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a predominantly female disease&#44;<span class="elsevierStyleSup">13</span> encompassing many ethnicities&#44;<span class="elsevierStyleSup">13</span> reduced muscle mass&#44;<span class="elsevierStyleSup">14</span> and with a wide range of renal function&#46;<span class="elsevierStyleSup">15</span> However&#44; there is a paucity of data regarding the equations for estimating renal function in patients with SLE&#46;<span class="elsevierStyleSup">15-17</span> Moreover&#44; almost half of the rheumatologists use CrCl in all of their patients in order to estimate GFR&#44; a method with a high rate of inappropriate collection and more expensive than the creatinine based equations&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">To our knowledge&#44; no study has determined the best equation for estimating renal function in patients with SLE&#44; starting from iothalamate urinary clearance as gold standard&#46; Therefore&#44; we performed this study to evaluate which is the best equation&#44; based on serum creatinine&#44; to assess renal function in patients with SLE&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHODS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We included&#44; in consecutive selection&#44; all patients with SLE according to the American College of Rheumatology &#40;ACR&#41; criteria&#46;<span class="elsevierStyleSup">19&#44;20</span></p><p class="elsevierStylePara">Exclusion criteria&#58; patients under 18 years old&#44; asthma&#44; hypothyroidism&#44; current smoking&#44; malignancy&#44; prednisone doses &#8805;30mg&#47;d &#40;or the equivalent dose of another glucocorticoid&#41;&#44; pregnancy and severe disease activity &#40;MEX-SLEDAI&#8805;8&#41;&#46;<span class="elsevierStyleSup">21</span> All patients signed informed consent and our study was approved by the Central Hospital Institutional Review Board&#46;</p><p class="elsevierStylePara">Ideal body weight &#40;IBW&#41; was calculated &#40;Robinson equation&#41;&#46;<span class="elsevierStyleSup">22</span> Body surface index &#40;BSI&#41; was calculated in accordance with the Dubois equation&#46;<span class="elsevierStyleSup">23</span></p><p class="elsevierStylePara">We divided this study into 2 phases&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Phase 1&#58; </span>We measured GFR with iothalamate urinary clearance in 14 patients with SLE&#46; GFR calculated through iothalamate was compared with the GFR estimated through cystatin and&#47;or creatinine based equations&#46; The main objective in this phase was to validate the best cystatin&#47;creatinine-based equation to use at the second phase as our reference standard &#40;Table 1&#41;&#46;<span class="elsevierStyleSup">11&#44;24-27</span> We selected cystatin-based equations for this study from equations developed in other studies taking into account&#58; studies were developed from adult patients&#44; with more than 100 patients&#44; and the measurement of cystatin C had been made by the same method used in our study &#40;immunonephelometry&#44; PENIA&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Phase 2&#58;</span> The best cystatin&#47;creatinine-based equation found in phase I was taken as the reference standard &#40;measured GFR&#41; to assess CrCl and creatinine-based equations &#40;Table 1&#41; in 55 patients &#40;estimated GFR&#41;&#46;<span class="elsevierStyleSup">5&#44;7&#44;28</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Laboratory tests</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We recalibrated serum creatinine values to standardized creatinine measurements by using the Roche enzymatic method as described elsewhere&#46;<span class="elsevierStyleSup">10&#44;29</span></p><p class="elsevierStylePara">Serum cystatin C was measured using a particle-enhanced immunonephelometric assay &#40;N Latex Cystatin C&#44; Dade Behring&#44; IL&#41;&#46; The between-day assay coefficient of variation was 3&#46;5&#37;&#46;</p><p class="elsevierStylePara">In phase 1&#44; all patients had a non-radiolabeled iothalamate clearance using a previously described standard laboratory method&#46;<span class="elsevierStyleSup">30</span> In brief&#44; after oral hydration with 4&#8211;6 glasses of water&#44; patients received a subcutaneous injection of non-radiolabeled iothalamate &#40;Conray<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Following a 1-h equilibrium period&#44; the patient voided&#44; the &#64257;rst serum sample was drawn and a timed urine collection was begun&#46; A sonographic scanner assessed bladder emptying and a bladder catheter was placed in patients with urinary retention&#46; Following the timed urine collection &#40;approximately 45&#8211;60min&#41;&#44; a second serum sample was obtained&#46; GFR was calculated by the clearance equation &#40;UIoV&#47;Pio where UIo and PIo are the urine and plasma concentrations of iothalamate&#44; and V is the urine &#64258;ow&#41; using the mean of two serum samples and one urine sample assayed for iothalamate via capillary electrophoresis&#46; All GFR measurements were standardized for BSI &#40;per 1&#46;73m<span class="elsevierStyleSup">2</span>&#41; by multiplying by 1&#46;73 and dividing by BSI&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We used R&#44; version 2 &#40;Free Software Foundation&#44; Boston&#44; Massachusetts&#41; to compute all analyses&#46;</p><p class="elsevierStylePara">Categorical variables are presented as