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Background The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. Methods In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP,130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. Results Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). Conclusions Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors. Copyright © 2018 by the American Society of Nephrology Background The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear. Methods In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP,130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events. Results Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%). Conclusions Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors.

Una delle conseguenze più importanti dell'insufficienza renale cronica (IRC) è il ricorso al trattamento dialitico: nella sola Campania sono oggi 5.000 i nefropatici in terapia dialitica, a fronte dei 45.000 dell'intera penisola. In letteratura è oramai riconosciuta l'importanza della dieta ipoproteica nel rallentare la progressione della patologia e dunque procrastinare l'accesso alla dialisi. Se a ciò si aggiunge che il costo del trattamento dialitico è di gran lunga superiore rispetto a quello della dieta, ne consegue che grazie alle dialisi evitate, si otterrebbero non solo ripercussioni positive sul benessere dei pazienti, ma altresì vantaggi economici nell'ottica del management sanitario. Al fine di sostenere questa tesi, nell'ambito di una valutazione di Health Technology Assessment (HTA) è stato implementato un modello di budget impact analisys attraverso il quale testare la reale convenienza economica della elargizione della dieta ipoproteica ai nefropatici della Campania. Il modello implementato prende in considerazione i soli costi diretti a carico del SSN; in particolare, vengono messi a confronto la spesa per le dialisi evitate e quelli della dieta con alimenti ipoproteici, in uno scenario che valuta differenti indici di NNT (Number Needed to Treat) e di compliance (aderenza + persistenza al trattamento). I risultati consentono di sostenere l'offerta della dieta ai nefropatici in fase pre-dialitica, vale a dire con eGFR >45 che, nel caso di specie e relativamente all'anno 2009, sono rappresentati da 25.000 soggetti. É opportuno però sottolineare che i risultati a sostegno della tesi principale appaiono subordinati al rispetto di una aderenza al trattamento di almeno il 50%, piuttosto che di un NNT non superiore a 50. In quest'ottica, gli AA sostengono che una distribuzione per conto dei suddetti prodotti, da parte delle farmacie territoriali, potrebbe rappresentare una scelta appropriata in quanto consentirebbe di usufruire di un prezzo scontato e, allo stesso tempo, di realizzare un setting favorente per aumentare l'aderenza al trattamento.

Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated. Design, setting, participants,measurements We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach.Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome.In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population.

Background and objectives: Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb variability and renal survival in nondialysis CKD. Design, setting, participants, & measurements: We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy). Results: Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P * 0.002). The area under the curve for Hb (11.56 * 0.87, 11.46 * 1.20, and 10.95 * 1.48 g/dl per yr; P * 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 * 2.0 to 3.0 * 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P * 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio [95% confidence interval]), risk for renal death was increased in the middle and higher tertiles (2.79 [1.36 to 5.73] and 2.94 [1.40 to 6.20]) and reduced by longer time in target (0.90 [0.83 to 0.98]). Conclusions: Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship

Background. End-stage renal disease care requires enormous economic resources. A timely dialysis start could reduce the costs of the renal replacement therapy (RRT). Our aim was to measure the time to dialysis in CKD patients, with an estimated glomerular filtration rate (eGFR) ≤11.0 mlmin1.73 m2 (MDRD derived), and to evaluate the safety, economic impact and the quality of life (QoL).Methods. In a prospective, observational study, 70 consecutive CKD patients, stage 5, were screened and 30 patients were selected and followed up monthly, for 24 months or until the start of RRT, set at an eGFR = 6.0 mlmin/ 1.73 m2 or at the occurrence of pre-defined urgent criteria. The SF-36 questionnaire to evaluate the QoL was performed at the first and the last visit.Results. The median time to the start of dialysis was 11.8 (25th and 75th: 5.5-17.3) months. Only seven patients urgently started dialysis, after 8 months (25th and 75th: 4.8-20). The mean monthly cost of care was € 1146 ± 917 per patient. The QoL was similar to that of the general population and did not change at the last assessment.Discussion. This is the first study evaluating the economic impact of intensive conservative management of CKD stage 5 to postpone start of dialysis in tertiary care. This strategy allows us to safely gain a significant amount of time free from dialysis, with good QoL and major savings in the costs of nation's dialysis budget. The present results, however, are applicable only to low comorbidity patients referred to nephrology care and may not be generalized to all patients starting RRT.

