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Background Physical activity (PA) levels are low in patients with advanced chronic kidney disease (CKD), and associate with increased morbidity and mortality. Reliable tools to assess PA in CKD are scarce. We aimed to develop and validate a novel PA questionnaire for use in CKD (CKD-PAQ). Methods In Phase 1, a prototype questionnaire was developed based on the validated recent PAQ (RPAQ). Structured feedback on item relevance and clarity was obtained from 40 CKD patients. In Phase 2, the questionnaire was refined in three iterations in a total of 226 CKD patients against 7-day accelerometer and RPAQ measurements. In Phase 3, the definitive CKD-PAQ was compared with RPAQ in 523 CKD patients. Results In the final iteration of Phase 2, CKD-PAQ data were compared with accelerometer-derived and RPAQ data in 60 patients. Mean daily metabolic equivalent of task (MET) and total energy expenditure (TEE) levels were similar by all methods. Intraclass correlation coefficients showed fair (MET) and good (TEE) agreement between accelerometry and both CKD-PAQ and RPAQ. Agreement between questionnaires was excellent. The mean [standard deviation (SD)] daily MET bias was 0.035 (0.312) for CKD-PAQ and 0.018 (0.326) for RPAQ. The mean (SD) TEE bias was 91 (518) for CKD-PAQ and 44 (548) kcal for RPAQ. Limits of agreement (LOA) were wide for both parameters, with less dispersion of CKD-PAQ values. In Phase 3, agreement between questionnaires was good (MET) and excellent (TEE). Bias of CKD-PAQ-derived mean (SD) daily MET from RPAQ-derived values was 0.031 (0.193), with 95% LOA −0.346 to 0.409. Corresponding mean (SD) values for TEE were 48 (325) and −588 to 685 kcal/day. CKD-PAQ appeared to improve discrimination between low activity groups. Conclusions CKD-PAQ performs comparably to the RPAQ though it is shorter, easier to complete, and may better capture low-level activity and improve discrimination between low activity groups.

Background Improved understanding and assessment of the complex physiology of volume regulation in haemodialysis (HD) patients are required to improve patient care and reduce mortality associated with fluid overload (FO). Methods We searched for FO-related biomarkers among 184 peptides associated with cardiovascular disease in a cohort of 30 HD patients. First, we assessed the direct impact of HD on the peptides of interest by comparing plasma concentrations before and after treatment. Then, we compared cardiovascular peptide profiles between patients with and without FO as defined by bioimpedance analysis (BIA). The plasma concentration of selected candidate biomarkers for FO was determined by enzyme-linked immunosorbent assay (ELISA) and correlated with previously described FO-related clinical and laboratory parameters. For validation, results were confirmed in an independent cohort of 144 HD patients. Results We found seven peptides positively [NT-proBNP, B-type natriuretic peptide (BNP), vascular endothelial growth factor D (VEGFD), tumour necrosis factor-related apoptosis-inducing ligand receptor 2, growth differentiation factor 15, tumour necrosis factor ligand superfamily member 13B, chitinase-3-like protein 1] and five negatively (leptin, renin, epidermal growth factor receptor, interleukin-1 receptor antagonist, myeloblastin) correlated to FO. In addition to natriuretic peptides, VEGFD emerged as third peptide highly correlated with BIA (ρ = 0.619, P Conclusion VEGFD is a novel FO-related biomarker with unique diagnostic and prognostic properties.