frequencies and percentages&#44; and continuous variables as means and standard deviations&#44; or medians and &#40;minimum-maximum&#41; for variables with skewed distributions&#46;</p><p class="elsevierStylePara">Measured GFR &#40;mGFR&#41; and estimated GFR &#40;eGFR&#41; were compared for each patient graphically by plotting mGFR and the difference &#40;mGFR - eGFR&#41; against eGFR&#46; A smoothed regression line is shown with the 95&#37; confidence interval &#40;95&#37; CI&#41; computed by using the lowest smoothing function in R&#44; and using quantile regression&#44; excluding the lowest and highest 2&#46;5&#37; of estimated GFR&#46; Bias was expressed as the median difference &#40;mGFR - eGFR&#41;&#44; with positive values indicating an under-estimation of mGFR&#46; Precision was expressed as interquartile range &#40;IQR&#41; for the differences &#40;dIQR&#41;&#46; Accuracy was expressed as the percentage of eGFR within 30&#37; of mGFR &#40;P30&#41;&#46; Confidence intervals &#40;CI&#41; were computed by using bootstrap methods &#40;2&#44;000 bootstraps&#41; for median differences and IQR of the differences and by the binomial method for P30&#46;</p><p class="elsevierStylePara">The reference method or mGFR was iothalamate for phase I&#44; and the best cystatin&#47;creatinine-based equation &#40;Stevens&#8217; equation&#41; for phase 2&#46;</p><p class="elsevierStylePara">The best equation in both phases was that which had less bias&#44; less dIQR and higher P30&#46;</p><p class="elsevierStylePara">In phase 2 we constructed a 2x2 contingency table to determine the sensitivity and specificity of each equation to classify if each one of the patients had or not had GFR&#60;60 ml&#47;min per 1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In the first phase we included 14 patients&#59; their median age was 32&#46;5 years old&#44; and 61&#46;5 months of mean SLE evolution time &#40;Table 2&#41;&#46; Table 3 shows the results of the first phase which highlights the fact that the equation based on creatinine and cystatin C developed by Stevens and colleagues<span class="elsevierStyleSup">11</span> &#40;Stevens&#8217; equation&#41; had the best bias and the most accuracy&#46;</p><p class="elsevierStylePara">Because our patients were selected for their low disease activity and drug doses&#44; and because of the interference of these factors may have on cystatin C levels&#44; for the clinician&#44; the better setting is to have a creatinine-based equation than a cystatin-based equation&#44; so we performed a second phase with more patients to determine the best creatinine-based equation to estimate GFR in patients with SLE &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">Table 4 shows how the bias&#44; precision and accuracy are better with the CKD-EPI equation than with the others&#46; In this phase&#44; 55 patients were included&#59; median age was 36 years old and SLE evolution time was 60 months &#40;Table 2&#41;&#46;</p><p class="elsevierStylePara">Figure 1 shows the difference between measured and estimated versus estimated GFR in phase 2&#46; A smoothed regression line is shown with the 95&#37; CI&#44; using quantile regression&#46; Notice how the CKD-EPI equation has a good performance both at high and low GFR&#46;</p><p class="elsevierStylePara">Table 5 shows sensitivity and specificity of each equations to detect GFR less than 60ml&#47;min&#47;1&#46;73&#46; Eleven patients had GFR less than 60ml&#47;min&#47;1&#46;73 according to Stevens&#8217; equation&#44; CKD-EPI misclassified 1 patient &#40;1&#46;8&#37;&#41;&#44; sMDRD 2 &#40;3&#46;6&#37;&#41;&#44; CG 4 &#40;7&#46;3&#37;&#41;&#44; CGi 6 &#40;10&#46;9&#37;&#41;&#44; MCQ 5 &#40;9&#46;1&#41; and CrCl 4 &#40;7&#46;3&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The GFR should be determined as accurately as possible&#44; ideally with an accessible and inexpensive method which does not cause harm to the patient&#46; Several factors affect serum creatinine level other than GFR&#44; including its generation from muscle metabolism&#59; these factors compromise the generalization of the equations in patients with SLE&#46; Cystatin-based equations has no dependence on muscle mass&#44; but previous studies showed evidence for non-GFR determinants of cystatin C &#40;inflammation&#44; glucocorticoids&#44; thyroid disease and cytotoxic drugs&#41;&#59; variation in these factors can restrict the use of this protein for measuring GFR in patients with SLE&#46;<span class="elsevierStyleSup">31</span> Even though we reported previously that Cystatin C does not correlate with disease activity and drug doses&#44;<span class="elsevierStyleSup">32</span> we selected our patients avoiding these factors&#46;</p><p class="elsevierStylePara">Because there are multiple equations to estimate GFR&#44; the management guidelines of patients with SLE are based on studies in other different diseases from SLE and we think that the results on these diseases cannot be extrapolated to SLE&#46;<span class="elsevierStyleSup">8</span> National Kidney Foundation &#40;NKF&#41; guidelines suggest using the GFR estimating equations &#40;not the CrCl&#41; to achieve a better assessment of renal function&#46;<span class="elsevierStyleSup">6&#44;7</span> In spite of these recommendations&#44; 24 h urine collection to determine CrCl is a widely used method for assessing GRF in patients with SLE &#40;including clinical trials&#41;&#46;<span class="elsevierStyleSup">16&#44;33-35</span></p><p