Publications by authors named "Claudio Pozzi"

35 Publications

Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

Clin J Am Soc Nephrol 2021 04 29;16(4):575-587. Epub 2021 Mar 29.

Unit of Nephrology and Dialysis, Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy.

Background And Objectives: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis.

Design, Setting, Participants, & Measurements: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization.

Results: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; =0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls.

Conclusions: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis.

Clinical Trial Registry Name And Registration Number: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.
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http://dx.doi.org/10.2215/CJN.12940820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092055PMC
April 2021

The low-protein diet for chronic kidney disease: 8 years of clinical experience in a nephrology ward.

Clin Kidney J 2020 Apr 8;13(2):253-260. Epub 2019 Nov 8.

Salus Medical Center, Lecco, Italy.

Background: Guidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice.

Methods: The analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist. The patients included 43 patients on a controlled protein diet (CPD) of 0.8 g/kg/day [estimated glomerular filtration rate (eGFR) 20-30 mL/min/1.73 m body surface (b.s.)], 171 patients on an LPD of 0.6 g/kg/day and 85 patients on an unrestricted protein diet (UPD) who were not followed by our nutritionist (LPD and UPD, eGFR <20 mL/min/1.73 m b.s.).

Results: eGFR was higher in CPD patients than in UPD and LPD patients (21.9 ± 7.4 mL/min/1.73 m versus 17.6 ± 8.00 mL/min/1.73 m and 17.1 ± 7.5 mL/min/1.73 m; P = 0.008). The real daily protein intake was higher in UPD patients than in LPD and CDP patients (0.80 ± 0.1 g/kg/day versus 0.6 ± 0.2 and 0.63 ± 0.2 g/kg/day; P = 0.01). Body mass index (BMI) was stable in the LPD and CPD groups but decreased from 28.5 ± 4.52 to 25.4 ± 3.94 kg/m in the UPD group (P < 0.001). The renal survival of UPD, LPD and CPD patients was 47.1, 84.3 and 90.7%, respectively, at 30 months (P < 0.001), 42.4, 72.0 and 79.1%, respectively, at 50 months (P < 0.001) and 42.4, 64.1 and 74.4%, respectively, at 70 months (P < 0.001). The LPD patients started dialysis nearly 24 months later than the UPD patients. Diet was an independent predictor of dialysis [-67% of RR reduction (hazard ratio = 0.33; confidence interval 0.22-0.48)] together with a reduction in BMI.

Conclusions: An LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.
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http://dx.doi.org/10.1093/ckj/sfz141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147315PMC
April 2020

Long-term blood pressure behavior and progression to end-stage renal disease in patients with immunoglobulin A nephropathy: a single-center observational study in Italy.

J Hypertens 2020 05;38(5):925-935

Department of Internal Medicine, Ospedale Policlinico San Martino, Genoa.

Background: Antihypertensive treatment by the use of RAAS inhibitors (RAAS-is) is of paramount importance in the management of slowly progressive IgA nephropathy (IgAN). With the aim of better understanding the relationship between BP behavior and progression, we looked at time-averaged SBP and time-averaged proteinuria and renal outcome in a single-center cohort of IgAN patients.

Methods: Among 248 consecutive patients referred to the Clinic of Nephrology of San Martino Hospital from 1996 to 2018 for native renal biopsy with a diagnosis of IgAN, we retrospectively analyzed 145 with available data at baseline and during follow-up. All patients received Supportive Care, 39% were on RAAS-is alone, 45% plus steroids, and 16% plus steroids and immunosuppressors. Renal replacing treatment (RRT) was the primary endpoint.

Results: During a mean follow-up of 67 ± 6 months, 23% of study patients (n = 33) progressed to RRT and 6% (n = 9) died. Patients who reached the renal endpoint, had lower baseline eGFR and higher proteinuria and proteinuria indexed at baseline. Moreover, they had higher TA-SBP (139 ± 17 vs. 130 ± 13, P = 0.0016). The incidence of RRT was higher in IgAN patients in the highest time-averaged SBP tertile as compared with the others (32 vs. 23 vs. 9%, χ 6.8, P = 0.033). After adjusting for baseline SBP, baseline and time-averaged proteinuria indexed, MEST-C score, and treatment, the association between TA-SBP and RRT persisted.

Conclusion: Time-averaged low BP values were independently associated to a decreased risk of renal progression in IgAN with no evidence of a J-curve relationship even at SBP levels below 125 mmHg.
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http://dx.doi.org/10.1097/HJH.0000000000002354DOI Listing
May 2020

Uraemic symptom burden and clinical condition in women and men of ≥65 years of age with advanced chronic kidney disease: results from the EQUAL study.

