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The evaluation of estimated GFR (eGFR) is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The interaction between histopathological diagnosis and ultrasound parameters in eGFR determination has not been fully investigated yet. The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between ultrasound parameters and eGFR. After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52 years for patient age, 11 cm for bipolar kidney diameter, 16 mm for parenchymal thickness, 2.5 g/day for proteinuria and 70 ml/min/1.73 m 2 for eGFR. The bipolar kidney diameter and the parenchymal thickness were directly related with eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006). Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis are associated with eGFR. The relationship between kidney length and the level of eGFR depends on the nature of the kidney disease., (© 2024. The Author(s).)

Background: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy., Methods: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression., Results: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective., Conclusions: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Lower limb ischemia affects the quality of life, physical activity and life expectancy of dialysis patients. The aim of this study was to investigate the risk factors associated with ischemic foot ulcers considering clinical, laboratory and therapeutic domains., Methods: This observational cohort study was based on data from the Nephrology and Dialysis Department database of Alessandro Manzoni Hospital, Lecco (Italy). All of the incident patients who started dialysis between 1 January 1999 and 29 February 2012 were enrolled, excluding temporary guests, patients with acute renal failure and patients with previous limb ischemia or amputation. Multivariate Cox regression analysis identified the predictors in each domain, which were matched in the final model. A time-dependent approach was used to take into account the evolution of some of the prognostic covariates., Results: Of the 526 incident dialysis patients, 120 developed a lower limb ischemic lesion after a median of 13 months. The incidence of new ulcers was constant during the study period (6 per 100 person-years), but higher in the diabetics with a relative rate of 4.5. The variables significantly related to an increased risk of lower limb ulcers were age, male gender, diabetes, ischemic heart disease, treatment with proton pump inhibitors, iron, anticoagulants and calcium-based binders, and blood levels of phosphorus, triglycerides and C-reactive protein., Conclusion: The incidence of lower limb ulcers was highest during the early dialysis follow-up and was associated with, in addition to diabetes, modifiable laboratory and therapeutic predictors such as anticoagulants, proton pump inhibitors, calcium-containing binders, calcimimetics and iron.

Objectives: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV., Methods: In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity., Results: Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed., Conclusions: MTX may be effective and safe for remission-maintenance in AAV., Trial Registration: clinicaltrials.gov NCT00751517.

Primary distal renal tubular acidosis is a rare genetic disease. Mutations in SLC4A1, ATP6V0A4, and ATP6V1B1 genes have been described as the cause of the disease, transmitted as either an autosomal dominant or recessive trait. Particular clinical features, such as sensorineural hearing loss, have been mainly described in association with mutations in one gene instead of the others. Nevertheless, the diagnosis of distal renal tubular acidosis is essentially based on clinical and laboratory findings, and the series of patients described so far are usually represented by small cohorts. Therefore, a strict genotype-phenotype correlation is still lacking, and questions about whether clinical and laboratory data should direct the genetic analysis remain open. Here, we applied next-generation sequencing in 89 patients with a clinical diagnosis of distal renal tubular acidosis, analyzing the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and the clinical phenotype. A genetic cause was determined in 71.9% of cases. In our group of sporadic cases, clinical features, including sensorineural hearing loss, are not specific indicators of the causal underlying gene. Mutations in the ATP6V0A4 gene are quite as frequent as mutations in ATP6V1B1 in patients with recessive disease. Chronic kidney disease was frequent in patients with a long history of the disease. Thus, our results suggest that when distal renal tubular acidosis is suspected, complete genetic testing could be considered, irrespective of the clinical phenotype of the patient., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Oxidative stress has been related to hypo-response to erythropoiesis-stimulating agents (ESAs) in hemodialysis (HD) patients. The aim of this study was to verify whether vitamin E (ViE) on a synthetic polysulfone dialyzer can improve ESA responsiveness., Methods: This controlled, multicenter study involved 93 HD patients on stable ESA therapy, who were randomized to either ViE-coated polysulfone dialyzer or to a low-flux synthetic dialyzer. The primary outcome measure was the change in ESA resistance index (ERI) from baseline., Results: Mean ERI decreased in the ViE group by 1.45 IU/kg*g/dl and increased in the control group by 0.53 IU/kg*g/dl, with a mean difference of 1.98 IU/kg*g/dl (p = 0.001 after adjusting for baseline ERI, as foreseen by the study protocol). Baseline ERI was inversely related to its changes during follow-up only in the control group (R2 = 0.29)., Conclusions: The ViE dialyzer can improve ESA response in HD patients. Changes in ERI during follow-up are independent from baseline ERI only in the ViE group. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=453442., (© 2017 S. Karger AG, Basel.)

Background: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted acensusof the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to theyear 2014., Methods: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit., Results: Renal and dialysis activity was performed by over 2718 physicians (45 pmp). The management of the acute renal failure was one of the most frequent activities in the public renal units (12,206 patients in ICU and 140.00 dialysis sessions). There were performed about 9000 AV fistulas and 1700 central vascular catheters insertions. In the census, there are a lot of data regarding organization, workforce and workload of the renal unit in Italy. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Background: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to the year 2014., Methods: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit., Results: 615 renal units were identified. From these 615 units, 332 were public renal centres (of which 318 centres answered to the census) and 283 were private dialysis centres (of which 113 centres answered to the census). The results show 6 public renal units pmp. Renal biopsies were 4624 (81 pmp). The nephrology beds are about 41 pmp. There are 7.304 nurses working in HD wards, 1.692 in the nephrology wards and only 613 for outpatients clinics. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

