Evidence based review of management of cardiorenal syndrome type 1

Table 1 Characteristics and main findings of included studies

Ref.	Population	Sample size	Intervention	Duration of follow-up	Main findings
Owan et al[10], 2008	ADHF with renal dysfunction	72	Standard therapy vs standard therapy plus nesiritide (bolus of 0.2 mcg/kg followed by 0.01 mcg/kg per min)	72 h	Nesiritide produced greater reduction in blood pressure and preserved renal function
Bart et al[11], 2012	ADHF with worsened renal function	188	Ultrafiltration therapy vs stepped pharmacologic therapy (intravenous diuretics)	96 h	Stepped pharmacologic-therapy with intravenous diuretics was superior to ultrafiltration
Fedele et al[12], 2014	ADHF and renal impairment	21	Levosimendan (loading dose 6 μg/kg + 0.1 μg/kg per min) for 24 h vs placebo	72 h	Levosimendan improves the laboratory markers of renal function and renal hemodynamic parameters
Chen et al[13], 2013	AHF and renal dysfunction	360	Low dose dopamine (2 μg/kg per min for 72 h) vs low dose nesiritide (0.005 μg/kg per min for 72 h) vs placebo	72 h	Neither low dose dopamine nor low dose nesiritide improved renal function when added to diuretic therapy
Inomata et al[14], 2017	HF with diuretic resistance and renal impairment	81	Additive tolvaptan (≤ 15 mg/d) vs increased furosemide (≤ 40 mg/d)	7 d	Additive tolvaptan increased urine volume compared with patients receiving an increased dose of furosemide
Lannemyr et al[15], 2018	Chronic HF and impaired renal function	32	Levosimendan (loading dose 12 μg/kg + 0.1 μg/kg per min) vs dobutamine (7.5 μg/kg per min) for 75 min	60 mo and 75 mo after treatment	Levosimendan is the preferred inotropic agent compared to dobutamine

ADHF: Acute decompensated heart failure; HF: Heart failure.

Table 2 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		Cystatin C (mg/L)		Weight loss (kg)	Cumulative urine volume (mL)
		Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Mean changes
Nesiritide	Owan et al[10], 2008	1.85 ± 0.71	0.04 ± 0.44	44.8 ± 23.3	-1.3 ± 12.8	NA	NA	-2.75 ± 3.27	NA
	Owan et al[10], 2008 (placebo)	1.65 ± 0.42	0.09 ± 0.25	38.3 ± 16.6	2.4 ± 6.8	NA	NA	-4.25 ± 3.42	NA
	Chen et al[13], 2013	1.65	0.02	NA	NA	1.66	0.07	NA	8574
	Chen et al[13], 2013 (placebo)	1.70	0.02	NA	NA	1.86	0.11	NA	8296

BUN: Blood urea nitrogen; NA: Not available.

Table 3 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		Cystatin C (mg/L)		Weight loss (kg)		Urine output (mL/d)
		Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes
Furosemide	Inomata et al[14], 2017	1.6	0.20 ± 0.27	NA	NA	NA	NA	61	-2.1 ± 2.6	1251 ± 540	79 ± 341

BUN: Blood urea nitrogen; NA: Not available.

Table 4 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		Cystatin C (mg/L)		GFR (mL/min)		Urine output (mL/d)
		Baseline	72 h	Baseline	72 h	Baseline	72 h	Baseline	72 h	Baseline	72 h
Levosimendan	Fedele et al[12], 2014	1.76 ± 0.37	1.51 ± 0.5	45.08 ± 22.19	33.14 ± 16.63	2577.5 ± 700.6	2083 ± 731.4	38.71 ± 7.94	53.34 ± 14.93	1766.4 ± 514.2	2663.5 ± 721.2
	Fedele et al[12], 2014 (placebo)	1.6 ± 0.2	1.7 ± 0.2	44.4 ± 13.1	47 ± 12.8	2498.5 ± 262	2470 ± 409.9	43.33 ± 7.99	40.24 ± 6.58	1571.4 ± 125.3	1778.51 ± 798.1
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		RBF (mL/min)		GFR (mL/min)		FF
		Baseline	Treatment	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment
	Inomata et al[14], 2017	NA	NA	NA	NA	426 ± 197	518 ± 276	36.5 ± 18.3	44.5 ± 19.0	0.146 ± 0.080	0.143 ± 0.069

BUN: Blood urea nitrogen; FF: filtration fraction; GFR: glomerular filtration rate; NA: Not available; RBF: renal blood flow.

Table 5 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		Cystatin C (mg/L)		Weight loss (kg)		Cumulative urine volume (mL)
		Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes
Dopamine/dobutamine	Chen et al[13], 2013 (dopamine)	1.59	0.00	NA	NA	1.71	0.12	NA	NA	8524
	Chen et al[13], 2013 (placebo)	1.63	0.02	NA	NA	1.66	0.11	NA	NA	8296
	Ref.	Creatinine (mg/dL)		Change in BUN (mg/dL)		RBF (mL/min)		GFR (mL/min)		FF
		Baseline	Treatment	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment	Baseline	Treatment
	Lannemyr et al[15], 2018 (dobutamine)	NA	NA	NA	NA	397 ± 121	499 ± 154	47.1 ± 14.5	47.3 ± 16.9	0.193 ± 0.070	0.161 ± 0.075

BUN: Blood urea nitrogen; FF: filtration fraction; GFR: glomerular filtration rate; NA: Not available; RBF: renal blood flow.

Table 6 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Study	Creatinine (mg/dL)		Change in BUN (mg/dL)		Cystatin C (mg/L)		Weight loss (kg)		Urine output (mL/d)
		Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes	Baseline	Mean changes
Tolvaptan	Inomata et al[14], 2017	1.5	0.06 ± 0.32	NA	NA	NA	NA	62	-2.1 ± 1.8	1306 ± 494	459 ± 514

BUN: Blood urea nitrogen; NA: Not available.

Table 7 Changes in clinical parameters of the included studies

Intervention	Clinical parameters evaluated
	Study	Creatinine (mg/dL)		Change in BUN (mg/dL)		GFR (mL/min per 1.73 m2)	Weight loss (Ib)		Urine output (mL/d)
		Baseline	Mean changes	Baseline	Mean changes	Mean changes	Baseline	Mean changes	Baseline	Mean changes
Ultrafiltration	Bart et al[11], 2012	2.09	-0.04 ± 0.53	50.5	5.68 ± 18.29	1.67 ± 10.94	234	12.1 ± 11.3	NA	NA
	Bart et al[11], 2012 (pharmaco-logic therapy)	1.90	+0.23 ± 0.70	48.7	12.54 ± 24.81	0.93 ± 14.60	207	12.6 ± 8.5	NA	NA

BUN: Blood urea nitrogen; GFR: Glomerular filtration rate; NA: Not available.