Titus Augustine

Corneal Confocal Microscopy Detects Early Nerve Regeneration in Diabetic Neuropathy After Simultaneous Pancreas and Kidney Transplantation

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas–kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

Encapsulating peritoneal sclerosis:: clinical significance and implications

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). This review discusses the current understanding of the aetiology and pathogenesis of EPS, highlighting histological features which differentiate it from simple sclerosis of the peritoneal membrane which develops with time on PD. Diagnostic criteria are presented, including the role of imaging techniques. To date there are no randomised controlled trials to guide therapy; however, surgical techniques are an important treatment option. Collaborative research will be essential if this serious problem facing PD is to be solved.

Outcome of pancreas transplantation in recipients older than 50 years: a single-centre experience.

Background. Pancreas transplantation (PT) remains the only treatment that can restore insulin independence among insulin-dependent diabetics. An ageing population in developed countries has led to an increasing number of older patients who may be suitable for PT. Some investigators argue that PT in recipients older than 50 years has an inferior outcome compared with the younger group. Methods. The object of this study was to compare the outcomes of 31 PT in patients aged 50 and above 105 PT in recipients below 50 years performed between June 2001 and December 2007. Results. The incidence of general posttransplant complications were similar in both; 60% in less than 50 vs. 58% in more than or equal to 50, P=0.539. So, as the incidence of other surgical complication in the more than or equal to 50 group compared with less than 50 (graft thrombosis 13% vs. 11.5%; bleeding 19% vs. 6.7%; abdominal abscess 23% vs. 19%; pancreatic leak 13% vs. 9.6%). There was no significant difference in the incidence of urinary tract infection and early rejection in either group. However, the incidence of respiratory tract infection was significantly higher in more than or equal to 50 (38.7% in ≥50 vs. 9.6% in <50, P=0.003). One-year patient survival was 88% in more than or equal to 50 vs. 92% in less than 50 group, P=0.399; and pancreas graft survival rate was similar (79% in the ≥50 and 74% in <50, P=0.399). Conclusion. This study demonstrates that it is feasible to safely transplant potentional PT recipients aged 50 and above. However, good medical assessment and careful patient selection is strongly recommended.

Mortality in diabetes: pancreas transplantation is associated with significant survival benefit

BACKGROUND Pancreas transplantation in complicated type 1 (insulin dependent) diabetes mellitus improves the quality of life, increases longevity and stabilizes diabetic complications. There may be clinician reticence due to perceived poor outcomes with published associated mortality rates of 5-8% due to significant co-morbidities, particularly cardiovascular impairment. METHODS Retrospective analysis was performed on patients undergoing pancreas transplantation in a single centre since the programmes initiation [simultaneous pancreas kidney (SPK) = 148, pancreas after kidney (PAK) = 33 and pancreas transplant alone (PTA) = 11] compared with a control group accepted contemporaneously onto the waiting list. The primary endpoint was patient mortality. The risk factors including medical and diabetic history, demographics, transplant type and waiting time were analysed. RESULTS The waiting list mortality was 30% (35 of 120) compared with a mortality of 9% (20 of 193) post-transplantation (P < 0.001). Deaths on the waiting list compared with transplantation up to 1 year had a relative risk of 2.67 (95% CI: 0.81-3.51; P = 0.19), whilst those surviving >1 year had a relative risk of 5.89 of dying on the waiting list (95% CI: 1.70-3.20; P < 0.0005). There were no differences in terms of cardiovascular or renal-associated risk factors, nor in other potential confounding factors other than duration of diabetes (P = 0.02). Median survival from listing was shorter in younger patients (<50; P < 0.0001). CONCLUSIONS Type 1 diabetics with renal failure listed for pancreas transplantation are at a significant risk of mortality even without surgery. Transplantation offers considerable survival benefits, despite associated surgical and immunosuppressive risks. In selected patients, pancreas transplantation remains the benchmark treatment for type 1 diabetes mellitus.

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

Study Type – Therapy (case series)

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.

