Long-term outcomes of en-bloc renal transplantation from paediatric donors into adult recipients.

INTRODUCTION: Transplant units are exploring strategies to increase the availability of donor kidneys. The use of en-bloc kidney transplantation (EBKT) from paediatric donors represents one potential solution. We present our long-term experience with paediatric EBKT among adult recipients. METHODS: Twenty-three paediatric to adult EBKTs were performed by the Irish National Kidney Transplant Service between 1990 and 2016. The primary outcome variable was long-term en-bloc allograft survival rate. Secondary outcome variables were incidence of allograft thrombosis, incidence of delayed graft function, overall patient survival and serum creatinine at most recent follow-up. Outcomes were compared to single kidney transplant recipients from the same time period. RESULTS: Mean donor age was 1.8 ± 0.97 years (range: 7 months to 3 years). Recipient age was 46 ± 12 years. Mean follow-up was 133 ± 64 months (range: 36-264). Overall graft survival was 100%, 91% and 80% after 1, 5 and 10 years respectively, compared to 92%, 79% and 61% in single kidney transplant recipients (p = 0.04). There were 5 cases of allograft failure, 3 due to death from unrelated causes. Median time to graft failure was 108 months (range: 36-172). Mean serum creatinine was 72.6 ± 21.6 µmol/l after the follow-up period. There were no cases of graft thrombosis or delayed graft function. Overall survival was 96.4%, 88.0%, 76.23% and 50.5% at 1, 5, 10 and 20 years respectively. CONCLUSION: En-bloc paediatric kidney transplantation is associated with excellent long-term allograft and patient survival and is a feasible strategy for increasing the transplant donor pool in carefully selected recipients.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

Incidence and long-term outcomes of squamous cell bladder cancer after deceased donor renal transplantation.

OBJECTIVE: To review the incidence and long-term outcomes of squamous cell carcinoma (SCC) of the bladder in patients after kidney transplantation. METHODS: Between January 1976 and March 2013, five patients from one center (0.0013%) developed SCC of the bladder after undergoing a deceased donor kidney transplant. Their relevant risk factors included long-term self-intermittent catheterization/indwelling catheter (n = 2), smoking history (n = 2), and a prior history of cyclophosphamide treatment for vasculitis (n = 1). Primary outcome variables were overall patient survival and latency period between transplantation and SCC diagnosis. RESULTS: The duration of long-term follow-up was 94 ± 89 (range: 4-239) months. The latency period between transplantation and bladder SCC was 87 ± 87 (range: 2-228) months, and all five patients were immunosuppressed with tacrolimus, mycophenolate mofetil, and prednisone. Four patients had suspected metastases upon presentation, and one patient presented with organ-confined disease. This patient underwent a radical cystectomy and remains disease free eight months post-operatively. Despite radical treatment, the remaining four patients died from metastatic disease 7 ± 4.4 (range: 2-11) months after their initial diagnosis. CONCLUSION: SCC of the bladder has a poor prognosis particularly in renal transplant patients. Early detection with flexible cystourethroscopy in patients with risk factors for SCC may improve long-term outcomes in this patient cohort.

A review of inpatient urology consultations in an Irish tertiary referral centre.

INTRODUCTION: Our institution is a 680-bed tertiary referral centre with broad medical and surgical subspecialty services. We retrospectively audited the pattern of inpatient consultations from all specialities within our institution to the urology department over a 1-year period. METHODS: All consultations to the urology service were identified from our computerised inpatient consultation system from July 2010 to June 2011. Follow up data on investigations, interventions and subsequent outpatient appointments were also identified by review of individual patient discharge letters. RESULTS: Seven hundred and twenty five inpatient consultations were received over the period. The male to female ratio was 7:3. Mean age of patients was 66 (15-96) years. Seventy three percent of referrals were from medical sub-specialities, most commonly nephrology (17%), gastroenterology (11%) and respiratory medicine (9%). The remainder were from general surgery (16%) and other surgical sub specialities (11%). Interns (66%) and senior house officers (SHO) (28%) communicated the majority of consults. Male lower urinary tract/benign prostate related issues resulted in 25% of all consultations. Less than half of consults (47%) resulted in interventions initiated by urology, most commonly of which were catheter insertions (48%) and endoscopic procedures (35%). Only 43% of consultations were followed up in the outpatients setting. CONCLUSIONS: Inpatient consultations constitute a significant workload for urology services. The majority of these referrals did not require any urological intervention and could have been seen routinely in the outpatient setting. Providing structured referral guidelines and achieving better communication with referring teams may help to optimise this service.

