Background: Living kidney donation, while generally safe with proper candidate selection, is not entirely risk-free. Predicting the risk of long-term complications appears particularly difficult for candidates classified as “marginal”, namely those with suboptimal demographic or clinical features. Glomerular Filtration Rate (GFR) measurement, namely the primary parameter used to assess eligibility for donation, does not provide comprehensive information to adequately estimate the risk of future adverse events, especially when its value is not entirely within the normal range; it may, however, reflect a potential decline in Renal Functional Reserve (RFR). Given the growing tendency to include marginal candidates in donor lists, it is necessary to develop new risk assessment methods. A promising approach seems to be the preoperative assessment of RFR, which is the kidney's capacity to increase GFR in response to greater functional demands: assessing the renal response to stressors can help predict the compensatory capacity following a potential nephrectomy, improving the analysis of the risk of complications in both the donor and the recipient. In addition, estimating the donor's RFR can improve the prediction of the recipient's outcome. Unfortunately, the application of RFR measurement in clinical practice has been hindered so far by its complexity and the cost of the available tests, which are mainly based on the oral load of animal proteins. Recently, a simple, practical, and cost-effective method for measuring RFR has been validated: the Intra-parenchymal Renal Resistive Index Variation (IRRIV) test, which consists of inducing a stimulus by increasing abdominal pressure and measuring the renal response through parenchymal hemodynamic variations using color Doppler ultrasound. In clinical practice, this test is performed by conducting the so-called Renal Stress Test (RST). Objective of the study: To evaluate the feasibility and technical or clinical complications of using the IRRIV test to measure RFR in living kidney donors pre- and post-nephrectomy through the administration of the RST. To estimate the sample size required for a future, larger study on the use of the IRRIV test for measuring RFR in kidney donors. To evaluate the variation in test results 12 months after the procedure and compare it with the variation in eGFR and serum creatinine levels. Material and methods: The project is a prospective observational cohort pilot study with a sample consisting of 11 healthy living kidney donors. The participants underwent the RST with the IRRIV test the day before the donation and 12 months later. At the same time points, serum creatinine levels were measured and eGFR was calculated using the CKD-EPI formula. Results: No technical difficulties or clinical complications, nor discomfort, were encountered during the execution of the RST. Twelve months after nephrectomy, a significant mean increase in serum creatinine levels and a significant mean decrease in eGFR were observed, while only one of the four parameters assessed in the RST showed a statistically significant variation. A sample size of 48 subjects was estimated for a future study. Conclusions: The pilot study confirmed the feasibility, practicality, and safety of the RST in living kidney donors. The small sample size likely affected the study's power, leading to results that are not unequivocally interpretable. A future study with a sample of 48 subjects may better clarify the ability of the RST to measure changes in RFR following kidney donation.
Presupposti dello studio: La donazione di rene da vivente, per quanto generalmente sicura con un’adeguata selezione dei candidati, non è del tutto esente da rischi. Predire il rischio di complicanze nel lungo termine appare particolarmente difficile per i candidati definiti “marginali”, ovvero con caratteristiche demografiche o cliniche non ottimali. La misurazione del Glomerular Filtration Rate (GFR), principale parametro utilizzato per valutare l’eleggibilità alla donazione, non fornisce informazioni esaustive per un’adeguata stima del rischio di futuri eventi avversi, soprattutto quando il suo valore non risulta completamente nel range di normalità; essa può tuttavia esprimere una potenziale riduzione della Riserva Funzionale Renale (RFR). Data la crescente tendenza a includere candidati marginali nelle liste dei donatori, si rende necessario lo sviluppo di nuovi mezzi di valutazione del rischio. Un promettente strumento sembra essere la quantificazione preoperatoria della RFR, ovvero della capacità di aumentare il GFR in risposta a un’aumentata richiesta funzionale: valutare la reazione renale a fattori stressogeni può aiutare a predire la capacità di compenso dopo un’eventuale nefrectomia, migliorando l’analisi del rischio di complicanze sia nel donatore che nel ricevente. In aggiunta, la stima della RFR del donatore può migliorare la predizione dell’outcome del ricevente. Purtroppo, l’impiego della misurazione della RFR nella pratica clinica è stato finora ostacolato dalla sua complessità e dal costo dei test disponibili, basati principalmente sul carico orale di proteine animali. Recentemente è stata validata una metodica semplice, pratica ed economica per la valutazione della RFR: l’Intra-parenchymal Renal Resistive Index Variation (IRRIV) test, che prevede l’induzione di uno stimolo aumentando la pressione addominale e la quantificazione della risposta renale misurando le variazioni emodinamiche parenchimali tramite ecocolorDoppler. Nella pratica clinica tale test viene condotto eseguendo il cosiddetto Renal