class="elsevierStylePara">Our study identifies several important findings&#58; 1&#41; The equation developed by Stevens and colleagues based on creatinine and cystatin C is the best equation to estimate renal function for our specifically selected SLE patients &#40;with low disease activity&#44; low doses of glucocorticoids&#44; no smoking&#44; no hypothyroidism&#41;&#46; 2&#41; Because of all those factors that the clinicians must take into account when using cystatin C in a patient with SLE &#40;smoking&#44; hypothyroidism&#44; etc&#46;&#41;&#44; we looked for an equation based only on serum creatinine in which there is not the influence of these factors and our results were&#58; the CKD-EPI equation should be used in patients with SLE&#46;</p><p class="elsevierStylePara">The importance of our results is that we do not need a 24h urine collection to evaluate renal function in SLE patients as was done in several clinical trials&#46;<span class="elsevierStyleSup">33-35</span> Moreover&#44; CKD-EPI is more reliable than CrCl and the other equations&#44; as our study describes&#46; Rheumatologists can estimate renal function easily with the demographic data&#44; standardized creatinine and with the help of internet or a smart phone &#40;using CKD-EPI&#41;&#46;</p><p class="elsevierStylePara">There are several limitations to this analysis&#46; First&#44; the study population was composed only of Mexican patients&#59; however&#44; the main objective of the current work was to find the best available creatinine-based equation&#44; and&#44; in this way&#44; our results can be generalized&#46; Finally&#44; these equations were not tested for assessment of change in GFR over time&#44; but this is a diagnostic study in which we wanted to clarify the best equation and not the change over time&#46;</p><p class="elsevierStylePara">With our results&#44; we suggest that the initial classification of patients with SLE should be with CKD-EPI&#44; because of its reproducibility&#44; ability to predict GFR in patients with low or high GFR&#44; and ease of performance&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara">We are very grateful to Mr&#46; John W Covey for his suggestions in manuscript preparation&#44; and with Juan Ram&#243;n Torres Anguiano and Carlos Alberto Hern&#225;ndez Nieto for their participation in selection of patients&#46;&#160;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that there is no conflict of interest associated with this manuscript&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;19898&#95;en&#95;f111101i6&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_19898_en_f111101i6_copia.jpg" alt="Difference between measured and estimated versus estimated GFR"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Difference between measured and estimated versus estimated GFR</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39618&#95;en&#95;t111101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39618_en_t111101i2_copia.jpg" alt="Equations for estimating GFR"></img></a></p><p class="elsevierStylePara">Table 1&#46; Equations for estimating GFR</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39619&#95;en&#95;t211101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39619_en_t211101i2_copia.jpg" alt="Clinical and demographic characteristics"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and demographic characteristics</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39621&#95;en&#95;t311101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39621_en_t311101i2_copia.jpg" alt="Phase 1&#46; Precision&#44; bias&#44; and accuracy"></img></a></p><p class="elsevierStylePara">Table 3&#46; Phase 1&#46; Precision&#44; bias&#44; and accuracy</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39623&#95;en&#95;t411101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39623_en_t411101i2_copia.jpg" alt="Phase 2&#46; Precision&#44; bias&#44; and accuracy"></img></a></p><p class="elsevierStylePara">Table 4&#46; Phase 2&#46; Precision&#44; bias&#44; and accuracy</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39624&#95;en&#95;t511101i2&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39624_en_t511101i2.jpg" alt="Sensitivity and specificity of each equation to classify patients as having or not GFR less than 60ml&#47;min&#47;1&#46;73"></img></a></p><p class="elsevierStylePara">Table 5&#46; Sensitivity and specificity of each equation to classify patients as having or not GFR less than 60ml&#47;min&#47;1&#46;73</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58;</span> Ning&#250;n estudio ha podido determinar cu&#225;l es la mejor ecuaci&#243;n para calcular la funci&#243;n renal en pacientes con lupus eritematoso sist&#233;mico &#40;LES&#41; partiendo del an&#225;lisis de una evaluaci&#243;n de referencia&#46; <span class="elsevierStyleBold">Objetivo&#58;</span> Evaluar el rendimiento de las ecuaciones basadas en cistatina&#47;creatinina en la estimaci&#243;n de la funci&#243;n renal en pacientes con LES&#46; <span class="elsevierStyleBold">M&#233;todos&#58;</span> Realizamos el estudio en dos fases&#58; la primera inclu&#237;a 14 pacientes en los que el aclaramiento de yotalamato se utiliz&#243; para determinar la tasa de filtraci&#243;n glomerular &#40;FG&#41; y se compar&#243; con diferentes ecuaciones basadas en cistatina C y&#47;o creatinina En la segunda fase&#44; utilizamos la mejor ecuaci&#243;n &#40;basada en cistatina y creatinina&#41; como &#171;est&#225;ndar