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    "textoCompleto" => "<p class="elsevierStylePara">&#8220;Take nothing on its looks&#59; take everything on evidence&#46; There&#39;s no better rule&#46;&#8221; &#40;Charles Dickens&#41;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Different studies have analysed the clinical and biochemical parameters related to the risk of long-term progression in patients with IgA nephropathy &#40;IgAN&#41;&#46; Classically&#44; proteinuria greater than 1g&#47;day&#44; the presence or development of high blood pressure &#40;HBP&#41; and a low glomerular filtration rate on diagnosis have been prognostic factors significantly related to the development of chronic kidney disease &#40;CKD&#41;&#46;<span class="elsevierStyleSup">1-3</span> However&#44; and unlike other glomerular processes&#44; in IgAN patients&#44; proteinuria between 0&#46;5 and 1g&#47;day is also associated with a risk of developing CKD&#46;<span class="elsevierStyleSup">4-6</span> Many studies on IgAN prognosis do not include patients who only have microhaematuria and low proteinuria &#40;0&#46;5-1g&#47;day&#41; at diagnosis&#46; This represents a high percentage of patients&#44; particularly in countries with &#8220;very active&#8221; renal biopsy policies&#46; From a histological point of view&#44; the two strongest predictors of progression of the nephropathy have been tubulointerstitial damage and the presence of glomerulosclerosis&#46; Hence&#44; it can be inferred that most prognostic factors used to predict the risk of long-term kidney function loss refer to chronic and advanced lesions&#46; Therefore&#44; we can justify the need to carry out studies to identify prognostic variables from data obtained at diagnosis or before advanced renal fibrosis lesions appear in renal biopsies&#46;</p><p class="elsevierStylePara">The recent Oxford classification&#44; validated for the North American and Asian adult and child populations and pending definitive validation for the European population &#40;VALIGA study&#41;&#44; highlights that histological lesions of mesangial proliferation &#40;M1&#41;&#44; endocapillary proliferation &#40;E1&#41;&#44; focal segmental hyalinosis &#40;S1&#41; and tubulointerstitial involvement &#40;T1-2&#41; are independent predictors of progression beyond clinical parameters &#40;including proteinuria and glomerular filtration rate&#41;&#46;<span class="elsevierStyleSup">7&#44;8</span> However&#44; this classification was not validated in a population that displayed normal kidney function and low proteinuria &#40;proteinuria &#8804;0&#46;5g&#47;day&#41; clinically&#46;</p><p class="elsevierStylePara">The study recently published under the title &#8220;Long-term outcome of IgA nephropathy presenting with minimal or no proteinuria&#8221; presented the results of 141 Caucasian patients diagnosed histologically with IgAN with normal kidney function&#44; proteinuria equal to or lower than 0&#46;5g&#47;day and persistent microhaematuria&#46;<span class="elsevierStyleSup">9</span> This was a study by GLOSEN &#40;Spanish Society of Nephrology Glomerular Disease Study Group&#41; that retrospectively included patients from eight Spanish hospitals that had an &#8220;active&#8221; renal biopsy policy over an extended period &#40;1975-2008&#41;&#46; 64&#37; of patients studied were males&#44; with a mean age of 23&#46;7&#44; followed up over a median period of 108 months&#44; and no patient had renal failure on diagnosis&#46; After this extended follow-up period&#44; only 5 &#40;3&#46;5&#37;&#41; patients suffered a 50&#37; increase in their baseline creatinine level&#44; and only 1 &#40;0&#46;7&#37;&#41; patient had a 100&#37; increase and no patient developed end-stage renal disease&#46; At the end of the study&#44; only 21 &#40;14&#46;9&#37;&#41; patients had proteinuria higher than 0&#46;5g&#47;day and only 6 &#40;4&#46;2&#37;&#41; of the 21 had proteinuria higher than 1g&#47;day&#44; which is a significant risk factor for developing end-stage renal disease&#46;<span class="elsevierStyleSup">1</span> Furthermore&#44; the increase in HBP in the population studied was very small &#40;from 16&#46;3&#37; to 21&#46;3&#37;&#41;&#46; This study contributed information on the percentage of patients who achieved &#8220;spontaneous&#8221; clinical remission and we consider this clinical information to be very important&#46; Although spontaneous clinical remission had previously been well-described&#44; it had not been studied specifically&#46;<span class="elsevierStyleSup">10</span> In this study&#44; 53 patients &#40;37&#46;5&#37;&#41; achieved spontaneous clinical remission&#44; defined by the disappearance of microhaematuria&#44; proteinuria of less than or equal to 0&#46;2g&#47;day and