Introduction. Neutrophil Gelatinase-Associated Lipocalin (NGAL) belongs to the family of lipocalins and it is produced by several cell types, including renal tubular epithelium. In the kidney its production increases during acute damage and this is reflected by the increase in serum and urine levels. In animal studies and clinical trials, NGAL was found to be a sensitive and specific indicator of acute kidney injury (AKI). Purpose. The aim of this work was to investigate, in a prospective manner, whether urine NGAL can be used as a marker in preeclampsia, kidney transplantation, VLBI and diabetic nephropathy. Materials and methods. The study involved 44 consecutive patients who received renal transplantation; 18 women affected by preeclampsia (PE); a total of 55 infants weighing ≤1500 g and 80 patients with Type 1 diabetes. Results. A positive correlation was found between urinary NGAL and 24 hours proteinuria within the PE group. The detection of higher uNGAL values in case of severe PE, even in absence of statistical significance, confirms that these women suffer from an initial renal damage. In our population of VLBW infants, we found a positive correlation of uNGAL values at birth with differences in sCreat and eGFR values from birth to day 21, but no correlation was found between uNGAL values at birth and sCreat and eGFR at day 7. systolic an diastolic blood pressure decreased with increasing levels of uNGAL. The patients with uNGAL <25 ng/ml had significantly higher levels of systolic blood pressure compared with the patients with uNGAL >50 ng/ml ( p<0.005). Our results indicate the ability of NGAL to predict the delay in functional recovery of the graft. Conclusions. In acute renal pathology, urinary NGAL confirms to be a valuable predictive marker of the progress and status of acute injury.

Background/Aims. Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work. Methods. We studied 225 prevalent dialysis patients from two Italian Centres. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluation (MNSI_P). Patients without any disease possibly inducing secondary neuropathy and with MNSI score  3 have been diagnosed as affected by UN. Electroneurographic (ENG) lower limbs examination was performed in these patients to compare sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) with the MNSI results. Results. Thirtyseven patients (16.4%) were identified as being affected by UN, while 9 (4%) presented a score <3 in spite of neuropathic symptoms. In the 37 UN patients a significant correlation was found between MNSI_P and SCV (r2 = 0.1959; p<0.034) as well as SNAP (r2 = 0.3454; p=0.027) both measured by ENG. Conclusions. UN is an underestimated disease among the dialysis population even though it represents a huge problem in terms of pain and quality of life. MNSI could represent a valid and simple clinical-instrumental screening test for the early diagnosis of UN in view of an early therapeutic approach. / Principale scopo dello studio è la stima della prevalenza della neuropatia uremica nel paziente emodializzato. Sono stati studiati 225 pazienti in emodialisi cronica trisettimanale. Il Michigan Neuropathy Score Instrument (MNSI) è stato utilizzato per la diagnosi di neuropatia. I pazienti con Michigan score > di 3, in assenza di altre patologie potenzialmente causa di neuropatia, hanno ricevuto diagnosi di neuropatia uremica. Trentasette pazienti (16.4%) sono stati clinicamente identificati affetti da neuropatia uremica, mentre 9 (4%) pur lamentando sintomi avevano un Michigan score < di 3. I pazienti con diagnosi di neuropatia uremica sono stati sottoposti a elettroneurografia ed è stata stabilita una correlazione statisticamente significativa fra il Michigan score e la “sensory conduction velocity (SCV)” (r2 = 0.1959; p < 0.034) cosi come fra Michigan score e “sensory nerve action potential (SNAP)” (r2 = 0.3454; p < 0.027). Inoltre lo studio in regressione logistica ha mostrato una correlazione fra neuropatia ed età del paziente (p > 0.001) e sesso femminile (p < 0.036); nessuna correlazione invece fra neuropatia e la tecnica di dialisi utilizzata.

