PAlliative Care in chronic Kidney diSease: the PACKS study--quality of life, decision making, costs and impact on carers in people managed without dialysis.

BACKGROUND: The number of patients with advanced chronic kidney disease opting for conservative management rather than dialysis is unknown but likely to be growing as increasingly frail patients with advanced renal disease present to renal services. Conservative kidney management includes ongoing medical input and support from a multidisciplinary team. There is limited evidence concerning patient and carer experience of this choice. This study will explore quality of life, symptoms, cognition, frailty, performance decision making, costs and impact on carers in people with advanced chronic kidney disease managed without dialysis and is funded by the National Institute of Health Research in the UK. METHODS: In this prospective, multicentre, longitudinal study, patients will be recruited in the UK, by renal research nurses, once they have made the decision not to embark on dialysis. Carers will be asked to 'opt-in' with consent from patients. The approach includes longitudinal quantitative surveys of quality of life, symptoms, decision making and costs for patients and quality of life and costs for carers, with questionnaires administered quarterly over 12 months. Additionally, the decision making process will be explored via qualitative interviews with renal physicians/clinical nurse specialists. DISCUSSION: The study is designed to capture patient and carer profiles when conservative kidney management is implemented, and understand trajectories of care-receiving and care-giving with the aim of optimising palliative care for this population. It will explore the interactions that lead to clinical care decisions and the impact of these decisions on informal carers with the intention of improving clinical outcomes for patients and the experiences of care givers.

A key role for interferon regulatory factors in mediating early-life metabolic defects in male offspring of maternal protein restricted rats.

An adverse intra-uterine environment, induced by maternal consumption of diets high in saturated fat or low in protein have been implicated as a potential trigger for development of metabolic disease in later life. However, the underlying mechanisms responsible for this programming of obesity have yet to be described. Recent studies have demonstrated that interferon regulatory factors 3 (IRF3) and 4 (IRF4) function to repress adipogenesis. We investigated whether impaired IRF3 and IRF4 function may predispose to development of metabolic disease in a model of programmed obesity. Changes in IRF3 and IRF4 levels, adipogenic gene expression, and adiponectin signalling were measured in white adipose tissue from programmed male offspring of rat dams fed a low-protein diet (MLP), which are predisposed to obesity. 3T3L1 adipocytes were used to determine novel regulatory mechanisms governing IRF expression. IRF3 and IRF4 levels were suppressed in MLP rats, together with raised lipogenic and adipogenic gene expression. Adiponectin and adiponectin receptor 1 and 2 mRNA levels were reduced in MLP rats, along with levels of PPARα and activity of AMP-activated protein kinase (AMPK), 2 downstream targets of adiponectin. Further studies determined that both IRF3 and IRF4 are induced by adiponectin, with adiponectin-AMPK and adiponectin-PPARα signalling regulating IRF3 and IRF4, respectively. We have demonstrated that impaired ability to repress adipogenesis and lipogenesis, through dysregulated adiponectin-PPARα-AMPK-IRF signalling, may play a causal role in predisposing MLP offspring to development of obesity and metabolic disease in later life.

Progression of chronic kidney disease in a multi-ethnic community cohort of patients with diabetes mellitus.

AIMS: Ethnicity is a risk factor for the prevalence of severe chronic kidney disease among patients with diabetes. We studied the effect of ethnicity on progression of chronic kidney disease in people with diabetes managed in community settings. METHODS: A 5-year retrospective, community-based cohort study of 3855 people with diabetes mellitus of white, black or South Asian ethnicity with an estimated glomerular filtration rate of < 60 ml min⁻¹ 1.73 m⁻² was undertaken. From 135 general practices in east London, all cases with at least 3 years clinical data were included. Using repeated-measures analysis, the annual decline in estimated glomerular filtration rate was calculated. Comparisons between the rate of decline in the three main ethnic groups, with and without proteinuria at baseline, were made. RESULTS: The annual adjusted decline in estimated glomerular filtration rate for this cohort was 0.85 ml min⁻¹ 1.73 m⁻². The rate of chronic kidney disease progression was significantly greater in South Asian groups (-1.01 ml min⁻¹ 1.73 m⁻²) compared with white groups (-0.70 ml min⁻¹ 1.73 m⁻²) (P = 0.001). For those with proteinuria at baseline, the annual decline was greater at 2.05 ml min⁻¹ 1.73 m⁻², with both South Asian and black groups having a significantly faster rate of decline than white groups. CONCLUSIONS: For patients with diabetes and chronic kidney disease managed in primary care, the annual decline of renal function is less than previously thought and approximates the age-related annual decline of 1 ml min⁻¹ 1.73 m⁻². Patients with proteinuria and those of South Asian and Black ethnicity need additional monitoring as they are at greater risk of rapid chronic kidney disease progression.

