Two novel APOA1 gene mutations in a Japanese renal transplant recipient with recurrent apolipoprotein A-I related amyloidosis.

Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder of APOA-1 gene characterized by the deposition of apolipoprotein A-I in various organs and can be classified into either hereditary or nonhereditary form in the absence of a family history. Renal disease caused by Apolipoprotein A-I amyloidosis commonly manifested as slowly progressive renal function impairment without heavy proteinuria. Apolipoprotein A-I-related amyloidosis of kidney is of pathogenetic interest because the renal failure is due to peritubular and interstitial amyloid deposits without glomerular deposits. Tubulointerstitial lesion of amyloid deposits was diagnosed in half of carriers of APOA1 gene mutation, only 13% of patients progressed to renal failure requiring hemodialysis or kidney transplantation. Recurrence of apolipoprotein A-I-related amyloidosis after kidney transplantation is very rare. We report a case of a 63-year-old Japanese female without a family history of kidney and/or liver disease who showed slowly progressive renal graft dysfunction without overt proteinuria. Graft biopsy revealed characteristic Congo red stain positive amyloid deposits localized in the renal interstitial area. No glomerular, vascular and tubular amyloid deposits were noted. Laser microdissection-liquid chromatography tandem mass spectrometry-based proteomic analysis elucidated the type of amyloidosis as apolipoprotein A-I amyloidosis. Genetic analysis of DNA sequence study revealed two novel APOA1 gene mutations of Leu202Arg and Lys262Asn. This is a first and very rare case report of the recurrence of non-familial hereditary apolipoprotein A-I amyloidosis in Japanese transplant recipient.

Surgical Techniques and Procedures for Kidney Transplant Recipients With Severe Atherosclerosis.

OBJECTIVES: Atherosclerosis is becoming a more common problem for dialysis patients. Therefore, transplant surgeons are faced with the need to develop surgical techniques and procedures for severe atherosclerosis. This study aimed to clarify the clinical features, the usefulness of examinations, and operative procedures for kidney transplant recipients with the complication of severe atherosclerosis. MATERIALS AND METHODS: Among 220 kidney transplant candidates, 13 patients (severe atherosclerosis group) were predicted complications due to arterial calcification in the bilateral iliac arterial system using a computed tomographic scan. They were compared with the remaining 207 patients (mild atherosclerosis group) based on patient characteristics. The severe atherosclerosis group was evaluated by additional examination, anastomosis procedure of the graft artery, and patient outcome. RESULTS: The severe atherosclerosis group had significantly higher rates of mean recipient age, glycosylated hemoglobin A1c, past smoking, and administration of antithrombotics. Past vascular surgery related to atherosclerosis in the aortoiliac region had been performed in 8 patients from the severe atherosclerosis group. A three-dimensional computed tomography angiography and an intraoperative periarterial echography were useful to determine the kidney transplant site. A balloon catheter effectively blocked blood flow. A polytetrafluoroethylene vascular graft was used for bypass between the graft artery and abdominal aorta. All kidney grafts of the severe atherosclerosis group were functioning well. CONCLUSIONS: Kidney transplant for patients with severe atherosclerosis can be achieved successfully by additional examinations and vascular surgical techniques.

MiR-142-5p and miR-486-5p as biomarkers for early detection of chronic antibody-mediated rejection in kidney transplantation.

De novo donor-specific HLA antibody (DSA) would not necessarily contribute to chronic antibody-mediated rejection (CAMR) in kidney transplantation. Here, we investigated whether PBMC miRNAs could be predictable biomarkers for CAMR. Microarray profiling of 435 mature miRNAs in pooled samples was conducted. Individual analysis revealed that miR-142-5p was significantly (p < 0.01) underexpressed in patients with DSA. After DSA production, miR-486-5p and its target PTEN/foxO3 mRNA were significantly overexpressed (p < 0.01) and underexpressed (p < 0.01), respectively, in patients with biopsy-proven CAMR, compared with non-CAMR. Our studies suggest that miRNA expression patterns may serve as noninvasive diagnostic biomarkers to evaluate immune response and kidney allograft status.

Association of Dialysis Duration with Outcomes after Transplantation in a Japanese Cohort.

