Pediatric renal transplantation: a single-center experience

A retrospective analysis was performed on 33 pediatric renal transplants performed over last 8 years. The mean age and weight at the time of transplantation was 12.5 +/- 3.86 years and 28.75 +/- 9.04 kg, respectively. Twenty-six children were boys and 7 were girls. Thirteen children had underlying glomerular disease and 17 had tubulointerstitial disease. All transplants were living related except two, which were from deceased donors. The median duration of hemodialysis and peritoneal dialysis before transplantation were 2.75 and 4 months, respectively. The most common posttransplant complication was urinary tract infection. Immunosuppression medications in the majority included cyclosporine, azathioprine, and corticosteroids. Actuarial graft survivals at 1, 3, and 5 years were 94%, 90%, and 82%, respectively.     

Offspring-to-mother and husband-to-wife renal transplantation: a single-center experience

BACKGROUND: It has been demonstrated that graft survival rates of offspring-to-mother and husband-to-wife renal transplants are equivalent to those of other living donors. Although the vast majority of these transplants proceed without incident, hyperacute rejection can result from an anamnestic reaction subsequent to the in utero exposure of the mother to human leukocyte antigen (HLA) of the fetus with sensitization developing during the pregnancy. PATIENTS AND METHODS: Among 1350 renal transplants performed at our center, 12 corresponded to offspring-to-mother (G1) and 9 were husband-to-wife transplantations (G2). All recipients were multiparous (2 to 5 children). We compared these patients with other multiparous women (n = 150) who received grafts from living unrelated donors (G3). RESULTS: Two subjects in G1 (16.6%), two in G2 (22.2%), and none in G3 developed hyperacute rejection, which led to graft loss. One, 3-, and 5-year patient and graft survival rates were different between the remaining patients. CONCLUSIONS: Our limited experience suggested that, for some women, pregnancy is in fact a sensitizing event. A pretransplantation cross-match testing negative result was by no means an absolute guarantee that an adverse anamnestic immunological event would not occur.     

Sirolimus-induced pneumonitis after renal transplantation: a single-center experience

Purpose

Sirolimus is a potent immunosuppressive agent used with increasing frequency in kidney transplantation. However, sirolimus can increase the rate of unexplained interstitial pneumonitis. The aim of this study was to evaluate the clinical characteristics of sirolimus-induced pneumonitis and the therapeutic results in renal transplant recipients.

Patients and methods

Seventy-two patients received sirolimus, conversion or de novo regimen, at our center between January 2007 and April 2011. Twelve of the 72 patients (16.7%) developed interstitial pneumonitis. The patients were divided into three groups according to the following indications of sirolimus use: de novo, early conversion, and late conversion groups.

Results

The mean duration of follow-up was 11.0 ± 11.5 months. The mean blood level of sirolimus measured by microparticulate enzyme immunoassay was 16.5 ± 7.4 ng/mL at the time of diagnosis. The mean time from the start of sirolimus to pneumonitis onset was 14.7 ± 8.0 months. The clinical presentation included fever, cough, dyspnea, general weakness, and periorbital edema. In most cases, radiological imaging tests revealed bilateral lower-lobe involvement. Bronchoalveolar lavage was performed in three patients and two patients showed lymphocytic alveolitis. Sirolimus was discontinued or reduced for the treatment of pneumonitis. All cases of pneumonitis were resolved within 2 to 4 weeks.

Conclusion

Sirolimus blood level should be monitored tightly and early intervention is important when sirolimus-induced pneumonitis is suspected.     

Operational tolerance in living-related renal transplantation: a single-center experience

Introduction

Various methods have been tried to induce operational tolerance in organ transplantation. We present a single-center experience using 6 tolerance induction protocols (TIP) in living-related renal transplantation.

