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Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have the potential to improve native kidney function. Objective This work aimed to elucidate the possible protective effects of GLP-1 RAs on kidney graft function after successful kidney transplantation (KTX). Methods This retrospective cohort study included all KTX recipients (KTRs) at our facility with type 2 diabetes who were followed up from 1 month post-transplantation for 24 months or longer as of December 31, 2020. We investigated associations between the use of GLP-1 RAs and other antidiabetic medications (non–GLP-1 RAs) and the risk of sustained estimated glomerular filtration rate (eGFR) reduction (40% reduction compared with baseline for 4 months) for KTRs with type 2 diabetes. We calculated the propensity score of initiating GLP-1 RAs compared with that of initiating non–GLP-1 RAs as a function of baseline covariates using logistic regression. The inverse probability of the treatment-weighted odds ratio was estimated to control for baseline confounding variables. Sodium-glucose cotransporter 2 inhibitor use was a competing event. The primary outcome was sustained eGFR reduction of at least 40% from baseline for 4 months post-transplantation. Results Seventy-three patients were GLP-1 RA users and 73 were non–GLP-1 RA users. Six patients and 1 patient in the non–GLP-1 RA and GLP-1 RA groups had sustained eGFR reduction. GLP-1 RA use after KTX was associated with a lower risk of sustained eGFR reduction. Conclusion GLP-1 RAs resulted in lower eGFR reduction compared with non–GLP-1 RAs and may contribute to better kidney graft survival after KTX.

Introduction Owing to organ shortage, the number of kidney transplantation (KT) involving older adult living donors is increasing. We aimed to investigate the effects of living-donor age and donor-recipient age differences on KT outcomes. Methods This single-center, retrospective cohort study involved 853 adult LDKTs performed between January 2008 and December 2018. Recipients were stratified into the following 5 groups based on donor age and donor-recipient age difference: donor age, 30 to 49 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, −10 to 15 years; donor age, 50 to 69 years and age difference, 15 to 40 years; donor age, 70 to 89 years and age difference, −10 to 15 years; and donor age, 70 to 89 years and age difference, 15 to 40 years (groups 1, 2, 3, 4, and 5, respectively). As a primary outcome, the risk of graft loss was investigated. The secondary outcomes were postoperative estimated glomerular filtration rates (eGFRs) and mortality rates of recipients. Results Group 4, representing KT between older adult donors and older adult recipients, had the highest graft loss risk and mortality. The eGFRs of the recipients from donors aged 70 to 89 years (groups 4 and 5) were significantly lower than those from donors in the other groups. Although the differences in the eGFR between groups 4 and 5 were not significant, the eGFR of group 4 was lower than that of group 5 at 6 months post-KT. Conclusion LDKTs from older adult donors to older adult recipients resulted in the worst graft survival and mortality rates.

Light chain deposition disease (LCDD) is a rare manifestation of monoclonal gammopathy, which can lead to renal failure. We previously reported a detailed recurrence process in a case of LCDD after renal transplantation. To the best of our knowledge, no report has described the long-term clinical course and renal pathology findings of recurrent LCDD in patients after renal transplantation. In this case report, we describe the long-term clinical presentation and changes in renal pathology of the same patient after early LCDD relapse in a renal allograft. A 54-year-old woman with recurrent immunoglobulin A λ-type LCDD in an allograft was admitted one year post-transplant for bortezomib plus dexamethasone therapy. At 2 years post-transplantation, a graft biopsy performed after complete remission was achieved, showing some glomeruli with residual nodular lesions similar to the pre-treatment renal biopsy findings. However, the enlarged subendothelial space disappeared. She remained in complete remission serologically for 6 years. Subsequently, the ratio of serum κ/λ-free light chains decreased gradually. She underwent a transplant biopsy approximately 12 years after renal transplantation due to increased proteinuria and decreased renal function. Compared with the previous graft biopsy, almost all glomeruli showed advanced nodule formation and subendothelial expansion. Because the LCDD case relapsed after long-term remission following renal transplantation, protocol biopsy monitoring might be necessary.

