Diabetes as a risk factor of acute kidney injury in vancomycin users: an observational and prospective study

Santana, George Misael Ferreira de; Santana, Danielle Cristine Almeida Silva de; Santana, Fernando José Malagueño de

doi:10.1590/s2175-97902020000118401

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 56 • 2020 • https://doi.org/10.1590/s2175-97902020000118401 copy

Diabetes as a risk factor of acute kidney injury in vancomycin users: an observational and prospective study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Diabetes was investigated as a risk factor for nephrotoxicity induced by vancomycin. In the present study, the drug’s nephrotoxic effect was indirectly evaluated by Glomerular Filtration Rate, albuminuria and serum levels of creatinine and urea on the 1^st, 7^th and 14^th days of vancomicyn therapy in a group of diabetic and non-diabetic patients, with and without previous nephropathy. The correlations between investigated variables (including the population’s epidemiological profile and hospital care) were measured by the Spearman test. The sample consisted of 132 patients, predominantly male diabetic patients with previous nephropathy, over 40 years, receiving ≥ 10 grams of vancomycin for the treatment of infectious diseases and showing satisfactory clinical outcomes. A risk of vancomycin drug interaction with potential nephrotoxic outcome was observed in 36.4% of patients who used multiple drugs. Furthermore, 80% of patients had an increase of at least 0.5 mg.dL^-1 in baseline serum levels of creatinine and urea at the end of the study. This was more common among the diabetic patients with previous nephropathy, showing higher albuminuria and a reduction in the Glomerular Filtration Rate. Therefore, it has been recommended that the use of vancomycin in diabetic patients should be in careful dosages and that kidney functioning be monitored.

Keywords:
Vancomycin; Nephrotoxicity; Diabetes Mellitus; Kidney damage; Outpatient clinics; Drug synergism

	n	%	p-values^{¹ 1 p-values from Pearson's chi-squared test, if p-values < 0.05 there is a significant difference in frequency between categorical data sets.}
Gender
Males	73	55.3	0.223
Females	59	44.7	0.223
Age group, y
18-30	10	7.6	0.005
31-40	25	18.9
41-50	32	24.2
51-60	35	26.6
> 60	30	22.7
Groups
1. Diabetics with nephropathy	50	37.9	0.006
2. Non-diabetics with nephropathy	29	22.0
3. Diabetics without nephropathy	23	17.4
4. Non-diabetics without nephropathy	30	22.7

Factor evaluated	n	%	p-values^{¹ 1 p-values from Pearson's chi-squared test, if p-values < 0.05 there is a significant difference in frequency between categorical data sets; DI, Drug interaction with vancomycin.}
Outpatient hospital sector
Infectious Diseases	30	22.7	0.006
Nephrology	36	27.3
Intensive care unit	19	14.4
Internal Medicine	47	35.6
Reason for indication of vancomycin
Non-specific bacterial infections	81	61.4	<0.001
Pneumonia	27	1.5
Septicemia	16	3.0
Ankle and foot injuries	4	12.1
Osteomyelitis	2	20.5
Infective endocarditis	2	1.5
Total dose of vancomycin
Under 10 g	38	28.8	<0.001
Over 10 g	94	71.2	<0.001
DI with nephrotoxic effect
No potential risk	84	63.6	0.002
Potential risk	48	36.4	0.002
Drugs with potential risk of DI and nephrotoxic effect
Piperacillin	14	29.2	<0.001
Furosemide	17	35.4
Polymyxin	5	10.4
Amikacin	4	8.3
Ciprofloxacin	3	6.2
Tobramycin	2	4.2
Amphotericin	1	2.1
Gentamicin	1	2.1
Moxifloxacin	1	2.1

Measured value	Kidney function biomarkers values			p-values¹ 1 p-values from Friedman test, if p-values < 0.05 there is a significant difference in kidney function biomarkers values between categorical data sets.
Measured value	1st day (n=132)	7th day (n=132)	14th day (n=37)
1. Diabetics with nephropathy
Creatinine (mg.dL^-1)*	1.13±0.46	1.42±0.50	1.50±0.45	<0.001
Urea (mg.dL^-1)*	48.57±19.51	61.81±24.46	72.07±20.77	<0.001
GFR (mL.min^-1 1.73 m^{2 -1}) *	72.94±27.81	43.90±17.10	35.11±16.88	<0.001
2. Non-diabetics with nephropathy
Creatinine (mg.dL^-1)*	1.07±0.46	1.40±0.71	1.93±0.78	0.097
Urea (mg.dL^-1)*	50.51±14.36	67.73±37.60	119.33±46.61	0.097
GFR (mL.min^-1 1.73 m^{2 -1})*	64.50±24.37	56.12±27.14	44.04±20.92	<0.001
3. Diabetics without nephropathy
Creatinine (mg.dL^-1)*	1.14±0.38	1.42±0.48	1.71±0.41	0.002
Urea (mg.dL^-1)*	54.94±16.05	67.86±22.70	93.57±28.07	0.002
GFR (mL.min^-1 1.73 m2 ^-1) *	61.44±17.43	47.52±14.85	46.00±21.32	0.097
4. Non-diabetics without nephropathy
Creatinine (mg.dL^-1)*	1.13±0.40	1.45±0.57	1.48±0.73	0.121
Urea (mg.dL^-1)*	52.07±16.97	70.20±27.78	88.00±40.64	<0.001
GFR (mL.min^-1 1.73 m^{2 -1}) *	75.97±26.90	46.60±16.77	47.60±22.84	0.011

Group	Albuminuria (mg 24h^-1)	Vancomycin (g)
1. Diabetics with nephropathy	1904±457	17.56±7.50
2. Non-diabetics with nephropathy	707±268	14.35±8.25
3. Diabetics without nephropathy	1609±474	17.85±8.17
4. Non-diabetics without nephropathy	258±209	18.03±8.53
p-values¹ 1 p-values from Kruska-Wallis test, if p-values < 0.05 there is a significant difference in albuminuria and dose of vancomycin between categorical data sets.	<0.001	0.108

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: F. J. M. de Santana, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Avenida Prof. Moraes Rego 1235, Cidade Universitária, 50670-901, Recife, Pernambuco, Brazil. Tel: +55 (81) 2126.8510 Fax: +55 (81) 2126.8511. E-mail: fmalagueno@hotmail.com.