Renal cell carcinoma preceded by a rheumatoid­like paraneoplastic syndrome: A case report.

A man with polycystic kidney disease and a history of renal transplantation at the age of 55 years developed seronegative rheumatoid arthritis (RA) at the age of 68 years. Treatment with a biological derivative led to remission; however, the patient relapsed 2 years later. After being switched to baricitinib, the patient again achieved remission. After 2 years, when the patient was aged 72 years, RA recurred, and the right native kidney became enlarged due to the presence of a large tumor. Surgical nephrectomy was performed, and the tumor was classified as renal cell carcinoma (RCC), not otherwise specified. The cancer tissue comprised sarcomatoid and rhabdoid cells with marked neutrophil infiltration, and the tumor cells were positive for interleukin-6. The patient, aged 73 years, experienced a resolution of joint pain following surgical intervention; however, they died because of systemic metastases ~10 weeks post-operation. Based on the clinical course, the RA-like lesions and subsequent RCC were considered to represent a paraneoplastic syndrome.

Early diagnosis of tuberculous peritonitis in peritoneal dialysis patients using the T-SPOT test.

A 49-year-old man was admitted with peritonitis nine months after starting continuous ambulatory peritoneal dialysis (CAPD) for kidney failure. Ceftazidime and cefazolin were started. Peritoneal dialysate culture was negative for bacteria, but antibiotic treatment was continued because peritonitis improved. Twenty days later, the patient was discharged with no signs of peritonitis. However, 40-day culture of the original peritoneal dialysate detected Mycobacterium tuberculosis, and peritonitis recurred, leading to readmission. A T-SPOT test was performed and was positive in 4 days. Anti-tuberculosis therapy was started, which cured the peritonitis. The T-SPOT test may enable early diagnosis of tuberculosis.

De novo posttransplant membranous nephropathy after COVID-19 vaccination 9 years after renal transplantation in a patient with polycystic kidney disease.

A 63-year-old man with polycystic kidney disease underwent kidney transplantation from his wife. Nine years later, after the first and second doses of the COVID-19 vaccination, he developed proteinuria, hematuria, and elevated C-reactive protein. Kidney biopsy 7 months after the initial appearance of proteinuria showed immunoglobulin (Ig)-G granular stain, predominantly IgG1, and spike formation in the glomerular basement membrane. Electron microscopy revealed mainly subepithelial deposits, which corresponds to membranous nephropathy (MN) stage 3 of the Ehrenreich-Churg classification indicating chronic disease, but it also showed electron-dense deposits and endothelial damage. Because a kidney biopsy was performed 1 h after renal transplantation and a biopsy of the patient's native kidney showed intact glomeruli, atypical de novo posttransplant membranous nephropathy (MN) was diagnosed, and a close relationship with COVID-19 vaccination was assumed. Clinicians should consider the involvement of COVID-19 vaccination in de novo posttransplant MN with unclear pathogenesis.

Gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder after kidney transplantation: A case report.

We report on a 53-year-old Japanese man diagnosed with gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder (B-PTLD) after endoscopy for gastric discomfort 28 months after the patient underwent renal transplantation in Ethiopia. Serum Epstein-Barr virus (EBV) tests were negative before transplantation, but the tumor cells collected from a gastric biopsy showed positive EBV-encoded small RNAs (EBER) at B-PTLD onset. Intensive treatment started with R(rituximab)-CHOP therapy and continued with DA-EPOCH-R therapy has been effective, and relapse has not yet occurred. Burkitt lymphoma has a poor prognosis, but B-PTLD may be effectively treated with high-dose chemotherapy. This is a rare case of gastric B-PTLD in a Japanese patient.

Cytokine modulation in abdominal septic shock via the crucial role of IL-6 signaling in endothelial dysfunction.

Background: Early recovery from shock improves prognosis in septic shock patients. We determined whether cytokine modulation by Continuous Renal Replacement Therapy (CRRT) following acute care surgery resulted in stable hemodynamics in them. To investigate our hypothesis, we measured proinflammatory cytokines IL-6, IL-1ra and the coagulation cascade activator plasminogen activator inhibitor-1 (PAI-1) following CRRT with polymyxin B immobilized fiber (PMX-DHP) which has been utilized as an adjuvant treatment option for patients with severe septic shock. Methods: 66 septic shock patients requiring 2 h direct hemoperfusion therapy PMX-DHP were included. 36 patients of them also received continuous hemodiafiltration (CHDF) after performing PMX-DHP. Circulatory dynamics and levels of inflammatory mediators, namely IL-6, IL-1ra, and PAI-1 were assessed before, immediately after, and 24 h initiation of PMX-DHP. Results: Mean Arterial Pressure (MAP) rose intentionally by PMX-DHP just after enforcement 24 h later (p < 0.01). Levels of IL-6, IL-1ra, and PAI-1 significantly decreased after PMX-DHP (p < 0.05) and this trend was observed up to 24 h post initiation of PMX-DHP (p < 0.05). IL-6 modulation by PMX-DHP was enhanced with using CHDF and there was a significant correlation between IL-6 and MAP (p < 0.0001). In addition, levels of Il-6 and PAI-1 showed a significant correlation. Conclusion: Our data showed employing CRRT as cytokine modulators could be an additional therapeutic strategy to improve septic shock outcomes via the crucial role of IL-6 signaling in endothelial dysfunction.

