DEPARTMENT OF RENAL MEDICINE STAFF Head

Piero RUGGENENTI, M.D.

Laboratory of Biostatistics Head

Annalisa PERNA, Dr.Sci.Stat., M.Sc.

Laboratory of Coordination and Conduction of Controlled Clinical Trials Head

Giulia GHERARDI, Res.N.

Laboratory of Pharmacokinetics and Clinical Chemistry Head

Flavio GASPARI, Chem.D.

Laboratory of Advanced Development of Drugs Head

Norberto PERICO, M.D.

Unit of Early Clinical Evaluation of Drugs Head

Aneliya ILIEVA PARVANOVA, M.D.

Laboratory of Clinical Pathophysiology of Renal Disease and Transplantation Head

Paolo CRAVEDI, M.D., PhD.

Laboratory of Pharmacovigilance and Monitoring for Clinical Investigations Head

Nadia RUBIS, Res.N.

Laboratory of Regulatory Affairs for Clinical Studies Head

Paola BOCCARDO, Bio.Sci.D.

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Piero Ruggenenti got his Medicine degree in 1983 at the University of Milan, Italy; he got his specialization in Cardiology in 1985 and in Clinical Nephrology in 1989 at the same University; he specialized in Pharmacological Research in 1988 at IRFMN. Educational training: in 1980-1983 researcher at "Centro di Fisiologia Clinica e Ipertensione, Clinica Medica IV", Università degli Studi di Milano; in 1984 Researcher at IRFMN, Bergamo, Italy in 1987-1988 Honorary Registrar of the Unit for Metabolic Medicine, Division of Medicine (University of London) of Guy's and St. Thomas's Hospitals, London; in 1988-1989 Assistant Professor of the Division of Nephrology and Dialysis of the Ospedali Riuniti di Bergamo. Areas of interest: mechanisms of chronic renal disease progression, diabetes and diabetic complications, clinical transplantation, thrombotic microangiopathies, cardiovascular complications of chronic renal disease, clinical trials, clinical pharmacology. Employment: from 1990 Assistant Professor of the Division of Nephrology and Dialysis of the Ospedali Riuniti di Bergamo; in 1994-1999 Head, Unit of Advanced Development of Drugs, Daccò Center, Ranica, Bergamo, Italy; since 2000 Head, Department of Renal Medicine, Daccò Center, Bergamo, Italy. Selected publications:  Trillini M, Cortinovis M, Ruggenenti P, Reyes Loaeza J, Courville K, Ferrer-Siles C, Prandini S, Gaspari F, Villa A, Perna A, Gotti E, Caruso M R, Martinetti D, Remuzzi G, Perico N. Paricalcitol for secondary hyperparathyroidism in renal transplantation. J Am Soc Nephrol E-pub: (2014).  Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F, Bresin E, Tripodo C, Bettoni S, Donadelli R, Valoti E, Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E, Remuzzi G. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 124: 1715-1726 (2014)  Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro R M, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G, Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol 25: 850-863 (2014).  Ruggenenti P, Cravedi P, Remuzzi G. Mechanisms and treatment of CKD. J Am Soc Nephrol. 2012 Dec; 23 (12): 1917-28.  Ruggenenti P, Porrini E, Motterlini N, Perna A, Ilieva AP, Iliev IP, Dodesini AR, Trevisan R, Bossi A, Sampietro G, Capitoni E, Gaspari F, Rubis N, Ene-Iordache B, Remuzzi G; BENEDICT Study Investigators. Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes. J Am Soc Nephrol. 2012 Oct; 23 (10): 1717-24.  Ruggenenti P, Cravedi P, Chianca A, Perna A, Ruggiero B, Gaspari F, Rambaldi A, Marasà M, Remuzzi G. Rituximab in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012 Aug; 23 (8): 1416-25.  Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G; GFR Study Investigators. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care. 2012 Oct; 35 (10): 2061-8.  Martinelli I, Ruggenenti P, Cetin I, Pardi G, Perna A, Vergani P, Acaia B, Facchinetti F, La Sala GB, Bozzo M, Rampello S, Marozio L, Diadei O, Gherardi G, Carminati S, Remuzzi G, Mannucci PM; HAPPY Study Group. Heparin in pregnant women with previous placentamediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial. Blood. 2012 Apr 5; 119 (14): 3269-75.  Vegter S, Perna A, Postma MJ, Navis G, Remuzzi G, Ruggenenti P. Sodium intake, ACE inhibition, and progression to ESRD. J Am Soc Nephrol. 2012 Jan; 23 (1): 165-73.  Ruggenenti P, Lauria G, Iliev IP, Fassi A, Ilieva AP, Rota S, Chiurchiu C, Barlovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi G, DEMAND Study investigators. Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clincal trial. Hypertension. 2011 Set; 58: 776783.  Ruggenenti P, Fassi A, Parvanova Ilieva A, Petrov Iliev I, Chiurchiu C, Rubis R, Gherardi G, Ene-Iordache B, Gaspari G, Perna A, Cravedi P, Bossi A, Trevisan R, Motterlini N, Remuzzi G, for the BENEDICT-B Study Investigators. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. J Hypert. 2011, 29: 207-216  Ruggenenti P, Cattaneo D, Loriga G, Ledda F, Motterlini N, Gherardi G, Orisio S, Remuzzi G. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy. Hypertension, 2009 Sep; 54 (3): 567-74.  Rigotti P, Ekser B, Furian L, Baldan Nm Valente ML, Boschiero L, Motterlini N, Perna A, Remuzzi G, Ruggenenti P. Outcome of renal transplantation from very old donors. New Engl J Med 2009, 360: 1464-1465.  Remuzzi G, Cravedi P, Perna A, Dimitrov BD, Turturro M, Locatelli G, Rigotti P, Baldan N, Beatini M, Valente U, Scalamogna M, Ruggenenti P, Dual Kidney Transplant Group. Long-term outcome of renal transplantation from older donors. N Engl J Med, 2006; 354: 343352.  Ruggenenti P, Fassi A, Parvanova A, Bruno S, Iliev I, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G for the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med, 2004; 351: 1941-1951.  Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet, 2004 Aug 7-13; 364 (9433): 503-12.  Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P. Rituximab for idiopathic membranous nephropathy. Research Letter. Lancet, 2002; 360: 923-924.  Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G. Renoprotective properties of ACEinhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet ,1999; 354: 359-364.

Paola Boccardo got her classic High School Diploma in 1979 and the Biol. Sci. Degree at the University of Pisa in 1985. In 1987 she passed the qualifying examination and got the license of Biologist. Educational training: she performed her training first at Mutagenesis and Differentiation Institute, CNR, of Pisa, and then at Mario Negri Institute for Pharmacological Research, where in 1990, got her diploma of “Specialist in Pharmacological Research”. Since 1987 has been working as full-time researcher at Mario Negri Institute, till 1995 at Molecular Medicine Department and then at Renal Medicine Department. Area of interest: since 1995 she is in charge of Regulatory Affairs and attends to the planning, organizing and conducting of clinical studies in accordance with the principles of Good Clinical Practice and with the laws in force. Employment: since June 2006 to October 2009 Responsible of Clinical Trials Office; since November 2009 Head, Laboratory of Regulatory Affairs for Clinical Studies. Member of Internal Staff for Security, since May 2008 she is Security Manager at Clinical Research Center for Rare Diseases Aldo e Cele Daccò. Selected publications:  Perico N, Delaini F, Lupini C, Benigni A, Galbusera M, Boccardo P, Remuzzi G. Blunted excretory response to atrial natriuretic peptide in experimental nephrosis. Kidney Int, 1989; 36: 57-64.  Benigni A, Perico N, Dadan J, Gabanelli M, Galbusera M, Boccardo P, Mennini T, Remuzzi G. Functional implications of decreased renal cortical ANP binding in experimental diabetes. Circ Res, 1990; 66: 1453-60.  Benigni A, Boccardo P, Noris M, Remuzzi G, Siegler RL. Urinary excretion of platelet-activating factor in hemolytic uremic syndrome. Lancet, 1992; 339: 835-6.  Noris M, Benigni A, Boccardo P, Aiello S, Gaspari F, Todeschini M, Figliuzzi M, Remuzzi G. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int, 1993; 44: 445-450.  Benigni A, Boccardo P, Galbusera M, Monteagudo J, De Marco L, Remuzzi G, Ruggeri ZM. Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia. Am J Kidney Dis, 1993; 22: 668-676.  Boccardo P, Noris M, Remuzzi G. Prevention and therapeutic management of bleeding in dialysis patients. In: Dialysis Therapy, 3rd edition. 

Edited by Nissenson A.R., Fine R.N. Hanley & Belfus, Inc., Philadelphia 2001; 3: 190-194. Remuzzi G, Galbusera M, Boccardo P. Disorders of hemostasis in dialysis patients. In: Heinrich, W.L. Ed. Principles and Practice of Dialysis, 4th ed. Philadelphia, PA: Lippincot W & W, 2009.