Nephrol Dial Transplant 2019 07;34(7):1189-1196

ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, Amsterdam Public Health Research Institute, University of Amsterdam, Amsterdam, The Netherlands.

Background: The epidemiology and prognosis of chronic kidney disease (CKD) differ by sex. We aimed to compare symptom prevalence and the clinical state in women and men of ≥65 years of age with advanced CKD receiving routine nephrology care.

Methods: The European QUALity study on treatment in advanced chronic kidney disease (EQUAL) study follows patients from six European countries of ≥65 years of age  years whose estimated glomerular filtration rate (eGFR) dropped to ≤20 mL/min/1.73 m2 for the first time during the last 6 months. The Dialysis Symptom Index was used to assess the prevalence and severity of 33 uraemic symptoms. Data on the clinical state at baseline were collected from medical records. Prevalence was standardized using the age distribution of women as the reference.

Results: The results in women (n = 512) and men (n = 967) did not differ with age (77.0 versus 75.7 years) or eGFR (19.0 versus 18.5). The median number of symptoms was 14 [interquartile range (IQR) 9-19] in women, and 11 (IQR 7-16) in men. Women most frequently reported fatigue {39% [95% confidence interval (CI) 34-45]} and bone/joint pain [37% (95% CI 32-42)] as severe symptoms, whereas more men reported difficulty in becoming sexually aroused [32% (95% CI 28-35)] and a decreased interest in sex [31% (95% CI 28-35)]. Anaemia [73% (95% CI 69-77) versus 85% (95% CI 82-87)] was less common in women than in men, as were smoking history and cardiovascular comorbidity. However, a diagnosis of liver disease other than cirrhosis, psychiatric disease and mild malnutrition were more common among women.

Conclusions: Women in secondary care with an incident eGFR ≤20 mL/min/1.73 m2 reported a higher symptom burden, while their clinical state was considered similar or even more favourable as compared with men.
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http://dx.doi.org/10.1093/ndt/gfy155DOI Listing
July 2019

Sudden Death in End Stage Renal Disease: Comparing Hemodialysis versus Peritoneal Dialysis.

Blood Purif 2017 1;44(1):77-88. Epub 2017 Apr 1.

Nephrology Unit, San Gerardo Hospital, Monza, Italy.

Background/aims: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD).

Methods: This is a multicenter retrospective cohort study.

Results: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) ≤35%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF ≤35% (p < 0.05).

Conclusions: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=464347.
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http://dx.doi.org/10.1159/000464347DOI Listing
April 2017

Effect of oral anticoagulant therapy on mortality in end-stage renal disease patients with atrial fibrillation: a prospective study.

J Nephrol 2017 Aug 11;30(4):573-581. Epub 2016 Nov 11.

Nephrology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.

Background: The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage.

Methods: Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHADS-VAS and HAS-BLED scores were considered as predictors of risk of death, thromboembolism and bleeding events. In patients taking OAT, the international normalized ratio (INR) was assessed and the percentage time in the target therapeutic range (TTR) was calculated.

Results: At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28-0.90), p = 0.04], with a decrease of thromboembolic events [HR 0.36 (0.13-1.05), p = 0.06], and an increase of bleedings [HR 1.79 (0.72-4.39), p = 0.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14-0.53), p < 0.001] and cardiovascular [HR 0.21 (0.11-0.40), p < 0.001] mortality compared to patients stopping OAT.

Conclusions: In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality.
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http://dx.doi.org/10.1007/s40620-016-0364-8DOI Listing
August 2017

Opponent's comments.

Authors:
Claudio Pozzi

Nephrol Dial Transplant 2016 11;31(11):1775-1776

Division of Nephrology, Bassini Hospital, Cinisello Balsamo, Milan, Italy.

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http://dx.doi.org/10.1093/ndt/gfw286aDOI Listing
November 2016

Pro: STOP immunosuppression in IgA nephropathy?

Authors:
Claudio Pozzi

Nephrol Dial Transplant 2016 11 11;31(11):1766-1770. Epub 2016 Aug 11.