Methods

We evaluated 6 TIP protocols: (1) peripheral blood stem cells employed (n = 38); (2) midified the protocol by portal infusion (n = 292); (3) the second protocol plus TIP+DST+BM+intrathymic and intramarrow infusion plus low-dose, nonmyeloablative conditioning employed (n = 174), (4) the third protocol of TIP plus cultured hematopoietic stem cells (HSC) with target-specific irradiation (n = 290); (5) TIP 4 plus thymus, intramarrow infusion, and target-specific irradiation converted to total lymphoid irradiation (TLI) (n = 366); and (6) TIP 5 plus bortzomib-TLI (n = 165). Patient/donor demographics were comparable.

Results

We evaluated patient and graft survival, rejection episodes, recurrence, drug toxicity, and chimerism revealed; groups 4 and 5 showed better survival, graft function, chimerism, and decreased rejection episodes compared with previous protocols. Serum creatinine (mg/dL) at 1 year was 1.5, 1.39, 1.5, 1.51, 1.46, and 1.41, and at 5 years, 1.69, 1.72, 1.82 and 1.59, in groups 1-6, respectively. Chronic rejection episodes were 10.5%, 14.1%, 10.4%, 9.3%, 3.5%, 1.7%, and 1.8% respectively. Patient survival of groups 1, 2, and 3 at 1, 5, and 10 years was 86.5%, 56.8%, and 40.1%; 89.4%, 69.1%, and 56.4%; and 89.6%, 67.7%, and 64.6%, respectively; of group 4 for 1 and 5 years was 92.4% and 81.8%; for groups 5 and 6 for 1 year was 94% and 96.3%, respectively. The death-censored graft survival of groups 1, 2, and 3 at 1, 5, and 10 years was 91.9%, 70.3%, and 64.7%; 89%, 66%, and 57.6%; and 86.7%, 67%, and 42.5%, respectively. In group 4 for 1 and 5 years was 87.9% and 74.7%; and for groups 5 and 6 for 1 year was 94% and 96.5%, respectively.

Conclusion

TIP results showed improved graft/patient survivals, minimum immunosuppression, and fewer rejection episodes and recurrence.     

Urinary tract infections following renal transplantation: a single-center experience

BACKGROUND: Although infectious complications are the second most common cause of death after transplantation, there appears to be insufficient data regarding the impact of urinary tract infections (UTIs) on graft outcome and patient mortality and morbidity. In this study, we evaluated the incidence, risk factors, and long-term effects of UTIs on graft function. METHOD: We performed a retrospective cohort study reviewing the medical records of patients who received a renal transplant at our center from January 1999 to December 2006. All UTIs, risk factors, long-term graft function, graft loss, and death were recorded. Outcomes among patients with UTIs were compared with those without UTIs. RESULTS: Fifty-six of 136 patients (41.2%) had at least one UTI over a mean period of 38+/-25 months after transplantation. While there was a tendency toward graft loss among patients with UTIs (16.1% vs 6.3%, P=.08), there was no increased risk of death. The patients with UTIs displayed higher serum creatinine levels (1.7+/-1.4 vs 2.3+/-2.5 mg/dL, P=.07) compared to non-UTI patients in the long term. Upon multivariate analysis, female gender was the only risk factor for posttransplant UTIs. We did not determine any immunosuppressive drug as a risk factor for UTIs. The most frequent pathogens isolated in urine culture were Escherichia coli (n=72, 59.1%) and Klebsiella spp (n=21, 16.9%), and there were eight cases of bacteremia. CONCLUSION: UTIs are a frequent problem after kidney transplantation. Female recipients are at greatest risk. In the long-term, UTIs should be considered as a potential risk for poorer graft outcomes.     

