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Abstract Background Sodium polystyrene sulfonate (SPS) is a cation-exchange resin used to treat hyperkalemia. Although colorectal ulcers are known side effects of long-term SPS use, few studies have reported SPS-associated gastric ulcers. Herein, we report a case of repeated gastric ulcers during SPS administration. Case presentation The patient was a 55-year-old man who was on SPS treatment of hyperkalemia since the initiation of hemodialysis (HD) at the age of 51 years. At the age of 54 years, he started taking vonoprazan fumarate after developing a bleeding duodenal ulcer. The patient underwent laparoscopic pylorus-preserving gastrectomy for four recurrent bleeding gastric ulcers. The resected specimen showed an ulcerative lesion in the pyloric curvature of the stomach, and pathological findings showed deposition of a basophilic crystalline substance resembling a cation-exchange resin at the base of the ulcer. Conclusion In this case, various factors, including diabetic gastroenteropathy, use of multiple calcium channel blockers and phosphate binders, obesity, and lifestyle, contributed to decreased gastrointestinal peristalsis. This may have promoted SPS deposition in the stomach, potentially leading to ulceration.

Introduction Transplant renal vein thrombosis is a serious post‐transplant complication. We report a case in which a thrombus was found in the transplant renal vein and rescued the transplanted kidney utilizing interventional radiology. Case presentation A 56‐year‐old woman underwent ABO‐compatible living donor renal transplantation due to impaired renal function caused by IgA nephropathy. On postoperative Day 13, there was a finding on transplant renal echocardiography that appeared to be an interruption of peripheral renal blood flow in diastole. Contrast‐enhanced computed tomography revealed that the vein was occluded due to the hematoma, and thrombosis was observed within, and distal contrast showed regurgitation into the collateral vessels. The stenosis was breached and balloon dilation restored progressive blood flow through interventional radiology. Conclusion Although open surgical thrombectomy is mainly considered for treatment for transplant renal vein thrombosis, interventional radiology might be the alternative treatment option.

Abstract The humoral response of kidney transplant recipients (KTR) to the mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is generally poor. We evaluated the booster effect of the third dose (D3) of two SARS-CoV-2 mRNA vaccines 6 months after the second dose (D2) in Japanese KTR. The anti-spike (anti-S) antibody titer 1 and 3 months after the D3 was evaluated in 82 Japanese KTR. The primary endpoint was the seropositivity rate, and factors associated with the lack of a response were evaluated in a logistic regression model. Overall, the anti-S antibody seropositivity rate 1 and 3 months after the D3 was 74.7% and 76.0%. The anti-S antibody titers after the first and second doses were higher in patients vaccinated with the mRNA-1273 than with the BNT162b2 vaccine. Among the 38 KTR who were seronegative 5 months after the D2, 18 (47.4%) became seropositive following the D3. Factors associated with a non-response were mycophenolic acid dose, post-transplant duration, hemoglobin, and lymphocyte count. A humoral response 1 and 3 months after the D3 was obtained in ~ 75% of KTR, but 20% were non-responders. Additional studies are needed to clarify the factors hindering a vaccine response.

Controlling the immune response with only clinically approved immunosuppressant drugs is difficult in renal heterotransplantation from pigs to nonhuman primates. Moreover, to the best of our knowledge, no reports exist on the use of fetal pigs as kidney donors. This study aimed to compare the degree of transplant rejection between neonatal and fetal kidneys, with genetically unmodified pigs as donors and cynomolgus monkeys as recipients. The left kidneys of the recipient monkeys were removed, followed by transplantation of neonatal as well as fetal pig kidneys, which had undergone vascular anastomosis at the same site, into the retroperitoneum. Immunosuppression was performed with only US Food and Drug Administration-approved drugs. The fetal kidneys were transplanted into the omentum and para-aortic regions of cynomolgus monkeys. Consequently, the engraftment and development of the transplanted tissues were pathologically examined by sampling over time (twice in each experiment). An acute rejection was observed after a few weeks in neonatal renal grafts with vascular anastomosis. However, fetal pig kidneys were spared from rejection despite the administration of the same immunosuppressive protocol to the monkeys and the recipient blood vessels flowing into the fetal kidneys. The immunogenicity of fetal kidneys in pig–monkey renal heterotransplantation was lower than that of neonatal kidneys.

