The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation.

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.

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.

A Case Report of Successful Kidney Transplantation in a Patient With Chronic Myelogenous Leukemia (CML) Who Has Been in Remission for 15 Years on Imatinib.

For chronic myeloid leukemia (CML), a Philadelphia chromosome-positive myeloproliferative neoplasm, the introduction of tyrosine kinase inhibitors has transformed CML from a lethal disease into a manageable chronic disease with a close-to-normal life expectancy. Active malignancy is an absolute contraindication to kidney transplantation. However, it is controversial whether kidney transplantation can be safely performed in patients with a history of CML who are in remission. We describe the clinical course of a 64-year-old male patient with chronic kidney disease from diabetic nephropathy (DMN) who underwent living donor kidney transplantation. The patient was diagnosed with CML 15 years ago and promptly achieved cytogenetic and molecular biological remission after starting imatinib. After that, he continued imatinib treatment for 15 years and was in remission, but his chronic kidney disease from DMN gradually worsened. A preemptive living donor kidney transplant was performed in July 2020. Imatinib for CML was discontinued because the patient maintained deep molecular remission (DMR) of major molecular response for more than 15 years before kidney transplantation. After kidney transplantation, the transplanted kidney function remained good at approximate serum creatinine levels of 1.1 mg/dL without histopathologic rejection, and the 3 monthly BCR-ABL1 measurement results were negative and are in progress. Thus, he continues to maintain treatment-free remission status without imatinib for 26 months after renal transplantation. In conclusion, this result suggests that CML with long-lasting DMR on imatinib therapy can be considered an inactive malignancy and therefore a relative indication for kidney transplantation.

A Case Report of Successful Kidney Transplantation in a Patient With Autosomal Dominant Polycystic Kidney Disease Who Underwent Thoracic Endovascular Aortic Repair for Type B Aortic Dissection.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with several cardiovascular disorders, including aortic dissection, which preferentially occurs at the thoracic or abdominal level. Because there are few case reports describing surgical repair for aortic dissection followed by renal transplantation in patients with ADPKD, kidney transplantation performed after repair for aortic dissection remains challenging. CASE PRESENTATION: A 34-year-old Japanese man with end-stage renal disease secondary to ADPKD underwent thoracic endovascular aortic repair for complicated acute type B aortic dissection 12 months earlier. A contrast computed tomography scan before transplantation revealed an aortic dissection involving the descending aorta proximal to the common iliac arteries and confirmed multiple large bilateral renal cysts. After simultaneous right native nephrectomy, the patient underwent preemptive living-donor kidney transplantation obtained from his mother. Intraoperatively, we noted that dissection of the external iliac vessels was difficult because of dense adhesions. Arterial clamping was performed immediately below the bifurcation of the internal iliac artery to prevent further aortic dissection of the external iliac artery. After end-to-end anastomosis to the internal iliac artery was completed and the vascular clamp was released, the kidney began to produce urine immediately. CONCLUSION: This case suggests that kidney transplantation in patients undergoing endovascular aortic repair for aortic dissection can be performed by adequately applying a vascular clamp proximal to the internal iliac artery during vascular anastomosis.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection.

BACKGROUND: Aortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. CASE PRESENTATION: A 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. CONCLUSION: Patients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

Role of Early Serial Renal Transplant Allograft Protocol Biopsies in Living Kidney Transplantations.