Paolo Cravedi got his Medicine degree (cum laude) in 1999 at the University of Milan, Italy; he got his specialization in Nephrology (cum laude) in 2004 at the University of Parma. In 2009 got a Ph.D. degree from the Open University of London. Educational training: in 2005 Master on Organ Transplant at the University of Milano Bicocca; in 2006 researcher at the Mario Negri Institute, Bergamo; since 2007 to 2008 Research Fellow at the Transplant Branch of the National Institutes of Health (NIH) (Mentor Dr. Roslyn Mannon); since 2009 researcher at the Mario Negri Institute, Bergamo. Areas of interest: mechanisms of chronic renal disease progression, diabetes and diabetic complications, clinical transplantation, membranous nephropathy, clinical pharmacology. Employment: since 2010, Head Laborary of Clinical Pathophysiology of Renal Disease and Transplantation. Selected publications:  Remuzzi G, Cravedi P, Perna A, Dimitrov BD, Turturro M, Locatelli G, Rigotti P, Baldan N, Beatini M, Valente U, Scalamogna M, Ruggenenti P Dual Kidney Transplant Group. Long-term outcome of renal transplantation from older donors. N Engl J Med, 2006; 354: 343352.  Cravedi P, Ruggenenti P, Remuzzi G. Sirolimus to replace calcineurin inhibitors? Too early yet. Lancet, 2009; 373:1235-6.  Ruggenenti P, Cravedi P, Sghirlanzoni MC, Gagliardini E, Conti S, Gaspari F, Marchetti G, Abbate M, Remuzzi G. Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy. Clin J Am Soc Nephrol, 2008; 3: 1652-9.  Cravedi P, Ruggenenti P, Sghirlanzoni MC, Remuzzi G. Titrating rituximab to circulating B cells to optimize lymphocytolytic therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol, 2007; 2: 932-7.  Remuzzi G, Cravedi P, Costantini M, Lesti M, Ganeva M, Gherardi G, Ene-Iordache B, Gotti E, Donati D, Salvadori M, Sandrini S, Segoloni G, Federico S, Rigotti P, Sparacino V, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial. J Am Soc Nephrol, 2007; 18: 1973-85.

Flavio Gaspari got his Chemistry degree in 1977 at the University of Milano, Italy, and the specialization in the same University in 1979. Educational training: in 1981-1985 Fellow and Researcher at IRFMN, Milan; in 1985-1991 at IRFMN, Bergamo, Italy. Areas of interest: pharmacokinetics and the metabolism of xanthines in different animal species; drug pharmacokinetics in uremic patients and in subjects with different degrees of renal function; analytical methods to measure the most important immunosuppressive drugs to determine their pharmacokinetics in kidney, heart, and liver transplant recipients; evaluation of the renal function by using different approaches, in the study of renal disease progression, and in the comparison of different methods for albuminuria determination. Employement: he is Head of Laboratory of Pharmacokinetics and Clinical Chemistry since January 2000 and he was Head of this Unit since 1991. Selected publications:  Gaspari F, Ruggenenti P, Porrini E, Motterlini N, Cannata A, Carrara F, Jiménez Sosa A, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Trevisan R, Bossi A, Zaletel J, Remuzzi G. The GFR and GFR decline cannot be accurately estimated in type 2 diabetics. Kidney Int. 2013; 84: 164-173.

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Ruggenenti P, Porrini E, Gaspari F, Motterlini N, Cannata A, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G for the GFR Study Investigators. Glomerular Hyperfiltration and Renal Disease Progression in Type 2 Diabetes. Diabetes Care. 2012 Oct;35(10):2061-2068. Sangalli F, Carrara F, Gaspari F, Corna D, Zoja C, Botti L, Remuzzi G, Remuzzi A. Effect of ACE inhibition on glomerular permselectivity and tubular albumin concentration in the renal ablation model. Am J Physiol Renal Physiol. 2011 Jun;300(6):F1291-300. Ruggenenti P, Fassi A, Ilieva AP, Iliev IP, Chiurchiu C, Rubis N, Gherardi G, Ene-Iordache B, Gaspari F, Perna A, Cravedi P, Bossi A, Trevisan R, Motterlini N, Remuzzi G; BENEDICT-B Study Investigators. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. J Hypertens. 2011 Feb;29(2):207-16. Perico N, Antiga L, Caroli A, Ruggenenti P, Fasolini G, Cafaro M, Ondei P, Rubis N, Diadei O, Gherardi G, Prandini S, Panozo A, Flores Bravo R, Carminati S, Rodriguez De Leon F, Gaspari F, Cortinovis M, Motterlini N, Ene-Iordache B, Remuzzi A, Remuzzi G. Sirolimus therapy to halt the progression of ADPKD. JASN 2010; 21: 1031-1040. Gaspari F, Cravedi P, Mandalà M, Perico N, de Leon FR, Stucchi N, Ferrari S, Labianca, R, Remuzzi G, Ruggenenti P. Predicting CisplatinInduced Acute Kidney Injury by Urinary Neutrophil Gelatinase-Associated Lipocalin Excretion: A Pilot Prospective Case-Control Study. Nephron Clin Pract 2010;115:c154-c160. Ruggenenti P, Perna A, Tonelli M, Loriga G, Motterlini N, Rubis N, Ledda F, Rota S Jr, Satta A, Granata A, Battaglia G, Cambareri F, David S, Gaspari F, Stucchi N, Carminati S, Ene-Iordache B, Cravedi P, Remuzzi G; for the ESPLANADE Study Group. Effects of Add-on Fluvastatin Therapy in Patients with Chronic Proteinuric Nephropathy on Dual Renin-Angiotensin System Blockade: The ESPLANADE Trial. Clin J Am Soc Nephrol. 2010; 5:1928-38. Perico N, Zoja C, Corna D, Rottoli D, Gaspari F, Haskell L, Remuzzi G. V1/V2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. Kidney Int, 2009 Nov; 76(9): 960-7. Ruggenenti P, Cravedi P, Sghirlanzoni MC, Gagliardini E, Conti S, Gaspari F, Marchetti G, Abbate M, Remuzzi G. Effects of rituximab on morphofunctional abnormalities of membranous glomerulopathy. Clin J Am Soc Nephrol, 2008 Nov; 3(6): 1652-9. Gotti E, Perico N, Gaspari F, Cattaneo D, Lesti MD, Ruggenenti P, Segoloni G, Salvadori M, Rigotti P, Valente U, Donati D, Sandrini S, Federico S, Sparacino V, Mourad G, Bosmans JL, Dimitrov BD, Iordache BE, Remuzzi G. Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial. Transplant Proc, 2005 Jun; 37(5): 2037-40. Perico N, Gaspari F, Remuzzi G. Assessing renal function by GFR prediction equations in kidney transplantation. Am J Transplant, 2005 Jun; 5(6): 1175-6. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G; Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med, 2004 Nov 4; 351 (19): 1941-51.

Giulia Gherardi got her Scientific High School Diploma in 1989 at the Liceo Scientifico Marie Curie in Zogno (Bergamo), the Nurse Diploma in 1995 at the Scuola per Infermieri Professionali, Ospedali Riuniti, Bergamo and the 1st Level Master in Clinical Research in 2008 at the Medicine and Surgery Faculty of the University in Milan. Educational training: Clinical Research Nurse Diploma on 1997 at IRFMN –Daccò Center. Areas of interest: statistical methodology of long-term randomised clinical trials in nephrology, and diabetology; the coordination, conduction and monitoring of controlled clinical trials. Employement: in 1997-2003 involved as co-organazing, speaker, co-speaker and tutor for the Clinical Research Course for Nurse at IRFMN – Daccò Center (Ranica – Bergamo). Several training activities for Nurses in Clinical Research area. In 1997-1999, Clinical Research Monitor at IRFMN – Daccò Center; in 2000-2008 Head of the Monitoring Drug Unit at IRFMN – Daccò Center. Since 2009 Head of the Laboratory of Coordination and Conduction of Controlled Clinical Trials at IRFMN – Daccò Center. Selected publications:  Martinelli I, Ruggenenti P, Cetin I, Pardi G, Perna A, Vergani P, Acaia B, Facchinetti F, La Sala G B, Bozzo M, Rampello S, Marozio L, Diadei O, Gherardi G, Carminati S, Remuzzi G, Mannucci P M, Happy Study Group. Heparin in pregnant women with previous placentamediated pregnancy complications: a prospective, randomized, multicenter, controlled clinical trial. Blood 119: 3269-3275 (2012).  Ruggenenti P, Cattaneo D, Loriga G, Ledda F, Motterlini N, Gherardi G, Orisio S, Remuzzi G. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy. Hypertension, 2009 Sep; 54 (3): 567-74.  Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G; Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med, 2004 Nov 4; 351 (19): 1941-51.  Remuzzi G, Lesti M, Gotti E, Ganeva M, Dimitrov BD, Ene-Iordache B, Gherardi G, Donati D, Salvadori M, Sandrini S, Valente U, Segoloni G, Mourad G, Federico S, Rigotti P, Sparacino V, Bosmans JL, Perico N, Ruggenenti P. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet, 2004 Aug 7-13; 364 (9433): 503-12.  Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet, 1998 Oct 17; 352 (9136): 1252-6.