de referencia&#187; para comparar 5 ecuaciones basadas en creatinina en 55 pacientes con LES&#46; <span class="elsevierStyleBold">Resultados&#58;</span> En la primera fase&#44; la ecuaci&#243;n desarrollada por Stevens et al&#46; &#40;basada en creatinina y cistatina C&#41; fue considerada la mejor&#46; En la fase dos&#44; la ecuaci&#243;n CKD-EPI &#40;Chronic Kidney Disease Epidemiology Collaboration&#41; fue considerada la mejor con una desviaci&#243;n de &#8211;2&#44;1&#160;ml&#47;min&#47;1&#44;73&#44; exactitud &#40;P30 &#37;&#41; del 94&#44;5 &#37; y precisi&#243;n &#40;rango intercuart&#237;lico de las diferencias &#41; de &#8211;2&#44;1&#160;ml&#47;min&#47;1&#44;73&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> Nuestros datos sugieren que la ecuaci&#243;n CKD-EPI es la mejor ecuaci&#243;n basada en creatinina para estimar la FG en pacientes con LES&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span><span class="elsevierStyleBold">&#160;</span>No study has determined the best equation for estimating renal function in patients with systemic lupus erythematosus &#40;SLE&#41;&#44; starting from a gold standard test&#46; <span class="elsevierStyleBold">Objective&#58;</span><span class="elsevierStyleBold">&#160;</span>To evaluate the performance of cistatin&#47;creatinine based equations for estimating renal function in patients with SLE&#46; <span class="elsevierStyleBold">Methods&#58;</span><span class="elsevierStyleBold">&#160;</span>We conducted two phases&#58; the first phase included 14 patients in which iothalamate clearance was used to determine the glomerular filtration rate &#40;GFR&#41; and compared with different equations based on cystatin C and&#47;or creatinine&#46; In the second phase&#44; we used the best equation &#40;a cystatin and creatinine-based equation&#41; as &#8220;reference standard&#8221; to compare 5 creatinine-based equations in 55 patients with SLE&#46; <span class="elsevierStyleBold">Results&#58;</span><span class="elsevierStyleBold">&#160;</span>In the first phase the equation developed by Stevens and colleagues &#40;based on creatinine and cystatin C&#41;&#44; was the best equation&#46; In phase 2&#44; the CKD-EPI &#40;Chronic Kidney Disease Epidemiology Collaboration&#41; equation was the best equation with bias of -2&#46;1ml&#47;min&#47;1&#46;73&#44; accuracy &#40;P30&#41; of 94&#46;5&#37; and precision &#40;interquartile range of differences&#41; of -2&#46;1 ml&#47;min&#47;1&#46;73&#46; <span class="elsevierStyleBold">Conclusions&#58;</span><span class="elsevierStyleBold">&#160;</span>Our data suggest that CKD-EPI is the best creatinine-based equation to estimate GFR in patients with SLE&#46;</p>"
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CKD-EPI is the most reliable equation to estimate renal function in patients with systemic lupus erythematosus
La ecuación CKD-EPI es la más fiable para estimar la función renal en pacientes con lupus eritematoso sistémico
Marco U. Martínez-Martíneza, Marco Ulises Martínez-Martínezb, Peter Mandevillec, Lilia Llamazares-Azuarad, Lilia Llamazares-Azuarae, Carlos Abud-Mendozab
a Regional Unit of Rheumatology and Osteoporosis, Hospital Central Dr. Ignacio Morones Prieto and Faculty of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México,
b Regional Unit of Rheumatology and Osteoporosis, Hospital Central¿Dr. Ignacio Morones Prieto¿ and Faculty of Medicine, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México,
c Statistics and Epidemiology, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México,
d Department of Nephrology and Renal Diseases, Universidad Autónoma de San Luis Potosí, San Luis Potosí, San Luis Potosí, México,
e Department of Nephrology and Renal Diseases, Universidad Autónoma de San Luis Potosí, San Luis Potosí, México,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Renal damage is an important factor of both</span> morbidity and mortality in patients with lupus erythematosus &#40;SLE&#41;&#46;<span class="elsevierStyleSup">1</span> Determination of renal function has an important bearing on the clinical management&#44; risk stratification and medication dosage adjustment&#46;<span class="elsevierStyleSup">2</span></p><p class="elsevierStylePara">Measurement of urine clearance markers &#40;like inulin&#41; are the gold standard to calculate glomerular filtration rate &#40;GFR&#41;&#59; these methods are complex&#44; expensive and cumbersome to perform&#59;<span class="elsevierStyleSup">3&#44;4</span> the GFR predictive creatinine-based equations offer a rapid method for assessing kidney function by reliance on serum creatinine and anthropometric data&#59; these equations include&#58; Cockcroft-Gault equation &#40;CG&#41;&#44; the Modification of Diet in Renal Disease study &#40;MDRD&#41; equation&#44; the Mayo Clinic Quadratic &#40;MCQ&#41; equation and the CKD-EPI equation&#46;<span class="elsevierStyleSup">5-7</span> Creatinine clearance &#40;CrCl&#41; is one other method&#44; commonly used by rheumatologists&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Performance of creatinine-based equations is known to vary among populations&#46; For example&#44; the MDRD study equation performs well in patients with chronic kidney disease&#44; but is less accurate in potential kidney donors&#44; young people with type-1 diabetes&#44; and patients with substantially reduced muscle mass&#59;<span class="elsevierStyleSup">9-11</span> moreover&#44; CG is an estimate of CrCl originally developed in a