Hany Riad

Effect of conversion from mycophenolate mofetil to enteric‐coated mycophenolate sodium on maximum tolerated dose and gastrointestinal symptoms following kidney transplantation

Despite the potential tolerability advantage of enteric‐coated mycophenolate sodium (EC‐MPS), no prospective, randomized trial has evaluated whether conversion from mycophenolate mofetil (MMF) to EC‐MPS permits mycophenolic acid dose to be increased or gastrointestinal side‐effects to be ameliorated. In a randomized, multicenter, open‐label trial, kidney transplant recipients experiencing gastrointestinal side‐effects either remained on MMF or switched to an equimolar dose of EC‐MPS, adjusted 2 weeks subsequently to target the highest tolerated dose up to 1440 mg/day (EC‐MPS) or 2000 mg/day (MMF). Patients were followed up to 12 weeks postrandomization. One hundred and thirty‐four patients were randomized. The primary efficacy endpoint, the proportion of patients receiving a higher mycophenolic acid (MPA) dose at week 12 than at randomization, was significantly greater in the EC‐MPS arm (32/68, 47.1%) than the MMF arm (10/61, 16.4%; P < 0.001). At the final visit, 50.0% (34/68) of EC‐MPS patients were receiving the maximum recommended dose versus 26.2% (16/61) of MMF patients (P = 0.007). Kidney transplant patients receiving reduced‐dose MMF because of gastrointestinal side‐effects can tolerate a significant increase in MPA dose after conversion to EC‐MPS. Patient‐reported gastrointestinal outcomes with higher doses of EC‐MPS remained at least as good as in MMF‐treated controls.

Management of transplant renal artery stenosis and its impact on long term allograft survival: a single centre experience

BACKGROUND Transplant renal artery stenosis (TRAS) is a recognized complication resulting in post-transplant hypertension associated with allograft dysfunction. It is a commonly missed but potentially treatable complication that may present from months to years after transplant surgery. In this retrospective study, we compared management strategies and outcomes of TRAS from 1990 to 2005. METHODS Case notes of transplant recipients with TRAS demonstrated by angiography were reviewed. Angiography and was carried out when there was a clinical or Doppler ultrasound suspicion of TRAS. The clinical diagnosis of TRAS was based on uncontrolled refractory/new-onset hypertension and/or unexplained graft dysfunction in the absence of another diagnosis, such as rejection, obstruction or infection. The two-tailed Student t-test was used to analyse the differences between mean arterial pressure, serum creatinine, and estimated glomerular filtration rate before and after the intervention. RESULTS Sixty-seven patients with angiogram-confirmed TRAS were included. Forty-four, 9 and 14 patients were managed with primary percutaneous transluminal renal angioplasty (PTRA), surgical intervention and conservative treatment, respectively. Uncontrolled hypertension was the most common presentation noted in 74.62%. Post-anastamotic single stenosis was the commonest occurrence (n = 53). Angioplasty had the highest 1- and 5-year graft survival rate of 91% and 86%, respectively. The worst prognosis was noted in patients treated with secondary PTRA after failed surgery or secondary surgery after failed primary PTRA. CONCLUSIONS TRAS is a recognized complication resulting in loss of renal allografts. Early Doppler ultrasound is a good primary diagnostic tool. Early intervention is associated with a good long-term graft function.

Factors influencing glomerular filtration rate in renal transplantation after cyclosporine withdrawal using sirolimus-based therapy: a multivariate analysis of results at five years.

Abstract:  Changes in calculated glomerular filtration rate (GFR) from baseline to five yr were analyzed in relation to risk factors among renal transplant recipients. At three months after transplantation (baseline), 430 eligible patients receiving sirolimus (SRL), cyclosporine (CsA), and steroids (ST) were randomly assigned (1:1) to continue SRL–CsA–ST or have CsA withdrawn and SRL trough levels increased (SRL–ST group). For each risk factor, changes from baseline were compared within each treatment using a t‐test and between treatments using ANCOVA. Univariate then multivariate robust linear regression analyses were also performed. In the SRL–ST group, changes from baseline were not significantly different for any risk factor. With the exception of cold ischemia time >24 h, GFR values declined significantly for all risk factors in SRL–CsA–ST patients. For all risk factors, except second transplant or cold ischemia time >24 h, renal function was significantly different between groups. By order of significance in the multivariate analysis, treatment (p < 0.001), donor age (p < 0.001), proteinuria (p < 0.001), and biopsy‐confirmed rejection (p = 0.010) were significant predictors of GFR change from baseline. In conclusion, patients with risk factors for reduced renal function benefit from SRL maintenance therapy without CsA vs. those remaining on CsA.