Division of Nephrology, Bassini Hospital, Cinisello Balsamo, Milan, Italy.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest a 6-month course of corticosteroids (CS) for IgA nephropathy (IgAN) patients with persistent proteinuria ≥1 g/day despite 3-6 months of renin-angiotensin system (RAS) blockers and glomerular filtration rate (GFR) >50 mL/min/1.73 m In December 2015, Rauen et al. (N Engl J Med 2015; 373: 2225-2236) published an article entitled 'Intensive supportive care plus immunosuppression in IgA nephropathy' (STOP-IgAN), which presented results from 379 IgAN patients from 32 nephrology centres in Germany. During a run-in phase of 6 months, patients received supportive care therapy including RAS blockers, dietary counselling, advice to stop smoking and avoid nephrotoxic drugs, and statins if required. After 6 months, 177 patients with proteinuria >0.75 g/day (non-responder patients) were randomized to either receive continued supportive care or supportive care plus immunosuppression (monotherapy with CS or combined therapy with three immunosuppressants). The authors reported that, after 36 months of observation, the addition of immunosuppressants to ongoing comprehensive supportive care was not beneficial in IgAN patients with moderate proteinuria and chronic kidney disease stages 1-3. These conclusions are questionable for several reasons: (i) studies on time-average proteinuria have shown that beneficial effects on renal survival, not evident after 36 months, emerge over the course of longer observation periods; (ii) supportive care in the STOP-IgAN study resulted in a small loss of renal function during the 36 months of observation (annual decrease in the estimated GFR of 1.6 mL/min/1.73 m), but was unable to reduce proteinuria below 1 g/day; in contrast, 6 months of steroid therapy lowered proteinuria below 1 g/day; and (iii) the lack of any assessment of the histological data does not allow the importance of the morphological lesions on renal survival and therapy effects to be monitored. Further evaluation with a longer follow-up period is needed to obtain more reliable answers than the weak evidence of this study.
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http://dx.doi.org/10.1093/ndt/gfw285DOI Listing
November 2016

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

PLoS One 2016 14;11(7):e0158584. Epub 2016 Jul 14.

Department of Nephrology and Dialysis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy.

The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158584PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945016PMC
July 2017

Changes in Proteinuria and Side Effects of Corticosteroids Alone or in Combination with Azathioprine at Different Stages of IgA Nephropathy.

Clin J Am Soc Nephrol 2016 06 29;11(6):973-81. Epub 2016 Apr 29.

Department of Nephrology and Dialysis, E. Bassini Hospital, Cinisello Balsamo, Milan, Italy;

Background And Objective: Time-average proteinuria (TAp) is the strongest predictor of renal survival in IgA nephropathy (IgAN). Little is known about the utility and safety of corticosteroids (CS) to obtain TAp<1 g/d in patients with advanced IgAN. This study sought to evaluate TAp at different degree of baseline renal function and histologic severity during CS use and to investigate treatment safety.

Design, Setting, Participants, & Measurements: We performed one-stage individual-patient data meta-analysis among 325 patients with IgAN enrolled in three prospective, randomized clinical trials. Patients were divided into three groups according to treatment: no treatment (NT; supportive therapy), CS, and CS plus azathioprine (CS+A). Associations of TAp with histologic grading, treatment, and eGFR at baseline were performed with linear regression models for repeated measures. The median follow-up duration was 66.6 months (range, 12-144 months).

Results: In the first 6 months, proteinuria did not change in the NT group and decreased substantially in the other groups(CS: from a mean±SD of 2.20±1.0 to 0.8 [interquartile range, 0.4-1.2] g/d; CS+A: from 2.876±2.1 to 1.0 [interquartile range, 0.5-1.7] g/d), independent of the degree of histologic damage and baseline eGFR. The percentage of patients who maintained TAp<1 g/d was 30.2% in the NT, 67.3% in the CS, and 66.6% in the CS+A group. Thirty-four patients experienced adverse events: none in the NT, 11 (6.4%) in the CS, and 23 (20.7%) in the CS+A group. The risk of developing adverse events increased with decreasing levels of eGFR (from 2.3% to 15.4%). The addition of azathioprine to CS further increased the percentage of patients with adverse events (16.8% versus 5.7% in study 2 and 30.0% versus 15.4% in study 3; overall P<0.001).

Conclusions: In patients with IgAN, CS can reduce proteinuria and increase the possibility of maintaining TAp<1 g/d, regardless of the stage of CKD and the histologic damage. The risk of major adverse events is low in patients with normal renal function but increases in those with impaired renal function and with the addition of azathioprine.
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http://dx.doi.org/10.2215/CJN.02300215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891742PMC
June 2016

Treatment of IgA nephropathy with renal insufficiency.