Thalamic projection fiber integrity in de novo Parkinson disease.

BACKGROUND AND PURPOSE: Postmortem studies of advanced PD have revealed disease-related pathology in the thalamus with an apparent predilection for specific thalamic nuclei. In the present study, we used DTI to investigate in vivo the microstructural integrity of 6 thalamic regions in de novo patients with PD relative to healthy controls. MATERIALS AND METHODS: Forty subjects (20 with early stage untreated PD and 20 age- and sex-matched controls) were studied with a high-resolution DTI protocol at 3T to investigate the integrity of thalamic nuclei projection fibers. Two blinded, independent raters drew ROIs in the following 6 thalamic regions: AN, VA, VL, DM, VPL/VPM, and PU. FA values were then calculated from the projection fibers in each region. RESULTS: FA values were reduced significantly in the fibers projecting from the AN, VA, and DM, but not the VPL/VPM and PU, in the PD group compared with the control group. In addition, there was a reduction in FA values that approached significance in the VL of patients with PD. These findings were consistent across both raters. CONCLUSIONS: The present study provides preliminary in vivo evidence of thalamic projection fiber degeneration in de novo PD and sheds light on the extent of disrupted thalamic circuitry as a result of the disease itself.

A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

An unusual case of cancer of the urachal remnant following repair of bladder exstrophy.

INTRODUCTION: We report the first case of cancer of the urachal remnant following repair of bladder exstrophy, in a renal transplant recipient. METHOD: A retrospective review of this clinical case and the associated literature were performed. CONCLUSION: This unusual case highlights two very rare entities. Bladder exstrophy has an incidence of 1 in 50,000 newborns, whereas urachal cancer accounts for less than 1% of all bladder tumours.

Thalamic integrity underlies executive dysfunction in traumatic brain injury.

OBJECTIVE: To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury. METHODS: High-resolution (voxel size: 0.78 mm x 0.78 mm x 3 mm(3)) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age- and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei). RESULTS: Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory. CONCLUSIONS: The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition.

Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI.

BACKGROUND: People with schizophrenia demonstrate perceptual organization impairments, and these are thought to contribute to their face processing difficulties. METHOD: We examined the neural substrates of emotionally neutral face processing in schizophrenia by investigating neural activity under three stimulus conditions: faces characterized by the full spectrum of spatial frequencies, faces with low spatial frequency information removed [high spatial frequency (HSF) condition], and faces with high spatial frequency information removed [low spatial frequency (LSF) condition]. Face perception in the HSF condition is more reliant on local feature processing whereas perception in the LSF condition requires greater reliance on global form processing. Past studies of perceptual organization in schizophrenia indicate that patients perform relatively more poorly with degraded stimuli but also that, when global information is absent, patients may perform better than controls because of their relatively increased ability to initially process individual features. Therefore, we hypothesized that people with schizophrenia (n=14) would demonstrate greater face processing difficulties than controls (n=13) in the LSF condition, whereas they would demonstrate a smaller difference or superior performance in the HSF condition. RESULTS: In a gender-discrimination task, behavioral data indicated high levels of accuracy for both groups, with a trend toward an interaction involving higher patient performance in the HSF condition and poorer patient performance in the LSF condition. Patients demonstrated greater activity in the fusiform gyrus compared to controls in both degraded conditions. CONCLUSIONS: These data suggest that impairments in basic integration abilities may be compensated for by relatively increased activity in this region.

Benign prostatic hyperplasia presenting with renal failure--what is the role for transurethral resection of the prostate (TURP)?

