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HLA matching has been the cornerstone of deceased donor kidney allocation policies worldwide but can lead to racial inequity. Although HLA matching has been shown to improve clinical outcomes, the long-term impacts of nonallogenic factors are being increasingly recognized. This has led some transplant programs to include points for nonallogenic factors, for example, age. Our study looks at long-term graft and patient outcomes based on allocation cohorts rather than individual number of HLA mismatches.Using the Australia and New Zealand Dialysis and Transplant Registry, we analyzed 7440 adult deceased donor transplant events from 2000 to 2018. Transplants were classified as HLA matched or nonmatched according to the OrganMatch score and the local allocation algorithms. Graft function was studied with linear mixed modeling and graft rejection with logistic and binomial regression. Time to graft failure and recipient survival were examined with Kaplan-Meier curve and Cox regression models.Forty percent of transplants were HLA matched. Mean glomerular filtration rate was 1.76 mL/min/1.73 mMatched transplants showed benefits in graft and recipient outcomes; however, some of these results were of small magnitude, whereas others seemed to be due in part to a reduction in time on dialysis. The benefit for the matched cohort came at the expense of the nonmatched cohort, who spent longer on dialysis and were more likely to be of a minority racial background.

Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control. Mass cytometry allowed comprehensive phenotyping of circulating lymphocytes and revealed that CD4+ T cells were profoundly depleted by ATG, while CD8+ T cells, B cells, NK cells and monocytes were relatively spared. Multiple abnormalities in CD4+ T cell phenotype were stably present in the patient before disease onset. These included a population of CCR4−CCR6− effector/memory CD4+ T cells expressing intermediate levels of the Th1-related chemokine receptor CXCR3 and abnormally high multi-drug resistance type 1 transporter (MDR1) activity as assessed by a rhodamine 123 excretion assay. Expression of MDR1 has been implicated in steroid resistance and may have contributed to the severity and lack of a sustained steroid response in this patient. The number of CD4+ rhodamine 123-excreting cells was reduced > 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression. Electronic supplementary material The online version of this article (10.1007/s00262-017-2107-7) contains supplementary material, which is available to authorized users.

Background Lymphocele development following renal transplantation is a significant adverse event. It may cause acute graft dysfunction or venous obstruction. There are no consistent risk factors reported in literature. Perioperative fluid balance may lead to increased lymphocele formation and has never been studied. We aimed to analyse incidence and risk factors for lymphocele formation. We hypothesized that overhydration in perioperative period is a risk factor. Methods We analysed 250 consecutive renal transplant recipients from 2006 to 2014. All recipients had undergone protocol screening by computerized tomography and ultrasound scan at 3 months post-transplant. We analysed risk factors for lymphocele formation. Comparisons between lymphocele and no-lymphocele groups were made with binary logistic regression analyses. Renal function was compared between treated, untreated and no-lymphocele groups with linear regression analyses. Results Thirty-one of 250 (12.4%) transplant recipients developed lymphocele. Fourteen of 31 (45.4%) recipients required intervention due to symptoms (venous obstruction being the most common). Surgical drainage was done in all symptomatic patients (11 laparoscopic and three open). Two of 11 (18%) recipients had recurrence after laparoscopic drainage. There were no significant differences in risk factors between the lymphocele and no-lymphocele groups. Renal function was comparable between no-lymphocele and treated lymphocele groups. Untreated lymphocele group trended towards better graft function at 1 year (P = 0.051). Conclusion Post-transplant lymphocele developed one in eight transplant recipients and tended to occur in those with good renal function. Around half of the recipients with lymphocele required intervention with good recovery of long-term renal function. No risk factor for lymphocele development was established.

Thrombotic microangiopathy (TMA) after renal transplantation can be a diagnostic challenge. TMA can occur with calcineurin inhibitors, allograft rejection, infection, mutations in complement regulatory proteins and autoimmunity. A 52-year-old male renal transplant recipient presented with extensive deep vein thrombosis. He developed transfusion-dependent microangiopathic haemolytic anaemia with thrombocytopenia. He did not respond calcineurin inhibitor cessation, eculizumab or plasma exchange. ADAMTS13 and complement levels were normal. Infection and autoimmune screens were negative. A diagnosis of metastatic adenocarcinoma was made on bone marrow biopsy. This represents a rare case of malignancy-associated TMA in a renal transplant recipient. Early diagnosis can facilitate the prompt initiation of chemotherapy which is the only treatment option.