J Nephrol 2016 Aug 7;29(4):551-8. Epub 2016 Jan 7.

Nephrology and Dialysis Department, Bassini Hospital, Cinisello Balsamo, Italy.

IgA Nephropathy leads young people to dialysis more often than other glomerular diseases, because often diagnosis and therapy are made late. Nephrologists waive to treat IgAN pts with chronic renal insufficiency, believing that treatment may not be effective and safe. Moreover, studies in IgAN pts with reduced renal function are lacking. Small studies seem to indicate a possible utility of RAS blockers and corticosteroids in these patients. Recently, VALIGA study showed that corticosteroids and immunosuppressants were more frequently used in pts with eGFR <30 ml/min than in those with eGFR >30 ml/min (60 vs. 44 %, respectively; p = 0.004). The goal of treating IgAN pts is to obtain a time-average proteinuria <1 g/day, regardless of the degree of renal function and histological damage. RASB and corticosteroids seem to be able to obtain this result. However, it's important to pay attention to the appearance of adverse events of CS. In the literature, major side effects occurred in 29 of 463 (6.2 %) patients enrolled in RCTs. However, scarce informations are obtained about the safety of CS in patients with reduced renal function. To better evaluate this aspect, we considered three studies, that used similar schemes of therapy and included patients with different degrees of renal function (1: GFR 90 ml/min/1.73 m(2), 2: 81 ml/min/1.73 m(2), 3: 34 ml/min/1.73 m(2)). The occurrence of adverse events increased with the worsening of renal function (2.3, 5.7 and 15.4 % in studies 1, 2 and 3 respectively). The aim of the treatment for a patient with an eGFR <30 is to slow the progression and to delay the need for dialysis. Therefore, in stage CKD 2, 3 and 4 with a proteinuria >1 g/day a 6-month course of corticosteroids could be useful and safe.
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http://dx.doi.org/10.1007/s40620-015-0257-2DOI Listing
August 2016

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region.

J Nephrol 2016 Oct 29;29(5):673-81. Epub 2015 Dec 29.

Division of Nephrology and Dialysis, A. Manzoni Hospital, Via dell'Eremo 9/11, 23900, Lecco, Italy.

Background: The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy.

Materials And Methods: A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (β) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics.

Results: Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11-100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [β =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [β = 6.7 (-2.32; 18.30), p = 0.199] or for all-confounding factors [β = 5.6 (-5.50; 17.08), p = 0.337].

Conclusions: This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.
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http://dx.doi.org/10.1007/s40620-015-0254-5DOI Listing
October 2016

Treatment of IgA nephropathy.

Authors:
Claudio Pozzi

J Nephrol 2016 Feb 17;29(1):21-5. Epub 2015 Nov 17.

Department of Nephrology and Dialysis, E. Bassini Hospital, Via Gorki, 50, 20092, Cinisello Balsamo, Milan, Italy.

The therapy of IgA nephropathy (IgAN) is cause for debate among nephrologists. Since the early 1980s, many therapeutic attempts have been proposed, but most of them did not prove efficacy. The recent KDIGO Clinical Practice Guideline for Glomerulonephritis recommend long-term ACE-I or ARB treatment when proteinuria is more than 1 g/day, with up-titration of the drug. For patients with GFR >50 ml/min and proteinuria persistently higher than 1 g/day, they suggest a 6-month course of corticosteroid therapy. Based on our experience and the results of the literature, we propose a progressive treatment, which takes into account the time the IgAN is recognized and the clinical conditions present at that time. The treatment can be summarize as follows: (1) in patients with macro-microscopic haematuria, in case with proteinuria less than 0.3 g/day, only annual controls; (2) in patients with proteinuria between 0.3 and 0.9 g/day, ACE-I and/or ARB, with titration of the drugs; (3) in patients with proteinuria higher than 1 g/day, in case with the presence of arterial hypertension and GFR up to 30 ml/min, 6 months course of corticosteroids, in addition to ACE-I and/or ARB; (4) in patients with GFR less than 30 ml/min, ACE-I/ARB, dialysis and kidney transplantation; corticosteroids should be in case considered for patients with persistently high or increasing proteinuria; (5) the immunosuppressants (cyclophosphamide and azathioprine) should be reserved for patients with progressive renal insufficiency or with vasculitic lesions on renal biopsy.
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http://dx.doi.org/10.1007/s40620-015-0248-3DOI Listing
February 2016

Mortality, sudden death and indication for cardioverter defibrillator implantation in a dialysis population.