A 57-year-old man presented with multiple pulmonary nodules. Thoracoscopic lung biopsy led to a pathological diagnosis of pulmonary hyalinizing granuloma (PHG) at the age of 39 years. The disease was progressive, refractory to therapy, and necessitated home oxygen therapy 10 years after the diagnosis. Hyponatremia progressed gradually along with lung disease. His serum sodium level was 129 mEq/L but serum osmolality was normal (287 mOsm/kg). Concomitant hyperproteinemia (12.1 g/dL) was attributable to hyperglobulinemia. Direct ion-selective electrode measurement revealed a normal sodium level (137 mmol/L). We herein report a case of PHG characterized by pseudohyponatremia due to hyperproteinemia, an uncommon finding in this rare entity. A left lung transplant was successfully performed, and no pseudohyponatremia was observed. Pseudohyponatremia should be suspected and diagnosed to prevent a misdiagnosis that could lead to complications from inappropriate treatment with sodium supplementation or restriction of drinking water. The direct ion-selective electrode measurement was useful for diagnosing pseudohyponatremia.

The ventromedial hypothalamus regulates systemic glucose metabolism. Here the authors show that cytosolic phospholipase A2 mediated phospholipid metabolism contributes to this regulation in healthy animals but exert deteriorating effects on glucose homeostasis under high-fat-diet feeding.

BackgroundThe mortality rate due to COVID-19 in kidney transplant recipients (KTRs) is 16.8 to 32%. Vaccination against COVID-19 is expected to contribute to the prevention of infection, severe disease, and mortality; however, it has been reported that the humoral response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in KTRs is poor. Vaccination strategies against COVID-19 vary from country to country, and in Japan, the third dose is given 6 months after the second dose. Few studies have evaluated long-term humoral responses after the second dose of SARS-CoV-2 mRNA vaccine. In addition, the superiority of BNT162b2 vaccine and mRNA-1,273 vaccine in KTRs regarding humoral response is controversial.MethodsNinety-four KTRs were administered a second dose of the BNT162b2 or mRNA-1,273 vaccines, and anti-spike (anti-S) and anti-nucleocapsid (anti-N) SARS-CoV-2 antibody levels were measured 5 months (149.2 ± 45.5 days) later. The cutoff value of anti-S antibodies was defined ≥50 AU/ml and 1.4 Index for anti-N antibodies. The primary outcome was the rate of seropositivity, and factors associated with an appropriate humoral response were assessed by univariate and multivariate analysis.ResultsOf 94 KTRs, only 45 (47.9%) patients were positive for anti-S antibodies. The median anti-S SARS-CoV-2 IgG antibody titers was 35.3 (Interquartile range 3.8 to 159.7). Anti-N SARS-CoV-2 IgG antibodies in all patients were

BackgroundA positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood.CasesIn five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor’s T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes.DiscussionFalse-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed.ConclusionFalse-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.

BackgroundAngiotensin-converting enzyme 2 (ACE2) works as an endogenous counter-regulator of the renin-angiotensin system, which has pivotal roles in preventing both cardiovascular disease (CVD) and inflammation. In general populations, higher plasma soluble ACE2 levels were reported to be associated with increased risks of all-cause death and major CVD. Because infections are fatal in patients on maintenance hemodialysis, we aimed to explore whether soluble ACE2 levels are associated with an increased risk of infection-related hospitalization in these patients.MethodsUsing data from a prospective, multicenter, cohort study conducted in Tokyo, Japan, we performed a post-hoc analyses of 724 clinically stable patients on maintenance hemodialysis. We measured baseline serum soluble ACE2 levels and assessed potential determinants of its with infection-related hospitalization as a primary outcome as well as all-cause death and CVD as secondary outcomes using a Cox proportional hazards model.ResultsThe soluble ACE2 level (median, 0.16 ng/ml; interquartile range, 0.07–0.57 ng/ml) showed a weak negative association with age. During a median follow-up of 39 months, 106 patients (14.6%) were hospitalized with infectious diseases. Compared with the lower half of soluble ACE2 levels, the higher half was associated with an increased risk of infection-related hospitalization (hazard ratio, 1.57; 95% confidence interval, 1.02–2.41) with adjustment by other risk factors. On the other hand, there were no significant associations between soluble ACE2 and risks of all-cause death and CVD.ConclusionHigher soluble ACE2 levels may associate with an increased risk of infection-related hospitalization in patients on maintenance hemodialysis.