predominantly male&#44; Caucasian population&#46;<span class="elsevierStyleSup">12</span> Conclusions of these and other studies about equations may not be appropriate in SLE&#44; a predominantly female disease&#44;<span class="elsevierStyleSup">13</span> encompassing many ethnicities&#44;<span class="elsevierStyleSup">13</span> reduced muscle mass&#44;<span class="elsevierStyleSup">14</span> and with a wide range of renal function&#46;<span class="elsevierStyleSup">15</span> However&#44; there is a paucity of data regarding the equations for estimating renal function in patients with SLE&#46;<span class="elsevierStyleSup">15-17</span> Moreover&#44; almost half of the rheumatologists use CrCl in all of their patients in order to estimate GFR&#44; a method with a high rate of inappropriate collection and more expensive than the creatinine based equations&#46;<span class="elsevierStyleSup">18</span></p><p class="elsevierStylePara">To our knowledge&#44; no study has determined the best equation for estimating renal function in patients with SLE&#44; starting from iothalamate urinary clearance as gold standard&#46; Therefore&#44; we performed this study to evaluate which is the best equation&#44; based on serum creatinine&#44; to assess renal function in patients with SLE&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">PATIENTS AND METHODS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We included&#44; in consecutive selection&#44; all patients with SLE according to the American College of Rheumatology &#40;ACR&#41; criteria&#46;<span class="elsevierStyleSup">19&#44;20</span></p><p class="elsevierStylePara">Exclusion criteria&#58; patients under 18 years old&#44; asthma&#44; hypothyroidism&#44; current smoking&#44; malignancy&#44; prednisone doses &#8805;30mg&#47;d &#40;or the equivalent dose of another glucocorticoid&#41;&#44; pregnancy and severe disease activity &#40;MEX-SLEDAI&#8805;8&#41;&#46;<span class="elsevierStyleSup">21</span> All patients signed informed consent and our study was approved by the Central Hospital Institutional Review Board&#46;</p><p class="elsevierStylePara">Ideal body weight &#40;IBW&#41; was calculated &#40;Robinson equation&#41;&#46;<span class="elsevierStyleSup">22</span> Body surface index &#40;BSI&#41; was calculated in accordance with the Dubois equation&#46;<span class="elsevierStyleSup">23</span></p><p class="elsevierStylePara">We divided this study into 2 phases&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Phase 1&#58; </span>We measured GFR with iothalamate urinary clearance in 14 patients with SLE&#46; GFR calculated through iothalamate was compared with the GFR estimated through cystatin and&#47;or creatinine based equations&#46; The main objective in this phase was to validate the best cystatin&#47;creatinine-based equation to use at the second phase as our reference standard &#40;Table 1&#41;&#46;<span class="elsevierStyleSup">11&#44;24-27</span> We selected cystatin-based equations for this study from equations developed in other studies taking into account&#58; studies were developed from adult patients&#44; with more than 100 patients&#44; and the measurement of cystatin C had been made by the same method used in our study &#40;immunonephelometry&#44; PENIA&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Phase 2&#58;</span> The best cystatin&#47;creatinine-based equation found in phase I was taken as the reference standard &#40;measured GFR&#41; to assess CrCl and creatinine-based equations &#40;Table 1&#41; in 55 patients &#40;estimated GFR&#41;&#46;<span class="elsevierStyleSup">5&#44;7&#44;28</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Laboratory tests</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We recalibrated serum creatinine values to standardized creatinine measurements by using the Roche enzymatic method as described elsewhere&#46;<span class="elsevierStyleSup">10&#44;29</span></p><p class="elsevierStylePara">Serum cystatin C was measured using a particle-enhanced immunonephelometric assay &#40;N Latex Cystatin C&#44; Dade Behring&#44; IL&#41;&#46; The between-day assay coefficient of variation was 3&#46;5&#37;&#46;</p><p class="elsevierStylePara">In phase 1&#44; all patients had a non-radiolabeled iothalamate clearance using a previously described standard laboratory method&#46;<span class="elsevierStyleSup">30</span> In brief&#44; after oral hydration with 4&#8211;6 glasses of water&#44; patients received a subcutaneous injection of non-radiolabeled iothalamate &#40;Conray<span class="elsevierStyleSup">&#174;</span>&#41;&#46; Following a 1-h equilibrium period&#44; the patient voided&#44; the &#64257;rst serum sample was drawn and a timed urine collection was begun&#46; A sonographic scanner assessed bladder emptying and a bladder catheter was placed in patients with urinary retention&#46; Following the timed urine collection &#40;approximately 45&#8211;60min&#41;&#44; a second serum sample was obtained&#46; GFR was calculated by the clearance equation &#40;UIoV&#47;Pio where UIo and PIo are the urine and plasma concentrations of iothalamate&#44; and V is the urine &#64258;ow&#41; using the mean of two serum samples and one urine sample assayed for iothalamate via capillary electrophoresis&#46; All GFR measurements were standardized for BSI &#40;per 1&#46;73m<span class="elsevierStyleSup">2</span>&#41; by multiplying by 1&#46;73 and dividing by BSI&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Statistical