Successful third kidney transplantation with intensive immunosuppression in a highly sensitized recipient

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.     

Multiple Gouty Arthritis With Tophi Formation in a Patient With End-Stage Kidney Disease Treated After Kidney Transplant

BackgroundHyperuricemia is a common condition in patients with chronic kidney disease and end-stage kidney disease. It occurs even after kidney transplant because of the use of calcineurin inhibitors and transplanted kidney failure. We describe the case of a patient with end-stage kidney disease who had multiple gouty arthritis with tophi formation despite receiving appropriate treatment but was successfully cured after kidney transplant.Case ReportA 36-year-old male patient undergoing hemodialysis treatment was treated with febuxostat for multiple gouty arthritis and underwent tophi removal twice. He received a deceased donor kidney transplant 10 years after dialysis treatment. He received immunosuppressants (basiliximab, tacrolimus, mycophenolate mofetil) and steroids. Results of renal biopsy performed on days 7 and 21 postoperation showed no specific findings and normal renal function. The uric acid level before transplant was 3.1 mg/dL, and when renal function was normal, it reached 6-7 mg/dL and remained stable. Although hyperuricemia was still present, the tophi disappeared 3 months after transplant. It is presumed that the high-dose steroids interfered with the activation of inflammatory responses during tophi formation, which may have caused the tophi to disappear. It is also presumed that the patient adhered to the diet well after transplant, which suppressed tophi formation.ConclusionsOur findings suggest that disappearance of multiple tophi and arthritis in patients undergoing hemodialysis can be achieved with kidney transplant, especially when uric acid–lowering drugs are not effective.     

The effect of liver transplantation in a 13-year-old boy with erythropoietic protoporphyria

A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.     

Cyclosporine and long-term kidney graft survival

BACKGROUND: Previous analysis of kidney transplant data from the Collaborative Transplant Study database showed that patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 7 years posttransplantation. Longer-term and additional analyses have now been performed. METHODS: Data from cadaver kidney transplants performed between 1985 and 1998 were analyzed retrospectively. Patients were included if they had a functioning graft 1 year posttransplantation, and the daily cyclosporine dose administered 1 year posttransplantation was reported. Data on cyclosporine dose, serum creatinine concentration, and systolic blood pressure were recorded 1 and 5 years after transplantation; information on graft survival was documented at yearly intervals. RESULTS: Patients receiving cyclosporine 3-6 mg/kg/day 1 year posttransplantation had the best graft survival rate 10 years posttransplantation. Cyclosporine <2 mg/kg/day was least beneficial overall and in subanalyses based on age, risk level, and 1-year serum creatinine concentration. The microemulsion cyclosporine formulation (Neoral) was associated with a significantly higher 4-year graft survival rate than the conventional formulation (Sandimmune; P=0.0001). Median systolic blood pressure 5 years posttransplantation was similar in each 1-year cyclosporine dose category (range of medians 139.0-140.0 mmHg). The percentages of patients with serum creatinine concentrations of <130, 130-260, 260-400, or >400 micromol/L 1 and 5 years posttransplantation were similar across 1-year cyclosporine dose categories, with the exception of >6 mg/kg/day, where there was a shift toward a less favorable serum creatinine concentration over time. CONCLUSIONS: The 1-year cyclosporine dose was significantly associated with long-term graft survival, with evidence of underimmunosuppression at doses <3 mg/kg/day and overimmunosuppression at doses >6 mg/kg/day, but had little influence on systolic blood pressure or serum creatinine concentration at doses up to 6 mg/kg/day.     

