Renal Transplantation in Augmented Bladders

Botulinum toxin A’s (Onabotulinum toxin A – OnabotA) utility in the pediatric population is evolving, and is currently being used in the treatment of lower urinary tract dysfunction, both in children with neuropathic compromise, and non-neuropathic overactive bladders. The results of having OnabotA injected directly into the bladder wall cystoscopically are: a more compliant bladder with reduced bladder pressure, avoiding renal compromise and upper urinary tract deterioration; increased bladder capacity; and the ability for children to reach an improved degree of urinary continence through a minimally invasive approach. A growing body of research in patients with either neuropathic bladders or overactive bladders (OAB), have shown excellent results when looking at urodynamic parameters, patient satisfaction and improvement in symptomatology. One of the main indications for the use of OnabotA in children with neuropathic bladders is to delay or avoid the need for augmentation cystoplasty. By achieving the aforementioned results, some children can delay or avoid this more invasive and permanent procedure. Prospective studies are needed to answer questions regarding optimal dosage and frequency, ideal patient selection criteria and assessment of long-term outcomes and complications.     

Interventions for impaired bladders in paediatric renal transplant recipients with lower urinary tract dysfunction

Dysfunctional bladders in paediatric patients were thought to be a contraindication for renal transplantation, but advances in surgical techniques have meant that surgical correction can allow safe transplantation. This study compares the outcomes of renal transplantation for different interventions, and the timing of such interventions, in relation to transplantation. We identified all paediatric renal transplant recipients with LUTD that received intervention for their impaired bladders at two hospitals between 2002 and 2010. Outcome measures included patient and graft survival, perioperative complications, UTI incidence, acute rejection episodes and serum creatinine levels. A total of 288 allografts were transplanted, 77 were in 75 children with LUTD, of which 46 received intervention. Patient survival was 100% in the intervention group and 97% in the nonintervention group (P = 0.815). Death‐censored graft survival was 96% and 100% respectively (P = 0.688). In the groups receiving intervention pretransplant or post‐transplant, graft survival rates were 95% and 100% respectively (P = 0.476). The follow‐up serum creatinine levels were higher in the pretransplant intervention group (P < 0.001). Interventions for dysfunctional bladders can be performed safely in paediatric renal transplant recipients. The mode of intervention and timing of intervention, in relation to transplant, do not influence outcomes if guided by careful assessment and investigation.     

Renal Transplantation

Summary BACKGROUND: Clinical renal transplantation has been performed successfully since 1955. With the introduction of Cyclosporin A to the market, 1982, results markedly improved, and allogeneic renal transplantation became a standard therapy in the treatment of end stage kidney failure. Life expectancy and quality of life is superior in kidney recipients in comparison with patients on dialysis. METHODS: In our center 699, renal transplantations have been performed since 1968. 98.1 % of the transplanted kidneys were from cadaveric donors, 1.9 % from living related donors. Mean age of the recipients was 30.7 ± 13.9 years from 1968 to 1983, and is now 45.9 ± 13.1 (1999 to 2002). The kidneys are normally transplanted to the common iliac vessels in end-to-side fashion. A Politano-Leadbetter antirefluxive implantation of the ureter is obligatory. RESULTS: 5-year graft survival was 19.4 % from 1968 to 1983, 74.3 % from 1984 to 1995, and 81.2 % from 1995 to 1998. Typical surgical complications are hematoma, lymphocele, ureter stenosis and ureter necrosis. The rate of necessary reoperations is 3.9 %. 5-year patient survival is 90 %. Heart disease (50 %), cancer (16 %), and sepsis (15 %) are the most frequent causes of death after renal transplantation. CONCLUSIONS: Renal transplantation continues to be the optimal treatment of terminal kidney failure. New immunosuppressive agents have improved the outcome after kidney transplantation. Enlargement of the donor pool is being attempted by the acceptance of older organs and by the acceptance of pediatric organs for adult recipients, too.     

Negative Pressure Wound Therapy Used to Heal Complex Urinary Fistula Wounds Following Renal Transplantation into an Ileal Conduit

Transplantation into an ileal conduit is an established option for patients with end‐stage renal failure and a nonfunctioning urinary tract. Urinary fistulae are more common following these complex transplants. Urinary fistula in this scenario can cause substantial morbidity and even result in graft loss. The management options depend on the viability of the transplant ureter, the level of local sepsis and the overall condition of the patient. Urinary diversion with a nephrostomy and ureteric stents has been described in aiding the healing of urinary leaks in renal transplants into a functioning urinary tract. We describe the successful use of negative wound pressure therapy to eradicate the local sepsis and help the healing of a recurrent urinary fistula following kidney transplantation into an ileal conduit. To our knowledge these are the first such cases reported in the literature.     