analysis</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We used R&#44; version 2 &#40;Free Software Foundation&#44; Boston&#44; Massachusetts&#41; to compute all analyses&#46;</p><p class="elsevierStylePara">Categorical variables are presented as frequencies and percentages&#44; and continuous variables as means and standard deviations&#44; or medians and &#40;minimum-maximum&#41; for variables with skewed distributions&#46;</p><p class="elsevierStylePara">Measured GFR &#40;mGFR&#41; and estimated GFR &#40;eGFR&#41; were compared for each patient graphically by plotting mGFR and the difference &#40;mGFR - eGFR&#41; against eGFR&#46; A smoothed regression line is shown with the 95&#37; confidence interval &#40;95&#37; CI&#41; computed by using the lowest smoothing function in R&#44; and using quantile regression&#44; excluding the lowest and highest 2&#46;5&#37; of estimated GFR&#46; Bias was expressed as the median difference &#40;mGFR - eGFR&#41;&#44; with positive values indicating an under-estimation of mGFR&#46; Precision was expressed as interquartile range &#40;IQR&#41; for the differences &#40;dIQR&#41;&#46; Accuracy was expressed as the percentage of eGFR within 30&#37; of mGFR &#40;P30&#41;&#46; Confidence intervals &#40;CI&#41; were computed by using bootstrap methods &#40;2&#44;000 bootstraps&#41; for median differences and IQR of the differences and by the binomial method for P30&#46;</p><p class="elsevierStylePara">The reference method or mGFR was iothalamate for phase I&#44; and the best cystatin&#47;creatinine-based equation &#40;Stevens&#8217; equation&#41; for phase 2&#46;</p><p class="elsevierStylePara">The best equation in both phases was that which had less bias&#44; less dIQR and higher P30&#46;</p><p class="elsevierStylePara">In phase 2 we constructed a 2x2 contingency table to determine the sensitivity and specificity of each equation to classify if each one of the patients had or not had GFR&#60;60 ml&#47;min per 1&#46;73m<span class="elsevierStyleSup">2</span>&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS </span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In the first phase we included 14 patients&#59; their median age was 32&#46;5 years old&#44; and 61&#46;5 months of mean SLE evolution time &#40;Table 2&#41;&#46; Table 3 shows the results of the first phase which highlights the fact that the equation based on creatinine and cystatin C developed by Stevens and colleagues<span class="elsevierStyleSup">11</span> &#40;Stevens&#8217; equation&#41; had the best bias and the most accuracy&#46;</p><p class="elsevierStylePara">Because our patients were selected for their low disease activity and drug doses&#44; and because of the interference of these factors may have on cystatin C levels&#44; for the clinician&#44; the better setting is to have a creatinine-based equation than a cystatin-based equation&#44; so we performed a second phase with more patients to determine the best creatinine-based equation to estimate GFR in patients with SLE &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">Table 4 shows how the bias&#44; precision and accuracy are better with the CKD-EPI equation than with the others&#46; In this phase&#44; 55 patients were included&#59; median age was 36 years old and SLE evolution time was 60 months &#40;Table 2&#41;&#46;</p><p class="elsevierStylePara">Figure 1 shows the difference between measured and estimated versus estimated GFR in phase 2&#46; A smoothed regression line is shown with the 95&#37; CI&#44; using quantile regression&#46; Notice how the CKD-EPI equation has a good performance both at high and low GFR&#46;</p><p class="elsevierStylePara">Table 5 shows sensitivity and specificity of each equations to detect GFR less than 60ml&#47;min&#47;1&#46;73&#46; Eleven patients had GFR less than 60ml&#47;min&#47;1&#46;73 according to Stevens&#8217; equation&#44; CKD-EPI misclassified 1 patient &#40;1&#46;8&#37;&#41;&#44; sMDRD 2 &#40;3&#46;6&#37;&#41;&#44; CG 4 &#40;7&#46;3&#37;&#41;&#44; CGi 6 &#40;10&#46;9&#37;&#41;&#44; MCQ 5 &#40;9&#46;1&#41; and CrCl 4 &#40;7&#46;3&#37;&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The GFR should be determined as accurately as possible&#44; ideally with an accessible and inexpensive method which does not cause harm to the patient&#46; Several factors affect serum creatinine level other than GFR&#44; including its generation from muscle metabolism&#59; these factors compromise the generalization of the equations in patients with SLE&#46; Cystatin-based equations has no dependence on muscle mass&#44; but previous studies showed evidence for non-GFR determinants of cystatin C &#40;inflammation&#44; glucocorticoids&#44; thyroid disease and cytotoxic drugs&#41;&#59; variation in these factors can restrict the use of this protein for measuring GFR in patients with SLE&#46;<span class="elsevierStyleSup">31</span> Even though we reported previously that Cystatin C does not correlate with disease activity and drug doses&#44;<span class="elsevierStyleSup">32</span> we selected our patients avoiding these factors&#46;</p><p class="elsevierStylePara">Because there are multiple equations to estimate GFR&#44; the management guidelines of patients with SLE are based on studies in other different diseases from SLE and we think that the results on these diseases cannot be extrapolated to SLE&#46;<span class="elsevierStyleSup">8</span> National Kidney Foundation &#40;NKF&#41; guidelines suggest using the GFR estimating equations &#40;not