Comparative Analysis of Real-World Efficacy and Safety of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Kidney Transplant Recipients Versus Nontransplant Individuals: A Single-Center Study.

OBJECTIVES: To compare the efficacy and safety of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHis), a novel agent for management of anemia in chronic kidney disease (CKD), between transplant recipients and nontransplant individuals. METHODS: A retrospective analysis was conducted on nondialysis-dependent CKD stage 3 to 5 patients treated with the HIF-PHi roxadustat or daprodustat at a single institution. Patients were categorized as kidney transplant recipients (KTRs) and non-KTRs. Efficacy outcomes (hemoglobin and creatinine levels) and safety profiles (rate of adverse events [AEs], descriptions, and discontinuations due to AEs) were assessed 3 months before and 6 months after HIF-PHi initiation within and then between the groups. RESULTS: The study comprised 82 patients (KTR: 43, non-KTR: 39). Median ages significantly differed between the KTR (52.7 years) and non-KTR (82.9 years) groups (P < .001). Roxadustat was predominantly used in the KTR group (88.4%), while daprodustat was used in the non-KTR group (94.9%, P < .001). Both groups exhibited significant increases in Hb levels at 1, 3, and 6 months post-HIF-PHi initiation (P for trend, <.001), with a relative increase in Hb level at 6 months of 16% for KTRs and 13% for non-KTRs. Creatinine levels showed no significant changes over 6 months. Although no difference was observed in drug discontinuation due to AEs, the KTR group experienced a significantly higher rate of thrombotic events (18.6 vs 2.6%, P = .049). CONCLUSIONS: HIF-PHis demonstrate comparable efficacy for managing anemia in CKD, regardless of transplant status. However, heightened vigilance for thrombosis events is necessary during follow-up for KTRs.

Case Report: Suspected Hyperacute Rejection During Living Kidney Transplantation.

BACKGROUND: We report a case of suspected hyperacute rejection during living kidney transplantation. CASE REPORT: A 61-year-old man underwent kidney transplantation in November 2019. Before the transplantation, immunologic tests revealed the presence of anti-HLA antibodies but not donor-specific HLA antibodies. The patient was intravenously administered 500 mg of methylprednisolone (MP) and basiliximab before perioperative blood flow reperfusion. After blood flow restoration, the transplanted kidney turned bright red and then blue. Hyperacute rejection was suspected. After the intravenous administration of 500 mg of MP and 30 g of intravenous immunoglobulin, the transplanted kidney gradually changed from blue to bright red. The initial postoperative urine output was good. On the 22nd day after the renal transplantation, the patient was discharged with a serum creatinine level of 2.38 mg/dL, and the function of the transplanted kidney gradually improved. CONCLUSIONS: In this study, non-HLA antibodies may have been a cause of the hyperacute rejection, which was managed with additional perioperative therapies.

A case of novel coronavirus disease after combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma.

INTRODUCTION: We present a case of novel coronavirus disease-2019 that underwent combination therapy with nivolumab and ipilimumab for metastatic renal cell carcinoma. CASE PRESENTATION: A 50-year-old man complained of anorexia and weight loss. Contrast-enhanced computed tomography revealed a solid mass of 57 mm in diameter with cysts in the right kidney, along with liver, lung, and multiple bone metastases. Computed tomography-guided biopsy of the right kidney was performed, and a diagnosis of clear cell renal cell carcinoma was made. Three weeks after nivolumab and ipilimumab administration, the patient contracted coronavirus disease-2019. Anticoagulation therapy (dalteparin) was administered for 4 days once infection was confirmed, after which dexamethasone was administered for 10 days. The patient survived without experiencing worsened respiratory symptoms. CONCLUSION: We administered nivolumab and ipilimumab combination therapy as treatment for metastatic renal cell carcinoma. No side effects or immune-related adverse events were observed for a short time.

Case Report of COVID-19 Infection After Kidney Transplant Treated With Casirivimab-Imdevimab and Mycophenolate Mofetil Changed to Everolimus.

