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.

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.

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%.

Single fixed low-dose rituximab as induction therapy suppresses de novo donor-specific anti-HLA antibody production in ABO compatible living kidney transplant recipients.

This study was conducted to evaluate de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA) production leading to antibody-mediated rejection (ABMR) after rituximab induction in non-sensitized ABO-compatible living kidney transplantation (ABO-CLKTx). During 2008-2015, 318 ABO-CLKTx were performed at the Department of Surgery III at Tokyo Women's Medical University Hospital. To reduce confounding factors, we adopted a propensity score analysis, which was applied with adjustment for age, gender, duration of pretransplant dialysis, HLA mismatch count, preformed DSA, non-insulin-dependent diabetes mellitus, immunosuppressive treatment, and estimated glomerular filtration rate (eGFR) on postoperative day 7. Using a propensity score matching model (1:1, 115 pairs), we analyzed the long-term outcomes of 230 ABO-CLKTx recipients retrospectively. Recipients were classified into a rituximab-treated (RTX-KTx, N = 115) group and a control group not treated with rituximab (C-KTx, N = 115). During five years, adverse events, survival rates for grafts and patients, and incidence of biopsy-proven acute rejection (BPAR) and dnDSA production for the two groups were monitored and compared. All recipients in the RTX-KTx group received rituximab induction on preoperative day 4 at a single fixed low dose of 100 mg; the CD19+ B cells were eliminated completely before surgery. Of those recipients, 13 (11.3%) developed BPAR; 1 (0.8%) experienced graft loss. By contrast, of C-KTx group recipients, 25 (21.7%) developed BPAR; 3 (2.6%) experienced graft loss. The RTX-KTx group exhibited a significantly lower incidence of BPAR (P = .041) and dnDSA production (13.9% in the RTX-KTx group vs. 26.9% in the C-RTx group, P = .005). Furthermore, lower incidence of CMV infection was detected in the RTX-KTx group than in the C-KTx group (13.9% in the RTX-KTx group vs. 27.0% in the C-KTx group, P = .014). No significant difference was found between groups for several other factors: renal function (P = .384), graft and patient survival (P = .458 and P = .119, respectively), and the respective incidences of BK virus infection (P = .722) and leukopenia (P = .207). During five-year follow-up, single fixed low-dose rituximab therapy is sufficient for ensuring safety, reducing rejection, and suppressing dnDSA production for immunological low-risk non-sensitized ABO-CLKTx.

Single Graft Utilization From Donors With Severe Acute Kidney Injury After Circulatory Death.

Chronic shortages of organs for transplantation have led to the use of marginal kidneys from donors after circulatory death with acute kidney injury (AKI), but the utilization of kidneys with severe AKI is not well established. We retrospectively analyzed eight kidney transplantation (KTx) cases from donation after circulatory death (DCD) with terminal creatinine (t-Cr) concentrations higher than 10.0 mg/dL and/or oliguria for more than 5 days (AKI network criteria: stage III). Although all patients showed delayed graft function, no cases of primary nonfunction (PNF) were found. Five patients maintained stable renal function for approximately 15.5, 10, 10, 5, and 0.5 years after KTx. Only 1 patient showed biopsy-proven acute rejection. Also, 2 patients developed graft failure: one attributable to chronic antibody mediated rejection at 11.3 years after KTx, and one attributable to recurrence of IgA nephropathy at 4.6 years after KTx. Kidneys with AKI stage III yielded great outcomes without the risk of primary nonfunction and rejection. Although the AKI kidneys were associated with delayed graft function, these results suggest that even the most severe kidneys with AKI stage III from DCD donors can be considered a valid alternative for recipients on a waiting list for KTx.

Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine.