Cold agglutinin disease is a rare cause of acute graft loss after renal transplantation. A 71-year-old female with end stage renal failure was diagnosed to have cold agglutinin disease when investigated for recurrent clotting of hemodialysis circuits. Kidney transplantation was a major challenge due to unavoidable exposure of the transplant kidney to cold temperatures. Large volume plasma exchange given pre-transplant and infusion of warm saline prior to anastomosis resulted in successful renal transplantation with good graft function despite initial delayed graft function. This challenging case illustrates the complete removal of cold agglutinin antibodies with therapeutic large volume plasma exchange. J. Clin. Apheresis 32:56-58, 2017. © 2016 Wiley Periodicals, Inc.

Background. The transplantation of kidneys after cancer excision (restored kidney transplantation, RKT) warrants further evaluation as a source of kidneys for transplantation. We determined whether larger cancers can be safely transplanted, the risks of adverse events from RKT, and whether RKT confers a survival advantage for patients waiting for transplantation. Methods. In a retrospective cohort study, 23 dialysis patients awaiting transplant underwent RKT at John Hunter Hospital, Australia between 2008 and 2015. Patients were >60 years old and accepted onto the National Organ Matching Service. This RKT Group was divided into donor renal cancers ≤30 mm and >30–≤50 mm. Adverse event profiles for RKT recipients were compared with 22 standard live donor recipients using logistic regression analyses. Recipient and transplant survivals for RKT were compared with 2050 controls from Australian New Zealand Dialysis Transplant Registry using Cox regression models. To increase statistical power for survival analyses, data from 25 RKT recipients from Princess Alexandra Hospital, Brisbane were added, thus creating 48 RKT recipients. Results. There were no significant differences in mortality, transplant failure nor AEs between the 2 cancer Groups. RKT increased the risks of Adverse event profiles (odds ratio: 6.48 [2.92–15.44]; P < 0.001). RKT reduced mortality risk by 30% (hazard ratio [HR]: 0.70 [0.36–1.07]; P = 0.299) compared with those continuing on the transplant list who may or may not be transplanted. RKT significantly reduced mortality risk for those remaining on dialysis (HR: 2.86 [1.43–5.72]; P = 0.003). Transplant survival for RKT was reduced compared with control deceased donor (HR: 0.42 [0.21–0.83]; P = 0.013) and live donor transplants (HR: 0.33 [0.02–0.86]; P =0.023). Conclusions. The use of larger carefully selected cancer-resected kidneys for transplantation appears safe and effective. RKT confers a possible survival advantage compared with waiting for transplantation, an increased survival compared with those remaining on dialysis but reduced transplant survival.

Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677GC) and one from her mother (c.384 +1 GA).The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively.The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associated with adult-onset renal failure, but no ocular abnormalities. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin-angiotensin blockade.

To measure the risk of cancer in renal transplantation for recipients who had previously been treated with immunosuppressive agents for primary renal disease.A retrospective population-based cohort study of 5970 renal transplant recipients in Australia registered on the Australia and New Zealand Dialysis and Transplant Registry between 1982 and 1997 and followed until 2007. Data about the incidence of a range of cancer types from this Registry were compared with cancer incidence data for the general population matched for cancer type, year of incidence, age, and gender derived from national cancer records. Outcome measures for each cancer group with or without pretransplantation immunosuppression were cancer-specific standardized incidence ratios and a multivariate hazard ratio (HR) standardized to 1.For those treated with pretransplantation immunosuppression, the risks for four cancer groups during renal transplantation were significantly increased: anogenital cancer (HR, 3.13; confidence interval [CI], 1.92-5.11; P0.0001), non-Hodgkin's lymphoma (HR, 2.37; CI, 1.53-3.68; P=0.0001), breast cancer (HR, 2.52; CI, 1.13-5.61; P=0.024), and urinary tract cancer (excluding kidney) (HR, 1.84; CI, 1.13-3.01; P=0.015). However, the risks of cancer in the oral cavity and pharynx, kidney, thyroid, colon, leukemia, lung, melanoma, prostate, and stomach were not significantly increased.Pretransplantation immunosuppression for primary renal disease increases the risks of four cancer types in renal transplantation while sparing the others. Patients in whom this treatment is being considered should be informed of these risks.

