Badri Shrestha

Clinical practice guidelines for peritoneal access.

Faculdade de Enfermagem, Nutricao e Fisioterapia,1 Pontificia Universidade Catolica do Rio Grande do Sul, Brazil; Department of Nephrology,2 Serdang Hospital, Jalan Puchong, Kajang, Selangor, Malaysia; Sheffield Kidney Institute,3 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Nephrology,4 Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia; Renal Services,5 Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom; Nephrology,6 Sri Ramachandra University, Chennai, India; Dialysis Unit,7 Dianet Dialysis Centers and Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Reduction of ischemia-reperfusion injury in the rat kidney by FTY720, a synthetic derivative of sphingosine.

Background. The current shortage of organ donors has led many centers to use marginal and nonheart-beating donors (NHBDs). Recent research has implicated the infiltration of lymphocytes as an important mediator of ischemia–reperfusion injury (IRI). FTY720 is an immunosuppressant that promotes lymphocyte sequestration into lymph nodes. The purpose of this study was to examine the potential for FTY720 to abrogate IRI when subjected to increasing ischemic times. Methods. Male Sprague–Dawley rats underwent bilateral flank incision with removal of the right kidney and clamping of the left hilum. Groups were divided into ischemia times of 45, 55, and 65min; each group was further divided into a control group (IRI only), IRI+FTY720 (1 mg/kg/d), and IRI+cyclosporine (15 mg/kg/d), n=4 per group. Results. Thre days after 45 min of ischemia, serum creatinine in the ischemia only (477±37 &mgr;mol/L) and cyclosporine groups (698±32 &mgr;mol/L) was significantly increased compared with the FTY720-treated animals (194±66 &mgr;mol/L). The beneficial effect of FTY720 was also observed at 55 and 65 min; indeed, FTY720-treated animals demonstrated signs of recovery from 65 min of ischemia whereas control and cyclosporine-treated animals required sacrifice between days 3 and 5. Treatment with FTY720 reduced renal damage assessed histologically and also reduced apoptosis and increased cell proliferation. Conclusion. Treatment with FTY720 reduced IRI and prevented unrecoverable acute renal failure after significant ischemic injury. This study suggests that FTY720 may help improve the quality of grafts from NHBD and marginal donors by abrogating the IRI insult.

Inflammatory lymphangiogenesis in a rat transplant model of interstitial fibrosis and tubular atrophy

We have previously reported de novo lymphangiogenesis in human renal allograft nephrectomy specimens that exhibited interstitial fibrosis and tubular atrophy (IFTA). This study examined whether a similar pathology developed in an experimental model of renal transplantation in the rat. Renal transplants were carried out in rats comprising both isografts (Lewis kidneys → Lewis rats) and allografts (Fisher kidneys → Lewis rats). Animals were immunosuppressed in the immediate postoperative period and sacrificed at 12 months. Experimental readouts included lymphatic vessel number and location, inflammatory cell infiltration, interstitial fibrosis, renal function, blood pressure and proteinuria. Rat allografts demonstrated the characteristic features of IFTA with increased macrophage and T cell infiltration and scattered B cells aggregates. Rat allografts exhibited impaired renal function and proteinuria. Although there was no difference in the number of perivascular lymphatic vessels, there was a striking 18‐fold increase in the number of interstitial lymphatic vessels in renal allografts. Furthermore, the lymphatic vessel number correlated with the extent of interstitial fibrosis. This rat allograft model of IFTA demonstrates a marked increase in the number of interstitial lymphatic vessels and mirrors previous work in failing human renal allografts.

Historical perspectives in kidney transplantation: an updated review

The present state of success in kidney transplantation, including its benefits to patients with end-stage renal failure, was achieved through relentless research, both in experimental animal models and human volunteers. Kidney transplantation has evolved during the past century thanks to various milestones in surgical techniques, immunology, immunosuppressive drugs, expansion of donor sources, organ preservation, transplant against immunological barriers (ABO blood group-incompatible and positive crossmatch transplants), and research on induction of tolerance, xenotransplants, and stem cell technology. Despite significant improvements in graft and patient survival, several issues still must be addressed to reduce the growing number of patients with kidney failure waiting to receive organs. This article provides an up-to-date review of the milestones in the history of kidney transplantation and highlights strategies to resolve current problems faced by patients and the transplant community.

