Table 3.

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

Measures of hemoconcentration		Continuous	Quartile 1 Least rapid decongestion	Quartile 2	Quartile 3	Quartile 4 Most rapid decongestion
CKD Stage ≥4
Hematocrit Per 1% increase per week	N	2885	736	730	708	711
	Event	250	60	60	83	47
	FU time (y)	2344	553	603	598	590
	Rate (100py)	10.7	10.9	9.9	13.9	8.0
	Unadjusted	0.90 (0.79, 1.02)	1.00 (1.00, 1.00)	0.92 (0.64, 1.31)	1.27 (0.91, 1.77)	0.73 (0.50, 1.07)
	Adjusted	0.73 (0.64, 0.84)	1.00 (1.00, 1.00)	0.61 (0.43, 0.89)	0.66 (0.46, 0.95)	0.47 (0.31, 0.69)
Albumin Per 0.1 g/dL increase per week	N	3067	781	775	754	757
	Event	274	63	66	79	66
	FU time (y)	2499	611	674	602	612
	Rate (100py)	11.0	10.3	9.8	13.1	10.8
	Unadjusted	1.00 (0.89, 1.12)	1.00 (1.00, 1.00)	0.95 (0.67, 1.34)	1.27 (0.91, 1.77)	1.05 (0.74, 1.48)
	Adjusted	0.72 (0.63, 0.82)	1.00 (1.00, 1.00)	0.76 (0.53, 1.08)	0.56 (0.39, 0.80)	0.43 (0.30, 0.64)
Total Protein Per 0.1 g/dL increase per week	N	3113	796	764	776	777
	Event	281	63	61	81	76
	FU time (y)	2536	608	639	648	641
	Rate (100py)	11.1	10.4	9.6	12.5	11.9
	Unadjusted	1.00 (0.89, 1.13)	1.00 (1.00, 1.00)	0.92 (0.65, 1.31)	1.20 (0.86, 1.67)	1.14 (0.82, 1.60)
	Adjusted	0.72 (0.62, 0.83)	1.00 (1.00, 1.00)	0.63 (0.43, 0.91)	0.63 (0.43, 0.92)	0.50 (0.34, 0.75)
eGFR Decline by >40%
Hematocrit Per 1% increase per week	N	3196	799	799	799	799
	Event	227	54	52	71	50
	FU time (y)	2606	603	665	675	664
	Rate (100py)	8.7	9.0	7.8	10.5	7.5
	Unadjusted	0.96 (0.84, 1.09)	1.00 (1.00, 1.00)	0.83 (0.57, 1.22)	1.11 (0.78, 1.58)	0.81 (0.55, 1.20)
	Adjusted	0.82 (0.71, 0.95)	1.00 (1.00, 1.00)	0.77 (0.53, 1.14)	0.72 (0.49, 1.06)	0.59 (0.40, 0.88)
Albumin Per 0.1 g/dL increase per week	N	3406	851	852	852	851
	Event	245	63	62	61	59
	FU time (y)	2783	679	737	679	687
	Rate (100py)	8.8	9.3	8.4	9.0	8.6
	Unadjusted	1.00 (0.88, 1.13)	1.00 (1.00, 1.00)	0.88 (0.62, 1.25)	0.95 (0.67, 1.36)	0.93 (0.65, 1.32)
	Adjusted	0.81 (0.71, 0.93)	1.00 (1.00, 1.00)	0.76 (0.53, 1.08)	0.59 (0.40, 0.86)	0.52 (0.35, 0.77)
Total Protein Per 0.1 g/dL increase per week	N	3465	866	866	867	866
	Event	251	61	64	59	67
	FU time (y)	2833	669	726	727	711
	Rate (100py)	8.9	9.1	8.8	8.1	9.4
	Unadjusted	0.97 (0.85, 1.10)	1.00 (1.00, 1.00)	0.94 (0.66, 1.34)	0.84 (0.59, 1.21)	1.00 (0.70, 1.41)
	Adjusted	0.81 (0.70, 0.94)	1.00 (1.00, 1.00)	0.86 (0.60, 1.24)	0.62 (0.41, 0.92)	0.66 (0.44, 0.99)

Cause-specific hazard modeling for slope of markers of hemoconcentration during hospitalization for AHF. Hazard ratios are interpreted per each standard deviation of slope per week (i.e., for hematocrit, standard deviation of slope per week is 1% increase in hematocrit on absolute scale), allowing for some uniformity across the diferent variables of rates of change in decongestion.

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: 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