Aim Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function. Methods Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia. Seventy-five patients were randomized to receive either usual exposure (n = 33) or reduced exposure (n = 42) CsA, EC-MPS 720 mg twice daily, basiliximab and corticosteroids. Results There was no significant difference in mean Cockcroft-Gault CrCl (creatinine clearance) (60.2 ± 17.6 mL/min per 1.73 m2 vs 63.2 ± 24.3, P = 0.64 for usual versus reduced exposure respectively) at 6 months. There was no significant difference between treatment groups in the incidence of treatment failure defined as biopsy proven acute rejection, graft loss or death (secondary endpoint: 30.3% full exposure vs 35.7% reduced exposure). At 12 months the incidence of overall adverse events was the same in both groups. Conclusion This exploratory study suggests de novo renal transplant patients can safely receive a treatment regimen of either full or reduced exposure CsA in combination with EC-MPS, corticosteroids and basiliximab, with no apparent difference in efficacy or graft function during the first year after transplant.

In this study we aimed to determine whether Castanospermine, a transplant immunosuppressive agent, impaired mononuclear/endothelial cell binding and expression of their cell adhesion molecules.The binding of human umbilical vein endothelial cells with peripheral blood mononuclear cells was measured by a binding assay using Chromium 51 label; the membrane expression of cell adhesion molecules was measured by flow cytometry expressed as mean fluorescence intensity ratios.Castanospermine decreased mononuclear/endothelial cell binding if and only if both cell types were treated with Castanospermine: this impairment occurred if endothelial cells were treated with a range of doses of Castanospermine and mononuclear cells were treated with a constant dose of Castanospermine (p0.001 versus untreated p=0.978) or vice versa (p=0.004 versus untreated p=0.582). Upon human umbilical vein endothelial cells Castanospermine reduced the mean fluorescence intensity ratios of E-selectin (p=0.003), ICAM-1 (p0.001), ICAM-2 (p=0.004) and PECAM-1 (p0.001) but increased it for P-selectin (p0.001). Upon peripheral blood mononuclear cells Castanospermine reduced the mean fluorescence intensity ratios of L-selectin (P0.001), LFA-1α (p0.001), VLA-4 (p0.001), Mac-1 (P0.001) and CR4 (p0.001) but increased the mean fluorescence intensity ratios of PSGL-1 (p0.001) and PECAM-1 (p=0.001). Similar changes in mean fluorescence intensity ratios were found in the subset of lymphocytes and monocytes but the reductions in LFA-1α and VLA-4 on lymphocytes and Mac-1 and CR4 on monocytes were greater.The reduction in mononuclear/endothelial cell binding mediated by CAST and the reduction in expression of multiple cell adhesion molecules on these cell types help to explain the mechanism of its established immunosuppressive effect.

• In the first 4 weeks after transplant, a diet providing at least 1.4 g protein/kg body weight may reverse negative nitrogen balance and lead to increased muscle mass in kidney transplant recipients. (Level III) • Until there is stronger evidence to suggest otherwise, low protein intake (i.e. 0.55 g/kg) in kidney transplant recipients with chronic graft rejection should be avoided, as this may be associated with negative nitrogen balance. (Level III) • Restricting dietary protein in kidney transplant recipients with chronic allograft nephropathy or chronic rejection may be beneficial with respect to kidney function, however, the magnitude of the benefit and a safe level of intake has yet to be identified. (Level III and IV) • In the absence of supporting evidence, when treatment with high doses of prednisone is required (for example during episodes of acute rejection), it is reasonable to assume that protein requirement may be elevated to a level similar to that of the early post-transplant period. • There is currently no evidence available regarding the long-term protein requirements of stable kidney transplant recipients. Stable kidney transplant recipients on a maintenance immunosuppression regimen, irrespective of renal function, should not exceed the NHMRC recommended daily intake of protein for the general population of 0.75 g protein/kg body weight for females and 0.84 g protein/kg body weight for males. • Regular review by a dietitian is desirable in the long term to ensure that protein requirements are neither exceeded (potentially placing unnecessary pressure on the kidney graft) nor inadequate (possible in periods of acute rejection when prednisone dose may be increased).

A rapid decline in bone mineral density occurs in the early post-transplant period. Though the rate of bone loss may decelerate or cease by around 3 years post-transplant, bone mineral density remains below normal. The risk of bone fractures among kidney transplant recipients is four times that among the general population. At the time of transplantation, there are usually already significant abnormalities of bone remodelling related to chronic kidney disease. Reduced calcium absorption due to prednisone, hyperparathyroidism and abnormal vitamin D metabolism are among the factors contributing to the further weakening of bones and the risk of bone disease post-transplantation. There is an increased risk of bone loss among females, particularly post-menopausal. This review set out to explore and collate the evidence to support the use of particular nutrition interventions for the prevention and management of bone disease in kidney transplant recipients, based on the best evidence up to and including September 2006.

