Safety and effectiveness of remdesivir in hospitalized patients with COVID-19 and severe renal impairment: experience at a large medical center

Figures & data

Table 1. Baseline characteristics of study population.

Variables	eGFR < 30 mL/min/1.73 m^2 N = 307	eGFR ≥ 30 mL/min/1.73 m^2 N = 1,036	p value
Age, yr, median (IQR)	79.3 (69.0–89.9)	81.2 (67.3–90.7)	0.727
Male, n (%)	181 (59.0)	680 (65.6)	0.038
BMI, kg/m^2, median (IQR)	22.41 (20.4–25.4)	22.29 (19.8–25.2)	0.407
Comorbidity, n (%)
CCI, median (IQR)	4.0 (3.0–6.0)	3.0 (2.0–4.0)	<0.001
Hypertension	225 (73.3)	585 (56.6)	<0.001
Diabetes mellitus	143 (46.6)	300 (29.0)	<0.001
Cardiovascular disease	159 (51.8)	394 (38.0)	<0.001
Chronic lung disease	31 (10.1)	105 (10.1)	1.000
Chronic liver disease	33 (10.7)	174 (16.8)	0.013
Cancer	95 (30.9)	326 (31.5)	0.918
Cerebrovascular accident	56 (18.2)	225 (21.5)	0.217
Hemodialysis	122 (39.7)	0 (0.0)
Smoking, n (%)			0.473
Non-smoker	253 (82.4)	872 (84.2)
Ever smoker	31 (10.1)	106 (10.2)
Current smoker	23 (7.5)	58 (5.6)
COVID-19 disease severity (n, %)			0.015
Mild to moderate	93 (30.3)	314 (30.3)
Severe	185 (60.3)	670 (64.7)
Critical	29 (9.4)	52 (5.0)
Ct value, cycle, median (IQR)	15.7 (13.4–19.3)	15.2 (13.0–18.7)	0.181
Concomitant nephrotoxic drug, n (%)	0.0 (0.0–1.0)	0.0 (0.0–1.0)	0.022
Vancomycin	14 (4.6)	4 (0.4)	<0.001
Aminoglycoside	1 (0.3)	1 (0.1)	0.405
Acyclovir	1 (0.3)	14 (1.4)	0.214
TMP/SMX	9 (2.9)	37 (3.6)	0.717
Amphotericin B	2 (0.7)	0 (0.0)	0.052
ACEIs/ARBs	70 (22.8)	217 (20.9)	0.537
Loop/thiazide diuretics	67 (21.8)	168 (16.2)	0.029
Tacrolimus/cyclosporine	15 (4.9)	20 (1.9)	0.008
NSAIDs	2 (0.7)	58 (5.6)	<0.001
Voriconazole	0 (0.0)	3 (0.3)	1.000
Adjuvant COVID-19 therapies, n (%)
Dexamethasone	172 (56.0)	553 (53.4)	0.452
Tocilizumab	19 (6.2)	33 (3.2)	0.026
Antibiotics, n (%)	209 (68.1)	602 (58.1)	0.002
No. of days to start RDV after diagnosing, median (IQR)	2.0 (1.0-3.0)	2.0 (1.0-3.0)	0.602
5-Day RDV regimen, n (%)	214 (69.7)	722 (69.7)	1.000
Oxygen requirement, n (%)			0.008
Room air	118 (38.4)	399 (38.5)
Nasal cannula	115 (37.5)	478 (46.1)
Simple mask	0 (0.0)	2 (0.2)
Venturi mask	16 (5.2)	47 (4.5)
Nonrebreather mask	19 (6.2)	40 (3.9)
High-flow nasal cannula	5 (1.6)	12 (1.2)
Bi-level positive airway pressure	5 (1.6)	6 (0.6)
Mechanical ventilator	29 (9.4)	52 (5.0)
Laboratory data, median (IQR)
ALT (U/L)	16.0 (10.0–28.0)	18.0 (12.0–29.0)	0.001
Total bilirubin (mg/dL)	0.4 (0.3–0.6)	0.5 (0.3–0.7)	0.002
eGFR (mL/min/1.73 m^2)	15.0 (8.0–24.0)	70.0 (51.0–95.0)	<0.001
SCr (mg/dL)	3.6 (2.4–5.7)	1.0 (0.7–1.2)	<0.001
Heart rate, bpm, median (IQR)	73.0 (66.0–84.0)	75.0 (66.0–85.0)	0.158
COVID-19 vaccine doses, median (IQR)	2.0 (0.0–3.0)	2.0 (0.0–3.0)	0.131

Bold values indicate statistical significance at the p < 0.05 level.

ACEIs/ARBs: angiotensin converting enzyme inhibitors / angiotensin receptor blockers, ALT: alanine transaminase, bpm: beats per minute, BMI: body mass index, COVID-19: coronavirus disease 2019, CCI: Charlson Comorbidity Index, Ct: cycle threshold, eGFR: estimated glomerular filtration rate, calculated using MDRD formula, IQR: interquartile range, NSAIDs: non-steroidal anti-inflammatory drug, RDV: remdesivir, SCr: serum creatinine, TMP/SMX: trimethoprim/sulfamethoxazole.

Figure 1. Flow diagram summarizing the process of enrollment.

Figure 2. Kaplan-Meier survival curves of the COVID-19 cohort receiving remdesivir (A) acute kidney injury (B) bradycardia (C) mortality in COVID-19 dedicated ward (D) Mortality in hospital.