Sirtuin 3 regulates mouse pancreatic beta cell function and is suppressed in pancreatic islets isolated from human type 2 diabetic patients.

AIMS/HYPOTHESIS: Sirtuin (SIRT)3 is a mitochondrial protein deacetylase that regulates reactive oxygen species (ROS) production and exerts anti-inflammatory effects. As chronic inflammation and mitochondrial dysfunction are key factors mediating pancreatic beta cell impairment in type 2 diabetes, we investigated the role of SIRT3 in the maintenance of beta cell function and mass in type 2 diabetes. METHODS: We analysed changes in SIRT3 expression in experimental models of type 2 diabetes and in human islets isolated from type 2 diabetic patients. We also determined the effects of SIRT3 knockdown on beta cell function and mass in INS1 cells. RESULTS: SIRT3 expression was markedly decreased in islets isolated from type 2 diabetes patients, as well as in mouse islets or INS1 cells incubated with IL1ß and TNFα. SIRT3 knockdown in INS1 cells resulted in lowered insulin secretion, increased beta cell apoptosis and reduced expression of key beta cell genes. SIRT3 knockdown also blocked the protective effects of nicotinamide mononucleotide on pro-inflammatory cytokines in beta cells. The deleterious effects of SIRT3 knockdown were mediated by increased levels of cellular ROS and IL1ß. CONCLUSIONS/INTERPRETATION: Decreased beta cell SIRT3 levels could be a key step in the onset of beta cell dysfunction, occurring via abnormal elevation of ROS levels and amplification of beta cell IL1ß synthesis. Strategies to increase the activity or levels of SIRT3 could generate attractive therapies for type 2 diabetes.

Plasma sodium and blood pressure in individuals on haemodialysis.

To study the relationship between pre-dialysis plasma sodium and blood pressure (BP), we performed an audit of patients who were on stable haemodialysis at St Bartholomew's and The Royal London Hospital from 1 June 2009 to 15 June 2010. There were 651 patients with 7445 dialysis sessions where both plasma biochemistry and BP were measured before haemodialysis. We found a significant association between plasma sodium and both systolic and diastolic BP. A 1 mmol l(-1) increase in plasma sodium was related to 0.65/0.36 mm Hg increase in BP (P<0.001 for both systolic and diastolic BP) after adjusting for potential confounding factors, including weight gain between dialyses and plasma albumin, both of which are crude indices of extracellular fluid volume. A separate analysis excluding individuals who were on BP treatment showed a similar relationship, with a 1-mmol l(-1) increase in plasma sodium associated with 0.82/0.56 mm Hg increase in BP (P<0.001 for both, N=177). These results provide further support for the accumulating evidence that plasma sodium has an important role in regulating BP, which may be independent of extracellular volume. Our findings in conjunction with other evidence suggest that small changes in plasma sodium could be an important mechanism for the beneficial effects of lower dialysate sodium and lower salt intake on BP in haemodialysis patients.

Applying research in nutrition education planning: a dietary intervention for Bangladeshi chronic kidney disease patients.

BACKGROUND: Effective nutrition health interventions are theory-based, as well as being drawn from practice and research, aiming to successfully accomplish dietary behavioural changes. However, the integration of theory, research and practice to develop community dietary educational programmes is a challenge that many interventionists feel ill equipped to achieve. METHODS: In the present study, a community-based education programme was designed for Bangladeshi patients with chronic kidney disease and hypertension. The goal of this programme was to reduce dietary salt intake in this population group, with a view to reducing their blood pressure and slowing kidney disease progression. RESULTS: The present study sets out the first four steps of a six-step model for creating a behaviour change programme. CONCLUSIONS: These four steps were concerned with the translation of theory and evidence into intervention objectives, and illustrate how a practical, community-based intervention was developed from behavioural theory, relevant research, knowledge of practice and the target patient group. Steps 5 and 6, which are concerned with implementation and evaluation, will be reported separately.

Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function.

AIMS/HYPOTHESIS: Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD(+) biosynthesis, exists as intracellular NAMPT (iNAMPT) and extracellular NAMPT (eNAMPT). eNAMPT, secreted from adipose tissue, promotes insulin secretion. Administration of nicotinamide mononucleotide (NMN), a product of the eNAMPT reaction, corrects impaired islet function in Nampt ( +/- ) mice. One of its potential targets is the NAD(+)-dependent deacetylase sirtuin 1. We hypothesised that altered NAMPT activity might contribute to the suppression of islet function associated with inflammation, and aimed to determine whether NMN could improve cytokine-mediated islet dysfunction. METHODS: Acute effects of NMN on cytokine-mediated islet dysfunction were examined in islets incubated with TNFα and IL1ß, and in mice fed a fructose-rich diet (FRD) for 16 weeks. Changes in iNAMPT, eNAMPT and inflammation levels were determined in FRD-fed mice. RESULTS: FRD-fed mice displayed markedly lower levels of circulating eNAMPT, with impaired insulin secretion and raised islet expression of Il1b. NMN administration lowered Il1b expression and restored suppressed insulin secretion in FRD-fed mice. NMN also restored insulin secretion in islets cultured with pro-inflammatory cytokines. The changes in islet function corresponded with changes in key markers of islet function and differentiation. The anti-inflammatory effects of NMN were partially blocked by inhibition of sirtuin 1. CONCLUSIONS/INTERPRETATION: Chronic fructose feeding causes severe islet dysfunction in mice. Onset of beta cell failure in FRD-fed mice may occur via lowered secretion of eNAMPT, leading to increased islet inflammation and impaired beta cell function. Administration of exogenous NMN to FRD-fed mice corrects inflammation-induced islet dysfunction. Modulation of this pathway may be an attractive target for amelioration of islet dysfunction associated with inflammation.

Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db/db mice.

AIM: AMPK activates SIRT1 in liver and skeletal muscle. Impaired circadian function is associated with development of obesity. SIRT1 regulates circadian function and is suppressed in white adipose tissue (WAT) of obese patients. We examined the potential role of AMPK and SIRT1 in regulation of circadian components in WAT of obese db/db mice and in mice fed a high-fat diet (HFD), and investigated whether metformin-mediated activation of AMPK opposed any deleterious changes in the WAT clock mechanism. METHODS: db/+ and db/db mice were administered metformin (250 mg/kg/day; 7 days). Separately, mice were fed HFD for 16-weeks. 3T3-L1 adipocytes were incubated with metformin, EX527 or FK866, inhibitors of SIRT1 and NAMPT, respectively. Gene and protein expression were measured by qRT-PCR and immunoblotting. RESULTS: AMPK activity, NAMPT expression and SIRT1 expression were decreased in WAT of db/db and HFD mice, in association with suppressed expression of the core circadian components CLOCK and BMAL1. Expression of Pparγ and the adipogenic repressors Irf3 and Irf4 were also suppressed. Metformin increased AMPK activity in WAT of db/db mice and in metformin-treated adipocytes, with increased NAMPT, SIRT1 and circadian component expression. Metformin-mediated induction of Clock mRNA in adipocytes was blocked by inhibition of NAMPT and SIRT1. CONCLUSIONS: Decreased AMPK-SIRT1 signalling in db/db and HFD mice impacts WAT circadian function causing dysregulated lipid regulation, favouring an obese phenotype. Metformin mediates a phenotypic shift away from lipid accretion through AMPK-NAMPT-SIRT1 mediated changes in clock components, supporting chronotherapeutic treatment approaches for obesity.

Barriers and facilitators of dietary sodium restriction amongst Bangladeshi chronic kidney disease patients.

