Martin Drage

Kidney transplantation in HIV-positive adults: the UK experience.

HIV-positive patients are at increased risk of end-stage kidney disease (ESKD). Kidney transplantation (KT) is an established treatment modality for ESKD in the general population. Recent data have confirmed the feasibility of kidney transplantation in HIV-positive patients, and kidney transplantation is increasingly offered to ESKD patients with well-controlled HIV infection. We report clinical outcomes in a national cohort study of kidney transplantation in HIV-positive patients. In all, 35 HIV-positive KT recipients who had undergone KT up to December 2010 (66% male, 74% black ethnicity) were identified; the median CD4 cell count was 366, all had undetectable HIV RNA levels at kidney transplantation, and 44% received a kidney from a live donor. Patient survival at 1 and 3 years was 91.3%, and graft survival 91.3% and 84.7%, respectively. At one-year post-kidney transplantation, the cumulative incidence of acute rejection was 48%, and the median (IQR) eGFR was 64 (46, 78) mL/min/1.73 m2. Although HIV viraemia and HIV disease progression were uncommon, renal complications were relatively frequent. Our study corroborates the feasibility of kidney transplantation in HIV-positive patients. The high rates of acute rejection suggest that the optimal immune suppression strategy in this population remains to be refined.

Nondepleting anti-CD4 and soluble interleukin-1 receptor prevent autoimmune destruction of syngeneic islet grafts in diabetic NOD mice

Background. Successful islet transplantation in type 1 diabetes requires tolerance induction of both allo- and autoreactive T-cell responses. Monoclonal antibodies targeting the CD4 coreceptor on T-helper cells have been shown to be effective in this regard. In type 1 diabetes, there is some evidence to suggest that cytokines such as interleukin (IL)-1 may be involved in &bgr;-cell destruction. The high glucose levels associated with type 1 diabetes are also known to be toxic to beta cells. Method. The tempo of T-cell and macrophage infiltration into syngeneic islets transplanted into diabetic nonobese diabetic (NOD) mice was examined by immunohistochemistry. We investigated the ability of a nondepleting anti-CD4 monoclonal antibody (YTS177) to induce tolerance to syngeneic islet grafts in female spontaneous diabetic NOD mice and in an adoptive transfer model of diabetes in NOD mice. The spontaneous model was used to test the effect on graft function of perioperative insulin therapy in mice treated with YTS177. The ability of soluble interleukin (sIL)-1 receptor (R) type II (sIL-1RII) to inhibit IL-1 effects in syngeneic islet transplants was also assessed. Results. Cellular infiltration of CD3+ cells and macrophages into the islet graft coincided with loss of graft function in untreated mice. Self-tolerance to beta cells was restored with YTS177, allowing long-term graft survival in a proportion of animals. The use of perioperative insulin therapy increased the number of successful grafts in spontaneously diabetic NOD mice treated with YTS177. The combination of YTS177 with sIL-1RII significantly improved the rates of graft survival compared with graft survival in YTS177-treated spontaneously diabetic NOD mice. Conclusions. Nondepleting anti-CD4 antibodies restore self tolerance to syngeneic islet transplants in diabetic NOD mice. Insulin therapy improves graft survival in mice treated with YTS177. Preventing the action of IL-1 greatly improves graft survival induced with YTS177.

Stem Cells and Their Role in Renal Ischaemia Reperfusion Injury

Background: Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. Aim: To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Methods: Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. Results: The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Conclusions: Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC.

Outcome of surgical complications following simultaneous pancreas–kidney transplantation

BACKGROUND Simultaneous pancreas-kidney (SPK) transplantation carries a higher risk of surgical complications than kidney transplantation alone. We aimed to establish the incidence of surgical complications after SPK transplantation and determine the effect on graft and patient survival. METHODS Outcomes of all SPK transplants performed at our centre were compared between patients who experienced a surgical complication (SC group) and those who did not (NSC group). RESULTS Our centre performed 193 SPK transplants in a 15-year period; 44 patients (23%) experienced a surgical complication. One-year and 5-year pancreatic graft survival was 89 and 80%, respectively; this was lower in the SC group. There was no significant difference in patient or kidney graft survival between the SC and NSC groups at 5 years (92 and 83%, respectively.) CONCLUSION Surgical complications following SPK transplantation can cause significant morbidity and adversely affect pancreas graft survival, but do not affect long-term kidney or patient survival.

