P1441SURVIVAL AND RESIDUAL KIDNEY FUNCTION IN HEMODIALYSIS PATIENTS TREATED WITH HIGH DOSES OF FUROSEMIDE. A PROSPECTIVE LONG TERM STUDY
Authors: Siga Esteban , Alcuaz Romina , Nozzi Eduardo , Melon Gil Eugenia , Vivas Nora , Aiziczon David 
Published: June 2020

Abstract

Background and Aims
Many patients (PTS) starting dialysis have significant residual kidney function (RKF), with 45 % having an estimated glomerular filtration rate ≥10 mL/min/1.73 m2 . Preservation of this residual kidney function has been associated with improved outcomes, and nephrologists should try to preserve this residual kidney function as long as possible. In this setting, furosemide (FURO) could play an important role but there are no guidelines for its use and, given the need of high doses, there are safety concerns which limit its use. Besides, its long term utility has not been established. In this study, our first aim was to determine an effective and safe dose for incident PTS; and the second was to evaluate its effects on the RKF in the first year and the survival of these PTS in the long term.

Method
Protocol I: cross-over, single blind study, consisting of three weekly periods. During the first week (W1), after signing an informed consent, PTS were randomly assigned to receive 250 (F250) or 500 (F500) mg.of oral FURO once a day. W2 was a washout period and patients received placebo (F0). During the third week, the remaining dose was prescribed. At the end of each W, total urinary volume and Natriuresis of 24 hours was measured. All Capsules were identical, made by the Hospital´s Pharmacist, and PTS were not aware of their content.
Protocol II: prospective, open label, long term study. Daily diuresis was measured In all Incident PTS from 01/01/11 to 01/06/19. Those PTS with daily diuresis lower than 200 ml. were the control sample. Those with higher than 200 ml.day, after signing an informed consent, received 500 mg. of oral FURO once a day. At the beginning and the end of the FURO period, 24 hours diuresis was colected to measure volume and Na, K y P. In some PTS, Beta 2 seric microglobulin (B2M) was also measured. All PTS ( n = 101 ) were followed until their obitus, or were censored by transplant, change of centre or completion of the follow up period = 4 years.

Results
Protocol I: n= 34. Basal diuresis (F0) was 970 ml.day. Effect of F250 and F500 on diuresis was similar. Both increased 24 hs urinary volumen by 30%. By contrast, the increase of Sodium excretion was significantly higher with F500 than with F250: 56 vs 7%, P =0.000
Protocol II: The table shows the long term effect (11.8 +/- 4.7 months) of 500 mg. once a day of oral FURO in 33 incident PTS (8 DBT, 8 women). Data are presented as median and interquartil range (IR).
In the first year of HD, FURO was able to maintain the basal diuresis and the median excretion of P. Noteworthy, Natriuresis increased by 29%. Seric B2M was asociated with diuresis: r = -0.59, and was significantly lower than B2M measured in control PTS: 36.7 vs. 48.1 mg.dl (P = 0.011).
FURO and Control PTS were followed up to four years. Kaplan Meier analisis ( Figure ) ilustrated that survival in FURO PTS was 96, 90,5 and 73,5 % at 2, 3 and 4 years, respectively, whereas In control PTS it was 76, 65 and 53 %. (P = 0.042, logrank test ).
Four PTS stopped FURO ingestion before six months and were excluded. One due to cramps and three by cutaneous manifestations. All symptoms remitted when Furosemide was suspended. No patient reported hearing impairments

Conclusion
Results of this long term prospective study suggest that Furosemide is effective to maintain RKF in the first year of HD, without major adverse effects. Furthermore, survival was significantly higher in those PTS that ingested Furosemide