Background: The role of change in proteinuria as a surrogate end point for randomized trials in immunoglobulin A nephropathy (IgAN) has previously not been thoroughly evaluated., Study Design: Individual patient-level meta-analysis., Setting & Population: Individual-patient data for 830 patients from 11 randomized trials evaluating 4 intervention types (renin-angiotensin system [RAS] blockade, fish oil, immunosuppression, and steroids) examining associations between changes in urine protein and clinical end points at the individual and trial levels., Selection Criteria for Studies: Randomized controlled trials of IgAN with measurements of proteinuria at baseline and a median of 9 (range, 5-12) months follow-up, with at least 1 further year of follow-up for the clinical outcome., Predictor: 9-month change in proteinuria., Outcome: Doubling of serum creatinine level, end-stage renal disease, or death., Results: Early decline in proteinuria at 9 months was associated with lower risk for the clinical outcome (HR per 50% reduction in proteinuria, 0.40; 95% CI, 0.32-0.48) and was consistent across studies. Proportions of treatment effect on the clinical outcome explained by early decline in proteinuria were estimated at 11% (95% CI, -19% to 41%) for RAS blockade and 29% (95% CI, 6% to 53%) for steroid therapy. The direction of the pooled treatment effect on early change in proteinuria was in accord with the direction of the treatment effect on the clinical outcome for steroids and RAS blockade. Trial-level analyses estimated that the slope for the regression line for the association of treatment effects on the clinical end points and for the treatment effect on proteinuria was 2.15 (95% Bayesian credible interval, 0.10-4.32)., Limitations: Study population restricted to 11 trials, all having fewer than 200 patients each with a limited number of clinical events., Conclusions: Results of this analysis offer novel evidence supporting the use of an early reduction in proteinuria as a surrogate end point for clinical end points in IgAN in selected settings., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Doppler ultrasound has been extensively used in detecting reno-vascular diseases, showing to be a non-invasive, safe, low cost and repeatable tool. The Renal Resistive Index (RRI) [(peak systolic velocity - end diastolic velocity)/peak systolic velocity] is a semi-quantitative index derived by Doppler evaluation of renal vascular bed. Normally RRI is in the range of 0.47-0.70, it increases with aging and, usually, it shows a difference between the two kidneys less than 5-8 %. RRI is an important prognostic marker in chronic kidney diseases (CKD), both in diabetic and non-diabetic kidney diseases, because, in longitudinal prospective studies, it significantly correlated with hemodynamic (ABPM, SBP, DBP, pulse pressure) and histopathological parameters (glomerular sclerosis, arteriolosclerosis, interstitial fibrosis/tubular atrophy, interstitial infiltration). In acute kidney injury (AKI) RI is a valid tool in differentiating between pre-renal and renal failure and in predicting renal response to vaso-active agents. In addition a RRI >0.74 can predict the onset of AKI in septic patients. Renal Resistive Index is a useful marker in allograft diseases because it has been widely showed a correlation with histological lesions during worsening of renal function, both in acute rejection and in chronic allograft nephropathy. Recent studies suggest its role in the risk of new onset diabetes after transplantation and it could be one of the parameters to evaluate to shift or withdrawal immunological and/or hypertensive therapy., Competing Interests: Compliance with ethical standards Conflict of interests The authors declare that they have no competing or conflicting interests. Informed consent For this type of study formal consent is not required. Human and animal studies The study described in this article does not contain studies with animal and human subjects performed by any of the authors.

Background: Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial., Methods: This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients)., Results: CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P < 0.001) and sevelamer (P < 0.001), pre-dialysis bicarbonate levels (P < 0.001) and pre-dialysis blood K levels (P < 0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P < 0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P., Conclusions: In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309)., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

In this article, the Italian Society of Nephrology discusses the risks for the Medical Specialty in Nephrology and the possible lack of job opportunities by young nephrologists, that arises from the actions taken in the last years by National and Regional Italian Governments. The article reports the main legislative rules required to access the work system both in public and private hospital. Finally, we examined the different criteria and the standards requested for Regional Accreditation by Italian National Health System, and to obtain reimbursement by private and public providers. These requirements might be useful to guarantee both the specificity of nephrology specialty in the assistance to patients affected by kidney diseases, and a stable and qualified job for young nephrologists.

Objective: A high prevalence (60%) of central adrenal insufficiency (CAI) has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. We have assessed CAI in adults with PWS using the low-dose short synacthen test (LDSST)., Design: Basal cortisol and ACTH, and 30-min cortisol after the administration of 1 μg synacthen, were determined in 53 PWS adults (33 females). A peak cortisol value of ≥500 nmol/l was taken as normal. Hormonal profiles were analysed in relation to gender, genotype and phenotype. Deficient patients were retested by high-dose short synachten test (HDSST) or a repeat LDSST., Results: Mean ± SD basal cortisol and ACTH were 336·6 ± 140·7 nmol/l and 4·4 ± 3·7 pmol/l respectively. Cortisol rose to 615·4 ± 135·0 nmol/l after LDSST. Eight (15·1%) patients had a peak cortisol response <500 nmol/l, with a lower mean ± SD (range) basal cortisol of 184·9 ± 32·0 (138·0-231·7) compared with 364·1 ± 136·6 (149·0-744·5) in normal responders (P < 0·001). Seven of the eight patients underwent retesting, with 4 (7·5%) showing persistent suboptimal responses. Basal and peak cortisol correlated in females (r = 0·781, P < 0·001). Logistic regression revealed that only female gender and baseline cortisol were predictors of cortisol peaks (adjusted R square 0·505)., Conclusions: Although CAI can be part of the adult PWS phenotype, it has a lower prevalence (7·5%) than previously reported. Clinicians are advised to test PWS patient for CAI. Our study also shows that basal cortisol is closely correlated with adrenal response to stimulation, indicating that its measurement may be helpful in selecting patients for LDSST., (© 2013 John Wiley & Sons Ltd.)