Antiphospholipid Syndrome Nephropathy with Acute Thrombotic Microangiopathy after Renal Transplantation.

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

Kidney Transplantation From a Diabetic Donor to a Nondiabetic Recipient: A Case Report.

We performed a deceased-donor kidney transplantation on a 64-year-old woman. The donor was a 57-year-old man with a history of diabetes mellitus. A kidney biopsy showed nodular sclerosis, Tervaert class 3 diabetic nephropathy. Six months after surgery, serum creatinine had dropped to 1.1 mg/dL and urinary protein decreased to 0.21 g/day. A second renal biopsy showed class 3 diabetic nephropathy. This case suggests that renal tissue damage caused by a long history of diabetes mellitus does not necessarily contribute to proteinuria but is rather the result of metabolic factors including hyperglycemia and hemodynamic factors including fluid overload.

Therapeutic Effect of Roxadustat on Patients With Posttransplant Anemia.

BACKGROUND: Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has been reported to be effective in treating conservative renal failure and renal anemia in patients undergoing dialysis. Nonetheless, its effect on posttransplant anemia (PTA) has not yet been analyzed. METHODS: This study was conducted in accordance with the 1975 Declaration of Helsinki, as revised in 2013. Roxadustat was administered in 31 patients with a hemoglobin level ≤11 g/dL after renal transplant. The mean hemoglobin, serum iron, ferritin, and low-density lipoprotein (LDL) cholesterol levels and the estimated glomerular filtration rate at 4, 8, 12, 16, and 20 weeks after administration were compared with those before administration. RESULTS: The average (standard deviation) hemoglobin level in 25 patients (6 patients dropped out) increased from 9.8 (0.78) g/dL before administration to 12.1 (1.44) g/dL (P < .001) after 12 weeks of roxadustat administration. The mean ferritin level in patients decreased from 107.6 (84.95) ng/mL before administration to 51.7 (44.04) ng/mL (P = .022) after 8 weeks of roxadustat administration. The mean LDL cholesterol level decreased from 114.1 (31.67) mg/dL before administration to 78.7 (18.26) mg/dL (P = .0012) after 8 weeks of roxadustat administration. Complications observed in patients after roxadustat administration included reduced hemoglobin levels in 3 patients, gastrointestinal symptoms in 2 patients, and myocardial infarction in 1 patient. CONCLUSIONS: Hemoglobin levels significantly increased, whereas ferritin and LDL cholesterol levels significantly decreased in patients with PTA after roxadustat administration. Roxadustat seems to be an effective treatment for patients with PTA; however, the blood clotting tendency due to iron deficiency should be monitored in patients.

Efficacy and Safety of Machine Perfusion for Brain Death Marginal Donor Kidney Transplantation: A Report of 2 Cases.

BACKGROUND: After the revised organ transplant law came into effect in Japan, donations of organs under brain death have been increasing; however, because of the expansion of donor indications, donations from expanded criteria donors and cardiac arrest donors (donation after cardiac death) have also increased. In kidney transplantation, ischemia-reperfusion injury results in a high rate of delayed graft function, which adversely affects patients' long-term prognoses. Hypothermic machine perfusion preservation results in superior postoperative function and survival rates compared with cold storage preservation. We used an organ preservation device for kidneys and performed a graft viability evaluation before to kidney transplantation. METHODS: We used the CMP-X08 perfusion device (Chuo-Seiko Co, Ltd, Asahikawa, Hokkaido, Japan) and Belzer MPS solution to preserve the donated organ. The perfusion pressure and temperature were monitored during cold storage with continuous perfusion. Standard renal transplantation protocols were followed. A renal biopsy was performed 1 hour after transplantation and the renal function was evaluated. This study followed the principles of the Declaration of Helsinki. RESULTS: The first presented case is of a 63-year-old woman who received a kidney from a middle-aged man with brain death due to hypoxic encephalopathy. The creatinine at the time of admission was 0.9 mg/dL and at the time of excision was 2.86 mg/dL. The total perfusion time was 120 minutes. The total ischemia time was 7 hours and 15 minutes. The recipient urinated 115 minutes postoperatively, and no dialysis was required. The second presented case is of a 47-year-old man with a 15-year history of dialysis who received a kidney from a middle-aged woman with brain death due to subarachnoid hemorrhage. The creatinine at the time of admission was 0.8 mg/dL and at the time of excision was 0.77 mg/dL. The total perfusion time was 240 minutes. The total ischemia time was 13 hours and 14 minutes. The recipient urinated 38 minutes postoperatively, and no dialysis was required. CONCLUSIONS: Mechanical perfusion storage performed for 2 to 4 hours resulted in a viable organ that was successfully transplanted in both cases.