L’anticoagulazione regionale con citrato (RCA) è una valida opzione in pazienti ad alto rischio emorragico. Lo scopo del nostro studio è stato di valutare, in pazienti critici sottoposti a CRRT per insufficienza renale acuta post-cardiochirurgica, efficacia e sicurezza di un protocollo di RCA in CVVH con l’impiego di una soluzione di citrato a bassa concentrazione (12mmol/L). Metodi: L’RCA-CVVH è stata adottata come alternativa all’eparina o alla CRRT senza anticoagulante (no-AC). Criteri per lo switch verso l’RCA: coagulazione dei circuiti entro 24h o complicanze legate all’eparina. Per facilitare l’impostazione dei parametri CVVH, abbiamo sviluppato un modello matematico per stimare il carico metabolico di citrato e la perdita di calcio. Risultati: In 36 mesi, sono stati sottoposti a RCA-CVVH 30 pazienti. La durata dei circuiti con RCA (50.5 ± 35.8 h, mediana 41, 146 circuiti) è risultata significativamente maggiore (p<0.0001) rispetto all’eparina (29.2±22.7 h, mediana 22, 69 circuiti) o alla no-AC CRRT (24.7±20.6 h, mediana 20, 74 circuiti). Il numero di circuiti funzionanti a 24, 48, 72 h è risultato maggiore durante RCA (p<0.0001). I target di Ca++ sistemico e del circuito sono stati facilmente mantenuti (1.18±0.13 e 0.37±0.09 mmol/L). Durante l’RCA-CVVH nessun paziente ha avuto complicanze emorragiche e il fabbisogno trasfusionale si è ridotto rispetto alle altre modalità (0.29 vs 0.69 unità/die, p<0.05). Le piastrine (p=0.012) e l’AT-III (p=0.004) sono aumentate durante RCA riducendo la necessità di supplementazione. L’RCA è stata interrotta per accumulo di citrato in un solo paziente (calcemia totale/s-Ca++ >2.5). Conclusioni: L’RCA ha consentito di prolungare la durata dei circuiti riducendo il fabbisogno trasfusionale e la necessità di supplementazione di AT-III e piastrine. L’utilizzo di un modello matematico ha facilitato l’impostazione dei parametri CVVH. L’RCA appare meritevole di maggiore considerazione come metodica di anticoagulazione di prima scelta in pazienti ad alto rischio emorragico sottoposti a CRRT. / Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding. The aim was to evaluate the efficacy and safety of RCA-CVVH using a low concentration citrate solution in critically ill patients at high risk of bleeding undergoing Continuous Renal Replacement Therapies (CRRT) for Acute Kidney Injury (AKI) following cardiac surgery. Methods: In cardiac surgery patients we adopted, as alternative to heparin or no anticoagulation (no-AC), RCA-CVVH using a 12 mmol/L citrate solution. Criteria for switching to RCA: early circuit clotting or heparin related complications. To facilitate CVVH settings, we developed a mathematical model to estimate metabolic citrate load and calcium loss. Results: Thirty patients were switched to RCA-CVVH from no-AC or heparin. RCA-CVVH filter life (50.5 ± 35.8 hrs, median 41, 146 circuits) was significantly longer (p<0.0001) if compared to heparin (29.2±22.7 hrs, median 22, 69 circuits) or no-AC (24.7±20.6 hrs, median 20, 74 circuits). Probability of circuit running at 24, 48, 72 hrs was higher during RCA-CVVH (p<0.0001). Targets circuit and systemic Ca++ were easily maintained inside the target range (0.37±0.09 and 1.18±0.13 mmol/L). During RCA-CVVH no patients had bleeding complications and transfusion rate was lower if compared to other AC modalities (0.29 vs 0.69 blood units/day, p<0.05). PLT count (p=0.012) and AT-III activity (p=0.004) increased throughout days of RCA reducing supplementation needs. RCA has been stopped for citrate accumulation in one patient (total calcemia/s-Ca++ >2.5). Conclusions: In this study, RCA allowed to safely prolong filter life decreasing transfusion rate and supplementation needs for AT-III and PLT. The use of a mathematical model allowed to simplify CVVH settings. Therefore, RCA should be worthy of more consideration as first choice CRRT anticoagulation modality in patients at high risk of bleeding.