Int J Cardiol 2015 17;186:170-7. Epub 2015 Mar 17.

Electrophysiology and Cardiac Pacing Unit, San Gerardo Hospital, Monza, Italy.

Background: The incidence of sudden death among dialysis patients is high, but end stage renal disease was an exclusion criterion in the trials that demonstrated the benefit of implantable cardioverter defibrillator (ICD) for sudden death prevention.

Methods: Dialysis patients alive on January 2010 or starting dialysis between January 2010 and January 2013 were enrolled and retrospectively evaluated. Patients were divided into three groups: No-Indication, Indication-With ICD and Indication-Without ICD. Cox and Fine and Gray regression models were used to estimate the total and cause-specific (sudden or non-sudden) mortality hazard ratio (HR, HR(cpRisk)), respectively. Survival was defined as the time from start of dialysis to the time of death.

Results: 154/2072 patients (7.4%) had indication for ICD implantation and 52 (33.8%) of them received the device; 688 (33.2%) deaths were recorded. Mortality was different among groups [Indication-With ICD vs No-Indication: HR 1.59 (95% CI 1.06-2.38) and Indication-Without ICD vs No-Indication: HR 2.67 (95% CI 2.09-3.39, p < 0.001)]. 84/688 (12.2%) were sudden deaths. The cumulative incidence of sudden death was higher in patients with ICD indication [Indication-With ICD vs No-Indication HR(cpRisk) 3.21 (95% CI 1.38-7.40) and Indication-Without ICD vs No-Indication: HR(cpRisk) 4.19 (95% CI 2.38-7.39), p < 0.001], but also No-Indication patients showed a high rate of sudden death [8.5% (95% CI.6.5-10.9) at 8 years of follow-up].

Conclusions: Dialysis patients with ICD indication had a worse survival than No-Indication subjects and the prognosis was particularly poor for the Indication-Without ICD group. Sudden death incidence was much higher than in the general population, even among No-Indication subjects.
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http://dx.doi.org/10.1016/j.ijcard.2015.03.178DOI Listing
March 2016

[Assisted peritoneal dialysis].

G Ital Nefrol 2014 Nov-Dec;31(6)

Peritoneal dialysis (PD) has a prevalence in Italy that does not exceed 10% of patients in substitution treatment. Among the barriers, which hinder access to DP, the lack of patient autonomy or family support has great importance. In 2012 in Lombardy, the lack of support has prevented 155 new patients to use DP and has forced 17 to stop it. According to the Italian Census of 2012, made by the Peritoneal Dialysis Study Group, Assisted DP involved the 24.5% of patients in 2010. In these cases, the caregiver was a family member in 80.8% of cases, a carer in 12.4%, a homecare nurse in 2.5% and the retirement home staff in 3.9%. In Italy, several regional Governments have sought to encourage home dialysis with economic contributions to the patient or the family. However, so far, none of these interventions has managed to increase the use of DP. In January 2004, we started a program of Assisted PD, using health worker as caregiver, in agreement with ASL Milano and ICP Milano Hospital. In the first 6 months of activity we treated 4 patients, 3 of them had been treated with hemodialysis. We had no critical cases and patients have welcomed this solution. In addition, the costs related to the Assisted PD are lower in comparison with the costs of the hospital hemodialysis. Considering the reliability of the first results, ASL has decided to raise the economic contribution for this activity, allowing us to increase the number of patients to include in Assisted PD.
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November 2016

Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation.

Nephrol Dial Transplant 2015 Mar 28;30(3):491-8. Epub 2014 Oct 28.

Nephrology Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.

Background: Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory.

Methods: The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events.

Results: At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10-2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00-3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15-13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01-0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09-4.35, P = 0.03).

Conclusions: In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range.
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http://dx.doi.org/10.1093/ndt/gfu334DOI Listing
March 2015

The nephrologist's anticoagulation treatment patterns/regimens in chronic hemodialysis patients with atrial fibrillation.

J Nephrol 2014 Apr 16;27(2):187-92. Epub 2014 Jan 16.

Department of Health Science, University of Milano-Bicocca, Monza, Italy,

Background: The prevalence of atrial fibrillation (AF) is high in hemodialysis (HD) patients. It was suggested that oral anticoagulant therapy (OAT), the choice treatment for reducing the thromboembolic risk in AF patients, increases the incidence of both ischemic and hemorrhagic strokes in the HD population. Moreover, the therapy-related bleeding risk is particularly high in these patients. For these reasons there is no agreement on the use of OAT in HD patients with AF. The aim of this study was to evaluate the criteria adopted by nephrologists in prescribing OAT in HD patients with AF.

