Acute kidney injury in adult patients with COVID-19: an integrative review

Integrative review carried out in the databases CINAHL, Embase, LILACS, Livivo, PubMed, SCOPUS, Web of Science and in the grey literature (Google Scholar) on January 12, 2022. Articles were included in English, Spanish and Portuguese, published from November 2019 to January 2022, in hospitalized patients over 18 years old with COVID-19 and AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The selected studies were read in full for extraction, interpretation, synthesis and categorization according to the level of evidence.

Results

A total of 699 articles were found and 45 included. Older age, male gender, hypertension, chronic kidney disease, mechanical ventilation, increased C-reactive protein, use of vasoactive drugs and certain classes of antihypertensives were associated with AKI. AKI is related to a higher frequency of mortality. AKI occurred in 30% of patients hospitalized with COVID-19. The mortality rate from AKI was 5% and the case fatality rate was 18%.

Conclusion

These results highlight the relevance of AKI as a significant complication of COVID-19 and suggest that more careful and early control of associated factors could potentially reduce mortality and lethality. It is crucial to intensify research in this field to better clarify the mechanisms involved in kidney injury in COVID-19 patients, as well as to identify more effective therapeutic strategies for its prevention and treatment in this context.

COVID-19; Coronavirus infections; Acute kidney injury; Incidence; Risk factor; Patient acuity; Adult

Pubmed	“adult” AND “covid-19” and “Acute Kidney Injury” and “risk factors”
Embase	“adult” AND “covid-19” and “Acute Kidney Injury” and “risk factors”
Scopus	“adult” AND “covid 19” and “Acute Kidney Injury” and “risk factors”
Livivo	“adult” AND “covid-19” and “Acute Kidney Injury” and “risk factors”
Web of science	“adult” AND “covid-19” and “Acute Kidney Injury” and “risk factors”
Cinhal	“covid-19” and “Acute Kidney Injury” and “risk factors”
Lilacs	“covid-19” and “Acute Kidney Injury” and “risk factors”
Google scholar	allintitle: “Acute Kidney Injury” “risk factors” “covid 19”