Usefulness of Tolvaptan for the Postoperative Control After Kidney Transplantation in a Patient With Cardiac Hypofunction: A Case Report.

BACKGROUND: Kidney transplantation in patients with cardiac hypofunction is challenging. Even if the surgery is successfully performed, these patients may suffer from low output cardiac function. We report the case of a patient with severe cardiac hypofunction who developed heart failure (HF) complicated with low output cardiac function, which markedly improved after the administration of tolvaptan, after successful living kidney transplantation. CASE PRESENTATION: A 70-year-old man was diagnosed with chronic renal failure of unknown etiology 4 years previously, for which hemodialysis was initiated. Three years previously, percutaneous coronary intervention was performed because of acute myocardial infarction. Since then, he had been hospitalized for the control of HF. He was referred to our department because he wished to undergo kidney transplantation. We decided to perform the transplantation after determining that he could tolerate the operation. On postoperative day 6, however, his urine discharge volume suddenly declined, leading to an increase in his body weight despite administration of an adequate amount of furosemide, and he was diagnosed with acute HF. The patient's condition markedly improved after the introduction of tolvaptan. CONCLUSION: To our knowledge, this is the first report of improvement in postoperative HF after tolvaptan administration. Although numerous kidney transplantations have been performed at our institute, it is relatively rare that we decide to operate in a patient with severe cardiac hypofunction.

Favorable Short-Term Outcome of Living Donor Kidney Transplantations in Flow Cytometry Crossmatch Positive Cases by Pretransplant Splenectomy: A Case Report.

BACKGROUND: The introduction of rituximab has contributed to successful living donor kidney transplantations in ABO-incompatible recipients and has replaced splenectomy for desensitization. However, several reports still suggest that postoperative splenectomy may be effective in preventing graft failure in patients with acute antibody-mediated kidney transplant rejection (AAMR) in kidney transplantation. Therefore, we aim to assess if preoperative splenectomy also could be an alternative practical choice to avoid AAMR in high-risk rejection cases such as flow cytometry crossmatch (FCXM)-positive cases. MATERIAL AND METHOD: We carried out 4 living donor kidney transplantations in FCXM-positive cases: 3 underwent pretransplant splenectomy, and 1 did not. RESULTS: All 3 cases in whom pretransplant splenectomy was performed were discharged without rejection. On the contrary, in the case where pretransplant splenectomy was not performed, there was graft rejection and additional desensitization therapies were needed. CONCLUSION: While larger clinical studies with longer observation periods are needed, our report suggested that pretransplant splenectomy may lead to successful short-term kidney transplantation outcomes in FCXM-positive cases.

Effectiveness of Nephrectomy and Transcatheter Arterial Embolization Before Kidney Transplantation in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) remains a feasible option because no recurrence has been reported. Transcatheter arterial embolization (TAE) for patients with ADPKD is performed to control infection, pain, or bleeding and can help reduce kidney volume. However, nephrectomy may be needed for inadequate kidney shrinkage. The effects of these procedures performed before transplantation on transplant outcomes or kidney functions are not discussed. We retrospectively evaluated the effectiveness of nephrectomy and TAE before transplantation. METHODS: Forty-four patients who underwent renal transplantation in our center between 2008 and 2018 were classified into 4 groups according to whether nephrectomy or TAE was performed. We collected information on sex, age, type of transplantation, history of nephrectomy or TAE, renal function, postoperative complications, graft acceptance, and survival rates. RESULTS: Of the 17 patients who underwent TAE and those who did not, 8 and 7 underwent nephrectomy, respectively; 16 underwent bilateral TAE and primitive transplantation. The patients who underwent both nephrectomy and TAE had significantly better kidney function than those who underwent neither. With TAE alone, without nephrectomy, the mean volume reduction rate was 23.5% and 28.4% on the left and right, respectively; in patients who underwent neither procedure, the mean volume reduction rates were 24.8% and 28.4%, respectively. CONCLUSIONS: Patients who underwent both nephrectomy and TAE had better renal function than those in any other group. However, if the recipient's pelvis has sufficient space, nephrectomy is unnecessary because the kidney volume decreases after transplantation by approximately 25%.

