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Hypoxic pre-conditioning in a rat renal ischemia model: an evaluation of the use of hydralazine

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Abstract

Introduction

With the advent of improved diagnostic and imaging techniques, it is now possible to detect renal cancers in their very early stages, when they are still present as small renal masses. In these situations, use of laparoscopic partial nephrectomy (LPN) techniques are indicated and have gained acceptance in major medical institutions worldwide, offering comparable oncological outcomes and improving quality of life in the patient when contrasted with open nephrectomy procedures. However, a complication that may occur during or after this surgery is the possibility of compromising renal function, as a result of extended ischemia times of more than 30 min. We have undertaken a systematic study of the potential of several agents that may enhance renal parenchymal preservation without causing unwanted renal dysfunction as a result of enhanced ischemia times. In this study, we have evaluated the potential of one such agent under study, namely hydralazine, which was shown earlier to enhance hypoxia inducible factor-1α (HIF-1α) levels in experimental animal systems. Our aim was to determine whether enhanced levels of HIF-1α via pre-treatment with hydralazine had a reno-protective effect after ischemic injury.

Materials and methods

Rats were injected with hydralazine or saline for 5 days prior to right nephrectomy and 40 min of cross-clamping of the left renal pedicle. Ischemic damage was monitored via serum chemistry and renal pathology.

Results

In our system, we found that hydralazine pre-treatment, even though it enhanced HIF-1α levels in the kidney, it also increased serum creatinine and worsened the morphological damage to the renal tubules in the ischemic kidney.

Conclusions

We conclude that even though this agent was described as a powerful inhibitor of prolyl hydroxylases, enhancing the levels of HIF-1α, it should be approached with caution when it is considered to enhance warm ischemia time and minimize the renal damage subsequent to LPN.

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Abbreviations

LPN:

Laparoscopic partial nephrectomy

HIF:

Hypoxia inducible factor

PAS:

Periodic acid-Schiff

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

PHD:

Prolyl hydroxylase

BUN:

Blood urea nitrogen

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Acknowledgments

This work was supported in part by the Susan Schott Memorial Fund and the Department of Urology, Saint Vincent Medical Center.

Conflict of interest statement

There is no conflict of interest.

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Authors and Affiliations

  1. Department of Urology, Saint Vincent Medical Center, 170 West 12th Street, Cronin-205, New York, NY, 10011, USA

    Catherine Michels, Thambi Dorai & Michael Grasso

  2. Renal Pathology Division, Department of Pathology, Westchester Medical Center, New York Medical College, Valhalla, NY, 10595, USA

    Praveen Chander

  3. Department of Urology, New York Medical College, Valhalla, NY, 10595, USA

    Catherine Michels & Muhammad Choudhury

Authors
  1. Catherine Michels
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  2. Thambi Dorai
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  5. Michael Grasso
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Corresponding authors

Correspondence to Thambi Dorai or Michael Grasso.

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Michels, C., Dorai, T., Chander, P. et al. Hypoxic pre-conditioning in a rat renal ischemia model: an evaluation of the use of hydralazine. World J Urol 27, 817–823 (2009). https://doi.org/10.1007/s00345-009-0415-z

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  • DOI: https://doi.org/10.1007/s00345-009-0415-z

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