the CrCl&#41; to achieve a better assessment of renal function&#46;<span class="elsevierStyleSup">6&#44;7</span> In spite of these recommendations&#44; 24 h urine collection to determine CrCl is a widely used method for assessing GRF in patients with SLE &#40;including clinical trials&#41;&#46;<span class="elsevierStyleSup">16&#44;33-35</span></p><p class="elsevierStylePara">Our study identifies several important findings&#58; 1&#41; The equation developed by Stevens and colleagues based on creatinine and cystatin C is the best equation to estimate renal function for our specifically selected SLE patients &#40;with low disease activity&#44; low doses of glucocorticoids&#44; no smoking&#44; no hypothyroidism&#41;&#46; 2&#41; Because of all those factors that the clinicians must take into account when using cystatin C in a patient with SLE &#40;smoking&#44; hypothyroidism&#44; etc&#46;&#41;&#44; we looked for an equation based only on serum creatinine in which there is not the influence of these factors and our results were&#58; the CKD-EPI equation should be used in patients with SLE&#46;</p><p class="elsevierStylePara">The importance of our results is that we do not need a 24h urine collection to evaluate renal function in SLE patients as was done in several clinical trials&#46;<span class="elsevierStyleSup">33-35</span> Moreover&#44; CKD-EPI is more reliable than CrCl and the other equations&#44; as our study describes&#46; Rheumatologists can estimate renal function easily with the demographic data&#44; standardized creatinine and with the help of internet or a smart phone &#40;using CKD-EPI&#41;&#46;</p><p class="elsevierStylePara">There are several limitations to this analysis&#46; First&#44; the study population was composed only of Mexican patients&#59; however&#44; the main objective of the current work was to find the best available creatinine-based equation&#44; and&#44; in this way&#44; our results can be generalized&#46; Finally&#44; these equations were not tested for assessment of change in GFR over time&#44; but this is a diagnostic study in which we wanted to clarify the best equation and not the change over time&#46;</p><p class="elsevierStylePara">With our results&#44; we suggest that the initial classification of patients with SLE should be with CKD-EPI&#44; because of its reproducibility&#44; ability to predict GFR in patients with low or high GFR&#44; and ease of performance&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acknowledgements</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara">We are very grateful to Mr&#46; John W Covey for his suggestions in manuscript preparation&#44; and with Juan Ram&#243;n Torres Anguiano and Carlos Alberto Hern&#225;ndez Nieto for their participation in selection of patients&#46;&#160;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that there is no conflict of interest associated with this manuscript&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;19898&#95;en&#95;f111101i6&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_19898_en_f111101i6_copia.jpg" alt="Difference between measured and estimated versus estimated GFR"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Difference between measured and estimated versus estimated GFR</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39618&#95;en&#95;t111101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39618_en_t111101i2_copia.jpg" alt="Equations for estimating GFR"></img></a></p><p class="elsevierStylePara">Table 1&#46; Equations for estimating GFR</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39619&#95;en&#95;t211101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39619_en_t211101i2_copia.jpg" alt="Clinical and demographic characteristics"></img></a></p><p class="elsevierStylePara">Table 2&#46; Clinical and demographic characteristics</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39621&#95;en&#95;t311101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39621_en_t311101i2_copia.jpg" alt="Phase 1&#46; Precision&#44; bias&#44; and accuracy"></img></a></p><p class="elsevierStylePara">Table 3&#46; Phase 1&#46; Precision&#44; bias&#44; and accuracy</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39623&#95;en&#95;t411101i2&#95;copia&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39623_en_t411101i2_copia.jpg" alt="Phase 2&#46; Precision&#44; bias&#44; and accuracy"></img></a></p><p class="elsevierStylePara">Table 4&#46; Phase 2&#46; Precision&#44; bias&#44; and accuracy</p><p class="elsevierStylePara"><a href="grande&#47;11101&#95;16025&#95;39624&#95;en&#95;t511101i2&#46;jpg" class="elsevierStyleCrossRefs"><img src="11101_16025_39624_en_t511101i2.jpg" alt="Sensitivity and specificity of each equation to classify patients as having or not GFR less than 60ml&#47;min&#47;1&#46;73"></img></a></p><p class="elsevierStylePara">Table 5&#46; Sensitivity and specificity of each equation to classify patients as having or not GFR less than 60ml&#47;min&#47;1&#46;73</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes&#58;</span> Ning&#250;n estudio ha podido determinar cu&#225;l es la mejor ecuaci&#243;n para calcular la funci&#243;n renal en pacientes con lupus eritematoso sist&#233;mico &#40;LES&#41; partiendo del an&#225;lisis de una evaluaci&#243;n de referencia&#46; <span class="elsevierStyleBold">Objetivo&#58;</span> Evaluar el rendimiento de las ecuaciones basadas en cistatina&#47;creatinina en la estimaci&#243;n de la funci&#243;n renal en pacientes con