BACKGROUND: Hydrogen sulfide (H2S) has recently been reported to demonstrate both antiinflammatory and cytoprotective effects; however, its efficacy has not been well documented in large animal models. In this study, we examined whether the administration of H2S offers cytoprotective effects on renal ischemia-reperfusion injury (IRI) in a preclinical miniature swine model. METHODS: Major histocompatibility complex-inbred, CLAWN miniature swine (n = 9) underwent a right nephrectomy, followed by induction of a 120-min period of warm ischemia via placement of clamps on the left renal artery and vein. Group 1 (n = 3) underwent renal ischemia without H2S administration. Groups 2 (n = 3) and 3 (n = 3) received Na2S (prodrug of H2S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na2S postreperfusion intravenously (group 2) or selective administration of Na2S via the left renal artery (group 3). IRI was assessed by kidney biopsies, levels of inflammatory cytokines in sera and kidney tissue. RESULTS: Animals in group 1 had significantly higher serum creatinine levels compared with animals in groups 2 and 3 (P < 0.01). Histology showed severe tubular damage with TUNEL-positive cells in group 1 on postoperative day 2 compared with mild damage in group 2 and minimal damage in group 3. Furthermore, levels of inflammatory cytokines in both serum (interleukin-6 [IL-6], tumor necrosis factor-α, and high-mobility group box 1) and renal tissue (IL-1 and IL-6) in group 3 were markedly lower than in group 2, suggesting beneficial effects of selective Na2S administration. CONCLUSIONS: Na2S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.

Longterm renal allograft survival after sequential liver-kidney transplantation from a single living donor.

Combined liver-kidney transplantation (CLKT) is well established as a definitive therapy with the potential to provide complete recovery for certain liver-kidney diseases, although the results might be contingent on the cause of transplantation. The purposes of the present study were to review the longterm outcome of renal allografts in CLKT patients from single living donors and to investigate the beneficial factors, compared with solitary renal transplantation. Thirteen patients underwent sequential liver transplantation (LT) and kidney transplantation (KT) from single living donors. The indications for KT were oxaluria (n = 7), autosomal recessive polycystic disease (n = 3), and others (n = 3). The same immunosuppressive regimen used after LT was also used after KT. KT was performed between 1.7 and 47.0 months after the LT. The overall patient survival rate was 92.3% at 10 years. In 12 of the 13 surviving patients, the renal allografts were found to be functioning in 11 patients after a mean follow-up period of 103.6 months. The death-censored renal allograft survival rate at 10 years was 100%, which was better than that of KT alone (84.9%) in Japan. Immunological protection conferred by the preceding liver allograft may have contributed to the longterm outcomes of the renal allografts. In addition, the donation of double organs from a single living and related donor may have a favorable impact on the graft survival rate. In the future, investigations of factors affecting the longterm outcome of renal allografts, including details of the involvement of de novo donor-specific antibody, will be needed. Liver Transplantation 23 315-323 2017 AASLD.

Successful Long-term Graft Survival of a Renal Transplantation Patient with Wiskott-Aldrich Syndrome.

Wiskott-Aldrich syndrome, a rare X-linked hereditary syndrome, is characterized by immunodeficiency, thrombocytopenia, and eczema. The underlying T-cell defect renders renal transplantation and immunosuppressive treatments uncertain. The present case exhibited the mild clinical manifestation, regarded as X-linked thrombocytopenia. He successfully underwent a living-donor ABO-compatible renal transplantation and splenectomy in 2002, and thereafter experiencing no severe rejection, serious infection, or malignancy for more than 10 years. Though IgA nephropathy was detected 8 months after transplantation, the patient's renal function and proteinuria were stable without any treatment. The present case showed a successful long-term graft survival and the importance of splenectomy added to renal transplantation.

A case of cryopyrin-associated periodic syndrome with kidney transplant failure.

The cryopyrin-associated periodic syndrome (CAPS) is an autosomal dominant autoinflammatory disease characterized by fever, skin rash, and joint involvement with acute inflammatory response. The genetic defect involves the NLRP3 gene that encodes cryopyrin and leads to an abnormal production of interleukin-1 (IL-1). Therefore, anti-IL-1 treatment represents an effective therapy. One of the most severe manifestations of the disease is secondary amyloidosis that causes renal failure. We present a patient with CAPS who underwent renal transplantation for renal insufficiency caused by amyloidosis. The function of the transplanted kidney deteriorated because of the late administration of IL-1 receptor antagonist, anakinra. This case may indicate the importance of early initiation of anti-IL-1 treatment in CAPS patients who have undergone kidney transplantation.