Evaluation of colistin nephrotoxicity administered at different doses in the rat model

Figures & data

Table 1. Plasmatic level of Cr and CysC in the control and treated rats with colistin in doses of 150,000, 300,000 or 450,000 (IU/kg/day) over 7days.

		Doses of colistin (IU/kg/day)
Parameters	Control	150,000	300,000	450,000
Cr (mg/dL)	0.47 ± 0.04	0.46 ± 0.02	0.5 ± 0.01	0.47 ± 0.02
CysC(µg/mL)	2.88 ± 0.18	2.94 ± 0.17	3.02 ± 0.20	5.58 ± 0.36**

Notes: Values are expressed as mean ± SD of six rats.

**p < 0.01 versus control rats.

Cr, creatinine; Cys C, cystatine C.

Table 2. Urinary level of AST, ALT, LDH, ALP, GGT and NGAL in the control and treated rat with colistin in doses of 150,000, 300,000 or 450,000 (IU/kg/day) over 7days.

		Doses of colistin (IU/kg/day)
Parameters	Control	150,000	300,000	450,000
AST (U/g Cr)	26.9 ± 3.3	27.9 ± 1.1	25.8 ± 4.5	28.8 ± 4.2
ALT (U/g Cr)	23.2 ± 6.8	24.2 ± 5.0	25.3 ± 1.7	24.8 ± 4.0
LDH (U/g Cr)	85.3 ± 5.1	93.6 ± 5.6	91.1 ± 4.7	87.3 ± 5.1
ALP (U/g Cr)	80.7 ± 4.6	87.8 ± 8.6	85.7 ± 6.3	90.3 ± 3.2
GGT (U/g Cr)	669 ± 91	633 ± 102	649 ± 116	826 ± 124*
NGAL (ng/mL)	17.4 ± 2.8	19.4 ± 3.5	23.8 ± 5.5*	31.8 ± 5.6**

Notes: Values are expressed as mean ± SD of six rats, *p < 0.05 and **p < 0.01 versus control rats.

AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; ALP, alkaline phosphatase; GGT, γ-glutamyltransferase; NGAL, neutrophil gelatinase associated lipocaline.

Figure 1. Kidney of control rat treated with saline for 7 days showing normal renal cortex and glomeruli (HE × 100).

Figure 2. Kidney of rat administered colistin in doses of 150,000 IU/kg/day for 7 days showing mild tubular damage with vacuolisation (HE × 100).

Figure 3. Kidney of rat administered colistin in doses of 300,000 IU/kg/day showing mild tubular dilatation with few pales casts (HE × 200).

Figure 4. (A) Kidney of rat administered colistin in doses of 450,000 IU/kg/day showing acute tubular necrosis with glomerular preservation (_*) (HE × 200). (B) Kidney of rat administered colistin in doses of 450,000 IU/kg/day showing acute cortical necrosis with numerous tubular casts (↗) (HE × 400).

Table 3. Histological examination of renal lesions of colistin treated rats over 7 days.

		% Kidney slice affected in individual rats in each group (n = 6)
Abnormality grade	Control	Colistin in doses of 150,000 IU/kg/day	Colistin in doses of 300,000 IU/kg/day	Colistin in doses of 450,000 IU/kg/day
1	0, 0, 0, 0, 0, 0	0, 0, 0, 1, 0, 0	1, 1, 5, 1, 1, 5	0, 0, 0, 0, 0, 0
2	0, 0, 0, 0, 0, 0	0, 0, 0, 0, 0, 0	0, 0, 0, 0, 0, 0	20, 15, 15, 20, 15, 30
3	0, 0, 0, 0, 0, 0	0, 0, 0, 0, 0, 0	0, 0, 0, 0, 0, 0	0, 0, 0, 0, 0, 0
SQS for individual rats	0, 0, 0, 0, 0, 0	0, 0, 0, +1, 0, 0	+1, +1, +1, +1, +1, +1	+2, +1, +1, +2, +1, +3

Notes: Grade 1: mild acute tubular damage with tubular dilation, prominent nuclei and a few pale tubular casts. Grade 2: severe acute tubular damage with necrosis of tubular epithelial cells and numerous tubular casts (acute tubular necrosis). Grade 3: acute cortical necrosis/infarction of tubules and glomeruli with or without papillary necrosis.

A semi-quantitative score (SQS) for an individual rat was used to grade lesion severity. Scores of 0, +1, +2, +3, +4, and +5 correspond to no change, mild change, mild to moderate change, moderate change, moderate to severe change, and severe change, respectively.