Proteomic analysis of plasma proteins of high-flux haemodialysis and on-line haemodiafiltration patients reveals differences in transthyretin levels related with anaemia.

A large proportion of end-stage renal disease (ESRD) patients under long-term haemodialysis, have persistent anaemia and require high doses of recombinant human erythropoietin (rhEPO). However, the underlying mechanisms of renal anaemia have not been fully elucidated in these patients. In this study, we will be focusing on anaemia and plasma proteins in ESRD patients on high-flux haemodialysis (HF) and on-line haemodiafiltration (HDF), to investigate using two proteomic approaches if patients undergoing these treatments develop differences in their plasma protein composition and how this could be related to their anaemia. The demographic and biochemical data revealed that HDF patients had lower anaemia and much lower rhEPO requirements than HF patients. Regarding their plasma proteomes, HDF patients had increased levels of a protein highly similar to serotransferrin, trypsin-1 and immunoglobulin heavy constant chain alpha-1, and lower levels of alpha-1 antitrypsin, transthyretin, apolipoproteins E and C-III, and haptoglobin-related protein. Lower transthyretin levels in HDF patients were further confirmed by transthyretin-peptide quantification and western blot detection. Since ESRD patients have increased transthyretin, a protein that can aggregate and inhibit transferrin endocytosis and erythropoiesis, our finding that HDF patients have lower transthyretin and lower anaemia suggests that the decrease in transthyretin plasma levels would allow an increase in transferrin endocytosis, contributing to erythropoiesis. Thus, transthyretin could be a critical actor for anaemia in ESRD patients and a novel player for haemodialysis adequacy.

Arteriovenous fistulae after renal biopsy: diagnosis and outcomes using Doppler ultrasound assessment.

BACKGROUND: Percutaneous renal biopsy (PRB) is an important technique providing relevant information to guide diagnosis and treatment in renal disease. As an invasive procedure it has complications. Most studies up to date have analysed complications related to bleeding. We report the largest single-center experience on routine Doppler ultrasound (US) assessment post PRB, showing incidence and natural history of arteriovenous fistulae (AVF) post PRB. METHODS: We retrospectively analysed 327 consecutive adult PRB performed at Ramon Cajal University Hospital between January 2011 and December 2014. All biopsies were done under real-time US guidance by a trained nephrologist. Routine Doppler mapping and kidney US was done within 24 h post biopsy regardless of symptoms. Comorbidities, full blood count, clotting, bleeding time and blood pressure were recorded at the time of biopsy. Post biopsy protocol included vitals and urine void checked visually for haematuria. Logistic regression was used to investigate links between AVF, needle size, correcting for potential confounding variables. RESULTS: 46,5% were kidney transplants and 53,5% were native biopsies. Diagnostic material was obtained in 90,5% (142 grafts and 154 native). Forty-seven AVF's (14.37%) were identified with routine kidney Doppler mapping, 95% asymptomatic (n = 45), 28 in grafts (18.4%) and 17 natives (9.7%) (p-value 0.7). Both groups were comparable in terms of comorbidities, passes, cylinders or biopsy yield (p-value NS). 80% were <1 cm in size and 46.6% closed spontaneously in less than 30 days (range 3-151). Larger AVF's (1-2 cm) took a mean of 52 days to closure (range 13-151). Needle size was not statistically significant factor for AVF (p-value 0.71). CONCLUSIONS: Contrary to historical data published, AVF's are a common complication post PRB that can be easily missed. Routine US Doppler mapping performed by trained staff is a cost-effective, non-invasive tool to diagnose and follow up AVF's, helping to assess management.

Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.

BACKGROUND: Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence-practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. METHODS: Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. RESULTS: We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = -0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients. CONCLUSIONS: We found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

Progression of residual renal function with an increase in dialysis: haemodialysis versus peritoneal dialysis.