Clinically Significant Peripancreatic Fluid Collections After Simultaneous Pancreas-Kidney Transplantation

Background Peripancreatic fluid collections (PPFC) are a serious complication after simultaneous pancreas-kidney transplantation (SPKTx). Methods Retrospective study for all 223 SPKTx performed from December 8, 1996, to October 10, 2011, to evaluate the risk factors (RF) and impact of PPFCs on outcomes was conducted. Results Clinically significant PPFCs were seen in 36 (16%) cases, all within 3 months after transplantation. Radiologic drainage resolved 2 (6%) cases, and 34 required laparotomy (mean [SD], 4 [7]). Compared with the non-PPFC group (n=186), the PPFC group had similar patient and total kidney graft survivals but significantly lower total pancreas survival (68% vs. 85%) and greater incidence of infections (75% vs. 46%, all P<0.05) at 5 years. PPFCs were associated with early graft pancreatitis in 18 (50%), pancreatic fistula in 20 (56%, 9 with obvious duodenal stump leak) and infection in the collection in 20 (56%) cases. Comparison of PPFCs with pancreas graft loss to the PPFCs with surviving grafts showed that the incidence of pancreatic fistula was greater in the former (90% pancreas graft loss vs. 42% pancreas graft survival, P<0.01). Binary logistic regression analysis of RF for developing PPFC showed a donor age >30 years to be significant (P=0.03; odds ratio, 3.4; confidence interval, 1.1–10.5) and a trend of association with donor body mass index >30 and pancreas cold ischemia time greater than 12 hr. Conclusions PPFCs are associated with significant reduction in pancreas allograft survival and impact resource use. Donor age >30 years is a significant RF for their development. PPFCs associated with pancreatic fistula carry a greater risk for pancreas graft loss.

Acute Cytomegalovirus Cholecystitis Following Renal Transplantation

Solid organ transplant recipients are at risk of infection from cytomegalovirus (CMV). A wide range of disease is associated with CMV infection and we report two cases of CMV cholecystitis in patients following renal transplantation. Both patients presented with severe hemorrhagic cholecystitis, which required immediate resuscitation and emergency cholecystectomy. The diagnosis of CMV infection was confirmed in both cases using CMV‐specific staining of the gallbladder. The diagnosis of CMV cholecystitis must be considered in all patients with upper abdominal pain after renal transplantation.

A registry analysis of damage to the deceased donor pancreas during procurement.

Surgical injury to the pancreas is thought to occur commonly during procurement. The UK Transplant Registry was analyzed to determine the frequency of pancreatic injuries, identify factors associated with damage, and assess the impact of injuries on graft survival. Twelve hundred ninety‐six pancreata were procured from donation after brain death donors, with 314 (19.5%) from donation after circulatory death donors. More than 50% of recovered pancreata had at least one injury, most commonly a short portal vein (21.5%). Liver donation, procurement team origin, hepatic artery (HA) arising from the superior mesenteric artery (SMA), and increasing donor BMI were associated with increased rates of pancreas damage on univariate analyses; on multivariate analysis only the presence of an HA from the SMA remained significant (p = 0.02). Six hundred forty solid organ pancreas transplants were performed; 238 had some form of damage. Overall, there was no difference in graft survival between damaged and undamaged organs (p = 0.28); however, graft loss was significantly more frequent in pancreata with arterial damage (p = 0.04) and in those with parenchymal damage (p = 0.05). Damage to the pancreas during organ recovery is more common than other organs, and meticulous surgical technique and awareness of damage risk factors are essential to reduce rates of procurement‐related injuries.

Pancreatic transplantation: surgical technique, normal radiological appearances and complications

Pancreas transplantation is a surgical treatment for diabetes mellitus. More than 23,000 pancreas transplants have now been reported to the International Transplant Registry (IPTR). Early diagnosis and therapy for graft-related complications are essential for graft survival. Radiologists must therefore understand the surgical procedure and the potential complications. During the course of this review, we will illustrate the normal post-operative anatomy and the imaging appearances of common potential complications.

A longitudinal interpretative phenomenological analysis of the process of kidney recipients’ resolution of complex ambiguities within relationships with their living donors

Much previous research into living kidney donation has focused on the decision-making of the donor, despite evidence suggesting this may be a more psychologically challenging time for the recipient. This longitudinal study explores the experiences of four recipients of kidneys from living donors throughout the transplant process. Transcripts were analysed using interpretative phenomenological analysis. Three themes arose from the data, which were as follows: changing perceptions of relationships with kidney donors; upbeat, temporal strategies for remaining positive and journey of the self. Findings from the first theme are presented in detail here. It was found that each participants’ relationship with their donor grew and developed in different ways, presenting their own complex challenges in terms of developing relationships and ambiguity around the decision to use the chosen donor.

Rituximab may not lead to increased infection rates in transplant recipients

A major concern is the inappropriate comparison of patients who received rituximab for various therapeutic reasons with all other kidney transplant recipients. We would argue that these are fundamentally incomparable groups, even with the attempts made to subdivide the control group. For example, the immunological hurdles posed by patients treated with rituximab to allow transplantation across a B-cell positive crossmatch in the presence of DSA are very different than those posed by patients needing treatment for acute rejection. Simply put, neither the experimental nor control groups are sufficiently homogeneous to allow comparison.