Objective: The regulation of food intake is a major research area in the study of obesity, which plays a key role in the development of metabolic syndrome. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behavior, but the deletion of a gene has a long-term effect on neurophysiology. Our understanding of short-term changes such as appetite under physiological conditions is therefore still limited. Methods: Targeted recombination in active populations (TRAP) is a newly developed method for labeling active neurons by using tamoxifen-inducible Cre recombination controlled by the promoter of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), a member of immediate early genes. Transgenic mice for TRAP were fasted overnight, re-fed with normal diet, and injected with 4-hydroxytamoxifen 1 h after the refeeding to label the active neurons. The role of labeled neurons was examined by expressing excitatory or inhibitory designer receptors exclusively activated by designer drugs (DREADDs). The labeled neurons were extracted and RNA sequencing was performed to identify genes that are specifically expressed in these neurons. Results: Fasting-refeeding activated and labeled neurons in the compact part of the dorsomedial hypothalamus (DMH) that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of the labeled DMH neurons decreased food intake and developed place preference, an indicator of positive valence. Chemogenetic activation or inhibition of these neurons had no influence on the whole-body glucose metabolism. The labeled DMH neurons expressed prodynorphin (pdyn), gastrin-releasing peptide (GRP), cholecystokinin (CCK), and thyrotropin-releasing hormone receptor (Trhr) genes. Conclusions: We identified a novel cell type of DMH neurons that can inhibit food intake and promote feeding-induced positive valence. Our study provides insight into the role of DMH and its molecular mechanism in the regulation of appetite and emotion.

Abstract Methods for estimating nephron number in a clinical setting may be useful for predicting renal outcomes. This study aimed to establish such a method using unenhanced computed tomography (CT) and biopsy-based stereology. Patients or living kidney donors simultaneously subjected to enhanced and unenhanced CT examinations were randomly assigned to development and validation groups. The enhanced CT-measured arterial phase and the venous phase images of kidneys were regarded as the true values for cortical volume and parenchymal volume, respectively. Linear multiple regression analysis was used to create models for estimating cortical volume using explanatory variables including unenhanced CT-measured parenchymal volume. Nephron number was determined as the product of cortical volume and the glomerular density in biopsies of donors. Five equations for estimating cortical volume were created and verified. In donors, estimated nephron number by unenhanced CT was consistent with that by enhanced CT, with minimal errors in all models (636–655 ± 210–219 vs. 648 ± 224 × 103/kidney). Clinical characteristics combined with parenchymal volume did not improve the equation over parenchymal volume alone. These results support the feasibility of estimating nephron number by a combination of unenhanced CT and biopsy-based stereology, with a possible application for renal disease patients who are often not suitable for contrast media.

Abstract Background Sebaceous carcinoma is a rare but progressive malignant skin cancer, and the incidence is approximately five times higher in post-transplant patients than in people who have not received kidney transplants. Sebaceous carcinoma is sometimes found concurrently with visceral cancers and a genetic abnormality, Muir–Torre syndrome. We report the case of a female kidney transplant recipient with sebaceous carcinoma concurrent with colon cancer 10 years after transplantation. Case presentation A 43-year-old woman was admitted due to a rapidly progressive tumor on her head. Histologically, the tumor was diagnosed as sebaceous carcinoma. We diagnosed her with Muir–Torre syndrome based on the following evidence: 1) high prevalence of microsatellite instability in gene locus assay, 2) absence of mismatch repair proteins in the sebaceous carcinoma on immunohistochemical analysis, and 3) a genetic mutation of 1226_1227delAG in the MSH2 exon 7 in the lesion detected by DNA sequencing analysis. Several reports have shown an association between immunosuppressive agents and latent Muir–Torre syndrome progression. Therefore, the progression of colon cancer in this case originated from her genetic mutation for Muir–Torre syndrome and long-term use of immunosuppressive agents. Conclusion This case report not only highlights the importance of adequate diagnosis and therapy for Muir–Torre syndrome, but also suggests the further prevention of the development of malignant tumors in kidney transplant recipients. Physicians should be mindful that sebaceous carcinoma in kidney transplant recipients is highly concurrent with Muir–Torre syndrome.

Background: Recurrence of IgA nephropathy (IgAN) in the transplanted kidney is associated with graft survival, but no specific treatment is available. Tonsillectomy (TE) reportedly arrests the progression of IgAN in the native kidney. Thus, we conducted a single-center retrospective cohort study to evaluate the effect of TE prior to IgAN recurrence.Methods: Of the 36 patients with biopsy-proven IgAN who underwent kidney transplantation, 27 were included in this study. Nine patients underwent TE at 1 year after kidney transplantation (group 1), and the remaining 18 did not undergo TE (group 2).Results: The rate of histological IgAN recurrence was significantly lower in group 1 than in group 2 (11.1 vs. 55.6%, log-rank p = 0.046). In addition, half of the recurrent patients in group 2 exhibited active lesions, compared to none in group 1. Serum Gd-IgA1 levels decreased after TE in group 1, whereas they remained stable or increased slightly in group 2. In the recurrent cases, IgA and Gd-IgA1 were found in the germinal center in addition to the mantle zone of tonsils. Finally, mesangial IgA and Gd-IgA1 immunoreactivity was reduced after TE in some cases.Conclusion: Our data suggest that TE at 1 year after kidney transplantation might be associated with the reduced rate of histological IgAN recurrence. TE arrested or reduced serum Gd-IgA1 and mesangial Gd-IgA1 immunoreactivity. Therefore, we generated a hypothesis that serum Gd-IgA1 derived from the tonsils may play a pivotal role in the pathogenesis of IgAN. Based on these findings, we need to conduct verification in a prospective randomized controlled trial.