Value of Routine Voiding Cystourethrography After Renal Transplantation

The impact of vesicoureteral reflux (VUR) on renal allograft outcomes is debatable, with small cohort studies reporting controversial results. The objective of this retrospective study was to evaluate long‐term clinical effects of early VUR in a large cohort of kidney transplant patients. Posttransplantation voiding cystourethrography was used to evaluate 646 consecutive kidney transplant recipients before discharge. The study endpoints included VUR grade, death‐censored graft or patient survival, renal function, proteinuria and occurrence of urinary tract infections (UTIs). Of the 646 recipients, 263 (40.7%) were diagnosed with VUR. VUR grade II was most common (19.8%), followed by grades III (10.2%), I (7.9%) and IV (2.8%). VUR was less common in transplantations performed by experienced compared to inexperienced surgeons (36% vs. 48%; p = 0.004). VUR did not affect death‐censored graft or patient survival and was not associated with proteinuria or occurrence of UTIs. Patients with VUR had a lower eGFR at 1 year after transplantation than did patients without VUR (60 vs. 52 mL/min/1.73 m²; p = 0.02), although this difference was not observed at 3 and 5 years after transplantation. We conclude that early VUR, a common finding among renal transplant patients, may not have a meaningful impact on long‐term transplant outcomes.     

Acute Polymyositis Following Renal Transplantation

Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.     

Renal Transplantation for Fibromuscular Dysplasia

This is the first report that presents renal transplantation after bilateral nephrectomy as the final treatment for severe renovascular hypertension due to fibromuscular dysplasia (FMD). We describe the history of a 1‐year‐old girl who suffered from renovascular hypertension due to FMD. Imaging revealed multiple bilateral stenoses of the renal artery extending into the distal branches. The hypertension proved unresponsive to pharmacologic treatment and the intrarenal peripherally located stenoses rendered a conventional approach such as transluminal or surgical angioplasty not feasible. At the age of 5 years, a unilateral nephrectomy of the most affected kidney was performed, but she remained hypertensive and developed progressive cardiomyopathy and retinopathy. At the age of 6 years the remaining kidney was removed, followed by a living related renal transplantation with a kidney donated by her mother. Posttransplantation, she developed mild hypertension due to a postanastomotic stenosis, which was easily controlled with antihypertensives. Now 8 years after transplantation, she has experienced no further blood pressure related problems. Although there is a risk of recurrence of FMD after performing a living related transplantation, our report suggests that this procedure is relatively safe, provided appropriate preoperative evaluation and follow up is performed.     

Renal Transplantation for Chronic Renal Failure in Acute Porphyria

A woman with acute intermittent porphyria and a man with variegateporphyria developed chronic renal failure in middle age. Afterperiods on haemodialysis, both received successful cadavericrenal transplants. On the basis of animal porphyrinogenicitystudies prednisolone and azathioprine were used in preferenceto cyclosporin as immunosuppressive agents. Neither of the patientsshowed any evidence of activation of their porphyria during,or following, transplantation. The findings in these two patientsand a review of two previous reports indicate that acute porphyriais not a contraindication to renal transplantation.     

Preemptive Renal Transplantation: Why Not?

Dialysis has been the long-established initial choice of treatment for persons with end-stage renal disease. Transplantation before dialysis, or preemptive renal transplantation (PRT), has been controversial because of the paucity of clinical evidence that has clarified the benefits vs. risks of this approach. However, several recent observational analyses indicate that PRT is the optimal strategy to benefit patients requiring renal replacement therapy. This current review will discuss the advantages that are associated with PRT, and will summarize studies that have investigated the impact of the timing of transplantation on outcomes. We will also discuss the utility of PRT from various perspectives, and describe the challenges ahead in expanding the opportunity of PRT for more patients.     

Renal transplantation in patients with urinary diversion: a case-control study.

BACKGROUND: Renal transplantation in Sweden in patients with ileal conduits or continent reservoirs was investigated in order to compare the outcome with regard to graft and patient survival as compared to controls. METHODS: Patient data from the four transplantation centres in Sweden were collected on: treatment prior to transplantation, time needed for the operative procedure, and postoperative care and outcome in terms of renal function as well as graft and patient survival at 1 and 5 years. The pattern of urinary tract infection was also investigated. Each case with urinary diversion was matched with two non-diabetic controls. RESULTS: Ten male and 12 female cases were found who had received 27 grafts between 1982 and 1996. Five patients had a Kock reservoir and 17 had a Bricker conduit. The time needed for the transplant procedure was significantly longer in the case group. After matching the case group with 54 controls, we found that the renal function was similar in both groups. Graft and patient survival was similar in both groups, over 90% after 1 year. Graft survival was about 70% after 5 years. Postoperative surgical complications in the case group were only seen in a few cases. The pattern of bacteria causing urinary tract infection was slightly different among the patients with ileal conduits or continent reservoirs. CONCLUSION: Patients with ileal conduits or continent reservoirs have similar graft and patient survival rates as the general kidney transplant population. The presence of constant bacteriuria did not adversely affect survival. Prophylactic antibiotic treatment seems not to be warranted. There appears to be no indication for native nephrectomy, except in selected cases. The study did not show any advantage with regard to continent reservoirs vs ileal conduits.     

