EFFICACY OF ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR (ARNI) WITH BETA BLOCKERS AND MINERALOCORTICOD RECEPTOR ANTAGONIST(MRA) FOR PREVENTION OF RECURRENT FLASH PULMONARY OEDEMA IN PATIENTIS ON MAINTENANCE HEMODIALYSIS- A PILOT COMPARATIVE STUDY

Recurrent flash pulmonary oedema (RFPE) is a life threatening complication  and a rare manifestation of end-stage renal failure (ESRF); often necessitating frequent  hospitalization and emergency hemodialysis (HD). Pulmonary oedema in ESRF is usually attributed to volume overload. RFPE is commonly described in patients with unilateral or bilateral renal artery stenosis. ARNI therapy has demonstrated benefits in heart failure with reduced ejection fraction (HFrEF) and also in patients with preserved ejection fraction (HFpEF).This study aims to identify potential contributory factors for RFPE and to study the efficacy of ARNI, beta-blockers, and MRA in RFPE

We conducted a single-center, prospective pilot comparative study involving a cohort of 145 patients on maintenance hemodialysis for period of three years from January 2022 to December 2024. All relevant investigations, including echocardiography and  renal ultrasound doppler  were done. From this cohort,16 patients were identified with RFPE; defined  by minimum of 2 episodes of flash pulmonary oedema (FPE) per month  requiring emergency dialysis or hospitalization (Group B). Rest of the the cohort comprised  129 patients without RFPE identified as Group A.  16 patients with RFPE were non randomly allocated in to two treatment arms. 8 patients (Group C) received titrated dose of ARNI, beta-blocker, MRA in addition to nitro glycerin infusion and hemodialysis.  8 patients( Group D) received standard antihypertensive medications, nitro glycerin infusion and hemodialysis as per requirement. Both groups were followed up for 3 months. The primary outcome was assessed by the number of FPE episodes requiring hospitalization or emergency HD and the secondary outcome by all cause mortality at the end of 3 months

A total of 145 patients on hemodialysis during the three year period  were studied . Of these, 16 patients (11.03%) presented with RFPE (Group B), while  129 patients (88,96%)  were without RFPE classified as Group A. Compared to Group A, patients in Group B exhibited more severe  left ventricular hypertrophy (LVH), left ventricular diastolic dysfunction (LVDD),  increased Left ventricular mass index (LVMI) pulmonary arterial hypertension (PAH), and accelerated hypertension on presentation. None of the patients had renal artery stenosis. At the end of 3 months, patients in Group C (8 patients) exhibited less number of FPE episodes and less hospitalizations ( 5 vs 36 Incidence rate ratio (IRR) 7.2 P-value <0.001) and less number of emergency HD compared to Group D (6 vs 42; IRR 7.0;P-value <0.001) 2 patients in Group D died during the study period and none in Group C. No patients in Group C discontinued ARNI due to any side effects. Hyperkalemia was managed with low K dialysate.

Recurrent flash pulmonary oedema is a rare manifestation of ESRF. In this cohort, renal artery stenosis was not identified as a cause for RFPE. Possible contributing factors for RFPE include LVH, LVDD and accelerated hypertension probably secondary to RAAS activation. Volume overload is unlikely to be the cause of RFPE in our cohort of patients. Treatment with ARNI, beta-blockers, and MRA may help to control the episodes of FPE, thereby reducing number of hospitalizations  and the need for more or frequent hemodialysis. ARNI may offer a promising therapeutic strategy for controlling RFPE. Further large scale randomized control trials are warrented.