Methods: All the patients presenting AF (paroxysmal, persistent or permanent) at 31/10/2010 (n = 290) were recruited from 1529 HD patients from ten Italian HD centres. To detect factors related to OAT administration the main clinical features, CHADS2 and HASBLED scores were evaluated in logistic regression models.

Results: The presence of permanent AF (OR = 4.28, p < 0.0001) was the only clinical factor directly associated to OAT administration, while previous bleedings (OR = 0.35, p = 0.004) were inversely related. The CHADS2 score was not associated with OAT prescription (OR = 0.85, p = 0.08), while an inverse relation was found with the hemorrhagic risk score (OR = 0.74, p = 0.03).

Conclusion: A high AF prevalence was observed in our HD population, but less than 50 % of these patients received OAT. Patients with permanent AF were more frequently treated with warfarin, while OAT administration was uncommon in those with previous bleedings. The thromboembolic risk score was not associated with warfarin prescription, while there was an inverse relation with the hemorrhagic risk score.
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http://dx.doi.org/10.1007/s40620-013-0030-3DOI Listing
April 2014

[What future for today young nephrologists?].

G Ital Nefrol 2013 Nov-Dec;30(6)

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.
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August 2015

-374 T/A RAGE polymorphism is associated with chronic kidney disease progression in subjects affected by nephrocardiovascular disease.

PLoS One 2013 4;8(4):e60089. Epub 2013 Apr 4.

Nephrology and Dialysis Unit, Bassini Hospital, Cinisello Balsamo, Milan, Italy.

Background: Chronic kidney disease (CKD) patients present elevated advanced glycation end products (AGEs) blood levels. AGEs promote inflammation through binding to their receptor (RAGE), located on the membrane of mesangial cells, endothelial cells and macrophages. Several genetic polymorphisms influence RAGE transcription, expression and activity, including the substitution of a thymine with an adenine (T/A) in the position -374 of the gene promoter of RAGE. Our study investigates the role of -374 T/A RAGE polymorphism in CKD progression in subjects affected by nephrocardiovascular disease.

Methods: 174 patients (119 males (68.4%) mean age 67.2±0.88 years; 55 females (31.6%): mean age 65.4±1.50 years) affected by mild to moderate nephrocardiovascular CKD were studied. Each subject was prospectively followed for 84 months, every 6-9 months. The primary endpoint of the study was a rise of serum creatinine concentrations above 50% of basal values or end stage renal disease.

Results: Carriers of the A/A and T/A genotype presented higher plasma levels of interleukin 6 (A/A 29.5±15.83; T/A 30.0±7.89, vs T/T 12.3±5.04 p = 0.01 for both) and Macrophages chemoattractant protein 1 (A/A 347.1±39.87; T/A 411.8±48.41, vs T/T 293.5±36.20, p = 0.04 for both) than T/T subjects. Carriers of the A allele presented a faster CKD progression than wild type patients (Log-Rank test: Chi square = 6.84, p = 0,03). Cox regression showed that -374 T/A RAGE polymorphism (p = 0.037), albuminuria (p = 0.01) and LDL cholesterol (p = 0.038) were directly associated with CKD progression. HDL cholesterol (p = 0.022) and BMI (p = 0.04) were inversely related to it. No relationship was found between circulating RAGE and renal function decline.

Conclusions: -374 T/A RAGE polymorphism could be associated with CKD progression and inflammation. Further studies should confirm this finding and address whether inhibiting RAGE downstream signalling would be beneficial for CKD progression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0060089PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617170PMC
November 2013

IgA nephropathy with severe chronic renal failure: a randomized controlled trial of corticosteroids and azathioprine.

J Nephrol 2013 Jan-Feb;26(1):86-93

Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy.

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.
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http://dx.doi.org/10.5301/jn.5000110DOI Listing
August 2013

Corticosteroids in patients with IgA nephropathy and severe chronic renal damage.

Case Rep Nephrol 2012 10;2012:180691. Epub 2012 Oct 10.

Department of Nephrology, Dialysis, and Renal Transplant, Alessandro Manzoni Hospital, Via dell'Eremo 9, 23900 Lecco, Italy.