normal kidney function and blood pressure&#46;</p><p class="elsevierStylePara">From a histological point of view&#44; this was the first study published in which the Oxford classification was applied to patients with IgAN and proteinuria of less than 0&#46;5g&#47;day and the data obtained is interesting&#46; The first thing that it showed&#44; as was expected&#44; is that endocapillary proliferation and focal segmental hyalinosis lesions were uncommon &#40;8&#46;5&#37; and 15&#46;6&#37; respectively&#41;&#44; and that 95&#37; did not have significant tubulointerstitial involvement&#46; However&#44; mesangial proliferation lesions appeared in 46 &#40;32&#46;6&#37;&#41; patients in the study&#46; These results are of great importance&#44; since despite the low number of events&#44; the multivariate study showed that focal segmental hyalinosis lesions were the only independent factor significantly associated with renal survival &#40;increase &#62;50&#37; baseline serum creatinine&#44; primary objective&#41;&#46; In addition&#44; an absence of mesangial proliferation greater than 50&#37; was significantly and independently associated with the possibility of achieving spontaneous remission in the multivariate study&#46; Furthermore&#44; patients with hyalinosis lesions had higher baseline proteinuria figures with a significantly more marked increase during follow-up with respect to those who did not have them&#46; The only patient whose baseline serum creatinine figures doubled during the follow-up period had M1E1S1T1 lesions&#46; All these data confirm the usefulness of the Oxford classification in patients who present with a &#8220;benign&#8221; profile&#46;</p><p class="elsevierStylePara">As has been described in randomised&#44; controlled clinical trials&#44; proteinuria level has an important influence on long-term kidney progression&#44; even in these types of patients who have a favourable presentation and progression&#46;<span class="elsevierStyleSup">1-6&#44;11&#44;12</span> In this study&#44; in confirmation of previous assertions&#44; we were able to demonstrate that the only clinical variable that influenced long-term renal survival was mean proteinuria during follow-up &#40;time-average &#91;TA&#93;-proteinuria&#41;&#46; TA-proteinuria was the only independent clinical risk factor that predicted an increase in baseline creatinine by more than 50&#37; and at the same time baseline proteinuria was significantly related with the probability of achieving remission&#46; These results highlight the crucial role of proteinuria level on the long-term progression of this disease&#46; In addition&#44; we should mention that this favourable progression was achieved without the need for immunosuppressant treatment&#46; In patients who had proteinuria higher than 0&#46;5g&#47;day or HBP&#44; angiotensin converting enzyme &#40;ACE&#41; inhibitors or angiotensin II receptor blockers &#40;ARBs&#41; were used&#46; At the end of the follow-up period&#44; 55 &#40;41&#46;8&#37;&#41; patients were receiving ACE inhibitors&#47;ARBs&#46;</p><p class="elsevierStylePara">Before this study&#44; only Asian studies described the prognosis of patients with IgAN and low proteinuria&#46; These studies&#44; unlike the study mentioned in this article&#44; highlight that renal prognosis was not so favourable in these patients&#46;<span class="elsevierStyleSup">13-15</span> Indeed&#44; in the study by Szeto et al&#46; that analysed 72 Chinese patients with normal kidney function&#44; normal blood pressure and proteinuria lower than 0&#46;4g&#47;day&#44; 33&#37; developed proteinuria higher than 1g&#47;day&#44; 26&#37; developed HBP and kidney function deteriorated in 7&#37;&#46;<span class="elsevierStyleSup">14</span> These results were also confirmed in a more recent study&#44; carried out on 177 Chinese patients with normal blood pressure and proteinuria lower than 0&#46;4g&#47;day&#44; in which 24&#37; developed renal failure and only 9&#37; achieved clinical remission&#46;<span class="elsevierStyleSup">15</span> In addition to the potential pathological differences that there may be in the different studies&#44; it is likely that the differences in genetic susceptibility of the Asian population explain prognostic differences&#46; There are many and an increasing number of observations that suggest a significant genetic contribution to the pathogenesis of IgAN&#44; based on family and demographic studies&#46; These observations began with differences in prevalence of the nephropathy in the different ethnic groups and there continue to be major genome-wide association studies that identify the DQ loci of the HLA histocompatibility system involved consistently in the susceptibility to develop IgAN in patient groups of European and Asian