Table 2.

Hazard ratios for incident CKD Stage ≥4 and eGFR decline by >40% based on rates of change in measures of volume overload

Marker of Volume Overload		Continuous	Quartile 1 Least rapid decongestion	Quartile 2	Quartile 3	Quartile 4 Most rapid decongestion
CKD Stage ≥4
BNP Per 6% decrease per week	N	2128	535	525	527	541
	Event	170	53	54	48	15
	FU time (y)	1429	302	347	387	394
	Rate (100py)	11.9	17.6	15.6	12.4	3.8
	Unadjusted	0.69 (0.61, 0.79)	1.00 (1.00, 1.00)	0.86 (0.59, 1.26)	0.68 (0.46, 1.01)	0.21 (0.12, 0.38)
	Adjusted	0.68 (0.58, 0.79)	1.00 (1.00, 1.00)	0.91 (0.62, 1.35)	0.68 (0.45, 1.03)	0.25 (0.14, 0.45)
NT-proBNP Per 12% decrease per week	N	1049	232	261	273	283
	Event	123	39	40	28	16
	FU time (y)	1250	221	283	350	396
	Rate (100py)	9.8	176	14.1	8.0	4.0
	Unadjusted	0.64 (0.55, 0.76)	1.00 (1.00, 1.00)	0.81 (0.52, 1.26)	0.43 (0.26, 0.70)	0.23 (0.13, 0.41)
	Adjusted	0.71 (0.58, 0.88)	1.00 (1.00, 1.00)	0.89 (0.56, 1.41)	0.62 (0.37, 1.06)	0.35 (0.18, 0.68)
Congestion Score Per 1 point decrease per week	N	3071	774	779	772	746
	Event	282	72	56	80	74
	FU time (y)	2497	559	667	645	624
	Rate (100py)	11.3	12.9	8.4	12.4	11.9
	Unadjusted	0.99 (0.87, 1.12)	1.00 (1.00, 1.00)	0.65 (0.46, 0.92)	0.95 (0.69, 1.31)	0.89 (0.64, 1.24)
	Adjusted	0.82 (0.71, 0.94)	1.00 (1.00, 1.00)	0.61 (0.43, 0.87)	0.66 (0.47, 0.92)	0.59 (0.41, 0.86)
eGFR Decline by >40%
BNP Per 6% decrease per week	N	2357	589	590	589	589
	Event	133	42	41	33	17
	FU time (y)	1591	330	393	434	432
	Rate (100py)	8.4	12.7	10.4	7.6	3.9
	Unadjusted	0.69 (0.59, 0.80)	1.00 (1.00, 1.00)	0.75 (0.49, 1.16)	0.53 (0.34, 0.85)	0.29 (0.16, 0.50)
	Adjusted	0.68 (0.57, 0.80)	1.00 (1.00, 1.00)	0.65 (0.42, 1.02)	0.54 (0.34, 0.87)	0.31 (0.17, 0.56)
NT-proBNP Per 12% decrease per week	N	1188	297	297	297	297
	Event	135	46	34	34	21
	FU time (y)	1401	270	335	372	424
	Rate (100py)	9.6	17.0	10.2	9.1	5.0
	Unadjusted	0.67 (0.58, 0.78)	1.00 (1.00, 1.00)	0.58 (0.37, 0.90)	0.47 (0.30, 0.74)	0.26 (0.16, 0.44)
	Adjusted	0.74 (0.63, 0.88)	1.00 (1.00, 1.00)	0.65 (0.41, 1.03)	0.55 (0.34, 0.90)	0.30 (0.17, 0.53)
Congestion Score Per 1 point decrease per week	N	3412	853	853	853	853
	Event	247	63	51	62	71
	FU time (y)	2787	627	728	721	710
	Rate (100py)	8.9	10.0	7.0	8.6	10.0
	Unadjusted	0.96 (0.84, 1.09)	1.00 (1.00, 1.00)	0.64 (0.45, 0.93)	0.78 (0.55, 1.11)	0.88 (0.62, 1.24)
	Adjusted	0.81 (0.69, 0.94)	1.00 (1.00, 1.00)	0.61 (0.42, 0.88)	0.60 (0.42, 0.87)	0.58 (0.39, 0.86)

Cause-specific hazard modeling for slope of markers of volume overload during hospitalization for AHF. Hazard ratios are interpreted per each standard deviation of slope per week (i.e., for BNP, standard deviation of slope was 6% decrease per week), allowing for some uniformity across the different variables of rates of change in decongestion. BNP and NT-proBNP are transformed on the log scale, enabling hazard ratios to be interpreted per percent decrease per week. Hazard ratios for slope of congestion score (range 0 to 12, with higher score indicative of greater congestion) are per every 1 point decrease per week.

Adjusted: Adjusted for age, sex, race, randomization group (tolvaptan vs placebo), BMI, medication use (ACEI or ARB, MRA), ejection fraction, New York Heart Association functional class, systolic blood pressure, eGFR at discharge and respective baseline biomarker level.

Abbreviations: BNP, b-type natriuretic peptide; NT-proBNP: N-terminal pro b-type natriuretic peptide; BMI, body mass index; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; MRA, mineralocorticoid receptor antagonist; eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease, FU time (y), total follow-up time in years, 100py, 100 person-years