant patients. Herein, we examined the association between polyclonal sFLC concentrations and renal function among a population of renal transplant patients. We studied 102 kidney allograft recipients and 53 CKD patients classified according to KDOQI (Kidney Disease Outcomes Quality Initiative) stages. None of them had been diagnosed with monoclonal gammopathy. sFLCs were quantified by nephelometry. Both serum κ and λ free light chain concentrations rose progressively through each stage of KDOQI among both transplant and nontransplant patients (P<.0001). In the former setting, sFLC concentrations significantly correlated, using a Spearman coefficient, with serum creatinine, and serum cystatin concentrations as well as estimated glomerular filtration rate: namely, 0.723, 0.797, and -0.711 for sκFLC and 0.705, 0.759, and -0.694 for sλFLC, respectively (P<.0001 in all cases). Spearman correlation coefficients in nontransplant patients were: 0.559, 0.848, and -0.766 for sκFLC and 0.702, 0.875, and -0.855 for sλFLC, respectively (P<.0001 in all cases). In conclusion, sFLCs must be interpreted cautiously due to their clear association with renal function. Therefore, renal transplantation did not produce changes that were different from those dependent on renal function.

Number of peripheral blood regulatory T cells and lymphocyte activation at 3 months after conversion to mTOR inhibitor therapy.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are effective for induction and maintenance of regulatory T cells (Tregs). OBJECTIVE: To assess the effects of conversion from calcineurin inhibitors (CNIs) to mTOR on the number of circulating Tregs and lymphocyte activation. PATIENTS AND METHODS: In 18 renal transplant recipients receiving CNI therapy (cyclosporine in 9, and tacrolimus in 9), treatment was converted to mTOR inhibitors (everolimus in 14, and rapamycin in 4). Peripheral blood samples were obtained before and 3 months after conversion. The number of circulating Tregs was measured using flow cytometry, and defined as CD4+/CD25high/CD127low/CD27+/CD62L+/CD45RO+/Foxp3+. Lymphocyte activation was assessed indirectly according to production of intracellular adenosine triphosphate (iATP) on polyclonal activation using a phytohemaglutinin assay (Immuknow; Cylex, Inc, Columbia, Maryland). RESULTS: In 15 patients (83.3%), the absolute number of Tregs increased significantly (P=.001) after conversion (median, 16.35 cells/mm3; 95% confidence interval [CI], 13.97-21.94) vs 3 months after conversion (32.03 cells/mm3; 95% CI, 26.25-41.66). The iATP production decreased from 326 ng/mL (95% CI, 302-419) to 248 ng/mL (95% CI, 196-318; P=.02), and increased in 4 patients (22.22%). No significant correlation was demonstrated between Treg concentration and change in iATP production. No rejection episodes were reported during follow-up. CONCLUSIONS: Despite the small number of patients in whom therapy was converted from CNI inhibitors to mTOR inhibitors, the data suggest an increase in the absolute number of Tregs after conversion. In addition, the concentration of activated peripheral CD4+ T cells decreased to nearly that associated with risk of infection due to overimmunosuppression.

Kidney transplant recipients show an increase in the ratio of T-cell effector memory/central memory as compared to nontransplant recipients on the waiting list.

Studies of allotolerance in animal models do not usually consider the presence of preexisting memory T cells and activated immune status. However, humans are exposed throughout life to a multitude of external agents that enhance the immune memory. In this article, we consider the effect that a previous kidney transplant has on the number of regulatory T cells (Tregs), effector memory T cells (TEM), and central memory T cells (TCM). Sixty-three patients with end-stage renal disease were studied just before being transplanted (51 first transplants and 12 retransplants). The numbers of Tregs (CD4+ CD25highCD127lowCD27+CD62L+CD45RO+FOXP3+), TEM (CD3+CD45RO+CD62L+), and TCM (CD3+CD45RO+CD62L-) cell subsets were quantified in peripheral blood by flow cytometry. The absolute number of Tregs was slightly lower in patients with previous allografts (median, 95% confidence interval [CI]: 16.7 cells/mm3, 12-20.5) than in those who received their first transplants (median, 95% CI: 19.6 cells/mm3, 19.3-29.6; P-NS). Clearer differences were found with the number of CD3+ TCM, since the transplanted patients had lower numbers (238 cells/mm3, 153-323) than those who had not yet received transplants (378 cells/mm3, 317-439; P=.029). As a result, the TEM/TCM ratios of both CD4+ and CD8+ T cells in patients with previous allografts were higher than in those who received first transplants. In conclusion, the assessment of just the number of Tregs in renal transplant patients is not enough and must be read together with the number of TEM and TCM. The TEM:TCM ratio increases in patients with previous allografts, probably due to activation of the immune response in renal transplantation.

[Changes in the pre-transplant bone-mineral metabolism do not affect the initial progress of the renal graft]. / Las alteraciones del metabolismo óseo-mineral pretrasplante no influyen en la evolución inicial del injerto renal.

BACKGROUND: Abnormalities in serum calcium, phosphate, and Parathyroid Hormone (PTH) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality. One of the most common problems in the first weeks after renal transplantation is Delayed Graft Function (DGF). There are several well-known risk factors for DGF development, but the role of calcium phosphate-PTH homeostasis as a risk factor for early graft dysfunction is controversial. This issue was addressed in the current study. METHODS: Pretransplant PTH, calcium and phosphate values were gathered in 449 patients that received a renal transplant in our center between 1994 and 2007. Other variables expected to influence the risk for delayed graft function were included from the clinical charts. RESULTS: The incidence of DGF was 27.3%. DGF development was significantly associated with recipient age, type and need of renal replacement therapy, peak panel reactive antibodies, transfusion number and donor age. There were no significant differences in the mean pretransplant values of calcium (9.4 +/- 1.0 vs. 9.5 +/- 0.9 mg/dl, p = 0.667), phosphate (5.7 +/- 1.8 vs. 5.5 +/- 1.5 mg/dl, p = 0.457), calcium-phosphate product (53.5 +/- 17.2 vs. 51.8 +/- 14.6 mg(2)/dl(2), p = 0.413) and PTH (315 +/- 312 vs. 340 +/- 350 pg/ml, p = 0.530) between patients with and without DGF. CONCLUSIONS: In our study population pretransplant serum PTH, calcium and phosphorus levels have no influence on the risk for DGF.