To prevent excessive weight gain • Kidney transplant recipients should be referred to a dietitian as soon as practicable after transplantation, for written and verbal advice for preventing weight gain. (Level III) • Regular follow-up should be arranged to prevent excessive weight gain. (Level III) • As obesity is associated with an increased risk of steroid induced diabetes and cardiovascular disease risk factors as well as long-term graft function and poor graft survival: – all members of the health care team should monitor the weight of individual transplant recipients and arrange review by a dietitian if weight gain is a problem. • Evidence from studies in the general population indicates that dietary advice should be individualized and include meal plans, exercise plans and specific goals.

• Physicians should be aware that phosphate supplementation has the potential to worsen hyperparathyroidism and may mask phosphorus deficiency beyond 3 months post-transplant. (Level IV) • Kidney transplant recipients should be advised to consume phosphate-rich foods as early as possible after transplantation, once good graft function is achieved. • Supplementation may be considered if hypophosphataemia persists despite an adequate dietary phosphate intake. The serum phosphate level at which supplementation may be considered and the dose of replacement to be given are unclear and clinical judgement is required.

Once graft is functioning: • A diet rich in wholegrain, low glycaemic index and high fibre carbohydrates as well as rich sources of vitamin E and monounsaturated fat should be recommended to adult kidney transplant recipients with elevated serum total cholesterol, LDL-cholesterol and triglycerides. (Level III–IV) • Weight reduction in overweight or obese kidney transplant recipients should be encouraged and supported. (Level IV) (Refer to CARI Guideline: Nutritional management of overweight and obesity in adult kidney transplant patients) • Kidney transplant recipients with dyslipidaemia should be advised to eat a diet which reflects the evidence described above while being in line with lipid management guidelines for the general population as follows: 1 Carbohydrate Carbohydrate should be consumed predominantly in the form of wholegrains and foods with a low energy density and/or low glycaemic index, aiming for a daily fibre intake of 25 g for females and 30 g for males. The inclusion of the soluble fibre beta-glucan should be encouraged as it has been shown to lower LDLcholesterol in non-transplant populations. 2 Fat Total fat should contribute 30–35% of total energy intake. Saturated and trans fatty acids together should contribute no more than 8% of total energy intake. n-6 polyunsaturated fat should contribute 8–10% of total energy. Monounsaturated fat may contribute up to 20% of total energy intake. n-3 polyunsaturated fat should be included in the diet as both plant and marine sources. 3 Plant sterols and stanols Include plant foods which are naturally rich in phytosterols as well as 2–3 g phytosterol-enriched food products (such as margarine, breakfast cereal, low fat yoghurt or milk enriched with phytosterols. Australian regulations allow a minimum of 0.8 g and a maximum of 1.0 g phytosterols per serve of food, thus two or three serves of phytosterol-fortified foods should be recommended. • Alcohol should be limited to no more than two standard drinks on any day for both men and women. This advice is based on NHMRC guidelines for lifetime health risks associated with daily alcohol consumption by ‘healthy’ men and women. The potential direct effect of alcohol consumption on serum lipids, as well as the energy yield of alcohol (29 kilojoules per gram) and the contribution it may make to excessive energy intake and weight gain, should also be considered.

• Stable hypertensive kidney transplant recipients should be advised to restrict sodium intake to 80–100 mmol/day. (Level III evidence) • Based on studies in the general population kidney transplant recipients should: – When overweight or obese, be encouraged and supported to reduce their weight. (Refer to CARI Guideline: Nutritional management of overweight and obesity in adult kidney transplant patients). – Be encouraged to do at least 30 min of moderate intensity physical activity on at least 5 days per week. • Alcohol should be limited to no more than two standard drinks on any day for both men and women. This advice is based on NHMRC guidelines for lifetime health risks associated with daily alcohol consumption by ‘healthy’ men and women. • Lowering sodium intake to 65–70 mmol per day may cause a greater lowering of blood pressure.

