Search

Il paziente nefropatico cronico facilmente presenta alterazioni morfologiche e funzionali dell'apparato gastroenterico. I segni più comuni e precoci nella sindrome uremica cronica sono rappresentati dai disturbi gastrointestinali. Da alcuni decenni abbiamo a disposizione dei farmaci con potente azione inibente la secrezione acida gastrica: gli inibitori di pompa protonica (IPP) hanno una struttura chimica affine, uno stesso meccanismo d'azione e sono molto importanti per il trattamento delle patologie acido correlate, per l'eradicazione dell'Helicobacter Pylori, per la prevenzione e la cura della gastropatia da farmaci antinfiammatori non steroidei (FANS). Somministriamo ai nostri pazienti questa classe di farmaci, con terapie che continuano nel tempo, nonostante la risoluzione della malattia (gastroprotezione). Ma gli IPP possono essere utilizzati indistintamente nei nefropatici cronici oppure sarebbe utile conoscere il profilo del farmaco per una corretta scelta? In questo articolo si argomenta che i loro effetti collaterali non sono molto rilevanti e sono abbastanza simili: il loro impiego nel lungo termine è sicuro. La potenza e l'efficacia dei vari IPP, dall'analisi comparativa dei vari trial clinici, risulta essere molto simile sulla base dei milligrammi di sostanza utilizzata. L'unica eccezione illustrata in questo lavoro è rappresentata da 6 pazienti in emodialisi, trattati con lansoprazolo (15 mg), che presentavano gastriti e ulcere peptiche complicate da gravi episodi di ematemesi e melena con conseguente anemia. Tutti gli IPP hanno dimostrato un'efficacia clinica sovrapponibile, tuttavia vanno valutati di volta in volta i vantaggi (relativi) di ciascun IPP. I criteri di scelta di un IPP sembrano basati, principalmente sulle indicazioni autorizzate, sulle formulazioni disponibili, sul profilo di sicurezza del farmaco.

Maschio di 56 anni con familiarità positiva per nefrolitiasi ed anamnesi positiva per numerosi episodi di colica renoureterale da ambo i lati, si presenta al nostro ambulatorio nefrologico di ecografia per ennesimo episodio recidivo di colica renale destra. All'ultimo controllo ecografico dei reni presentava microlitiasi bilaterale in assenza di dilatazione delle vie escretrici. È in terapia dietetico-idropinica associata a citrato di potassio. All'ecografia renale presenta idronefrosi del rene destro in assenza di idrouretere. La TAC, eseguita senza mezzo di contrasto per pregresso episodio di allergia al mdc in corso di precedente esame radiologico conferma la dilatazione delle vie escretrici a carico del rene destro. La successiva RMN dell'addome ribadisce l'idronefrosi destra riscontrata all'ecografia e alla TAC, sino alla giunzione pieloureterale con uretere a valle non dilatato che depongono per ostruzione del giunto pieloureterale (OGPU). Il paziente operato di plastica del giunto pieloureterale è al momento libero da coliche. Il caso riportato ribadisce come nei casi di idronefrosi accanto alle più comuni cause di uropatia ostruttiva (calcolosi, IPB, neoplasie) occorra sempre considerare le patologie congenite che possono manifestarsi anche in età adulta e tra queste in particolare la sindrome del giunto pieloureterale. In questi pazienti l'ecografia renale rappresenta un importante esame di primo livello in base alla quale indirizzare il paziente ai successivi step diagnostici di imaging e ai conseguenti provvedimenti terapeutici.

Abstract non disponibile

La prevenzione primaria e secondaria della insufficienza renale cronica da nefroangiosclerosi è rappresentata dallo stretto controllo dei valori pressori e dalla riduzione della proteinuria. In presenza di proteinuria, il controllo pressorio va ottenuto con il blocco del sistema renina-angiotensina anche in pazienti con importante riduzione della funzione renale. La terapia di associazione di ACE inibitore con sartano non sembra portare vantaggi aggiuntivi ma può essere saggiata in pazienti selezionati con proteinuria persistente superiore al grammo/die. L'associazione ACE inibitore con antialdosteronico sembra promettere bene ma occorrono ulteriori studi, possibilmente multicentrici.