Norberto Perico got his Medicine degree in 1983 at the University of Milano, Italy. He got his specialization in Pharmacological Research in 1986 at IRFMN, Bergamo and in Clinical Nephrology in 1989 at the University of Verona, Italy. Educational training: in 1982 Fellow, Department of Pharmacology, New York Medical College, Valhalla, New York, USA; in 1984-1988 Post Doctoral Fellow, Laboratory of Kidney Diseases, IRFMN, Bergamo, Italy; in 1988-1989 Researcher in the same laboratory. Areas of interest: pathophysiology and pharmacology of cyclosporine nephrotoxicity; new immunosuppressive strategies to prevent renal graft rejection; innovative approach to induce tolerance to organ transplantation;

mechanism(s) and management of progression of chronic renal diseases, novel therapies for autosomal dominant polycystic kidney disease. Employment: in 1990-1994 Head, Renal Physiology Unit, Laboratory of Kidney Diseases, IRFMN, Bergamo, Italy; in 1990-2000 Assistant Professor, Division of Nephrology and Dialysis, Ospedali Riuniti di Bergamo, Italy; in 1994 – 1999 Head, Laboratory of Transplant Immunology, IRFMN, Bergamo, Italy; from January 2000 Head, Laboratory of Drug Development, Department of Renal Medicine, IRFMN, Bergamo, Italy; from September 2000 Health Director, Daccò Center, IRFMN, Bergamo, Italy. From October 2004 he’s Member, ISN Research & Prevention Committee of the International Society of Nephrology. Selected publications:  Garattini S, Perico N. Drug development: how academia, industry and authorities interact. Nat Rev Nephrol. 2014 Oct;10(10):602-10. doi: 10.1038/nrneph.2014.133. Epub 2014 Aug 5.  Trillini M, Cortinovis M, Ruggenenti P, Reyes Loaeza J, Courville K, Ferrer-Siles C, Prandini S, Gaspari F, Cannata A, Villa A, Perna A, Gotti E, Caruso MR, Martinetti D, Remuzzi G, Perico N. Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation. J Am Soc Nephrol. 2014 Sep 5. pii: ASN.2013111185. [Epub ahead of print]  Sharma SK, Ghimire A, Carminati S, Remuzzi G, Perico N. Management of chronic kidney disease and its risk factors in eastern Nepal. Lancet Glob Health. 2014 Sep;2(9):e506-7. doi: 10.1016/S2214-109X(14)70281-5. Epub 2014 Aug 27.  Casiraghi F, Remuzzi G, Perico N. Mesenchymal stromal cells to promote kidney transplantation tolerance. Curr Opin Organ Transplant. 2014 Feb;19(1):47-53. doi: 10.1097/MOT.0000000000000035. Review.Lozano R, Naghavi M, Foreman K, Perico N, Remuzzi G, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15; 380 (9859): 2095-128.  Cravedi P, Sharma SK, Bravo RF, Islam N, Tchokhonelidze I, Ghimire M, Pahari B, Thapa S, Basnet A, Tataradze A, Tinatin D, Beglarishvili L, Fwu CW, Kopp JB, Eggers P, Ene-Iordache B, Carminati S, Perna A, Chianca A, Couser WG, Remuzzi G, Perico N. Preventing renal and cardiovascular risk by renal function assessment: insights from a cross-sectional study in low-income countries and the USA. BMJ Open. 2012 Sep 22; 2(5).  Casiraghi F, Azzollini N, Todeschini M, Cavinato RA, Cassis P, Solini S, Rota C, Morigi M, Introna M, Maranta R, Perico N, Remuzzi G, Noris M. Localization of mesenchymal stromal cells dictates their immune or proinflammatory effects in kidney transplantation. Am J Transplant. 2012 Sep;12 (9): 2373-83.  Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, Visciano B, Imbriaco M, Messa P, Cerutti R, Dugo M, Cancian L, Buongiorno E, De Pascalis A, Gaspari F, Carrara F, Rubis N, Prandini S, Remuzzi A, Remuzzi G, Ruggenenti P, ALADIN Study Group. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomized, placebo-controlled, multicenter trial. Lancet 382: 1485-1495 (2013).  Todeschini M, Cortinovis M, Perico N, Poli F, Innocente A, Cavinato R A, Gotti E, Ruggenenti P, Gaspari F, Noris M, Remuzzi G, Casiraghi F. In kidney transplant patients, alemtuzumab but not basiliximab/low-dose rabbit anti-thymocyte globulin induces B cell depletion and regeneration, which associates with a high incidence of de novo donor-specific anti-HLA antibody development. J Immunol 191: 2818-2828 (2013).  Perico N, Casiraghi F, Gotti E, Introna M, Todeschini M, Cavinato R A, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Noris M, Remuzzi G. Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation. Transplant Int 26: 867-878 (2013).  Remuzzi G, Benigni A, Finkelstein F O, Grunfeld J P, Joly D, Katz I, Liu Z, Miyata T, Perico N, Rodriguez-Iturbe B, Antiga L, Schaefer F, Schieppati A, Schrier R W, Tonelli M. Kidney failure: aims for the next 10 years and barriers to success. Lancet 382: 353-362 (2013).

Annalisa Perna obtained a degree in Statistical Sciences from the University of Bologna (Italy) and a Master of Science in Clinical Trials at the London School of Hygiene & Tropical Medicine - Faculty of Epidemiology and Population Health of the University of London (UK). Educational training: She completed her research training at IRFMN, Bergamo Labs. and at the Daccò Center. Areas of interest: Her research interests spread from statistical methodology of long-term randomised clinical trials, mainly in nephrology and diabetology, to statistical methods for calculating sample size, to development of predictive models and to meta-analytic techniques. She is also involved in performing systematic reviews within the Cochrane Collaboration – Renal Review Group. Employment: she is Head of the Laboratory of Biostatistics - Department of Renal Medicine at Daccò Center - IRCCS IRFMN, Ranica (Bergamo). Selected publications:  Trillini M, Cortinovis M, Ruggenenti P, Reyes Loaeza J, Courville K, Ferrer-Siles C, Prandini S, Gaspari F, Cannata A,Villa A, Perna A, Gotti E, Caruso MR, Martinetti D, Remuzzi G, Perico N. Paricalcitol for secondary hyperparathyroidism in renal transplantation - Controlled Clinical Trial. J Am Soc Nephrol 2014 Sep 5. pii: ASN.2013111185. [Epub ahead of print]  Rodger MA, Carrier M, Le Gal G, Martinelli I, Perna A, Rey E, de Vries JI, Gris JC. Meta-analysis of low molecular weight heparin to prevent recurrent placenta-mediated pregnancy complications. Blood. 2014; 123(6):822-8  Chen Y, Schieppati A, Chen X, Cai G, Zamora J, Giuliano GA, Braun N, Perna A. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. 2014 Oct 16;10:CD004293. [Epub ahead of print]  Rodger MA, Langlois NJ, de Vries JI, Rey E, Gris JC, Martinelli I, Schleussner E, Ramsay T, Mallick R, Skidmore B, Middeldorp S, Bates S, Petroff D, Bezemer D, van Hoorn ME, Abheiden CN, Perna A, de Jong P, Kaaja R. Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM). Protocol Syst Rev. 2014 Jun 26;3(1):69.  Gentile G, Mastroluca D, Perna A, Remuzzi G, Ruggenenti P. Glomerular hyperfiltration is a common risk factor for accelerated GFR decline in young adults with autosomal polycystic kidney disease (ADPKD). Kidney Week - American Society of Nephrology, Philadelphia, PA, November 11-16, 2014  Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G. Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. J Am Soc Nephrol 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30.