OBJECTIVE: The main objective of the study was to analyse the progression of residual renal function according to the dialysis technique (peritoneal dialysis or haemodialysis) and the frequency of treatment (two or three sessions of haemodialysis per week). As secondary objectives, we studied the progression of the serum concentration levels of ß2 microglobulin and the response of anaemia to erythropoietic agents. MATERIAL AND METHOD: 193 non-anuric patients were included and began renal replacement therapy with dialysis in our hospital between 1 January 2006 and 31 December 2011, with a follow-up period of over three months. 61 patients (32%) began treatment with two haemodialysis sessions per week, 49 patients (25%) with three haemodialysis sessions per week and 83 patients (43%) with peritoneal dialysis. The glomerular filtration rate was measured as the mean of the renal clearances of urea and creatinine. RESULTS: The rate of decrease in glomerular filtration was the same in patients who began treatment with two haemodialysis sessions per week and with peritoneal dialysis (median 0.18 ml/min/month) and it was higher in patients who began treatment with three sessions of haemodialysis per week (median 0.33 ml/min/month, P<.05). Throughout progression, the glomerular filtration rate did not display differences between the group that began with two weekly sessions of haemodialysis and the group on peritoneal dialysis, and it was lower in the group that began treatment with three sessions of haemodialysis per week with statistical significance during the first 24 months of follow up. In the three patient groups, ß2-microglobulin concentration increased as the glomerular filtration rate decreased and it was higher in the group on three weekly haemodialysis sessions for the first 12 months of follow up. In all the controls carried out, there was a negative correlation between the beta-2 microglobulin concentration and the glomerular filtration rate (P<.001). The erythropoietin dose was negatively related to glomerular filtration. Patients who began with two sessions of haemodialysis per week required a lower dose of erythropoietin than patients that began renal replacement therapy with three weekly sessions. The erythropoietin dose in the peritoneal dialysis group was below that of the group of two weekly haemodialysis sessions despite maintaining a similar glomerular filtration rate. CONCLUSIONS: Patients who begin treatment with two sessions of haemodialysis per week experience the same rate of decrease in residual renal function as patients treated with peritoneal dialysis. The progression of the concentration of ß2-microglobulin is parallel to that of the glomerular filtration rate. Patients treated with two haemodialysis sessions require a lower dose of erythropoietin than those who receive three sessions per week, but a significantly higher dose than those treated with peritoneal dialysis, which suggests that the response of anaemia to erythropoietic agents is not only related to residual renal function, but also to other factors that are inherent to the dialysis technique.

Analysis of concordance between the bioelectrical impedance vector analysis and the bioelectrical impedance spectroscopy in haemodialysis patients.

INTRODUCTION: The values of body composition provided by the two most commonly used bioelectrical impedance systems in Spain, single-frequency bioelectrical impedance vector analysis (SF-BIVA) and multi-frequency bioelectrical impedance spectroscopy (MF-BIS) are different and not comparable. OBJECTIVE: Analyse whether the inter-method variability is due to bioelectrical variables measured by the different monitors, or rather due to the equations used to calculate body volume and mass. Another objective was to determine whether, despite the inter-method variability, the classification of hydration status by the two methods is consistent. MATERIAL AND METHODS: Bioelectrical impedance was measured by SF-BIVA and MF-BIS immediately before a dialysis session in 54 patients on haemodialysis. In 38 patients, the study was repeated by SF-BIVA at the end of the same dialysis session. RESULTS: Resistance and phase angle values provided by the two monitors at a frequency of 50kHz were consistent. For resistance, variability was 1.3% and the intra-class correlation coefficient was 0.99. For phase angle, variability and the intra-class correlation coefficient were 11.5% and 0.92, respectively. The volume values for total body water, extracellular water, fat mass and body cell mass were biased, with a level of variability that would not be acceptable in clinical practice. The intra-class correlation coefficient also suggested a poor level of agreement. SF-BIVA systems define overhydration or dehydration as a vector below or above the tolerance ellipse of 75% on the longitudinal axis. MF-BIS uses two criteria for pre-dialysis hyper-hydration: overhydration (OH) greater than 2.5 litres, or greater than 15% of extracellular water. The degree of equivalence with the results of the SF-BIVA monitor was better with the second criterion (kappa: 0.81, excellent agreement) than with the first one (kappa: 0.71, acceptable agreement). The MF-BIS system defines post-dialysis normal hydration as a difference between OH and ultrafiltratation volume between ­1.1 and 1.1 litres and agreement with the SF-BIVA system for this parameter was acceptable (weighted kappa index: 0.64). CONCLUSIONS: The MF-BIS and SF-BIVA systems provide similar readings for bioelectrical parameters, and the wide variation in the quantification of volume and body mass must be attributed to the different equations used for calculation. Furthermore, the criteria used by both systems to define both pre- and post-dialysis hydration have an acceptable level of equivalence.

Recovery of renal function in patients receiving haemodialysis treatment.

The aim of this study was to review all cases of recovery of renal function in chronic haemodialysis patients, observed in the last ten years. During the study period, 218 chronic renal failure patients were managed on haemodialysis for a minimum of 90 days. In 17 cases (8%), it was possible to interrupt dialysis after 95 to 529 days. The probability of renal function recovery was higher in patients with chronic interstitial nephritis (P=.04) or autoimmune diseases (P=.07), as well as in those starting haemodialysis treatment at a frequency of two sessions per week (P=.02). No significant differences in age, gender, glomerular filtration rate at the beginning of haemodialysis treatment, or comorbidity rate were observed. Seven patients returned to haemodialysis treatment after a dialysis-free period of 11 +/- 7 months. Two patients died for reasons unrelated to renal failure treatment, and another patient was moved to another hospital following 35 months without dialysis. The other 14 patients are alive and 8 are dialysis-free, with a monitoring period of 13 to 106 months. The conclusion reached is that there is no reason why residual kidney function should inexorably worsen after the start of haemodialysis treatment, and that functional recovery is possible in some patients.