Little is known about the utility of treating patients with advanced IgA nephropathy (IgAN). From 2001 to 2005, four patients came to our observation because of serum creatinine higher than 3 mg/dL, proteinuria ranging from 1.8 to 5.1 g/day, and a histological picture of diffuse sclerotic lesions. A corticosteroid course of 12 months was given. Patients were observed for a mean follow up of 84 months. At the end of the steroid course, proteinuria lowered quickly below 1 g/day in two patients, whereas the other two experienced a slower and less persistent decrease of proteinuria. Despite similar lesion severity at renal biopsy, renal function stabilized only in these two ones. In conclusion, these preliminary observations suggest a possible efficacy of corticosteroids in slowing down the progression of renal disease and in postponing the need of dialysis in IgAN patients with stage IV CKD and severe chronic histological lesions.
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http://dx.doi.org/10.1155/2012/180691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914212PMC
February 2014

[The ambiguous concept of predialysis: proposal for a model].

G Ital Nefrol 2011 Sep-Oct;28(5):541-50

U.O. Nefrologia e Dialisi, Ospedale Bassini, Azienda ICP Milano, Cinisello, Balsamo, Italy.

In 2009, 90% of nephrology centers in Lombardy declared to have a ''predialysis'' outpatient department, without, however, specifying its meaning. Research carried out in 2008 among nephrology centers in Piemonte showed how ambiguous this term was. According to the 2007 EDTA-ERA Registry, about 68% of European nephrology centers stated that they had an outpatient department for stage 4-5 CKD patients, but no information was available about the role of patients in the choice of dialysis. It is known that when the predialysis phase is poorly managed, the patient's rehabilitation will be more difficult. Dissatisfaction with dialysis often leads to withdrawal from dialysis, as several registries have shown. For this reason, we created a predialysis course at our center, involving a nephrologist, a nurse, and a dietician. The nephrologist helps the patient choose the most suitable therapeutic strategy, which means that doctor and patient share the responsibility for the treatment choice. The offered options are hemodialysis, peritoneal dialysis, preemptive kidney transplant, and a conservative dietary-pharmacological program. The nurse plans at least 4 meetings: 1) to talk with the patient in order to get to know him or her and his/her family; 2) to provide information about the dialysis procedure and establish the patient's preferences; 3) to clear any doubts about the treatment and deliver a booklet with information about the chosen dialysis procedure; 4) to explain the chosen dialysis procedure; 5) to meet the patient after their preparation for dialysis (vascular access or peritoneal catheter). The dietician manages the dietary programs both for patients who are close to starting dialysis and those on a longlasting conservative program. The predialysis course includes a meeting among all those involved with the patient (nephrologists, nurses, dieticians) to exchange information with the purpose of shared evaluation and decision-making.
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January 2012

Addition of azathioprine to corticosteroids does not benefit patients with IgA nephropathy.

J Am Soc Nephrol 2010 Oct 15;21(10):1783-90. Epub 2010 Jul 15.

Department of Nephrology and Dialysis, Ospedale A. Manzoni, Lecco, Italy.

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.
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http://dx.doi.org/10.1681/ASN.2010010117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013548PMC
October 2010

Pregnancy and progression of IgA nephropathy: results of an Italian multicenter study.

Am J Kidney Dis 2010 Sep;56(3):506-12

Department of Nephrology, Dialysis and Transplantation, A. Manzoni Hospital, Lecco, Italy.

Background: Whether pregnancy impacts on the long-term outcome of immunoglobulin A (IgA) nephropathy is unknown. This study aims to compare the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function who did and did not become pregnant.

Study Design: Multicenter longitudinal cohort study.

Setting & Participants: Women of childbearing age with biopsy-proven IgA nephropathy, serum creatinine level
Predictors: Pregnancy, treated as a time-dependent variable; baseline proteinuria; hypertension; and kidney biopsy histologic characteristics.

Outcome & Measures: Rate of change in estimated creatinine clearance, change in proteinuria, and new-onset hypertension.

Results: 245 patients were enrolled. Of these, 223 women (136 and 87 in the pregnancy and nonpregnancy groups, respectively) had serum creatinine levels
Limitations: Unrecognized or unmeasured factors associated with the decision of becoming pregnant might have influenced results.

Conclusions: Pregnancy does not seem to affect the long-term outcome of kidney disease in women with IgA nephropathy and preserved kidney function.
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http://dx.doi.org/10.1053/j.ajkd.2010.03.033DOI Listing
September 2010

Mechanisms of renal damage in plasma cell dyscrasias: an overview.

Contrib Nephrol 2007 ;153:66-86

Amyloidosis Center, Biotechnology Research Laboratories, Fondazione, IRCCS Policlinico San Matteo and Department of Biochemistry, University of Pavia, Pavia, Italy.