Abstract Background Patients with Alport syndrome (AS) develop progressive kidney dysfunction due to a hereditary type IV collagen deficiency. Survival of the kidney allograft in patients with AS is reportedly excellent because AS does not recur. However, several studies have implied that the type IV collagen in the GBM originates from podocytes recruited from the recipient’s bone marrow-derived cells, suggesting the possibility of AS recurrence. Limited data are available regarding AS recurrence and graft survival in the Japanese population; the vast majority were obtained from living related kidney transplantation (LRKTx). Methods In this retrospective study, twenty-one patients with AS were compared with 41 matched patients without AS from 1984 to 2015 at two centers using propensity scores. Nineteen of the 21 patients with AS underwent LRKTx. The mean post-transplant follow-up period was 83 months in the AS group and 110 months in the control group. Histopathological AS recurrence was assessed by immunoreactivity of α5 (type IV collagen) antibody and electron microscopy. Results The graft survival rate was equivalent between patients with and without AS (86.7% vs. 77.1% and 69.3% vs. 64.2% at 5 and 10 years; p = 0.16, log-rank test). Immunoreactivity to α5 antibody showed strong linear positivity with no focal defect in six patients. Electron microscopy showed no GBM abnormalities in two patients who were exhibiting long-term kidney allograft survival. Conclusions We confirmed that α5 and the GBM structure were histopathologically maintained in the long term after kidney transplantation. The patient and graft survival rates were equivalent between Japanese patients with and without AS.

Abstract Background Both prevention and treatment of recurrent immunoglobulin A nephropathy (IgAN) in kidney transplant recipients are important since recurrent IgAN seems to affect long-term graft survival. We present here a case of recurrent IgAN that was successfully treated using steroid pulse therapy plus tonsillectomy 10 years after kidney transplantation. Case presentation A 46-year-old male was admitted for an episode biopsy with a serum creatinine level of 1.8 mg/dl and proteinuria (0.7 g/day). Histological features showed recurrent IgAN (only focal segmental mesangial proliferation) and severe arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity, with limited interstitial fibrosis and tubular atrophy (5%) (IF/TA) 8 years after transplantation. Sodium restriction and conversion from cyclosporine to tacrolimus successfully reduced his proteinuria to the level of 0.15 g/day. However, 2 years later, his proteinuria increased again (1.0 g/day) and a second episode biopsy showed global mesangial proliferation with glomerular endocapillary and extracapillary proliferation accompanied by progressive IF/TA (20%). The steroid pulse therapy plus tonsillectomy successfully decreased his proteinuria and he achieved clinical remission 3 years after this treatment. Conclusion This case, presented with a review of relevant literature, demonstrates the difficulty and importance of the treatment of recurrent IgAN and calcineurin inhibitor arteriolopathy, especially in long-term kidney allograft management.

Alterations in glomerular filtration can considerably influence the dynamics and functions of the Bowman capsule. Despite the potentially important role in maintaining normal renal functions, few studies have focused on Bowman capsule volume in normal human kidneys. Methods: We analyzed specimens from biopsies performed 1 hour after kidney transplantation from living donors without apparent renal disease. The measurements of all cross-sectional areas of the Bowman capsules and glomerular capillaries were used to estimate the mean Bowman capsule volume (BV) and glomerular capillary volume (GV) in each subject. The G/B ratio was defined as the ratio of GV to BV. The morphometric findings were examined in relation to the clinical findings in donors just before kidney transplantation. Results: We analyzed 37 adults with a mean creatinine clearance of 111 ml/min. The mean BV and GV of these subjects were 6.10 ± 2.46 × 106 μm3 and 3.83 ± 1.52 × 106 μm3, respectively. Both the BV and GV varied up to 6-fold and were significantly higher in elderly, obese, or hypertensive subjects in comparison to nonelderly, nonobese, or normotensive subjects, whereas the renal function of each subgroup was similar. The G/B ratio (0.63 ± 0.05) was unaffected, and BV and GV were strongly correlated regardless of these clinical factors (r = 0.980 [95% confidence interval = 0.961−0.990], P < 0.001). Conclusion: In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.