Aneliya Parvanova Ilieva got her Medical Doctor degree at the Faculty of Medicine, Thracian University (former Higher Medical Institute), Stara Zagora, Bulgaria in 1988, and the specialization in Pharmacology in the Department of Pharmacology, University of Medicine, Sofia in 1992. Her medical degree is recognized in Italy in 2009. In 2013 she has been awarded the PhD degree by the Medical University of Sofia, Bulgaria. Educational training: in 1989-1998 teaching of 3rd, 4th and 5th-year medical students and 2nd and 3rd-year clinical nurses in a general pharmacology and clinical pharmacology, Thracian University, Stara Zagora, Bulgaria; examiner of these students in theoretical and practical, oral and written exams and tests and State examination. In 1993 Course on investigation of isolated organs – Bulgarian Academy of Sciences, Sofia. In 1998 visiting scientist, IRFMN, Ranica, Bergamo, Italy. In 1998 proficiency in the methods for insulin sensitivity evaluation (hyperinsulinemic euglicaemic clamp technique), in renal hemodynamic measurements - glomerular filtration rate (plasma clearance of iohexol and inulin), in renal plasma flow (plasma clearance of para-aminohippuric acid), glomerular size selectivity (plasma clearance of neutral dextrans) and in twenty four-hour blood pressure monitoring. Areas of interest: prevention and treatment of micro- and macrovascular diabetic complications; role of insulin resistance, arterial hypertension, dyslipidemia and hyperhomocysteinemia in micro- and macrovascular diabetic complications; clinical trials. Employment: Researcher at the Clinical Research Center for Rare Diseases Aldo and Cele Daccò, Ranica, Bergamo. She is Head of The Unit of Early Clinical Evaluation of Drugs at IRFMN since 2000. She is a member of the Union of Bulgarian Doctors (since 1989), of the Union of Pharmacologists in Bulgaria (since 1990), of the Union of Scientists in Bulgaria (since 1991), and member of the Union of Medical Doctors and Dentists, Bergamo, Italy (since 05.03.2009). Selected publications:  Parvanova A, van der Meer IM, Iliev I, Perna A, Gaspari F, Trevisan R, Bossi A, Remuzzi G. Benigni A, Ruggenenti P, for the daglutril in Diabetic Nephropathy Study Group. Effect on blood pressure of combined inhibitio of endothelin-converting enzyme and neutral endopeptidase with daglutril in patients with type 2 diabetes who have albuminuria: a rsandomised, crossover, double-blind, placebocontrolled trial. Lancet Diabetes Endocrinol 2013; 1: 19-27.  Ruggenenti P, Porrini E, Motterlini N, Perna A, Ilieva AP, Iliev IP, Dodesini AR, Trevisan R, Bossi A, Sampietro G, Capitoni E, Gaspari F, Rubis N, Ene-Iordache B, Remuzzi G, for the BENEDICT Study Investigators. Measurable urinary albumin predicts cardiovascuilar risk among normoalbuminuric patients with type 2 diabetes. J Am Soc Nephrol. 2012 Oct; 23(10):1717-1724. Epub 2012 Aug 30.  Ruggenenti P, Lauria G, Iliev IP, Fassi A, Ilieva AP, Rota S, Chiurchiu C, Barlovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi G; for the DEMAND Study Investigators. Effects of Manidipine and Delapril in hypertensive patients with type 2 diabetes mellitus.The Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) Randomized Clinical Trial. Hypertension. 2011 Set; 58:776-783.  Ruggenenti P, Fassi A, Ilieva AP, Iliev IP, Chiurchiu C, Rubis N, Ghepardi G, Ene-Iordache B, Gaspari F, Perna A, Cravedi P, Bossi A, Trevisan R, Motterlini N, Remuzzi G. for the BENEDICT-B Study Investigators. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. Journal of Hypertension 2011 Feb; 29:20716.  Ruggenenti P, Cattaneo D, Rota S, Iliev I, Parvanova A, Diadei O, Ene-Iordache B, Ferrari S, Bossi AC, Trevisan R, Belviso A, Remuzzi G. Effects of combined ezetimibe and simvastatin therapy as compared with simvastatin alone in patients with type 2 diabetes: a prospective randomized double-blind clinical trial. Diabetes Care 2010 Sep; 33(9): 1954-6. Epub 2010 Jun 21.  Ruggenenti P, Iliev I, Costa GM, Parvanova A, Perna A, Giuliano GA, Motterlini N, Ene-Iordache B, Remuzzi G. Preventing left ventricular hypertrophy by ACE inhibition in hypertensive patients with type 2 diabetes: a perspecified analysis of the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT). Diabetes Care, 2008 Aug; 31 (8): 1629-34.  Parvanova A, Trevisan R, Iliev I, Dimitrov BD, Vedovato M, Tiengo A, Remuzzi G, Ruggenenti P. Insulin resistance and microalbuminuria, A Cross-sectional, case-control study of 158 patients with type 2 diabetes and different degrees of urinary albumin excretion. Diabetes, 2006; 55: 1456-1462.  Parvanova A, Chiurchiu C, Ruggenenti P, Remuzzi G. Inhibition of the renin-angiotensin system and cardio-renal protection: focus on losartan and angiotensin receptor blockade. Expert Opinion on Pharmacotherapy, 2005 Sep; 6 (11):1931-1942.  Ruggenenti P, Fassi A, Parvanova A, Bruno S, Iliev I, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini A, Remuzzi G. Preventing Microalbuminuria in Type 2 Diabetes. NEJM, 2004;351 (19): 1941-51.  Parvanova A, Iliev I, Filipponi M, Dimitrov BD, Vedovato M, Tiengo A, Trevisan R, Remuzzi G, Ruggenenti P. Insulin resistance and proliferative retinopathy: a cross-sectional, case-control study in 115 patients with type 2 diabetes. J Clin Endocrinol Metab, 2004 Sep; 89 (9): 4371-6.  Parvanova A, Iliev I, Dimitrov BD, Arnoldi F, Zaletel J, Remuzzi G, Ruggenenti P. Hyperhomocysteinemia and increased risk of retinopathy: a cross-sectional, case-control study in patients with type 2 diabetes. Diabetes Care, 2002; 25 (12): 2361.

Nadia Rubis got her degree in licensed practical nurse in 1995 at the Nursing School of Azienda Ospedaliera Ospedali Riuniti di Bergamo. Education training: she completed her research training at IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò – Bergamo, Clinical Research Nurse Course (1998). Areas of interest: coordination of clinical studies, monitoring activities and data management, pharmacovigilance. Employment: in 1998-2003 involved as co-promoter and tutor for the Clinical Research Course for Nurse at IRFMN Centro Daccò. In 1998-2008 clinical monitor, Drug Monitoring Unit of Centro Daccò. In 2008-2012 Head of the Drug Monitoring Unit. Since September 2012 Head of the Laboratory of Pharmacovigilance and Monitoring for Clinical Investigations. Since January 2014 responsible of the Course for Clinical Monitor at IRFMN - Centro Daccò. Selected publications:  Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, Visciano B, Imbriaco M, Messa P, Cerutti R, Dugo M, Cancian L, Buongiorno E, Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro

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RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G. Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol. 2014 Apr;25(4):850-63. doi: 10.1681/ASN.2013030251. Epub 2014 Jan 30. Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, Visciano B, Imbriaco M, Messa P, Cerutti R, Dugo M, Cancian L, Buongiorno E, De Pascalis A, Gaspari F, Carrara F, Rubis N, Prandini S, Remuzzi A, Remuzzi G, Ruggenenti P; ALADIN study group. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet. 2013 Nov 2;382(9903):1485-95. doi: 10.1016/S0140-6736(13)61407-5. Epub 2013 Aug 21. Ruggenenti P, Porrini E, Motterlini N, Perna A, Parvanova Ilieva A, Petrov Iliev I, Dodesini AR, Trevisan R, Bossi A, Sampietro G, Capitoni E, Gaspari F, Rubis N, Ene-Iordache B, Remuzzi G; Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patient with type 2 diabetes. J Am Soc Nephrol. 2012 Oct;23(10):1717-24. Epub 2012 Aug 30. Ruggenenti P, Lauria G, Iliev IP, Fassi A, Alieva AP, Rota S, Chiurchiu C, Barloovic DP, Sghirlanzoni A, Lombardi R, Penza P, Cavaletti G, Piatti ML, Frigeni B, Filipponi M, Rubis N, Noris G, Motterlini N, Ene-Iordache B, Gaspari F, Perna A, Zaletel J, Bossi A, Dodesini AR, Trevisan R, Remuzzi GR; DEMAND Study Investigators. Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial. Hypertension. 2011 Nov;58(5):776-83. Epub 2011 Sep 19.

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Piero Ruggenenti, Anna Fassi, Aneliya Parvanova Ilieva, Ilian Petrov Iliev, Carlos Chiurchiu, Nadia Rubis, Giulia Gherardi, Bogdan EneIordache, Flavio Gaspari, Annalisa Perna, Paolo Cravedi, Antonio Bossi, Roberto Trevisan, Nicola Motterlini, Giuseppe Remuzzi, for the BENEDICT-B Study Investigators. Effects of verapamil added-on trandolapril therapy in hypertensive type 2 diabetes patients with microalbuminuria: the BENEDICT-B randomized trial. J Hypertens 29:207-216, 2011.

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Piero Ruggenenti, Annalisa Perna, Marcello Tonelli, Giacomina Loriga, Nicola Motterlini, Nadia Rubis, Franca Ledda, Stefano Rota Jr., Andrea Satta, Antonio Granata, Giovanni Battaglia, Francesco Cambareri, Salvatore David, Flavio Gaspari, Nadia Stucchi, Sergio Carminati, Bogdan Ene-Iordache, Paola Cravedi and Giuseppe Remuzzi for the ESPLANADE study group. Effects of Add-on Fluvastatin Therapy in Patients with Chronic Proteinuric Nephropathy on Dual Renin-Angiotensin System Blockade: The ESPLANADE Trial. Clin J Am Nephrol 5: 1928-1938, 2010.

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Ene-Iordache B, Carminati S, Antiga L, Rubis N, Ruggenenti P, Remuzzi G and Remuzzi A. Developing regulatory-compliant electronic case report forms for clinical trials: experience with the demand trial. J Am Med Inform Assoc, 2009 May-Jun;16 (3): 404-8.