Authors, year of publication and country	Type of study	Level of evidence	N COVID-19 patients % AKI (n)	Factors associated with AKI	% mortality in patients with AKI associated with COVID-19	% lethality in patients with AKI associated with COVID-19 (mortality by AKI )
Almeida DC, Franco MCP, Santos DRP, Santos MC, Maltoni IS, Mascotte F, et al., 2021, Brazil.⁽¹⁶⁾	Retrospective cohort	IV	278 71% (198)	Hypertension and vasoactive drugs	28%	40% (79)
Doher MP, Carvalho FRT, Scherer PF, Matsui TN, Ammirati AL, Silva BC, et al., 2020, Brazil.⁽¹⁷⁾	Retrospective cohort	IV	201 50% (101)	↑ initial creatinine level, use of diuretics and use of mechanical ventilation	12%	24% (24)
Neves PDMM, Sato VAH, Mohrbacher S, Ferreira BMC, Oliveira ES, Pereira LVB, et al., 2021, Brazil.⁽¹⁸⁾	Retrospective	IV	95 57% (54)	Hypertension and use of mechanical ventilation	16%	28% (15)
Zamoner W, Santos CAS, Magalhães LE, de Oliveira PGS, Balbi AL, Ponce D, 2020, Brazil.⁽¹⁹⁾	Prospective cohort	IV	101 50% (51)	Obesity, use of corticosteroids, ↑ APACHE II* and SOFA† scores	34%	67% (34)
Casas-Aparicio GA, León-Rodríguez I, Alvarado-de la Barrera C, González-Navarro M, Peralta-Prado AB, Luna-Villalobos Y, et al., 2021, Mexico.⁽²⁰⁾	Retrospective cohort	IV	99 59% (58)	↑ age, obesity and use of invasive mechanical ventilation	38%	66% (38)
Martínez-Rueda AJ, Álvarez RD, Méndez-Pérez RA, Fernández-Camargo DA, Gaytan-Arocha JE, Berman-Parks N, et al., 2021, Mexico.⁽²¹⁾	Retrospective cohort	IV	1170 30% (349)	Chronic kidney disease, hypertension, ↑ CHF‡, ↑ SOFA† score. For hospital-acquired acute kidney injury: mechanical ventilation, ↑ troponin I levels and ↑ glucose admission	16%	52% (182)
Azam TU, Shadid HR, Blakely P, O’Hayer P, Berlin H, Pan M, et al., 2020, United States.⁽²²⁾	Multicentric	IV	352 26% (91)	↑ age, male gender, ↑ BMI§, diabetes mellitus, hypertension, mechanical ventilation, ↓ GFR\|\|, ↑ ferritin, ↑ d-dimer and ↑ LDH¶.	-	-
Bowe B, Cai M, Xie Y, Gibson AK, Maddukuri G, Al-Aly Z, 2020, United States .⁽²³⁾	Cohort	IV	5216 32% (1665)	↑ age, male gender, black ethnicity, diabetes mellitus and hypertension, ↓ baseline GFR\|\|, use of iECA** and diuretics	11%	34% (559)
Fisher M, Neugarten J, Bellin E, Yunes M, Stahl L, Johns TS, et al., 2020, United States.⁽²⁴⁾	Retrospective	IV	3345 57% (1903)	↑ age, male gender and black ethnicity	19%	34% (641)
Hirsch JS, Ng JH, Ross DW, Sharma P, Shah HH, Barnett RL, et al., 2020, United States .⁽²⁵⁾	Retrospective	IV	5449 37% (1993)	↑ age, blacks, diabetes mellitus, hypertension, cardiovascular disease, use of mechanical ventilation and vasopressors	13%	35% (694)
Nimkar A, Naaraayan A, Hasan A, Pant S, Durdevic M, Suarez CN, et al., 2020, United States .⁽²⁶⁾	Retrospective	IV	327 55% (179)	↑ age, African-American ethnicity, chronic kidney disease and hyperlipidemia	32%	58% (104)
Zahid U, Ramachandran P, Spitalewitz S, Alasadi L, Chakraborti A, Azhar M, et al., 2020, United States .⁽²⁷⁾	Retrospective cohort : single center	IV	469 27% (128)	male gender, hypertension, use of iECA**, hemodynamic instability, more severe refractory hypoxemia and mechanical ventilation	19%	71% (91)
See YP, Young BE, Ang LW, Ooi XY, Chan CP, Looi WL, et al., 2020, Cingapure.⁽²⁸⁾	Retrospective cohort	IV	707 8% (57)	↑ age, hypertension, dyslipidemia, use of drugs: iECA** or ARB††, vancomycin and NSAID‡‡, severity of COVID {hypoxemia}	1%	12% (7)
Chebotareva N, Berns S, Berns A, Androsova T, Lebedeva M, Moiseev S, 2021, Russia.⁽²⁹⁾	Cohort	IV	1280 29% (371)	↑ age, ↓ GFR\|\|, ↑ C-reactive protein, ↑ ferritin, ↑ activated partial thromboplastin time, ↑ maximum d-dimer and acute respiratory distress syndrome	9%	31% (114)