Background and Aims Incremental HD is a method of individualising haemodialysis (HD) dose according to level of residual renal function(RRF) such that as RRF reduces, HD dose is upwardly adjusted. Retrospective data suggest potential benefit of this approach in preserving RRF, a key predictor of survival for dialysis patients. Method A randomised, intention-to-treat, multi-centre trial was designed to determine the feasibility of a future definitive trial of incremental HD to establish if this approach preserves RRF. The trial was designed to estimate effect size of potential benefit in terms of RRF. 55 patients with RRF urea clearance≥3ml/min/1.73m2 BSA and within 3 months of starting HD were randomised across 4 UK dialysis centres to either conventional 3x weekly HD for 3.5-4 hours or incremental HD. The incremental HD protocol involved initiation of HD 2x weekly after randomization and upward adjustment of HD frequency and time as RRF was lost. In the conventional HD arm, patients were dialysed to ensure Standard Kt/VDialysis>2.0. In the incremental HD arm, patients were dialysed to ensure Standard Kt/VDialysis+Standard Kt/VResidual Renal Function>2.0 so both groups were dialysed to the same urea clearance target, except that urea clearance incorporated RRF in the incremental HD arm. Follow up was for 6 months (primary outcome data) but secondary outcome data will be for 12m. Patients were withdrawn for transplant, dialysis modality change or for patient choice. The primary outcome was rate of change of RRF in the first 6 months after randomization (effect size of intervention). Recruitability, retainability, protocol adherence and rate of adverse events were also measured as a primary objective. As a secondary outcome, we determined proportion of patients with urea clearance≥2 and ≥3ml/min /1.73m2 BSA at the 6 month time point. Impact of dialysis treatment was measured using questionnaire-based assessments at baseline and 6 months. Results 26 patients were randomised to standard HD and 29 to incremental HD. Baseline demographics including age, weight, haemoglobin, blood pressure, Charleson Comorbidity Index, were not significantly different between study arms. Baseline residual renal urea clearance was 5.1 ± SD 1.8 ml/min/1.73m2 BSA in the standard HD arm and 5.72 ± SD 2.49 in the incremental HD arm. 6 months, residual renal urea clearance reduced to 2.68±SD 1.73 in the standard HD arm and 3.80±SD 1.85 in the incremental arm. In the first 6 months, 3 patients recovered to dialysis independence (standard arm=1, incremental arm=2). Slope of RRF was not significantly different between two arms (p=0.39). The proportion of patients with significant urea clearance>2ml/min/1.73m2 BSA at 6 months was significantly higher in the incremental HD arm (92%) compared to the standard HD arm (65%), p=0.032. Rate of major adverse cardiac events, fluid overload, hyperkalaemia, vascular access events, deaths and infections did not differ significantly between groups. There were 2 deaths in the standard HD arm (in 4025 patient days) versus 1 in the incremental HD arm in the first 6 months(4666 patient days). There was no significant difference in Clinical Frailty Score, Montreal Cognitive Assessment score, depression score (PHQ-9), Quality of Life (EQ-5D-5L) and Illness Intrusiveness Rating Scale between groups at baseline and 6m time points. Conclusion Rate of loss of RRF (slope) was not significantly different between incremental HD and standard HD arms but incremental HD was associated with significantly higher probability of retaining urea clearance>2ml/min/1.73m2. There was no evidence of any clinical detrimental effect of incremental HD in terms of mortality, fluid overload or hyperkalaemic events. Incremental HD does not appear to be harmful and may confer a small benefit to preservation of residual renal function. A definitive study is required to define clinical benefits further.

Background and Aims Haemodialysis (HD) is one of the life-saving procedures which prolonged life of chronic kidney disease stage 5, however, the long-termed complications such as cardiovascular disease (CVD), immune and endothelial dysfunction are commonly occurred. The high incidence of CVD in haemodialysis patient associated with traditional and non-traditional risk factors. The novel non-traditional risk factors such as p-cresol, Advance Glycosylation End Products (AGEs), Ankle-Brachial Index (ABI), Cardio-Ankle Vascular Index (CAVI). The ischemic modified albumin (IMA) is the new marker for cardiovascular disease in various populations including haemodialysis. We aimed to explored the factors associate with higher IMA in chronic haemodialysis patients. Method Cross sectional study 196 chronic haemodialysis patients were collected blood sample for Ischemic modified albumin (IMA), measured Ankle-Brachial Index (ABI), Cardio-Ankle Vascular Index (CAVI), and skin autofluorescence advanced glycosylation end products (SAF). Results 53% were female, 21% were smoker, 57% were diabetes, 93% were hypertension, 33% were coronary artery disease, 12% on HDF. Mean Age were 69.2±13.2 year, ABI 1.1±0.15, CAVI 9.3±1.5, SAF 3.1±0.8 arbitrary unit, IMA 37.5±15.2 U/ml, and serum albumin 3.7±0.4 g/dl. In multivariate adjustment showed factors associate with higher IMA were low ABI (B co-efficiency -13.4, P=0.049) and high serum albumin (B co-efficiency 1.68, P=0.000002). Conclusion Lower ABI and high serum albumin associate with higher IMA. The finding underlines the association between the atherosclerosis, vascular endothelial function and cardiac injury in haemodialysis. These results should be confirmed and explored in larger and longer clinical trials. Figure Regression analysis of factors associate with IMA accumulation.

