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&#945;1-microglobulin &#40;&#945;1M&#41;&#44; &#946;2-microglobulin &#40;&#946;2M&#41; and the kidney injury molecule &#40;KIM-1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The aim of this study was to search for the effects of urinary cadmium excretion on markers of early renal injury in population living in suburban communities in central Mexico&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study was done in 7 communities located close to Queretaro city in Central Mexico&#59; farming and agricultural practices are common but these areas are rounded by manufacturing activities&#46; We evaluated 90 voluntary healthy subjects &#40;&#8805;20 years old&#41;&#44; using a simple probabilistic sampling procedure on every of the communities studied&#46; Those with current urinary tract infection&#44; previous diagnosis of kidney disease&#44; liver disease&#44; cancer&#44; or other chronic disease&#44; as well as pregnant women were excluded&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A questionnaire was used to obtain information on personal health history&#44; and risk factors to Cd exposure&#46; Blood pressure measurements were obtained with an aneroid sphygmomanometer after a 5<span class="elsevierStyleHsp" style=""></span>min resting in sitting position&#44; and blood samples were taken after a fasting &#8805;8<span class="elsevierStyleHsp" style=""></span>h during the same visit&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">GFR was calculated with the CKD-Epi formula and spot urine samples for albumin&#44; &#945;1-microglobulin and cadmium analysis were collected in cadmium-free containers&#46; Albumin and &#945;1M were creatinine adjusted&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cd measurements were done at the Department of Environmental Toxicology Laboratory &#40;San Luis Potosi Medical School&#41;&#59; and quantification was carried out with a Perkin-Elmer 3110 atomic absorption spectrometer&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We categorized urinary Cd excretion in two groups according to CdU excretion and multivariate analysis was performed to identify risk factors for high Cd levels&#44; albuminuria and higher urinary &#945;1M&#46; A <span class="elsevierStyleItalic">p</span> value &#8804;0&#46;05 was considered as statistically significant and data were analyzed using the SPSS 23&#46;0 software&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The overall analysis included 90 adults with no antecedent of occupational exposure to Cd&#44; 66&#46;6&#37; of all participants were women and the mean age was 41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 years&#59; CdU median levels were 0&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr and few patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; had CdU &#8805;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Those subjects with CdU<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;37<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr had higher levels of &#945;1M &#40;9&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9 vs 3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#44; 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<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; and albumin &#40;11&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18 vs 3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;gCr&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#59; CdU was associated with a higher risk for &#945;1M<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr &#40;OR 4&#46;1&#44; CI95 1&#46;1&#8211;19&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; and CdU was the most important factor associated with higher &#945;1M excretion&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">This is the first study done in Mexico to evaluate the effects of Cd on kidney injury markers such as albumin and &#945;1M&#44; and in this study we showed that in this population living in central Mexico the non-critical levels of urinary Cd excretion had an important effect on markers of tubular injury&#44; though association with low GFR was not found&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Cadmium levels in this study were just above to those reported in other countries such as the United States &#40;media 0&#46;26<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44; Spain &#40;media 0&#46;28<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44; or Korea &#40;media 0&#46;30<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a>&#59; however&#44; comparing the results with other studies that had shown nephrotoxicity associated to CdU&#44; the threshold reported for CdU is higher &#40;0&#46;8&#8211;1&#46;0<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> so our finding is of interest because the CdU levels analyzed in our study are in a range considered as non-nephrotoxic&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Tubular injury and urinary excretion of tubular injury markers are the first clinical manifestations of Cd nephrotoxicity&#44; and some studies have found association between urinary &#945;1M and tubular atrophy&#44; GFR decline&#44; and higher mortality&#59; however its role in progressive kidney disease is controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Some limitations of this study are the small number of patients&#44; the high representation of women&#44; the lack of Cd environmental levels and of reliable epidemiological data about the prevalence of low GFR in the communities studied&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows that non-critical Cd excretion is a risk factor associated with an increased excretion of markers of tubular injury and further work need to be done to test Cd as a possible toxin in the occurrence of CKD of unknown etiology in Mexico &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1&#8211;2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they do not have conflicting interest&#46;</p></span></span>"