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Fassi A, Rubis N, Parvanova A, Iliev I, Zamora J, Giuliano GA, Ene-Iordache B, Perna A, Anabaya A, Motterlini N, Ruggenenti P, Remuzzi G for the BENEDICT Study Investigators. Randomized and non-randomized patients in the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT). Abstract. 29th Annual Meeting of the Society for Clinical Trials St Louis, Missouri, May 18-21, 2008. Ruggenenti P, Fassi A, Parvanova Ilieva A, Bruno S, Petro Iliev I, Brusegan V, Rubis N, Gherardi G, Arnoldi A, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G, for the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med, 2004; 351: 1941-51.

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Ruggenenti P, Perna A, Gherardi G, Benini R, Rubis N, Gritti D, Ciocca I, Stucchi N and Remuzzi G for the GISEN Group. In chronic renal disease, hypertension and type 2 diabetes predict fast progression. Proteinuria < 2 g/24 hours, type 2 diabetes and polycystic kidneys are associated with poor response to ACE inhibition. ASN, November 5-8, 1999.

INTRODUCTION TO THE DEPARTMENT'S ACTIVITIES

The Department of Renal Medicine was established on 1999 at the Clinical Research Center for Rare Diseases “Aldo e Cele Daccò” – Villa Camozzi, Ranica to coordinate the activities of 6 Laboratories and 2 Units. The activities of the Department are mainly focused on the study of the mechanisms of progression of chronic nephropathies, of new prevention and intervention strategies for diabetic nephropathy, non diabetic chronic nephropathies, chronic allograft dysfunction, of cardiovascular complications of diabetes, chronic renal disease, dialysis and transplantation and of thrombotic microangiopathies. The main aims of these activities are: 1. To identify screening and intervention strategies aimed to prevent the onset of nephropathy and of other chronic complications in subjects with diabetes and/or hypertension as well as in the general population. 2. To define intervention strategies to prevent or slow the progression of chronic nephropathies and eventually obtain remission/regression of renal dysfunction. 3. To optimize immunosuppressive protocols in kidney transplantation and to define new donor selection criteria in order to expand the pool of available organs. These aims will be pursued through the following modalities: 1. Pilot pathophysiology and clinical pharmacology studies fully finalized at the Clinical Research Center to test new pathogenetic hypotheses and new treatment modalities. 2. National and international networks and multicenter trials aimed to verify the efficacy of treatments of potential interest identified as described at point 1. 3. Meta-analyses and probabilistic models to test new risk factors and treatments in large samples of patients and to transfer this information at individual level. 4. To identify novel treatments for primary glomerular diseases such as idiopathic membranous nephropathy, focal and segmental glomerulosclerosis and minimal change disease. Many of these activities rest on the possibility of a tight cooperation with the Department of Molecolar Medicine, the Department of Bioengineering and the Public-Private Department of Specialist and Transplant Medicine. This cooperation allows to plan the research activities of the Department on the basis of new information derived from basic research and of problems of major clinical relevance emerging from routine clinical activities.

FINDINGS/MAIN RESULTS Definition and validation of specific treatments aimed to prevent the development and progression of nephropathy and related micro and macrovascular complications in subjects with type 2 diabetes. Implementation of screening programs in the general population to early identify and treat subjects at rioisk of renal and cardiovascular events Definition and validation of new integrated treatment protocols aimed to slow the progression and/or to achieve remission/regression of diabetic and non-diabetic chronic nephropathies. Institution of a standardized protocol “on line” (The “Remission Clinics”) finalized to achieve regression/remission of chronic nephropathies and limit overall renal and radiovascular risk in hospital practice in the setting of a multicenter Network. Characterization of the antiproteinuric, nephroprotective and cardioprotective effect of maximized and polypharmacologic renin-angiotensin system inhibition, intensified blood pressure and lipid control and identification of novel treatments to reduce the blood pressure and ameliorate insulin sensitivity in subjects at increased cardiovascular risk.

Identification of acquired or congenital risk factors for chronic complications of diabetes and cardiovascular morbidity and mortality Identification and validation of early markers of acute kidney failure and of methods for direct and indirect measurements of kidney function and GFR decline. Identification of safety and efficacy profile of new treatments for the Autosomal Polycistic Kidney Disease (APKD). Definition and validation of new, specific treatments for idiopathic membranous nephropathy and for HUS forms associated with genetic defect of complement factors including the standardization of combined liver and kidney transplantation to prevent post transplant recurrence of genetic associated HUS. Definition and validation of new laboratory procedures and predictive models to help monitoring and optimizing immunosuppressive therapy in clinical transplantation with particular focus on pharmacokynetic markers of drug exposure and genetic predictors of drug tolerability and efficacy. Definition and validation of selection and allocation criteria of kidneys from marginal and old-very old donors to increase the donor pool and the transplant activity. Finalization and activation of multicenter clinical trials aimed to prevent onset and progression of diabetic and non-diabetic chronic nephropathies, to achieve remission of the nephrotic syndrome in primary glomerular diseases, minimize maintenance immunosuppression in kidney transplantation and prevent cardiovascular morbidity and mortality in chronic hemodialysis. Computerization of data acquisition and monitoring procedures for the conduction of controlled clinical trials.

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AO Bolognini Seriate, Ospedale Bolognini, Seriate (BG) AO Papa Giovanni XXIII, Bergamo AO Treviglio, Ospedale di Treviglio, Treviglio (BG) AO Treviglio, Ospedale SS. Trinità, Romano di Lombardia (BG) AO Treviglio, Poliambulatorio extra-ospedaliero, Brembate (BG) ASL Bergamo, Bergamo Istituto Humanitas Gavazzeni, Bergamo Policlinico San Pietro di Istituti Ospedalieri Bergamaschi, Gruppo Ospedaliero San Donato, Ponte San Pietro (BG) AO Spedali Civili di Brescia, Presidio Ospedaliero di Montichiari, Montichiari (BS) AO Spedali Civili, Spedali Civili, Brescia AO Ospedale Sant’Anna, Presidio Ospedaliero Sant’Anna, Como Azienda Ospedaliera Istituti Ospedalieri di Cremona, Cremona AO Provincia di Lodi, Presidio Ospedaliero di Lodi, Lodi AO di Desio e Vimercate, Vimercate (MB) AO Ospedale San Carlo Borromeo, Milano AO Polo Universitario, Ospedale Luigi Sacco, Milano AO San Gerardo, Ospedale Bassini, Cinisello Balsamo (MI) AO San Gerardo, Ospedale San Gerardo, Monza (MI) AO San Paolo – Polo Universitario, Milano ASL Provincia di Milano 2, Ospedale A. Uboldo, Cernusco sul Naviglio (MI) Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano IRCCS Fondazione Centro San Raffaele del Monte Tabor, Milano

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IRCCS Istituto Clinico Humanitas, Rozzano (MI) IRCCS Multimedica di Sesto San Giovanni, Sesto San Giovanni (MI) AO Guido Salvini, Ospedale Caduti Bollatesi, Bollate (MI) AO Ospedale Civile di Legnano, Ospedale Legnano, Legnano (MI) AO Ospedale Civile di Legnano, Ospedale G. Fornaroli di Magenta, Magenta (MI) AO Pavia, Ospedale Civile di Voghera, Voghera (PV) AO Valtellina e Valchiavenna, Ospedale di Sondrio, Sondrio AO Universitaria, Ospedale di Circolo e Fondazione Macchi, Varese ASO Santa Croce e Carle, Ospedale Santa Croce, Cuneo AO Ospedale Infantile Regina Margherita-Sant’Anna di Torino, Ospedale Infantile Regina Margherita, Torino AO Ordine Mauriziano, Ospedale Mauriziano Umberto I, Torino ASL TO2, Ospedale San Giovanni Bosco, Torino AULSS 17 Este, Ospedale di Monselice, Monselice (PD) AULSS 9 di Treviso, Ospedale Santa Maria di Cà Foncello, Treviso AO Universistaria degli Ospedali Riuniti di Trieste, Ospedale di Cattinara, Trieste IRCCS Materno-Infantile Burlo Garofalo, Trieste AO Universitaria di Bologna, Policlinico Sant’Orsola-Malpighi, Bologna AUSL Forlì, Ospedale G. B. Morgagni - L. Pierantoni, Forlì AO Universitaria di Parma, Ospedale di Parma, Parma AUSL Ravenna, Ospedale Santa Maria delle Croci, Ravenna AO Reggio Emilia, Arcispedale Santa Maria Nuova, Reggio Emilia AUSL Rimini, Ospedale Infermi, Rimini AO Universitaria Careggi, Firenze Università degli Studi, Firenze AUSL 2 Lucca, Ospedale Campo di Marte, Lucca AO Universitaria Pisana, Ospedale Santa Chiara, Pisa AUSL 3 di Pistoia, Ospedale SS. Cosma e Damiano di Pescia, Pescia (PT) ASUR Zona Territoriale 13, Ospedale Mazzoni, Ascoli Piceno IRCCS Pediatrico Bambino Gesù, Roma ASL Roma G, Ospedale San Giovanni Evangelista, Tivoli (RM) AUSL Rieti, Rieti AO Ospedale San Giuseppe Moscati, Avellino AO Antonio Cardarelli, Napoli AO Pediatrica Santobono-Pausilipon, Ospedale Santobono, Napoli Università Azienda Ospedaliera Universitaria Federico II, Napoli Università Azienda Ospedaliera Universitaria Federico II, Policlinico Nuovo, Napoli ASL Salerno, Ospedale Maria SS. Addolorata, Eboli (SA) ASL Teramo, Presidio Ospedaliero Giuseppe Mazzini, Teramo Centro Nazionale Ricerche, Reggio Calabria AS 3 Rossano, Ospedale Civile Nicola Giannettasio, Rossano (CS) ASP Agrigento, Ospedale San Giovanni di Dio, Agrigento AO Ospedale Cannizzaro, Catania AO Ospedale Garibaldi, Nesima (CT) AO Universitaria Policlinico-Vittorio Emanuele, Presidio Ospedaliero Vittorio Emanuele, Catania AUSL 3 Catania, Presidio Ospedaliero di Acireale, Acireale (CT) ASP 5 Messina, Ospedale di Milazzo, Milazzo (ME) AO Civico-Di Cristina-Benfratelli, Presidio Ospedaliero Civico e Benfratelli, Palermo AO Universitaria Policlinico Paolo Giaccone, Università degli Studi, Palermo Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IsMeTT), Palermo Fondazione Istituto San Raffaele – G. Giglio di Cefalù, Cefalù (PA) Azienda Ospedaliera, Ospedale Umberto I, Siracusa IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG) AUSL Le/1, Ospedale Vito Fazzi, Lecce ASL Taranto 1, Presidio Ospedaliero Valle D’Itria di Martina Franca, Martina Franca (TA) AO Brotzu, Ospedale San Michele, Cagliari