A Case of Acute Kidney Injury Caused by Myoglobin Cast Nephropathy With Sars-Cov-2 Infection in a Living-Donor Kidney Transplant Recipient

When COVID-19 affects patients with risk factors such as chronic kidney disease or on immunosuppressive drugs, they often rapidly become seriously ill. We describe a 50-year-old man who was affected with SARS-CoV-2 and had undergone an ABO-compatible living-donor kidney transplantation from his father 14 years ago because of end-stage renal failure due to hypertensive nephrosclerosis. He had continued on immunosuppressive drugs and completed vaccination twice (9 months ago and 6 months ago) with messenger RNA (mRNA) vaccines against SARS-CoV-2. However, he was temporarily on a mechanical ventilator due to respiratory failure and hemodialysis due to acute kidney injury (AKI). He was finally weaned from the ventilator and hemodialysis by taking steroid and antiviral drugs. Echo-guided renal biopsy revealed myoglobin cast nephropathy. We experienced 14 outpatients after living-donor kidney transplantation infected with SARS-CoV-2, but only this case developed AKI.     

Kidney Transplant from the Same Donor without Maintenance Immunosuppression after Previous Hematopoietic Stem Cell Transplant

In January 2005, an 18‐year‐old male patient with acute myeloid leukemia (AML) received a haploidentical hematopoietic stem cell transplantation (HSCT) from his father. He developed hemolytic uremic syndrome and end‐stage renal disease (ESRD) requiring hemodialysis on day 357 after HSCT. On day 1020 after HSCT, a living kidney donation from the stem cell donor was carried out. The creatinine before kidney transplantation (KT) was ≈450 μmol/L, 268 μmol/L on day 2 after KT, 88 μM on day 38 and 89 μmol/L on day 960 (day 1980 after HSCT). Immunosuppression was gradually discontinued: cortisone on day 28, tacrolimus on day 32 and MMF on day 100 after KT (day 1120 after HSCT). As of June 2010, 66 months after HSCT and 32 months after KT, the patient has had neither rejection episodes nor clinical manifestations of transplantation‐related complications. The patient reached 100% hematopoietic donor chimerism prekidney transplant and retained this state postkidney transplant. This unique case is the first report of a successful kidney transplant without immunosuppression after HSCT from the same haploidentical donor.     

Eculizumab Salvage Therapy for Antibody‐Mediated Rejection in a Desensitization‐Resistant Intestinal Re‐Transplant Patient

The presence of elevated calculated panel reactive antibody (cPRA) and anti‐HLA donor specific antibodies (DSA) are high risk factors for acute antibody‐mediated rejection (AAMR) in intestinal transplantation that may lead to graft loss. Eculizumab has been used for the treatment of AAMR in kidney transplantation of sensitized patients that do not respond to other treatment. Here, we report a case where eculizumab was used to treat AAMR in a desensitization‐resistant intestinal re‐transplant patient. A male patient lost his intestinal graft to AAMR 8.14 years after his primary transplant. He received a second intestinal graft that had to be explanted a month later due to refractory AAMR. The patient remained highly sensitized despite multiple treatments. He received a multivisceral graft and presented with severe AAMR on day 3 posttransplantation. The AAMR was successfully treated with eculizumab. The patient presently maintains an elevated cPRA level above 90% but his DSAs have decreased from 18 000 MFI (mean fluorescent intensity) to below the positive cut‐off value of 3000 MFI and remains rejection free with a 2‐year follow‐up since his multivisceral transplant. Eculizumab offers an alternative to treat AAMR in intestinal transplantation in desensitization‐resistant patients.     

A case of acute vascular rejection after overseas deceased kidney transplantation

Abstract:  A 54-yr-old Japanese male received overseas deceased kidney transplantation in January 2006. His allograft functioned immediately and he received immunosuppression with cyclosporine A (CyA), mycophenolate mofetil (MMF), and prednisone (PR). On day 24 after transplantation, he came back to Japan. His serum creatinine level (s-Cr) was 1.39 mg/dL at two months after transplantation when he was admitted into Toda Central General Hospital on March 2006, for follow-up his renal allograft. He had taken only two immunosuppressive drugs, MMF and PR, and had not taken CyA at that time. His serum creatinine gradually rose after hospitalization. Allograft biopsy performed on April 6, 2006, showed acute vascular rejection (Banff 97 acute/active cellular rejection Grade III), together with suspicious for acute humoral rejection (Banff 97 antibody-mediated rejection Grade II). After treatment of two courses of steroid pulses and five d of gusperimus, acute vascular rejection and acute humoral rejection were relieved, which had been proven by the third allograft biopsy. In conclusion, this was a case of acute vascular rejection after overseas deceased kidney transplantation, resulted from non-compliance with immunosuppressive therapy.     