Cytokine gene polymorphisms have been associated with poor outcomes after renal transplantation such as chronic allograft nephropathy (CAN), graft rejection (GR) and graft failure (GF), but the effects of these polymorphisms are still controversial. We therefore conducted a systematic review, with individual patient data (IPD) where possible, to determine the association between cytokine polymorphisms (TGF-beta1, TNF-alpha and IL-10) and outcomes after renal transplantation.Five investigators were willing to participate and provided IPD. The outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age.One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6-1.8 for/=3 HLA-A, -B, -DR mismatches compared with those with3 mismatches) and age (OR = 1.2-1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-beta1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0-2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-beta1 at c10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0-2.3). Three polymorphisms of the IL-10 gene at -1082, -819, -592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6-1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events compared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9-1.6).Pooled results to date suggest possible association between both the TGF-beta1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies.

Summary Immunosuppressants are used to control severe manifestations of allergic, autoimmune and transplant-related diseases. Some drugs have a diffuse effect on the immune system while others have specific targets. Drugs with diffuse effects are more likely to cause damaging adverse effects, but the effectiveness of the more specific drugs may be reduced if their action can be bypassed by alternative metabolic pathways. Treatment protocols therefore frequently use drug combinations to minimise adverse effects and to prevent resistance to treatment. Although protocols are essential to allow scientific evaluation, the clinician must be prepared to tailor treatment based on the ongoing assessment of drug effects, disease activity and the robustness of the individual patient.

The aim of this study was to determine the bioequivalence of Cysporin, a generic cyclosporine A, compared with Neoral in stable renal transplant recipients.Study design consisted of an open label, two-way crossover, randomized controlled trial of Cysporin versus Neoral in stable renal transplant recipients. In all, 33 patients were enrolled; 31 were randomized and 28 were evaluable. AUCs(0-12) were done on day 14 and 28; C(0) and C(2) were done on days 0, 7, 21 and 35. Dose conversion was 1:1. Outcome measures for serum cyclosporin A concentrations expressed as the mean+/-SD were AUC(0-12) (microg x hr/L), C(max) (microg/L), C(2) (microg/L), T(max) (hr) and T(1/2) (hr). Mean and 90% CI of the ratio Cysporin/Neoral of log-transformed data were calculated using a general linear model.The main pharmacokinetic features were: AUC(0-12): Cysporin 3495+/-1319, Neoral 3853+/-1378 (P0.05); C(max): Cysporin 755+/-301, Neoral 881+/-368 (P0.05); C(2): Cysporin 613+/-235, Neoral 672+/-255 (P0.05); T(max): Cysporin 1.9+/-0.8, Neoral 1.4+/-0.6 (P0.005); and T1/2: Cysporin 8.8+/-4.3, Neoral 8.7+/-6.2 (P0.05). Estimated ratios of Cysporin/Neoral were: AUC 0.93 (90% CI 0.88-0.98; P0.05); C(max) 0.88 (90% CI 0.80-0.97; P0.05); and T(max) 1.32 (90% CI 1.14-1.53; P0.005).Both the extent and rate of absorption of Cysporin are significantly less than those of Neoral. The 90% CI for the ratios of Cysporin/Neoral for AUC and C(max) lie within 0.80-1.25. Hence in this clinical context Cysporin is pharmacologically bioequivalent with Neoral. This study illustrates the importance of testing bioequivalence of generic cyclosporine A products in transplant recipients not healthy volunteers.

α v β 6 integrin expression in diseased and transplanted kidneys. Background Integrins have been implicated in the pathogenesis of a diverse range of kidney diseases. Herein, we provide the first detailed description of an epithelial restricted integrin, α v β 6 , in kidney biopsies from patients suffering acute and chronic renal diseases and after transplantation. Methods Immunoperoxidase staining for β 6 was performed on 267 selected biopsy specimens from native ( N = 126) and transplanted kidneys ( N = 141) and scored semiquantitatively. The site of β 6 expression in tubules was determined using haematoxylin counterstaining and by colocalization with Tamm-Horsfall protein. Comparisons were made between subcategories of diseases of native kidneys and between "service" and "protocol" biopsies of transplanted kidneys. Results β 6 , when present, is largely confined to the distal tubules and collecting ducts, colocated with Tamm-Horsfall protein. When sparsely present, it was often restricted to the tubular segment associated with the juxtaglomerular apparatus. It was found in tubular cells shed into the urine. β 6 was not expressed in thin membrane nephropathy, or in nonproliferative forms of glomerulonephritis, with the exception of focal and segmental glomerulosclerosis (FSGS). It was diffusely expressed where there was glomerular necrosis or thrombosis and in most forms of acute or chronic tubulointerstitial disease. β 6 was diffusely up-regulated in allografts biopsied for delayed function, in almost all kidneys that have clinical or subclinical rejection episodes and was prominent in chronic allograft nephropathy. Conclusion β 6 integrin is not normally expressed in adult native or transplanted kidneys but is commonly up-regulated in the distal tubule in disease. Our descriptive study suggests that it is a molecule worthy of further study.