Introduction:Persistent Hyperparathyroidism after transplantation (HPT),bone disease and vertebral fractures are an important clinical problem in renal transplant patients. Several factors such as renal osteodystrophy, immunosuppressive therapy, deficit/insufficiency Vitamin D may contribute to that.In literature are described different percentages of HPT, vertebral fractures and Osteoporosis/Osteopenia that may be due to the different therapy and to the different employ of steroid. We analyzed 90 patients who received a renal graft between 2005 e 2010. Patients and Methods: 44 male and 46 female. Average age 52,2± 10,1 years, follow-up 31,3±16,6 months, time on dialysis 37±29,6 months. Patients who had creatinine level greater than 2,5 mg/dl were excluded. Immunosuppressive therapy was based on basiliximab, steroids (1.6 to 2 mg/kg/day progressively reduced to 5 mg/day after 45 days from the transplantation) in all patients + calcineurin inhibitor+ mycophenolate mophetil/mycophenolic acid in 88,8% of patients or Everolimus± calcineurin inhibitor in the others. Patients were studied with X-ray of the spine, dual-energy-X-ray, PTH, 25(OH)VitD. Results: 41,1% had HPT; 41,1% had osteopenia at femoral neck and 36,7% at vertebral column; 16,7% had osteoporosis at femoral neck and 15,6% at vertebral column. 10 patients (11%) had vertebral fractures. Patients with normal bone mineral density, compared to those with osteoporosis/osteopenia, are more younger (average age 46,4±11,7 years vs 54.3±8,6); they have spent less time on dialysis (26,5±14,8 months vs 40,7±32,6) and they have values of 25(OH)VitD higher (22,1±7,6 ng/ml vs 17,8±8,5). Patients with vertebral fractures have values of 25(OH)VitD lowest (14,1±6,4 ng/ml vs 19,7±8,5) and they had transplant since more time (29,1±16,2 vs 48,1±8,7 months). There is a significant correlation between HPT and PTH pre transplantation; HPT and levels of VitD (p<0,05) Conclusion: Prevention of Bone disease and vertebral fractures after renal transplant includes: a)treatment before transplantation b)supplementation of vitamin D with cholecalciferol or calcidiol c)shorten the dialysis time.

INTRODUCTION. Late chronic allograft disfunction (CAD) is one of the more concerning issues in the management of patients (pts) with renal transplant (tx). Humoral immune response seems to play an important role in CAD pathogenesis. AIM OF THE STUDY. To identify the causes of late chronic allograft disfunction. METHODS. This study (march 2004-august 2011) enrolled pts who underwent renal biopsy (BR) because of CAD (increase of creatininemia (s-Cr) >30% and/or proteinuria >1g/day at least one year after tx). BR were classified according to 1997/2005 Banff classification. Histological evaluation of C4d (positive if >25%), glomerulitis, tubulitis, intimal arteritis, atrophy/fibrosis and arteriolar-hyalinosis were performed. Ab anti-HLA research at BR was an inclusion criteria. Pts were divided into two groups: with or without transplant glomerulopathy (CTG). RESULTS. Evaluated BR: 93/109. BR indication: impaired s-Cr (52/93), proteinuria (23/93), both (18/93). Time Tx-BR: 7.4±6.3 yrs; s-Cr at BR: 2.7±1.4 mg/dl. CTG group(n=49) not-CTG group(n=44) p Time tx-BR (yrs) 9.3±6.7 5.3±5.2 0.002 Follow-up post-BR (yrs) 2.7±1.8 4.1±1.4 0.0001 s-Cr at BR (mg/dl) 2.9±1.3 2.4±1.5 NS Rate (%) of pts: Proteinuria at BR 61% 25% 0.0004 C4d+ 84% 25% <0.0001 Ab anti-HLA+ 71% 30% 0.0001 C4d+ and/or Ab antiHLA 92% 43% 0.0001 Glomerulitis 76% 16% <0.0001 Tubulitis 6% 32% 0.0014 Intimal arteritis 18% 0% 0.002 Arteriolar hyalinosis 65% 50% NS Atrophy/fibrosis 80% 77% NS Graft survival 45% 86% 0.00005 Histological Diagnosis: CTG group (n=49:Chronic rejection 94%;IgA recurrence + humoral activity 4%;IIA acute rejection + humoral activity 2%. Not-CTG group (n=44: GN recurrence 27%;IF/TA 23%; acute rejection 23%;BKV nephritis 9%; mild not specific alterations 18%. CONCLUSIONS: CTG is the morphological lesion mainly related to CAD. In the 92% of the cases it is associated with markers of immunological activity. It causes graft failure within five years after diagnosis in 55% of pts.