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease., Graphical Abstract Graphical Abstract

Background Accurate volume status evaluation and differentiation of cardiac and non-cardiac components of overhydration (OH) are fundaments of optimal haemodialysis (HD) management. Methods This study, by combining bioimpedance measurements, cardiovascular biomarkers and echocardiography, aimed at dissecting OH into its major functional components, and prospectively tested the association between cardiac and non-cardiac components of OH with mortality. In the first part, we validated soluble CD146 (sCD146) as a non-cardiac biomarker of systemic congestion in a cohort of 30 HD patients. In the second part, we performed a prospective 1-year follow-up study in an independent cohort of 144 HD patients. Results sCD146 incrementally increased after the short and long intervals after HD (+53 ng/mL, P = 0.006 and +91 ng/mL, P

Morbid obesity is reported to be a survival factor for haemodialysis patients compared with those with a normal body mass index (BMI), yet morbid obesity (BMI35) is a mortality risk factor for obese patients in the general population. Traditionally, haemodialysis dosing is prescribed to achieve a target Kt/V corrected for total body water (TBW). As obese patients typically have increased body fat, which contains less water than muscle, then obese patients may have lower levels of body water than their slimmer counterparts, and as such delivered Kt/V could be greater than that estimated using standard anthropomorphic equations, and so increased dialysis dose may help explain the increased survival reported for obese patients.We compared multi-frequency bioelectrical impedance analysis (MF-BIA) measurements of TBW in healthy haemodialysis outpatients, and compared TBW with that calculated from the Watson equation derived from anthropomorphic measurements.Three hundred and sixty-three adult patients, mean age 58.1 ± 16.7 years, 60.9% male and 29.9% diabetic were studied. MF-BIA-measured body composition showed that as BMI increased from20 to35, the percentage skeletal muscle mass fell from 42.8 ± 4.9 to 29.2 ± 5.5% (P0.01) whereas the % fat mass increased from 24.5 ± 11.6 to 46.7 ± 6.8% (P0.01). As such, TBW measured by MF-BIA was significantly lower from that predicted by the Watson equation at higher BMIs (BMI35; 38.9 ± 6.8 versus 44.7 ± 6.9 L, P0.01 and BMI = 30-35; 37.2 ± 7.5 versus 41.9 ± 7.3 L, P0.01), and as such the delivered Kt/V using MF-BIA was much greater than that using the Watson-based urea volume of distribution for the obese patients (BMI35; spKt/V 1.63 ± 0.48 versus 1.41 ± 0.35 and BMI 30-35; 1.65 ± 0.3 versus 1.46 ± 0.26, both P0.01).Prescribing dialysis or quantifying on-line clearance based on the anthropomorphically derived Watson equation leads to underestimation of the delivered dose to obese patients, due to changes in underlying body composition. As such, when using a 'one size fits all' target Kt/V, obese patients have an advantage over patients with normal BMI, in that they will receive a greater delivered dose of dialysis, and this may potentially explain the paradoxical survival advantage of the morbidly obese haemodialysis patient.