Pregnancy after renal transplantation: A single-center experience

Objectives:   To examine women with renal transplants who became pregnant, and delivered at our hospital.
Methods:   Twenty-six women who had undergone renal transplantation between 1977 and 2002 became pregnant, and delivered at Osaka University Hospital. Complete medical records of twenty of them were retrieved and retrospectively analyzed.
Results:   Overall, twenty-nine pregnancies occurred in these twenty women after renal transplantation. There were spontaneous abortions in three cases, whereas pregnancy was artificially terminated five times. Thus, neonates were delivered in 21 of 29 pregnancies. One woman delivered twice and two women delivered twins. As a result, a total of 23 neonates were delivered. Mean gestational period was 35.4 weeks (range, 27–41 weeks), and mean birth weight was 2229 g (range, 724–3544 g). Regarding fetal complications, intrauterine growth retardation was observed in three cases. One child with intrauterine growth retardation died at 3 months old due to respiratory distress syndrome. One child displayed double-outlet right ventricle and another child had congenital unilateral hydronephrosis. Regarding maternal complications, prevalence of toxemia of pregnancy was 38.1%. In four of the 21 deliveries (19.0%), renal function exacerbated after delivery. Rates of graft survival for the 20 women at 1, 5 and 10 years after delivery were 100%, 85.1% and 74.4%, respectively. Prognosis for renal transplant resulted to be significantly poorer for recipients with hypertension before pregnancy than for recipients without hypertension before pregnancy (log-rank test, P  = 0.043).
Conclusions:   Rates of graft survival after delivery were mostly favorable. However, prognosis for renal function was poorer for recipients who displayed hypertension prior to pregnancy.     

Pregnancy after renal transplantation: ten-year single-center experience

There has been an increase in the number of pregnancies among renal transplant recipients. Our experience included 61 pregnancies in 53 patients from January 1997 to April 2007, with 6 patients having multiple pregnancies. Patients were studied for clinical, obstetrical, and perinatal outcomes. The mean patient age was 24.5 years (range, 19-38). They all received living donor kidneys. The mean transplantation-pregnancy interval was 2.7 years (range, 1.7-5.3 years). Immunosuppressive drugs consisted of cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone (pred) in 38 patients (72%); CsA, azathioprine (AZA), plus pred were used in 15 patients (28%). Pregnancy complications were chronic hypertension in 21 patients (40%), anemia in 28 (52.6%), and urinary tract infection in 18 (34%). Twelve patients (22.6%) received blood transfusions. Pre-eclampsia was diagnosed in 14 cases (26.4%) and renal dysfunction in 11 (20.7%) with pre-eclampsia assumed to be the main cause. Three patients (5.6%) had graft losses as a result of hemorrhagic shock, sepsis, and eclampsia. Premature rupture of membranes occurred in 6 cases (11.3%), and preterm delivery occurred in 14 cases (26.4%). Eleven (20.7%) newborns were small for gestational age. One club foot and one large facial hemangioma occurred in 2 infants, respectively. One case of neonatal death was registered as a result of excessive prematurity. One mother died due to sepsis. Cesarean section was performed in 24 patients (45.2%), the main indications being related to hypertension and fetal distress. There were no significant differences between MMF-treated and AZA-treated patients with respect to clinical, obstetrical, and perinatal outcomes. This group of patients was characterized by a wide range of antenatal and perinatal problems that must be managed in specialized tertiary units to achieve the best results. MMF may be as safe as AZA in pregnancy.     

Outcome of renal transplantation in Alport's syndrome: a single-center experience

Background

Anti-glomerular basement membrane (anti-GBM) nephritis post-renal transplantation (RTx) is known to cause graft loss in Alport's syndrome (AS). We evaluated the results of RTx in AS patients vis à vis patient and graft survivals, incidence of anti-GBM nephritis, and causes of graft failure.

Materials and methods

Between 1993 and 2009 we performed 31 RTx on AS patients (28 males and three females) of overall mean age of 22 ± 7.9 years from six deceased and 27 living donors. Two patients underwent second RTx.

Results

Over a follow-up of 1, 3, 5, and 10 years, the mean serum creatinines (mg/dL) were 1.51 ± 0.52, 1.59 ± 0.26, 1.61 ± 0.30, and 1.63 ± 0.32, respectively. Patient survivals at 1, 5, and 10 years were 89.71%, 81.32% and 81.32% with graft survival for all periods of 81.2%. Twenty-one percent experienced biopsy-proven acute rejection episodes. Graft failures were due to anti-GBM nephritis in 12.2% (n = 4), chronic allograft nephropathy in 3.2% (n = 1), and acute rejection or cyclosporine toxicity 3.2% (n = 1 each). The mean duration to graft loss was 4.9 ± 2.4 months.