Cyclosporine trough (C0) and 2-hour postdose (C2) levels: which one is a predictor of graft loss?

BACKGROUND: Compared with conventionally measured trough level (C0), cyclosporine 2-hour postdose (C2) concentrations show a better correlation with the area under the curve and acute graft rejection. OBJECTIVES: We evaluated the relationships of C0 and C2 with long-term graft survival among kidney transplant recipients. METHODS: In a case-control design, we selected 215 adult kidney recipients. Inclusion criteria were more than 18 years of age at transplantation and at least 6 months of follow-up. The case group consisted of patients with graft loss (n=17) and a control group, patients with functioning grafts (n=198). The C0 and C2 levels for the first 6 months posttransplantation, along with demographic and clinical data, were compared between the two groups using univariate analysis. P<.05 was considered to be significant. RESULTS: The mean age at transplantation was 40.5 +/- 16.5 years. The mean follow-up duration was 18 +/- 14 months. The mean C0 values for the case and control groups were 257.8 +/- 126.5 and 248.5 +/- 104.4 mumol/L, respectively (P>.05). The values for C2 were 712.7 +/- 273.2 and 886.2 +/- 266.9 mumol/L, respectively (P=.01). CONCLUSIONS: We observed that C2, but not C0, in the first 6 months posttransplantation were a predictor of long-term graft survival. The findings here in supported the results of other studies that have proposed cyclosporine concentration monitoring by C2 rather than C0 measurements.     

Sirolimus (rapamycin) reduces the incidence of acute rejection episodes in renal transplantation: an initial experience in Taiwan

BACKGROUND: Acute rejection is the major cause of graft loss in renal transplantation. Sirolimus (rapamycin) inhibits the effects of cytokines on T and B cells; therefore, it provides prophylaxis against acute renal rejection. This open-label trial assessed the incidence of biopsy-confirmed acute rejection episodes, variation in renal function, as well as graft and patient survival rates up to 12 months posttransplantation when using sirolimus in combination with cyclosporine and prednisolone as immunosuppressants. METHODS: Ten kidney transplant recipients received sirolimus 2 mg daily after a 6-mg loading dose. Doses were then adjusted to keep the whole-blood trough level between 5 and 20 mg/mL. All patients received sirolimus in combination with cyclosporine and prednisolone. RESULTS: At 12 months after renal transplantation, the graft and patient survival rates were 90% and 90%, respectively. One patient died at 2 months due to sepsis with a functioning graft. The mean serum creatinine levels at 1, 3, and 6 months were 1.59 mg/dL, 1.71 mg/dL, and 1.65 ml/dL, respectively. There was no biopsy-confirmed acute rejection episode within 12 months. CONCLUSIONS: Sirolimus in combination with cyclosporine and prednisolone significantly protected kidney transplant recipients from acute rejection for up to 1 year of follow-up.     

Spontaneous tendon rupture after ofloxacin treatment in renal transplant recipients on high-dose corticosteroids

Acute tendon rupture without any history of trauma, a rare complication occurring mainly in metabolic diseases, is increasingly reported after treatment with fluoroquinolones. We report here on the occurrence of Achilles tendinitis and Achilles tendon rupture after ofloxacin treatment for uncomplicated urinary tract infection in four patients receiving high-dose corticosteroid treatment after renal organ transplantation and compare them with a control group without this complication. Patients experiencing tendon rupture had been on regular dialysis treatment for 54.5 ± 39.5 months before receiving cadaveric kidney transplants. All had secondary hyperparathyroidism, with parathyroid hormone levels ranging from 247 to 707 ng/L, had low or normal serum phosphate levels (1.21 to 2.69 mg/dL), and had moderately elevated alkaline phosphatase levels (75 to 285 U/L). Tendon ruptures occurred at a median of 49 days after organ transplantation and 15.3 ± 9.6 days after initiation of quinolone treatment. Mean time of treatment was 5 days. All patients received triple-regimen immunosuppression consisting of methylprednisolone, cyclosporin A, and mycophenolate mofetil. Transplant function was stable, and none had experienced transplant rejection. Mean ingestion of prednisolone ranged from 6 to 16 mg/d, and mycophenolate mofetil from 1 to 2 g/d; cyclosporin A serum levels were 208 ± 76 μg/L. After kidney transplantation, spontaneous large tendon rupture after quinolone treatment is deleterious during the early posttransplantion phase. Secondary risk factors are high-dose corticosteroid treatment and history of secondary hyperparathyroidism. Quinolones should be restricted for treatment of severe urinary tract infection only, which failed to respond to other antibiotic regimens in the early posttransplantation period after kidney transplantation under high-dose corticosteroid treatment.     