Background: Therapeutic nihilism is common in IgA nephropathy (IgAN) and renal insufficiency., Methods: In a randomized controlled trial comparing steroids alone or combined with azathioprine in 253 IgAN patients, we used a separate randomization list for patients with creatinine >2.0 mg/dL. Twenty patients (group 1) were randomized to 3 intravenous pulses of methylprednisolone 1 g at months 1, 3 and 5, and oral prednisone 0.5 mg/kg every other day plus azathioprine 1.5 mg/kg/day for 6 months, followed by oral prednisone 0.2 mg/kg every other day plus azathioprine 50 mg/day for a further 6 months; 26 patients (group 2) received steroids alone. The primary outcome was renal survival (50% increase in plasma creatinine from baseline); secondary outcomes were proteinuria over time and adverse events., Results: Six-year renal survival was not different between the 2 groups (50% vs. 57%; log-rank p=0.34). Median proteinuria decreased during follow-up in the whole population (from 2.45 g/day [interquartile range (IQR) 1.50-3.78] to 1.09 g/day [IQR 0.56- 2.46]; p<0.001), with no between-group difference. Multivariate predictors associated with renal survival were sex of patient, proteinuria during follow-up, number of antihypertensive drugs, angiotensin-converting enzyme inhibitors and treatment including azathioprine. Six patients in group 1 (30%) and 4 in group 2 (15%) did not complete the therapy, because of side effects (p=0.406)., Conclusions: Six-year renal survival was similar in the 2 groups. At Cox analysis the addition of azathioprine may be slightly more effective than corticosteroids alone in patients with chronic renal insufficiency, although with an increase of side effects.

Diagnosis of diabetic nephropathy is generally based, rather than on histological confirmation, on clinical criteria (long history of diabetes, presence of proteinuria, diabetic retinopathy or peripheral neuropathy). This clinical approach has perhaps limited utility in DM2 patients, because only 50% of them show microvascular complications in presence of nephropathy. Eco-colour-Doppler sampling of interlobular renal arteries and determination of their resistance indices (RI), was proposed in the differential diagnosis of numerous nephropathies. Aim of this study was to evaluate whether RI can be useful in discerning non-diabetic renal disease (NDRD), in order to better define indications to perform renal biopsy among proteinuric DM2 patients. All patients were submitted to: echo-colour-Doppler study of renal vessels; systematic screening for diabetic retinopathy; needle renal biopsy. RI resulted to be significantly higher in diabetic glomerulosclerosis (GSD) group as compared with NDRD group, while no significant difference was found with respect to NDRDs overlapping GSD (overlapping group). The last one showed however median RI significantly higher than isolated NDRD group. Normalized chi square Pearson for the hypothesis that RI can predict GSD resulted 0.73, while it resulted 0.43 for the hypothesis that diabetic retinopathy can predict GSD. Echo-colour-Doppler can significantly contribute, more than the other parameters proposed (nephritic or nephrotic syndrome, hematuria, diabetic retinopathy), to the identification of underlying nephropathy in DM2 subjects. In the light of our experience, it seems that the detection of RI values > 0.72 suggests the diagnosis of GSD or mixed forms, reducing the indications to renal biopsy only in presence of values < 0.72.

Contrast-enhanced ultrasound (CEUS) is one of the most interesting and promising clinical applications of imaging and ultrasound. Thanks to the absence of ionizing radiation, the lack of nephrotoxicity and low cost it has the potential to become a reference in imaging of the kidney. This review, besides providing a brief description of the proper methodology, presents possible applications of CEUS in nephrology and urology, including renal ischemia, the differential diagnosis of cystic and solid lesions, follow-up of ablative therapies, kidney trauma, kidney transplant, inflammatory diseases, ischemic nephropathy and vesicoureteral reflux.

Background: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH., Methods: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH., Results: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq., Conclusions: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation. Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy. Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded. TAPSE was reduced (<23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score. TAPSE showed a bimodal distribution, with a subpopulation "low TAPSE - high PAPs", next to a population characterized by normal values ??for both parameters. A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.

Background: Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes., Methods: Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients)., Results: CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta(2) 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170)., Conclusions: In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

Objective: A recent study evidenced by metyrapone test a central adrenal insufficiency (CAI) in 60% of Prader-Willi syndrome (PWS) children. These results were not confirmed in investigations with low [Low-Dose Tetracosactrin Stimulation Test (LDTST), 1 μg] or standard-dose tetracosactrin stimulation tests. We extended the research by LDTST in paediatric patients with PWS., Design: Cross-sectional evaluation of adrenal stress response to LDTST in a PWS cohort of a tertiary care referral centre., Patients: Eighty-four children with PWS., Measurements: Assessment of adrenal response by morning cortisol and ACTH dosage, and 1-μg tetracosactrin test. Response was considered appropriate when cortisol reached 500 nm; below this threshold, patients were submitted to a second test. Responses were correlated with the patients' clinical and molecular characteristics to assess genotype-phenotype correlation., Results: Pathological cortisol peak responses to the LDTST were registered in 12 patients (14.3%) who had reduced basal (169.4 ± 83.3 nm) and stimulated (428.1 ± 69.6 nm) cortisol levels compared to patients with normal responses (367.1 ± 170.6 and 775.9 ± 191.3 nm, P < 0.001). Body mass index standard deviation score was negatively correlated with basal and peak cortisol levels (both P < 0.001), and the patients' ages (P < 0.001). In patients with deletion on chromosome 15, the cortisol peak was significantly lower than that in uniparental disomy (UPD) cases (P = 0.030). At multiple regression analysis, the predictors of peak response were basal cortisol, age, and UPD subclass (r(2) = 0.353, P < 0.001). Standard-dose (250 μg) tetracosactrin test confirmed CAI in 4/12 patients (4.8% of the cohort)., Conclusions: Our results support the hypothesis that, albeit rare, CAI may be part of the PWS in childhood., (© 2012 Blackwell Publishing Ltd.)

