Stefano Rota
Mario Negri Institute for Pharmacological Research
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Stefano Rota.
Kidney International | 2011
Howard Trachtman; Fernando C. Fervenza; Debbie S. Gipson; Peter Heering; David Jayne; Harm Peters; Stefano Rota; Giuseppe Remuzzi; L. Christian Rump; Lorenz Sellin; Jeremy Heaton; James B. Streisand; Marjie L. Hard; Steven R. Ledbetter; Flavio Vincenti
Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m2, and a urine protein to creatinine ratio over 1.8 mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4 mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73 m2). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2 mg/mg with all three Black patients having a mean decline of 3.6 mg/mg. The half-life of fresolimumab was ∼14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary.
Hypertension | 2011
Piero Ruggenenti; Giuseppe Lauria; Ilian Iliev; Anna Fassi; Aneliya Parvanova Ilieva; Stefano Rota; Carlos Chiurchiu; Drazenka Pongrac Barlovic; Angelo Sghirlanzoni; Raffaella Lombardi; Paola Penza; Guido Cavaletti; Maria Luisa Piatti; Barbara Frigeni; Marco Filipponi; Nadia Rubis; Greta Noris; Nicola Motterlini; Bogdan Ene-Iordache; Flavio Gaspari; Annalisa Perna; Jelka Zaletel; Antonio Bossi; Alessandro Roberto Dodesini; Roberto Trevisan; Giuseppe Remuzzi
To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m2 (IQR: 0.16–0.50 mL/min per 1.73 m2) on combined therapy, 0.36 mL/min per 1.73 m2 (IQR: 0.18–0.53 mL/min per 1.73 m2) on delapril, and 0.30 mL/min per 1.73 m2 (IQR: 0.12–0.50 mL/min per 1.73 m2) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04–0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07–0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24–0.87; P=0.017) and 0.52 (0.27–0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.
Kidney International | 2013
Anna Caroli; Simone Manini; Luca Antiga; Katia Passera; Bogdan Ene-Iordache; Stefano Rota; Giuseppe Remuzzi; Aron S. Bode; Jaap Leermakers; Frans N. van de Vosse; Raymond Vanholder; Marko Malovrh; Jan H. M. Tordoir; Andrea Remuzzi
Vascular access dysfunction is one of the main causes of morbidity and hospitalization in hemodialysis patients. This major clinical problem points out the need for prediction of hemodynamic changes induced by vascular access surgery. Here we reviewed the potential of a patient-specific computational vascular network model that includes vessel wall remodeling to predict blood flow change within 6 weeks after surgery for different arteriovenous fistula configurations. For model validation, we performed a multicenter, prospective clinical study to collect longitudinal data on arm vasculature before and after surgery. Sixty-three patients with newly created arteriovenous fistula were included in the validation data set and divided into four groups based on fistula configuration. Predicted brachial artery blood flow volumes 40 days after surgery had a significantly high correlation with measured values. Deviation of predicted from measured brachial artery blood flow averaged 3% with a root mean squared error of 19.5%, showing that the computational tool reliably predicted patient-specific blood flow increase resulting from vascular access surgery and subsequent vascular adaptation. This innovative approach may help the surgeon to plan the most appropriate fistula configuration to optimize access blood flow for hemodialysis, potentially reducing the incidence of vascular access dysfunctions and the need of patient hospitalization.