descent&#44; as has been demonstrated in recent studies by Feehally et al&#46; and Yu et al&#46;<span class="elsevierStyleSup">16&#44;17</span>&#46; Familiar linkage studies have provided the strongest evidence for genetic factors involved in the development and progression of IgAN&#46; These studies also demonstrate their strong influence on hyperglycosylated IgA composition in serum&#46;<span class="elsevierStyleSup">18</span> Different genetic loci have been identified in familial forms of IgAN and they have been related to the nephropathy&#8217;s pathogenesis &#40;6q22-q23&#44; 2q36&#44; 4q26-q31&#44; 17q12-q22&#41;&#44; although a specific gene has not yet been identified&#46;<span class="elsevierStyleSup">19 </span>Even so&#44; one of the most important studies is that published by Gharavi et al&#46;&#44; which demonstrated&#44; after studying European and Asian populations&#44; mutations in complement regulatory factor H &#40;CFH&#41; 1 and 3 of chromosome 1q32&#44; only in the Asian population with IgAN&#44; findings that bring to the table the potential involvement of the alternative complement pathway in the pathogenesis of this disease&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">The information contributed by the study on 141 Caucasian patients is important for establishing the progression profile of IgAN and selecting the clinical and&#47;or histological findings that may predict poor progression&#46; Given the good current policy of not performing biopsies on this patient group&#44; it is very unlikely that a study of these characteristics can be repeated&#46; However&#44; given that these patients can develop proteinuria&#44; HBP and renal failure&#44; a lifetime annual follow-up is recommended to monitor these parameters and start treatment with ACE inhibitors&#47;ARBs in those who develop the abovementioned abnormalities&#46; However&#44; we must bear in mind that in this patient group&#44; it is essential to perform a broad differential diagnosis that includes benign familial haematuria &#40;thin basement membrane disease&#41;&#44; as well as more common causes of microhaematuria with low proteinuria&#44; without forgetting all urological diseases that should be ruled out beforehand&#46; Perhaps the most important decision is to explain what microhaematuria should be assessed and followed-up clinically&#44; given its high frequency in normal clinical practice&#44; and even more so following the study published by Vivante et al&#46; in <span class="elsevierStyleItalic">JAMA</span>&#44; which has revolutionised the potential prognostic role of microhaematuria&#46;<span class="elsevierStyleSup">21</span> Haematuria is a common finding in diseases that cause glomerular damage and its estimated frequency varies between 0&#46;18&#37; and 16&#46;1&#37;&#44; depending on the population studied&#46; Isolated microhaematuria&#44; when not accompanied by HBP&#44; significant proteinuria or kidney function abnormalities&#44; has traditionally been related to a good prognosis&#46;<span class="elsevierStyleSup">22</span> However&#44; the information contained in the study by Vivante et al&#46; of a population of one million Israeli soldiers who presented with isolated microhaematuria following screening studies&#44; has partially changed the image that people had about this clinical finding&#46; In this young population &#40;16-25 years of age&#41;&#44; microhaematuria prevalence was 0&#46;4&#37; in males and 0&#46;2&#37; in females after almost 22 years of follow-up&#44; which was associated with an adjusted hazard ratio of 18&#46;5 for developing end-stage renal disease&#46; However&#44; and without detracting from the importance of the study&#44; it has a lack of follow-up over time and a lack of essential clinical data such as proteinuria and HBP development&#46; Although the study on which this article is based sheds light on the potential long-term progression of patients with IgAN and few renal manifestations&#44; it has not been able to answer the question &#8220;what is the prognosis of patients with microhaematuria&#63;&#8221; or determine whether microhaematuria is an independent risk factor for developing end-stage renal disease&#46; Although we suspect that the disappearance of microhaematuria may be related to a &#8220;benign&#8221; progression of IgAN&#44; studies whose primary objective is this assumption are required&#46; In the Spanish multicentre study&#44; we attempted to relate the disappearance of microhaematuria to better renal progression&#44; but perhaps the lack of renal events made it impossible to establish this association&#46;</p><p class="elsevierStylePara">Classical studies related macroscopic haematuria outbreaks with good renal prognosis in IgAN patients&#44; but recent