Convective therapies can be a good additional option in extracorporeal renal replacement therapy, but so far the clinical evidence in their favor is rather scarce. In this review the results of the most important studies are discussed, grouped by main outcomes: intradialytic cardiovascular stability, beta2-microglobulin, mortality, calcium-phosphorus metabolism, and possible effect on anemia. In general, the use of convective therapies for reimbursement reasons but without any clear clinical benefit is not justified. The fractional division of convective therapies into various subtypes and the use of different levels of convection among centers make their widespread clinical implementation unlikely in the near future. No firm conclusions can be drawn right now and more controlled clinical trials on convective therapies will be needed to clarify their role in renal replacement therapy.

Therapeutic plasma exchange is an extracorporeal plasmapheresis method for removing high-molecular-weight pathogens and toxins from the circulation. It can be indicated in many clinical conditions, both kidney-related and non-kidney-related. This review focuses on clinical trials related to Goodpasture syndrome, thrombotic thrombocytopenic purpura, and acute renal insufficiency due to multiple myeloma. It also discusses the difficulties and opportunities associated with the development of a randomized controlled multicenter study and of a web-based database. Finally, we report a summary of the risks and complications of therapeutic plasma exchange and how we can update the information on their frequency and seriousness by means of a longitudinal prospective multicenter study open to all centers performing the procedure.

Background: Diagnostic imaging of acute pyelonephritis (APN) in renal transplanted patients is an important clinical issue. While conventional ultrasonography (US) has a limited diagnostic role, contrast-enhanced computer tomography and magnetic resonance imaging (MRI) represent the gold standard diagnostic tests. However, nephrotoxicity of either iodinated or paramagnetic contrast medium limits their use, especially in patients with kidney disease. Contrast-enhanced US (CEUS) may detect poorly perfused parenchymal renal areas, a useful feature in the diagnosis of APN. The aim of this study was to evaluate the diagnostic value of CEUS in APN compared with MRI as the reference test., Methods: From a pool of 389 kidney transplant patients, we prospectively recruited 56 patients with clinical suspicion of APN of the transplanted kidney. They underwent both CEUS and MRI, performed in a blinded manner by two different operators. Sensitivity, specificity, accuracy, positive and negative predictive values, and K statistics were calculated., Results: Thirty-seven out of 56 patients (66.1%) resulted positive for APN with the reference test, gadolinium-enhanced MRI. Thirty-five out of these 37 patients showed positive results for APN with CEUS, and 19 patients showed negative results for APN with both MRI and CEUS: sensitivity 95% (CI 82-99), specificity 100% (CI 83-100), accuracy 96% (CI 88-99), positive predictive value 100% (CI 90-100), negative predictive value 90% (CI 71-97) and K statistics 0.92 (P<0.01)., Conclusions: Our results suggest, for the first time, the feasibility of CEUS, a low-cost and low-risk diagnostic procedure, in the diagnosis of APN in kidney transplant patients.

The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.

Symptomatic intradialytic hypotension is a common complication of hemodialysis (HD). The application of convective therapies to the outpatient setting may improve outcomes, including intradialytic hypotension. In this multicenter, open-label, randomized controlled study, we randomly assigned 146 long-term dialysis patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or online predilution hemodiafiltration (HDF; n = 40). The primary end point was the frequency of intradialytic symptomatic hypotension (ISH). Compared with the run-in period, the frequency of sessions with ISH during the evaluation period increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF (10.6 to 5.2%) (P < 0.001). Mean predialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF, respectively (P = 0.038). Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward higher dropout for those who were assigned to HF (P = 0.107). In conclusion, compared with conventional HD, convective therapies (HDF and HF) reduce ISH in long-term dialysis patients.

Background: Oxidative stress, a recently identified factor related to the response to erythropoiesis-stimulating agents (ESAs), is increased in hemodialysis patients. The aim of this study was to verify whether ESA responsiveness improves if the anti-oxidant vitamin E (Vi-E) is placed on the blood-side layer of a synthetic polysulfone (PS) dialyzer., Methods: This 8-month, controlled and open randomized study involved 2 groups of patients on stable ESA therapy undergoing hemodialysis using a PS dialyzer with or without Vi-E treatment. Hemoglobin, albumin, high-sensitivity C-reactive protein, interleukin-6, iron status, parathyroid hormone (PTH), Vi-E (alpha- and gamma-tocopherol levels) and the oxidative stress markers, advanced oxidation protein products, carbonyls and advanced glycation end products were evaluated every 2 months. The primary outcome measure was ESA resistance, the weekly ESA dose divided by the product between hemoglobin level and end-dialysis body weight., Results: Nineteen of the 20 randomized patients completed the study. During the follow-up, the ESA resistance significantly decreased (p = 0.024), greater in the Vi-E group (37%) than in the PS group (20%), but this difference was not statistically significant (p = 0.596). Baseline PTH and Vi-E levels were associated with ESA resistance. In the secondary analysis, including these covariates in the model, the difference between groups in ESA resistance became significant (p = 0.042)., Conclusions: Vi-E placed on the blood-side of a dialyzer may have a possible beneficial effect on ESA resistance in hemodialysis patients; baseline PTH levels seem to predict ESA resistance and were useful in showing the possible beneficial effect of Vi-E and should be considered in designing adequate-sized trials for testing this hypothesis.