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ASL Sanluri, Presidio Ospedaliero Nostra Signora di Bonaria, San Gavino Monreale (VS) ASL 8, Cagliari ASL Olbia, Ospedale San Giovanni di Dio, Olbia (OT) ASL Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari

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University Medical Center, Ljubljana (Slovenia) Service de Pharmacologie Clinique, Faculté de Médecine, Lyon (France) Hospital Universitario de Canarias, La Laguna, Tenerife (Spain) Drug Prescribing Unit Navarre Regional Health Service, Pamplona (Spain) Department of Primary Health Care, University of Oxford, Oxford (UK) The George Institute for Global Health Nuffield Department for Population Health, Oxford Martin School , University of Oxford, Oxford (UK) The Ottawa Hospital, Centre for Practice-Changing Research, Ottawa (Canada) Department of Clinical Sciences/Diabetes & Endocrinology Lund University, Skåne University Hospital, Malmö (Sweden) University Medical Center Groningen, Groningen, (The Netherlands) Department of Clinical Pharmacology, Groningen (The Netherlands) Leiden University Medical Center, Leiden (The Netherlands) University Medical Center, Groningen (The Netherlands) Department of Gastroenterology & Hepatology, Radboud University Nijmegen Medical Center, Nijmegen (The Netherlands) Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen (The Netherlands) Mariinskaya Hospital, Saint-Petersburg (Russia) Moscow State University of Medicine and Dentistry, Mosca (Russia) Chişinău Hospital, Chişinău (Moldova) Damanhour Medical National Institute, Damanhour, Beheira (Egypt) Health Sciences University, Ulaanbaator (Mongolia) BP Kerala Institute of Health, Dharan (Nepal) Division of Cardiology, Brigham and Women's Hospital, Boston, MA (USA) National Kidney Foundation, New York, NY (USA) New England Medical Center, Boston, MA (USA) Complejo Hosp Metropolitano de la Caja de Seguro Social, Panama City (Panama) Hospital Juan XXIII, La Paz (Bolivia) Hospital Maciel, Montevideo (Uruguay) Cochrane Collaboration, Cochrane Renal Group, Centre for Kidney Research, NHMRC Centre for Clinical Research Excellence in Renal Medicine, The Children's Hospital at Westmead, Westmead, (Australia).

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Current Diabetes Reviews (Piero Ruggenenti) Journal of Nephrology (Piero Ruggenenti) The Open Hypertension Journal (Paolo Cravedi) World Journal of Nephrology (Paolo Cravedi)

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Acta Diabetologica Acta Pharmacologica Sinica American Journal of Hypertension American Journal of Kidney Diseases American Journal of Pathology American Journal of Transplantation Archives of Medical Science Bentham Science Blood Purification British Medical Journal (BMJ) Circulation American Hearth Association (AHA) Clinical Journal of the American Society of Nephrology (CJASN) Clinical Nephrology EMBO Molecular Medicine Expert Opinion on Pharmacotherapy Expert review of Clinical Immunology Heart Failure Reviews Indian Journal of Nephrology Internal Urology and Nephrology International Journal of Clinical Practice Islets Journal of the American Society of Nephrology (JASN) Journal of Hypertension Journal of Nephrology Kidney International Mediterranean Journal of Hematology And Infection Diseases Nature Communications Nature Reviews Nephrology Nephrology Dialysis Transplantation Nephron New England Journal of Medicine PloS Medicine PloS One The International Journal of Artificial Organs The Lancet Translational research Transplant International Transplantation

PARTICIPATION IN EVENTS IN WHICH THE DEPARTMENT WAS INVOLVED Estimated vs measured GFR for disease progression. International Society of Nephrology Nexus Symposium. Bergamo (Italy), April 3rd-6th 2014. HUS updated for the transplant nephrologist. Hot topics in renal transplantation: endothelial injury. Genova (Italy), April 12th 2014. Therapies for ADPKD: somatostatin therapy. 51° ERA-EDTA Congress. Amsterdam (Holland), June 2nd 2014.

MSCs in transplantation: immunoregulatory or pro-inflammatory. Clinical Scientist Summer Symposium on Translational Medicine. Berlin (Germany), June 19th 2014. Long-acting somatostatin analogue and renal function in ADPKD patients: the ALADIN trial. Science Research Conferences of the Federation of American Societies for Experimental Biology. Lucca (Italy), August 5th 2014. La malattia renale policistica autosomica dominante. Il rene nelle malattie rare (e dintorni…). Piacenza (Italy), September 26th 2014. L’eculizumab contrasta la microangiopatia trombotica complemento-mediata e migliora la prognosi in pazienti adulti con sindrome emolitico-uremica atipica (SEUa). 55° Congresso Nazionale della Società Italiana di Nefrologia. Catania (Italy), October 8th-11th 2014. Early diastolic left ventricular function in autosomal dominant polycystic kidney disease: a matched-cohort, speckle-tracking echocardiographic study. 55° Congresso Nazionale della Società Italiana di Nefrologia.Catania (Italy), October 8th-11th 2014. New biomarkers in kidney transplantation. 55th Congress of the Italian Society of Nephrology. Catania, (Italy), October 10th 2014. Il rene nel paziente diabetico: il punto di vista del nefrologo. Corso della Società Italiana di Diabetologia “Ruolo degli inibitori del cotrasportatore SGLT2 nel paziente con diabete mellito di tipo 2: dalla fisiopatologia alla pratica clinica”. Milano (Italy), October 10th 2014. Pathogenesis of and novel treatments for Autosomal Dominant Polycystic Kidney Disease (ADPKD). ISNSRC Program. Moscow (Russian Federation), October 14th 2014. The ISN “0 by 25” initiative to tackle preventable and treatable acute renal failure in resource-por settings. ISN-SRC Program. Moscow (Russian Federation), October 14th 2014. Mesenchymal stromal cells: can they make the difference?. ESOT-AST Joint Meeting. Madrid (Spain), October 19th 2014. Glomerular hyperfiltration in renal disease, 30 years of debate. Continuing Medical Education Course “DIABESITY: Diabetes and Obesity in Renal Disease”. Tenerife (Spain), November 1st-2nd 2014. Calorie restriction in renal disease. Continuing Medical Education Course “DIABESITY: Diabetes and Obesity in Renal Disease”. Tenerife (Spain), November 1st-2nd 2014. Estimation of GFR in diabetes and obesity: is it reliable?. Continuing Medical Education Course “DIABESITY: Diabetes and Obesity in Renal Disease”. Tenerife (Spain), November 1st-2nd 2014. Future directions in Diabesity and renal disease. Continuing Medical Education Course “DIABESITY: Diabetes and Obesity in Renal Disease”. Tenerife (Spain), November 1st-2nd 2014. Hypertension associated with CKD. American Society of Nephrology Kidney Week. Philadelphia (Pennsylvania, USA), November 11th-16th 2014. Rituximab for primary glomerular disease: an update. Nephrologisches Forum Munchen. Monaco (Germany), December 9 th 2014.