Renal impairment is a common complication of multiple myeloma (MM) and is supported in virtually all patients by a tubulointerstitial pathology that results from high serum concentrations of monoclonal free light chains (FLCs). The proteins involved in the kidney injury and the analysis of their binding interactions have been thoroughly investigated and the main pathogenic mechanisms are being elucidated. Early sustained reduction of circulating FLC leads to improved renal recovery rates that translate into improved quality of life and survival. The mainstay of therapy is presently the removal of aggravating factors (dehydration, hypercalcaemia, nephrotoxic drugs) and the prompt institution of rapidly acting novel chemotherapy combinations. This approach allows the rescue of kidney function in more than two-thirds of patients. High cut-off haemodialysis dialysers may potentially add clinical benefits and the outcomes of controlled trials are eagerly awaited. Basic research findings have led to the design of targeted drugs that prevented the functional manifestations of acute kidney injury in animal models. There is now hope to prevent the renal damage in patients with MM.

Hepatorenal syndrome (HRS) is defined as the occurrence of renal dysfunction in a patient with end-stage liver cirrhosis in the absence of another identifiable cause of renal failure. The prognosis of HRS remains poor, with a median survival without liver transplantation of

Background Brain natriuretic peptide (BNP) has been reported to be a powerful predictor of peritoneal dialysis patient survival. However, it is unclear as to whether this is related to cardiac dysfunction or chronic volume overload. Methods To investigate the relationship between BNP, cardiac function and fluid volume overload, we reviewed multifrequency bioimpedance, transthoracic echocardiography and serum N-terminal probrain-type natriuretic peptide (NTproBNP) in 115 stable peritoneal dialysis outpatients attending for assessment of peritoneal dialysis and transport status. Results In this cross-sectional study, the median NTproBNP was 251 (118-605) pmol/L. On simple univariate analysis, NTproBNP was associated with markers of residual renal function, volume overload, hypertension and hypertensive cardiac disease and inflammation [reduced serum albumin and raised C-reactive protein]. However, on multivariate logistical regression analysis, the strongest association for log NTproBNP was with the estimated right ventricular end-systolic pressure (β = 0.02, F = 11.5, P = 0.001), followed by log 24-h urine volume (β = -0.19, F = 10.7, P = 0.002), extracellular/total body water ratio (β = 13.5, F = 6.1, P = 0.017) and the number of different antihypertensive medications prescribed (β = 0.15, F = 8.7, P = 0.005). Conclusion In this cross-sectional study, although NTproBNP was associated with residual renal function, cardiac hypertrophy, volume overload and inflammation on simple univariate analysis, on further examination NTproBNP was predominantly affected by factors associated with volume overload, and these results require confirmation in a prospective study.

Introduction. Patients often report symptoms during haemodialysis (HD). To better understand patients’ experience, we surveyed routine HD outpatients, to quantify the burden and duration of dialysis-associated symptoms. Methods. Five hundred and eight symptom questionnaires were returned from 550 HD outpatients (92.4%). The symptoms in relation to the HD session were analysed using a visual analogue score. Multivariate logistical regression analysis was used to identify characteristics associated with total symptom burden and time to recover following a HD session. Results. Fifty-four percent of the cohort were male, median age 64 years, 36% diabetic and median age unadjusted Charlson comorbidity score 3.0 (2–5). Fatigue (82%), intradialytic hypotension (76%), cramps (74%) and dizziness (63%) were the commonest symptoms reported, followed by headache (54%), pruritus (52%) and backache (51%), with fatigue occurring with a median frequency of 50% of dialysis sessions and intradialytic hypotension and cramps in 30%. Some 23% reported recovering from dialysis within minutes, 34% by the time they returned home, 16% by bed time, 24% the following morning and 3% just before the next dialysis session. Symptom burden was associated with female sex, younger age, longer duration of dialysis sessions, ethnicity and dialysis centre practice. The time taken to recover from dialysis varied from minutes to hours and was shorter for men and greater dialysis vintage but longer with increasing session time and those with increased intradialytic symptom burden. Conclusions. Despite advances in HD, intradialytic symptoms were frequently reported by our patients. There was substantial unexplained variation in symptom burden across centres, suggesting that clinical practice or policies may play a role in preventing the adverse effects of dialysis. Symptom burden was worse in women, patients of South Asian as opposed to African origin and also in those receiving a longer duration of dialysis. These patients may therefore benefit from a different approach to dialysis prescription.