Renovascular disease is a complex disorder, most commonly caused by fibromuscular dysplasia and atherosclerotic diseases. It can be found in one of three forms: asymptomatic renal artery stenosis (RAS), renovascular hypertension, and ischemic nephropathy. Particularly, the atherosclerotic form is a progressive disease that may lead to gradual and silent loss of renal function. Thus, early diagnosis of RAS is an important clinical objective since interventional therapy may improve or cure hypertension and preserve renal function. Screening for RAS is indicated in suspected renovascular hypertension or ischemic nephropathy, in order to identify patients in whom an endoluminal or surgical revascularization is advisable. Screening tests for RAS have improved considerably over the last decade. While captopril renography was widely used in the past, Doppler ultrasound (US) of the renal arteries (RAs), angio-CT, or magnetic resonance angiography (MRA) have replaced other modalities and they are now considered the screening tests of choice. An arteriogram is rarely needed for diagnostic purposes only. Color-Doppler US (CDUS) is a noninvasive, repeatable, relatively inexpensive diagnostic procedure which can accurately screen for renovascular diseases if performed by an expert. Moreover, the evaluation of the resistive index (RI) at Doppler US may be very useful in RAS affected patients for predicting the response to revascularization. However, when a discrepancy exists between clinical data and the results of Doppler US, additional tests are mandatory.

Variations in the course of the blood vessels are often incidental findings during clinical examination. Persistent left superior vena cava (PLSVC) is an uncommon anomaly, estimated to be present in about 0.3-0.5% of healthy individuals and in about 3-10% of patients with congenital heart disease. It results from the failure of the left anterior cardinal vein to degenerate during embryological development. Serious complications such as shock, angina and cardiac arrest have been described during catheterization in adults with a PLSVC. Since it frequently goes undiagnosed because of lack of symptoms when not accompanied by other anomalies, variations of the superior vena cava should be considered, especially when central venous catheterization via the subclavian or internal jugular vein is difficult. The embryological development, diagnosis, and clinical implications of a PLSVC are therefore reviewed in this article.

Objective: The aim of our study was to assess the role of Doppler ultrasonography (DU) by resistive index (RI) and the difference of the RI (DeltaRI) in patients with acute unilateral renal obstruction., Patients and Methods: We studied 36 consecutive patients (12 female, 24 male; mean age 45.6 +/- 8.4 years) with suspected renal colic by intravenous pyelography (IVP) and DU with determination of the RI and the Delta RI. A RI of >= 0.70 and a DeltaRI of >= 0.06 were considered suggestive of obstruction. IVP was considered as the "gold standard"., Results: In the studied population, RI was 0.664 +/- 0.060 in the affected kidney site of symptoms and 0.614 +/- 0.025 in the contralateral one, with an overall Delta RI of 0.049 +/- 0.062. At IVP, 14 patients resulted within normal range (Group A; 39%), 6 patients showed lithiasis without obstruction (Group B; 17%), 8 patients showed delayed excretion of the contrast medium (Group C; 22%), and 8 patients showed a functional exclusion of the kidney (Group D; 22%). One-way analysis of variance showed the IVP group significantly related to Delta RI with the highest values in Groups C (DeltaRI of 0.093 +/- 0.051; p<0.001) and D (DeltaRI of 0.116 +/-0.030; p<0.001) in comparison with Group A (DeltaRI of 0.001 +/-0.038) and Group B (DeltaRI of 0.015 +/-0.024). No differences were detected between Groups C and D (p=0.223) and between Groups A and B (p-0.472). DeltaRI measurement with DU permitted to predict the renal obstruction with a sensitivity of 93.8%, a specificity of 95.0% and an accuracy of 94.4%., Conclusions: Intrarenal Doppler ultrasonography represents a sensitive and highly specific test that can significantly contribute to the diagnosis of obstruction in patients with acute renal colic. It should be used as the first line imaging method in suspected acute renal colic, as well as for patients with renal insufficiency, pregnant women or for patients with adverse reactions to contrast media

The aim of the study was to investigate the diagnostic value of the colour Doppler twinkling artefact (TA) in renal stone disease. To enhance the evidence of TA, a preliminary in vitro study was performed to optimise the setting of colour Doppler sonography. In the in vitro study, an oxen kidney was examined using an high-frequency (12.5 MHz) linear array probe in a water bath before and after the inoculation of an aliquot of powder obtained by fragmentation of a calcium oxalate stone. In the clinical study, 67 patients with diagnosis of urinary stone based on B-mode sonography and 67 matched control subjects were examined with colour Doppler sonography using a low-frequency (2.5 MHz) curvilinear phased array probe. In vitro, the injection of calcium oxalate powder in a bovine kidney sample induced the appearance of spots without any back shadowing appearance on B mode but with a large number of TA on colour Doppler. In vivo, TA was much more frequent in patients with stone disease (95.5%) compared to controls (9.0%) (P < 0.001). TA was highly associated to renal stone disease and was also present in renal areas where a stone was undetected with B mode approach suggesting its diagnostic role although further studies are needed to confirm its accuracy. The type of instrumentation and its setting is crucial to obtain reproducible results.