BACKGROUND: Casirivimab-imdevimab is a cocktail of 2 monoclonal antibodies designed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Casirivimab-imdevimab has been approved in Japan for treating mild to moderate COVID-19; however, to our knowledge, there are no reports of its use after kidney transplant from a live donor. Everolimus, an antineoplastic chemotherapy drug, is expected to be effective in inhibiting the spread of SARS-CoV-2 and preventing its replication, which may facilitate treatment. Here, we report a case of COVID-19 infection after kidney transplant that was initially treated with casirivimab-imdevimab and mycophenolate mofetil but was later changed to everolimus. CASE REPORT: A 47-year-old man underwent living donor kidney transplant from his mother in 2017. Immunosuppression therapy was underway through the administration of tacrolimus, mycophenolate mofetil, and methylprednisolone. In early September 2021, he was diagnosed as having COVID-19 and was hospitalized on day 3. On hospitalization, mycophenolate mofetil was discontinued and casirivimab-imdevimab and heparin were started. The patient started an everolimus regimen on day 5. The clinical course was successful without rejection. There was no exacerbation of COVID-19; the patient's serum creatinine levels and renal function had otherwise remained stable. CONCLUSIONS: We could safely treat a patient with casirivimab-imdevimab after kidney transplant. It is suggested that casirivimab-imdevimab can prevent COVID-19 from becoming severe and can be administered without worsening renal function. In addition, everolimus may have inhibited the spread of the virus and prevented it from replicating.

Japanese Single-Center Experience of Kidney Transplant: Experience in a Japanese Private Hospital.

BACKGROUND: We reviewed the results of cases of kidney transplant (KTx) that were conducted at the Toda Chuo General Hospital, a private hospital located in Saitama, Japan. METHODS: A total of 312 patients with end-stage renal failure underwent KTx between January 1992 and December 2019 at Toda Chuo General Hospital. There were 191 men and 121 women. Their mean age was 45.7 years. Of the 312 cases, 310 were living-related KTx, while 2 were deceased donor KTx. The immunosuppressive treatment protocol mainly consisted of 4-drug therapy with methylprednisolone, tacrolimus, mycophenolate mofetil, and basiliximab. RESULTS: Patient survival was 99.7% at 1 year, 99.3% at 5 years, and 97.3% at 10 years. Renal allograft survival was 98.4% at 1 year, 91.7% at 5 years, and 86.5% at 10 years. However, death-censored renal allograft survival was 98.7% at 1 year, 92.4% at 5 years, and 89.0% at 10 years. Among the 312 patients, 33 grafts were lost during the observation period. The loss was because of chronic antibody-mediated rejection in 19 patients, death with function in 6 patients, and acute antibody-mediated rejection in 2 patients. CONCLUSIONS: The prognosis of patients and their grafts, which were managed following the immunosuppression protocol at our institute, was relatively good. KTx in a private hospital in Japan is at par with the global standard.

Two Laparotomy Surgeries to Achieve Hemostasis After Kidney Transplantation in a Patient With Frailty: A Case Report.

BACKGROUND: The assessment of frailty before and after kidney transplantation is becoming more important in the aging population. It is recommended to recognize the post-transplant risks and establish a treatment strategy. We report the case of a patient who underwent 2 laparotomy hemostasis procedures due to frailty after kidney transplantation. CASE REPORT: A 72-year-old woman presented with end-stage renal failure due to an unknown primary disease. She was also found to be frail when assessed using the physical frailty phenotype. She underwent ABO-incompatible kidney transplantation from her husband at the end of March 2020. On the first postoperative day, re-operation for hematoma evacuation was performed. The bleeding point could not be identified at that time. Progression of anemia was observed on the sixth postoperative day, and computed tomography showed no obvious bleeding. Subsequently, the renal allograft started functioning immediately, without rejection. However, emergency laparotomy for hematoma removal was performed on the 22nd postoperative day. Bleeding had occurred from the anastomotic region of the renal allograft artery and the external iliac artery. Her serum creatinine levels and renal function remained stable one month after surgery. CONCLUSIONS: We encountered a case of living-donor kidney transplantation in a frail older woman who underwent 2 laparotomies due to hemorrhage. Perioperative risk management is necessary for patients with a high risk of postoperative bleeding. To ensure a good outcome, preoperative and postoperative rehabilitation is important for patients with frailty.