PURPOSE: This study aimed to analyze the incidence of subclinical rejection (SCR) in kidney transplantation patients and risk factors associated with SCR. METHODS: We assessed 80 protocol biopsies taken within 2 years postoperatively in 41 adult patients who underwent living donor kidney transplantation between 2017 and 2020. All patients were on immunosuppressant therapy that included tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The prevalence of Banff Borderline classification at 3, 6, and 12 months after transplantation was 4%, 5%, and 8 %, respectively, whereas none of the biopsies met the Banff criteria for acute T cell-mediated rejection throughout the study period. Active antibody-mediated rejection (ABMR) was only present in 8% of patients at 3 months after transplantation and chronic active ABMR at 6, 12, and 24 months after transplantation was detected in 10%, 13%, and 11% of the patients, respectively. Subgroup analysis revealed that 50% of the 6 patients with preformed anti-donor specific antibodies (DSAs) developed clinical or subclinical active ABMR within 3 months after transplantation, followed by chronic active ABMR according to serial histologic assessment. Conversely, only a small proportion of patients (3%) without preformed DSAs exhibited clinically active ABMR. CONCLUSIONS: SCR occurs too infrequently in patients with low immunologic risk and strong contemporary immunosuppression therapy to justify the diagnostic effort of serial protocol biopsies. However, protocol biopsies remain an indispensable tool in renal transplant monitoring and may be especially important in immunologically high-risk patients with pre-existing DSAs.

Does mirabegron deteriorate spermatogenesis? A lesson from spinal cord injury cases.

OBJECTIVES: To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. METHODS: Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. RESULTS: We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P < .05). CONCLUSIONS: From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

Clinicopathological analysis of acute vascular rejection cases after renal transplantation.

UNLABELLED: Histopathological change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathological analysis of AVR cases after renal transplantation (RTX). PATIENTS: AVR was diagnosed in 17 patients from 17 renal transplant patients followed in our institute between January 2003 and September 2008. We retrospectively reviewed these 17 patients. RESULTS: Among 17 cases of AVR, 10 cases were mild (v1 in Banff 07 classification), five were moderate (v2), and two were severe (v3). Interstitial inflammation (i1-i3) was present in all 17 biopsies. Moderate to severe tubulitis (t2-t3) was present in seven biopsies, and transplant glomerulitis (g1-g3) was present in 11, peritubular capillaritis (ptc1-ptc3) was in 15 of 17 biopsies. C4d deposition in peritubular capillary (PTC) was observed in 6 of 17 cases. By assaying with plastic beads coated with anti-human leukocyte antigen (HLA) antigen performed in 17 cases, the circulating ant-HLA alloantibody was detected in 10 patients, of which 5/10 were donor-specific antibodies (DSA). Acute antibody-mediated rejection (AAMR) was diagnosed in three cases. Many of v1 cases, steroid pulse therapy (SP) were effective. In v2 and v3 cases, six of seven were steroid-resistant rejection and were need more anti-rejection therapy (ART), such as muromonab CD3 (OKT3) injection, gusperimus (DSG) injection, plasmapheresis, intravenous immune globulin, and injection of rituximab. Ten of 17 patients recovered their renal allograft functions by ART, and 16 of 17 patients' grafts are functioning. Deterioration of renal allografts' function after biopsies was seen in seven patients with one of them lost their graft. CONCLUSIONS: In some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good in present immunosuppression and ART.

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.

Identification of a highly conserved region in the human cytomegalovirus glycoprotein H gene and design of molecular diagnostic methods targeting the region.

Genomic polymorphism of human cytomegalovirus (HCMV) leads to difficulties in the design of molecular diagnostic systems; therefore, a suitable target region was determined in the glycoprotein H (gH) gene, which has been reported to be the most conserved gene. A highly conserved region was identified from codon 1,282 to 1,988 of the gH gene by alignment of 23 nucleotide sequences (14 registered in the DNA Data Bank of Japan and 9 sequenced in this laboratory). Diagnostic methods based on nested PCR, real-time PCR and loop-mediated isothermal temperature amplification (LAMP) were designed for this region. Primers and a probe for nested and real-time PCR were designed for the completely conserved sequences in all HCMV strains. However, a few mismatched nucleotides could not be excluded from the LAMP primers due to the need for eight primer-binding sites in a 200bp-region. The sensitivities of the nested PCR, real-time PCR and LAMP reactions were 5, 10 and 100 copies/tube, respectively. An analysis of clinical specimens showed that both nested and real-time PCR detected HCMV with greater sensitivity than did a pp65 antigenemia assay and were expected to minimize the incidence of false-negative results, whereas the sensitivity of the LAMP reaction was comparable with that of the antigenemia assay.