Background: The relative role of IgA anomalies and genetic factors in IgA nephropathy (IgAN) recurrence after transplantation has never been investigated in a single cohort., Methods: Sixty-one transplanted patients who had IgAN as an original disease (30 with biopsy-proved early recurrence, median 2.9 yr post-transplant), and 120 controls, were investigated for aberrantly glycosylated IgA1, IgA binding to mesangial matrix, macromolecular IgA (IgA/fibronectin and uteroglobulin/IgA/fibronectin complexes), and polymorphisms of cytokines [tumor necrosis factor alpha (TNFalpha), interleukin 10 (IL-10), IL-6, interferon gamma and transforming growth factor beta 1] and renin-angiotensin system (angiotensinogen converting enzyme, angiotensin II receptor 1, and angiotensinogen) genes., Results: At multivariate logistic regression analysis, recurrence showed a border-line association with aberrantly glycosylated IgA1 [odds ratio (OR) 8.172, p = 0.077], and was significantly less frequent in carriers of -308 AG/AA TNF-alpha"high producer" genotype (OR 0.125, p = 0.036) and -1082, -819, -592 ACC/ATA IL-10 "low producer" (OR 0.038, p = 0.009) genotypes., Conclusion: High levels of aberrantly glycosylated IgA1 do not appear to play a strong crucial role in recurrence of IgAN. Polymorphisms of TNFalpha and IL-10 known to condition Th1 prevalence were associated with protection from early recurrence of IgAN.

Percutaneous transluminal angioplasty (PTA) is a possible treatment for stenosis. This study aimed to verify the impact of a vascular access (VA) surveillance protocol, based on the detection of functional changes and their correction by a new PTA method for VA performed under color Doppler ultrasonography (CDU) guidance. We divided the patients into two groups: group A, before May 1999 (retrospective study) without the surveillance protocol, and group B, from 1 May 1999 to January 2001 (prospective study) with the surveillance protocol. Access blood flow (Qa) was assessed every 4 weeks by ultrasound velocity dilution. In cases of a reduction of >or=35% from the baseline value, VA was examined using CDU: if a stenosis >50% was detected, angioplasty was performed. In cases of Qa reduction <35% we continued monitoring. By Coxs multivariate analyses, only the use of PTA with or without stenting reduced the relative risk of thrombosis by 64% during the follow-up (p=0.017 confidence intervals 88%-15%) in group B patients. Secondary patency was 80% for VA in which we performed PTA with or without stenting at 18 months, and 58% at 18 months in which we did not perform PTA. Our data show how PTA under CDU is useful to maintain and to improve graft patency. This PTA under CDU guidance allows patients to avoid surgical intervention, hospitalization, and adverse reactions to contrast media and exposure to ionizing radiation, with reduced cost and with better graft survival.

The main purpose of statistics in the analysis of clinical and epidemiological studies is to summarize data and information, as well as assess variability, trying to distinguish between chance findings and results that may be replicated upon repetition. Statistical analyses only convey the effect of chance element in data (random error). Statistics cannot control non-sampling errors concerning study design, conduct and methods adopted. At the end of the study, a result is defined statistically significant if the observed difference in the outcome variable is too large to be attributed to chance. A small P value provides evidence against the null hypothesis (of no effect), since data have been observed that would be unlikely if the null hypothesis was true. However, confidence intervals estimate separate the two data dimensions (strength of the relation between exposure and disease, and precision with which the relation is measured), and add to the hypothesis testing useful information for finding interpretation and further research.

Few studies have investigated IgA nephropathy patients presenting with 'favorable' clinical features at onset, such as normal renal function, proteinuria<1 g/24 hours and the absence of hypertension, and no controlled clinical trials have tested the effects of treatment in such patients who may nevertheless develop end-stage renal disease. It is therefore important to find a well-tolerated and economic therapy capable of decreasing their risk of high proteinuria and blood pressure levels. The aim of this multicenter open-label randomized clinical trial is to test whether blocking the renin-angiotensin system (RAS) decreases the risk of progression in patients aged 3-60 years with biopsy-proven benign IgA glomerulonephritis, proteinuria levels of 0.3-0.9 g/24 hours, and normal renal function and blood pressure. The RAS is blocked by first using a single drug class (angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker), and then combining the 2 classes as soon as the 1-drug blockade has become ineffective. We plan to enroll 378 patients over the next 3 years and randomize them to receive ramipril 5 mg/day (3 mg/m2 in children) (group A), irbesartan 300 mg/day (175 mg/m 2 in children) (group B) or supportive therapy (group C); if an increase in proteinuria of at least 50% from baseline is detected after 6 months of treatment, the other RAS inhibitor will be added. The observation period will be at least 5 years (except in the case of the development of the primary end point).

Despite an increase in the use and average dose of erythropoiesis-stimulating agents (ESA) over the past 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. A clear relationship among hemoglobin or hematocrit levels, ESA dose, and increase in dialysis dose has been pointed out by a number of prospective or retrospective studies. This is particularly true in patients receiving inadequate dialysis. Increasing attention also has been paid to the relationship between dialysis, increased inflammatory stimulus, and ESA response because dialysate contamination and low-compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. The biocompatibility of dialysis membranes and flux are other important factors. However, in highly selected, adequately dialyzed patients without iron or vitamin depletion, the effect of these treatment modalities on anemia seems to be smaller than expected. The role of on-line treatments still is controversial given that it is still difficult to discriminate between the effect of on-line hemodiafiltration per se from that of an increased dialysis dose. Very preliminary results obtained with short or long nocturnal daily hemodialysis on anemia correction are encouraging.

