Comparison of Sensitivity of Immunocomplex Capture Fluorescence Analysis for Detecting Donor-specific Anti-HLA Class II Antibodies in Kidney Transplant Patients.

BACKGROUND: Immunocomplex capture fluorescence analysis (ICFA) detects donor-specific antihuman leukocyte antigen (HLA) antibodies (DSA), but the detection sensitivity of HLA class II antibodies using conventional ICFA is as low as 57%. The aim of the study was to improve the detection sensitivity of HLA class II antibodies by ICFA, and compare the ICFA results with the Luminex single-antigen bead test. METHODS: Six DSA-negative kidney transplant donors and recipient pairs and 10 HLA class II DSA-positive pairs were included in the study. The detection sensitivity of modified ICFA was compared with conventional ICFA, and the ICFA results were compared with the Luminex single-antigen bead test. RESULTS: The index value of modified ICFA was higher than that of conventional ICFA. The cutoff value of conventional ICFA was 30,686 (MFI), which was improved to 19,405 using modified ICFA. Regarding the HLA-DQ antibody, 5 samples found to be positive by Luminex single-antigen bead testing were all negative using modified ICFA. The reason for this discrepancy could be related to: (1) the difference in detection sensitivity; (2) the difference in HLA antigen surface expression between naive lymphocytes and synthetic beads; or (3) the structure of synthetic HLA DQ antigen on the Luminex single-antigen beads. CONCLUSION: The index value of the modified ICFA was higher than that of conventional ICFA, and the detection sensitivity of HLA class II antibodies was improved by modified ICFA. Further assessment is necessary to clarify the reasons for divergence between ICFA and Luminex single-antigen bead test results.

Diffusion Tensor Imaging MRI With Spin-Echo Sequence and Long-Duration Measurement for Evaluation of Renal Fibrosis in a Rat Fibrosis Model.

BACKGROUND: Renal fibrosis (RF) is a well-known marker for chronic kidney disease (CKD) progression, including chronic renal injury after renal transplantation. However, invasive biopsy is an available examination for evaluation of RF. Diffusion MRI was once recognized as a promising option for RF. However, it is now controversial for RF evaluation in a unilateral ureteral obstruction (UUO) model. METHODS: To seek an optimal imaging method applicable for RF in UUO model kidneys, we attempted a series of MRI methods, including proton density-weighted imaging, T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging (DTI). RESULTS: We identified DTI MRI by spin-echo sequence plus a special kidney attachment as the best option for evaluation of renal UUO fibrosis, compared with normal kidney on the opposite side. To confirm these results, we applied this technique to a rat UUO therapeutic model with the anti-fibrotic reagent Fasudil. Fractional anisotropy values calculated from DTI MRI showed statistically significant linear correlation with the RF area measured by use of Sirius red or Masson trichrome staining of the positive area [cortex (r = 0.6397, P = .0283) and outer stripe of the outer medulla (r = 0.7810, P = .0039)]. CONCLUSIONS: By use of the DTI MRI with spin-echo sequence, it may be possible to accurately evaluate RF in CKD.

Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients.

BACKGROUND: Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. METHODS: In all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. RESULTS: At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. CONCLUSIONS: PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.

Adherence to Dietary Recommendations in Maintenance Phase Kidney Transplant Patients.