The kidney is a target organ in plasma cell dyscrasias. Usually the offending molecules are the monoclonal light chains (LCs), but the complete immunoglobulins can participate in the pathogenesis of organ damage. The primary structure of the monoclonal proteins is at the basis of the ultrastructural organization of their aggregates which translates into characteristic kidney injuries. The kidney targeting is due to the concurrence of several factors such as the local catabolism of monoclonal LCs, specific interactions of the monoclonal proteins with tissue and cellular components, and local environmental conditions. Glomerulopathic LCs interact with mesangial cells producing, through two distinct pathways, LC amyloidosis or monoclonal immunoglobulin deposition disease. Tubulopathic LCs damage the proximal tubule causing Fanconi's syndrome or precipitate in the distal tubule determining the cast nephropathy. The use of electronmicroscopy combined with immuno-labeling has allowed the identification of other rare patterns of kidney damage. In patients with known plasma cell dyscrasia, the recognition of these patterns of renal injury should lead to appropriate therapeutic intervention.
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http://dx.doi.org/10.1159/000096761DOI Listing
January 2007

ACE inhibitors and angiotensin II receptor blockers in IgA nephropathy with mild proteinuria: the ACEARB study.

J Nephrol 2006 Jul-Aug;19(4):508-14

Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy.

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).
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November 2006

IgA nephritis: ACE inhibitors, steroids, both or neither?

Nephrol Dial Transplant 2006 Dec 15;21(12):3357-61. Epub 2006 Sep 15.

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http://dx.doi.org/10.1093/ndt/gfl508DOI Listing
December 2006

IgA glomerulonephritis: beyond angiotensin-converting enzyme inhibitors.

Nat Clin Pract Nephrol 2006 Jan;2(1):24-31

Department of Nephrology and Dialysis, Ospedale A Manzoni, Via dell'Eremo, 23900 Lecco, Italy.

IgA glomerulonephritis accounts for 25-50% of renal biopsy diagnoses. About 25-50% of patients progress to end-stage renal disease within 20 years of diagnosis. Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor blockers slow progression of IgA nephropathy (IgAN); however, as drugs of this class are not IgAN specific and are therefore unlikely to alter significantly its natural course, many other therapeutic approaches have been proposed. Most have been tested in a relatively small number of patients and have not yet proven to be effective in the long term. Conflicting and variable data, and a lack of long-term prospective randomized studies, mean that most treatments cannot be recommended as standard therapy for IgAN. Steroids seem to be the best treatment for patients with proteinuria, as drugs in this class ameliorate this symptom and protect against deterioration of renal function. Combined treatment with corticosteroids and cytotoxic drugs has yielded interesting results in several studies, especially in progressive patients with severe IgAN. In this review, we critically analyze the data on these treatments.
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http://dx.doi.org/10.1038/ncpneph0055DOI Listing
January 2006

Does pregnancy influence the course of IgA nephropathy? Proposal for an observational study.

J Nephrol 2006 Mar-Apr;19(2):192-5

Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy.

Whether or not pregnancy adversely affects the course of IgA nephropathy (IgAN) remains a matter of debate. Studies have produced conflicting results to date, probably due to differences in patient selection, renal disease severity, grades of hypertension and proteinuria or the administration of different therapies. Since numerous variables can influence the long-term outcome, it is necessary to evaluate data from a large number of patients to minimize the effect of confounding factors. However, the number of patients considered in most studies is small, and long-term prognosis is not yet reported in the literature. In the case of a chronic disease with a slow course such as IgAN, a long observation period is needed to draw substantial conclusions about the prognostic value of pregnancy. We propose a multicenter, retrospective, observational study to clarify whether pregnancy negatively affects the long-term prognosis of women with IgAN. Data of women who became pregnant and of women who did not conceive during the follow-up will be collected at the time of renal biopsy and every 5 yrs to evaluate possible differences in the course of maternal renal disease between the two groups. In particular, the following endpoints will be compared: renal function and the onset of hypertension and proteinuria. Possible differences in therapy will be analyzed to investigate whether different treatment approaches in the two groups could have influenced the disease course.
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December 2006

Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial.

J Am Soc Nephrol 2004 Jan;15(1):157-63

Department of Nephrology and Dialysis, A. Manzoni Hospital, Lecco, Italy.

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.
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http://dx.doi.org/10.1097/01.asn.0000103869.08096.4fDOI Listing
January 2004
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