BACKGROUND: People of Bangladeshi origin have the highest mortality ratio from coronary heart disease of any minority ethnic group in UK and their rate of kidney disease is three- to five-fold higher than that of the European UK population. However, there is little information regarding their dietary customs or knowledge, beliefs and attitudes towards health and nutrition. This multi-method qualitative study aimed to identify: (i) barriers and facilitators to dietary sodium restriction; (ii) traditional and current diet in the UK; and (iii) beliefs and attitudes towards development of hypertension, and the role of sodium. METHODS: Methods included focus group discussions, vignettes and food diaries. Twenty female chronic kidney disease patients attended four focus group discussions and maintained food diaries; ten responded to vignettes during telephone interviews. Triangulation of the results obtained from the three methods identified categories and themes from qualitative thematic analysis. RESULTS: Identified barriers to sodium restriction were deeply-rooted dietary beliefs, attitudes and a culturally-established taste for salt. Facilitators of change included acceptable strategies for cooking with less salt without affecting palatability. Dietary practices were culturally determined but modified by participants' prosperity in the UK relative to their previous impoverished agrarian lifestyles in Bangladesh. CONCLUSIONS: Cultural background and orientation were strong determinants of the group's dietary practices and influenced their reception and response to health communication messages. Efforts to understand their cultural mores, interpret and convey health-promotion messages in culturally-appropriate ways met with a positive response.

Blood pressure guidelines in chronic kidney disease: a critical review.

The primary purpose of guidelines should be to improve patient care by providing an avenue for healthcare professionals to participate in the assessment of appropriate care, based on sound medical reasoning and robust scientific knowledge. Guidelines are usually meant to be evidence-based when they are derived from systemic reviews of the relevant literature. Nephrology as a medical subspeciality lags behind other clinical disciplines when it comes to availability of high-quality clinical studies with hard clinical outcomes. In the absence of robust clinical evidence, recommendations in renal guidelines are overwhelmingly opinion-based and reflect the experience of the various experts. Unfortunately, no guidelines are detailed enough to provide recommendations for individual patients with different types and severity of co-morbidities. We propose that guidelines should be viewed as desirables and should not replace a common sense clinical approach to patient care by an autonomously practicing competent clinician.

The effect of ethnicity on the prevalence of diabetes and associated chronic kidney disease.

BACKGROUND: The effect of ethnicity on the prevalence of diabetes mellitus (DM) and associated chronic kidney disease (CKD) is unknown. AIM: To establish the impact of ethnicity on the prevalence and severity of diabetes mellitus and associated CKD. DESIGN: Cross-sectional study of 34 359 adult diabetic patients in three primary care trusts in the UK. METHODS: Read coded data from general practice computers was used to analyse the relationship between ethnicity, DM and CKD. RESULTS: The prevalence of DM was 3.5% for Whites, 11% for South Asians and 8% for Black groups. The prevalence of CKD (stages 3-5) among diabetics was 18%. CKD stage 3 was more prevalent in Whites compared to South Asians--OR 0.79 (95% CI: 0.71-0.87) and Blacks--OR 0.49 (95% CI: 0.43-0.57). Among all CKD patients severity (CKD stages 4, 5) was associated with Black (OR 1.39, 95% CI: 1.06-1.81) and South Asian (OR 1.54, 95% CI: 1.26-1.88) ethnicity compared to Whites. Less than 50% of diabetics with CKD met the target blood pressure (BP) of 130/80 mmHg. The prevalence of a blood pressure > 150/90 mmHg in diabetics with CKD was South Asian 15.6%, White 13.9%, Black 21.8% (P < 0.001). Proteinuria was present in 8.6% of all diabetic patients. However, this increased to 18.6% in patients with CKD, and was more frequent in Black (22.6%) and South Asian (21%) patients compared to White patients (14.1%) (P < 0.001). CONCLUSION: Significant disparities exist between the major ethnic groups in both disease prevalence and management. Future studies examining the management of CKD need to take variation by ethnicity into account.

Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombotic microangiopathy.

De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed. We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients.

Randomized controlled study of biocompatible peritoneal dialysis solutions: effect on residual renal function.