Sarkisian DK, Chebotareva NV, McDonnell V, Oganesyan AV, Krasnova TN, Makarov EA, 2021, Russia.⁽³⁰⁾	Retrospective	IV	37 46% (17)	Age > 60 years, ↑ C-reactive protein and ↓ platelets. Proteinuria and hematuria.	35%	76% (13)
Chan KW, Hung IF-N, Tsang OT-Y, Wu TC, Tso EY-K, Lung KC, et al., 2021, China.⁽³¹⁾	Retrospective cohort	IV	591 4% (22)	↑ age, smoking, diabetes mellitus, hypertension, use of iECA**/BRA††, ↑ C-reactive protein, ↑ LDH¶ and ↑ creatine kinase, ↓ serum albumin, ↓ GFR\|\|, presence of pulmonary abnormality	1%	14% (3)
Chen Z, Gao C, Yu H, Lu L, Liu J, Chen W, et al., 2021, China.⁽³²⁾	Retrospective cohort	IV	823 5% (44)	↓ platelets, ↓ albumin ↑ phosphate, ↑ LDH¶, ↑ procalcitonin, ↑ C-reactive protein, ↑ prothrombin time and uremia	4%	82% (36)
Cheng Y, Luo R, Wang X, Wang K, Zhang N, Zhang M, et al., 2020, China.⁽³³⁾	Retrospective cohort	IV	1392 7% (99)	severe COVID-19, ↑ baseline serum creatinine, ↑ d-dimer and lymphopenia	5%	72% (71)
Cui X, Yu X, Wu X, Huang L, Tian Y, Huang X, et al., 2020, China.⁽³⁴⁾	Retrospective: multicentric	IV	116 18% (21)	↑ creatinine kinase, ↑ clinical complexity, use of mechanical ventilation, shock state, ↑ SOFA†	10%	57% (12)
Dai Y, Liu Z, Du X, Wei H, Wu Y, Li H, et al., 2021, China.⁽³⁵⁾	Retrospective cohort	IV	492 7% (36)	male gender, chronic kidney disease, hypertension, leukocytosis, use of diuretics and use of glucocorticoids	5%	64% (23)
Jin K, Xie T, Seery S, Ye L, Jiang J, Yang W, et al., et al., 2020, China.⁽³⁶⁾	Retrospective cohort	IV	342 13% (46)	↑ Age, leukocytosis, ↑ C-reactive protein, ↑ fibrinogen, and severity of pneumonia	10%	76% (35)
Li W-X, Xu W, Huang C-L, Fei L, Xie X-D, Li Q, et al., 2021,China.⁽³⁷⁾	Retrospective cohort	IV	1249 7% (91)	Age > 60 years, male gender, obesity, hypertension, diabetes mellitus, ↑ C-reactive protein, use of lopinavir/ritonavir and ↓ lymphocyte count	0,2%	3% (3)
Peng S, Wang H-Y, Sun X, Li P, Ye Z, Li Q, et al., 2020, China.⁽³⁸⁾	Retrospective cohort	IV	4020 7% (285)	↑ Age, hypertension, chronic kidney disease, ↑ inflammatory biomarkers and ↑ ferritin	3%	39% (112)
Sang L, Chen S, Zheng X, Guan W, Zhang Z, Liang W, et al., 2020, China.⁽³⁹⁾	Retrospective	IV	210 44% (92)	↑ Age, sepsis, use of nephrotoxic drugs, use of mechanical ventilation and ↑ baseline creatinine	31%	71% (65)
Wang J, Wang Z, Zhu Y, Li H, Yuan X, Wang X, et al., 2020, China.⁽⁴⁰⁾	Retrospective cohort	IV	116 10% (12)	clinical classification of COVID-19, ↑ procalcitonin, ↓ GFR	-	-
Wang RR, He M, Kang Y, 2021, China.⁽⁴¹⁾	Retrospective cohort	IV	389 7% (28)	↑ age, hypertension, cardiovascular disease, ↑ mean arterial pressure, ↓ SpO2§§, ↑ leukocytes, ↑ neutrophils, ↑ TGO, ↑ C-reactive protein, ↑ serum creatinine, ↑ serum uric acid, ↓ lymphocytes, ↓ platelets and ↓ albumin	4%	61% (17)
Xu J, Xie J, Du B, Tong Z, Qiu H, Bagshaw SM, 2020, China.⁽⁴²⁾	Retrospective cohort : 19 hospitals	IV	671 39% (263)	higher severity scores (SOFA† and APACHE II*), longer use of vasopressors, use of mechanical ventilation and extracorporeal membrane oxygenation	28%	71% (188)
Bell JS, James BD, Al-Chalabi S, Sykes L, Kalra PA, Green D, 2021, England.⁽⁴³⁾	Retrospective cohort	IV	448 26% (118)	chronic kidney disease, use of mechanical ventilation, ↑ maximum heart rate, atrial fibrillation and ↓ lymphocytes	14%	54% (64)
Parker K, Hamilton P, Hanumapura P, Castelino L, Murphy M, Challiner R, et al., 2021, England.⁽⁴⁴⁾	Retrospective cohort	IV	1032 20% (210)	male gender, hypertension, previous kidney disease and ↑ C-reactive protein	11%	52% (110)
Sullivan MK, Lees JS, Drake TM, Docherty AB, Oates G, Hardwick HE, et al., 2022, England .⁽⁴⁵⁾	Cohort	IV	41294 31% (13000)	admission respiratory rate > 30 rpm/min, chronic kidney disease and black ethnicity	-	-