BACKGROUND AND OBJECTIVES: Evidence regarding the differences in clinical outcomes after preemptive kidney transplantation (PKT) and non-PKT in Japan is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study at a single center in Japan. Consecutive patients ages >18 years old who had received a kidney transplant from a living donor between November of 2001 and December of 2013 at our institution (n=786) were enrolled. The primary study outcome was the occurrence of clinical events before the end of 2014. Clinical events were defined as any of the following: death with functioning graft (DWFG), graft loss, or post-transplant cardiovascular disease (CVD). RESULTS: The median follow-up period was 61.0 (35.3-94.0) months. PKT was performed in 239 patients (30.4%). Clinical events occurred in 78 (9.9%). In the Cox proportional hazard model for univariate analysis, factors found to be associated with higher risk of clinical events included older age, men, ABO incompatibility, longer dialysis duration, diabetes, pretransplant CVD, and large ventricular mass index. PKT was associated with lower risk. Clinical event rate in patients who received a PKT was 3.3% compared with 10.8%, 11.1%, 10.4%, 10.2%, 16.7%, and 16.2% among patients who were on dialysis for <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, and ≥5 years before transplant, respectively (P=0.002). The multivariate analysis showed that ABO incompatibility (hazard ratio [HR], 2.98; 95% confidence interval [95% CI], 1.89 to 4.71), duration of dialysis per year (HR, 1.07; 95% CI, 1.03 to 1.11), and diabetes (HR, 3.54; 95% CI, 2.05 to 6.12) were only three independent risk factors for the incidence of clinical events. CONCLUSIONS: Even in Japan, where the long-term outcomes of patients on hemodialysis are excellent, PKT could be beneficial to reduce DWFG, graft loss, and post-transplant CVD.

De Novo Anti-HLA DSA Characteristics and Subclinical Antibody-Mediated Kidney Allograft Injury.

BACKGROUND: It is unclear whether all donor-specific antibodies (DSA) can cause chronic antibody-mediated rejection (AMR). Subclinical stage before manifestation of renal dysfunction may be a critical period for reversing AMR. The aim of our study was to identify factors related to the development of subclinical AMR and to clarify the characteristics of de novo DSA. METHODS: Eight hundred ninety-nine renal transplants were screened for HLA antibody. De novo DSA were detected in 95 patients. Forty-three patients without renal dysfunction who underwent renal biopsies were enrolled in this study. Eighteen patients (41.9%) were diagnosed with biopsy-proven subclinical AMR and treated with plasmapheresis and rituximab-based therapy, whereas 25 showed no findings of AMR. RESULTS: Significant subclinical AMR-related factors were younger recipients, history of acute T cell-mediated rejection and DSA class II, especially DR-associated DSA. Mean fluorescence intensity (MFI) values of DR-DSA were significantly higher, whereas DQ-DSA was not different between subclinical AMR and no AMR. The ΔMFI (>50%), DSA-MFI values greater than 3000, and C1q binding DSA were also significant subclinical AMR-related factors (P < 0.05). Among 18 patients treated for subclinical AMR, 8 patients (44.4%) obtained over 50% reduction of DSA-MFI and/or improvement or no deterioration of pathological findings. In contrast, 25 patients without subclinical AMR did not show renal dysfunction clinically. Moreover, all of the 8 patients with rebiopsy after 2 years continued to demonstrate no AMR. CONCLUSIONS: About 40% of patients with de novo DSA demonstrated biopsy-proven subclinical AMR, leading to progressive graft injury. To validate the intervention and treatment for de novo DSA-positive patients without renal dysfunction, further study is necessary.

Virus-associated hemophagocytic syndrome in renal transplant recipients: report of 2 cases from a single center.

