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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="letter"><?properties open_access?><front><journal-meta><journal-id journal-id-type="nlm-ta">Korean J Intern Med</journal-id><journal-id journal-id-type="iso-abbrev">Korean J. Intern. Med</journal-id><journal-id journal-id-type="publisher-id">KJIM</journal-id><journal-title-group><journal-title>The Korean Journal of Internal Medicine</journal-title></journal-title-group><issn pub-type="ppub">1226-3303</issn><issn pub-type="epub">2005-6648</issn><publisher><publisher-name>The Korean Association of Internal Medicine</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23682235</article-id><article-id pub-id-type="pmc">3654139</article-id><article-id pub-id-type="doi">10.3904/kjim.2013.28.3.374</article-id><article-categories><subj-group subj-group-type="heading"><subject>Letter to the Editor</subject></subj-group></article-categories><title-group><article-title>The renoprotective effects of pentoxifylline: beyond its role in diabetic nephropathy</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Kapoor</surname><given-names>Shailendra</given-names></name><xref ref-type="aff" rid="A1-kjim-28-374"/></contrib></contrib-group><aff id="A1-kjim-28-374">Mechanicsville Clinic, Mechanicsville, VA, USA.</aff><author-notes><corresp>
Correspondence to Shailendra Kapoor, M.D. Mechanicsville Clinic, Rt 360, Mechanicsville, VA 23111, USA. Tel: +1-865-567-4567, Fax: +1-865-678-6787, <email>shailendrakapoor@yahoo.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>5</month><year>2013</year></pub-date><pub-date pub-type="epub"><day>01</day><month>5</month><year>2013</year></pub-date><volume>28</volume><issue>3</issue><fpage>374</fpage><lpage>376</lpage><history><date date-type="received"><day>26</day><month>10</month><year>2012</year></date><date date-type="rev-recd"><day>21</day><month>11</month><year>2012</year></date><date date-type="accepted"><day>22</day><month>11</month><year>2012</year></date></history><permissions><copyright-statement>Copyright &#xA9; 2013 The Korean Association of Internal Medicine</copyright-statement><copyright-year>2013</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><kwd-group><kwd>Pentoxifylline</kwd><kwd>Renal insufficiency, chronic</kwd><kwd>Renal</kwd></kwd-group></article-meta></front><body><p>To the Editor,</p><p>I read with great interest the article by Sun et al. [<xref ref-type="bibr" rid="B1-kjim-28-374">1</xref>]. Pentoxifylline may exert a number of renoprotective effects, besides its role in attenuating diabetic nephropathy. Pentoxifylline attenuates kidney damage secondary to hepatic ischemia/reperfusion injury. It mediates this action by decreasing malondialdehyde levels [<xref ref-type="bibr" rid="B2-kjim-28-374">2</xref>]. Simultaneously, it restores intracellular glutathione. As a result, oxidative injury to the kidneys is mitigated. Obviously, conditions such as hepato-renal syndrome can be avoided with pentoxifylline pretreatment. The coming years may very well see increased use of pentoxifylline as a prophylactic agent to prevent hepatorenal syndrome in patients with concurrent cirrhosis and ascites.</p><p>Pentoxifylline is also beneficial in chronic renal disease. It benefits the kidneys by stabilizing renal function and the glomerular filtration rate. Concurrent decreases in inflammatory markers such as tissue necrosis factor-&#x3B1; and high-sensitivity C-reactive protein reflect the attenuation of inflammatory damage in the kidneys. The interleukin-6 level also decreases at the same time [<xref ref-type="bibr" rid="B3-kjim-28-374">3</xref>]. In addition, pentoxifylline helps reduce proteinuria in chronic kidney disease (CKD) patients. Renke et al. [<xref ref-type="bibr" rid="B3-kjim-28-374">3</xref>] recently reported a 26% decline in proteinuria following pentoxifylline therapy in comparison with placebo therapy. Pentoxifylline also decreases proteinuria in CKD patients following renal transplantation. Moreover, pentoxifylline modulates hepcidin function and augments iron release, thereby improving hemoglobin levels in CKD patients.</p><p>By virtue of its antioxidant properties, pentoxifylline also mitigates and reduces renal damage secondary to exposure to cigarette smoke. Similarly, pentoxifylline is of benefit in cardiac surgery because it prevents and attenuates acute renal injury [<xref ref-type="bibr" rid="B4-kjim-28-374">4</xref>]. When used in conjunction with albumin, pentoxifylline protects the kidneys from injury following endotoxemic shock, by decreasing inducible nitric oxide synthase expression in the kidneys [<xref ref-type="bibr" rid="B5-kjim-28-374">5</xref>]. Similarly, the postlaparoscopy administration of pentoxifylline attenuates renal ischemia associated with laparoscopy.</p><p>These examples clearly illustrate the renoprotective effects of pentoxifylline.</p></body><back><fn-group><fn fn-type="conflict"><p>No potential conflict of interest relevant to this article is reported.