Background. Depression in end-stage renal disease patients is detrimental to quality of life, and is also associated with adverse clinical outcomes. The aim of this study was to examine whether depression symptoms in ‘incident dialysis’ patients predicted survival. Methods. One hundred and sixty incident haemodialysis and peritoneal dialysis patients completed a self-report depression questionnaire (Beck Depression Inventory-II, BDI) at a point soon after dialysis initiation. Over the study period (May 2007–December 2009), patients were followed up with all-cause mortality recorded as the end point. Results. The median follow-up time for the cohort was 511 days (min 47 days and max 1027 days). There were 27 deaths (16.9%). Depression symptoms were evaluated both as a continuous variable and using a defined cut-off for depressed patients (BDI ≥16). In a Cox proportional hazards model, adjusted for several covariates including albumin and extra renal comorbidity, depression score was an independent predictor of mortality (HR = 1.07, 95% CI 1.02–1.11, P = 0.002). In an additional adjusted model, a BDI score ≥16 was associated with a 2.7 times increase in the hazard for death (HR = 2.7, 95% CI 1.06–6.8, P = 0.037). Conclusions. The severity of depression symptoms following the start of dialysis treatment is an independent predictor of survival. Further studies will be required to determine whether the treatment of depression would alter health-related outcomes, including survival.

Introduction. Intradialytic hypotension remains the commonest complication of routine outpatient haemodialysis treatments. Multifrequency bioimpedance allows assessment of body fluid volumes. Multifrequency bioimpedance can potentially monitor changes in extracellular volume during dialysis and may therefore help to reduce intradialytic hypotension. Hypotension-prone patients have been reported to start dialysis with relatively more fluid distributed in the trunk than the arms. However, as arterio-venous fistulae are the preferred form of vascular access and fistulae could potentially affect fluid retention in the arm, we investigated whether multifrequency bioimpedance could detect differences in fluid distribution in the arms with haemodialysis in patients with different vascular access modalities.Methods. We audited the change in extracellular water (ECW) and total body water (TBW) in the arms following haemodialysis in 100 patients attending for routine outpatient haemodialysis at a university centre by multifrequency bioimpedance using an eight-electrode contact technique.Results. Patients with fistulae had greater ECW/TBW % in the fistula arm both prior to and post dialysis compared with central venous catheter (CVC) (pre 38.9 ± 0.1 vs 38.3 ± 0.1 and post 38.4 ± 0.1 vs 37.8 ± 0.1, P < 0.01), with a greater absolute difference between arms (0.53 ± 0.01 vs 0.05 ± 0.01, P < 0.01) and greater arm ECW/TBW % compared with total body ECW/TBW % predialysis (forearm fistula 99.4 ± 0.4 vs CVC 97.2 ± 0.3, P < 0.01).Conclusion. Absolute and also relative extracellular fluid volumes are increased in the fistula arm of haemodialysis patients. Thus, if algorithms are to be developed to monitor relative segmental changes in extracellular volumes to help prevent intradialytic hypotension using bioimpedance, then the dialysis vascular access and site will have to be considered, particularly if using relative changes in the upper limbs. Thus, alterative sites which are not so affected by vascular access, such as the calf, may prove advantageous.

Peter A. McCullough, Mikko Haapio, Sunil Mankad, Nereo Zamperetti, Barry Massie, Rinaldo Bellomo, Stefan D. Anker, Inder Anand, Nadia Aspromonte, Sean M. Bagshaw, Ilona Bobek, Dinna N. Cruz, Luciano Daliento, Andrew Davenport, Hans Hillege, Andrew A. House, Nevin Katz, Alan Maisel, Alexandre Mebazaa, Alberto Palazzuoli, Piotr Ponikowski, Federico Ronco, Andrew Shaw, Geoff Sheinfeld, Sachin Soni, Giorgio Vescovo, Pierluigi Zanco, Claudio Ronco and Tomas Berl 7,* for the Acute Dialysis Quality Initiative (ADQI) Consensus Group