The aim of the study was to determine the role of transurethralresection of prostate (TURP) in normalising renal function in men presenting with obstructive renal failure secondary to benign prostatic hyperplasia. We reviewed the cases of 14 men who presented in the last 5 years with renal impairment associated with symptoms of bladder outflow obstruction and radiological evidence of obstructive uropathy. The mean serum creatinine at presentation was 632 ng/mL (range 1299 - 225). The mean age at presentation was 68.2 years (range 50 - 83 years). Duration of symptoms prior to presentation ranged between 1 - 118 months (mean 21.5 months). Following catheter insertion, all patients underwent TURP. Six of the 14 patients required dialysis prior to surgery. Histology of the resected prostate confirmed benign prostatic hypertrophy and/or hyperplasia in all cases. Patients with carcinoma of the prostate were excluded from the study. Following TURP, 2 of the 14 men (14%) failed to void spontaneously following removal of catheter - one patient performs clean self intermittent catheterization (CSIC), the other man has an in-dwelling catheter in situ. One patient died 7 months following TURP due to a myocardial infarction. However, 8 patients, (57%) remained dialysis dependent following TURP. Two of these patients have since undergone successful renal transplantation. Of the remaining 6 patients, only 3 have normal renal function with the other 3 experiencing moderately elevated serum creatinine (range 236 - 344 ng/mL). In patients presenting with renal failure due to bladder outflow obstruction, TURP restores normal voiding pattern in many cases. However renal failure due to bladder outflow obstruction tends to be more refractory and only 3 of 14 patients experienced return to normal renal function post treatment.

Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study.

OBJECTIVE: Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIV+ men, though HIV+ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women. METHODS: Participants included 54 HIV+ and 12 HIV- women (mean age = 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task. RESULTS: HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIV+ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory. CONCLUSIONS: Verbal episodic memory deficits are evident in HIV+ women and may be associated with hippocampal dysfunction at both encoding and retrieval.

High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease.

BACKGROUND: In the midbrain of patients with Parkinson disease (PD), there is a selective loss of dopaminergic neurons in the ventrolateral and caudal substantia nigra (SN). In a mouse model of PD, investigators have administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and found that measures derived using diffusion tensor imaging (DTI) were correlated with the number of dopamine neurons lost following intoxication. METHODS: Twenty-eight subjects (14 with early stage, untreated PD and 14 age- and gender-matched controls) were studied with a high-resolution DTI protocol at 3 Tesla using an eight-channel phase array coil and parallel imaging to study specific segments of degeneration in the SN. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. RESULTS: Fractional anisotropy (FA) was reduced in the SN of subjects with PD compared with controls (p < 0.001). Post hoc analysis identified that reduced FA for patients with PD was greater in the caudal compared with the rostral region of interest (p < 0.00001). A receiver operator characteristic analysis in the caudal SN revealed that sensitivity and specificity were 100% for distinguishing patients with PD from healthy subjects. Findings were consistent across both raters. CONCLUSIONS: These findings provide evidence that high resolution diffusion tensor imaging in the substantia nigra distinguishes early stage, de novo patients with Parkinson disease (PD) from healthy individuals on a patient by patient basis and has the potential to serve as a noninvasive early biomarker for PD.

Rabbit antithymocyte globulin related decrease in platelet count reduced risk of pediatric renal transplant graft thrombosis.

Graft thrombosis is a serious complication in pediatric renal transplantation. We assess a potential protective effect for the decrease in platelet count associated with RATG therapy against pediatric renal transplant graft vascular thrombosis. Between January 1986 and December 1998, 120 kidney transplants were performed in 95 pediatric recipients. Patients were divided into two groups. Group 1 (n = 61), non-RATG group received cyclosporine, azathioprine and steroids, while group 2 (n = 59), RATG group, received in addition, RATG at day 1 and continued for 4-10 days postoperatively. Platelet count prior to transplant, median change in absolute platelet count at 1 and 3 days post-transplant was recorded. Graft thrombosis incidence was examined. Six grafts (5%) developed thrombosis. All were in group 1 (p = 0.028). Median pretransplant platelet count (x10(9)/L) in group 1 was 283 vs. 280 in group 2 (p = 0.921). Median decrease in absolute platelet count (x10(9)/L) from pretransplant levels at one and three days post-transplant for group 1 and 2 was 18 vs. 83 (p

Long-term outcome of cadaveric renal transplant after treatment of symptomatic lymphocele.