Lowe R, Ferrari M, Nasim-Mohi M, Jackson A, Beecham R, Veighey K, et al., 2021, United Kingdom.⁽⁴⁶⁾	Retrospective cohort : single center	IV	81 44% (36)	↑ age, ↑ severity of comorbidities, diabetes mellitus, immunosuppression, ↑ APACHE II*, use of mechanical ventilation, vasopressor or inotropic support, ↑ creatinine, ↑ C-reactive protein, ↑ d-dimer, ↑ neutrophil/lymphocyte ratio, ↓ lymphocytes	11%	25% (9)
Lumlertgul N, Pirondini L, Cooney E, Kok W, Gregson J, Camporota L, et al., 2021, United Kingdom .⁽⁴⁷⁾	Retrospective	IV	313 77% (240)	↑ age, ↑ BMI§, ↓ serum bicarbonate (acidosis), ↓ platelets, ↑ C-reactive protein and ↑ serum lactate	26%	34% (82)
Geri G, Darmon M, Zafrani L, Fartoukh M, Voiriot G, Le Marec J, et al., 2021, France.⁽⁴⁸⁾	Retrospective	IV	379 51% (195)	↑ age, male gender, diabetes mellitus, chronic kidney disease, use of mechanical ventilation and vasopressors	19%	37% (73)
Joseph A, Zafrani L, Mabrouki A, Azoulay E, Darmon M, 2020, France.⁽⁴⁹⁾	Retrospective: single center	IV	100 81% (81)	↑ age, SOFA† and use of mechanical ventilation	28%	35% (28)
Alfano G, Ferrari A, Fontana F, Mori G, Magistroni R, Meschiari M, et al., 2020, Italy.⁽⁵⁰⁾	Retrospective	IV	307 22% (69)	↑ age, admission to the intensive care unit, ↑ SOFA†, severe hypoxemia, ↑ interleukin-6, ↑ LDH¶, ↑ d-dimer, ↓ albumin, ↓ platelets and ↓ hemoglobin	13%	57% (39)
Scarpioni R, Valsania T, Albertazzi V, Blanco V, DeAmicis S, Manini A, et al., 2021, Italy.⁽⁵¹⁾	Retrospective cohort	IV	1701 14% (233)	age, male gender, use of mechanical ventilation	8%	57% (132)
Diebold M, Schaub S, Landmann E, Steiger J, Dickenmann M, 2021, Switzerland.⁽⁵²⁾	Retrospective cohort	IV	188 22% (41)	↑ age, male gender, chronic kidney disease, hypertension, ↑ leukocytes, ↑ C-reactive protein, ↑ creatinine kinase and ↑ potassium and use of pre-admission medication: BRA††	6%	27% (11)
Hardenberg J-HB, Stockmann H, Aigner A, Gotthardt I, Enghard P, Hinze C, et al., 2021, Germany.⁽⁵³⁾	Retrospective cohort	IV	223 52% (117)	hypertension, mechanical ventilation, vasopressor, leukocytosis and ↑ procalcitonin	15%	28% (33)
Trifi A, Abdellatif S, Masseoudi Y, Mehdi A, Benjima O, Seghir E, et al., 2021, Tunise.⁽⁵⁴⁾	Case control	IV	109 44% (48)	↑ D-dimer and sepsis	38%	85% (41)
Rahimzadeh H, Kazemian S, Rahbar M, Farrokhpour H, Montazeri M, Kafan S, et al., 2021, Ira.⁽⁵⁵⁾	Retrospective cohort	IV	516 38% (194)	↑ age, male gender, COVID-19 severity, hypertension, diabetes mellitus, heart disease, chronic kidney disease, iECA**/BRA†† use, ↑ neutrophil/lymphocyte ratio, ↑ urea and ↑ C-reactive protein	15%	40% (77)
Elkholi MH, Alrais ZF, Algouhary AR, Al-Taie MS, Sawwan AA, Khalafalla AA, et al., 2021, United Arab Emirates .⁽⁵⁶⁾	Retrospective cohort	IV	198 65% (129)	↑ age, ↑ vasopressor dose μg/kg/min, hypertension, CHF‡, ↑ SOFA† and ↑ cardiovascular SOFA†, ↓ mean arterial pressure	43%	66% (85)
Ghosn M, Attallah N, Badr M, Abdallah K, Oliveira B, Nadeem A, et al., 2021, United Arab Emirates .⁽⁵⁷⁾	Retrospective cohort	IV	110 54% (59)	↑ age, use of mechanical ventilation, ↑ admission creatinine and use of extracorporeal membrane oxygenation	21%	39% (23)
Kanbay M, Medetalibeyoglu A, Kanbay A, Cevik E, Tanriover C, Baygul A, et al. 2021, Turkey.⁽⁵⁸⁾	Retrospective cohort : 2 university centers	IV	770 12% (92)	↑ age, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure and cancer, ↑ urea, ↑ glucose, ↑ gamma glutamyl transferase, ↑ alkaline phosphatase, ↑ LDH¶, ↑ C-reactive protein, ↑ d-dimer, ↑ troponin, ↑ brain natriuretic peptide, ↑ international normalized ratio, ↑ activated partial thromboplastin time, ↑ creatinine and ↓ hemoglobin.	5%	46% (42)
Kolhe NV, Fluck RJ, Selby NM, Taal MW, 2020, United Kingdom.⁽⁵⁹⁾	Retrospective cohort : 2 hospitals	IV	1161 26% (304)	age > 65, congestive heart failure, chronic liver disease, chronic kidney disease, use of mechanical ventilation	16%	61% (184)