Clinical Journal of The American Society of Nephrology | 2010
Piero Ruggenenti; Annalisa Perna; Marcello Tonelli; Giacomina Loriga; Nicola Motterlini; Nadia Rubis; Franca Ledda; Stefano Rota; Andrea Satta; Antonio Granata; Giovanni Battaglia; Francesco Cambareri; Salvatore David; Flavio Gaspari; Nadia Stucchi; Sergio Carminati; Bogdan Ene-Iordache; Paolo Cravedi; Giuseppe Remuzzi
BACKGROUND AND OBJECTIVES This open, prospective, randomized trial aimed to assess the effects of statins in chronic kidney disease patients on optimized antiproteinuric treatment with combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS After 1-month benazepril therapy followed by 1-month benazepril-valsartan combined therapy (run-in), 186 consenting patients with residual proteinuria >0.5 g/24 h were randomized to 6-month benazepril-valsartan therapy alone or combined with fluvastatin. Between-groups changes in proteinuria (primary outcome), serum lipids, and GFR were compared by ANCOVA. Analyses were blinded and by intention to treat. RESULTS During the run-in, proteinuria decreased more on benazepril-valsartan than on benazepril alone. Proteinuria reduction correlated with concomitant reduction in total, LDL, and HDL cholesterol, and apolipoprotein B and apolipoprotein A levels. After randomization, median proteinuria similarly decreased from 1.2 (0.6 to 2.2) to 1.1 (0.5 to 1.7) g/24 h on fluvastatin and from 1.5 (0.8 to 2.7) to 1.0 (0.5 to 2.4) g/24 h on benazapril-valsartan therapy alone. Fluvastatin further reduced total and LDL cholesterol and apolipoprotein B versus benazepril-valsartan alone, but did not affect serum triglycerides and GFR. Treatment was well tolerated. CONCLUSIONS In chronic kidney disease patients with residual proteinuria despite combined angiotensin-converting enzyme inhibitor and angiotensin receptor blockade therapy, add-on fluvastatin does not affect urinary proteins, but further reduces serum lipids and is safe. Whether combined angiotensin-converting enzyme inhibitor, angiotensin receptor blockade, and statin therapy may improve cardiovascular outcomes in this high-risk population is worth investigating.
Diabetes Care | 2010
Piero Ruggenenti; Dario Cattaneo; Stefano Rota; Ilian Iliev; Aneliya Parvanova; Olimpia Diadei; Bogdan Ene-Iordache; S. Ferrari; Antonio Bossi; Roberto Trevisan; Antonio Belviso; Giuseppe Remuzzi
OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients. RESEARCH DESIGN AND METHODS In a multicenter prospective randomized double-blind placebo-controlled trial, we primarily compared by ANCOVA the effect of 2-month ezetimibe (10 mg/day) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria <200 μg/min and total cholesterol concentrations >135 mg/dl despite simvastatin treatment (40 mg/day). RESULTS Unlike placebo, ezetimibe decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl, total cholesterol from 162 ± 36 to 124 ± 30 mg/dl, and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl (P < 0.0001 for all changes versus placebo). A total of 72 and 17% of patients on ezetimibe or placebo achieved LDL levels <70 mg/dl, respectively (P < 0.0001). Treatment was well tolerated. CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone.
The Lancet Diabetes & Endocrinology | 2018
Aneliya Parvanova; Matias Trillini; Manuel A Podestà; Ilian Iliev; Barbara Ruggiero; Manuela Abbate; Annalisa Perna; Francesco Peraro; Olimpia Diadei; Nadia Rubis; Flavio Gaspari; Fabiola Carrara; Nadia Stucchi; Antonio Belviso; Antonio Bossi; Roberto Trevisan; Giuseppe Remuzzi; Martin H. de Borst; Piero Ruggenenti; Norberto Perico; Stefano Rota; Maria Carolina Aparicio; Silvia Prandini; Daniela Cugini; Giulia Gherardi; Anna Maria Corsi; S Yakymchuk; Veruscka Lecchi; Ruggero Mangili; Wally Calini