PURPOSE: Between January 1993 and December 2002 a total of 1,289 renal transplants were performed at our institution. Symptomatic post-transplant lymphocele presenting as increased creatinine and hydronephrosis of the allograft was recorded at 0.02%. Records of the 27 patients in whom symptomatic lymphocele developed and of those who underwent contralateral kidney transplant (control group) were compared to determine the long-term effects of lymphocele formation on allograft function. MATERIALS AND METHODS: A total of 37 procedures for the treatment of lymphocele were performed in 24 patients. Open marsupialization (12) and laparoscopic marsupialization (3) procedures were performed as primary treatments. Two patients underwent repeat open marsupialization. Aspiration and percutaneous catheter drainage were performed as a primary procedure in 7 and 1 cases, respectively. Percutaneous nephrostomy was required in 4 cases before definitive treatment. RESULTS: The mean time to development of a lymphocele was 121 days (range 35 to 631). Symptomatic lymphocele did not require treatment in 3 patients. Of 19 patients undergoing primary marsupialization, recurrence in 2 necessitated repeat surgery. However, aspiration and percutaneous drainage proved to be definitive in only 2 cases. In total 8 patients required more than 1 procedure. At a mean followup of 63 months (SD 30.3) 21 allografts continued to function with a mean serum creatinine of 152 mumol/l (SD 67.9). In the control group 3 patients experienced graft failure and mean serum creatinine was 154 mumol/l (SD 51.9). Five patients died in the lymphocele group, 2 with functioning grafts compared to 4 deaths in the control group. CONCLUSIONS: Surgical marsupialization is the preferred primary treatment for symptomatic lymphocele and is associated with excellent long-term allograft outcome.

Vascular complications of allograft nephrectomy.

OBJECTIVES: To identify risk factors that predisposes patients to vascular complications from allograft nephrectomy and to determine the safe management of this group of patients. DESIGN: This is a retrospective review of 1543 renal transplants performed in our institution between January 1990 and January 2002. PATIENTS AND METHODS: During this period, 161 (10.4%) transplant nephrectomies were performed, of which we identified nine patients (5.6%) who sustained significant vascular complications. RESULTS: Seven patients required ligation of external iliac artery for control of haemorrhage. Immediate vascular reconstructions (femoral-femoral cross-over bypass in two cases and one vein patch to an external iliac artery defect) were performed in three patients. Two patients had endovascular stenting of their external iliac artery pseudoaneurysm. No patient suffered limb loss. However, three patients died-two died from overwhelming sepsis and one patient died of an intra-cerebral haemorrhage. CONCLUSIONS: While vascular complications associated with transplant nephrectomy are relatively rare, they are associated with a significantly poor outcome. Immediate attempts to reconstruct the vascular supply to the lower limb are associated with a high complication rate. We advocate that where possible, vascular reconstruction should be deferred and that external iliac artery ligation can be performed safely with surprisingly low limb ischaemia rate.

Rabbit antithymocyte globulin as induction immunotherapy for pediatric deceased donor kidney transplantation.

PURPOSE: There is scant literature describing the long-term outcome of the use of antithymocyte globulin induction immunotherapy in pediatric deceased donor kidney transplants. We retrospectively studied the long-term results and safety of antithymocyte globulin as induction immunotherapy in all children undergoing transplantation at our institution since 1991. MATERIALS AND METHODS: A total of 120 kidney transplants were performed in 95 patients 18 years or younger between January 1986 and December 1998. Patients were divided into 2 groups. The control group (63 patients) received cyclosporine, azathioprine and prednisolone, while the treatment group (59 patients) received rabbit antithymocyte globulin (RATG) induction immunotherapy for 6 to 10 days, combined with cyclosporine, azathioprine and prednisolone. RESULTS: Actuarial patient survival rates at 1, 3, 5 and 10 years were 96%, 95%, 95% and 90%, respectively. Actuarial graft survival rates at 1, 3, 5 and 10 years were 76%, 69%, 64% and 49%, respectively. The 1, 3, 5 and 10-year graft survival rates in the control group were 62%, 57%, 51% and 36%, respectively, compared to 90%, 82%, 79% and 69%, respectively, in the RATG group (p = 0.001). There was a significant difference in the incidence of graft loss secondary to acute cellular rejection between the control and RATG groups (19.7% vs 3.3%, p = 0.008). There was no difference in infectious complications between the control and RATG groups (13% vs 20%, p = 0.33), and there was no case of post-transplant lymphoproliferative disorder encountered in either group. CONCLUSIONS: The use of rabbit antithymocyte globulin in pediatric deceased donor kidney transplant recipients resulted in significant improvement in graft survival and was relatively safe.