Background: Factors predictive of renal outcome were investigated in 219 cases of biopsy-proven Henoch-Schönlein purpura nephritis (HSPN); 83 children and 136 adults enrolled in a national study were followed up for up to 27 years (median, 4.5 years)., Methods: The criterion for defining disease progression was time elapsed until doubling of baseline creatinine level and until dialysis therapy. Age, sex, data at onset (renal function, proteinuria, hematuria, hypertension, and crescents), and data during follow-up (proteinuria and therapy) were tested as covariates., Results: Multivariate Cox regression analysis indicated the following parameters as independent prognostic predictors: age (adults versus children, relative risk, 3.57; 95% confidence interval, 1.18 to 10.79; P = 0.024 for creatinine level doubling; relative risk, 14.89; 95% confidence interval, 1.72 to 129.07; P = 0.014 for dialysis therapy), sex (females versus males, relative risk, 5.71; 95% confidence interval, 1.67 to 19.55; P = 0.006 for creatinine level doubling; relative risk, 26.03; 95% confidence interval, 2.64 to 256.73; P = 0.005 for dialysis therapy), and mean proteinuria during follow-up (for each 1 g/d of protein increase, relative risk, 1.77; 95% confidence interval, 1.35 to 2.32; P < 0.001 for creatinine level doubling; relative risk, 1.73; 95% confidence interval, 1.18 to 2.52; P = 0.005 for dialysis therapy). Information for mean proteinuria levels during follow-up increased the sensitivity at logistic regression to 62.5%, with dialysis therapy as the end point. No data detected at diagnosis, including renal function impairment, proteinuria, hypertension, and crescentic nephritis (involving > 50% of glomeruli in only 2.6%), were significantly related to functional decline at multivariate Cox., Conclusion: This analysis indicates that, even more than when decreased renal function, severe proteinuria, hypertension, or crescents are present at onset, the risk for progression of HSPN (greater in adults and females) was associated with increasing mean proteinuria levels during follow-up.

Background: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation., Methods: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders., Results: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22)., Conclusions: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.

The critical appraisal process of available evidence includes the evaluation of clinical importance of the study findings. This should coincide with the minimum worthwhile effect expected by the investigators in the study design and planning. In hard outcome studies it can be quantified by the absolute risk difference between groups and its reciprocal, known as number needed to treat to avoid one adverse event, or benefit (NNTB). The number needed to treat to produce harmful consequences of treatment (NNTH) should also be taken into account. Finally these effect measures, like risks and incidence proportions, are usually rough estimates of the true effects, due to non-complete follow-up of the observations under study. Underlying assumptions and design issues are especially important to assess the clinical relevance of any results.

The peritoneal equilibration test (PET) with 3.86% glucose concentration (3.86%-PET) has been suggested to be more useful than the standard 2.27%-PET in peritoneal dialysis (PD), but no longitudinal data for 3.86%-PET are currently available. A total of 242 3.86%-PETs were performed in 95 incident PD patients, who underwent the first test during the first year of treatment and then once a year. The classical parameters of peritoneal transport, such as peritoneal ultrafiltration (UF), D/D(0), and D/P(Creat), were analyzed. In addition, the absolute dip of dialysate sodium concentration (DeltaD(Na)), as an expression of sodium sieving, was studied. D/D(0) was stable, and a progressive decrease in UF was observed after the second PET, whereas D/P(Creat) firstly increased and then stabilized. DeltaD(Na) was the only parameter showing a progressive decrease over time. On univariate analysis, D/D(0) and DeltaD(Na) were found to be significantly associated with the risk of developing UF failure (risk ratio (RR) 0.987 (0.973-0.999), P=0.04, and RR 0.768 (0.624-0.933), P=0.007, respectively), but on multivariate analysis only DeltaD(Na) showed an independent association with the risk of developing UF failure (RR 0.797 (0.649-0.965), P=0.020). UF, D/D(0), and D/P(Creat) changed only in those patients developing UF failure, reflecting increased membrane permeability, whereas DeltaD(Na) significantly decreased in all patients. The 3.86%-PET allows a more complete study of peritoneal membrane transport than the standard 2.27%-PET. DeltaD(Na) shows a constant and significant reduction over time and is the only factor independently predicting the risk of developing UF failure in PD patients.

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

Background: On-line determination of ionic dialysance (ID) has been used to measure the clearance of small solutes like urea. However, attempts to determine the in vivo relationship between ID and urea clearance have led to discordant findings. The aim of this study was to determine the relationship between the mean values of repeated instantaneous determinations of ID throughout a dialysis session ((m)ID), obtained using a single-step inlet dialysate conductivity profile, and the mean values of urea clearance corrected for access recirculation (K(eu1)), total recirculation (access plus cardiopulmonary recirculation, K(eu2)), and the entire postdialysis urea rebound (K(wb))., Methods: Eighty-two anuric patients on chronic thrice-weekly hemodialysis were studied using an Integra machine equipped with the Diascan module for the automatic determination of ID. The mean values of repeated ID measurements made at 30-minute intervals were compared with K(eu1) (available for only 31 patients), K(eu2), and K(wb)., Results: The results in all 82 patients were: (m)ID = 176 +/- 23 mL/min; K(eu2) = 181 +/- 25 mL/min; K(wb) = 159 +/- 22 mL/min. The mean (m)ID/K(wb) and (m)ID/K(eu2) ratios were, respectively, 1.11 +/- 0.06 and 0.98 +/- 0.06. The results in the 31 patients for whom K(eu1) values were available were: (m)ID = 179 +/- 24 mL/min and K(eu1) = 200 +/- 27 mL/min; the mean (m)ID/K(eu1) ratio was 0.90 +/- 0.05., Conclusion: The mean value of repeated ID determinations obtained using a single-step conductivity profile underestimates urea clearance corrected for access recirculation, and may be considered an adequate estimate of urea clearance corrected for total recirculation.