OBJECTIVES: Current adherence to dietary recommendations for chronic kidney disease was evaluated in kidney transplant patients in the maintenance phase. METHODS: A total of 268 maintenance phase kidney transplant patients were included in the study. Estimated daily intakes of oral protein and salt were calculated from 24-h urinary excretion of nitrogen and sodium, respectively. Dietary recommendations for chronic kidney disease, as issued in 2014 by the Japanese Society of Nephrology, were used as the basis for assessing diet. RESULTS: The study included 114 female patients and 154 male patients. The mean age, posttransplantation years, body mass index, estimated glomerular filtration rate, and 24-h urinary excretion of protein were 56.3 years, 11.2 years, 22.0 kg/m(2), 42.6 mL/min/1.73 m(2), and 321 mg/d, respectively. Estimated daily protein and salt intakes were 0.98 ± 0.26 g/kg/d and 9.3 ± 3.9 g/d. Only 47 patients (17.5%) in the case of salt intake and 105 patients (39.2%) in the case of protein intake were within reference values. The 24-h urinary protein excretion of the daily salt intake-adherent group (<6 g) was significantly less than that of the nonadherent group (≥6 g) (P = .021). CONCLUSIONS: The adherence rate to dietary recommendations for chronic kidney disease in kidney transplant patients was low. The 24-h urinary protein excretion of the daily salt intake-adherent group was significantly less than that of the nonadherent group. Dietary therapy for these patients may have the potential to improve kidney graft function and survival.

Risk factors and incidence for lipid abnormalities in kidney transplant patients.

BACKGROUND: Lipid abnormalities (LA) are related to an increased risk for cardiovascular diseases in kidney transplantation patients. PATIENTS AND METHODS: Multivariable logistic regression models were used to estimate the risk of LA associated with potential risk factors, including immunosuppressant use, patient background characteristics, and laboratory data. RESULTS: In total, 386 patients who were undergoing kidney transplantation were included in the study. Statins were prescribed to 43% of patients. The LA composite outcome was defined as statin use and/or low density lipoprotein cholesterol level ≥120 mg/dL, and 229 patients (59.3%) developed LA as a result. LA was significantly related to everolimus, corticosteroid, age, and estimated glomerular filtration ratio in the multiple logistic regression analysis. The odds ratios were 2.264, 3.119, 1.186, and 0.870, respectively. Mycophenolate mofetil, mizoribine, azathioprine, cyclosporine (CYA), tacrolimus, proteinuria, body mass index, and male sex were not related to LA. DISCUSSION: CYA influenced lipid metabolism but was not related to LA in our study. The mean post transplantation period was 8.4 years, and the CYA dose decreased over time. The CYA blood concentration was 70.0 ng/mL, which is relatively low, but it decreased the susceptibility to LA. Serum lipid levels were well controlled by statins, and the estimated glomerular filtration rate was maintained stably. CONCLUSIONS: Everolimus and corticosteroid use, as well as a lower estimated glomerular filtration rate and higher age, were significant risk factors for LA. CYA is known for its adverse LA effects, but it was not a significant risk factor for LA in patients undergoing maintenance phase kidney transplantation.

Beneficial effects of tonsillectomy for mesangial immunoglobulin A (IgA) deposition and clinical outcome in five kidney transplant patients with recurrent IgA nephropathy: case report.

INTRODUCTION: Tonsillectomy has been applied for recurrent immunoglobulin (Ig)A nephropathy (IgAN) in kidney transplantation recipients, but allograft histologic changes after this treatment remain unclear. METHODS: Five patients with recurrent IgAN underwent tonsillectomy for persistent proteinuria (average, 397.2 mg/d; >6 months). Six repeated biopsies were taken 33.8 ± 17.1 months after treatment. Glomerular IgA deposition was detected by immunofluorescence staining on frozen tissue. Histologic and clinical data have been collected. RESULTS: An average of 11.2 months (range, 6-20) after tonsillectomy, proteinuria decreased to 60.8 ± 49.3 mg/d. Serum creatinine (SCr) slightly decreased (1.33 ± 0.31 before vs 1.24 ± 0.29 after treatment; P > .05). In 5 of the 6 repeated biopsy samples month after tonsillectomy, there was decreased mesangial IgA deposition. Glomerular crescent and endothelial proliferation were no longer found, although there was increased focal sclerosis and adhesion. After tonsillectomy, there were increased interstitial fibrosis and tubular atrophy, with no significant differences in Banff scores. CONCLUSIONS: Tonsillectomy can reverse not only persistent proteinuria, but also mesangial IgA deposition in patients with recurrent IgAN. Tonsillectomy may have both favorable clinical and histologic effects in recurrent IgAN after kidney transplantation.