Aim Bacterial and fungal infections are serious, life-threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization. Methods This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety-five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8-10 months after kidney transplantation. Twenty-five patients developed candidiasis (Candida-onset group) and 497 did not (non-Candida-onset group). The follow-up periods were 67 (37-86) months in the Candida-onset group and 55 (34-89) months in the non-Candida-onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded. Results Severe infection developed in 9/25 (36%) patients in the Candida-onset group and in 77/497 (15%) patients in the non-Candida-onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06-6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12-2.93; p = .016) were significant predictors of subsequent severe infection. Conclusion Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over-immunosuppressive state, which should prompt evaluation of immunosuppression.

It is unknown whether cholecalciferol supplementation improves allograft outcomes in kidney transplant recipients (KTRs). We conducted a single‐center randomized, double‐blind, placebo‐controlled trial of daily 4000 IU cholecalciferol supplementation in KTRs at 1‐month posttransplant. The primary endpoint was the change in eGFR from baseline to 12‐month posttransplant. Secondary endpoints included severity of interstitial fibrosis and tubular atrophy (IFTA) at 12‐month posttransplant and changes in urinary biomarkers. Of 193 randomized patients, 180 participants completed the study. Changes in eGFR were 1.2 mL/min/1.73 m2 (95% CI; −0.7 to 3.1) in the cholecalciferol group and 1.8 mL/min/1.73 m2 (95% CI, −0.02 to 3.7) in the placebo group, with no significant between‐group difference (−0.7 mL/min/1.73 m2 [95% CI; −3.3 to 2.0], p = 0.63). Subgroup analyses showed detrimental effects of cholecalciferol in patients with eGFR, A randomized, double‐blind, placebo‐controlled trial shows that vitamin D supplementation fails to protect renal transplants, as assessed by estimated glomerular filtration rate and allograft histology.

The number of the patients with chronic kidney disease is now increasing in the world. The pathophysiology of renal hyperparathyroidism is closely associated with Klotho-FGF-endocrine axes, which must be solved definitively as early as possible. It was revealed that the expression of fgf23 is activated by calciprotein particles, which induces vascular ossification. And it is well known that phosphorus overload directly increases parathyroid hormone and hyperparathyroid bone disease develops in those subjects. On the other hand, low turnover bone disease is often recently. Both the patients with chronic kidney disease suffering from hyperparathyroid bone disease or low turnover bone disease are associated with increased fracture risk. Micropetrosis may be one of the causes of increased fracture risk in the subjects with low turnover bone disease. In this chapter, we now describe the diagnosis, pathophysiology and treatments of renal hyperparathyroidism.

OBJECTIVES Our aim was to investigate effects of surgery on living donors' body composition and clarify factors related to it. MATERIALS AND METHODS We evaluated preoperative computed tomography images of 335 living kidney donors (127 men, 209 women) to calculate 3 body composition parameters and changes with aging by sex: (1) skeletal muscle mass, quantified by skeletal muscle index; (2) fat distribution, calculated by visceral adipose tissue/subcutaneous adipose tissue ratio; and (3) muscle quality, quantified by intramuscular adipose tissue content. Thereafter, with pre- and postoperative computed tomography images from 75 living kidney donors (25 men, 50 women) after hand-assisted laparoscopic donor nephrectomy, we compared pre- and postoperative body composition changes. RESULTS Annual change in intramuscular adipose tissue content with age was 0.0049 in men and 0.0091 in women. Of 75 patients, 49 had lower quality of muscle, intramuscular adipose tissue content was significantly higher after nephrectomy (P < .001), and median change in intramuscular adipose tissue content was 0.061 (range, 0.018-0.11) in men and 0.052 (range, 0.017-0.18) in women. Univariate analysis revealed that skeletal mass index and visceral adipose tissue/subcutaneous adipose tissue ratio changes were significantly different between the intramuscular adipose tissue content improvement and deterioration groups. Multivariate analysis revealed skeletal mass index change was an independent factor for intramuscular adipose tissue content change (P = .0019). Intramuscular adipose tissue content change was negatively correlated with skeletal mass index change (r = -0.40). CONCLUSIONS Although muscle quality deteriorates after nephrectomy, maintaining muscle mass is important to retaining muscle quality.

