[doi: 10.5505/2017ichc.PP-227]

Can Urine Alkalinisation Be A Treatment Option On Colistin Induced Nephrotoxicity: An Ultrastructural And Histochemical Study In Rats

¹Hacettepe University Faculty of Medicine, Department of Internal Medicine, Ankara,Turkey
²Hacettepe University Faculty of Medicine, Department of Histology and Embryology,Ankara,Turkey
³Ankara University Faculty of Veterinary Medicine, Department of Biyochemistry,Ankara,Turkey
⁴Hacettepe University Laboratory Animal Research Center, Ankara,Turkey
⁵Hacettepe University Faculty of Medicine, Department of Preventive Oncology, Ankara,Turkey
⁶Hacettepe University Faculty of Medicine, Medical Student, Ankara,Turkey
⁷Hacettepe University Faculty of Medicine, Department of Infectious Diseases, Ankara,Turkey
⁸Hacettepe UniversityFaculty of Medicine, Department of Nephrology, Ankara,Turkey

Colistin is a vital antibiotic that is used in drug-resistant nosocomial infections. The most important side effect is nephrotoxicity (Acute tubular necrosis). Colistin is a weak acid. The aim of this study is to evauate the possible protection of urine alkalinisation that is used in toxicities of weak acids. Sprauge Dawley rats were divided into four groups. Group-I (control) were injected intramuscular distilated water. Group-II (colistin) were injected 750000 IU/kg/day of colistin. Group-III (colistin-bicarbonate) were injected same dose of colistin, after they reach urinary pH >7 by addition of bicarbonate in their drinking water. Group-IV (colistin-NaCl ) were injected the same dose of colistin after reaching Group-III’s urine density by adding NaCl in their drinking water. Serum urea levels showed borderline statistical difference (p=0,046) but, it was not clinically correlated when compared histopathologically. Serum creatinine values showed no statistical difference (p=0,131). According to histological tubular degeneration average scores evaluated by light microscopy (scored 0-5,Table-1) and electron microscopy; Group-I scored “0”, Group-II scored “4,25±0,89”, Grup-III scored “2±1,26”, and Grup-IV scored “1,5±0,55”. In Group-III and Group-IV, protection was achieved against nephrotoxic agent (p<0,001).
Normal renal tubule epithelium were observed in the control group.
Mild-marked tubuler degeneration was detected in colistin-treated rats, the tubules had pyknotic nuclei, vacuolation in the cytoplasm and sloughed cells were seen within tubular lumina (protein casts) (Figure-1).
In colistin-bicarbonate group, less tubules were affected, and a small number of protein casts, vacuolization and necrosis were detected (Grade1-4 tubuler degeneration). In some areas pale basophilic accumulations were seen in tubule lumen, and basal membrane separation were detected.
In colistin-NaCl group there were a few dilatated tubules with separated epithelial cells. Interstitial edema and pyknotic nuclei of the spilled cells were observed in some of the tubule’s lumen (Figure-2).
Bicarbonate group was not superior to NaCl group(p=0,601). Urine densities and tubular degeneration scores were statistically correlated independent of the groups. The lower the urine density was, the
lower the tubular score(p=0.001). Bicarbonate hydration is not superior to NaCl hydration, and both are effective similarly. Decrease in urine density is correlated with tubular protection.

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Figure 2

Significant interstitial edema in the right, kidney biopsy ×20 objective H&E

Figure-1

Vacuolation of the cytoplasm, renal cortex. Original magnification×63 H&E

Table-1.

Score	Tubuler Degenaration Grade	Histopathological Findings
0	Normal	Normal renal tubuler epitelial cells
1	Minimal	Tubuler cells with brightly eosinophilic cytoplasm and pyknotic nuclei;
2	Slight	Occasional degenerate cells with pyknotic to karyorrhectic nuclei and sloughed cells within tubular lumina (protein casts)
3	Mild	Small clusters of 2–4 degenerate cells with pyknotic nuclei and protein casts
4	Moderate	Larger clusters and chains of degenerate cells, some with complete loss of chromatin, affecting numerous tubules
5	Marked	Majority of tubules affected by chains of degenerate cells, or entire tubular segments affected by degeneration.

The histopathological grading scheme for tubuler degeneration, Keirstead et all.