Background/Aims: Post-transplant hypertension is highly prevalent in renal transplant recipients and is a risk factor for graft loss, cardiovascular disease and death. Glucocorticoid is used to prevent rejection, but simultaneously increases the risk of post-transplant hypertension. The glucocorticoid-induced transcript 1 (GLCCI1) promoter polymorphism (rs37972) has been reported to be associated with response to glucocorticoid therapy in asthma. We therefore examined the association between GLCCI1 promoter polymorphism and post-transplant hypertension in renal transplant recipients. Methods: We conducted a retrospective cohort study of renal transplantation at a single university hospital from October 2003 to January 2014. Fifty consecutive adult recipients were analyzed, with clinical data retrieved from a prospectively collected database. Genotyping was carried out using genomic DNA derived from recipient’s blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively analyzed by immunohistochemical staining of recipients’ native kidney biopsy-specimens. The primary outcome measure was post-transplant hypertension. Results: Post-transplant hypertension was observed in 14/17 (82%) of recipients with CC, 18/20 (90%) with CT, and 2/13 (15%) with TT genotype. CC/CT genotype was significantly associated with post-transplant hypertension, even after adjustment for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P = 0.026). In addition, we observed that GLCCI1 immunoreactivity in arteriolar endothelial cells was higher in kidney specimens obtained from recipients with a CC/CT genotype than a TT genotype (P = 0.021). Conclusion: GLCCI1 promoter polymorphism rs37972 may be associated with post-transplant hypertension.

BACKGROUND:Several reports on patients with diabetes mellitus (DM) treated by peritoneal dialysis (PD) have shown a higher risk of PD-associated peritonitis compared to non-DM (NDM) patients. The aim of this study was to investigate the incidence of PD-associated peritonitis in DM patients. METHODS:We divided all patients who received PD at a single center between January 1980 and December 2012 into three groups according to era: Period 1 (n = 43, 1980-1993); Period 2 (n = 123, 1994-2004); and Period 3 (n = 207, 2005-2012). We investigated incidences of PD-associated peritonitis between patients with and without DM. RESULTS:In Periods 1 and 2, incidence of PD-associated peritonitis was higher in the DM group than in the NDM group (P

Despite the recent development of immunosuppressive agents, plasma cell-rich acute rejection (PCAR) has remained refractory to treatment. Herein, we report an unusual case of PCAR that responded well to pulse steroid therapy alone. A 47-year-old man was admitted for a protocol biopsy three months after kidney transplantation, with a stable serum creatinine level of 1.6 mg/dL. Histological examination showed focal aggressive tubulointerstitial inflammatory cell infiltration of predominantly polyclonal mature plasma cells, leading to our diagnosis of PCAR. Three months following three consecutive days of high-dose methylprednisolone (mPSL) therapy, an allograft biopsy performed for therapy evaluation showed persistent PCAR. We readministered mPSL therapy and successfully resolved the PCAR. Although PCAR generally develops more than six months after transplantation, we diagnosed this case early, at three months after transplantation, with focally infiltrated PCAR. This case demonstrates the importance of early diagnosis and prompt treatment of PCAR to manage the development and severity of allograft rejection.

O objetivo deste trabalho foi auxiliar o grupo produtivo da comunidade do Jardim Jaqueline, município de São Paulo, na elaboração de uma barra de cereais, avaliar sua aceitação por meio de análise sensorial e determinar sua composição nutricional com o uso das tabelas de composição de alimentos da Unicamp e do USDA. Foram realizadas: análise sensorial, por meio de teste afetivo da avaliação global da barra de cereais e avaliação da intenção de compra. Aos resultados das análises aplicaram-se os testes estatísticos de Análise de Variância (ANOVA) e de Tukey. A barra de cereais, formulada a partir de uma receita caseira, pode ser caracterizada como “fonte de fibras” e “zero gordura trans”. Observou-se aceitação do produto pelos julgadores, já que 88,3% das respostas encontram-se entre “gostei ligeiramente” e “gostei muitíssimo”. Nota-se boa expectativa quanto à intenção de compra, pois 51,66 % das respostas encontram-se entre “certamente compraria” e “provavelmente compraria”. É possível obter um alimento nutritivo e com padrão de aceitabilidade aliando o trabalho conjunto da comunidade e o conhecimento técnico dos agentes de desenvolvimento. As atividades desenvolvidas com a comunidade possibilitaram vivenciar o desenvolvimento da cooperativa popular, sendo possível criar condições favoráveis para geração de renda a partir dos princípios da economia solidária.