Long-Term Survival After Multidisciplinary Treatment Including Surgery for Metachronous Metastases of Small Intestinal Gastrointestinal Stromal Tumors after Curative Resection: A Case Report.

BACKGROUND Currently, 3 molecular targeted drugs are available for the treatment of unresectable and recurrent gastrointestinal stromal tumors (GISTs), and result in improved prognoses and rare occurrence of bone metastases. However, there is no established treatment guideline for bone metastases of GIST. CASE REPORT The patient was a 56-year-old male who was diagnosed with leiomyosarcoma in 1997. Partial resection of the small bowel was performed. As part of post-operative follow-up in 2004, a computed tomography scan showed metastatic lesions in the liver and the right femoral neck. Accordingly, partial hepatectomy was performed, followed by artificial femoral head replacement. In 2006, bone metastases were detected in the sternum, cervical and thoracic vertebra, and the right upper arm; therefore, the patient was subjected to radiotherapy. However, further histopathological examination revealed positive findings for CD34+ and KIT cells, prompting a diagnosis of GIST. Imatinib was started. The disease remained stable. However, in 2010, metastasis to the right ilium was detected, after which there was an increase in metastatic lesions in the thoracic vertebra, prompting a diagnosis of progressive disease. Thus, treatment with sunitinib was initiated. In 2012, the patient experienced spinal paralysis due to metastasis in the eighth thoracic vertebra. In 2013, metastases in the right ilium, lungs, and liver were detected. In 2014, the patient died. CONCLUSIONS Multidisciplinary treatment via radiotherapy and surgery for GIST with bone metastases indicates the possibility of extending the overall survival further.

Reduction in circulating level of HMGB-1 following continuous renal replacement therapy in sepsis.

Early recovery from shock improves prognosis in patients with severe sepsis and septic shock. During this period, cytokine imbalances mediate the development of organ damage and mortality. In Japan, we have access to hemoperfusion using an immobilized polymyxin B fiber column for endotoxin removal (PMX-DHP) and continuous hemodiafiltration (CHDF) as artificial support for patients with septic shock, with the aim of improving hemodynamics and organ dysfunction caused by elevated inflammatory cytokines and mediators. In this Short communication, we discuss recent findings showing anti-inflammatory treatment following these continuous renal replacement therapies in sepsis.

Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells.

The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity.

[A case that showed an improved quality of life for rectal gastrointestinal stromal tumor patient treated with cytoreductive surgery].

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

Irinotecan hydrochloride (CPT-11) in dialysis patients with gastrointestinal cancer.

We investigated changes in drug disposition and toxicities with CPT-11 in 15 dialysis patients with gastrointestinal cancers to clarify whether CPT-11 could be administered safely in such patients. For comparison, the same parameters were also investigated in 10 cancer patients not undergoing dialysis. Items investigated included (1) plasma concentrations of SN-38, SN-38G and CPT-11 at 0, 1, 12, 24, 36, 48 and 72 h after administration, together with a comparison of mean AUC values for 3 dose levels of CPT-11 (50, 60 and 70 mg/m2) in dialysis patients and controls; and (2) occurrence of adverse events. Several findings emerged from this study: (1) No significant difference was observed in the AUC for SN-38 or CPT-11 between the dialysis and control groups; (2) The AUC for SN-38G at each dose was significantly higher in dialysis patients; and (3) Grade 1-4 leucopenia was observed in 11 of the dialysis patients. One patient developed grade 4 leucopenia and died due to sepsis. Anorexia, diarrhea, nausea, alopecia and interstitial pneumonia occurred in 6 dialysis patients. We found changes in drug dispositions of CPT-11, SN-38 and SN-38G in dialysis patients, suggesting that hepatic excretion, especially that of SN-38G, was increased. No significant difference in occurrence of adverse events was observed between the 2 groups. This indicates that CPT-11 can be administered safely in patients on dialysis.

Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--.

The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral) and tacrolimus (TAC; Prograf) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C(2)) substituted for peak concentration (C(p)) and TAC at trough concentration (C(t)). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with C(p) and C(t) versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C(2) for CYA and C(t) for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, C(p), and C(t).