Demographic and clinical characteristics	Demographic: Older age ,^{(20,22-26,28-30,36-39,41,46-52,55-59)} male,^{(22-24,27,35,37,44,48,51,52,55)} black ethnicity,^(23-25,45) and African-American.⁽²⁶⁾ Clinics: ex-smoker,⁽³¹⁾ body mass index <25 kg/m²,^{(19,20,37,47)} diabetes mellitus,^{(22,23,25,31,46,55)} hypertension,^{(16,18,21,23,25,28,31,35,37,38,41,43,52,53,55,56,58)} greater severity of comorbidities (ICC*),^(46,56) chronic kidney disease,^{(21,26,35,43,45,48,52,55,59)} pre-existing kidney disease,⁽²⁵⁾ cardiovascular disease,^(25,41,55) coronary artery disease,⁽⁵⁸⁾ congestive heart failure,^(21,59) chronic liver disease,⁽²¹⁾ immunosuppression,⁽⁴⁶⁾ cancer⁽⁵⁸⁾ presence of serious illness.⁽³³⁾ Severity: severity of COVID-19,^(28,40,55) hemodynamic instability,⁽²⁷⁾sepsis,^(39,54) shock,⁽³⁴⁾ greater clinical complexity,⁽³⁴⁾ SOFA^{†(21,34,42,46,49,50,56,60)} and APACHE II‡ higher,^(46,60) Acute Respiratory Distress Syndrome,⁽²⁹⁾ greater severity of pneumonia,⁽³⁶⁾ lung abnormality,⁽³¹⁾ intense hypoxemia,^(27,50) intense hypoxemia O2,⁽⁴¹⁾ high respiratory rate on admission,⁽⁴⁵⁾ admission to the intensive care unit,⁽⁵⁰⁾ need for mechanical ventilation^{(17,18,20,22,27,34,40,43,46,48,49,51,57,59)} and extracorporeal membrane oxygenation.^(41,57)
Biomarkers	Inflammatory: increase in interleukin-6,⁽⁵⁰⁾ lactate dehydrogenase ,^{(22,31,32,50,58)} d-dimer ,^{(22,29,33,50,54,58)} C-reactive protein,^{(29-31,37,41,44,46,47,52,55,58)} fibrinogen,⁽³⁶⁾ procalcitonin^(32,40,53) and ferritin.^(22,29,38) Coagulatory: increase in prothrombin,⁽³²⁾ activated partial thromboplastin time^(29,58) and the INR^§,⁽⁵⁸⁾ reduction in platelets.^{(30,32,41,47,50)} Hematological and immunological: reduction in hemoglobin,⁽⁵⁰⁾ lymphopenia,^{(33,37,41,46)} leukocytosis,^{(35,36,52,53)} increased neutrophils and neutrophil/lymphocyte ratio^(46,55) Renal: reduction in estimated glomerular filtration rate,^{(22,23,29,31,40)} increase in serum creatinine,^{(17,33,39,41,57,58)}uremia,^(32,55,58) increased uric acid⁽⁴¹⁾ and reduced albumin.^{(31,32,41,50)} Other: decrease in serum bicarbonate,⁽⁴⁷⁾ increased creatine kinase,^(31,34,52) phosphate,⁽³²⁾ potassium⁽⁵²⁾, serum lactate,⁽⁴⁷⁾ glucose,^(21,58) triglycerides,⁽⁵⁸⁾ dyslipidemia,^(26,28) alkaline phosphatase,⁽⁵⁸⁾ troponin,^(21,58) glutamic-oxalacetic transaminase⁽⁴¹⁾ and BNP^\|\|.⁽⁵⁸⁾
Drugs	Angiotensin-converting enzyme inhibitor and angiotensin receptor blocker,^{(23,27,28,31,52,55)} diuretics,^(17,23,35) vasoactive drugs,^{(16,25,42,46,48,53,56)} glucocorticoids⁽³⁵⁾ and corticosteroids,⁽⁶⁰⁾ non-steroidal anti-inflammatory drugs,⁽²⁸⁾ nephrotoxic drugs,⁽³⁹⁾ lopinavir/ritonavir⁽³⁷⁾ and vancomycin.⁽²⁸⁾

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[1] Corresponding author: Priscilla Roberta Silva Rocha E-mail: priscillarocha@unb.br