**5. Kidney Transplantation**

There is a paucity of literature regarding the application of FST outside of the intensive care setting. The FST has been tested as a predictive tool after kidney transplantation with different approaches regarding timing of administration and furosemide dosage. McMahon et al. [55] published in 2018 a single-center retrospective analysis of a random sample of 200 deceased-donor kidney transplant recipients who received an intraoperative bolus of 100 mg furosemide. Urinary production was measured 2 and 6 h after furosemide administration. The primary outcome was the development of delayed graft function, defined as the need of dialysis within 7 days of transplantation. Authors included as secondary outcomes safety endpoints such as incidence of hypotension or hypokalemia during the first 24 h after the bolus, graft loss, rejection, death with functioning graft or length of hospital stay. Subjects who developed delayed graft function presented a significantly lower urine output 2 and 6 h after FST. A 6-h urinary output <600 mL (which defined FST non-responders) presented an AUC of 0.85 for the development of DGF. Regarding safety-related outcomes, no episodes of hypotension (defined as mean arterial pressure <60 mmHg) or change in plasma potassium levels were observed in the sample. Although FST non-responders showed longer length of in-hospital stay, the rates of graft loss or death were similar between both groups.

The usefulness of FST after kidney transplantation was also studied by Udomkarnjananun et al. [56]. The authors prospectively studied a sample of 59 adult deceased-donor kidney transplant recipients without hypoalbuminemia or surgical complications that required reoperation during the first 24 h after transplantation. Dry weight adjustment was used to ensure euvolemia prior to transplantation. An intravenous bolus dose of 1.5 mg/kg furosemide was administered 3 h after allograft reperfusion. Urinary production was registered for 6 h after the bolus. Each mL of urine produced during the first 24 h was replaced by 1 mL of saline to avoid volume depletion. The primary outcome was incidence of DGF, using the same definition applied by McMahon et al. Mean cumulative urine volume was significantly lower in those who developed DGF compared to that of non-DGF patients. A 4-h cumulative urine output <350 mL presented the highest accuracy to predict DGF with an AUC of 0.94. The FST was the only significant predictor of DGF in multivariate logistic regression analysis. Moreover, FST was the most accurate predictor of DGF when compared to urinary NGAL, resistive index of renal arteries measured by ultrasonography or effective renal plasma flow measured by 99mTc-MAG3 renography.

These two single-center studies show that FST could improve risk stratification in the early post-transplant period, promptly detecting patients with higher risk of DGF who could benefit from an early initiation of therapeutic interventions. FST was a more accurate predictor of DGF than oliguria (defined as a daily urinary production <400 mL) [55], ultrasonography, 99mTc-MAG3 renography or novel biomarkers such as urinary NGAL. The test was also safe and well tolerated, in line with published results in critically ill patients.

However, although these studies provide an interesting starting point for the application of FST as a predictive tool after kidney transplantation they also suffer significant limitations: both were small sized, single-center studies, limiting external validity of results. The analysis by McMahon et al., was a retrospective review, which means exposure or outcome assessment could not be controlled. Furthermore, furosemide dosage had different timing and dosage in both studies. The possibility of volume depletion after transplant surgery and/or obstructive uropathy due to urinary elimination of blood clots, complications which are commonly associated to active bleeding, were not adequately addressed in these studies. Therefore, additional prospective multi-center studies should be planned to analyze if FST could improve risk stratification and patient management after kidney transplantation.