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Trillini M, Cortinovis M, Ruggenenti P, Reyes Loaeza J, Courville K, Ferrer-Siles C, Prandini S, Gaspari F, Villa A, Perna A, Gotti E, Caruso M R, Martinetti D, Remuzzi G, Perico N. Paricalcitol for secondary hyperparathyroidism in renal transplantation. J Am Soc Nephrol E-pub. Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F, Bresin E, Tripodo C, Bettoni S, Donadelli R, Valoti E, Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E, Remuzzi G. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 124: 1715-1726. Mescia F, Piras R, Noris M, Marchetti F, Rossini G, Remuzzi G, Ruggenenti P. Kidney transplantation from a donor with acute kidney injury: an unexpected outcome. Am J Transplant 14: 977-978. Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, EneIordache B, Rudnicki M, Pollastro R M, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G, Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol 25: 850-863. Marasà M, Cravedi P, Ruggiero B, Ruggenenti P. Refractory focal segmental glomerulosclerosis in the adult: complete and sustained remissions of two episodes of nephrotic syndrome after a single dose of rituximab. BMJ Case Rep 2014: bcr2014205507. Inker L A, Levey A S, Pandya K, Stoycheff N, Okparavero A, Greene T, Remuzzi G, Ruggenenti P, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Early change in proteinuria as a surrogate end point for kidney disease progression: an individual patient meta-analysis. Am J Kidney Dis 64: 74-85. Siwy J, Schanstra J P, Argiles A, Bakker S J L, Beige J, Boucek P, Brand K, Delles C, Duranton F, Fernandez-Fernandez B, Jankowski M - L, Al Khatib M, Kunt T, Lajer M, Lichtinghagen R, Lindhardt M, Maahs D M, Mischak H, Mullen W, Navis G, Noutsou M, Ortiz A, Persson F, Petrie J R, Roob J M, Rossing P, Ruggenenti P, Rychlik I, Serra A L, Snell-Bergeon J, Spasovski G, Stojceva-Taneva O, Trillini M, von der Leyen H, Winklhofer-Roob B M, Zurbig P, Jankowski J. Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy. Nephrol Dial Transplant 29: 1563-1570. Bikbov B, Perico N, Remuzzi G. Mortality landscape in the global burden of diseases, ijuries and risk factors study. Eur J Intern Med 25: 1-5. Casiraghi F, Remuzzi G, Perico N. Mesenchymal stromal cells to promote kidney transplantation tolerance Curr Opin Organ Transplant 19: 47-53.

Garattini S, Perico N. Drug development: how academia, industry and authorities interact. Nat Rev Nephrol 10: 602-610. Gentile G, Mastroluca D, Ruggenenti P, Remuzzi G. Novel effective drugs for diabetic kidney disease? or not?. Expert Opin Emerg Drugs 19: 571-601. De Vries A P J, Ruggenenti P, Ruan X Z, Praga M, Cruzado J M, Bajema I M, D'Agati V, Lamb H J, Pongrac Barlovic D, Hojs R, Abbate M, Rodriquez R, Mogensen C E, Porrini E, ERA-EDTA Working Group Diabesity. Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2: 417-426. Schieppati A, Perico N, Remuzzi G. Eliminating treatable deaths due to acute kidney injury in resourcepoor settings. Semin Dial E-pub. Cravedi P, Remuzzi G, Ruggenenti P. Rituximab in primary membranous nephropathy: first-line therapy, why not?. Nephron Clin Pract E-pub. Gentile G, Remuzzi G, Ruggenenti P. Dual renin-angiotensin-system blockade for nephroprotection: still under scrutiny. Nephron Clin Pract E-pub. Bikbov B, Perico N, Remuzzi G, Global Burden of Disease Study Genitourinary Disease Expert Group. High serum cholesterol: a missed risk factor for chronic kidney disease mortality. Lancet Diabetes Endocrinol 2: 613-614. Cravedi P, Ruggenenti P, Remuzzi A, Remuzzi G. Current status of islet transplantation. Elsevier, London 583-598. Ruggenenti P, Remuzzi G. Dreaming of normoglycaemia with fewer diet restrictions. Lancet Diabetes Endocrinol 2: 350-351. Perico N, Remuzzi G. Chronic kidney disease in sub-Saharan Africa: a public health priority. Lancet Glob Health 2: e124-e125. Birmingham D J, Shidham G, Perna A, Fine D M, Bissell M, Rodby R, Remuzzi G, Petri M, Hebert P, Rovin B H, Hebert L A. Spot PC ratio estimates of 24-hour proteinuria are more unreliable in lupus nephritis than in other forms of chronic glomerular disease. Ann Rheum Dis 73: 475-476. Sharma S K, Ghimire A, Carminati S, Remuzzi G, Perico N. Management of chronic kidney disease and its risk facotrs in Eastern Nepal. Lancet Glob Health 2: e506-e507.

Luis-Lima S, Gaspari F, Porrini E, Garcia-Gonzalez M, Batista N, Bosa-Ojeda F, Oramas J, Carrara F, Gonzalez-Posada J M, Salido E, Torres A, Jimenez-Sosa A. Measurement of glomerular filtration rate: internal and external validations of the iohexol plasma clearance technique by HPLC. Clin Chim Acta 430: 84-85.

RESEARCH ACTIVITIES

Laboratory of Biostatistics A Long-term effects of the somatostatin analogue octreotide LAR in ADPKD patients with polycystic liver disease: a pre-specified substudy of the ALADIN trial

Short-term studies suggest that somatostatin-analogues may have a beneficial effect in patients with polycystic liver disease (PLD) associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) or considered as a single disease entity. Whether and to what extent these medications are effective and tolerated in the long-term is unknown In this substudy of 27 ADPKD patients with PLD, randomly allocated to 40 mg Octreotide-LAR (n=14) or placebo (n=13) monthly administered in the context of the “A LongActing somatostatin analogue on Disease progression In Nephropathy due to autosomal dominant polycystic kidney disease (ALADIN)” prospective, randomized, single-blind, parallel-group trial, we primarily evaluated the absolute and percent changes in total liver volume (TLV), as assessed by repeated Magnetic Resonance Imaging (MRI), at three years of treatment and two years after treatment withdrawal (Recovery) versus baseline. Analyses were by modified intention to treat. This study was registered with ClinicalTrials.gov, NCT00309283. Recruitment was between April 27, 2006, and May 12, 2008. In 2014 we performed final statistical analyses of the ALADIN-liver substudy.

Glomerular hyperfiltration is a common risk factor for accelerated GFR decline in young adults with autosomal polycystic kidney disease (ADPKD) Glomerular hyperfiltration is an independent risk factor for accelerated GFR decline in ADPKD children. Here we aimed to assess whether and to what extent this finding can be extended to young 140 mL/min/1.73m2, followed for at least 1 year with a minimum of 3 CrCl measurements. We identified 91 patients (45 males, 49.5%) aged40 year old, with type 2 diabetes (WHO criteria), serum creatinine >1.8 mg/dl and < 3.5 mg/dl, spot morning urine albumin to creatinine ratio >2000mg/g and no specific contraindications to the study drugs. Primary efficacy variable is ESRD and primary comparison will be between the benazepril plus valsartan and valsartan alone groups. During 2014 the first interim analysis has been completed.

A randomized, prospective, multicenter trial to compare the effect on chronic allograft nephropathy prevention of mycophenolate mofetil versus azathioprine as the sole immunosuppressive therapy for kidney transplant recipients (ATHENA study): first interim analysis The ATHENA study primarily compared the incidence of biopsy-proven chronic allograft nephropathy (CAN) three years post-transplant in kidney recipients randomly allocated to MMF or AZA, after induction therapy with basiliximab and low-dose RATG, and sequential steroid and CsA withdrawal. Secondarily, the

study compared acute rejections after CsA withdrawal, long-term patient and graft survival, and graft function and prevalence/severity of CAN at study end. This was an open, randomized, prospective, multicenter study to compare the cost/efficacy of low-dose MMF versus AZA as the sole immunosuppressive therapy in preventing CAN after induction therapy with basiliximab plus low-dose RATG combined with CsA during the first year after surgery in kidney transplant recipients. Two-hundredtwenty-four kidney transplant recipients from deceased donors given induction therapy with two 20 mg basiliximab injections 4 days apart and a seven-day course of RATG (0.5 mg/kg/day), were randomly allocated on a 1:1 basis to 3-year treatment with low-dose MMF or AZA, added-on CsA maintenance therapy. During 2014 the first interim analysis has been completed.