Suspected Pneumonia Caused by Coronavirus Disease 2019 After Kidney Transplantation: A Case Report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection. Patients might carry infection even though RT-PCR results are negative. CASE REPORT: A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit-glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days, and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted, and mycophenolate mofetil was discontinued. Anticoagulants were administered on the third day of hospitalization. Because of poor oxygenation, the patient was intubated in the intensive care unit on the fifth day, and sivelestat sodium was administered. The patient was extubated on the 12th day after improvement in oxygenation. There was no exacerbation, and CT showed improvements on day 51. CONCLUSION: We report a case of pneumonia with suspected COVID-19 infection 18 years after living donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken while considering the possibility of a positive result.

Allogeneic Kidney Transplantation After COVID-19: A Case Report.

BACKGROUND: Patients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection. CASE REPORT: A 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable. CONCLUSION: Living kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered.

Fluorescence In Situ Hybridization for the Origin of De Novo Renal Cell Carcinoma in a Kidney Allograft: A Case Report.

BACKGROUND: We present a rare case of de novo renal cell carcinoma that developed in an allograft kidney 14 years after transplantation. CASE REPORT: A 39-year-old man underwent living donor kidney transplantation from his mother. After 14 years, routine screening ultrasonography revealed a solid mass of 30-mm diameter in the kidney allograft. Partial nephrectomy was performed by clamping the renal artery under in situ cooling. Tissue histology revealed clear cell carcinoma with negative surgical margins. We explored the tumor's genetic origin using fluorescence in situ hybridization to analyze the X and Y chromosomes of the tumor cells. Postoperative hemodialysis was avoided, and the patient's serum creatinine level remained stable. CONCLUSIONS: Fluorescence in situ hybridization clearly indicated that the tumor originated from the donor and that the tumor vasculature originated from the recipient. The patient recovered well and remains without any tumor recurrence.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

A Prospective Randomized, Comparative Trial of High-Dose Mizoribine Versus Mycophenolate Mofetil in Combination With Tacrolimus and Basiliximab for Living Donor Renal Transplant: A Multicenter Trial.

OBJECTIVES: Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids. MATERIALS AND METHODS: We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses. RESULTS: During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group. CONCLUSIONS: High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Clinical and pathological analyses of interstitial fibrosis and tubular atrophy cases after kidney transplantation.

AIM: We carried out a clinicopathological analysis of cases presenting with interstitial fibrosis and tubular atrophy (IF/TA) after renal transplantation in an attempt to clarify the mechanisms underlying the development and prognostic significance of IF/TA. METHODS: IF/TA was diagnosed in 35 renal allograft biopsy specimens (BS) obtained from 35 renal transplant recipients under follow up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital, between January 2014 and March 2015. RESULTS: IF/TA was diagnosed at a median of 39.9 months after the transplantation. Among the 35 patients with IF/TA, 19 (54%) had a history of acute rejection. Among the 35 BS showing evidence of IF/TA, the IF/TA was grade I in 25, grade II in 9, and grade III in 1. Arteriosclerosis of the middle-sized arteries was observed in 30 BS (86%). We then classified the 35 BS showing evidence of IF/TA according to their overall histopathological features, as follows; IF/TA alone (6 BS; 17%), IF/TA + medullary ray injury (12 BS; 34%), and IF/TA + rejection (12 BS; 34%). Loss of the renal allograft occurred during the observation period in one of the patients (3%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 15 patients (43%). CONCLUSIONS: The results of our study suggests that rejection contributes to IF/TA in 30-40% of cases, medullary ray injury in 30-40% of cases, and nonspecific injury in 20% of cases. IF/TA contributes significantly to deterioration of renal allograft function.

Clinical and pathological analyses of chronic vascular rejection after kidney transplantation.

AIM: We discuss the clinicopathological analysis of cases of chronic vascular rejection (CVR) cases after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CVR. PATIENTS: CVR was diagnosed in 46 renal allograft biopsy specimens (BS) obtained from 34 renal transplant patients being followed up at the Department of Urology, Tokyo Women's Medical University, between January 2009 and December 2013. RESULTS: CVR was diagnosed at a median of 47.4 months post-transplant. Among the 36 patients, 23 had a history of acute rejection. Among the 46 BS showing evidence of CVR, the CVR was mild (cv1 in Banff's classification) in 23, moderate (cv2) in 17, and severe (cv3) in 6. Of the 40 samples obtained at the time of the biopsy and assayed with plastic beads coated with HLA antigen, 31 (78%) showed circulating ant-HLA alloantibody, and 15 (38%) showed donor-specific antibodies. We then classified the 46 BS showing evidence of CVR by their overall histopathological features, as follows; cv alone was seen in 16 (35%) BS, cv + antibody-mediated rejection (AMR) in 26 (56%), and cv + T-cell-mediated rejection in 9 (19%). Loss of the renal allograft occurred during the observation period in nine of the patients (26%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 11 patients (32%). CONCLUSION: The results of our study suggest that AMR may underlie CVR in many cases, while T cell-mediated rejection may play an important role in some cases.