Failure of anti-CD20 monoclonal antibody therapy to prevent antibody-mediated rejection in three crossmatch-positive renal transplant recipients

There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m(2)) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occurred in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m(2) at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients.     

Two cases of recurrent IgA nephropathy following kidney transplantation

Recurrence of immunoglobulin (Ig) A nephropathy following kidney transplantation has been described as occurring in 40% to 60% of cases. Although this type of recurrence was considered a benign condition for a long time, more recent data showed that recurrent transplant IgA nephropathy may be a significant contributor to graft loss. We present 2 cases of recurrent IgA nephropathy following kidney transplantation. In case 1, renal function remained stable with a creatinine level of 1.2 mg/dL at 5 months after diagnosis and 61 months after transplantation. In case 2, the patient lost his graft and returned to regular hemodialysis at 36 months after diagnosis and 125 months after kidney transplantation.     

Rituximab in highly sensitized kidney transplant recipients

OBJECTIVES: Rituximab, an anti-CD20 monoclonal antibody therapy, depletes B cells and suppresses antibody production. This study sought to describe the efficacy and safety of rituximab among seven highly sensitized kidney transplant patients. METHODOLOGY: A highly sensitized patient was defined as panel-reactive antibody (PRA) >30%, more than three pregnancies, or history of positive tissue crossmatch. Demographics, immunological risk profile, and immunosuppression were collected on all highly sensitized patients transplanted from March to July 2007 and given rituximab. We noted graft function as well as clinical events posttransplantation. RESULTS: The seven patients included in the study showed a mean age of 39 years (range = 17-60) and a mean follow-up of 3 months (range = 1.5-5). Their average PRA was 62% with mean HLA mismatches of three. Five patients (71%) were retransplantations; one had a history of a positive crossmatch, and two had multiple pregnancies. Two had donor-specific antibody, but negative tissue crossmatches. All had living donors. Six patients received a single dose of rituximab (375 mg/m(2)) 1 day prior to transplantation and one received two doses after 19 sessions of plasmapheresis. All were given tacrolimus, mycophenolate, and steroids combined with induction therapy using 30 mg alemtuzumab in 33%; two doses of 20 mg basiliximab in 33%; and seven doses of 1 mg/kg/dose of daclizumab in 14%. Mean shown creatinine levels were 1.1 and 1.2 mg/dL at 1 and 6 months posttransplantation. Two recipients experienced acute humoral rejections within 1 month after transplantation. Both were given steroid pulsing, one of whom was steroid-resistant necessitating alemtuzumab therapy and plasmapheresis. Graft function of both improved with creatinine values of 1.3 mg/dL on discharge. No episodes of infection were noted. CONCLUSIONS: Rituximab can be safely administered and may be effective to improve outcomes among highly sensitized kidney transplant patients.     