Residual kidney function is important for patient and technique survival in peritoneal dialysis (PD). Biocompatible dialysis solutions are thought to improve function and viability of peritoneal mesothelial cells and to preserve residual renal function (RRF). We conducted a randomized controlled study comparing use of biocompatible (B) with standard (S) solutions in 93 incident PD patients during a 1-year period. The demographics, comorbidities, and RRF of both groups were similar. At 3 and 12 months, 24-h urine samples were collected to measure volume and the mean of urea and creatinine clearance normalized to body surface area. Surrogate markers of fluid status, diuretic usage, C-reactive protein concentration, peritonitis episodes, survival data, and peritoneal equilibrium tests were also collected. Changes in the normalized mean urea and creatinine clearance were the same for both groups, with no significant differences in secondary end points. Despite non-randomized studies suggesting benefits of these newer biocompatible solutions, we could not detect any clinically significant advantages. Additional studies are needed to determine if advantages are seen with longer term use.

High glucose initiates calpain-induced necrosis before apoptosis in LLC-PK1 cells.

Cells exposed to high ambient glucose concentrations are subject to increases in intracellular calcium ([Ca(2+)](i)). We therefore considered it likely that the calcium-dependent cysteine protease calpain would play a role in the development of high glucose-induced cell injury. After 3 and 24 h, high glucose concentrations (25 mM D-glucose) produced almost identical increases in the degree of necrotic cell death in kidney proximal tubular epithelial cells (LLC-PK(1)) compared to cells treated with control glucose (5 mM D-glucose). Necrotic cell death could be restricted by inhibiting the activity of calpain. High glucose-treated LLC-PK(1) cells were found to have significantly elevated [Ca(2+)](i) concentrations within 1 h, and elevated calpain activity within 2 h compared to control treated cells. The DNA nick sensor poly(ADP-ribose) polymerase (PARP) has previously been shown to be an important driver of high glucose-induced cell death, but here we found that although PARP activity was increased after 24 h, it was unaltered after 3 h. Furthermore, PARP inhibition with PJ-34 did not restrict early high glucose-induced necrosis. Using a gene knockdown strategy with small interference RNA, we found that silencing calpain was effective in reducing the degree of early high glucose-induced necrosis. We conclude that high glucose concentrations evoke an early, calpain-mediated necrosis in cultured proximal tubular cells that is PARP-independent, and precedes the previously recognized activation of apoptosis.

Characterization of cationic amino acid transport systems in rat erythrocytes: lack of effect of uraemia on L-arginine influx.

1. Chronic renal failure (CRF) is associated with the abnormal regulation of nitric oxide (NO) synthesis at the systemic level. The transport of L-arginine, upregulated in blood cells from uraemic patients, modulates NO synthesis in this pathological condition. The model of partial nephrectomy in rats is widely accepted as a valid model of uraemia. Because there are no reports of L-arginine transport in blood cells from uraemic rats, the aim of the present study was to investigate L-arginine transport in red blood cells (RBCs) from these rats. 2. The kinetics of L-arginine transport in RBC and plasma and the amino acid profiles of RBC were investigated in control, sham-operated and subtotally nephrectomized rats. 3. L-Arginine transport was mediated via the cationic amino acid transport system y+ and a transport system with kinetics resembling the human system y+L. In control RBC, the apparent Ki for L-leucine inhibition of L-arginine transport via system y+L was 0.16 +/- 0.02 and 4.8 +/- 2 mmol/L in the presence of Li+ and Na+, respectively. 4. The Vmax values for L-arginine transport via system y+L and system y+ were similar in RBC from control sham-operated and uraemic rats. Moreover, L-arginine concentrations in plasma and RBC were not affected by uraemia. 5. The findings of the present study provide the first evidence that L-arginine transport in rat erythrocytes is mediated by two distinct cationic transport systems with characteristics of systems y+ and y+L, which accept neutral amino acids only in the presence of Li+. In contrast with previous studies in uraemic patients, plasma levels and maximal transport rates of L-arginine were not altered in this rat model of CRF.

Erythropoietin in experimental acute renal failure.