Experimental rat models of chronic allograft nephropathy: a review

Chronic allograft nephropathy (CAN) is the leading cause of late allograft loss after renal transplantation (RT), which continues to remain an unresolved problem. A rat model of CAN was first described in 1969 by White et al. Although the rat model of RT can be technically challenging, it is attractive because the pathogenesis of CAN is similar to that following human RT and the pathological features of CAN develop within months as compared with years in human RT. The rat model of RT is considered as a useful investigational tool in the field of experimental transplantation research. We have reviewed the literature on studies of rat RT reporting the donor and recipient strain combinations that have investigated resultant survival and histological outcomes. Several different combinations of inbred and outbred rat combinations have been reported to investigate the multiple aspects of transplantation, including acute rejection, cellular and humoral rejection mechanisms and their treatments, CAN, and potential targets for its prevention.

Biological pathways and potential targets for prevention and therapy of chronic allograft nephropathy.

Renal transplantation (RT) is the best option for patients with end-stage renal disease, but the half-life is limited to a decade due to progressive deterioration of renal function and transplant failure from chronic allograft nephropathy (CAN), which is the leading cause of transplant loss. Extensive research has been done to understand the pathogenesis, the biological pathways of fibrogenesis, and potential therapeutic targets for the prevention and treatment of CAN. Despite the advancements in the immunosuppressive agents and patient care, CAN continues to remain an unresolved problem in renal transplantation. The aim of this paper is to undertake a comprehensive review of the literature on the pathogenesis, biological pathways of RT fibrogenesis, and potential therapeutic targets for the prevention and therapy of CAN.

Innocuous-looking skin scab over an arteriovenous fistula: Case report and literature review.

Little is written on the management of an innocuous-looking skin scab over an autogenous arteriovenous fistula (AVF) used for haemodialysis. The seriousness of the underlying pathology can be under-estimated, and this may lead to early loss of the AVF, and major-life-threatening haemorrhage. We describe the management of a 78-year-old patient presenting with an innocuous-looking scab over an AVF and review the pertinent literature on this subject.

Recurrent epiploic appendagitis and peritoneal dialysis: A case report and literature review

Epiploic appendagitis (EA) is rare cause of acute or subacute abdominal pain in patients on peritoneal dialysis (PD), where the diagnosis can be challenging as the clinical features, laboratory markers and imaging characteristics have not been described previously in this group of patients. Here, we present the management of a case of EA in a patient on PD and review published literature pertinent to the subject. The importance of establishing the diagnosis early by laparoscopy is emphasised.

Upregulation of Transglutaminase and ε (γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy

Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 ± 17.61 versus 2.11 ± 0.17, P < 0.001; interstitium: 13.72 ± 1.62 versus 3.19 ± 0.44, P < 0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 ± 2.71 versus 1.98 ± 0.37, P < 0.01; interstitium: 37.96 ± 17.06 versus 0.42 ± 0.11, P < 0.05), TG2 enzyme activity (1.09 ± 0.13 versus 0.41 ± 0.03 nmol/h/mg protein, P < 0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 ± 198.4 nmol/24 h versus 57.2 ± 4.1 nmol/24 h, P < 0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CAN.

THE ANATOMY AND PATHOLOGY OF THE LESSER SAC: IMPLICATIONS FOR PERITONEAL DIALYSIS

Pathological conditions involving the lesser sac of the peritoneal cavity in patients on peritoneal dialysis (PD) can pose significant diagnostic and therapeutic challenges. Lack of appreciation of these challenges may delay diagnosis and compromise outcome. A case series by Li and colleagues in this issue of Peritoneal Dialysis International highlights the diagnostic challenges presented by lesser sac infection in PD patients, and in this accompanying commentary we discuss the development and anatomy of the lesser sac, as well as the pathological conditions and investigations relevant to the management of patients on PD.