BACKGROUND Macroalbuminuria predicts renal and cardiovascular events in patients with type 2 diabetes. We aimed to assess the albuminuria-lowering effects of salt restriction, paricalcitol therapy, or both, in this population. METHODS In this randomised, double-blind, placebo-controlled, crossover trial, we recruited adult patients with type 2 diabetes from six diabetology outpatient clinics in northern Italy, with 24 h albuminuria of more than 300 mg despite 100 mg per day losartan therapy, blood pressure of less than 140/90 mm Hg, serum creatinine concentration of less than 2 mg/dL, stable renal function on stable renin-angiotensin system inhibitor therapy with a fixed dose of losartan, parathyroid hormone concentration of 20 pg/mL to <110 pg/mL, serum calcium concentration of less than 9·5 mg/dL, and serum phosphate concentration of less than 5 mg/dL, who had been more than 80% compliant with placebo treatment during a 1 month placebo run-in. We allocated patients 1:1 with computer-generated randomisation to an open-label 3 month high-sodium (>200 mEq [4·8 g] per day) or low-sodium (<100 mEq [2·4 g] per day) diet and, within each diet group, to a 1 month double-blind treatment period of oral paricalcitol (2 μg per day) or placebo, followed by 1 month of placebo washout and then a further 1 month double-blind treatment period of paricalcitol or placebo in which patients crossed over to the opposite treatment period. The primary outcome was 24 h albuminuria (median of three consecutive measurements). Analyses were modified intention-to-treat (including all randomly allocated patients who took at least one dose of study drug and had an efficacy measurement after the first treatment period). Patients and investigators were masked to paricalcitol and placebo assignment. Those assessing outcomes were masked to both study drug and diet assignment. This study is registered with ClinicalTrials.gov, number NCT01393808, and the European Union Clinical Trials Register, number 2011-001713-14. FINDINGS Between Dec 13, 2011, and Feb 17, 2015, we randomly allocated 57 (50%) patients to a low-sodium diet (28 [49%] to paricalcitol then placebo and 29 [51%] to placebo then paricalcitol) and 58 (50%) to a high-sodium diet (29 [50%] to paricalcitol then placebo and 29 [50%] to placebo then paricalcitol). In the low-sodium group (30 mEq of daily sodium intake reduction, equivalent to approximately 1·7-1·8 g per day), 24 h albuminuria was reduced by 36·6% (95% CI 28·5-44·9) from 724 mg (441-1233) at baseline to 481 mg (289-837) at month 3 (p<0·0001), but no significant change occurred in the high-sodium group (from 730 mg [416-1227] to 801 mg [441-1365]; 2·9% [-16·8 to 16·4] increase; p=0·50). Changes between diet groups differed by 32·4% (17·2-48·8; p<0·0001) and correlated with changes in natriuresis (r=0·43; p<0·0001). On the high-sodium diet, paricalcitol reduced the salt-induced albuminuria increase by 17·8% (3·9-32·3) over the month of treatment compared with placebo (p=0·02), whereas on the low-sodium diet, paricalcitol did not have a significant effect versus placebo (increase of 4·1% [-9·3 to 21·6]; p=0·59). During placebo treatment, albuminuria decreased with the low-sodium diet (p=0·0002) and did not significantly change with the high-sodium diet, but changes were significantly different between diet groups (p=0·0004). Treatment was well tolerated and no patients withdrew from the study because of treatment-related effects. 67 adverse events occurred in 52 (45%) patients during paricalcitol treatment and 44 events occurred in 36 (31%) patients during placebo treatment. During paricalcitol therapy, 14 cases of hypercalciuria, six cases of hypercalcaemia, and five cases of hyperphosphataemia were reported in one patient each, all of which were possibly treatment related. One case of hypercalciuria was reported in one patient during the placebo treatment period. One stroke and one coronary event occurred during paricalcitol therapy. No patients died during the study. INTERPRETATION In patients with macroalbuminuria and type 2 diabetes, moderate salt restriction enhances the antialbuminuric effect of losartan, an effect that could be nephroprotective and cardioprotective in the long term. The finding that paricalcitol prevents a sodium-induced increase in albuminuria provides support for trials to test the long-term risk-benefit profile of paricalcitol add-on therapy in patients with type 2 diabetes and macroalbuminuria refractory to dietary salt restriction, including patients refractory to even moderate salt restriction. FUNDING AbbVie.
