Protective effect of ischaemic preconditioning on acute and chronic renal damage following ischaemia reperfusion injury: characterisation of fibrosis development after inflammation resolution.

OBJECTIVES: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are increasingly recognised as one disease continuum, rather than distinct entities, and are associated with a huge burden to healthcare services. The leading cause of AKI worldwide is Ischaemia Reperfusion Injury (IRI), most commonly seen in clinical settings of sepsis-driven hypotension. Ischaemic Preconditioning (IPC) is a strategy aimed at reducing the deleterious effects of IRI. The objectives of this study were to demonstrate an efficacious in vivo model of Kidney IRI, and the protective influence of IPC in attenuating AKI and development of renal fibrosis. METHODS: A rat model of bilateral kidney IRI was used: Male Lewis rats (n=84) were assigned to IRI, sham or IPC. In IRI, renal pedicles were clamped for 45 minutes. IPC groups underwent pulsatile IPC prior to IRI. Kidneys were retrieved at 24 hours, 48 hours, 7 days, 14 days and 28 days, and assessed histologically. RESULTS: IRI led to marked AKI (24-48 h) and renal fibrosis development by 28 days. IPC attenuated this damage, with 66% less fibrosis. Interestingly, at 14-days, the histological appearance of both IRI and IPC kidneys was rather similar, potentially representing an important transitional point at which kidneys commit to either fibrosis or recovery. This may provide a suitable inflexion point for introduction of novel anti-fibrotic therapies. CONCLUSIONS: In conclusion, we have characterised a model of kidney injury from acute to chronic phases, allowing detailed mechanistic understanding and which can be manipulated by effective treatment strategies such as IPC.

Robust Rat and Mouse Models of Bilateral Renal Ischemia Reperfusion Injury.

BACKGROUND/AIM: Acute and chronic kidney diseases are a major contributor to morbidity and mortality worldwide, with no specific treatments currently available for these. To enable understanding the pathophysiology of and testing novel treatments for acute and chronic kidney disease, a suitable in vivo model of kidney disease is essential. In this article, we describe two reliable rodent models (rats and mice) of efficacious kidney injury displaying acute to chronic kidney injury progression, which is also reversible through novel therapeutic strategies such as ischemic preconditioning (IPC). MATERIALS AND METHODS: We utilized adult male Lewis rats and adult male wildtype (C57BL/6) mice, performed a midline laparotomy, and induced warm ischemia to both kidneys by bilateral clamping of both renal vascular pedicles for a set time, to mimic the hypoxic etiology of disease commonly found in kidney injury. RESULTS: Bilateral ischemia reperfusion injury caused marked structural and functional kidney injury as exemplified by histology damage scores, serum creatinine levels, and kidney injury biomarker levels in both rodents. Furthermore, this effect displayed a dose-dependent response in the mouse model. CONCLUSION: These rodent models of bilateral kidney IRI are reliable, reproducible, and enable detailed mechanistic study of the underlying pathophysiology of both acute and chronic kidney disease. They have been carefully optimised for single operator use with a strong track record of training both surgically trained and surgically naïve operators.

Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score for Prediction of Pancreas Transplant Outcomes.

OBJECTIVES: The Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were designed to assist in the evaluation of pancreases for transplant. Preprocurement Pancreas Suitability Score <17 and PancreasDonor Risk Index ≤1.57 were deemed ideal.We aimed to determine the ability ofthese scores to predict pancreas transplant outcomes. MATERIALS AND METHODS: The Pancreas Donor Risk Index and the Preprocurement Pancreas Suitability Score were retrospectively calculated from a prospectively maintained database of consecutive pancreas transplants performed during a 13-year period (December 2004 to November 2017). Outcomes measuredwere rejection rate, graft and patient survival, and duration of hospital stay. RESULTS: Of 159 pancreas transplants (108 simultaneous pancreas and kidney transplants, 33 pancreas after kidney transplants, 18 pancreas-only transplants), full data were available for 155 (97%) to calculate Pancreas Donor Risk Indexes and 129 (81%) to calculate Preprocurement Pancreas Suitability Scores. Fortyseven patients (30%) experienced at least 1 episode of acute rejection. We calculated Pancreas Donor Risk Indexes for 155 patients, and 19 (23%) and 27 (38%) were in the ≤1.57 and >1.57 groups, respectively (P = .047). We calculated Preprocurement Pancreas Suitability Scores for 129 patients, and 12 (21%) and 27 (32%) were in the <17 and ≥17 groups, respectively (P = .202). Donor age and recipientfemale sex were the main predictors forrejection (binary logistic regression, P < .05). One-year graft survival rates were 95% and 81% forthe ≤1.57 and >1.57 PancreasDonor Risk Index groups,respectively, and 95% and 80% forthe <17 and ≥17 Preprocurement Pancreas Suitability Score groups, respectively (not significant). CONCLUSIONS: Pancreas Donor Risk Index and Preprocurement Pancreas Suitability Score were not helpful to predict graft/patient survival in our population. A higher Pancreas Donor Risk Index was associated with higher risk of graft rejection. Further studies with larger cohorts are required.

'Educational' Deprivation is Associated with PD Peritonitis.

BACKGROUND: Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion. METHODS: The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes. RESULTS: Peritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the 'Education' domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced '2 or more peritonitis' episodes (p = 0.04) and were hospitalized for antibiotics (p = 0.02). CONCLUSION: This study has shown that patients who live in more 'educationally' deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.

Improved limb salvage for patients with vascular disease and tissue loss associated with new model of provision targeted at the diabetic foot.

AIMS: The establishment of a vascular surgeon-led emergency diabetic foot service in 2006 has evolved to provide lower limb wound care for patients with and without diabetes. We aimed to determine whether the service was associated with sustained, improved limb salvage rates for the whole population, analyse key aspects of service provision and compare outcomes against published studies. METHODS: The vascular unit serves a largely rural population of approximately 240,000. Data was collected prospectively on lower limb amputations, arterial and minor surgical interventions from 2006 to 2015, and retrospectively retrieved for 2004-2005, prior to service commencement. Data was also collected on referral patterns, volume of patient admissions and attendances, and delays. Lower limb amputation rates were compared against published data and analysis of admission trends and delays employed non-parametric tests. RESULTS: Age/gender adjusted major lower limb amputations for the populations with and without diabetes were 412/100,000 in 2004 and 15/100,000 in 2005 respectively. Following service introduction, major amputations reduced and since 2012 have been sustained at between 15-44/100,000 and 1-3/100,000 for patients with and without diabetes respectively, comparing favourably with published data. Vascular interventions have remained static, but referrals of patients directly to the service and numbers of minor procedures have increased. CONCLUSIONS: The sustained decreases in all major lower limb amputations that have coincided with the development of a core team approach to providing rapid access and comprehensive care for patients with emergency diabetic foot problems may indicate that this service design benefits patients with and without diabetes.

Kikuchi disease.

Kikuchi-Fujimoto Disease or Necrotizing Lymphadenitis is a rare, benign, self-limiting disease. It usually effects young females in the third decade of life. The most common presentation is cervical lymphadenopathy, though the etiology of the disease is still controversial. Clinical findings, histological diagnosis and immunohistochemistry help in diagnosis. Once diagnosed, steroids have been found to alleviate symptoms in patients with systemic manifestations. Antibiotics should not be prescribed until infective element is identified. We report the case of a female patient who presented with tender cervical lymphadenopathy. She was diagnosed on excision biopsy of one of her lymph nodes. Anti-inflammatory drugs were started but the disease relapsed briefly after. Her symptoms have improved remarkably after initiation of steroid therapy, since her relapse.