Summary While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+CD127− regulatory T cells (edu.Tregs) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg; anti-A/B antibodies were not involved in the Treg-mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

BACKGROUND AND AIMS High-dose intravenous immunoglobulin (IVIG) therapy has not only immediate effects but also gradual effects via Fc receptors. To optimize IVIG therapy, we adopted a two-step desensitization protocol in kidney transplantation (KTx) with positive flow cytometry crossmatch (FCXM). METHOD In the first step, rituximab 200 mg and IVIG 2 g/kg were administered 2 months before KTx. In the second step, patients received additional rituximab 200 mg and IVIG 2g/kg for 2 weeks prior to transplantation in combination with plasmapheresis. RESULTS Of the six KTx with positive FCXM, there was no rejection except one (16.7%) subclinical antibody-mediated rejection within 1 month after transplantation. Average graft function was acceptable (serum creatinine level of 1.17 mg/dL). CONCLUSION The two-step desensitization protocol is an effective option for achieving successful transplant outcomes in KTx with positive FCXM, which can spare more aggressive and expensive treatments, such as C5 inhibitors, proteasome inhibitors and imlifidase.

Once-daily extended-release tacrolimus (TACER) is commonly administered following kidney transplantation (KTx); however, its optimal dosage remains unknown.In this multi-center, randomized controlled trial, 62 living donor KTx recipients were assigned to either standard-exposure (SE; n = 32) or low-exposure (LE; n = 30) TACER (Graceptor®, Astellas Pharm Inc.) groups. All patients received basiliximab and mycophenolate mofetil (MMF). The primary outcomes were acute rejection, graft/patient survival, and the secondary outcomes were incidence of cytomegalovirus infection, and de novo donor-specific antibodies (dnDSA) production.The tacrolimus trough level and estimated area under the blood concentration-time curve (eAUC) were significantly higher in SE than in LE (SE vs. LE; 1 year: 5.0 ± 0.9 ng/ml and 206.9 ± 26.8 ng h/ml vs. 3.4 ± 1.0 ng/ml and 153.9 ± 26.4 ng h/ml; 2 years: 4.8 ± 1.0 ng/ml and 204.9 ± 30.1 ng h/ml vs. 3.8 ± 0.9 ng/ml and 164.4 ± 27.0 ng h/ml). In contrast, the dosage and eAUC of MMF did not differ between groups. Two-year graft and patient survival rates were 100% in both groups, and acute rejection rates were 0% and 10% in the SE and LE, respectively (p = 0.11). The mean estimated glomerular filtration rates did not differ between the groups. Cytomegalovirus infection was slightly lower in the LE (SE: 12.5% and LE: 6.7%, p = 0.37). In the LE, four cases of dnDSA were noted within 2 years of transplantation; no case was observed in the SE (p = 0.034).Although the LE TACER regimen showed similar rates of acute rejection, as well as graft and patient survival compared with SE after KTx, LE was significantly more associated with dnDSA. Further investigation of its long-term effect on graft survival is warranted. (University Hospital Medical Information Network Clinical Trials Registry ID: UMIN000033089).

Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of -15%; 95% confidence interval [CI] -25 to -3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint

Introduction: Recent reports have described an increased risk of renal disease in living kidney donors compared with the general population. However, these reports do not detail the outcomes of medically complex living donors (MCLDs) with preoperative comorbidities (PCs), such as hypertension, dyslipidemia, glucose intolerance, and obesity. Analysis of living donors with end-stage renal disease (ESRD) has shown that these PCs may contribute significantly to the development of ESRD. We aimed to evaluate the effect of PCs on postoperative renal function and mortality in MCLDs. Methods: Between January 2008 and December 2016, 807 living-donor kidney transplants were performed in our unit. Of these, 802 donors completed postoperative follow-up of >5 months. Donors were stratified into 4 groups based on the number of PCs present: healthy living donors (HLDs) with no PCs (n = 214) or MCLDs with 1 PC (n = 302), 2 PCs (n = 196), or 3 PCs (n = 90) (denoted MCLD [PC 1], MCLD [PC 2], or MCLD [PC 3], respectively). We compared pathology observation data from baseline biopsy, postoperative estimated glomerular filtration rate (eGFR), postoperative urinary protein concentration, and mortality between HLD and MCLD groups. Results: Interstitial fibrosis, tubular atrophy, glomerulosclerosis, and arteriolosclerosis were more frequent in MCLDs (PC 3) than in HLDs. No significant differences were identified between HLDs and MCLDs in terms of postoperative eGFR and short-term mortality. Overt proteinuria and ESRD were not observed. Conclusions: Appropriate postdonation management of MCLDs with PCs may result in similar outcomes as for HLDs. Keywords: baseline biopsy, estimated glomerular filtration rate, kidney transplantation, medically complex living donor, preoperative comorbidities, proteinuria

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare variant of the classical anti-GBM antibody disease. Patients present with an undetectable anti-GBM antibody but show linear glomerular basement membrane staining for immunoglobulin. We present a 69-year-old man who underwent a living-donor kidney transplant. The aetiology of the renal failure was a focal segmental glomerulonephritis-like lesion resistant to immunosuppressive therapy. A renal graft biopsy revealed diffuse endocapillary hypercellularity, and mild mesangiolysis with linear GBM staining for IgG. The patient was diagnosed with atypical anti-GBM nephritis since the patient tested negative for circulating anti-GBM antibodies. Treatment involved intravenous methylprednisolone, plasma exchange, and rituximab administration. Protocol graft biopsy performed 1 year after the renal transplant showed a focal segmental glomerulonephritis-like lesion possibly progressing from endocapillary hypercellularity and mesangiolysis. These findings were similar to his native kidney biopsy findings. Although classical recurrent anti-GBM nephritis is rare when a renal transplant is performed after decreased disease activity, this case was considered as a case of recurrent atypical anti-GBM nephritis after renal transplant.

Introduction: Living kidney donation improves the lives of individuals with kidney failure; however, recent studies have suggested that living kidney donors may be at a relatively higher risk of reduced renal function than healthy non-donors. We therefore aimed to evaluate the clinical and pathological findings in living kidney donors who developed kidney disease. Methods: From January 1991 to May 2019, 1,625 live kidney donations were performed at our hospital. Among the donors, 7 developed kidney disease after donation and underwent open renal biopsy. We studied the clinical and pathological findings of these patients from their clinical records. Results: There were 3 patients with immunoglobulin A (IgA) nephropathy, 2 with membranous nephropathy, 1 with anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, and 1 with secondary focal segmental glomerulosclerosis (FSGS). All patients with IgA nephropathy had latent IgA deposition on their baseline biopsy. One patient with membranous nephropathy demonstrated findings of membranous nephropathy on the baseline biopsy, despite being asymptomatic. All patients, except for those with ANCA-associated nephropathy and secondary FSGS, recovered from the nephritis or maintained an adequate renal function after treatment. Discussion/Conclusion: Baseline biopsy is necessary for assessing the renal condition of kidney donors, and these donors require long-term follow-up based on their baseline biopsy findings. If donors develop kidney disease, appropriate diagnosis and treatment are essential.