NGAL (Neutrophil Gelatinase-associated Lipocalin ) is a protein of lipocalin superfamily. Recent literature focused on its biomarkers function in several pathological condition (acute and chronic kidney damage, autoimmune disease, malignancy). NGAL biological role is not well elucidated. Several are the demonstration of its bacteriostatic role. Recent papers have indeed highlight NGAL role in NFkB modulation. The aim of this study is to understand whether NGAL may exert a role in the activation (modulation) of T cell response through the regulation of HLA-G complex, a mediator of tolerance. From 8 healthy donors we obtained peripheral blood mononuclear cells (PBMCs) and we isolated by centrifugation on a Ficoll gradient. Cells were then treated with four concentrations of NGAL (40-320 ng/ml) with or without iron. We performed flow cytometry analysis and ELISA test. NGAL increased the HLA-G expression on CD4+ T cells, with an increasing corresponding to the dose. Iron effect is not of unique interpretation. NGAL adiction affects regulatory T cells increasing in vitro expansion of CD4+ CD25+ FoxP3+ cells. Neutralizing antibody against NGAL decreased HLA-G expression and reduced significantly CD4+ CD25+ FoxP3+ cells percentage. In conclusion, we provided in vitro evidence of NGAL involvement in cellular immunity. The potential role of NGAL as an immunomodulatory molecule has been evaluated: it has been shown that NGAL plays a pivotal role in the induction of immune tolerance up regulating HLA-G and T regulatory cells expression in healthy donors. As potential future scenario we highlight the in vivo role of NGAL in immunology and immunomodulation, and its possible relationship with immunosuppressive therapy efficacy, tolerance induction in transplant patients, and/or in other immunological disorders. / Ngal (Neutrophil Gelatinase-associated Lipocalin ) è una proteina appartenente alla famiglia delle lipocaline verso cui la recente letteratura ha mostrato una notevole attenzione, soprattutto in quanto biomarcatore in alcune condizioni patologiche (danno renale acuto e cronico, patologie autoimmuni, neoplasie). Il ruolo biologico di NGAL non è però ancora del tutto compreso. Numerose sono le dimostrazioni della sua azione batteriostatica. Recenti lavori hanno inoltre evidenziato un ruolo di NGAL nella modulazione di NFkB. Nessun lavoro ha valutato il ruolo di NGAL nell’immunità umorale. Lo scopo dello studio è quello di capire se NGAL possa esercitare un ruolo di attivazione (modulazione) della risposta T cellulare attraverso la regolazione del complesso HLA-G, un mediatore di tolleranza. Cellule mononucleate da sangue periferico (PBMCs) sono state ottenute da 8 donatori sani dopo consenso informato e isolate tramite centrifugazione (Ficoll). PBMC sono poi state trattate con 4 concentrazioni crescenti di NGAL (da 40 a 320 ng/mL), associate o meno a ferro e analizzate con tecnica fluorimetrica ed elisa.Alle analisi eseguite NGAL stimola l’espressione di HLA-G sulle cellule T CD4+ con un andamento dose dipendente. L’effetto del ferro sull’espressione di HLA-G non è di univoca interpretazione.Inoltre L’aggiunta di NGAL in vitro modifica il pattern di espressione delle cellule T, aumentando la popolazione delle cellule CD4+ CD25+ FoxP3. L’utilizzo di anticorpi anti NGAL limita l’espressione di HLA-G e diminuisce significativamente la percentuale di CD4+ CD25+ FoxP3+ . In conclusione abbiamo mostrato un coinvolgimento di NGAL nell’immunità cellulare. Valutando il ruolo di NGAL come molecola immunomodulatoria, abbiamo mostrato che NGAL gioca un ruolo chiave neell’immunotolleranza aumentando l’espressione di HLA-G e cellule T regolatorie nei donatori sani. Un possibilAs potential future scenario applicativo di tale studio riguarda l’utilizzo in vivo di NGAL nell’immunomodulazione dei pazienti sottoposti a trapianto o affetti da patologie autoimmuni.