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          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; SBP&#58; systolic blood pressure&#59; DBP&#58; diastolic blood pressure&#59; &#945;1M&#58; &#945;1-microglobuline&#59; AUE&#58; albumin urinary excretion&#59; GFR&#58; glomerular filtration rate&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cd<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;37 &#40;&#956;g&#47;gCr&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Cd<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>37 &#40;&#956;g&#47;gCr&#41;<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Females &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Smokers &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">112<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">122<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">DBP &#40;mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#945;1M &#40;&#956;g&#47;gCr&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AUE &#40;g&#47;gCr&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">eGFR &#40;ml&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#945;1M</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">AUE</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;172&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;111&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">BMI&nbsp;\t\t\t\t\t\t\n
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Letter to the Editor
Non-critical urinary cadmium excretion as a risk factor associated with tubular markers of early kidney injury in Central Mexico
Niveles no-críticos de excreción urinaria de cadmio como factor de riesgo asociado con marcadores tubulares de daño renal temprano en la región central de México
Ma. Ludivina Robles-Osorioa, Pablo García-Solísa, Juan Carlos Solís-Sainza, Diana Montero-Pereab, Itzel Avilés-Romob, Elizabeth Sabath-Silvac, Angeles Ochoa-Martínezd, Iván Pérez-Maldonadod, Ernesto Sabatha,e,
Autor para correspondencia
esabath@yahoo.com

Corresponding author.
a Endocrinology and Metabolism Laboratory, Universidad Autónoma de Querétaro, Mexico
b Medical School, Universidad Autónoma de Querétaro, Mexico
c Cellular Biology and Physiology Department, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico
d Department of Environmental Toxicology Laboratory, Medical School, Universidad Autónoma de San Luis Potosí, Mexico
e Renal Department, Hospital General de Querétaro, Mexico
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Cadmium &#40;Cd&#41; is an ubiquitous element in nature and high levels of Cd exposure is considered a risk factor for renal injury&#59; however&#44; their nephrotoxic effects at low-environmental exposure levels are debated&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Cd accumulates in the proximal tubule renal cells where inhibits the mitochondrial respiratory chain and this results in mitochondrial dysfunction and free radical formation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Some of the urinary markers used to evaluate Cd nephrotoxicity are N-acetyl-&#946;-<span class="elsevierStyleSmallCaps">d</span>-glucosaminidase &#40;NAG&#41;&#44; &#945;1-microglobulin &#40;&#945;1M&#41;&#44; &#946;2-microglobulin &#40;&#946;2M&#41; and the kidney injury molecule &#40;KIM-1&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The aim of this study was to search for the effects of urinary cadmium excretion on markers of early renal injury in population living in suburban communities in central Mexico&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The study was done in 7 communities located close to Queretaro city in Central Mexico&#59; farming and agricultural practices are common but these areas are rounded by manufacturing activities&#46; We evaluated 90 voluntary healthy subjects &#40;&#8805;20 years old&#41;&#44; using a simple probabilistic sampling procedure on every of the communities studied&#46; Those with current urinary tract infection&#44; previous diagnosis of kidney disease&#44; liver disease&#44; cancer&#44; or other chronic disease&#44; as well as pregnant women were excluded&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A questionnaire was used to obtain information on personal health history&#44; and risk factors to Cd exposure&#46; Blood pressure measurements were obtained with an aneroid sphygmomanometer after a 5<span class="elsevierStyleHsp" style=""></span>min resting in sitting position&#44; and blood samples were taken after a fasting &#8805;8<span class="elsevierStyleHsp" style=""></span>h during the same visit&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">GFR was calculated with the CKD-Epi formula and spot urine samples for albumin&#44; &#945;1-microglobulin and cadmium analysis were collected in cadmium-free containers&#46; Albumin and &#945;1M were creatinine adjusted&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Cd measurements were done at the Department of Environmental Toxicology Laboratory &#40;San Luis Potosi Medical School&#41;&#59; and quantification was carried out with a Perkin-Elmer 3110 atomic absorption spectrometer&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We categorized urinary Cd excretion in two groups according to CdU excretion and multivariate analysis was performed to identify risk factors for high Cd levels&#44; albuminuria and higher urinary &#945;1M&#46; A <span class="elsevierStyleItalic">p</span> value &#8804;0&#46;05 was considered as statistically significant and data were analyzed using the SPSS 23&#46;0 software&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The overall analysis included 90 adults with no antecedent of occupational exposure to Cd&#44; 66&#46;6&#37; of all participants were women and the mean age was 41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12 years&#59; CdU median levels were 0&#46;37<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;41<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr and few patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; had CdU &#8805;1<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Those subjects with CdU<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;37<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr had higher levels of &#945;1M &#40;9&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9 vs 3&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and albumin excretion &#40;13&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24 vs 3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;gCr&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Those patients with higher CdU excretion had a higher risk for &#945;1M<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10 &#40;OR 5&#46;0&#44; CI95 1&#46;4&#8211;18&#46;6&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and micro-albuminuria &#40;OR 20&#44; CI95 1&#46;0&#8211;39&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In multivariate analysis&#44; CdU was the most important risk factor associated with higher &#945;1M excretion and albuminuria after adjustments for age&#44; BMI&#44; smoking status&#44; blood pressure&#44; lead concentration and GFR&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In non-smoking subjects&#44; those with CdU<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;37<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr had higher urinary excretion of &#945;1M &#40;7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;2 vs 3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;7<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41; and albumin &#40;11&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18 vs 3&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;gCr&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#59; CdU was associated with a higher risk for &#945;1M<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr &#40;OR 4&#46;1&#44; CI95 1&#46;1&#8211;19&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; and CdU was the most important factor associated with higher &#945;1M excretion&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">This is the first study done in Mexico to evaluate the effects of Cd on kidney injury markers such as albumin and &#945;1M&#44; and in this study we showed that in this population living in central Mexico the non-critical levels of urinary Cd excretion had an important effect on markers of tubular injury&#44; though association with low GFR was not found&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Cadmium levels in this study were just above to those reported in other countries such as the United States &#40;media 0&#46;26<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44; Spain &#40;media 0&#46;28<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44; or Korea &#40;media 0&#46;30<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6&#44;7</span></a>&#59; however&#44; comparing the results with other studies that had shown nephrotoxicity associated to CdU&#44; the threshold reported for CdU is higher &#40;0&#46;8&#8211;1&#46;0<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;gCr&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> so our finding is of interest because the CdU levels analyzed in our study are in a range considered as non-nephrotoxic&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Tubular injury and urinary excretion of tubular injury markers are the first clinical manifestations of Cd nephrotoxicity&#44; and some studies have found association between urinary &#945;1M and tubular atrophy&#44; GFR decline&#44; and higher mortality&#59; however its role in progressive kidney disease is controversial&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Some limitations of this study are the small number of patients&#44; the high representation of women&#44; the lack of Cd environmental levels and of reliable epidemiological data about the prevalence of low GFR in the communities studied&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study shows that non-critical Cd excretion is a risk factor associated with an increased excretion of markers of tubular injury and further work need to be done to test Cd as a possible toxin in the occurrence of CKD of unknown etiology in Mexico &#40;<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1&#8211;2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that they do not have conflicting interest&#46;</p></span></span>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">77&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">122<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;057&nbsp;\t\t\t\t\t\t\n
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    "bibliografia" => array:2 [
      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current status of cadmium as an environmental health problem"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46; Jarup"
                            1 => "A&#46; Akesson"
                          ]
                        ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.taap.2009.04.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Toxicol Appl Pharmacol"
                        "fecha" => "2009"
                        "volumen" => "238"
                        "paginaInicial" => "201"
                        "paginaFinal" => "208"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19409405"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low-level cadmium exposure and effects on kidney function"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Wallin"
                            1 => "G&#46; Sallsten"
                            2 => "T&#46; Lundh"
                            3 => "L&#46; Barregard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/oemed-2014-102279"
                      "Revista" => array:7 [
                        "tituloSerie" => "Occup Environ Med"
                        "fecha" => "2014"
                        "volumen" => "71"
                        "paginaInicial" => "848"
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