Novel conservative management of chronic kidney disease via dialysis-free interventions.

AimsDespite several studies reporting similar outcomes for peritoneal dialysis (PD) and hemodialysis (HD), the former is underused worldwide, with a PD prevalence of 15% in Italy. In 2008, the Unit of Nephrology and Dialysis of the Healthcare Trust of the Autonomous Province of Trento implemented a successful PD program which has increased the proportion of PD incident patients from 7 to 47%. We aimed to assess the effect of this extensive use of PD by comparing HD and PD in terms of survival and time-to-transplantation.MethodsA total of 334 HD and 153 PD incident patients were enrolled between January 2008 and December 2014. After screening for exclusion criteria and propensity score matching, 279 HD and 132 PD patients were analyzed. Survival and time-to-transplantation were assessed by competing-risks regression models, using death and transplantation as primary and competing events.ResultsCrude and adjusted regression models for survival revealed the absence of significant differences between HD and PD cumulative incidence functions (subhazard ratio: 1.09, p = 0.62 and 1.34, p = 0.10, respectively). Differently, crude and adjusted regression models for transplantation revealed a lower time-to-transplantation for PD versus HD patients (subhazard ratio: 2.34, p < 0.01, and 2.57, p < 0.01, respectively). The waiting time for placement in the transplant waiting list was longer in HD than PD patients (330 vs. 224 days, p < 0.01).ConclusionsThe extensive use of PD did not lead to any statistically significant difference in mortality. Furthermore, PD was associated with lower time to transplantation. PD may be a viable option for large-scale dialytic treatment in the advanced chronic kidney disease population.

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The mTOR inhibitors (mTORi, mammalian target of rapamycin; sirolimus and everolimus) have been recently introduced in clinical practice to improve the therapeutic strategies for maintenance of organ transplant and to slow down the progression of chronic renal failure, thanks to their good immunosuppressive properties and absence of renal toxicity. Additionally, mTORi have some antineoplastic and cardioprotective effects. At the same time, mTORi have several collateral effects, often dose dependent and generally reversible after cessation or minimization of the drug dosage. In particular, in the last years, sirolimus-associated pulmonary toxicity has been reported. We describe a clinical case of a young woman with a renal transplant, followed at our Renal Transplant Center, hospitalized for fever and cough unresponsive to antibiotic therapy that, at the time of admission in our renal unit, showed a chest CT scan diagnosis compatible with a drug-related organizing pneumonia or interstitial infiltrates (BOOP). Based on the above diagnosis, we decided to significantly reduce the mTORi dosage reaching stable trough level of 2.5–3 ug/L. After few days, we assisted at an improvement of the clinical status, defervescence and reduction of the pulmonary symptoms. Besides, the microbiological and neoplastic laboratory tests performed on bronchial washing were negative. At day 15, a new chest CT showed a significant reduction of multiple parenchyma areas of thickening. After 3 months, the medical conditions have improved with stable renal function. Our case report describes an everolimus-related “lung syndrome” successfully treated with a significant minimization of mTORi dosage. Our experience may be useful to help clinicians treating mTORi-related pulmonary complications.

Gli inibitori di mTOR (mTORi, mammalian target of rapamycin; sirolimus ed everolimus) sono stati introdotti in clinica nel tentativo di migliorare le strategie terapeutiche in corso di trapianto d'organo, garantendo un adeguato potere immunosoppressivo ed evitando la nefrotossicità propria degli inibitori delle calcineurine. Inoltre, nel corso del tempo, è emerso dalla letteratura un buon potenziale antineoplastico e cardioprotettore di questa categoria farmacologica. Comunque, come altri immunosoppressori, tali farmaci sono accompagnati da effetti collaterali, spesso dose dipendenti, reversibili dopo minimizzazione o sospensione del farmaco. A tal proposito, sono sempre più evidenti le segnalazioni di quadri polmonari patologici correlati all'uso degli mTORi. Di seguito viene riportato il caso di una giovane donna nefrotrapiantata, in follow-up presso il nostro Centro e ricoverata per un quadro clinico caratterizzato da febbre e tosse persistente non responsivi alla terapia antibiotica. La TC Torace, al momento della ammissione nel nostro reparto, evidenziava un quadro molto suggestivo di polmonite organizzata o infiltrati interstiziali (BOOP), verosimilmente iatrogeno secondario all'uso cronico di everolimus. Sulla base della suddetta diagnosi abbiamo ridotto significativamente la posologia dell'mTORi raggiungendo trough level stabili di 2.5–3 ug/L. Dopo alcuni giorni dalla modifica terapeutica abbiamo assistito al miglioramento del quadro clinico con la defervescenza della paziente e la riduzione della sintomatologia polmonare. Inoltre, le ricerche microbiologiche e neoplastiche effettuate su broncoaspirato sono risultate negative. In 15^ giornata, la paziente eseguiva una nuova TC Torace di controllo che evidenziava, dopo confronto con la precedente, notevole attenuazione delle multiple aree di addensamento. A distanza di tre mesi, il quadro polmonare è ulteriormente migliorato, la funzionalità renale è stabile e le condizioni cliniche della paziente sono buone. Il nostro caso clinico descrive una verosimile Lung Syndrome correlata all'uso di everolimus risolta soltanto con significativa riduzione della posologia del farmaco. La nostra esperienza potrebbe essere utile per il trattamento delle complicanze polmonari sempre più frequenti nei pazienti nefrotrapiantati trattati con inibitori di mTOR.