Background: Chronic kidney disease (CKD) is one of the strongest risk factor for myocardial infarction (MI) and mortality. The aim of this study was to assess the association between renal dysfunction severity, short-term outcomes and the use of in-hospital evidence-based therapies among patients with non–ST-segment elevation myocardial infarction (NSTEMI). Methods: We examined data on 320 patients presenting with NSTEMI to Maggiore’s Emergency Department from 1st Jan 2010 to 31st December 2011. The study patients were classified into two groups according to their baseline glomerular filtration rate (GFR): renal dysfunction (RD) (GFR<60) and non-RD (GFR≥60 ml/min). Patients were then classified into four groups according to their CKD stage (GFR≥60, GFR 59-30, GFR 29-15, GFR <15). Results: Of the 320 patients, 155 (48,4%) had a GFR<60 ml/min at baseline. Compared with patients with a GFR≥60 ml/min, this group was, more likely to be female, to have hypertension, a previous myocardial infarction, stroke or TIA, had higher levels of uric acid and C-reactive protein. They were less likely to receive immediate (first 24 hours) evidence-based therapies. The GFR of RD patients treated appropriately increases on average by 5.5 ml/min/1.73 m2. The length of stay (mean, SD) increased with increasing CKD stage, respectively 5,3 (4,1), 7.0 (6.1), 7.8 (7.0), 9.2 (5.8) (global p <.0001). Females had on average a longer hospitalization than males, regardless of RD. In hospital mortality was higher in RD group (3,25%). Conclusions: The in-hospital mortality not was statically difference among the patients with a GFR value ≥60 ml/min, and patients with a GFR value <60 ml/min. The length of stay increased with increasing CKD stages. Despite patients with RD have more comorbidities then without RD less frequently receive guideline –recommended therapy. The GFR of RD patients treated appropriately improves during hospitalization, but not a level as we expected.

Ottimizzazione di un protocollo di anticoagulazione regionale con citrato in CRRT Introduzione: La necessità di un'anticoagulazione continua e l'ipofosforemia in corso di trattamento sono problemi costranti in corso di CRRT. Il nostro studio ha cercato di dimostrare l'efficacia e la sicurezza dell'anticoagulazione regionale con citrato in CVVH basato sull'utilizzo di una soluzione di citrato (18 mmol/L) associata ad una soluzione di reinfusione contenente fosfato, recentemente disponibile in commercio, al fine di ridurre l'ipofosfatemia in corso di CRRT. Metodi: Abbiamo utilizzato il nostro protocollo basato sull'utilizzo di una concentrazione di citrato contenente 18 mmol/l associata ad una soluzione di reinfusione contenente fosfato in un piccolo gruppo di pazienti ricoverati in terapia intensiva post-cardiochirurgica, sottoposti a CRRT per insufficienza renale acuta. Risultati: Il nostro protocollo ha garantito un'adeguata durata del circuito ed un ottimo controllo dell'equilibrio acido-base in ogni paziente. E' stata necessaria solo una minima supplementazione di fosforo in alcuni dei pazienti trattati. Conclusioni: Il nostro protocollo basato sull' utilizzo di una soluzione a concentrazione di citrato maggiore (18 mmol/l), permette un miglior controllo dell'equilibrio acido-base rispetto all'utilizzo della soluzione a più bassa concentrazione di citrato. L'uso di una minore dose di citrato ed il mantenimento di un target maggiore di calcio ionizzato all'interno del circuito sono comunque associati ad un'adeguata durata del circuito. I livelli di fosforemia sono rimasti sostanzialmente stabili nella maggior parte dei pazienti trattati, grazie alla presenza di fosfato nella soluzione utilizzata come reinfusione in post-diluizione. / Optimization of a regional citrate anticoagulation protocol in CRRT Purpose: Prolonged anticoagulation and hypophosphatemia are well known drawbacks of CRRT. The aim of our study was to show the efficacy and safety of a regional citrate anticoagulation protocol for CVVH combined with a phosphate containing replacement fluid. Methods: We used our protocol, based on a citrate solution (18 mmol/l) combined with in a phosphate containing replacement fluid, in a small cohort of heart surgery patients. Results: Our protocol provided an adequate circuit lifetime and an excellent acid-base status in every patient. A low amount of phosphorus supplememntation was required only in a very few patients. Conclusions: Our protocol based on a citrate solution (18 mmol/l) combined with a phosphate containing replacement fluid, allows a better buffer balance control than using of a lower citrate solution. Moreover, an adequate circuit lifetime was obtained. Serum phosphate was steadily maintained in all patients. Only in a very few patients a low supplementation was required.

