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LV End-Diastolic Pressure vs. Urine Flow Rate–Guided Hydration in Preventing AKI
Quick Takes
- This study demonstrated lower risk of contrast-associated acute kidney injury following coronary and peripheral angiograms and interventions with a urine flow-guided IV hydration strategy, as opposed to a LVEDP-guided strategy.
- Patients in the urine flow-guided group received a mean ~2.6L IV normal saline plus protocol-driven furosemide, while those in the LVEDP-guided group received ~1.7L IV normal saline plus furosemide only for pulmonary congestion or low urine output.
Study Questions:
For intravenous (IV) hydration to prevent contrast-associated acute kidney injury (CA-AKI), which guiding strategy is superior: one based on left ventricular end-diastolic pressure (LVEDP) or one based on urine flow rate (UFR)?
Methods:
This randomized, unblinded trial (REMEDIAL III [REnal Insufficiency Following Contrast MEDIA Administration triaL III]) was conducted at four Italian centers from July 2015 to June 2019. Funding was provided by Guerbet, a France-based manufacturer of contrast agents. All consecutive patients scheduled for coronary or peripheral angiography or angioplasty with estimated glomerular filtration rate (eGFR) ≤45 ml/min/1.73 m2 or at high risk for CA-AKI (Mehran’s score ≥11 or Gurm’s score >7%) were eligible. Patients were assigned in 1:1 ratio to LVEDP-guided and UFR-guided groups. LVEDP was estimated noninvasively based on transmitral flow velocity to mitral annular velocity ratio (E/e’), obtained from transthoracic echocardiography, before starting IV hydration.
In the LVEDP-guided group, IV normal saline was started 1 hour prior to the angiographic procedure and continued until 4 hours post-procedure. Fluid rate was determined by echo-estimated LVEDP and adjusted at the time of invasive LVEDP measurement. IV furosemide administration was permitted to treat pulmonary congestion or urine output <0.5 ml/kg/h.
In the UFR-guided group, the RenalGuard System (PLC Medical Systems, Franklin, MA) was used. This system measures urine output, requiring a Foley catheter, and replaces it in real time with an equal volume of IV saline. A priming bolus of normal saline was given, and physician-prescribed furosemide was given to achieve UFR ≥300 ml/h and ≥450 ml/h intraprocedurally, with continuation until 4 hours post-procedure.
The primary endpoint was a composite of CA-AKI (serum creatinine increase ≥25% or ≥0.5 mg/dl at 48 hours after contrast administration) and acute pulmonary edema (clinical diagnosis, within 24 hours of IV fluid initiation).
Results:
A total of 708 patients were randomized. Mean age was 74 ± 8 years in both groups. Mean LVEDP in both groups was 14 ± 7 mm Hg. Mean contrast volume was 72 ± 49 ml in the LVEDP-guided group and 67 ± 47 ml in the UFR-guided group (p = 0.18). The total IV hydration volume was greater in the UFR-guided group (2598 ± 1349 ml vs. 1709 ± 1116 ml; p < 0.001). Diuresis was greater in the UFR-guided group at 24 hours (2999 ± 592 ml vs. 1864 ± 761 ml; p < 0.001). In the UFR-guided group, mean total furosemide dose was 23 ± 17 mg; this was not reported for the LVEDP-guided group.
Based on a per-protocol analysis, the primary endpoint occurred in 20/351 patients (5.7%) of the UFR-guided group and 36/351 patients (10.3%) of the LVEDP-guided group (relative risk [RR], 0.56; 95% confidence interval [CI], 0.39-0.79; p = 0.036). Pulmonary edema occurred in one patient (0.3%) in the UFR-guided group and seven patients (2%) in the LVEDP-guided group (RR, 0.07; 95% CI, 0.02-1.16; p = 0.069). Based on an intention-to-treat analysis, at 1 month post-procedurally, major adverse events occurred in 25/353 patients (7.1%) in the UFR-guided group and 43/355 patients (12%) in the LVEDP-guided group (RR, 0.59; 95% CI, 0.33.0.94; p = 0.030). Progression of kidney disease, including dialysis and sustained kidney injury (GFR reduction ≥25% at 1 month), occurred in 19/353 patients (5.4%) in the UFR-guided group and in 36/355 patients (10.1%) in the LVEDP-guided group (RR, 0.54; 95% CI, 0.29-0.91; p = 0.036).
In the UFR-guided group, three patients (0.8%) experienced complications related to Foley insertion (hematuria and pain on micturition). Hypokalemia was more common in the UFR-guided group (6.2% vs. 2.3%, RR, 2.70; 95% CI, 1.21-6.37; p = 0.013).
Conclusions:
This study demonstrated lower risk of CA-AKI following coronary and peripheral angiograms and interventions with a UFR-guided IV hydration strategy, as opposed to a LVEDP-guided strategy. Patients in the UFR-guided group received markedly larger amounts of IV normal saline as well as protocol-specified furosemide and produced larger volumes of urine. Urinary tract complications were uncommon, although the UFR-guided group experienced more hypokalemia.
Perspective:
This manuscript challenges the LVEDP-guided IV hydration strategy championed by the POSEIDON trial (Brar SS, et al., Lancet 2014;383:1814-23). As patients in the LVEDP-guided group did not have urinary catheters, urine output measurements were likely less precise than in the UFR-guided group, and furosemide administration was probably less common; these factors could explain the higher incidence of pulmonary edema in the LVEDP-guided group. An unanswered question is how an algorithm using both urine output and invasively measured LVEDP to guide IV fluid administration, perhaps with relatively generous use of IV loop diuretics, would compare with the strategies presented here. Use of the RenalGuard System would be impractical for urgent and emergent interventions, and patient preference to avoid a urinary catheter would also preclude its use.
Clinical Topics: Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Statins, Acute Heart Failure, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging
Keywords: Acute Kidney Injury, Angiography, Angioplasty, Contrast Media, Coronary Angiography, Creatinine, Echocardiography, Furosemide, Diagnostic Imaging, Geriatrics, Glomerular Filtration Rate, Heart Failure, Hematuria, Hypokalemia, Myocardial Ischemia, Pulmonary Edema, Renal Dialysis, Secondary Prevention, Sodium Potassium Chloride Symporter Inhibitors, Urinary Catheters, Urination, Vascular Diseases
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