Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis

Table 1 Subgroup analysis of polymyxin-induced nephrotoxicity

Category	Subgroups	No. of studies	No. of nephrotoxicity patients	No. of patients	Events rate (95%CI)	Model	Heterogeneity (I2)		P value
Overall		83	4027	12234	0.348 (0.308-0.389)	Random		95.90	NA
Severity	Severe nephrotoxicitya	47	648	5163	0.127 (0.103-0.150)	Random		89.60	NA
	Mild nephrotoxicity	49	1378	5163	0.258 (0.216-0.299)	Random		96.80
Continent	Africa	4	53	209	0.215 (0.087-0.343)	Random		82.10	0.394
	Asia	31	1230	3099	0.340 (0.264-0.416)	Random		96.30
	Europe	35	1192	2904	0.364 (0.283-0.446)	Random		97.00
	South America	6	249	628	0.399 (0.295-0.503)	Random		84.60
	North America	6	1283	5213	0.329 (0.200-0.459)	Random		92.40
Polymyxins	Colistin	72	3623	11211	0.355 (0.311-0.398)	Random		96.10	0.151
	Polymyxin B	11	262	903	0.268 (0.171-0.364)	Random		92.20
Loading dose	Loading dose	32	1305	3233	0.391 (0.321-0.461)	Random		95.00	0.051
	No loading dose	48	2333	8340	0.309 (0.260-0.357)	Random		95.20
Maintenance doseb	Higher dose	5	109	281	0.395 (0.302-0.487)	Random		52.00	0.363
	Normal dose	62	2867	9588	0.324 (0.278-0.371)	Random		96.00
Dosing interval	Q12H or BID	32	1494	3200	0.421 (0.356-0.485)	Random		93.40	0.0011
	Q8-6H or TID	21	380	1322	0.251 (0.172-0.330)	Random		93.90
Nephrotoxicity Criteria	RIFLE	38	1667	3985	0.396 (0.339-0.454)	Random		93.80	0.0001
	KDIGO	10	627	1369	0.465 (0.359-0.571)	Random		93.80
	AKIN	8	284	761	0.373 (0.274-0.473)	Random		87.40
	Others	26	1473	6298	0.214 (0.159-0.269)	Random		94.20
Age (yr)c	< 65 yr	59	2450	8980	0.307 (0.263-0.351)	Random		95.10	0.0031
	≥ 65 yr	19	1123	2328	0.451 (0.382-0.520)	Random		91.40
Sex proportion	Males > 50%	60	3064	99908	0.344 (0.297-0.391)	Random		96.10	0.417
	Males ≤ 50%	8	332	757	0.406 (0.243-0.569)	Random		94.50
APACH II score	< 20	23	653	1690	0.305 (0.209-0.401)	Random		95.80	0.115
	≥ 20	29	1053	2601	0.384 (0.307-0.461)	Random		95.00
Publication yr	< 2010	10	42	333	0.138 (0.085-0.192)	Random		44.10	0.0001
	2010-2015	25	612	2099	0.270 (0.205-0.334)	Random		93.10
	2015-2022	48	3386	9875	0.421 (0.365-0.476)	Random		96.70
Study design	Cohort study	72	3685	11491	0.340 (0.296-0.384)	Random		96.50	0.785
	Case-control study	5	185	457	0.410 (0.164-0.656)	Random		96.70
	RCT	8	158	407	0.341 (0.224 - 0.459)	Random		82.70
Study qualityd	Low	11	1402	5715	0.215 (0.130-0.299)	Random		97.30	0.0031
	Fair	50	1912	4925	0.363 (0.314-0.411)	Random		93.70
	High	17	599	1324	0.412 (0.329-0.494)	Random		90.10
Sample size	≤ 50	30	284	1026	0.261 (0.199-0.323)	Random		87.00	0.0001
	50-100	27	657	1965	0.341 (0.260-0.423)	Random		95.40
	> 100	28	3130	9480	0.436 (0.370-0.501)	Random		97.30

¹Significant at P value < 0.05.

^aSevere nephrotoxicity defined as RIFLE grade of ‘failure’ or above, AKIN grade of 3 or KDIGO grade of 3 or required renal replacement therapy.

^bMaintenance dose varied among studies, higher dose as identified as > 9 MIU/d or > 2.5-5.0 mg CBA/kg/d for colistin, or > 2.5-3 mg/kg/d for polymyxin B in this study.

^cAge cut-off value based on the mean or median age of patients included.

^dQuality assessment was applied using Newcastle Ottawa Scale assessment for cohort studies and case control studies. Articles that scored less than 4 were classified as low methodological quality, articles with score between 5 and 7 were classified as fair quality, and those with score more than 8 were classified as high quality.

AKIN: Acute Kidney Injury Network; APACHE II: Acute Physiology and Chronic Health Evaluation II; BID: twice daily; CI: Confidence Interval; KIDGO: Kidney Disease Improving Global Outcomes; RCT: Randomized Controlled Trials; RIFLE: Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease; TID: Three times daily; NA: Not available.