studies have denied this assertion after demonstrating that there is at least a 25&#37; risk of developing CKD following these outbreaks&#44;<span class="elsevierStyleSup">23&#44;24</span> and as such&#44; we require more studies that analyse the factors potentially involved in the physiopathology of micro- and macrohaematuria&#44; which could help us understand the disease and its progression better&#46;<span class="elsevierStyleSup">25-28</span> As nephrologists&#44; a lot of our focus has been on proteinuria and perhaps haematuria has been neglected&#46; However&#44; this factor should receive more attention nowadays&#46;</p><p class="elsevierStylePara">In summary&#44; we consider that this study contributes important information to characterising the natural history and prognosis of IgAN&#44; and has demonstrated the usefulness of the Oxford classification in this patient group for the first time&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">ACKNOWLEDGEMENTS</span></p><p class="elsevierStylePara">This study has received help from the <span class="elsevierStyleItalic">Fondo de Investigaciones Sanitarias</span> &#40;FIS&#44; Health Care Research Fund&#41; through the projects FIS 10&#47;02668 and FIS 10&#47;02581&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">La cuant&#237;a de la proteinuria contin&#250;a siendo el par&#225;metro cl&#237;nico que mejor se relaciona con el desarrollo de insuficiencia renal a largo plazo en las patolog&#237;as glomerulares&#46; Esta cuant&#237;a es especialmente importante cuando se analiza la evoluci&#243;n de los pacientes afectos de una nefropat&#237;a IgA&#46; De esta manera&#44; la evoluci&#243;n natural de los pacientes con nefropat&#237;a IgA que se presentan cl&#237;nicamente con funci&#243;n renal normal&#44; microhematuria y proteinuria escasa no hab&#237;a sido analizada con profundidad hasta la elaboraci&#243;n de este trabajo multic&#233;ntrico espa&#241;ol que aqu&#237; se analiza&#46; Tras estudiar a 141 pacientes cauc&#225;sicos con nefropat&#237;a IgA biopsiada y presentaci&#243;n cl&#237;nica &#171;benigna&#187; y clasificarlos histol&#243;gicamente de acuerdo a la nueva clasificaci&#243;n de Oxford&#44; se puede concluir que el pron&#243;stico renal de estos enfermos es excelente&#46; Este es el primer trabajo de la literatura en el que se demuestra la utilidad de esta nueva clasificaci&#243;n en los pacientes que cl&#237;nicamente se presentan con funci&#243;n renal normal y proteinuria inferior a 0&#44;5 g&#47;d&#237;a&#46; Los nuevos avances en la gen&#233;tica de esta enfermedad&#44; as&#237; como en la colaboraci&#243;n de las v&#237;as del complemento en su fisiopatogenia&#44; hacen que estos resultados no sean extrapolables a todas las poblaciones estudiadas&#46; Por otro lado&#44; el an&#225;lisis y seguimiento de la microhematuria ha recobrado importancia como factor pron&#243;stico independiente para el desarrollo de insuficiencia renal&#44; aunque a&#250;n no existen estudios consistentes al respecto&#46; Sin embargo&#44; es un tema que debe ser nuevamente considerado por la comunidad nefrol&#243;gica&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara">The level of proteinuria continues to be the clinical parameter that is best related to the development of long-term renal failure in glomerular pathologies&#46; This quantity is particularly important when we analyse the progression of patients with IgA nephropathy&#46; As such&#44; the natural progression of patients with IgA who clinically present with normal kidney function&#44; microhaematuria and low proteinuria had not been analysed comprehensively until the Spanish multicentre study herein analysed&#46; After studying 141 Caucasian patients with biopsied IgA nephropathy and a &#8220;benign&#8221; clinical profile and after they were classified histologically in accordance with the new Oxford classification&#44; it could be concluded that the renal prognosis of these patients was excellent&#46; This is the first study in the literature that demonstrates the usefulness of this new classification in patients who clinically have normal renal function and proteinuria below 0&#46;5g&#47;day&#46; The latest advances in the genetics of this disease&#44; as well as in the collaboration of complement pathways in its pathophysiology mean that these results cannot be extrapolated to all the populations studied&#46; In addition&#44; the analysis and follow-up of microhaematuria has regained importance as an independent prognostic factor for developing renal failure&#44; although there are no consistent studies in this regard yet&#46; However&#44; it is a subject that should be examined again by the nephrology community&#46;</p>"
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