Campath-1H (alemtuzumab) as an induction agent for the prevention of graft rejection and preservation of renal function in kidney transplant patients: Philippine 3-year follow-up

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of induction with Campath-1H with low-dose cyclosporine (CsA) monotherapy using outcome measures of acute rejection episodes (ARE), chronic allograft nephropathy (CAN), graft and patient survivals, as well as malignancies and infections. MATERIALS AND METHODS: Fourteen kidney transplant recipients were randomized to receive either Campath 1H induction with CsA monotherapy (9 patients) or immunosuppression with CsA, azathioprine, and steroids (5 patients). Campath (20 mg IV) was administered within 6 hours after the anastomosis and repeated 24 hours later. Cyclosporine was started 72 hours after the first Campath dose (10 mg/kg on the first day, then 4 mg/kg/d), seeking to achieve target trough CsA levels of 90 to 110 ng/mL. This is a 3-year follow-up of the 9 patients who received Campath-1H induction. RESULTS: Six of 9 (67%) patients developed ARE (borderline ARE to Banff IB) in the Campath group compared with 1 of 5 (20%) in the other group (ARE Banff IIA). They all received methylprednisolone for 3 days with good responses. One of the 6 patients in the Campath group with ARE also displayed CAN and was converted to sirolimus; 2 others had mycophenolate mofetil and steroids added to their immunosuppression after the ARE. Creatinine levels ranged from 1 to 1.7 mg/dL at 24 to 36 months posttransplantation in both groups. Among the Campath group, 1 patient died 6 months posttransplantation with sepsis secondary to infectious diarrhea. Upper respiratory tract infections comprised the majority of infections at 24 to 36 months. No malignancies were observed. CONCLUSIONS: Three years posttransplantation, patients given Campath induction with CsA monotherapy showed a greater incidence of ARE, although renal function remained comparable to CsA-azathioprine-prednisone therapy. AREs were easily reversed with steriods. Infections were minor.     

在移植肾功能稳定的受者中主动撤除环孢素A的临床研究

目的 研究在移植肾功能稳定的受者中主动撤除环孢素A(CSA)对急性排斥反应发生率及肾功能的影响.方法 选择35例肾功能稳定的肾移植受者,其中尸体肾移植23例,亲属活体肾移植12例.除2例为再次肾移植外,其余均为初次肾移植.分别在肾移植术后6个月～6年时停用CsA,平均为术后(13.3±9.1)个月.撤除CsA后免疫抑制方案为:霉酚酸酯(MMF)+西罗莫司(SRL)+泼尼松(Pred).撤除CsA前有9例做了移植肾穿刺活检,8例测定了抗HLA抗体.结果 对35例受者随访6个月～4.5年,平均14.8个月.撤除CsA前、后血肌酐平均值分别为(88.1±15.5)μmol/L和(92.3±23.7)/μmol/L(P0.05).撤除CsA后,有2例经活检证实发生急性排斥反应,治疗后均逆转;CsA所致的毒副作用,如牙龈增生、糖耐量异常和多毛症等明显改善.9例移植肾活检中,有3例肾功能正常的受者已出现轻度慢性移植肾肾病表现.抗HLA抗体检测中,7例阴性者在撤除CsA前、后肾功能无明显变化.1例抗HLA抗体呈强阳性者在撤除CsA后进展为慢性移植肾肾病,恢复血液透析.结论 对移植肾功能稳定的受者在移植6个月后撤除CsA,转换为"霉酚酸酯+西罗莫司+泼尼松"的免疫抑制方案是安全的,不增加急性排斥反应风险;撤除CsA有利于消除一些与其相关的毒副作用;对抗HLA抗体呈强阳性者.撤除CsA后很难改变肾功能的进展.     