</p></fn></fn-group><ref-list><ref id="B1-kjim-28-374"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>HK</given-names></name><name><surname>Lee</surname><given-names>YM</given-names></name><name><surname>Han</surname><given-names>KH</given-names></name><name><surname>Kim</surname><given-names>HS</given-names></name><name><surname>Ahn</surname><given-names>SH</given-names></name><name><surname>Han</surname><given-names>SY</given-names></name></person-group><article-title>Phosphodiesterase inhibitor improves renal tubulointerstitial hypoxia of the diabetic rat kidney</article-title><source>Korean J Intern Med</source><year>2012</year><volume>27</volume><fpage>163</fpage><lpage>170</lpage><pub-id pub-id-type="pmid">22707888</pub-id></element-citation></ref><ref id="B2-kjim-28-374"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seifi</surname><given-names>B</given-names></name><name><surname>Kadkhodaee</surname><given-names>M</given-names></name><name><surname>Delavari</surname><given-names>F</given-names></name><name><surname>Mikaeili</surname><given-names>S</given-names></name><name><surname>Shams</surname><given-names>S</given-names></name><name><surname>Ostad</surname><given-names>SN</given-names></name></person-group><article-title>Pretreatment with pentoxifylline and N-acetylcysteine in liver ischemia reperfusion-induced renal injury</article-title><source>Ren Fail</source><year>2012</year><volume>34</volume><fpage>610</fpage><lpage>615</lpage><pub-id pub-id-type="pmid">22364443</pub-id></element-citation></ref><ref id="B3-kjim-28-374"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Renke</surname><given-names>M</given-names></name><name><surname>Tylicki</surname><given-names>L</given-names></name><name><surname>Rutkowski</surname><given-names>P</given-names></name><etal/></person-group><article-title>Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease: placebo controlled, randomized, cross-over study</article-title><source>Acta Biochim Pol</source><year>2010</year><volume>57</volume><fpage>119</fpage><lpage>123</lpage><pub-id pub-id-type="pmid">20309434</pub-id></element-citation></ref><ref id="B4-kjim-28-374"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barkhordari</surname><given-names>K</given-names></name><name><surname>Karimi</surname><given-names>A</given-names></name><name><surname>Shafiee</surname><given-names>A</given-names></name><etal/></person-group><article-title>Effect of pentoxifylline on preventing acute kidney injury after cardiac surgery by measuring urinary neutrophil gelatinase-associated lipocalin</article-title><source>J Cardiothorac Surg</source><year>2011</year><volume>6</volume><fpage>8</fpage><pub-id pub-id-type="pmid">21247431</pub-id></element-citation></ref><ref id="B5-kjim-28-374"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bansal</surname><given-names>S</given-names></name><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Falk</surname><given-names>S</given-names></name><name><surname>Schrier</surname><given-names>R</given-names></name></person-group><article-title>Combination therapy with albumin and pentoxifylline protects against acute kidney injury during endotoxemic shock in mice</article-title><source>Ren Fail</source><year>2009</year><volume>31</volume><fpage>848</fpage><lpage>854</lpage><pub-id pub-id-type="pmid">19925295</pub-id></element-citation></ref></ref-list></back><response id="RE1-kjim-28-374" response-type="reply"><front-stub><title-group><article-title>In reply</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sun</surname><given-names>Hui-Kyoung</given-names></name><xref ref-type="aff" rid="AC1-kjim-28-374"/></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Han</surname><given-names>Sang-Youb</given-names></name><xref ref-type="aff" rid="AC1-kjim-28-374"/></contrib></contrib-group><aff id="AC1-kjim-28-374">Division of Nephrology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea.</aff><author-notes><corresp>
Correspondence to Sang-Youb Han, M.D. Division of Nephrology, Department of Internal Medicine, Inje University Ilsan Paik Hospital, 170 Juhwa-ro, Ilsanseo-gu, Goyang 411-706, Korea. Tel: +82-31-910-7884, Fax: +82-31-910-7219, <email>hansy@paik.ac.kr</email></corresp></author-notes></front-stub><body><p>We thank Dr. Kapoor for the precise comments on the effect of pentoxifylline (PTX) in diabetic nephropathy [<xref ref-type="bibr" rid="BC1-kjim-28-374">1</xref>] and other diseases.</p><p>Currently, PTX is used to treat peripheral vascular and bronchoconstrictive diseases [<xref ref-type="bibr" rid="BC2-kjim-28-374">2</xref>,<xref ref-type="bibr" rid="BC3-kjim-28-374">3</xref>]. Recently, the effects of PTX have been determined under various conditions, including antiphospholipid syndrome, alcoholic hepatitis, and wound healing. Several clinical trials of PTX in nonalcoholic steatohepatiti), contrast-induced nephropathy, radiation injury, and other conditions have been conducted.</p><p>Unfortunately, the effects of PTX in patients with diabetic nephropathy are unclear. This might be due to the heterogeneous clinical nature of diabetic nephropathy. Of diabetics with chronic kidney disease, 24% to 51% do not have albuminuria [<xref ref-type="bibr" rid="BC4-kjim-28-374">4</xref>,<xref ref-type="bibr" rid="BC5-kjim-28-374">5</xref>]. The resistance of the intrarenal arteries was increased in type 2 diabetics with impaired renal function regardless of proteinuria [<xref ref-type="bibr" rid="BC6-kjim-28-374">6</xref>]. These findings suggest that vasculopathy is a very important risk factor for the progression of diabetic nephropathy. 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