Table 2. Incidence rates and hazard ratios for primary outcomes.

Outcome	eGFR < 30 N = 307			eGFR ≥ 30 N = 1,036			Adjusted HR (95% CI)
	Events	PD	IR	Events	PD	IR
Acute kidney injury	39^a	1365	28.6	76^b	8348	9.1	2.92 (1.93–4.44)^c
Bradycardia	63	2245	28.1	192	7465	25.7	1.15 (0.85–1.56)^d
Mortality in dedicated wards	36	2858	12.6	63	9140	6.9	1.43 (0.90–2.28)^e
Mortality in hospital	64	5498	11.6	126	16785	7.5	1.47 (1.06–2.05)^e

Bold values indicate statistical significance at the p < 0.05 level.

CI: confidence interval, eGFR: estimated glomerular filtration rate in mL/min/1.73 m2, calculated using MDRD formula, HR: hazard ratio, IR: Incidence rate per 1000-patient days, PD: Patient-days.

^a Excluded 122 patients on dialysis and 4 patients with data missing. Total number of observers was 181 in eGFR < 30 group.

^b Excluded 31 patients with data missing. Total number of observers was 1005 in eGFR ≥ 30 group.

^c Adjusted for age, sex, COVID-19 disease status, vaccine, CCI score, the 10 nephrotoxic drugs listed in Table 1.

^d Adjusted for age, sex, COVID-19 disease status, vaccine, CCI score, hypertension, diabetes mellitus, chronic heart disease, cerebrovascular accident.

^e Adjusted for age, sex, COVID-19 disease status, vaccine, CCI score, hypertension, diabetes mellitus, chronic heart disease, chronic lung disease, chronic liver disease, cancer, cerebrovascular accident, smoke, oxygen requirement.

Table 3. Secondary outcomes.

	eGFR < 30 N = 307	eGFR ≥ 30 N = 1,036	aOR/β (95% CI)	p value
Laboratory data change, median (IQR)
ALT^a	3.00 (-1.00–12.00)	4.00 (-1.00–15.25)	7.20 (-36.13–50.51)^b	0.745
Total bilirubin^c	0.03 (-0.11–0.17)	0.02 (-0.14–0.20)	−0.08 (-0.34–0.18)^b	0.549
eGFR^d	0.00 (-3.00–4.00)	1.00 (-10.50–11.00)	1.99 (-1.58–2.26)^e	0.273
SCr^f	−0.06 (-0.56–0.40)	−0.01 (-0.13–0.11)	0.08 (-0.04–0.19)^e	0.180
Progression of COVID-19 disease, n/N (%)^g	76/278 (27.3)	175/984 (17.8)	1.62 (1.16–2.26)^h	0.004
3-day remdesivir regimen	18/93 (19.4)	37/314 (11.8)	1.34 (0.68–2.61)^h	0.457
5-day remdesivir regimen^g	58/185 (31.4)	138/670 (20.6)	1.73 (1.17–2.55)^h	0.006
Length of stay in dedicated ward, median (IQR)	9.0 (7.0–15.0)	9.0 (7.0–14.0)	−0.08 (-0.97–0.81)^i	0.863
Length of oxygen requirement, median (IQR)^j	8.6 (3.4–17.1)	6.2 (2.6–13.7)	0.34 (-1.92–2.60)^h	0.769

Bold values indicate statistical significance at the p < 0.05 level.

ALT: alanine transaminase, aOR: adjusted odds ratio, CI: confidence interval, eGFR: estimated glomerular filtration rate in mL/min/1.73 m², calculated using MDRD formula, IQR: interquartile range, SCr: serum creatinine.

^a Excluded 5 patients in eGFR < 30 group and 34 patients in eGFR ≥ 30 group due to data missing.

^b Adjusted by age, sex, COVID-19 disease status, COVID-19 vaccine doses, CCI score, chronic liver disease.

^c Excluded 38 patients in eGFR < 30 group and 141 patients in eGFR ≥ 30 group due to data missing.

^d Excluded 122 patients on dialysis and 10 patients with data missing in eGFR < 30 group and 31 patients with data missing in eGFR ≥ 30 group.

^e Adjusted by age, sex, COVID-19 disease status, COVID-19 vaccine doses, CCI score, the 10 nephrotoxic drugs listed in Table 1.

^f Excluded 122 patients on dialysis and 12 patients with data missing in eGFR < 30 group and 31 patients with data missing in eGFR ≥ 30 group.

^g Excluded 81 ventilator users in the index date (29 in < 30 group and 52 in ≥ 30 group).

^h Adjusted by age, sex, COVID-19 disease severity, COVID-19 vaccine doses, CCI score, chronic lung disease, smoking status, oxygen requirement.

ⁱ Adjusted by age, sex, COVID-19 disease status, vaccine, CCI score, hypertension, diabetes mellitus, chronic heart disease, chronic lung disease, chronic liver disease, cancer, cerebrovascular accident, smoking status, and oxygen requirement.

^j Excluded patients on the 3-day remdesivir regimen as they did not require supplemental oxygen.

Data availability statement

The datasets created and examined in the present study cannot be accessed by the public due to the regulations of the Institutional Review Board at Taipei Veterans General Hospital. The dataset can be obtained from the corresponding author or IRB of TVGH upon request (email: [email protected]). Data can only be utilized for research purposes.