Pyoderma gangrenosum after radical prostatectomy: case report.

Pyoderma gangrenosum (PG) is a skin disease characterized by an unknown neutrophilic infiltration in dermis and a nonbacterial destructive ulcer. Post-operative PG is an extremely rare type that occurs around surgical sites during the immediate post-operative period. It is usually diagnosed as surgical site infection at the time of presentation. The condition rapidly worsens despite antibiotic treatment and debridement. We report on a case of post-operative PG in a 64-year-old man after radical prostatectomy. Following the operation, redness and pus from surgical site rapidly progress although repeated antibiotic therapy and debridement were performed. Although the patient received appropriate debridement and broad-spectrum antibiotic treatment, the ulcerative lesion spread surrounding drain region and the condition of the skin region deteriorated. The diagnosis of PG was made by a skin biopsy that presented only neutrophilic invasion in the dermis without vasculitis, tumor, or malignancy. Finally, the patient died of lesion progression in whole body and multiple organ dysfunction. Considering PG along with ulcers, wounds, and post-operative complications is critical for prompt diagnosis and proper treatment.

Association of the outcome of renal transplantation with antibody response to cytomegalovirus strain-specific glycoprotein H epitopes.

BACKGROUND: Cytomegalovirus (CMV) is the most important pathogen affecting the outcome of renal transplantation. The combination of CMV-seronegative transplant recipients with CMV-seropositive transplant donors places recipients at the highest risk of CMV disease. In cases of congenital CMV infection, existing immunity only partially protected mothers from reinfection with a different genotypic strain. The effect of differences in infected CMV strains between CMV-seropositive transplant donors and CMV seropositive transplant recipients on the outcome of transplantation remains unclear. METHODS: In this prospective multicenter study, the presence of antibodies against strain-specific glycoprotein H epitopes in 84 CMV-seropositive transplant donor/CMV-seropositive transplant recipient renal transplantation cases were determined, and their relationships to acute transplant rejection, CMV infection, degree of antigenemia, and CMV disease were evaluated. RESULTS: Among the 84 donor/recipient pairs, 45 and 32 had matched and mismatched strain-specific glycoprotein H antibodies, respectively. Acute transplant rejection in the mismatched group was more frequent than it was in the matched group (63% vs. 22%; P=.005). CMV disease was also more frequently observed in the mismatched group (28% vs. 9%; P=.026). The mismatched group had a higher level of antigenemia (P=.019). CONCLUSIONS: Our results illustrate more adverse events in the cases with a CMV-seropositive transplant donor and a CMV-seropositive transplant recipient in which the glycoprotein H antibodies are mismatched, suggesting that reinfection with a different CMV strain results in more complications.

Lack of correlation between results of ABO-incompatible living kidney transplantation and anti-ABO blood type antibody titers under our current immunosuppression.

In this study, we examined the impact of preoperative anti-A/B antibody titers on the results of ABO-incompatible living kidney transplantation (LKT). In all, 167 recipients underwent ABO-incompatible LKT at our institution between 1989 and 2002. These patients were subdivided into those transplanted under cyclosporine with azathioprine or mizoribine (Group 1, n=78) and those transplanted under tacrolimus or mycophenolate mofetil (Group 2, n=89). Overall patient survival at 5 and 10 years was 93.8% and 88.0%, respectively. Overall graft survival at 5 and 10 years was 76.9% and 55.9%, respectively. Graft survival in the patients with anti-A/B IgG titers over 1:128 was significantly lower in group 1, whereas no significant correlation between the anti-A/B IgG titers and graft survival was found in group 2. In conclusion, no correlation between anti-A/B antibody titers and the results of ABO-incompatible LKT was seen after tacrolimus or mycophenolate mofetil application.

Mycophenolate mofetil suppresses the production of anti-blood type anitbodies after renal transplantation across the abo blood barrier: ELISA to detect humoral activity.