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is an uncommon but potentially devastating complication of peritoneal dialysis. We have observed an increased incidence in our centre over the last few years. METHODS AND PATIENTS To look at potential risk factors for developing EPS, we reviewed 39 cases diagnosed between 2000 and 2009 and compared these with a control group of 71 patients who had been treated by peritoneal dialysis for a minimum of 4 years. Both groups extensively used icodextrin, >80% of patients. RESULTS Both groups had been treated by peritoneal dialysis for a similar time: EPS median 54 months (46-87.5), compared to controls 70 (54-79.5). However, more of the EPS group were treated with peritoneal cyclers (75% vs 46%, X(2) = 6.86, P = 0.009) and prescribed more peritoneal dialysate 14.2 l/day +/- 0.7 vs 10.8 +/- 0.5, P < 0.0001. Although both groups were fast transporters, those with EPS had higher D/P creatinine ratios on peritoneal equilibration testing, 0.84 +/- 0.1 vs 0.77 +/- 0.1, P < 0.05, and lower peritoneal test ultrafiltration volumes, 193 +/- 26 ml vs 283 +/- 21 ml, P < 0.05. Discussion. The patients in the EPS group were faster transporters, with lower peritoneal equilibration and 24-h ultrafiltration volumes, and were exposed to greater volumes of peritoneal dialysates compared to peritoneal dialysis vintage controls.

Background. Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumor necrosis factor-a, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular Volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. Methods. 50 patients were randomized to either 2,27% glucose or icodextrin (n = 28) ford long exchange following a month run in. Blood samples were obtained at - 1, 0, 3 and 6 months, coincident with measurements Of urine volume and fluid status. Results. In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine Volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007. in patients randomized to icodextrin, but not glucose. There were no relationships between fluid Status and any inflammatory markers at any point of the Study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated: the only predictor of between-patient variability oil multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily Ultrafiltration, urine volume, fluid or inflammatory status. Conclusions. This analysis supports observational data that changes in fluid status are associated with changes ill urine volume. Icodextrin was not associated with a greater fall ill urine Output despite its larger effect on ECFv Changes ill fluid status Could not be explained or did not appeal to influence systemic inflammation. Nor call they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution. (Less)

Background. It has been proposed that hepatitis C virus (HCV)-infected patients with end-stage renal disease undergoing maintenance haemodialysis may lack HCV antibody (anti-HCV) despite chronic HCV viraemia. This carries important implications for the design of surveillance policies. Methods. To characterize the prevalence of antibodynegative/RNA-positive HCV infection, patients attending seven haemodialysis units underwent antiHCV testing using a third-generation assay and HCV RNA testing using real-time PCR. Results. At screening, anti-HCV prevalence was 12/360 (3.3%; 95% CI 1.7–5.8%); 7/12 (58.3%) anti-HCV positive samples were HCV RNA positive. Among anti-HCV-negative samples, 2/348 (0.6%; 95% CI 0.2– 2.1%) tested HCV RNA positive (genotype 1a). Retrospective testing of stored sera dated the infections to a period of holiday in the Indian subcontinent. The two infections were unrelated by HCV-NS5B sequencing. Only one of the two newly infected persons showed raised transaminases. Both developed antiHCV within 8–13 weeks of follow-up. Prospective surveillance of travellers to resource-limited countries returning to the units showed a HCV incidence of 4/153 travel episodes (2.6%; 95% CI 0.7–6.6%) among 131 persons (3.1%; 95% CI 0.8–7.6%). Conclusions. Among haemodialysis patients in the United Kingdom, antibody-negative/RNA-positive HCV status is associated with newly acquired infection, rather than lack of antibody responses in chronic HCV infection. There is a significant risk of HCV infection associated with travel to resource-limited countries. Given that transaminase levels may be normal, HCV RNA testing is recommended in patients re-entering a dialysis unit following haemodialysis in settings where suboptimal infection control policies pose a risk of exposure to blood-borne viruses.