Proliferative glomerulonephritis with monoclonal immunoglobulin A light-chain deposits in the renal allograft.

We herein describe the unique case of a 59-year-old man who underwent living kidney transplantation for IgA nephropathy (IgAN) and developed progressive kidney failure associated with the appearance of proliferative glomerulonephritis. An early protocol biopsy revealed recurrent IgAN with mesangial IgA2 deposits restricted to a single immunoglobulin λ light-chain isotype. Despite treatment with tonsillectomy and rituximab, the patient eventually lost his allograft 31 months after transplantation. Serum electrophoresis showed a monoclonal IgA pattern. This case might share common pathological characteristics with the newly described entity referred to as proliferative glomerulonephritis with monoclonal IgG deposits.

Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation.

BACKGROUND: Mizoribine (MZR) was approved in 1984 in Japan for the suppression of rejection in renal transplantation with an approved administration dosage of 1-3 mg/kg/day. The action of MZR resembles that of mycophenolate mofetil (MMF), but MZR dosing is markedly lower than that of MMF. To examine whether higher dosing of MZR could obtain efficacy similar to MMF in renal transplantation, we conducted a comparative study of MZR and MMF using a high daily dose of MZR. METHODS: A prospective, randomized comparative study of MZR versus MMF using tacrolimus (FK) and steroids as the base was conducted in 35 patients who had undergone living-donor renal transplantation (ABO-incompatible patients were not included) at 8 institutions in Japan between July 2005 and June 2007. Starting doses were 12 mg/kg/day for MZR and 2 g/day for MMF. Dosages of FK and steroids were set according to the protocol of each institution. RESULTS: Patient and graft survival rate at 1 year after transplantation was 100 % in each group, with no significant difference in rejection rate apparent between groups. Adverse events found in both groups were characteristic, frequently involving infection and digestive organ disorder in the MMF group and elevated uric acid levels in the MZR group. CONCLUSIONS: Based on these results, MZR and MMF are considered almost equivalent in terms of efficacy and safety.

Decrease of blood type antigenicity over the long-term after ABO-incompatible kidney transplantation.

BACKGROUND: Few studies have investigated the changes in the antigenicities of the transplanted organs after transplantation. METHODS: We examined, by immunohistochemical assay, the changes in expression of the blood-type antigens on the transplanted kidneys over the long-term after ABO-incompatible kidney transplantation with A- or B-antigen incompatibility (blood type A to B and B to A). The subjects were six patients, including one case with graft loss, who had received ABO-incompatible kidney allografts more than ten years previously. As normal controls, four cases of ABO-compatible transplantation during the same period, including two recipient/donor pairs each with blood group A1 and blood group B were enrolled. RESULTS: Expression of the blood-type A or B antigens decreased gradually to 91.8% during the first three months after transplantation, 85.8% during the first five years, 64.1% during the first ten years, and 57.6% over ten years after transplantation on average in ABO-incompatible transplant recipients. In one patient with graft loss due to severe antibody-mediated rejection, the donor's type B blood-type antigens on the transplanted graft had changed but partially to the recipient's blood-type A antigen by 2582days after the transplantation, suggestive of the occurrence of blood-type chimerism on the endothelium. In ABO-compatible transplant recipients, such changes in expression were not observed. The average percentage of blood-type antigen-positive vessels at more than ten years after the renal transplantation was 99.8%. CONCLUSIONS: Decrease in the expression of the donor's blood-type antigen on the endothelium of the graft has been considered as one of the mechanisms underlying the accommodation occurring over the long-term after ABO-incompatible kidney transplantation. On the other hand, establishment of antigenic chimerism on the graft endothelium could be one of the hallmarks of the immunological reaction associated with antibody-mediated rejection.