The effect of parathyroidectomy (PTx) timing on serum calcium (Ca) levels and renal functions in renal transplant recipients with severe hyperparathyroidism (HPT) remains unclear. We retrospectively aimed to investigate and compare the clinical data of patients who underwent pre- and post-transplant PTx and elucidated the impact of PTx timing on serum Ca levels and renal graft outcomes after renal transplantation (RTx).During January 2000-December 2016, 53 and 55 patients underwent post-transplant PTx (Post-RTx group) and pretransplant PTx (Pre-RTx group), respectively. The serum Ca levels and estimated glomerular filtration rate (eGFR) were assessed in both groups.At the end of the follow-up, the serum Ca levels were significantly higher and the incidence of hypocalcemia was significantly lower in the Pre-RTx group than in the Post-RTx group [9.5 vs. 8.9 mg/dL, P 0.001; 14.5% vs. 34.0%, P = 0.024]. The decrease in the eGFR 12-36 months after RTx was more significant in the Post-RTx group than in the Pre-RTx group (-13.8% vs. -0.9%; P = 0.001). A logistic regression involving age, sex, dialysis period, and serum parathormone level revealed that post-transplant PTx is an independent risk factor for persistent hypocalcemia at the end of the follow-up (P = 0.034) and for a20% decrease in the eGFR 12-36 months after RTx (P = 0.029).In renal transplant candidates with severe HPT, pretransplant PTx should be considered to prevent persistent hypocalcemia and deterioration of the renal graft function.

Purpose We evaluated de novo donor-specific antibody (DSA) production of everolimus (EVR)-based immunosuppression for primary kidney transplant recipients involved in the A1202 study at our institute. Methods From March 2008 to August 2009, 24 recipients were prospectively randomized into 2 groups. The EVR group received reduced cyclosporin A and EVR. The standard protocol (STD) group received standard cyclosporin A and mycophenolate mofetil. Both groups received basiliximab and steroids. De novo DSA was identified using LABScreen single antigen beads (One Lambda, Canoga Park, Calif., United States). Mean fluorescence intensity (MFI) values > 1000 were considered positive. P Results Graft survival was 100% in the EVR group and 90.9% in the STD group. All patients remained on the primary protocol in the EVR group, but 3 patients in the STD group (27.3%) were converted to tacrolimus due to DSA and non-adherence. Estimated glomerular filtration rate was similar in both groups. No EVR group recipients and 9.1% of STD group recipients were treated for T-cell-mediated rejection. No recipients of the EVR group exhibited peritubular capillaritis, while 9.1% in STD group developed chronic active antibody-mediated rejection. LABScreen revealed an accumulative class II DSA production rate of 15.4% in the EVR group and 18.3% in the STD group at 10 years. When the MFI cut-off level was set to 6000, anti-HLA antibody and de novo DSA-free survival was significantly better in the EVR group. Conclusions EVR-based immunosuppression provided equivalent or even better clinical outcomes. EVR suppressed de novo DSA production at 10 years follow-up; however, further follow-up is inevitable.

Recently, in vitro experiments have demonstrated that anti-blood group A/B antibody binding to endothelial cells induce a protective effect against antibody-mediated injury. This study aimed to clarify the potential clinical benefit of ABO incompatibility in donor-specific HLA antibody (DSA)-induced chronic antibody-mediated rejection (ABMR). We enrolled 215 ABO-incompatible renal transplant (ABO-I) and 467 ABO-identical/compatible renal transplant recipients (ABO-Id/C). The prevalence of de novo DSA production and incidence of biopsy-proven chronic ABMR were compared between the two groups. The incidence of DR-associated de novo DSA was significantly lower in ABO-I than in ABO-Id/C (P = 0.028). Diagnostic biopsy for ABMR was conducted in 54 patients (11 ABO-I and 43 ABO-Id/C). Biopsy-proven chronic ABMR was lower in ABO-I than in ABO-Id/C (27.3% [3/11] vs. 44.2% [19/43]) patients. Our findings suggest that ABO incompatibility may cause low production of DR-associated de novo DSA, possibly resulting in a reduced incidence of chronic ABMR.