Diabetes | 2017
Piero Ruggenenti; Manuela Abbate; Barbara Ruggiero; Stefano Rota; Matias Trillini; Carolina Aparicio; Aneliya Parvanova; Ilian Iliev; Giovanna Pisanu; Annalisa Perna; Angela Russo StatSciD; Olimpia Diadei; Davide Martinetti; Antonio Cannata Chemist; Fabiola Carrara Chemist; Silvia Ferrari Chemist; Nadia Stucchi Chemist; Giuseppe Remuzzi; Luigi Fontana
In individuals with type 2 diabetes with abdominal obesity, hyperfiltration is a risk factor for accelerated glomerular filtration rate (GFR) decline and nephropathy. In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded end point trial, consenting patients with type 2 diabetes aged >18 years, with waist circumference >94 (males) or >80 (females) cm, serum creatinine <1.2 mg/dL, and normoalbuminuria were randomized (1:1) with permuted blocks to 6 months of a 25% calorie restricted (CR) or standard diet (SD). Primary outcome was measured GFR (iohexol plasma clearance). Analyses were by modified intention to treat. At 6 months, GFR significantly decreased in 34 patients on CR and did not change appreciably in 36 on SD. Changes were significantly different between the groups. GFR and body weight reduction were correlated. GFR reduction was larger in hyperfiltering (GFR >120 mL/min) than nonhyperfiltering patients and was associated with BMI, waist circumference, blood pressure, heart rate, HbA1c, blood glucose, LDL-to-HDL cholesterol ratio, C-reactive protein, angiotensin II, and albuminuria reduction and with increased glucose disposal rate (measured by hyperinsulinemic-euglycemic clamps). Protein and sodium intake and concomitant treatments were similar between the groups. CR was tolerated well. In patients with type 2 diabetes with abdominal obesity, CR ameliorates glomerular hyperfiltration, insulin sensitivity, and other cardiovascular risk factors, effects that might translate into long-term nephro- and cardioprotection.
International Journal of Artificial Organs | 2018
Michela Bozzetto; Paolo Brambilla; Stefano Rota; Bogdan Ene-Iordache; Sandro Sironi; Giuseppe Remuzzi; Andrea Remuzzi
Introduction: Autogenous arteriovenous fistula is the preferred vascular access for hemodialysis, but it has high rates of non-maturation and early failure due to vascular stenosis. Convincing evidence supports a key role of local hemodynamics in vascular remodeling, suggesting that unsteady and disturbed flow conditions may be related to stenosis formation in arteriovenous fistula. The purpose of our study was to explore the feasibility of coupling contrast-free magnetic resonance imaging and computational fluid dynamics in longitudinal studies to identify the role of local hemodynamic changes over time in inducing vessel wall remodeling in arteriovenous fistula. Methods: We acquired contrast-free magnetic resonance imaging of arm vasculature at 1 week and 6 weeks after arteriovenous fistula creation in a 72-year-old patient. We then generated three-dimensional models and evaluated lumen cross-sectional area of arteriovenous fistula limbs. We performed high-resolution computational fluid dynamics to evaluate changes in local hemodynamics over time. Results: Our contrast-free magnetic resonance imaging protocol provided good quality images in a short scan duration. We observed a homogeneous dilatation in the proximal artery, while there was a more pronounced lumen dilatation in the venous outflow as compared to a limited dilatation in the juxta-anastomotic vein. Furthermore, we observed a slight stabilization of the flow pattern over time, suggesting that vascular outward remodeling accommodates the flow to a more helicoidally phenotype. Conclusion: Coupling contrast-free magnetic resonance imaging and high-resolution computational fluid dynamics represents a promising approach to shed more light in the mechanisms of vascular remodeling and can be used for prospective clinical investigations aimed at identifying critical hemodynamic factors contributing to arteriovenous fistula failure.
Kidney International | 1991
Giulio Mingardi; Stefano Rota; Rocco Misiani; Stefanla Bernareggi; Ornella Facci; Donatella Marchesi; Arrigo Schieppati; Lucto Gualandris; Giancarlo Orlandini; Luca Bonetti; Ariela Benigni; Antonella Piccinelli; Romana Licini; Aristide Mangili; Giuliano Mecca; Enza Poletti; Giacomo Tiraboschi; Claudio Grassi; Oscar Bracchi; Giovanni Pedroni; Agnese Meterange-Lis; Marco Lorenz; Patrizia Ondei; Luciano A. Pedrini; Giorgio Cozzi; Pietro Faranna; Marcello Borghi; Giovanni Vendramin; Margherita Massazza; Luciano Rusconi
Kidney International | 1993
Daniela Macconi; Adrian Fabio Zanoli; Silvia Orisio; Lorena Longaretti; Luca Magrini; Stefano Rota; Antonella Radice; Cristiana Pozzi; Giuseppe Remuzzi