Virus-associated hemophagocytic syndrome (HPS) is a potentially fatal complication of immunosuppression for transplantation. However, it presents with heterogeneous clinical symptoms (fever, disturbed consciousness, and hepatosplenomegaly) and laboratory findings (pancytopenia, elevated hepatic enzyme levels, abnormal coagulation, and hyperferritinemia), impeding diagnosis. Case 1: A 39-year-old female developed fever 4 years after ABO-incompatible living-related renal transplantation. Laboratory findings revealed thrombocytopenia, elevated hepatic enzymes, Epstein-Barr virus (EBV) DNA seropositivity, and hyperferritinemia. EBV-associated HPS was confirmed by bone marrow aspiration. Steroid pulse therapy and etoposide were ineffective. Disseminated intravascular coagulation resulted in multiple organ failure, and the patient died 32 days after disease onset. Case 2: A 67-year-old male was admitted with rotavirus enteritis a month after living-unrelated renal transplantation. He developed sudden-onset high fever, disturbance of consciousness, and tachypnea 8 days after admission. Laboratory findings revealed elevated hepatic enzyme levels, hyperkalemia, and hyperferritinemia. Emergency continuous hemodiafiltration ameliorated the fever, and steroid pulse therapy improved abnormal laboratory values. Varicella-zoster virus meningitis was confirmed by spinal tap. Acyclovir improved consciousness, and he was discharged 87 days after admission. Fatal virus-associated HPS may develop in organ transplant patients receiving immunosuppressive therapy. Pathognomonic hyperferritinemia is useful for differential diagnosis.

Beneficial effects of preemptive kidney transplantation on calcium and phosphorus disorders in early post-transplant recipients.

BACKGROUND: Recently, preemptive kidney transplantation (PKT) has increased in Japan; however, the effects of PKT on calcium (Ca) and phosphorus (Pi) metabolism are poorly understood. METHODS: Thirty-two consecutive patients were enrolled in this study at Nagoya Daini Red Cross Hospital. Fifteen patients were in the PKT group and 17 patients were in the non-PKT group. Parameters of Ca and Pi metabolism, including fibroblast growth factor (FGF) 23 and intact parathyroid hormone, were measured before transplantation and 1, 3, and 24 weeks after transplantation. RESULTS: FGF 23 decreased dramatically in both groups after transplantation; however, FGF 23 before transplantation and at 1 and 3 weeks after transplantation was significantly lower in the PKT group than in the non-PKT group (p < 0.05). Although iPTH levels were higher in the PKT group than in the non-PKT group before transplantation, these levels were lower in the PKT group at 24 weeks after transplantation (p < 0.05). Corrected Ca was lower at 24 weeks in the PKT group (p < 0.05), whereas Pi was lower in the non-PKT group at 1 and 3 weeks (p < 0.05), but not significantly different at 24 weeks. Multivariate linear regression analysis revealed that FGF 23 before transplantation was the strongest predictor of Ca and Pi disorders in early post-transplant recipients. CONCLUSIONS: This study suggests that PKT has beneficial effects on Ca and Pi metabolism and pre-transplant FGF 23 levels are a good marker of post-transplant Ca and Pi metabolism disorders.

Clinical relevance of post-transplant pharmacodynamic analysis of cyclosporine in renal transplantation.

Although therapeutic drug monitoring based on blood concentration has been widely implemented in transplant recipients treated with immunosuppressive agents, clinical adverse events such as rejection, infection or drug-induced toxicity caused by inappropriate dosage cannot be completely controlled. Development of an effective assay for optimized immunosuppression would be desirable, which can potentially lead to personalized medicine in renal transplantation. Cyclosporine (CSA) pharmacodynamic analysis using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based T cell proliferation assay was examined in 66 kidney transplant recipients before and after transplantation. Two parameters, the 50% inhibitory concentration (IC50) and the percentage of T-cell proliferation values at the lower plateau (bottom), were compared with clinical events. A significant relation in CSA pharmacodynamic parameters was observed between pre- and post-transplantation. Analysis of the association between clinical outcomes and pharmacodynamic parameters in post-transplant samples demonstrated the following findings: (i) cytomegalovirus (CMV)/varicella zoster virus (VZV) reactivation and CSA-induced nephrotoxicity were significantly associated with high sensitivity to CSA (low bottom or low IC50), (ii) acute T cell-mediated rejection (ATMR) was significantly related to low sensitivity to CSA (high bottom), and (iii) de novo human leukocyte antigen (HLA) antibody production was associated with lower bottom and IC50 values, although the elucidation of those mechanisms is still in progress. It was suggested that CSA pharmacodynamics applied at post-transplantation would be useful for optimizing immunosuppressive therapy.

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.

The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches.

Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. Protocol biopsies within 1 year revealed subclinical CAMR in 36% of HLA-I, 5% of ABO-I and 3% of ABO-Id/C, although clinical acute AMR was observed in 8%, 3% and 1%, respectively. The incidence of CAMR was not different between class I and class II DSA. Most of class I DSA (94%) changed to negative 1 year after RTx, whereas 77% of class II DSA remained positive. In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR.