The haematopoietic factor erythropoietin (EPO) has recently been recognized to play a physiological role in the brain and other tissues. The EPO receptor is present in the glomerulus, mesangial and tubular epithelial cells in the kidney. We have reviewed the experimental use of EPO in animal models of acute renal failure. EPO attenuates the dysfunction and histological changes associated with ischaemia-reperfusion injury, with a reduction in apoptotic cell death. EPO has also shown benefit in animal models of systemic shock and cisplatin-induced nephrotoxicity. In vitro studies have shown that EPO has direct effects on proliferation and cell death in proximal tubular epithelial cells. There is increasingly strong experimental evidence that EPO may be of therapeutic use in acute renal failure, and clinical trials should be undertaken to determine its clinical applications in this field.

Sarcoid tubulo-interstitial nephritis: long-term outcome and response to corticosteroid therapy.

Sarcoidosis is a chronic relapsing multi-systemic disorder characterized by the development of non-caseating granulomas. Granulomatous tubulo-interstitial nephritis is an uncommon manifestation of this condition. We identified 39 patients with sarcoidosis and renal disease from a single center of whom 17 patients had biopsy-proven tubulo-interstitial nephritis. They were analyzed with respect to demographic and clinical features, including response to corticosteroids and length of follow-up. They all presented with significant renal impairment. At presentation the mean+/-s.d. estimated glomerular filtration rate (eGFR) was 26.8+/-14 ml/min by modification of diet in renal disease (MDRD) equation 7. With treatment there was a significant improvement in renal function with eGFR 49.6+/-5.2 ml/min (P<0.01) at 1 year, and 47.9+/-6.8 ml/min (P<0.05) at the last review. The median follow-up was 84 months (range 6-284 months). Patients with chronic kidney disease (CKD) 3, the mean eGFR was 38.30+/-2.4 ml/min at presentation and 60.2+/-7.4 ml/min at 1 year (P=0.02) and in CKD 4 it improved from 19+/-2 to 38+/-6.6 ml/min at 1 year (P<0.05). After the 1st year, the change in eGFR was +0.8 ml/min/year for CKD 3 and -2 ml/min/year for CKD 4 (P<0.05). Three patients ceased their therapy either due to complications or poor compliance and experienced a worsening of renal function which was then reversed on re-commencing corticosteroids. Corticosteroids are effective in advanced tubulo-interstitial nephritis due to sarcoidosis. Long-term treatment is necessary to preserve renal function and to delay the onset of end-stage renal disease.

Activation of L-arginine transport in undialysed chronic renal failure and continuous ambulatory peritoneal dialysis patients.

1. Treatment with haemodialysis and continuous ambulatory peritoneal dialysis (CAPD) presents different pathophysiological profiles and it has been suggested that clinical outcome in chronic renal failure may depend on the mode of dialysis. The transport of L-arginine, a precursor of nitric oxide, into blood cells is increased in uraemic patients on haemodialysis. The present study was designed to investigate L-arginine transport into red blood cells (RBC) in uraemic patients not yet on dialysis and on CAPD therapy. 2. Eleven uraemic patients not yet on dialysis and 17 on CAPD were included in the study. L-Arginine transport into RBC and plasma and RBC amino acid profiles were analysed in these sets of patients. 3. L-Arginine transport via system y(+), but not y(+)L, into RBC, was significantly increased in undialysed uraemic patients (459 +/- 40 micromol/L per cell per h) and CAPD patients (539 +/- 61 micromol/L per cell per h) compared with controls (251 +/- 39 micromol/L per cell per h). High-pressure liquid chromatography measurements demonstrated low levels of plasma L-arginine in uraemic patients both on CAPD (54 +/- 3 micromol/L) and not yet on dialysis (80 +/- 6 micromol/L) compared with control subjects (146 +/- 14 micromol/L). 4. Our findings provide the first evidence that uraemic patients not yet on dialysis and on CAPD present with an activation of L-arginine transport via system y(+) into RBC associated with reduced plasma levels of L-arginine.

High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, p<0.001) and NR (179 U/mL, range: 70-343, p<0.03). Moreover, patients with TIR had significantly lower sCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, p<0.05). sCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.