Lo studio CAVE PTX ha lo scopo di valutare la reale prevalenza della paratiroidectomia nei pazienti dializzati in Italia, verificare l’aderenza ai targets ematochimici proposti dalle linee guida internazionali K/DOQI e ricercare la presenza di fratture vertebrali e calcificazioni vascolari. Al momento attuale riportiamo i dati preliminari sulla prevalenza e le caratteristiche cliniche generali dei pazienti finora arruolati. Il nostro studio ha ricevuto contributi da 149 centri dialisi italiani, su un totale di 670, pari al 22%. La popolazione dialitica dalla quale sono stati ottenuti i casi di paratiroidectomia è risultata pari a 12515 pazienti;l’87,7% dei pazienti effettuava l’emodialisi mentre il 12,3% la dialisi peritoneale. Cinquecentoventotto, pari al 4,22%, avevano effettuato un intervento di paratiroidectomia (4,5%emodializzati, 1,9% in dialisi peritoneale;p<0.001). Abbiamo considerato tre gruppi differenti di PTH: basso (<150 pg/ml), ottimale (150 -300 pg/ml) ed elevato (>300 pg/ml). I valori medi di PTH e calcemia sono risultati significativamente diversi (più alti) tra casi e controlli nei due gruppi con PTH basso (PTX = 40±39 vs controllo = 92±42 pg/ml; p<.0001) e PTH alto (PTX= 630 ± 417 vs controllo 577 ±331; p<.05). La percentuale di pazienti con PTH troppo basso è risultata più elevata nei pazienti chirurgici rispetto al resto della popolazione (64vs23%; p<0.0001), mentre la percentuale dei casi con PTH troppo alto è risultata significativamente più alta nel gruppo di controllo (38%vs19%; p<0.003). Il 61% dei casi assumeva vitamina D rispetto al 64 % dei controlli; l’88% vs 75% un chelante del fosforo ed il 13%vs 35% il calciomimentico. In conclusione, la paratiroidectomia ha una bassa prevalenza in Italia, i pazienti sono più spesso di sesso femminile, in emodialisi e con età relativamente giovane ma da più tempo in dialisi. / CAVE PTX study aims to evaluate, in dialysis patients submitted to PTX, the control and therapies of divalent ions (phase I), and the prevalence of aortic calcifications and vertebral fractures (phase II). We report here the phase I results. Biochemistries and therapies of PTX patients were collected by means of an electronic data sheet from 149 Italian dialysis Units. A control group (C), comparable for age, sex and dialysis duration, was selected from the whole cohort. From a total of 12515 patients (HD = 87.7%;PD = 12.3%), 528(4.22%) had received PTX. Prevalence of PTX was definitely higher in HD(4.5%) compared to PD(1.9%). Respectively in PTX and C, PTH was low(<150) in 64 vs 23%; optimal (150-300) in 17 vs 39%; and high(>300) in 19 vs 38%. Ca, P and PTH values in the three K/DOQI PTH range groups are in table 2. Prescribed drugs, respectively in PTX and C, were: Vitamin D (61 vs 64%); Phosphate binders (88 vs 75%) and Calcimimetic (13 and 35%). Notably, Calcitriol and Ca based binders in PTX, and Paricalcitol and Sevelamer in C, were the most frequently prescribed drugs. PTX has a low prevalence in Italy, and mainly involves relatively young, females and long-term haemodialysis patients. In these patients PTH values are mostly low and therapeutic choices are accordingly different. Different hard outcomes can be hypothesized