Stable renal engraftment in a patient following successful tandem autologous/reduced-intensity conditioning allogeneic transplantation for treatment of multiple myeloma with del(17p) that developed as a post-transplantation lymphoproliferative disease following renal transplantation.

Multiple myeloma (MM) developing after renal transplantation is rare. From January 1972 to December 2011, a total of 1,485 patients underwent renal transplantation in Nagoya Daini Red Cross Hospital; 14 (0.9%) of these recipients developed post-transplantation lymphoproliferative disorders (PTLDs) including two plasma cell neoplasms. Here, we report the clinical course of a 35-year-old male with immunoglobulin G k-type MM of recipient origin that developed 5 years after renal transplantation from a human leukocyte antigen (HLA)-haploidentical female sibling donor, which was performed to address dialysis-dependent chronic glomerulonephritis. Cytogenetic analysis revealed significant del(17p) abnormalities in myeloma cells. After non-response to bortezomib treatment, the patient achieved partial response with a thalidomide-containing salvage regimen and underwent successful tandem autologous/reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated male donor matched for seven of eight HLAs. At the 8-month follow-up time point, the patient's performance status remained good, and the transplanted kidney remains functional without rejection. To the best of our knowledge, this is the first report of a successful use of allogeneic HSCT for a patient who developed MM as a PTLD after renal transplantation. This patient has a transplanted kidney and transplanted hematopoietic cells that currently coexist without rejection.

Kidney volume changes in patients with autosomal dominant polycystic kidney disease after renal transplantation.

BACKGROUND: Few studies have investigated whether the volume of native kidney and liver (when combined with polycystic disease) in patients with autosomal dominant polycystic kidney disease (ADPKD) decreases after renal transplantation. METHODS: Changes in the volume of native kidney (bilateral: n=28; unilateral: n=5) and liver (concomitant polycystic disease: n=18) were analyzed in 33 patients with ADPKD, who underwent renal transplantation. Volumetry was retrospectively conducted using simple computed tomography scan data 6 months before transplantation, at the time of transplantation, and 1, 3, and 5 years after transplantation. Volume change was calculated on the basis of the value at the time of transplantation. RESULTS: Mean±standard deviation values of bilateral native kidney volume were 3100±1417 (range: 756 to 6525; median: 2499) cm at the time of transplantation. Kidney volumes were significantly reduced in all but one patient after renal transplantation, decreasing by 37.7% and 40.6% at 1 and 3 years, respectively. The major proportion of the decrease was observed within the first year posttransplantation. In contrast, 16 of 18 patients showed significant increase of liver volumes after renal transplantation. The mean rates of increase were 8.6% and 21.4% at 1 and 3 years, respectively. CONCLUSIONS: As the volume of native polycystic kidneys could be reduced after renal transplantation, resection would be unnecessary if the space for kidney graft is available in the absence of infection, bleeding, or malignancy. When ADPKD is combined with polycystic liver disease, the possibility of intolerable symptoms caused by growing liver cysts should also be taken into account.

Significant association between chronic antibody-mediated rejection and donor-specific antibodies against HLA-DRB rather than DQB in renal transplantation.

De novo production of antidonor HLA antibody has been reported to be associated with chronic antibody-mediated rejection (CAMR). However, some donor-specific antibodies (DSA) do not seem to cause graft injury. Identification of the DSA responsible for CAMR and establishment of effective screening method for early detection of CAMR are therefore essential. All sera from 586 maintenance renal transplant recipients were examined for HLA antibody using ELISA and Luminex-based assay. Positive sera were divided into high (>20% of positive control), moderate (10-20%), and low (2-10%). Donor specificities were analyzed using single antigen beads. ELISA detected only about half of high HLA antibodies (class I: n = 19, class II: n = 46) measured by Luminex-based assay. DSA against class I and class II were identified in 42% and 87% of high antibodies, respectively, including 78% against DQB and 44% against DRB. Renal dysfunction due to CAMR was closely related to high/moderate DRB DSA (n = 11), but not low DRB DSA (n = 9) nor high/moderate/low DQB DSA alone (n = 20). It was speculated that DRB DSA would be more detrimental to the graft, while DQB DSA were readily detectable in blood circulation. Further study, including detailed pathologic analysis of graft biopsy and long-term follow-up, is necessary.