Cardiac Assessment for Renal Transplantation

Cardiac death is common in patients with end-stage renal failure. Screening for coronary artery disease prior to renal transplantation is advisable in high-risk patients. The optimal screening test has not been defined; however, myocardial perfusion studies are more sensitive than exercise electrocardiography and are less invasive than coronary angiography, which remains the gold standard. The management of coronary artery disease prior to transplantation is contentious. Revascularization of coronary artery stenoses is associated with high mortality and morbidity in the renal failure population, and there is little data to indicate that most patients with asymptomatic coronary lesions will benefit from prophylactic coronary intervention. In addition, beta-blockers and aspirin are under-utilized in the renal population. This paper reviews the literature and proposes algorithms for the cardiac assessment and management of patients prior to renal transplantation.     

The urological care and outcome of pregnancy after urinary tract reconstruction

OBJECTIVE: To assess the obstetric and urological outcomes during and after pregnancy following urinary tract reconstruction, as pregnancies after such surgery can have a significant effect on the function of the reconstructed urinary tract, and the reconstruction can significantly affect the delivery of the fetus. PATIENTS AND METHODS: We retrospectively reviewed the obstetric and urological history of 11 patients (12 pregnancies; 10 singletons and one twin) with previous urinary reconstruction, delivered between 1989 and 2003. Antepartum and postpartum urological function and obstetric outcomes were investigated. RESULTS: All the patients had some difficulty with clean intermittent catheterization (CIC) during pregnancy, and four needed continuous indwelling catheters. During pregnancy 10 women had several bladder infections and all received antibiotic suppression. There were eight Caesarean sections, two vaginal deliveries and one combined delivery. Six Caesareans were elective and three were emergent. The use of CIC returned to normal in all patients after delivery. CONCLUSIONS: Women with a urinary reconstruction can have successful pregnancies. The complexity of the surgery and the concern for possible emergency Caesarean section resulted in most patients having an elective Caesarean delivery before term. Antibiotic prophylaxis is recommended and patients may require indwelling dwelling catheters while pregnant but normal CIC can be resumed after delivery.     

Mycophenolate Mofetil and Sirolimus Combination in Renal Transplantation

Mycophenolate mofetil (MMF) and sirolimus (SRL) are potent non-nephrotoxic xenobiotic immunosuppressants. Their complementary properties may provide the rationale for their combination in induction and maintenance regimens. MMF, a reversible inhibitor of inosin monophosphate dehydrogenase (IMPDH) acts as an antiproliferative drug; and SRL, an mTOR (mammalian target of rapamycin) inhibitor, inhibits cell proliferation driven by growth factors. Early experiences with the use of the SRL, MMF and steroid combination yielded insufficient prophylaxis of acute rejection. However, the introduction of induction therapy with mono- or polyclonal antilymphocyte antibodies to the SRL-MMF and steroid combination brings an efficient acute rejection prophylaxis, while improving renal function and/or reducing of chronic allograft nephropathy (CAN). However, adverse events related to the use of this drug combination (mainly haematological and surgery-related) result in a high rate of discontinuations in some trials, which may hamper the potential benefits of this calcineurin-inhibitor (CNI)-free strategy. Also, currently under investigation is whether in long-term immunosuppression, in MMF-treated patients, CNIs can be replaced by SRL to avoid and/or halt progression of chronic nephropathy and to improve graft survival. However, some authors reported a high proportion of patients with oral ulcers and proteinuria after switching to SRL. In short, refining the use of MMF and SRL may provide a better risk/benefit ratio to pave the way towards non-nephrotoxic immunosuppression.     

Skeletal Complications Following Renal Transplantation

The occurrence of skeletal complications was examined in a series of 204 renal graft recipients who had maintained graft function for more than 12 months. Osteonecrosis was observed in 22 of the patients (11 per cent) from 5 to 46 months after the transplant operation. The lesions were often multifocal, with as many as 40 joints affected. The most common site was the femoral head, necrosis of which was recorded in 24 instances. The lesions here present a major clinical problem, and total hip replacement was deemed necessary in 4 cases, in all of which an excellent result was achieved.

Fractures had occurred after the transplantation in 53 patients (26 per cent), against only 6 before the operation. A total of 109 fractures had been sustained after periods ranging from 1 to 58 months, the most common site being the pelvic bones. The fractures were treated according to standard principles; no complications were encountered.

The skeletal complications were equally common among the males and females; they tended to occur at advanced ages.

They occurred to roughly the same extent whether the graft was from a related or a cadaveric donor and whether the patient had received one or more grafts.