Le cellule mesenchimali stromali (MSC) sono cellule multipotenti e numerosi studi hanno mostrato i loro effetti benefici nel danno renale acuto ma non sono ancora stati dimostrati potenziali effetti nella malattia renale cronica. L'ostruzione ureterale unilaterale (UUO) è un modello di fibrosi interstiziale nel quale l'attivazione di molecole vasoattive, citochine profibrotiche e infiammatorie gioca un ruolo patogenetico nello sviluppo dell'apoptosi e atrofia tubulare. Il sistema renina-angiotensina (RAS) gioca un ruolo chiave nello sviluppo della fibrosi renale e i farmaci che hanno come target l'angiotensina II, principale mediatore del RAS, sono attualmente la terapia più efficace nel ridurre la progressione della malattia renale cronica. E' noto che gli ACE-inibitori (ACEi) inducono un aumento compensatorio della renina plasmatica per la mancaza del feedback negativo sulla sua produzione. Tuttavia, la renina (R) promuove il danno renale non solo stimolando la produzione di ANGII, ma anche up-regolando geni profibrotici attraverso l'attivazione del recettore renina/prorenina. Lo scopo dello studio è stato indagare se l'infusione di MSC riduceva il danno renalein un modello animale di UUO e comparare gli eventuali effetti protettivi di ACEi e MSC in UUO. Abbiamo studiato 5 gruppi di ratti. A: sham operati. B: ratti sottoposti a UUO che ricevevano soluzione salina. C: ratti sottoposti a UUO che ricevavano MSC 3X106 nella vena della coda al giorno 0. D:ratti sottoposti a UUO che ricevevano lisinopril dal g 1 al g 21. E: ratti sottoposti a UUO che ricevevano MSC 3X106 nella vena della coda al giorno 0 e lisinopril dal g 1 al g 21. I ratti sono stati sacrificati al giorno 7 e 21. I risultati dello studio mostrano che MSC in UUO prevengono l'aumento della renina, riducono la generazione di ANGII e che in terapia combinata con ACEi riducono ulteriormente l'ANGII, determinando una sinergia nel miglioramento della fibrosi renale. / Mesenchymal stromal cells (MSC) are multipotent cells with immunomodulant and anti-inflammatory effect. Several studies have shown MSC beneficial effect in acute kidney injury but are not yet known MSC effects in chronic kidney disease. Unilateral ureteral obstruction (UUO) is a model of renal interstitial fibrosis, the final common pathway for progressive renal diseases where the activation of vasoactive molecules, inflammatory and profibrotic cytokines plays a pathogenetic role in the development of cell apoptosis and tubular atrophy. Renin-angiotensin system (RAS) plays a pivotal role in renal fibrosis and agents that target angiotensin II, principal mediator of RAS, are the most effective therapy to reduce progression of chronic kidney disease. Its known that angiotensin-converting enzyme inhibitors (ACEi) induce a compensatory increase in plasma renin levels because of the disruption of the negative feedback of its production. However renin (R) promotes renal injury not only by stimulating angiotensin II (ANG II) generation, but also up-regulating pro-fibrotic genes through renin/prorenin receptor activation. The aim of the study was to investigate whether MSC infusion attenuate renal injury in a rat model of UUO and to compare the protective effects of ACEi and MSC in UUO. We studied 5 groups of rats. A: rats sham operated. B: rats UUO received saline solution on day 0 (vehicle control). C: rats UUO received MSC 3X106 on day 0 via tail vein. D: rats UUO received lisinopril from d 1 to 21. E: rats UUO received MSC on d 0, and lisinopril from d 1 to 21. Rats were sacrified on d 7 and 21. Our results show that MSC in UUO rat model prevent renin increase, reduce angiotensin II generation and in combination therapy with ACEi suppress further angiotensin II block, thereby lead to a synergy in ameliorating renal fibrosis.