Clinical significance of regulatory T-cell-related gene expression in peripheral blood after renal transplantation.

BACKGROUND: Regulatory T cells (Tregs) have been suggested to be deeply associated with immune tolerance and long-term graft survival in transplantation. Some recipients with stable graft function (ST) could possibly minimize immunosuppression during the maintenance period. However, effective assays for assessing the suitability of patients have yet to be established. The purpose of this study was to elucidate the clinical relevance of Treg-related gene expression such as forkhead box P3 (Foxp3) in peripheral blood after renal transplantation. METHODS: Several key molecules related to the function of immune cells such as Treg, including Foxp3, transforming growth factor-ß, cytotoxic T-lymphocyte antigen-4, chemokine receptor 7, toll-like receptor 4, granzyme B, T-bet, GATA3, RORC, α1,2-mannosidase, and proteasome subunit ß 10 were examined in the peripheral blood of 272 renal transplant recipients by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression levels were compared between recipients with chronic rejection and ST. RESULTS: Foxp3 messenger RNA (mRNA) levels were reduced immediately after transplantation and gradually recovered. Pretransplantation levels were closely correlated with 1 year posttransplantation levels. Recipients with chronic rejection had significantly lower levels of Foxp3, chemokine receptor 7, and granzyme B mRNA, and higher levels of toll-like receptor 4 and proteasome subunit ß 10 mRNA compared with those with ST, although Foxp3 was the most relevant marker. CONCLUSION: There is a possibility that monitoring mRNA expression levels of Treg-related molecules in peripheral blood might offer useful information on patient selection and early detection of rejection when immunosuppression minimization strategy is implemented in renal transplantation.

1,25-dihydroxyvitamin D synthesis after renal transplantation: the role of fibroblast growth factor 23 and cyclosporine.

1,25-dihydroxyvitamin D(3) (1,25D) is tightly regulated by circulating factors, containing fibroblast growth factor 23 (FGF23). However, this control is disturbed in chronic kidney disease. Renal transplantation (RTX) alters 1,25D homeostasis. To examine the clinical relevance of 1,25D in RTX, we drew blood samples from 27 renal transplant recipients (20 cyclosporine-based, seven non-cyclosporine-based) and examined serum concentrations of 25-hydroxyvitamin D(3) (25D), 1,25D, and FGF23. Our protocol for cyclosporine was as follows, an initial dose of 8 mg/kg two d before RTX, and subsequently adjusted on the basis of the pharmacokinetic profile. No baseline differences were observed between cyclosporine-based and non-cyclosporine-based regimens before RTX. All variables except 1,25D levels changed similarly between the two groups. In the cyclosporine-based regimen, 1,25D levels increased steeply on day 2 and re-increased from days 7 to 21. Post-transplant FGF23 levels sharply decreased until day 14. Interestingly, the cyclosporine-treated group revealed an unexpected tendency between circulating 1,25D and FGF23 on day 21. Multiple regression analyses indicated the cyclosporine pharmacokinetic profile as a significant predictor for 1,25D levels. Post-transplant 1,25D production is induced by a steep fall in serum FGF23 and prompt graft function on day 2; 1,25D levels thereafter may be stimulated by circulating abundant cyclosporine.

Stimulation index for PCNA mRNA in peripheral blood as immune function monitoring after renal transplantation.

Although more effective and potent immunosuppressive agents have recently reduced the incidence of acute rejection, drug-induced toxicity and infection caused by over-immunosuppression occasionally elicit a serious problem. However, no effective assay for evaluating overall patient's immune condition is in widespread use at present. We attempted to measure the stimulation index for mRNA of proliferating cell nuclear antigen (PCNA), which is synthesized in early G1 and S phases of the cell cycle and would be expected to reflect the proliferation capacity of T lymphocytes under the immunosuppressive condition. The stimulation index for PCNA mRNA seemed to be closely related to the immunosuppressive state of renal transplant recipients. Patients with stimulation index less than 2.0 tended to have viral reactivation after transplantation. It was suggested that PCNA mRNA monitoring in peripheral blood could provide a warning of possible over-immunosuppression as one simple assay for immune function monitoring.

Evaluation of interleukin-2 mRNA in whole blood as a parameter for monitoring cyclosporine pharmacodynamics.