Background. Repetitive endothelial damage from dialysis membrane incompatibility is a probable cause of accelerated atherosclerosis in haemodialysis patients. Consequently pulse wave velocity (PWV), a measure of arterial stiffness, was utilized as a surrogate marker of vascular dysfunction during dialysis with two commonly used synthetic dialysers. Methods. PWV was monitored before, during and after haemodialysis using both polysulphone and polyamide membranes. PWV, an arterial stiffness measure, was calculated from the carotid to the femoral (C-F) and also to the radial (C-R) artery. In a further group, PWV was monitored while polysulphone and polyamide membranes were perfused with blood without dialysate. Results. Mean aortic (C-F) PWV was lower during dialysis with the polyamide membrane, being 14 and 16% less following 75 and 135 min of dialysis (P

Summary Renal allograft compartment syndrome is an under recognized cause of early allograft dysfunction which can be reversed by early intervention. It occurs early after renal transplantation where closure of the anterior abdominal wall seems to compress the transplant in the limited retroperitoneal space. The literature about this syndrome in renal transplantation is sparse. Our report describes the diagnostic criteria and the management of two renal transplant recipients with this syndrome. Its diagnosis depends upon duplex vascular scan findings of reversed or absent diastolic flow in the renal vasculature in the absence of any perigraft collection or severe acute tubular necrosis. In our hands emergency laparotomy, decompression of the transplant and closure with interposition mesh salvaged these kidneys.

• Pre-transplant weight and pre-transplant weight gain increase the risk of the development of diabetes therefore weight management strategies should be a priority for patients awaiting a kidney transplant. (Level III evidence) • There are no Level III or IV studies examining the safety and efficacy of dietary interventions for the prevention and management of diabetes in adult kidney transplant recipients. The following suggestions for clinical care are based on advice given for prevention and management of diabetes in the general population. • In addition to this, Dietary advice to all adult kidney transplant recipients should reflect the current recommendations for reducing the risk of and managing type 2 diabetes in the general population. • To reduce the risk of diabetes mellitus, the following dietary guidelines, which are in line with guidelines for the general population, should be the following: – consume a diet with

To investigate the interaction between castanospermine and cyclosporin A (CsA) and to provide an explanation for it.The alkaloid castanospermine was prepared from the seeds of Castanospermum austral consistently achieving purity. Rat heterotopic cardiac transplantation and mixed lymphocyte reactivity were done using genetically inbred strains of PVG (donor) and DA (recipient). For the mixed lymphocyte reaction stimulator cells were irradiated with 3000 rads using a linear accelerator. Cyclosporin A was administered by gavage and venous blood collected 2 h later (C2). The blood levels of CsA (Neoral) were measured by immunoassay which consisted of a homogeneous enzyme assay (EMIT) on Cobas Mira. Statistical analyses of interactions were done by an accelerated failure time model with Weibull distribution for allograft survival and logistic regression for the mixed lymphocyte reactivity.Castanospermine prolonged transplant survival times as a function of dose even at relatively low doses. Cyclosporin A also prolonged transplant survival times as a function of dose particularly at doses above 2 mg/kg. There were synergistic interactions between castanospermine and CsA in the prolongation of cardiac allograft survival for dose ranges of CsA by castanospermine of (0 to 2) mg/kg by (0 to 200) mg/kg (HR = 0.986; 95%CI: 0.981-0.992; P0.001) and (0 to 3) mg/kg by (0 to 100) mg/kg (HR = 0.986; 95%CI: 0.981-0.992; P0.001) respectively. The addition of castanospermine did not significantly increase the levels of cyclosporin A on day 3 or day 6 for all doses of CsA. On the contrary, cessation of castanospermine in the presence of CsA at 2 mg/kg significantly increased the CsA level (P = 0.002). Castanospermine inhibited mixed lymphocyte reactivity in a dose dependent manner but without synergistic interaction.There is synergistic interaction between castanospermine and CsA in rat cardiac transplantation. Neither the mixed lymphocyte reaction nor the metabolism of CsA provides an explanation.

Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function.Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia. Seventy-five patients were randomized to receive either usual exposure (n = 33) or reduced exposure (n = 42) CsA, EC-MPS 720 mg twice daily, basiliximab and corticosteroids.There was no significant difference in mean Cockcroft-Gault CrCl (creatinine clearance) (60.2 ± 17.6 mL/min per 1.73 m(2) vs 63.2 ± 24.3, P = 0.64 for usual versus reduced exposure respectively) at 6 months. There was no significant difference between treatment groups in the incidence of treatment failure defined as biopsy proven acute rejection, graft loss or death (secondary endpoint: 30.3% full exposure vs 35.7% reduced exposure). At 12 months the incidence of overall adverse events was the same in both groups.This exploratory study suggests de novo renal transplant patients can safely receive a treatment regimen of either full or reduced exposure CsA in combination with EC-MPS, corticosteroids and basiliximab, with no apparent difference in efficacy or graft function during the first year after transplant.

Objective The present article summarizes the key recommendations of the evidence-based guidelines developed for the nutritional management of adult kidney transplant recipients. Background and Methods Nutrition interventions play an important role in preventing and managing common health problems associated with renal transplantation such as obesity, hypertension, diabetes, and cardiovascular disease. Two sets of guidelines were developed by a working group of renal dietitians and nephrologists. They were subject to expert panel review, and public consultation by renal clinicians and consumers before final endorsement by 2 authorities in Australia - Caring for Australasians with Renal Impairment (CARI) and Dietitians Association of Australia (DAA). Protocol and rigor of guideline development were previously described and published in the Journal of Renal Nutrition , 2009. Results and Outcomes These guidelines address 13 priority topics identified by the renal community and complement each other with different emphasis, from research translation to day to day clinical practice recommendations. The published guidelines are available to the public through web-access of CARI and DAA, and journal publications. Information includes the guidelines themselves with level of evidence stated, grading of recommendations, suggestions for clinical care, search strategy, background and summary of evidence, recommendations of other guidelines, practice recommendations, appendices of useful tools, and suggestions for audits and future research. Conclusions Two sets of comprehensive evidence-based nutrition guidelines from CARI and DAA are now available to help improve health outcomes of adult kidney transplant recipients.

Evidence demonstrates that cardiovascular risk reduces after kidney transplantation, but is still a major cause of death. With increasing inclusion of diabetic patients for kidney transplantation, the evaluation of cardiovascular disease in this population becomes more important. We compared arterial stiffness and pulse wave reflection as well as other cardiovascular risk factors in kidney transplant patients with and without diabetes mellitus.One hundred kidney transplant recipients, including 33 diabetic patients, were evaluated for their renal-cardiovascular risk factors, including blood pressure, lipids, glucose control, homocysteine, and arterial stiffness indexes. The tests were repeated after 1 year in 47 individuals.There was no significant difference in pulse wave velocity (PWV) between the diabetic and nondiabetic groups, despite a greater augmentation index (AI) in the diabetic group (20.5 +/- 2.3 versus 13.1 +/- 2.2). Multivariable analysis revealed that diabetes mellitus was a significant determinant for AI independently of age, blood pressure, posttransplant time, gender, and glomerular filtration rate (R2 = 39%). Repeated test after 1 year demonstrated a significant reduction in the carotid-femoral PWV (P = .03) and systolic blood pressure (P = .007).In contrast to nontransplant groups, AI was significantly greater in diabetic kidney transplant patients compared to their nondiabetic counterparts, despite a comparable PWV. However, carotid-femoral PWV improved after 1 year. These may reflect progressive ventricular and large arterial function improvement despite remained small arterial defects after transplantation. It also suggests potential role of arterial evaluation in risk assessment among kidney transplant patients.

Objective This article documents the development of evidence-based guidelines for the nutritional management of adult kidney transplant recipients. Dietary interventions play an important role in preventing and managing common post-transplant health problems, such as cardiovascular disease and diabetes. However, there are currently no comprehensive, evidence-based guidelines for the nutritional management of kidney transplant recipients. Methods and Results Thirteen guideline topics were identified, including obesity, diabetes, dyslipidemia, and bone disease, following broad consultation with clinicians and transplant recipients in Australia and New Zealand. A systematic review of the scientific literature was undertaken, the protocol for which is published in the Cochrane Library . The evidence was graded and synthesized, and evidence-based recommendations formulated consistent with National Health and Medical Research Council of Australia standards. A total of 119 scientific papers were assessed. Conclusion There was no level I or II evidence to support any guideline; however, there was sufficient level III and IV evidence to support Grade C and D recommendations for six guideline topics. Experts from 18 transplant units in Australia and New Zealand were consulted to generate consensus-based recommendations for the remaining seven topics, using the Delphi method. Using evidence from a comprehensive literature search and expert opinion, guidelines that represent current best practice have been produced. These guidelines have been evaluated in transplant units throughout Australia and New Zealand and have been submitted to the Dietitians Association of Australia (DAA) and Caring for Australasians with Renal Impairment (CARI) for endorsement.