Conclusion

Graft and patient survivals were acceptable among transplant recipients with AS despite the risk of anti-GBM nephritis.     

亲属活体肾移植的伦理学审查:单中心经验总结

目的总结单中心亲属活体肾移植的伦理学审查经验。方法成立北京大学第三医院人体器官移植临床应用与管理伦理委员会(伦理委员会),对130例次在该院拟行亲属活体肾移植的供、受者进行伦理学审查。以国务院《人体器官移植条例》为依据,先对供、受者进行科内初审,然后召开伦理委员会会议进行审查,内容包括移植供、者双方关系是否为亲属,双方术前检查结果是否符合移植要求,供者是否具有完全民事能力,双方是否了解手术风险,供者是否完全自愿捐献,其亲属是否同意,双方是否签署书面知情同意书等。根据审查结果确定能否进行手术。结果 120例次得到批准并顺利完成了肾移植手术,供受双方恢复满意,无发生纠纷。10例次被否决,其中不能确定亲属关系5例次,双方术前检查结果不符合移植要求2例次,供者无完全民事能力1例次,供者配偶不同意移植1例次,非本人真实意愿捐肾1例次。结论成立伦理委员会,严格按照《人体器官移植条例》的要求对拟行亲属活体肾移植的供、受者双方进行伦理学审查可保证器官移植的规范性和医疗安全性。     

Outcome of kidney transplantation for renal amyloidosis:a single-center experience

The aim of this retrospective study was to investigate the results of kidney transplantation in patients with renal amyloidosis. We analyzed the results of renal transplantation in 13 amyloidotic transplant recipients compared with those in a control group of 13 nonamyloidotic patients. While the etiology of amyloidosis was rheumatoid arthritis in one patient, in all of the others it was secondary to familial Mediterranean fever. Acute rejection episodes developed once in six and twice in one patient. The renal function in these patients was improved by antirejection treatment. Chronic rejection did not develop in any patient. However six patients (46%) died due to various complications despite functional grafts. The others are still being followed with well-functioning grafts. Among the control group, acute and chronic rejection were diagnosed in three and two patients, respectively: one patient returned to hemodialysis after 26 months of transplantation, while the others are still alive with functional grafts. There was no death in the control group. The 5- and 10-year actuarial patient survival rates of the amyloidosis and control groups were 52.2%, 26.6%, and 100%, 100%, respectively (P = .002). However, the graft survivals of the amyloidosis versus control groups were 100%, 100%, versus 87.5%, 87.5, respectively (P = .47). In conclusion, we observed a high rate of early mortality among recipients with amyloidosis associated with infectious complications. Moreover, patient survivals were lower among amyloidotic renal recipients.     

Outcome of primary glomerular disease in pediatric renal transplantation: a single-center experience

INTRODUCTION: The recurrence of primary disease in transplantation is a well-known problem. We report our single-center experience to assess the frequency of the recurrence of primary glomerulonephritis in children after renal transplantation. PATIENTS AND METHODS: Medical reports of 14 children with primary glomerular disease were evaluated. Among the 14 grafts were 10 from living related and four from cadaveric donors. Ten were diagnosed as focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN), and two polyarteritis nodosa (PAN). The original diagnosis was biopsy-proven in every case. All patients were treated with calcineurin-based immunosuppressive therapy. RESULTS: The mean age was 15.5 +/- 5.4 years. The median transplantation duration was 47 months; however, one of the FSGS patient had hyperacute rejection. Five years later she received a second graft with a serum creatinine of 0.7 mg/dL at 7 years after transplantation. Posttransplant recurrence of FSGS was confirmed in two patients (20%), who were treated with plasmapheresis with no improvement of proteinuria, two FSGS patients had thromboses after transplantation. One had a cardiac thrombosis with heterozygote MTHFR mutation and one, a renal artery thrombosis and loss of graft with prothrombin 20210A mutation. They all have functioning grafts except these two. We did not observe recurrence of PAN or MPGN in patients. CONCLUSION: Although the number of patients is quite small, our recurrence rate was compatible with the previous reports. Additionally, we strongly recommend evaluation of all risk factors for thrombosis and give appropriate anticoagulation.     

