Proton pump inhibitors: are they safe on kidneys: a histopathological study

Ramachandra Prabhakar Limaye; Shabbir Rafik Pendhari; Kedar Shashikant Joshi

doi:10.18203/2319-2003.ijbcp20162220

Authors

Ramachandra Prabhakar Limaye Department of Pharmacology, Bharati Vidyapeeth Deemed University, Medical College and Hospital, Sangli, Maharashtra, India
Shabbir Rafik Pendhari Department of Pharmacology, Bharati Vidyapeeth Deemed University, Medical College and Hospital, Sangli, Maharashtra, India
Kedar Shashikant Joshi Department of Pharmacology, Bharati Vidyapeeth Deemed University, Medical College and Hospital, Sangli, Maharashtra, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20162220

Keywords:

AIN, Diclofenac, Histopathological examination, Ofloxacin, PPI

Abstract

Background: In India the utilization of PPI varies to 45-85%. PPI were used in 82.96% patient with chronic kidney disease. But now a day’s several case reports are suggesting PPI induces AIN. The exact rate of this rare adverse event is difficult to estimate because many patients are taking multiple medications, which also make it difficult to establish a causal relation between AIN and PPI. Early detection of AIN and immediate discontinuation of culprit drug may prevent progress of AIN to the end stage chronic kidney disease. So we planned a study to establish the relationship between PPI and AIN, if any.

Methods: Rats weighing 150-250 gm were used. In this study omeprazole, pantoprazole and rabeprazole were administered for 28 day group A - alone, Group B-with diclofenac and group C - ofloxacin, after 28^th day the animal with deranged RFTs were grouped 2 animals were sacrificed from each group. And there histopathological studies were carried out.

Results: At least 3 rats showed deranged RFTs in each group. And most of the histopathological studies show structural, vascular changes with or without AIN.

Conclusions: PPI alone are prone to cause AIN but the incidence of AIN is increases with addition of other nephrotoxic dugs.

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References

Geevasinga N, Patrik LC, Angela CW, Simon DR. Proton pump inhibitors and acute interstitial nephritis. Clin gastro hep. 2006;4:597-604.

U.S. Pharmaceutical Sales-2013. Available at www.drug.com/stat/top100/2013/sales on date 13/ 01/2016. Accessed on 13 January 2016.

Proton pump inhibitors: when is enough, enough? Brit J Pharmacol Issue. 2014:8-15.

Ingle P, Patil P, Lathi V. Study of rational prescribing and dispending of prescription with non-steroidal anti-inflammatory drug in orthopedic outpatient department. Asian J Pharmac Clinic Res. 2015:8(4):278-81.

Barot PA, Malhotra SD, Rana DA, Patel VJ, Patel KP. Drug utilization in emergency medicine department at a tertiary care hospital: a prospective study. J basic clin pharmacy. 2013;4(4):78-81.

Tamilsevan T, Veerapandiyan AK, Karthik N. study on drug utilization pattern of chronic renal failure patient in a tertiary care hospital. Int j pharm sci. 2014;6(9):482-4.

Ray S, Delaney M, Mullar AF. Proton pump inhibitors and acute interstitial nephritis. Brit Med J. 2010;34:668-70.

Linda H, Hans EVDW, Mark CHDG, van Grootheest AC. Proton pump inhibitors induced acute interstitial nephritis. Br J Clinpharmacol. 2007;64(6):819-23.

Sampathkumar K, Ramlingam R, Prabhakar A, Abraham A. Acute interstitial nephritis due to proton pump inhibitors. Ind Jnephro. 2013;23(4):304-7.

Sheila K, Joan CK, Ally PHP. Pantoprazole -induced acute interstitial nephritis. Can med Asso J. 2013;185(1):56-9.

Jeffrey R, Gil K, James S, Rene W. Acute allergic interstitial nephritis after use of pantoprazole. Can med Asso J. 2009;180(5):535-8.

Sierra F, Suarez M, Rey M, Vela MF. Systematic review: proton pump inhibitors - associated acute interstitial nephritis. Aliment pharmacol Ther. 2007;26:545-53.

Amy R, Tobe SW. Acute interstitial nephritis due to pantoprazole. Ann pharmacotherapy. 2004;38:41-5.

Mouli VP, Ahuja V. Proton pump inhibitors: concerns over prolonged use. Trop Gastro. 2011;32(3):175-84.

Gupta S. Basic principles of clinical research and methodology: first edition: Appendix III - animal toxicity (non-clinical toxicology studies). Jaypee brothers medical publishers (P) ltd. New Delhi; 2007:471-483.

Ghosh MN. Some standard techniques in, fundamentals of pharmacology. Third edition. Hilton and company Kolkata; 2005:15-18.

Fuchs TC, Frick K, Emde B, Czusch S, Landenberg FV, Hewitt P. evaluation of novel acute urinary rat kidney toxicity biomarker for Subacute toxicity studies in preclinical trial. Toxicologic pathology. 2012;40:1034-48.

Erdem A, Gundogan NV, Usubutun A, Kilinc K, Erdem R, Kara A. The protective effect of taurine against gentamycin-induced acute tubular necrosis in rats. Nephrol dial transplant. 2000;15:1175-82.

Keppler A, Gretz N, Schmidt R, Kloetzer HM, Groene HJ, Leiongt B, et al. Plasma creatinine determination in mice and rat: an enzymeatic method compares to variably with a high performance liquid chromatography assay. Kidney international. 2007;71:74-8.