Ahmed Halawa

The third and fourth renal transplant; technically challenging, but still a valid option.

At present, first and second kidney transplantation have established surgical techniques with few variations between surgeons. They also are considered the best renal replacement therapy for patients with end stage renal disease. Both offer better quality of life and longer survival compared to dialysis. However the third and fourth transplants are significantly more complex. Patients are often highly sensitized, comorbid with limited surgical options due to the previous operations, immunosuppression and long periods on dialysis. There is an incorrect belief that third and fourth retransplantation will not offer any advantage to this cohort of patients and considered to be poor utilization of the limited supply of organs. Recent work demonstrated that third and fourth transplantation offers a survival advantage however it slightly inferior to first and second transplantation, but still there is no established technique. In spite of the surgical challenge, the main cause of graft loss in this cohort of patient is immune mediated rather than the surgical complications. In this review article, we describe various techniques used in transplanting these surgically, immunologically and medically challenging patients demonstrating the effect of surgical complications on the outcome.

Corticosteroid minimization in renal transplantation: Careful patient selection enables feasibility

AIM To explore the benefits and harms of corticosteroid (CS) minimization following renal transplantation. METHODS CS minimization attempts to improve cardiovascular risk factors (hypertension, diabetes, dyslipidemia), to enhance growth in children, to ameliorate bone disease and to lead to better compliance with immunosuppressive agents. Nevertheless, any benefit must be carefully weighed against the reduction in net immunosuppression and the potential harm to renal allograft function and survival. RESULTS Complete CS avoidance or very early withdrawal (i.e., no CS after post-transplant day 7) seems to be associated with better outcomes in comparison with later withdrawal. However, an increased incidence of CS-sensitive acute rejection has been observed with all CS minimization strategies. Among the prerequisites for the safe application of CS minimization protocols are the administration of induction immunosuppression and the inclusion of calcineurin inhibitors in maintenance immunosuppression regimens. CONCLUSION Transplant recipients at low immunological risk (primary transplant, low panel reactive antibodies) are thought as optimal candidates for CS minimization. CS avoidance may also be undesirable in patients at risk for glomerulonephritis recurrence or with severe delayed graft function and prolonged cold ischemia time. Thus, CS minimization is not yet ready for implementation in the majority of transplant recipients.

“Contrast nephropathy” in renal transplantation: Is it real?

The risk of contrast-induced nephropathy (CIN) in renal transplant recipients is increased in diabetics, patients with impaired basal kidney function, patients in shock, patients presenting with acute emergency and in old age recipients. Approximately one-third of all hospitalized patients with acute kidney injury is attributed to CIN. In the United States, it is the third leading cause of hospital-acquired renal failure. Therefore, efforts should be directed to minimize CIN-related morbidity and mortality as well as to shorten hospital stay. While the role of peri-procedural prophylactic hydration with saline is unequivocal; the use of acetyl cysteine is not based on robust evidence. The utility of theophylline, aminophylline, calcium channel blockers, natriuretic peptide, and diuretics does not have proven role in attenuating CIN incidence. We aim to analyze the evidence for using various protocols in published literature to limit CIN-associated morbidity and mortality, particularly during surveillance of the renal allograft survival.

De novo glomerular diseases after renal transplantation: How is it different from recurrent glomerular diseases?

The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the de novo glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. De novo membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. De novo C3 disease is rather rare. Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent.

Systemic meta-analysis assessing the short term applicability of early conversion to mammalian target of rapamycin inhibitors in kidney transplant

AIM To consolidate the present evidence of effectiveness in renal functioning and graft survival following early introduction of mammalian target of rapamycin (mTOR) inhibitors with or without calcineurin inhibitors (CNIs) in renal transplant recipients. METHODS We analysed the current literature following PROSPERO approval describing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within six months of renal transplant by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus using MeSH terms. RESULTS Six articles of early withdrawal of CNI and introduction of mTOR-inhibitors within six months of renal transplantation were sought. Glomerular filtration rate (GFR) and serum creatinine were significantly better in mTOR inhibitor group with equivalent survival at 12 mo, even though Biopsy Proven Acute rejection was significantly higher in mTOR-inhibitor group. CONCLUSION The evidence reviewed in this meta-analysis suggests that early introduction mTOR-inhibitors substantial CNI minimization. The mTOR inhibitors such as everolimus and sirolimus, due to their complementary mechanism of action and favourable nephrotoxicity profile; better glomerular filtration, lower serum creatinine with equivalent survival. Having said that, due to the higher rejection rate, may influence the use of these regimens to patients with moderate to high immunological risk patients.

Liver Abscess; Uncommon Complication Following Renal Transplantation: Case Report with Review of Literatures

Intra-abdominal and biliary infections are significant cause of morbidity and mortality for the transplant recipients, specifically in the early post-operative period, reflecting substantial immunosuppression. In renal transplant recipients, there is no reported increased risk for pyogenic liver abscess as compared to general population. The diagnosis of hepatic abscess in a transplant recipient can be challenging since presentation could be atypical and the signs and symptoms might be insidious and subtle. If a hepatic abscess is missed and left untreated, it is potentially lethal; hence, an early diagnosis and timely initiation of appropriate therapy is of utmost importance, to improve patient outcomes. We present a case record of a 29 year old male patient who received a living unrelated renal transplant in 2007. He presented 8 years post-transplant with a fever of unknown origin; clinical and laboratory tests did not provide any clue to the diagnosis. However, labeled white cell scan (Leukoscan) followed by abdominal ultrasound scan (USS) revealed an unexpected finding of a large liver abscess (5.57 × 6.05 cm). He responded well to a course of antibiotics including metronidazole therapy besides requiring percutaneous abscess drainage.

Early urological complications after kidney transplantation: An overview

Urological complications, especially urine leaks, remain the most common type of surgical complication in the early post-transplant period. Despite major advances in the field of transplantation, a small minority of kidney transplants are still being lost due to urological problems. Many of these complications can be traced back to the time of retrieval and implantation. Serial ultrasound examination of the transplanted graft in the early post-operative period is of key importance for early detection. The prognosis is generally excellent if recognized and managed in a timely fashion. The purpose of this narrative review is to discuss the different presentations, compare various ureterovesical anastomosis techniques and provide a basic overview for the management of post-transplant urological complications.

Thrombotic microangiopathy after renal transplantation: Current insights in de novo and recurrent disease

Thrombotic microangiopathy (TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.

Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases

For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases. Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.

Vaccination practices in End Stage Renal Failure and Renal Transplantation; Review of current guidelines and recommendations

Due to the increased burden of infectious complications following solid organ transplantation, vaccination against common pathogens is a hugely important area of discussion and application in clinical practice. Reduction in infectious complications will help to reduce morbidity and mortality post-transplantation. Immunisation history is invaluable in the work-up of potential recipients. Knowledge of the available vaccines and their use in transplant recipients, donors and healthcare providers is vital in the delivery of quality care to transplant recipients. This article will serve as an aide-memoire to transplant physicians and health care professionals involved in managing transplant recipients as it provides an overview of different types of vaccines, timing of vaccination, vaccines contraindicated post solid organ transplantation and travel vaccines.