In this issue, Vilayur et al. describe the case of a patient with monoclonal gammopathy and glomerulopathy associated with chronic lymphocytic leukemia (CLL). Although 'conventional; immunosuppression with cyclophosphamide and prednisone was unsuccessful, two courses of rituximab reversed the clinical manifestations of CLL-associated glomerulopathy, and resulted in complete clearance of the glomerular deposits. Background A 42-year-old previously healthy man was referred to hospital with an 8-week history of fevers, night sweats, fatigue, and unintentional weight loss. There was no past history of medical illness or any medication use. Physical examination was unremarkable. On urinalysis, the patient had hematuria (grade 4+) and proteinuria (grade 4+). Investigations Urine phase-contrast microscopy, full blood count, renal function tests, 24-h urine collection for protein, serum immune electrophoresis, renal biopsies, phase-contrast microscopy, serological tests for antinuclear antibodies, extractable nuclear antigens, antineutrophil cytoplasmic antibodies, hepatitis B, hepatitis C and HIV, cryoglobulin test, complement testing, flow cytometry of the peripheral blood, and bone marrow biopsy. Diagnosis Monoclonal gammopathy and a glomerulopathy, with microtubular deposits, associated with chronic lymphocytic leukemia. Management Treatment with prednisone and cyclophosphamide did not improve proteinuria, although lymphocyte count returned to normal. The patient did not tolerate high-dose cyclophosphamide and was started on rituximab. His proteinuria completely resolved and there was complete disappearance of the microtubules.

Erythropoietin (EPO) is a haematopoietic cytokine, mainly generated in the renal cortex, and its secretion and action is impaired in chronic kidney disease (CKD). Early renal damage in diabetes mellitus (DM) is usually not detected because diabetes-induced nephron hypertrophy maintains glomerular filtration rate (GFR) and an elevated plasma creatinine concentration is a relatively late manifestation of diabetic nephropathy. However, anaemia occurs more frequently in subjects with DM when compared with those with non-DM renal disease. While reduced production and a blunted response to EPO occurs in DM with early renal damage, other factors including chronic inflammation, autonomic neuropathy and iron deficiency are also important. Although recombinant human erythropoietin (rhEPO) has been an effective therapeutic agent in CKD anaemia, it appears to be more effective in patients with DM, even in earlier stages. Nevertheless, patients with DM are also more likely to be iron deficient, a barrier to effective rhEPO therapy. The effect of treatment on the reliability of haemoglobin A(1c) as an index of glycaemic control must be remembered. It is proposed that anaemia and its causes must be important components of care in subjects with early diabetic renal damage.

SUMMARY: Aim: The importance of ‘conventional’ cardiovascular risk factors in haemodialysis (HD) patients has been questioned following evidence that pre-HD blood pressure (BP) might be inversely related to mortality in contrast to post-HD BP. To evaluate this reverse BP epidemiology in HD patients, HD-induced BP changes were compared with aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. Method: Aortic PWV was evaluated in a limited care HD cohort, all of whom were asymptomatic of cardiovascular disease. Results: Of 47 limited care patients, 45% were classified as HD responsive, with a 17% fall in mean arterial pressure compared with a 6% increase in the HD-unresponsive group. While there were no significant differences between the two groups in traditional vascular disease risk factors or interdialytic weight loss, PWV was significantly elevated in the HD-unresponsive group (12.9 ± 2.7 compared with 10.8 ± 2.9; P < 0.05). Furthermore, there was a positive correlation between the change in BP during HD and PWV in all subjects ( r = 0.500; P < 0.001 for systolic blood pressure (SBP), a correlation that also existed for diastolic blood pressure (DBP) ( P < 0.01). Conclusion: This study suggests that patients with HD-unresponsive BP are more likely to have vascular disease and this association between PWV and HD-induced BP changes might partly explain the apparent paradox of pre- and post-HD BP with mortality. It is proposed that a population with elevated post-HD BP is more likely to be composed of subjects with vascular disease (overt or occult), in contrast to a group with high pre-HD BP, which will be more heterogeneous.