Outcomes of Patients Who Develop Symptomatic Clostridium difficile Infection After Solid Organ Transplantation

Clostridium difficile-associated diarrhea is the most common cause of hospital-associated diarrhea in the UK. Infection can produce a spectrum of manifestations from mild diarrhea to toxic megacolon, colonic perforation, and death. The aim of this study was to evaluate the outcomes of patients who developed symptomatic Clostridium difficile infection (CDI) within the first year after solid organ transplantation. Between 2004 and 2007, we performed 682 transplantation: 433 from deceased-donor kidney, 143 live-donor kidney, 18 pancreas-only, and 88 simultaneous kidney and pancreas transplants. Within the first year of transplantation, 24 patients developed symptomatic CDI. No single risk factor or antimicrobial agent was associated with acquiring infection. Among this group, 2 patients developed toxic megacolon requiring subtotal colectomy and recovered. Although 5 patients who developed CDI died within the first year, CDI was not the primary cause of death. The overall mortality of patients who developed CDI within the first year of transplantation accounted for 0.7% of all transplanted patients. Increased awareness of CDI and barrier nursing can minimize the impact of CDI on the morbidity and mortality associated with transplantation. Patients should be informed of the risk of CDI during consenting for transplantation, because the 3.5% incidence is more common than that of graft loss due to thrombosis.

The outcomes of living donor renal transplants with multiple renal arteries: a large cohort study with a mean follow-up period of 10 years

BACKGROUND Living donor kidney transplants with multiple arteries are presumed to be associated with an increased risk of complications. OBJECTIVES The aim of the study was to compare the outcomes in living donor transplantation with the specific intention of comparing long-term outcomes in which the donor kidney had 1 or more renal arteries. The study was undertaken in 2 large transplant centers. METHODS A retrospective analysis of 201 living donor kidney transplants with multiple arteries that were performed between January 1985 and December 2004 was undertaken. We recorded patient and graft survivals, urological and vascular complications. Kaplan-Meier survival estimates were calculated, and 2-tailed Student t-test was used to compare outcomes. P < .05 was considered statistically significant. RESULTS Graft and patient survival at 1 year were 93% and 97% and at 5 years were 87% and 92%. The most common complications were vascular (8.9%), followed by urological (6%), acute tubular necrosis (5.5%), and posttransplant hypertension (4.0%). There was significantly higher incidence of acute tubular necrosis (ATN) in multiple-artery transplants. CONCLUSION In this large cohort of patients studied, apart from a higher incidence of ATN and vascular complications, it appears that the number of renal arteries did not have any adverse impact on the outcomes. The findings from this study suggest that live donor kidneys with multiple renal arteries can be safely utilized for renal transplantation.

Encapsulating peritoneal sclerosis-a rare but devastating peritoneal disease

Encapsulating peritoneal sclerosis (EPS) is a devastating but, fortunately, rare complication of long-term peritoneal dialysis. The disease is associated with extensive thickening and fibrosis of the peritoneum resulting in the formation of a fibrous cocoon encapsulating the bowel leading to intestinal obstruction. The incidence of EPS ranges between 0.7 and 3.3% and increases with duration of peritoneal dialysis therapy. Dialysis fluid is hyperosmotic, hyperglycemic, and acidic causing chronic injury and inflammation in the peritoneum with loss of mesothelium and extensive tissue fibrosis. The pathogenesis of EPS, however, still remains uncertain, although a widely accepted hypothesis is the “two-hit theory,” where, the first hit is chronic peritoneal membrane injury from long standing peritoneal dialysis followed by a second hit such as an episode of peritonitis, genetic predisposition and/or acute cessation of peritoneal dialysis, leading to EPS. Recently, EPS has been reported in patients shortly after transplantation suggesting that this procedure may also act as a possible second insult. The process of epithelial–mesenchymal transition of mesothelial cells is proposed to play a central role in the development of peritoneal sclerosis, a common characteristic of patients on dialysis, however, its importance in EPS is less clear. There is no established treatment for EPS although evidence from small case studies suggests that corticosteroids and tamoxifen may be beneficial. Nutritional support is essential and surgical intervention (peritonectomy and enterolysis) is recommended in later stages to relieve bowel obstruction.

Renal Allograft Failure After Ipilimumab Therapy for Metastatic Melanoma: A Case Report and Review of the Literature

Transplant recipients are at an increased risk of malignant melanoma, a result of chronic immunosuppression. Ipilimumab is a newer biological agent targeting T lymphocytes to potentiate an immune response against melanoma, and the use of this agent results in a new adverse effect profile that the clinician must be aware of while a patient is on therapy. We report the case of a male renal transplant recipient who developed graft failure while treated with ipilimumab and minimal immunosuppressive therapy for metastatic ocular melanoma, with biopsy evidence of glomerulonephritis and acute rejection. We highlight the immunological side effects that can manifest from ipilimumab therapy and conclude that it did influence graft function in this patient. Our case illustrates the importance of weighing the risks and benefits to graft function and long-term survival as well as the importance of considering other treatment modalities in this specific group of melanoma patients.