Stress Test (RST). Scopo dello studio: Valutare fattibilità e complicanze tecniche o cliniche dell’applicazione dell’IRRIV test per la misurazione della RFR in donatori di rene viventi pre- e post-nefrectomia mediante somministrazione dell’RST. Stimare la numerosità campionaria necessaria per un futuro studio più ampio sull’uso dell’IRRIV test per la misurazione della RFR nei donatori di rene. Valutare la variazione dei risultati del test a 12 mesi dall’operazione e confrontarla con la variazione di eGFR e creatininemia. Materiali e metodi: Il progetto consiste in uno studio pilota di tipo osservazionale prospettico di coorte, con campione rappresentato da 11 donatori di rene viventi sani. I partecipanti sono stati sottoposti a un RST con effettuazione dell’IRRIV test il giorno precedente la donazione e dopo 12 mesi da essa. Negli stessi periodi sono stati valutati creatininemia ed eGFR con formula CKD-EPI. Risultati: Non sono state riscontrate difficoltà tecniche o complicanze cliniche né discomfort durante l’esecuzione dell’RST. A 12 mesi dalla nefrectomia sono stati riscontrati un significativo incremento medio della creatininemia e una significativa riduzione media dell’eGFR, mentre solo uno dei quattro parametri valutati nell’RST ha mostrato una variazione statisticamente significativa. È stata stimata una numerosità campionaria di 48 soggetti per un futuro studio. Conclusioni: Lo studio pilota ha confermato fattibilità, praticità e sicurezza dell’RST nei donatori di rene. La ridotta numerosità campionaria ha verosimilmente inficiato la potenza dello studio, traducendosi in risultati non univocamente interpretabili. Un futuro studio con campione di 48 soggetti potrà meglio chiarire la capacità o meno dell’RST di misurare la variazione di RFR a seguito di una donazione di rene.
Il renal stress test nella valutazione della riserva funzionale renale nel trapianto da donatore vivente: validazione del protocollo di studio.
CARRARO, LUCA
2023/2024
Abstract
Background: Living kidney donation, while generally safe with proper candidate selection, is not entirely risk-free. Predicting the risk of long-term complications appears particularly difficult for candidates classified as “marginal”, namely those with suboptimal demographic or clinical features. Glomerular Filtration Rate (GFR) measurement, namely the primary parameter used to assess eligibility for donation, does not provide comprehensive information to adequately estimate the risk of future adverse events, especially when its value is not entirely within the normal range; it may, however, reflect a potential decline in Renal Functional Reserve (RFR). Given the growing tendency to include marginal candidates in donor lists, it is necessary to develop new risk assessment methods. A promising approach seems to be the preoperative assessment of RFR, which is the kidney's capacity to increase GFR in response to greater functional demands: assessing the renal response to stressors can help predict the compensatory capacity following a potential nephrectomy, improving the analysis of the risk of complications in both the donor and the recipient. In addition, estimating the donor's RFR can improve the prediction of the recipient's outcome. Unfortunately, the application of RFR measurement in clinical practice has been hindered so far by its complexity and the cost of the available tests, which are mainly based on the oral load of animal proteins. Recently, a simple, practical, and cost-effective method for measuring RFR has been validated: the Intra-parenchymal Renal Resistive Index Variation (IRRIV) test, which consists of inducing a stimulus by increasing abdominal pressure and measuring the renal response through parenchymal hemodynamic variations using color Doppler ultrasound. In clinical practice, this test is performed by conducting the so-called Renal Stress Test (RST). Objective of the study: To evaluate the feasibility and technical or clinical complications of using the IRRIV test to measure RFR in living kidney donors pre- and post-nephrectomy through the administration of the RST. To estimate the sample size required for a future, larger study on the use of the IRRIV test for measuring RFR in kidney donors. To evaluate the variation in test results 12 months after the procedure and compare it with the variation in eGFR and serum creatinine levels. Material and methods: The project is a prospective observational cohort pilot study with a sample consisting of 11 healthy living kidney donors. The participants underwent the RST with the IRRIV test the day before the donation and 12 months later. At the same time points, serum creatinine levels were measured and eGFR was calculated using the CKD-EPI formula. Results: No technical difficulties or clinical complications, nor discomfort, were encountered during the execution of the RST. Twelve months after nephrectomy, a significant mean increase in serum creatinine levels and a significant mean decrease in eGFR were observed, while only one of the four parameters assessed in the RST showed a statistically significant variation. A sample size of 48 subjects was estimated for a future study. Conclusions: The pilot study confirmed the feasibility, practicality, and safety of the RST in living kidney donors. The small sample size likely affected the study's power, leading to results that are not unequivocally interpretable. A future study with a sample of 48 subjects may better clarify the ability of the RST to measure changes in RFR following kidney donation.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/78888