Inhibition of cytokine production is the main immunosuppressive effect of cyclosporine (CsA), which is widely used in organ transplantation. Pharmacodynamic (PD) assay for evaluating the inhibition of interleukin-2 (IL-2) production for each patient could provide a more appropriate dosing regimen. We measured the suppression of IL-2 mRNA expression in whole blood following the addition of a range of CsA concentrations by a real-time reverse transcription-polymerase chain reaction (RT-PCR) method. Individual CsA sensitivity on the IL-2 mRNA expression was assessed with healthy subjects both in vitro and ex vivo. We also evaluated it in pre-transplant patients before taking immunosuppressive drugs. Sigmoid E(max) model was used to analyze the relationship between CsA concentration and IL-2 mRNA expression. The assay was completed within 8 h. The concentration that resulted in IC(50) showed high reproducibility and specificity among the healthy subjects (p<0.005, n=5). Ex vivo study indicated similar inhibition profiles to those of in vitro studies (n=3). The values of IC(50) obtained from patients (n=22) also showed large variations and were significantly lower than those from healthy subjects (p<0.05). Semi-quantitative RT-PCR was considered to be a rapid and reliable assay. Our data imply that measurement of IL-2 mRNA levels in whole blood could be valuable in monitoring CsA PD in transplant patients.

Incidence of parathyroid glands located in thymus in patients with renal hyperparathyroidism.

BACKGROUND: Parathyroid glands are frequently located in thymus, and it is essential to resect thymic tissue from the neck incision, especially in surgery for renal hyperparathyroidism (HPT). METHODS: In this study, we evaluated the incidence, location, and type of intrathymic parathyroid glands in 902 patients who underwent initial parathyroidectomy (PTx) for advanced renal HPT in our department. Removal of the thymic tongues on both sides was routinely performed from the neck incision, and the thymic tissue was carefully examined both macroscopically and microscopically. RESULTS: Of the 902 patients in the study, 269 had only inferior parathyroid glands in the thymus, in 62 patients only supernumerary glands were found in the thymic tongue, and in 78 patients both inferior and supernumerary glands were present in thymic tissue. Therefore the incidence of patients with intrathymic glands was 45.3% (269 + 62 + 78 = 409/902). In 129 (92.1%) of 140 patients with supernumerary glands in the thymic tongue, these glands were detected only on histopathological examination, and about half of them were classified as the parathyromatosis type. CONCLUSIONS: In the human, parathyroid glands might be located in the thymus in about 50%. If the inferior gland/glands cannot be found around the inferior pole of thyroid lobe, it is very important to search for glands in the thymic tongue. Moreover, to avoid missing supernumerary glands, removal of the thymic tongue on both sides is essential in surgery for renal HPT.

Enzyme-linked immunosorbent assay for human leukocyte antigen antibody detection and urine protein test recommended for follow-up monitoring after renal transplantation.

BACKGROUND: Although the usefulness of posttransplant human leukocyte antigen (HLA) antibody monitoring has been demonstrated, detailed recommendations have not been worked out in its frequency, the type of patients and methods to be used. Enzyme-linked immunosorbent assay is a simple and cost-efficient assay. The urine protein test that reflects renal dysfunction is performed everywhere. We assessed the clinical value of HLA antibody and urine protein monitoring after renal transplantation. METHODS: Serum samples were consecutively collected from outpatients (n=323) in 2004 and in 2006. Because 18 had graft failure and 8 died with functioning graft for 2 years, 297 paired sera were tested for HLA antibody using enzyme-linked immunosorbent assay. Urine protein was determined to be positive when the dipstick protein reaction was+/-or over (20 mg/dL). RESULTS: Total 297 patients were divided according to the change of HLA antibody status. Only patients with all of (i) de novo HLA antibody production, (ii) continuous detection from peripheral blood, and (iii) positive urine protein test had a significantly higher serum creatinine than the others and demonstrated rapid deterioration of Cr (DeltaCr 1.26 mg/dL during 2 years). Negative change of HLA antibody stopped the increase of serum creatinine. CONCLUSION: The status of HLA antibody and urine protein provides useful information on graft prognosis. Although the tempo of graft injury is relatively slow, a yearly routine HLA antibody test for all patients and the attempt to reduce HLA antibody to negative levels is recommended, when HLA antibody is newly detected and urine protein test is positive.