A prospective, randomized, prospective, open label, blinded end-point (PROBE) trial to evaluate whehter, at comparable blood pressure control, ACE inhibitor therapy more effectively than nonRAS inhibitor therapy reduces cardiovascular morbidity and mortality in chronic dialysis patients with left ventricular hypertrophy and/or arterial hypertension (ARCADIA study): report for Agenzia Italiana del Farmaco (AIFA) Angiotensin-converting-enzyme (ACE) inhibitors have a specific cardioprotective effect and, compared to treatment not directly interfering with the renin-angiotensin-system (RAS), significantly reduce cardiovascular (CV) mortality and morbidity in subjects with normal renal function. Patients with end stage renal disease (ESRD) have a 10-20 fold excess cardiovascular risk compared to subjects with normal renal function and excess risk is even higher in those with left ventricular hypertrophy (LVH). Despite CV events are the leading cause of death in these patients, no adequately powered trial so far evaluated the specific cardioprotective effect of ACE inhibitors in this population. This prospective, randomized, open label, blinded end point (PROBE) trial is primarily aimed at evaluating whether, at comparable blood pressure (BP) control, ACE inhibitor as compared to non-RAS inhibitor therapy significantly reduces the incidence of a composite end point of CV death (including sudden death) and nonfatal myocardial infarction or stroke in 624 patients with arterial hypertension (pre-dialysis systolic/diastolic BP >140/90 mmHg or postdialysis systolic/diastolic BP >130/80 mmHg or antihypertensive therapy) and/or echocardiography evidence of LVH (cardiac mass index >130 g/m2 for men and 100 g/m2 for women) who are on dialysis therapy since at least six months. Secondarily, the study will compare the incidence of single components of the primary outcome, new onset paroxysmal or persistent atrial fibrillation, thrombosis of the artero-venous fistula, new onset, progression or regression of LVH, changes in components of the metabolic syndrome, the safety profile of the two treatment regimens and their cost/effectiveness. During 2014 the ‘Agenzia Italiana del Farmaco’ (AIFA) report has been completed.

Rituximab versus Cyclophosphamide therapy in Idopathic Membranous Nephropathy: a propensity score guided comparison Idiopathic membranous nephropathy (IMN) is the most common cause of the nephrotic syndrome in adults. The initial treatment of iMN patients who present with nephrotic syndrome consists of anti-proteinuric and blood pressure lowering drugs such as ACE inhibitors and/or ARBs. In addition, for patients at high risk of progressive kidney failure KDIGO guidelines recommend treatment with cyclophosphamide, which is proven to be effective in reducing the risk of end stage kidney disease in iMN patients. However, the use of cyclophosphamide is associated with severe side effects. Rituximab is a monoclonal antibody against CD20 that can be found on B-lymphocytes. We recently reported the successful use of rituximab in a cohort of 100 consecutive patients with iMN. Our data suggested that rituximab as effective as cyclophosphamide , but with a more favourable safety profile. However no head-to-head comparisons of the currently recommended cyclophosphamide based regimen and rituximab have been reported. Clinical trials are difficult to perform in iMN due to its relative rarity and the long time follow-up needed to evaluate clinical end points, such as end stage renal disease and mortality. As a consequence very few randomized trials have been performed in iMN. Therefore, many guidelines rely on observational data to aid clinical decision making. Unfortunately, traditional regression models used to adjust for confounding factors in observational studies are hampered by sparse data as well. As a consequence, either over-fitting of a model to the data or residual confounding occurs. Propensity score methods, however, use a two stage approach in order to achieve confounder balance between treated and untreated patients before comparing outcomes in selected patient groups. Thus, propensity score methods are very close to randomization conceptually, and may offer a solution next best to

a clinical trial in comparing treatments for iMN. In the present study, we pooled data of cohorts of iMN patients, treated in two different centers, who have used treatment regimens using either rituximab or cyclophophamide respectively. We used propensity scores to pseudo-randomize patients, and directly compared the safety profiles of rituximab and the restrictive cyclophosphamide regimen in the treatment of iMN. In 2014 we performed statistical analyses of the above study.

The Glu936Asp CFH gene variant and Renal and Cardiovascular Events in Type 2 Diabetics: BENEDICT Study Group Despite optimal blood pressure and metabolic control and early treatment with angiotensin converting enzyme inhibitors (ACEi), approximately one third of type 2 diabetic patients develop microalbuminuria (i.e., a urinary albumin excretion [UAE] rate of 20-200 µg/min). These patients may progress to macroalbuminuria taken as an early marker of diabetic nephropathy, have progressive deterioration of renal function and are at excess risk of cardiovascular events. Indeed, forty to 50 percent of patients with type 2 diabetes who have microalbuminuria eventually die of cardiovascular disease; this is three times as high a rate of death from cardiac causes as among diabetic patients with no evidence of renal disease. On the other hand, ACEi therapy may induce regression to normoalbuminuria in 50% of microalbuminuric type 2 diabetic patients and regression is associated with 50% reduction in cardiovascular risk. Evidence is available that complement-mediated inflammation is implicated in the pathogenesis and progression of renal and extrarenal complications of type 2 diabetes. In a large and homogenous cohort of normoalbuminuric type 2 diabetic patients prospectively followed in the context of a randomized clinical trial, we evaluated the association between carriers of the Asp/Asp genotype of the Glu936Asp FH polymorphism and risk of progression to microalbuminuria than carriers of one or two wild-type Glu alleles. In 2014 we performed statistical analyses of the above study.

Laboratory of Coordination and Conduction of Controlled Clinical Trials The main aim of the Laboratory is to implement and coordinate all the activities needed to fulfil the trials planned by the Renal Medicine Department, according to the study protocols and the Good Clinical Practice (GCP). To Laboratory staff collaborates with all the Laboratories/Unit of the Mario Negri Institute involving in the clinical studies coordinated by the Renal Medicine Department taking care of: to guarantee the flow of the information between the Laboratories/Units of the Renal Medicine Department and to guarantee a continous updating of the trial status; to develop the case report form of studies; to develop the database of studies; to implement and update a centralized system of data management easily enjoyable by researchers of the Renal Medicine Department; to promote training activities for young investigators; to implement and update the SOPs needed for the trial protocols.

Laboratory of Pharmacokinetics and Clinical Chemistry Effects of L-Cysteine administration compared to placebo on residual renal function in stable peritoneal dialysis patients Over the last decades, peritoneal dialysis has grown worldwide to become one of the most common modalities of renal replacement therapy, particularly in developing or newly industrialized countries. Peritoneal dialysis has been associated with an initial survival benefit compared to hemodialysis, although this advantage becomes less apparent over time, likely due to the progressive loss of residual renal function and the development of pathological alterations of peritoneum. It has been recently shown that antioxidant therapy by N-acetyl-cysteine oral supplementation may improve residual renal function in peritoneal dialysis patients. This finding may have major clinical relevance, since preserving residual renal function in peritoneal dialysis patients may be associated with improved survival. Thus, we planned a randomized, double-blind, crossover study to confirm the preliminary evidence of the beneficial effects of antioxidant agents on residual renal function by using the L-enantiomeric form of

cysteine in 10 prevalent peritoneal dialysis patients with residual dieresis higher than 100 mL. Iohexol was selected as a gold standard for renal function determination. An intravenous bolus of 20 mL of iohexol solution was injected and 12 blood samples were drawn between 15 and 480 minutes after injection of the marker. Iohexol plasma clearance was determined according to a 2compartment open model and a simultaneous urinary collection was performed to calculate renal clearance of the marker. Iohexol dialytic clearance was determined by measuring the concentration of the marker in the dialysate exchanged during the nocturnal dialytic session. The effect of the antioxidant therapy by N-acetyl-cysteine oral supplementation was also assessed by evaluating the peritoneal equilibration test (PET). In addition to routine laboratory parameters evaluation, serum, plasma and dialytic liquid samples were collected for the determination of markers of inflammation as well oxidative stress. The study is in progress, and 4 out of the 6 enrolled patients, completed the study.

Systemic and renal response of Gal-/- pigs to human angiotensin II Transplantation is the best available treatment for many serious health problems including diabetes, kidney failure and heart disease. However, the shortage of donor organs severely limits the number of patients receiving transplants and the use of animals as a source of organs and tissues for xenotransplantation could overcome this growing problem. Despite immunological aspects of xenotransplantation have been extensively studied in the last years, less emphasis has been given to investigate the physiology of engineerized pig organs and their compatibility with human milieu. In the perspective of clinical application of kidney xenotransplantation we generated 1,3galactosyltransferase gene-knockout (GAL-KO) pigs and transgenic for human CD55 and CD59. In our study, we aimed to establish whether engineerized porcine kidneys properly respond to human vasoactive hormones that regulate renal function. To this purpose we developed a model to measure in vivo the glomerular filtration rate (GFR) in anesthetized pigs and to characterize the systemic and renal function response of animals to increasing doses of human Angiotensin II (hAng II). In 3 anesthetized Gal-/- pigs (weight range 60-165 kg), glomerular filtration rate was measured by renal clearance of unlabeled iohexol. Iohexol (1294 mg) was injected as an i.v. bolus into a peripheral vein followed by a continuous infusion by a volumetric pump at a rate of 9.61 mg/min. After 2 hour stabilization period, blood and urine samples were collected every 20 minutes for iohexol concentration assessment by HPLC and for the determination of creatinine, sodium, potassium, calcium, chloride, phosphorous, magnesium, by means of an automatic device. Urine protein to creatinine ratio (P/C) was calculated. Baseline GFR, evaluated during three 20 min clearance periods averaged 151±19 mL/min/100kg. Thereafter, increasing doses of 5 g/kg,10 g/kg and 35 g/kg of hAng II, administered as i.v. bolus injection, each at 40 min intervals, resulted in a progressive GFR decline to 79 ± 19, 78 ± 21, and 69 ± 27 ml/min/100 kg, respectively (p