OBJECTIVE: This study evaluated the usefulness of plasma Cystatin C (pCysC) along with urinary neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate (AST) and alanine (ALT) aminotransferase to monitor colistin nephrotoxicity. METHOD: Male rats were given intramuscular (i.m.) injections of colistin in doses of 150,000 (G1), 300,000 (G2) and 450,000 IU/kg/day (G3) or normal saline (Control), every 12 h for 7 days. After the 14th injection, animals were placed in metabolic cages and urine samples were collected in the next 12 h. Thereafter, animals were euthanized, blood samples were collected and kidneys were removed for histological assessment. RESULTS: Nephrotoxicity was completely dose-dependent according to pathologic findings. The major insults were acute tubular necrosis in the tubules of G3. No significant change in pCr was observed in all treated groups, but pCysC increased in the G3 compared to the control. In urinary markers, uNGAL level showed a dose dependant increase with significant change in the G2 and G3 groups compared to the control. However, there was no significant change in the AST, ALT, LDH or ALP activities but only GGT increased in the G3 compared to the control. CONCLUSION: Based on colistin doses used in our experimental study on rat model, histopathologic assessment remains the most accurate way to diagnose colistin nephrotoxicity. pCysC appears to be more reliable than pCr, and uNGAL seems to be the most sensitive factor of colistin nephrotoxicity.
OBJECTIVE: This study evaluated the usefulness of plasma Cystatin C (pCysC) along with urinary neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyltransferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate (AST) and alanine (ALT) aminotransferase to monitor colistin nephrotoxicity. METHOD: Male rats were given intramuscular (i.m.) injections of colistin in doses of 150,000 (G1), 300,000 (G2) and 450,000 IU/kg/day (G3) or normal saline (Control), every 12 h for 7 days. After the 14th injection, animals were placed in metabolic cages and urine samples were collected in the next 12 h. Thereafter, animals were euthanized, blood samples were collected and kidneys were removed for histological assessment. RESULTS:Nephrotoxicity was completely dose-dependent according to pathologic findings. The major insults were acute tubular necrosis in the tubules of G3. No significant change in pCr was observed in all treated groups, but pCysC increased in the G3 compared to the control. In urinary markers, uNGAL level showed a dose dependant increase with significant change in the G2 and G3 groups compared to the control. However, there was no significant change in the AST, ALT, LDH or ALP activities but only GGT increased in the G3 compared to the control. CONCLUSION: Based on colistin doses used in our experimental study on rat model, histopathologic assessment remains the most accurate way to diagnose colistin nephrotoxicity. pCysC appears to be more reliable than pCr, and uNGAL seems to be the most sensitive factor of colistin nephrotoxicity.
Authors: Paulo Novis Rocha; Michael Nascimento Macedo; Carla Dinamérica Kobayashi; Lis Moreno; Luiz Henrique Santos Guimarães; Paulo Roberto Lima Machado; Roberto Badaró; Edgar M Carvalho; Marshall Jay Glesby Journal: Antimicrob Agents Chemother Date: 2015-08-24 Impact factor: 5.191
Authors: Johnny X Huang; Geraldine Kaeslin; Max V Ranall; Mark A Blaskovich; Bernd Becker; Mark S Butler; Melissa H Little; Lawrence H Lash; Matthew A Cooper Journal: Pharmacol Res Perspect Date: 2015-05-15
Authors: Norman Zinne; Marcus Krueger; Doris Hoeltig; Burkhard Tuemmler; Erin C Boyle; Christian Biancosino; Klaus Hoeffler; Peter Braubach; Taufiek K Rajab; Anatol Ciubotaru; Judith Rohde; Karl-Heinz Waldmann; Axel Haverich Journal: PLoS One Date: 2018-03-05 Impact factor: 3.240
Authors: Aiping Zhang; Kitipong Uaesoontrachoon; Conner Shaughnessy; Jharna R Das; Sree Rayavarapu; Kristy J Brown; Patricio E Ray; Kanneboyina Nagaraju; John N van den Anker; Eric P Hoffman; Yetrib Hathout Journal: Toxicol Rep Date: 2015