Potential clinical implications of substitution of generic cyclosporine formulations for cyclosporine microemulsion (Neoral) in transplant recipients

Cyclosporine (CsA) is a critical-dose drug for which a minor change in absorption can have important clinical implications. Generic formulations of CsA are becoming more widely available, but standard criteria for bioequivalence require only that a single study in healthy volunteers demonstrate that mean pharmacokinetic parameters fall within 80–125% of the mean values for Neoral, the reference formulation of CsA. However, CsA absorption is known to differ between healthy volunteers and transplant patients and between different types of transplant patients, such that standard bioequivalence testing may be inadequate to ensure interchangeability of CsA formulations in all patients. The limited available clinical evidence has shown that stable renal transplant patients receiving Neoral have a significant reduction in mean CsA trough level after transfer to the Cicloral formulation. Mean pharmacokinetic values have been reported as equivalent following transfer to Gengraft in one study, but mean CsA trough fell and mean serum creatinine rose significantly in a separate trial. The only clinical outcomes data available are from a retrospective study of de novo renal transplant patients, which reported a significantly higher incidence of biopsy-proven acute rejection in patents receiving Gengraf versus Neoral (39% versus 25%, P<0.05). Until robust clinical data demonstrate that different formulations of CsA are interchangeable, it is advisable to prescribe CsA by brand, and any transfer to a different CsA formulation should be undertaken with close supervision and only at the direction of the transplant physician.

Extraperitoneal renal transplantation in small children results in a transient improvement in early graft function

Heap SL, Webb NJA, Kirkman MA, Roberts D, Riad H. Extraperitoneal renal transplantation in small children results in a transient improvement in early graft function.
Pediatr Transplantation 2011: 15: 362–366.

Recurrent tubulointerstitial nephritis and uveitis syndrome in a renal transplant recipient

We report for the time a patient with recurrence of tubulointerstitial nephritis and uveitis (TINU) following renal transplantation. Our patient was diagnosed at the age of 8 years and, despite treatment with systemic steroids, developed established renal failure. At the age of 17 years, he underwent a live-related donor renal transplant. Immunosuppression included tacrolimus, mycophenolate mofetil and prednisolone. Having had normal renal function for 3 years after transplantation, he developed uveitis and decline in the graft function. A biopsy of the allograft demonstrated recurrent granulomatous interstitial nephritis. The recurrence of TINU following transplantation suggests a role for circulating autoantibodies in the disease pathology.

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.

What delay should there be between primary infectious mononucleosis and renal transplantation

Abstract:  A 17‐yr‐old girl in end‐stage renal failure was due to undergo living‐related pre‐emptive renal transplantation when she developed acute infectious mononucleosis (AIM) from Epstein–Barr virus (EBV). In view of the risk of post‐transplant lymphoproliferative disorder (PTLD) we were unsure as to the optimal delay between AIM and renal transplantation. This report describes the process used to determine maturation of the immune response to EBV using a combination of serology, immunophenotyping and molecular viral load estimation. These tests showed that EBV had not been cleared and dialysis was instituted rather than proceed directly to transplantation. After EBV viral load became undetectable in the blood, living‐related donor was successfully performed 13 months after AIM. With 42‐month post‐transplant follow up there has been no evidence of PTLD.

Complete necrosis of allograft ureter after cadaveric renal transplantation.

Abstract:  Complete necrosis of a transplant ureter is a rare complication that needs to be considered early in cases of severe graft dysfunction if successful surgical intervention and restoration of graft function is to be achieved. We report on two cases of this complication occurring in children and discuss the surgical management. Surgical exploration of grafts where there is an early sudden decline in function is imperative as routine imaging will not exclude this potentially treatable problem.