Background and Aims Although elderly living donors are recognized as a marginal donor for kidney transplantation, the number of elderly living donors are increasing because of insufficiency. We investigated the impact of donor age on living donor kidney transplantation. Method A total 858 adult living donor kidney transplantation (LDKT) between January 2008 and December 2018 was included in this study and followed up until September 2020. LDKTs were stratified into 3 groups according to the donor age; 157 LDKTs from donors aged 30 – 49, 592 LDKTs from donors aged 50 – 69, and 109 LDKTs from donors aged 70 – 89. To investigate the impact of donor age on living donors, postoperative estimated glomerular filtration rates (eGFR), mortality rate and incidence of end stage renal disease were compared between 3 donor age groups. To investigate the impact of donor age on recipients, postoperative eGFR was compared between 3 donor age groups and the risk factors of graft loss were analyzed using Cox regression hazard model. Results The eGFRs of donors demonstrated a decline with increased donor age and significant differences at all time points among 3 donor age groups. (Figure 1) Mortality rate and incidence of end stage renal disease of donors were similar among 3 donor age groups. (Figure 2) The eGFRs of recipients demonstrated a decline with increased donor age and significant differences at all time points among 3 donor age groups. (Figure 3) Multivariate analysis using Cox regression hazard model demonstrated donor aged 70 – 89 as a significant risk of graft loss (P = 0.024, hazard ratio 3.053, 95% confidence interval 1.160 – 8.040). Conclusion The prognosis of living donors after donation were not affected by the donor age except for the lower eGFR with increased donor age. The eGFRs of recipients and graft loss rates were the worst in the recipients transplanted from donors aged 70 – 89.

Antibody-mediated allograft rejection (AMR) hinders patient prognosis after organ transplantation. Current studies concerning AMR have mainly focused on the diagnostic value of immunoglobulin G (IgG)-type donor-specific antihuman leukocyte antigen antibodies (DSAs), primarily because of their antigen specificity, whereas the clinical significance of immunoglobulin M (IgM)-type DSAs has not been thoroughly investigated in the context of organ transplantation because of their nonspecificity against antigens. Although consensus regarding the clinical significance and role of IgM antibodies is not clear, as discussed in this review, recent findings strongly suggest that they also have a huge potential in novel diagnostic as well as therapeutic application for the prevention of AMR. Most serum IgM antibodies are known to comprise natural antibodies with low affinity toward antigens, and this is derived from B-1 cells (innate B cells). However, some of the serum IgM-type antibodies reportedly also produced by B-2 cells (conventional B cells). The latter are known to have a high affinity for donor-specific antigens. In this review, we initially discuss how IgM-type antibodies of different origins participate in the pathology of various diseases, directly or through cell surface receptors, complement activation, or cytokine production. Then, we discuss the clinical applicability of B-1 and B-2 cell-derived IgM-type antibodies for controlling AMR with reference to the involvement of IgM antibodies in various pathological conditions.

In living kidney transplantation, predicting the risk of end-stage kidney disease in the organ donors though crucial remains to be resolved. Thus, any useful biomarker to predict kidney outcome would be highly desirable to safeguard donors. This retrospective study was conducted at Nagoya Daini Red Cross Hospital to confirm whether an increase in preserved kidney volume (PKV) was a predict marker of proteinuria. A change of PKV before and 1 year after kidney donation was measured, and its association with proteinuria 3 years after the donation was analyzed. A total of 119 kidney donors who met the Japanese donor guideline were enrolled. The mean age was 57.4 years, 46.2% were male. The mean values of the variables before kidney donation (baseline) were: BMI levels: 23.4 kg/m2, BSA-adjusted PKV: 132.9 cm3/1.73 m2, and estimated glomerular filtration rate (eGFRave): 82.9 mL/min/1.73 m2. A positive correlation was noted between BSA-adjusted PKV and eGFRave (r = 0.61, p