BACKGROUND: The introduction of novel immunosuppressive drugs has made it possible to achieve dramatic improvement in graft survival rates. In particular, the current immunosuppressive regimen including mycophenolate mofetil (MMF) has yielded excellent results including a nearly 100% 1-year graft survival rate at our institution in 2001. We used enzyme-linked immunosorbent assay (ELISA) to analyze humoral activity after ABO-mismatched renal transplantation using the MMF regimen. METHODS: The patient received an ABO-mismatched graft from a living related sibling. Preoperatively, he underwent plasma exchange (PEX) and double-filtration plasmapheresis (DFPP) several times to remove anti-blood type antibodies. Mycophenolate mofetil was used as one of the induction regimens, but a switch was made to other drugs because of persistent gastrointestinal tract discomfort. Mycophenolate mofetil was restarted, however, because of graft dysfunction caused by severe humoral rejection. Humoral activity in this patient was investigated by ELISA during the postoperative follow-up. RESULTS: Anti-blood type antibody immunoglobulin (Ig) M and IgG decreased immediately before the operation because of repeated PEX and DFPP. Both IgM and IgG were postoperatively stable and graft function was excellent. However, after switching from MMF to mizoribine (MZ), renal graft function gradually deteriorated, and the deterioration was associated with elevation of anti-blood type antibody, predominantly IgG. IgM antibody production was parallel to that of IgG, but was weaker. The elevated activity of anti-blood type antibody IgG decreased to the normal level as renal function recovered after MMF was restarted. CONCLUSIONS: Anti-blood type antibody IgG decreased after the administration of MMF after ABO-mismatched renal transplantation, and it increased after withdrawal of MMF. MMF seems to affect B-cell populations that produce anti-blood type antibodies after renal transplantation across the blood barrier.

Use of candesartan cilexetil decreases proteinuria in renal transplant patients with chronic allograft dysfunction.

BACKGROUND: Posttransplant proteinuria and hypertension are difficult to treat after renal transplantation. Therefore, we examined whether candesartan cilexetil is effective in reducing urinary protein excretion or in controlling hypertension in patients with renal allograft dysfunction. METHODS: Sixty-two renal transplant recipients with proteinuria were enrolled in this study. They underwent kidney transplantation under cyclosporine or tacrolimus immunosuppression between February 1983 and December 1998. Causes of proteinuria were chronic rejection in 28, glomerulonephritis in 16, cyclosporine or tacrolimus nephrotoxicity in 9, and unknown in 9 recipients. The dose of candesartan cilexetil ranged from 4 to 12 mg/day. Eleven patients with proteinuria who had not been treated with candesartan cilexetil constituted a matched control population. RESULTS: Hypertension was well controlled by administration of candesartan cilexetil. Both systolic blood pressure and diastolic blood pressure significantly decreased from 141.7+/-14.8 mm Hg to 118.7+/-11.9 mm Hg and 121.2+/-11.6 mm Hg, and from 89.0+/-13.0 mm Hg to 72.0+/-10.4 mm Hg and 74.9+/-9.4 mm Hg, at 2 months and 1 year after administration, respectively. Urinary protein excretion was reduced from 0.93+/-1.2 g/day to 0.34+/-0.7 g/day and 0.43+/-1.2 g/day at 2 months and 1 year after administration, respectively. The levels of creatinine clearance were 55.7+/-28.9 mL/min before treatment, 50.9+/-24.8 mL/min at 2 months, and 52.6+/-24.8 mL/min at 1 year after treatment, respectively. There was no clinically significant difference between them. Regarding the calcineurin inhibitor levels, there was no significant difference between the levels before and 1 year after treatment. There was a significant difference in all examinations (systolic blood pressure, diastolic blood pressure, proteinuria, and renal function) between the patients with and without candesartan at 1 year after treatment. No significant adverse effects occurred. CONCLUSIONS: Candesartan cilexetil can effectively control hypertension and proteinuria without deterioration in renal allograft function. These data suggest that treatment with candesartan cilexetil may be useful for maintaining long-term renal allograft function.

Successful renovascular reconstruction for renal allografts with multiple renal arteries.