BACKGROUND: This study is part of a 3-country study testing whether normal levels of hemoglobin (Hgb) delay the progression of left ventricular (LV) growth in chronic kidney disease (CKD) patients not on dialysis. METHODS: This was an open-label, randomized, multicenter, controlled trial conducted in 27 tertiary-care hospitals in Italy. Treated subjects (n=46) received epoetin-alpha (EPO-alpha) to maintain Hgb levels in the range 12-14 g/dL. Control subjects (n=49) were not treated unless their Hgb decreased to 9.0 g/dL. Primary outcome was LV mass index (MI) change after 24 months. Subcutaneous EPO-alpha was withdrawn in Europe and the study prematurely terminated; therefore, a 12-month analysis was carried out. RESULTS: Mean age was 57 years (38% were women, 18% with diabetes, 76% taking ACEI or ARB and 22% statins). EPO-alpha median final dose was 2,000 IU/week. Hgb significantly increased (12.4 -/+ 1.1 g/L) for the treatment group and decreased for controls (11.3 -/+ 1.3 g/L; p

Background and Objectives: Instability of hemoglobin levels during epoetin therapy is a new problem in hemodialysis. We evaluated extent and correlates of time in target, that is, the time spent with hemoglobin >11 g/dl during the first year of epoetin and its association with renal survival. Design, Setting, Participants, & Measurements: Data were collected in 917 visits for 12.0 mo in 119 patients with chronic kidney disease; thereafter, patients started renal survival analysis for 10.1 mo. At baseline, hemoglobin was 10.0 * 0.8 g/dl and GFR was 22.1 * 14.2 ml/min per 1.73 m2. Results: Hemoglobin target, reached in 1.5 mo, was steadily maintained in only 24% of patients. Time in target was not merely due to differences in time to target; after first achievement of target, in fact, a reduction of hemoglobin

The relationship between malnutrition and inflammation is by now well established. IL-6 and, probably, other proinflammatory cytokines (mainly IL-1 and TNF) may represent the link between these two entities since these interleukins may promote loss of appetite, muscle protein breakdown and reduced hepatic synthesis of "negative" acute phase proteins like albumin, prealbumin and transferrin. IL-6 also stimulates up to 1000 fold the hepatic synthesis of "positive" acute phase proteins, mainly C-reactive Protein (CRP) and Serum Amyloid A. The association between CRP and cardiovascular mortality in the general population, as well as in haemodialysed uraemic patients, is well established. These crucial interrelationships have modified the interpretation of serum albumin concentration in the diagnosis of malnutrition; a reduced serum albumin concentration, in fact, in the presence of high CRP values should point towards a diagnosis of inflammation, though the inflammation may often induce weight loss or a condition of malnutrition. After switching most patients to a more biocompatible dialysis membrane and improvement of the quality of the dialysis fluid (by adopting hydrophobic filters at the water entry of dialysis devices and bicarbonate powder cartridges) nephrologists have focused their attention on other sources of inflammation (e.g. artificial vascular protheses, presence of infected thrombi, Clamidiae, Helicobacter Pilori, dental granulomas etc.). Starting from these assumptions the diagnosis of malnutrition, once focused mainly on serum albumin reduction, must be based on other parameters (clinical history of body mass wasting, dietary and anthropometric assessment, subjective global assessment, bioimpedance analysis etc.). All these investigations, however, must be examined together to obtain suitable information on the risk of malnutrition in dialysis patients. A comprehensive approach to malnutrition-inflammation in dialysis patients is the object of the present nephrology conference.

Nephrol Dial Transplant Vol 17, suppl 1, pp 208

Background: Knowledge on anaemia management in non-dialysis chronic kidney disease (ND-CKD) patients regularly followed in renal clinics is scarce although being essential to identifying areas of therapeutic improvement. Methods: We prospectively evaluated anaemia management in two visits, performed 6 months apart, in 755 prevalent ND-CKD stage 3b-5 patients followed in 19 nephrology clinics from ≥6 months. Anaemia was defined as severe (Hb

Background/Aims: We evaluated prevalence and prognosis of mild anemia, defined as Hb (g/dl) 11–13.5 in males and 11–12 in females, in a prospective cohort of stage 3–5 chronic kidney disease (CKD) patients. Methods: We enrolled 668 consecutive patients in 25 renal clinics during 2003. Patients with frank anemia (Hb Results: Mild anemia was present in 41.3% at visit 1 and 34.1% at visit 2. We identified PER in 22% patients, RES in 10%, and PRO in 26%. In the subsequent 40 months, 125 patients developed end-stage renal disease (ESRD) and 94 died. At competing risk model, PER predicted ESRD (hazard ratio, HR, 1.82, 95% confidence interval, CI, 1.01–3.29) while PRO predicted both ESRD (HR 1.81, 95% CI 1.02–3.23) and death (HR 1.87, 95% CI 1.04–3.37). Conclusion: In non-dialysis chronic kidney disease, mild anemia is prevalent and it is a marker of risk excess when persistent or progressive over time.