Background and Aims Thrombotic microangiopathy (TMA) is characterized by mechanical hemolytic anemia, thrombocytopenia, and renal impairment. TMA that occurs in kidney transplant recipients has multiple etiologies and may be de novo or recurrent. Main causes of TMA among recipients are atypical hemolytic uremic syndrome (aHUS), immunosuppressive drugs, ischemia-reperfusion injury (IRI), viral infections, and antibody-mediated rejection (ABMR). Pathological findings of TMA with thrombosis in glomeruli and arterioles are not rare in graft biopsies, but the clinical signs vary widely by etiologies, and incidence and risk factors for each are uncertain. The purpose of this study is to clarify the current status of TMA after kidney transplantation. Method The subjects were 1,336 patients (5,425 biopsy specimens) who underwent kidney transplantation (851 ABO-compatible and 485 ABO-incompatible) at Japanese Red Cross Nagoya Daini Hospital and Masuko Memorial Hospital from January 1, 2000 to June 30, 2018. We investigated patient characteristics and graft survival in 69 patients with pathological findings of TMA (12 with symptomatic TMA and 57 with asymptomatic TMA) and 1,207 patients without findings of TMA. Sixty patients were excluded because of incomplete data or biopsy specimens. TMA patients with acute kidney injury (AKI) were defined as symptomatic TMA in this study. Results The incidence of post-transplant TMA was 5.2% (symptomatic TMA : 0.9%, asymptomatic TMA : 4.3%) in our cohort. Multivariate analysis revealed significant risk factors for TMA were presence of donor specific antibodies (DSA) and use of cyclosporine (odds ratio [OR] 3.52; 95% confidence interval [CI] 1.58-7.88; p=0.002 and OR 3.70; 95% CI 1.68-8.11; p=0.001, respectively). Causes of symptomatic TMA were ABMR : 66.7% (5 patients with ABO-incompatibility, 3 with preformed DSA), aHUS : 16.7%, cytomegalovirus and adenovirus infection : 8.3%, and causes of asymptomatic TMA were drug-induced: 40.4% (21 patients with calcineurin inhibitor, 2 with everolimus), ABMR: 31.6% (10 with ABO-incompatibility, 8 with de novo DSA), IRI : 14.0 %. Onset of post-transplant TMA was significantly associated with lower graft survival (Figure A), with a stronger correlation in symptomatic TMA than in asymptomatic TMA (Figure B and C). Conclusion TMA with AKI that occurred after kidney transplantation had a poor graft prognosis. Therefore, avoiding transplantation, changing donors or using tacrolimus instead of cyclosporine should be considered for patients with DSA or ABO-incompatibility.

Background and Aims Chronic antibody mediated rejection caused by de novo donor specific antibody (dnDSA) is one of the biggest reasons for graft failure. At present, because it is difficult to treat CAMR, prevention of de novo DSA production is important. We investigated the risk factor for dnDSA production in living donor kidney transplantation. Method 807 patients underwent living donor kidney transplantation between January 2008 and December 2016. 159 recipients were excluded because of preformed DSA (58 recipients), pediatric transplantation (35 recipients), pancreas transplantation after kidney transplantation (4 recipients), and insufficient data on DSA after transplantation (62 recipients). 648 recipients were enrolled in this study. In 84 out of 648 recipients, dnDSA were detected until December 2018. With cox regression analysis, the risk factors for de novo DSA production were investigated between dn DSA positive and negative groups. The impact of donor characteristics including age and sex, and recipient characteristics including age, sex, hemodialysis vintage, cold ischemic time, past history of transfusion, pregnancy, and transplantation, HLA mismatch, pre-operative Flow PRA results, ABO incompatibility, rituximab induction, splenectomy, pre-operative plasmapheresis, transplantation from first-degree relatives, conversion of calcineurin inhibitor (CNI), conversion of mycophenolate mofetil, mizoribin, and everolimus, CNI used for induction, induction with mycophenolate mofetil, mizoribin, and everolimus, CNI withdrawal, withdrawal of mycophenolate mofetil, mizoribin, and everolimus, and rejection within 6 months after transplantation were investigated. Results In the univariate analysis, male recipient, male donor, and CNI withdrawal were the significant risk factors (P=0.020, HR 1.795, 95%CI 1.095-2.942; P=0.027, HR 0.568, 95%CI 0.344-0.938; P Conclusion Calcineurin inhibitor withdrawal was the significant risk factor for de novo DSA production in living donor kidney transplantation