BACKGROUND: Kidney grafts with multiple renal arteries have been considered a relative contraindication because of the increased risk of complications. In the present study, we retrospectively reviewed multiple renal artery reconstruction in kidney transplantation to elucidate the usefulness of these grafts. METHODS: From January 1997 until August 2001, 431 recipients underwent kidney transplantation at our institution; 393 patients are reviewed. The surgical techniques of vascular reconstruction and short-term outcome are reported. The living kidney transplant recipients were divided into vascular reconstructed and nonreconstructed groups, and mean serum creatine levels, warm and total ischemic times, and incidences of acute rejection and posttransplantation hypertension were compared. RESULTS: We noted multiple renal arteries in 96 (24.4%) of the 393 grafts. Arterial reconstruction was performed on 53 (13.5%) grafts, whereas 43 (10.9%) small polar arteries were simply ligated. Surgical management of the multiple arteries was variable. The most common reconstruction was conjoined anastomosis (17 cases) between two arteries of equal size and end-to-side anastomosis (14 cases) of smaller arteries to larger arteries. In nine cases, autogenous hypogastric or epigastric artery grafts were used to reconstruct multiple renal arteries. Multiple anastomosis was performed in six cases. In seven cases, complicated surgical vascular reconstruction was performed. The mean total ischemic times in the reconstructed and nonreconstructed groups were 102.6 and 71.0 min, respectively (P<0.01). The incidences of posttransplantation hypertension in the reconstructed and nonreconstructed groups were 68.2% (30/44) and 48.6% (141/290), respectively (P<0.05). There was no significant difference between the reconstructed and nonreconstructed groups in mean warm ischemic times, mean creatinine levels, and incidences of acute rejection. CONCLUSIONS: Allografts with multiple renal arteries can be used successfully in kidney transplantation.

Effect of post-transplant double filtration plasmapheresis on recurrent focal and segmental glomerulosclerosis in renal transplant recipients.

In the present study, we reviewed the effect of post-transplant double filtration plasmapheresis (DFPP) on recurrent focal segmental glomerulosclerosis (FSGS) in the transplanted kidney allograft. Sixteen patients with post-transplant recurrent FSGS were enrolled in this study. Out of 16 patients with recurrent FSGS after transplantation, five did not receive DFPP and lost their grafts, while 11 did receive DFPP and four of these patients lost their grafts. Seven patients were able to maintain normal renal function for an average observation period of 57.1 +/- 40.7 months (range 7-125 months). In five patients who had a significant reduction in urinary protein after DFPP, the urinary protein level decreased from 26.60 +/- 23.05 g/day (range 3.34-62.6 g/day) to 2.95 +/- 3.42 g/day (range 0.02-8.64 g/day) and renal function was maintained. The beneficial effects of DFPP on graft outcome were more likely to occur if the patients experienced a marked drop in urinary excretion. Thus, post-transplant DFPP appears to be effective for reducing urinary protein levels and improving long-term graft survival. With the small numbers in this trial, however, none of the findings were statistically significant. We recommend the use of post-transplant DFPP to prevent the progression of recurrent FSGS.

[Treatment of bone disease in chronic kidney disease and in renal transplant recipients under K/DOQI clinical practice guidelines].

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) provides evidence based clinical practice guidelines developed for all phases of kidney disease and related complications, from diagnosis to monitoring and management. Bone disease sets in during the early stages of Chronic Kidney Disease (CKD). Bone disease is observed in almost patients with chronic renal failure and after renal transplantation. Hyperparathyroid (high turnover) bone disease in patients with chronic renal failure is found most frequently followed by mixed osteodystrophy, low-turn over bone disease, and osteomalasia. Ninety to one hundred percent of kidney transplant patients have histological evidence of osteodystrophy and osteopenia (reduction of bone mass) following renal transplantation. Furthermore, osteoporosis is also appeared in many renal transplant recipients. After renal transplantation, renal osteodystrophy generally improves but bone mineral density (BMD) often worsens. When renal bone disease is assessed using a combination of biochemical markers, histology and bone densitometry, early intervention and carefully effective therapies might be reduced the morbidity associated with these common problems.