A single-center experience of renal transplantation in elderly patients: a paired-kidney analysis

BACKGROUND: Chronic renal failure is a disease of the elderly. The elderly are the fastest growing population among dialysis patients and also on waiting lists for kidney transplantation. The objective for this study was to analyze the results of the renal transplantation in recipients elder than 60 years. To minimize the donor variability and bias, a paired kidney analysis was used. METHODS: The older renal transplantation (ORT) group included 44 patients (30 men, 14 women) aged 60 to 72 (mean 64+/-3) years. Their pairs created a younger renal transplantation (YRT) group consisting of 44 patients (30 men, 14 women) aged 14 to 59 (mean 40+/-12) years. RESULTS: Graft function estimated 1 year after transplantation applying abbreviated Modification of Diet in Renal Disease formula was significantly better in ORT (46.8+/-10.2 ml/min) versus YRT (43.7+/-16.8 ml/min). Studied groups (ORT vs. YRT) did not differ significantly with respect to 1-year patient survival (93.2% vs. 95.5%), 1-year graft survival (88.6% vs. 86.3%), 1-year death-censored graft survival (93% vs. 90.1%), and the incidences of delayed graft function and acute rejection. The most common complications noticed after ORT were cardiovascular complications, surgical complications, and infections. CONCLUSIONS: Our single-center results confirm that renal transplantation is a good option of renal replacement therapy in patients older than 60 years. Thorough recipient selection and preparation as well as customized immunosuppressive protocols are particularly important in that group of renal transplant recipients.     

Triple immunosuppression with tacrolimus in pediatric renal transplantation: single-center experience

AIM: In this single-center cohort, we retrospectively analyzed the efficacy and safety of tacrolimus in pediatric renal transplantation. METHODS: We examined the medical records of 22 consecutive renal transplantation recipients (12 boys, 10 girls) receiving tacrolimus, to evaluate occurrence of acute rejection (AR) episodes, glomerular filtration rates (GFR), and side effects. RESULTS: The mean recipient age was 15.07 +/- 3.96 years. Seven grafts came from cadaveric, and 15 from living related donors. The patients were placed on immunosuppression with prednisolone and tacrolimus plus azathioprine (n = 8) or mycophenolate mofetil (MMF) (n = 12) or enteric-coated mycophenolate sodium (n = 2). Eighteen patients received basiliximab on days 0 and 4. There were three AR episodes at 5, 9, and 12 months. Mean GFR at the end of 1 and 2 years were 97.1 +/- 24.0 mL/min/1.73 m(2) and 116.9 +/- 42.2 mL/min/1.73 m(2), respectively. There was no graft loss. Hypertension, hyperlipidemia, and hyperglycemia were present in 14 (63.6%), 3 (13.6%), and 3 (13.6%) patients, respectively, without gingival hyperplasia, tremor, or hypertrichosis. Supraventricular tachycardia was noticed in five patients (22.7%), three of whom needed antiarrhythmic drugs (13.6%). CONCLUSION: Our single-center experience with tacrolimus, steroid plus azathioprine or MMF or enteric-coated mycophenolate sodium regimen in pediatric kidney recipients showed a low rate of AR with excellent graft survival and function at 1 and 2 year posttransplantation. The increased rate of supraventricular tachycardia in this regimen had not been previously reported; this association merits further studies.     