Living Related Liver Transplantation in Crigler-Najjar Syndrome Type 1

Four children underwent living related liver transplantation because of Crigler-Najjar syndrome type 1. Three were infants aged 2, 8½, and 15 months, and weighed 5, 8, and 10 kg, respectively. Pretransplantation unconjugated bilirubin concentration was 22 to 30 mg/dL despite 12 to 14 hours of phototherapy daily. Patient 1, the 2-month-old infant, with unconjugated bilirubin concentration of 30 mg/dL, had a high-pitched cry, suggestive of bilirubin encephalopathy; results of neurologic examination were normal. Plasmapheresis and urgent liver transplantation were performed. Patient 4, a 13-year-old girl, had learning difficulties at school and attended a special class. Three patients received left lateral liver segments, and 1 patient received a left lobe. Biliary reconstruction was completed with duct-to-duct anastomosis. Bile leakage developed at the anastomosis in 2 patients, which was treated successfully with cholangioplasty. In all patients, the unconjugated bilirubin concentration normalized by day 1 posttransplantation, and no phototherapy was necessary. After transplantation, the 2-month-old infant with suspected encephalopathy exhibited hypotonia, spasticity of the lower extremities, and lack of head control. He died after vomitus aspiration during sleep at 10 months posttransplantation. The other 3 patients are alive with normal neurodevelopmental milestones. Irreversible brain damage may occur early in the course of Crigler-Najjar syndrome type 1. Urgent treatment including plasmapheresis, exchange transfusion, phototherapy, and liver transplantation may not reverse brain damage. Young infants must be evaluated carefully for subtle signs and symptoms of bilirubin encephalopathy. Liver transplantation is curative if performed before development of neurologic dysfunction.     

Sirolimus monotherapy: feasible immunosuppression for long-term follow-up of kidney transplantation--a pilot experience

Chronic allograft nephropathy (CAN), cardiovascular mortality, and posttransplant malignancy are complications of conventional immunosuppression after kidney transplantation. The aim was to study feasibility of sirolimus (SRL) maintenance monotherapy in a pilot experience. All patients with SRL monotherapy of at least 6 months follow-up were included. In 19 patients, age 58 (34-74) years, SRL monotherapy was introduced 98.1 (49-193) months after transplantation by withdrawing concomitant immunosuppressants from protocols already including SRL or introducing SRL and withdrawing other immunosuppressants. Follow-up is 20.0 (6-41) months. One patient died from hepatocellular carcinoma, diagnosed before SRL monotherapy, with functioning graft. No rejections occurred. SRL trough concentration was 10.7 (4.6-16.1) microg/L. Creatinine (1.77 [1.0-2.9] mg/dL vs. 1.68 [0.8-3.3] mg/dL after 6 months, 1.97 [0.8-4.6] mg/dL at last follow-up; P=NS). Proteinuria increased tendentially (333 [67-893] vs. 890 [46-4011] mg/day). No significant changes of hemoglobin, triglycerides, or cholesterol occurred. SRL monotherapy late after kidney transplantation is feasible in selected patients.     

Denovo urothelial carcinoma of the upper and lower urinary tract in kidney — transplant patients with end-stage analgesic nephropathy

Summary Patients with end-stage analgesic nephropathy bear a higher risk for urothelial cancer than do patients with other renal diseases. In a retrospective study in patients with analgesic nephropathy and kidney transplants we analyzed the prevalence and clinical course of de novo urothelial cancer. Diagnosis of analgesic nephropathy was based on the patients' history and clinical data. Only patients under cyclosporine treatment were included. Between 1968 and 1993, 2,371 kidney transplants were performed on 2,072 patients in the Department of Abdominal and Transplant Surgery. The prevalence of analgesic nephropathy was 3.1%. Of 65 patients with analgesic nephropathy and kidney transplants, 10 (15.4%) developed urothelial carcinoma; 10.8%, bladder cancer; and 9.1%, renal pelvic cancer. The mean age at diagnosis was 56.1 years. Urothelial cancer occurred on average at 33.6 months posttransplantation. On average, 6 of 10 patients with urothelial cancer died of the disease at 16.9 months after the diagnosis. All patients with urothelial bladder cancer had a muscle-infiltrating tumor of moderate or high grade. Since urothelial renal pelvic cancer occurred in 9.1% of our patients with analgesic nephropathy and urological screening is insufficient in patients on dialysis, we suggest that prophylactic nephroureterectomy be performed on one side before transplantation and on the contralateral side at 3–6 months after transplantation. An aggressive approach is indicated in patients with urothelial cancer of the bladder.     

Acute Renal Failure Caused by Hyperuremic Acidemia in ABO-Incompatible Kidney Transplant Maintained With Cyclosporine and High-Dose Mizoribine: A Case Report

Introduction

The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension.

Case Report

A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL.

Conclusion

Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.