Il nostro studio è stato pensato come un lavoro preliminare a un’applicazione universale in tutti i reparti, all’interno dello Stabilimento Ospedaliero, che inviino i loro pazienti ad eseguire esami radiologici con MdC in elezione. In tema nefro-protezione sarebbe importante iniziare a valutare il RIPC come procedura preventiva routinaria, da affiancare a quelle già attualmente in protocollo.
Un aspetto sicuramente importante, da non trascurare in tempi di spending review, è il basso costo della procedura, praticamente nullo se si esclude la “manodopera” per eseguire il RIPC.
La strada per la regolamentazione e l’inclusione in un protocollo preventivo è sicuramente lunga, il nostro primo passo sarà quello di intraprendere ulteriori studi su campioni più numerosi, randomizzati ed in doppio cieco per stabilirne l’effettivo valore in clinica.
In comune accordo con la U.O. di Radiologia Interventistica vogliamo intraprendere uno studio che indaghi l’efficacia del RIPC nella prevenzione della CIN in pazienti sottoposti a procedure angiografiche.
Ci troveremo di fronte a pazienti che ricevono dosi massicce di MdC, in cui la preservazione della funzionalità renale rappresenta un endpoint primario nell’evoluzione clinica di questi individui.
Come detto in precedenza si tratterà di uno studio randomizzato in doppio cieco, in cui oltre all’incidenza della CIN, e altri aspetti già presi in esame in questo primo studio, si valuterà l’outcome del RIPC in termini di:
• durata del ricovero in ospedale; • mortalità ospedaliera o a 30 giorni;
• necessità di terapia renale sostitutiva(emodialisi).
Valuteremo attentamente ogni possibile influenza negativa del RIPC, che comunque è un’ischemia/riperfusione della durata complessiva di 30 minuti (ad esempio potrebbe
indurre variazioni della pressione arteriosa), nonostante in letteratura si parli di un procedimento totalmente innocuo, scevro da complicazioni.
Quando abbiamo parlato dei marker esaminati, si sono evidenziati anche i limiti
dell’utilizzo della Creatinina, come la scarsa tendenza ad elevarsi precomente. Esistono oggi dei marker più precisi per individuare un danno acuto e sono: NGAL, Cistatina C,
β-trace, Beta2-microglobulina.
- NGAL
“Lipocalina granulocitaria associata a gelatinasi o siderocalina o lipocalina2(LCN2)”
E’ noto che i livelli della molecola possono risultare elevati anche in malattie sistemiche non necessariamente associate a processi infettivi, confermando così che molti tessuti possono rilasciare NGAL come fattore di fase acuta che segnala una
condizione di danno .
Nelle prime due ore che seguono un danno acuto renale, come quello inevitabilmente indotto dal passaggio del MdC i livelli di NGAL si dovrebbero innalzare sia a livello sierico sia urinario. Si tratta di una molecola piccola e resistente pertanto facilmente rilevabile nel campione urinario. L’aumento di NGAL in diversi studi è risultato proporzionale al livello di Acute Kidney Injury(AKI) riscontrato in diverse popolazioni di pazienti. Uno stretto monitoraggio di tale marker consente la precoce identificazione di eventuale AKI, l’impostazione e applicazione tempestiva di misure terapeutiche atte a contrastarlo e, in ultima analisi, ha la potenzialità di ridurre la mortalità e la morbidità ad esso associate[127].
Per tutti questi motivi riteniamo utile adottare NGAL come indice di danno ischemico renale da MdC e valutarne le differenti cinetiche in pazienti sottoposti o meno a RIP.
- CISTATINA-C
“Cistatina 3 o gamma-trace o post-gamma-globulin o neuroendocrine basic polipeptide”.
Codificata dal gene CST3, la Cistatina-C è una piccola molecola del peso molecolare di 13.3 kD nota per la sua utilità come biomarker d’insufficienza renale.
Per quanto riguarda la funzionalità renale il vantaggio dell’uso di tale biomarker è dato dal fatto che si dimostra relativamente indipendente da età, sesso, etnia e massa muscolare del paziente laddove comparato alla creatininemia sierica [128]. Inoltre la Cistatina-C è in grado di dare una buona stima del rischio di sviluppo di malattia renale cronica segnalando un eventuale stato di disfunzione renale preclinica [129]. E’ stato visto che è utile dosarla soprattutto nelle urine. In condizioni normali nelle urine la Cistatina-C dovrebbe essere assente: una concentrazione elevata di Cistatina-C nelle urine potrebbe indicare un danno all’epitelio tubulare; è stata quindi proposta come un marcatore urinario addizionale di danno renale acuto(AKI) [129].
- β-TRACE
“Prostaglandin-H2D-isomerase(PTDGS)” Appartiene alla stesse superfamiglia di NGAL.
Nella pratica clinica se ne fa uso per segnalare liquorrea, quindi nel campo del trauma cranico.
Secondo uno studio dell’Università di Tokyo pubblicato nel 2001 su Nephron, la β- trace urinaria s’innalza già negli stadi precoci del diabete mellito in funzione del
nefrologico di questo marker viene poi confermato da Hoffmann et al. [131], che riscontrarono elevate livelli di β-trace in pazienti con compromissione, anche lievissima, della funzione renale. Ulteriori studi ne hanno verificato l’attendibilità nella valutazione della funzione renale in pazienti cronicamente compromessi da tale punto di vista [129].
Nell’ambito del nostro studio appare dunque rilevante studiarne il trend nel periodo post-MdC ponendo dei confronti con le oscillazioni del similare NGAL e con la presenza o meno di RIP.
- β2-MICROGLOBULINA(B2M)
Fondamentale molecola del sistema maggiore d’istocompatibilità di tipo 1(MHC 1) presente su tutte le cellule nucleate e codificata dall’omonimo gene.
A livello renale è stato studiato il ruolo di questa proteina nel danno renale iatrogenicamente indotto(Dieterle et al., 2010 [132] )e nel monitoraggio della funzione glomerulare in popolazione pediatrica con affezioni croniche (Herrero- Morin et al., 2007 ).
L’adozione di questi nuovi marker, al fianco di quelli tradizionali, ci permetterà di valutare in maniera più approfondita la risposta renale acuta al MdC dopo l’applicazione del RIPC.
Un altro nostro obiettivo sarà analizzare le possibili interazioni dei farmaci con i mediatori del RIPC, evidenziando sinergismi o antagonismi, questo perché il nostro primo studio ha prodotto dei risultati incerti da questo punto di vista, anche alla luce del numero di pazienti esaminati, non ampio a sufficienza per raggiungere una significatività statistica.
gonfiaggio/sgonfiaggio manuale del bracciale della pressione con un dispositivo elettronico automatico. Lo strumento è attualmente in progettazione, la sua introduzione in tempi brevi permetterà uno svolgimento più preciso e meno difficoltoso della procedura di precondizionamento, da parte del personale medico e paramedico in ambito ospedaliero; e in un futuro forse nemmeno troppo lontano sarà possibile per il paziente effettuare la procedura comodamente a casa, sfruttando tutti quelli che sono i benefici del Precondizionamento, anche per situazioni di vita quotidiana che esulano dall’esecuzione di esami radiologici con MdC.
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