Outcomes of adult cadaveric renal transplantation in ireland 1986 to 2001.

BACKGROUND: Since the introduction of renal transplantation in the Republic of Ireland in 1964, the number of transplants performed annually has increased from single figures in the 1960s to the current rate of approximately 130 renal transplants per year. Improvements in graft and patient outcomes have been associated with the introduction of the immunosuppressive agent Cyclosporin (CSA) in the mid 1980s. AIMS: The aim of this study was to examine trends in outcomes and factors that influence outcomes for adult kidney transplantation from 1986 to 2001. METHODS: All adult cadaveric kidney transplantations carried out between 1986 and 2001 were included. We separated the transplanted grafts and patients into four time periods; 1986-1989, 1990-1993, 1994-1997, 1998-2001. Graft and patient survival outcomes were compared for the different periods. RESULTS: The one-year kidney graft survival rate increased from 82% during 1986-1989 to 86% during 1998-2001. Patient survival over the four time periods studied has remained stable at approximately 95% at one year. CONCLUSION: We report a significant improvement in kidney graft outcomes over the past 16 years. Patient survival has remained relatively stable during this period.

Cadaveric kidney transplantation in children < or =20 kg in weight: long-term single-center experience.

BACKGROUND: We report long-term follow-up data on cadaveric kidney transplantation in children < or =20 kg in weight. METHODS: Between January 1990 and October 2003, we performed 19 cadaveric renal transplants in 19 children < or =20 kg in weight. Mean age at transplantation was 4.7 years (range 18 months to 9 years). Mean weight at transplantation was 14.4 kg (range 9 to 20 kg). Nine patients had preemptive kidney transplantation, whereas 10 were maintained on renal replacement therapy before the transplant operation. RESULTS: Actuarial 1-, 3-, 5-, and 10-year patient survival rates were 89.5%, 89.5%, 89.5%, and 82%, respectively. Actuarial 1-, 3-, 5-, and 10-year graft survival rates were 79%, 73%, 73%, 65%, respectively. Three patients died. Eight grafts failed. Cause of graft failure was death with a functioning graft in 3 patients, chronic rejection in 1, acute cellular rejection in 1, vascular rejection in 1, hemolytic-uremic syndrome in 1, and unknown in 1. CONCLUSIONS: Our results indicate the success of cadaveric kidney transplantation in the very small child with results comparable to living related donor transplantation.

Long-term outcome of cadaveric pediatric en bloc transplantation--a 15-year experience.

Pediatric en bloc transplantation of infant organs into adult recipients is a recognized technique to expand the number of kidneys available for transplantation. We reviewed our experience with this technique over a 15-year period to determine the long-term outcomes. Twelve patients underwent pediatric en bloc transplantation from donors aged <4 years. All transplants functioned immediately with no graft thrombosis. Two patients died 12 and 10 years posttransplant with functioning grafts. The remaining 10 recipients experienced excellent graft function with a mean follow-up time of 73.8 months (range, 10 to 169 months) with no evidence of hyperfiltration injury. We conclude that pediatric en bloc transplantations achieve excellent long-term allograft function in selected recipients.

Toxoplasmosis after a simultaneous pancreas and kidney transplantation.

We report the case of a simultaneous kidney and pancreas transplant recipient who presented with vague neurologic symptoms 21 months following the surgery. Computed tomography, magnetic resonance imaging, and fundoscopy findings were normal. Serology titers for antitoxoplasmic antibodies were increased. This was an atypical presentation of toxoplasmosis in a simultaneous kidney and pancreas transplant patient.