Background. Cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. Post-dilution haemofiltration has been reported to be a method for improving cardiovascular stability; however, the limited removal of small molecular weight solutes together with the need for high blood flow from the fistula greatly restrict the use of this treatment. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in post-dilution mode, can be administered in pre-dilution mode. A high vascular stability has also been observed for pre-dilution haemofiltration. Since the lower morbidity may be due to less sodium removal when compared with haemodialysis, it would be important to characterize the sodium transport in this kind of treatment. Methods. Nine patients underwent nine pre-dilution haemofiltration treatments (one for each patient) with on-line prepared substitution fluid. Results. As mean values, total (NaFpw) and ionized (NaEpw) plasma water sodium concentrations increased from 149.4 ± 2.8 mEq/l to 151.1 ± 2.4 mEq/l, and from 143.1 ± 2.8 to 144.5 ± 1.2 mEq/l, respectively, during the treatment, suggesting a hypotonic concentration of net ultrafiltrate. Plotting the difference between final and initial ionized plasma water concentrations (fNaEpw - iNaEpw) against the difference between initial plasma water values and ionized sodium concentration in the reinfusate (iNaEpw - NaER), a significant negative correlation was found, with the regression line that intercepts the abscissa at the (iNaEpw - NaER) value of 8.8 mEq/l; this means that to avoid changes in NaEpw in our patients, the NaER should be lower than the iNaEpw by this amount. This is quite different from the theoretical value of ∼4 mEq/l necessary to avoid changes in NaEpw during haemodialysis. The ratio between the total sodium concentration in the ultrafiltrate (NaFuf) and NaFpw (α) at the post-reinfusion site was 0.96 and decreased to 0.94 when NaFpw values at the pre-reinfusion site were considered. This last value is quite close to the theoretical α value of post-dilution haemofiltration. Conclusion. As for post-dilution haemofiltration, less sodium removal, compared with haemodialysis, can partly explain the improved cardiovascular stability during pre-dilution haemofiltration. [ABSTRACT FROM AUTHOR]

Introduction. Every week, haemodialysis patients are exposed to ∼400 l of water used for the production of dialysis fluids which, albeit with the interposition of a semi-permeable artificial membrane, come into direct contact with the bloodstream. It is therefore clearly important to know and monitor the chemical and microbiological purity of dialysis water. Methods. In this review, we analyse the sources of chemical and microbiological water contamination, and the problems involved in water purification systems and modalities. We also analyse the compliance of dialysis units with the microbiological standards established by the most widely accepted guidelines relating to the quality of dialysis fluids. Results. The risk of chemical contamination is due mainly to the primary pollution of municipal water, whereas the most important microbiological problem is the control of bacterial growth in the water treatment and distribution system. Dialysis water treatment implies various levels of pre-treatment, a final purification module (which, in many cases, is reverse osmosis: RO) and a hydraulic circuit for the distribution of the purified water. RO-based treatment systems produce water of optimal chemical and microbial quality, and so dialysis units need to concentrate on maintaining this quality level in the long term by means of effective maintenance and disinfection strategies. The most widely accepted standards for water purity are those recommended by the Association for the Advancement of Medical Instrumentation and the European Pharmacopea, which respectively allow bacterial growth of <200 and <100 c.f.u./ml, and an endotoxin concentration of <2 and <0.25 IU/ml. However, a number of multicentre studies have reported that 7-35% of water samples have bacterial growth of >200 c.f.u./ml, and up to 44% have endotoxin levels of >5 IU/ml. Conclusions. The results of multicentre studies indicate that the microbial quality of dialysis fluids is still a too often neglected problem, particularly as there is evidence of a possible relationship between dialysis fluid contamination and long-term morbidity. The time has now come to take advantage of innovations in water treatment processes and improvements in dialysis machines in order to modify clinical practices and start improvement processes aimed at decreasing the risk of microbial contamination to the minimum, as it has already been successfully done in the case of chemical contamination. [ABSTRACT FROM AUTHOR]

The concept of dialysis adequacy has to be widened to include medium size and large molecule removal in addition to urea kinetics. The HEMO study found a non-significant trend toward a beneficial effect on mortality of high-flux dialysis compared with low-flux dialysis. In that study, the beneficial effect of convection could have been attenuated by the fact that 'internal filtration' in high-flux haemodialysis (HD) is lower than that expected by convection in haemofiltration (HF) or haemodiafiltration (HDF). To explore the putative beneficial effect of convection, this Italian multicentre study was planned, comparing on-line convective treatments (HF and HDF) with standard, low-flux HD. The enrolled patients will be evaluated prospectively on their usual treatment for 2 months (baseline period) and subsequently randomized to continue either with low-flux HD (50%) or to start on-line convective treatment (50%), HF or HDF according to a 1:1 ratio. The primary end point of the study will be cardiovascular stability and blood pressure control. As secondary aims of the study, the impact on symptoms, morbidity and mortality will be assessed. Feasibility and patient compliance during HF and HDF treatments will also be evaluated. The experimental phase of the study, of at least 2 years, is divided into a 3-month adaptation period and a subsequent evaluation period. A recruitment period of 1 year is planned. The study design has adequate power to detect an absolute reduction of 3% hypotensive episodes with the experimental convective treatments compared with standard low-flux HD. [ABSTRACT FROM AUTHOR]

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.