A single-center experience of renal transplantation in thirteen Jehovah's Witnesses

The beneficial effects of pretransplant blood transfusions on the success rate of renal transplantation have been so overwhelmingly emphasized that there is virtually no information on the fate of grafts in nontransfused patients transplanted during the last decade. Since 1979, all patients who have undergone renal transplantation at the University of Minnesota have routinely received random blood transfusions except Jehovah's Witnesses. Jehovah's Witnesses refuse transfusions but will accept renal allografts. From 1979 to May 30, 1987, primary renal allografts were placed in thirteen nontransfused Jehovah's Witnesses; six patients received kidneys from mismatched living-related donors, two patients received HLA-identical sibling grafts, and five patients received cadaveric renal allografts. The range of follow-up of the thirteen patients was 3-93 months, with a mean of 45 months and a median of 50 months. The outcomes after renal transplantation in Jehovah's Witnesses were compared with those of a paired control group (n = 25) matched for age, date of transplant, donor source, and diabetic status. The overall three-year actuarial patient and graft survival rates of the Jehovah's Witnesses were 83 per cent and 66 per cent, versus 80 per cent and 77 per cent for the controls. Although the outcomes after renal transplantation in Jehovah's Witnesses were similar to those of the control group, the Jehovah's Witnesses had an increased susceptibility to rejection episodes. The cumulative percentage of incidence of primary rejection episodes was 77 per cent at three months in the Jehovah's Witnesses versus 44 per cent at 21 months in the matched control group. The consequence of early allograft dysfunction from rejection was particularly detrimental to Jehovah's Witnesses who developed severe anemia (hemoglobin (Hgb)* 4.5 g per cent)-two early deaths occurred in the subgroup with this combination of problems. The overall results suggest that renal transplantation can be safely and efficaciously applied to most Jehovah's Witnesses but those with anemia who undergo early rejection episodes are a high-risk group relative to other transplant patients.     

Tacrolimus-related neurologic and renal complications in liver transplantation: A single-center experience

Among 71 patients, 19 (26.7%) experienced tacrolimus-related complications including 15 neurologic reactions and four problems with nephrotoxicity. Seven of these patients received grafts from cadaveric donors and 12 from living donors. Nine patients were children. The cohort included 5 female and 14 male subjects of mean age 26 +/- 20 (min 6, max 65) years. The common indications for the liver transplantation were cholestatic and metabolic diseases in pediatric patients, and viral hepatitis in adult patients. Blood tacrolimus levels were within the normal range. All patients with neurologic complications received antiepileptic therapy and drug conversion to rapamycin in 4 cases and to cyclosporine (CsA) in 11 cases. Six cases with Wilson disease and all cases with tyrosinemia experienced neurologic complications, which reversed in all but one case. In four cases with nephrotoxicity, we switched to rapamycin. Renal function improved in all cases. Patients with Wilson disease and tyrosinemia were more susceptible to the neurologic side effects of tacrolimus. In these cases we recommend the use of drugs with fewer neurologic side effects. Tacrolimus also has nephrotoxic effects, which can be reversed by converting to rapamycin.     

Outcomes of renal transplantation after end-stage renal disease due to diabetic nephropathy: a single-center experience

Background

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide. However, data on renal transplantation outcomes in diabetic nephropathy among Japanese remain inadequate. This retrospective study was conducted to summarize our renal transplantation experience in diabetic ESRD patients.

Methods

We retrospectively studied 462 patients who underwent kidney transplantation between 1989 and 2011, including 23 with diabetic ESRD (DM group) and 439 with nondiabetic ESRD (NDM group). We compared demographic and clinical variables between these 2 groups.

Results

Mean age was higher in the DM group (48.0 vs 38.2 years; P < .001), and there was no significant difference in gender or donor source. The 1-, 3-, and 5-year graft survival rates in the DM and NDM groups were 100% vs 98.3% (ns), 82.4% vs 94.9% (P < .05), and 66.7% vs 90.3% (P < .01), respectively. The 1-, 3-, and 5-year patient survival rates were 95.0% vs 96.5% (ns), 88.2% vs 95.2% (ns), and 84.6% vs 92.9% (ns), respectively. One patient (4.3%) in the DM group and 6 (1.4%) in the NDM group died from cardiovascular disease during the follow-up period (ns). The incidence of rejection did not differ between the DM and NDM groups. There were no significant differences in the total infection rate or the urinary tract infection rate.

Conclusions

Renal transplantation in diabetic ESRD patients yields good results in terms of patient survival and complications, suggesting that renal transplantation can be performed in these patients and should become a more established treatment option.