LES&#46; <span class="elsevierStyleBold">M&#233;todos&#58;</span> Realizamos el estudio en dos fases&#58; la primera inclu&#237;a 14 pacientes en los que el aclaramiento de yotalamato se utiliz&#243; para determinar la tasa de filtraci&#243;n glomerular &#40;FG&#41; y se compar&#243; con diferentes ecuaciones basadas en cistatina C y&#47;o creatinina En la segunda fase&#44; utilizamos la mejor ecuaci&#243;n &#40;basada en cistatina y creatinina&#41; como &#171;est&#225;ndar de referencia&#187; para comparar 5 ecuaciones basadas en creatinina en 55 pacientes con LES&#46; <span class="elsevierStyleBold">Resultados&#58;</span> En la primera fase&#44; la ecuaci&#243;n desarrollada por Stevens et al&#46; &#40;basada en creatinina y cistatina C&#41; fue considerada la mejor&#46; En la fase dos&#44; la ecuaci&#243;n CKD-EPI &#40;Chronic Kidney Disease Epidemiology Collaboration&#41; fue considerada la mejor con una desviaci&#243;n de &#8211;2&#44;1&#160;ml&#47;min&#47;1&#44;73&#44; exactitud &#40;P30 &#37;&#41; del 94&#44;5 &#37; y precisi&#243;n &#40;rango intercuart&#237;lico de las diferencias &#41; de &#8211;2&#44;1&#160;ml&#47;min&#47;1&#44;73&#46; <span class="elsevierStyleBold">Conclusiones&#58;</span> Nuestros datos sugieren que la ecuaci&#243;n CKD-EPI es la mejor ecuaci&#243;n basada en creatinina para estimar la FG en pacientes con LES&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Background&#58;</span><span class="elsevierStyleBold">&#160;</span>No study has determined the best equation for estimating renal function in patients with systemic lupus erythematosus &#40;SLE&#41;&#44; starting from a gold standard test&#46; <span class="elsevierStyleBold">Objective&#58;</span><span class="elsevierStyleBold">&#160;</span>To evaluate the performance of cistatin&#47;creatinine based equations for estimating renal function in patients with SLE&#46; <span class="elsevierStyleBold">Methods&#58;</span><span class="elsevierStyleBold">&#160;</span>We conducted two phases&#58; the first phase included 14 patients in which iothalamate clearance was used to determine the glomerular filtration rate &#40;GFR&#41; and compared with different equations based on cystatin C and&#47;or creatinine&#46; In the second phase&#44; we used the best equation &#40;a cystatin and creatinine-based equation&#41; as &#8220;reference standard&#8221; to compare 5 creatinine-based equations in 55 patients with SLE&#46; <span class="elsevierStyleBold">Results&#58;</span><span class="elsevierStyleBold">&#160;</span>In the first phase the equation developed by Stevens and colleagues &#40;based on creatinine and cystatin C&#41;&#44; was the best equation&#46; In phase 2&#44; the CKD-EPI &#40;Chronic Kidney Disease Epidemiology Collaboration&#41; equation was the best equation with bias of -2&#46;1ml&#47;min&#47;1&#46;73&#44; accuracy &#40;P30&#41; of 94&#46;5&#37; and precision &#40;interquartile range of differences&#41; of -2&#46;1 ml&#47;min&#47;1&#46;73&#46; <span class="elsevierStyleBold">Conclusions&#58;</span><span class="elsevierStyleBold">&#160;</span>Our data suggest that CKD-EPI is the best creatinine-based equation to estimate GFR in patients with SLE&#46;</p>"
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Article information
ISSN: 20132514
Original language: English
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2022 December 58 19 77
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2022 October 58 39 97
2022 September 62 22 84
2022 August 70 49 119
2022 July 50 42 92
2022 June 66 46 112
2022 May 100 49 149
2022 April 117 41 158
2022 March 152 76 228
2022 February 171 64 235
2022 January 126 63 189
2021 December 85 51 136
2021 November 78 45 123
2021 October 63 48 111
2021 September 40 45 85
2021 August 42 57 99
2021 July 60 67 127
2021 June 69 50 119
2021 May 75 46 121
2021 April 153 46 199
2021 March 60 43 103
2021 February 61 33 94
2021 January 59 24 83
2020 December 45 20 65
2020 November 54 14 68
2020 October 34 14 48
2020 September 60 22 82
2020 August 58 21 79
2020 July 62 18 80
2020 June 52 16 68
2020 May 51 13 64
2020 April 49 20 69
2020 March 49 16 65
2020 February 43 16 59
2020 January 63 22 85
2019 December 73 15 88
2019 November 44 20 64
2019 October 33 6 39
2019 September 40 19 59
2019 August 30 8 38
2019 July 56 16 72
2019 June 61 25 86
2019 May 78 27 105
2019 April 85 36 121
2019 March 60 18 78
2019 February 55 24 79
2019 January 32 28 60
2018 December 94 36 130
2018 November 167 25 192
2018 October 170 15 185
2018 September 205 14 219
2018 August 110 25 135
2018 July 110 17 127
2018 June 101 21 122
2018 May 93 19 112
2018 April 100 4 104
2018 March 87 11 98
2018 February 82 7 89
2018 January 84 6 90
2017 December 84 11 95
2017 November 117 18 135
2017 October 66 9 75
2017 September 85 11 96
2017 August 91 13 104
2017 July 75 15 90
2017 June 84 8 92
2017 May 99 18 117
2017 April 77 15 92
2017 March 83 7 90
2017 February 130 29 159
2017 January 74 17 91
2016 December 127 3 130
2016 November 173 18 191
2016 October 210 12 222
2016 September 399 6 405
2016 August 348 8 356
2016 July 282 13 295
2016 June 178 0 178
2016 May 202 0 202
2016 April 133 0 133
2016 March 112 0 112
2016 February 133 0 133
2016 January 144 0 144
2015 December 161 0 161
2015 November 136 0 136
2015 October 116 0 116
2015 September 96 0 96
2015 August 87 0 87
2015 July 95 0 95
2015 June 55 0 55
2015 May 63 0 63
2015 April 14 0 14
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¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?