Background: Loss of ultrafiltration (UF) of peritoneal membrane is one of the most important causes of peritoneal dialysis failure. UF is determined by osmotic forces acting mainly across small pores (UFSP) and ultrasmall pores or free water transport. At present, only semiquantitative estimates or complicated computer simulations are available to assess free water transport. The aim of this study was to assess free water transport during a 3.86% peritoneal equilibration test lasting 1 hour. In this condition, sodium transport is mainly due to convection, allowing the estimate of ultrafiltration of small pores and then of free water transport (total UF - UFSP)., Methods: In 52 peritoneal dialysis patients we performed a 3.86% peritoneal equilibration test (4 hours) and a 3.86% mini-peritoneal equilibration test (1 hour) and compared UF and small solute transports obtained with the two methods., Results: During the 3.86% mini-peritoneal equilibration test, UFSP and free water transport were 279 +/- 142 mL and 215 +/- 86 mL, respectively; free water transport well correlated to total UF during the 3.86% peritoneal equilibration test (r= 0.67). The groups of peritoneal transporters, categorized according to glucose dialysate ratio (D/D(0)) and to creatinine/plasma ratio (D/P(Creat)), were in good agreement for the two peritoneal equilibration tests (weighted kappa 0.62 and 0.61, respectively)., Conclusion: The 3.86% mini-peritoneal equilibration test is a simple and fast method to assess free water transport. It also gives information about total UF and small solute transports and it is in good agreement with the 3.86% peritoneal equilibration test.

Over the recent years, it has been clearly documented that hypertension and proteinuria are the major factors responsible for progression of chronic kidney disease (CKD). Therefore, a target BP of at least 130/80 mm Hg has been suggested in order to reduce the rate of progression and cardiovascular mortality. Some antihypertensive agents, such as ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and perhaps calcium channel blockers (CCBs), may also be capable of reducing CKD progression because they halt some of the pathogenetic mechanisms involved in renal damage, some of which is unrelated to reduction of proteinuria, per se. Although this specific effect seemed to be partially independent of blood pressure reduction, it remains controversial whether these drugs are really superior to other antihypertensive agents when blood pressure values recommended by guidelines are achieved. This issue is still a matter of debate because in published trials, target and achieved blood pressure values were constantly higher than those recommended today. Nevertheless, available findings seem to indicate that the renoprotective effect of these agents is at least partially independent of a better BP control. The only way to definitely solve this issue would be a new randomized trial. However, the clinical relevance of this trial is debatable, considering that we need all the drugs available to reach these recommended BP values.

Despite an increase in the use and average dose of recombinant human EPO (rh-EPO) over the last 15 years, a substantial percentage of patients still do not achieve hemoglobin targets recommended by international guidelines. The definition of rh-EPO resistance has been introduced to identify those patients in whom the target hemoglobin level is not attained despite a greater-than-usual dose of erythropoietin-stimulating agent (ESA). In recent years, increasing attention has been paid to the relationship between dialysis, increased inflammatory stimulus, malnutrition, and ESA response. About 35% to 65% of hemodialysis patients show signs of inflammation that could be a cause of anemia through the suppression of bone marrow erythropoiesis by a number of cytokines. A large proportion of chronic kidney disease patients also have protein-energy malnutrition and wasting; low serum albumin levels, together with other more specific nutritional markers, are predictors of rh-EPO response. A diminished nutritional state could then be a feature of patients who are resistant to ESA treatment, with malnutrition probably being a consequence of a chronic inflammatory state. Starting from the hypothesis that anemia, partially attributable to a reduced response to ESA, could be the link among malnutrition, inflammation, and the poor outcome of chronic kidney disease patients, we designed a multicenter observational study, the Malnutrition-Inflammation-Resistance-Treatment Outcome Study (MIRTOS), aimed at evaluating the impact and possible causes of resistance to ESA in a large sample of hemodialysis patients. We hope the results of MIRTOS will represent a step forward toward a better understanding of the factors influencing the response to ESA in hemodialysis patients.

Background: Every week, approximately 400 liters of water used for dialysate production come into direct contact, through the semi-permeable membrane of the dialyzer, with the dialysis patient's blood stream. Therefore, submitting municipal water to an adequate depuration process before its use for dialysis becomes necessary., Methods: Problems related to the implementation, updating and management of a dialysis water treatment system are analyzed. The results of the most recent multicenter studies on dialysis fluids quality are also reviewed., Results: The best approach to plan, implement and manage a dialysis water treatment system, first, consists of defining the standards of chemical and microbiological water quality. The most diffused and commonly accepted standards are those recommended by the Association for Advancement of Medical Instrumentation (AAMI) and the European Pharmacopea (EP), which allow a maximum bacterial growth of, respectively, 200 CFU/ml and 100 CFU/mL and a maximum endotoxin concentration of 2 IU/mL and 0.25 IU/mL. A modern dialysis water treatment system provides a final purification process, mainly by reverse osmosis (RO), together with different pre-treatment levels and a hydraulic distribution circuit. Therefore, as RO produces water of optimal chemical and microbial quality, all efforts in the dialysis unit must be aimed at keeping this quality as constant as possible over time, by carrying out effective maintenance strategies and system disinfection. Nevertheless, several multicenter studies reported that 7-35% of water samples exceed a bacterial growth of 200 CFU/mL and that 44% of them display endotoxin concentrations >5 IU/mL., Conclusions: The results of multicenter studies indicate that the microbial quality of dialysis fluids is, unfortunately, still an often neglected problem. Evidence of a possible relationship between dialysis fluid contamination and patient morbidity, as well as the availability of systems and machines allowing purity levels that were unimaginable only a few years ago, must be a stimulus for modifying clinical practices and starting the improvement processes aimed at maximally reducing the risk of microbial contamination in the dialysis water, as already done with chemical contamination.

Background: An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance., Methods: Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied., Results: V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001)., Conclusion: Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.