[Two cases of prostatic carcinoma causing a disorder of gastrointestinal transit due to rectal stenosis].

A 64-year-old man, was admitted to the Department of Gastroenterology at another hospital in October, 2005 because of constipation and urinary retention. Endoscopic and computed tomographic (CT) examinations of biopsy specimens obtained from the rectal mucous membrane which appeared to be thickened revealed evidence of proctitis but no evidence of malignancy. The patient was referred to our hospital because of a high prostate specific anyigen (PSA) level (74.17 ng/ml), and hydronephrosis accompanied with hydroureter at the right side. Biopsy specimens taken from a prostatic tumor through a transrectal route showed histological features consistent with anaplastic adenocarcinoma which was positively stained with PSA antibody. We treated the patient with maximium androgen blackade (MAB), resulting in a decrease in plasma PSA level and amelioration of constipation as well. A 77-year-old man, visited a hospital because of constipation and high plasma carcinoembryonic antigen and carbohydrate antigen (CA) 19-9 values in May, 2005, and was diagnosed as having hyperplastic mucous membrane and atypical glands of the rectum by means of a rectal biopsy. Having been referred to our hospital, the patient received a prostate biopsy, specimens of which revealed moderately differentiated adenocarcinoma with negative PSA staining. A pelvic evisceration was performed. The eviscerated samples showed no abnormality in the rectal mucous membrane but cancer with light PSA staining in the prostatic ducts. The hormone therapy was initiated in the patient under the diagnosis of anaplastic cancer in the prostate. Since the therapy for the invasion of prostatic cancer on the rectum differs markedly from that for a primary tumor in the rectum, it is very important to differentiate accurately the one from the other.

Association between antibody response against cytomegalovirus strain-specific glycoprotein H epitopes and HLA-DR.

The gH of CMV is a major target for strain-specific neutralizing antibodies. To verify whether there is a correlation between HLA-DR type and strain-specific antibodies, antibodies against CMV gH in potential donors and recipients for renal transplantation were investigated. Among 471 subjects, 404 (86%) showed reactivity to CMV gH, but no antibodies against gH were detected in 67 (14%) subjects. The positive rates were over 80% in most HLA subpopulations. Fewer subjects with HLA-DR10 and DR11 had antibodies to CMV gH than did those without HLA-DR10 and DR11. HLA-DR10 and DR11 may be associated with fewer/non-responders for strain-specific neutralizing antibodies.

Strain-specific seroepidemiology and reinfection of cytomegalovirus.

Although there have been some reports describing the serostatus of cytomegalovirus, strain-specific antibody responses and their distribution remain unknown. In this study, ELISA using fusion proteins encompassing epitope of glycoprotein H from both AD169 and Towne strains was used to test 352 blood donors. Of these 352 donors, 207 were analyzed for strain-specific glycoprotein H antibodies. Of the 44 donors whose serum contained antibodies against both AD169 and Towne, 27 (60%) were aged 50 years or over (p = 0.0003). This may indicate serological evidence of reinfection with cytomegalovirus in the elder population. The nucleotide sequence analysis of cytomegalovirus glycoprotein H from the peripheral blood of the cytomegalovirus-positive renal transplant recipients showed that our strain-specific ELISA can reveal cytomegalovirus reinfection after transplantation.

Immunological status in three patients, thirty years after living related renal transplantation: antibody production in long-term survivors.

There have been few studies of the immune status of long-term follow-up patients after living-donor kidney transplantation. We investigated the immune status from the immunologic and pathologic standpoint of three long surviving recipients who had received renal grafts more than 30 years earlier. Anti-HLA antibodies that had not been present before transplantation were detected in one recipient with three HLA mismatches. One recipient with identical HLA showed positive for the crossmatch test, but not for the panel reactive antibody test (PRA), thus showing that this patient had HLA antibodies against HLA minor histocompatibility antigens, etc. Only one patient with established microchimerism was stable without any antibody production. Pathologically, chronic allograft nephropathy with C4d staining suggestive of antibody-mediated rejection was observed in both patients with HLA antibodies. Physicians should clinically manage patients by always bearing in mind the presence of anti-donor antibodies during long-term regular follow-up of transplanted kidneys.