however, his liver extended 4 cm below the right costalmargin and the spleen was just palpable. Urine outputWe report two cases of renal, hepatic and respiratory was 20 ml/h with only red cells detected in his urine,failure occurring with the haemophagocytic syndrome of which

Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity.We measured serum aluminium and silicon levels from haemodialysis patients from four different centres.Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03).In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

We studied the effect of converting 100 established CAPD patients from aluminium- to calcium-based phosphate binders. After a follow-up of 1 year only 60% of patients remained on calcium carbonate. Hypercalcaemia was the major problem, with more than 40% of patients having a serum calcium in excess of 3.0 mmol/l. Several patients required hospitalization for symptomatic hypercalcaemia. Hypercalcaemia was more common in patients with normal serum parathyroid hormone concentrations (65 versus 25%, P less than 0.01). Serum phosphate control was better prior to commencing calcium carbonate when patients were treated with aluminium phosphate binders mean 1.71 +/- 0.15 mmol/l (SEM) than at the time of maximum serum calcium concentration, 1.81 +/- 0.25, P less than 0.05. This study does not confirm the findings of others, which have suggested that calcium carbonate is a safe and effective phosphate binder for patients with end-stage renal failure.

We prospectively followed 64 patients who had had no cytotoxic antibodies prior to first cadaveric renal allograft transplantation for post-transplant antibodies. During a mean follow-up period of 62 months (range 45-92) cytotoxic antibodies developed in 36 patients (56%). Sixteen grafts were lost due to chronic vascular rejection in the group of patients who developed antibodies compared to two in those who remained antibody negative, P < 0.01. Renal function was worse in the antibody-positive group, median serum creatinine 215 mumol/l (131-256) (interquartile range) versus 111 mumol/l (98-127) in the antibody-negative group, P = 0.002, and creatinine clearance 39 ml/min (25-55) versus 90 ml/min (55-104), P < 0.001. There were no significant differences in immunosuppressive protocol, HLA-mismatching, blood transfusion history, the number of acute rejection episodes, mean arterial blood pressure, or proteinuria between the groups. The presence of cytotoxic antibodies predated the classical manifestations of chronic vascular rejection. This suggests that humoral mechanisms may play a role in the development of chronic vascular rejection.

Urinary aluminium excretion was prospectively monitored during the first year following first cadaver renal allograft transplantation in 79 consecutive patients. Plasma and urinary aluminium concentrations steadily declined with time. Thirty-five patients had 0-1 episodes of acute graft rejection compared to 44 with two or more rejections; more of the former group had been prescribed aluminium-containing phosphate binders (74% versus 56%, P < 0.02), and following transplantation this group had a persistently greater urinary aluminium excretion, suggesting a greater aluminium body burden. There were no significant differences in terms of gender distribution, blood transfusion, or HLA matching between the groups, thus suggesting that either the subsequent mobilization of aluminium body stores following transplantation and/or the accumulation of aluminium in the reticulo-endothelial system prior to transplantation may have had an immunomodulatory effect in reducing the incidence of renal allograft rejection.

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.

We investigated the effect of an exogenous lactate load given during intermittent machine haemofiltration to three groups of patients with renal failure: those with dialysis-dependent end-stage renal failure (6 patients) and those with either acute renal (8 patients) and/or acute hepatorenal failure (6 patients). As expected, the hepatorenal group exhibited the greatest degree of hyperlactataemia, and this was associated with the development of a metabolic acidosis. There were correlations between the maximum blood lactate measured during treatment and the increase in arterial hydrogen ion concentration (r = 0.76, P less than 0.001), and between the decrease in serum bicarbonate (r = 0.89, P less than 0.001) and the mean arterial blood pressure prior to treatment (r = -0.57, P = 0.003). This suggests that hyperlactataemia is not as benign as previously thought and that lactate-buffered fluids should be used with care in patients with hepatorenal failure and cardiovascular instability.