Thus, the highly variable clinical course and unpredictable progression of IgAN hinder its treatment strategy. Urinary protein levels may provide acceptable indicators of prognosis [1, 6–10]. However, assessing IgAN activity based on proteinuria should be carefully considered because proteinuria may partly be due to secondary focal segmental glomerulosclerosis (FSGS), known as ‘burned-out IgAN’, depending on the timing of biopsy during the clinical course JNK inhibitor purchase [9]. Hematuria is the most important indicator of IgAN activity [1, 6, 7], but clinical evaluation using hematuria can be problematic because there are limitations to its quantification because of

false-positive/negative reactions in dipstick tests. The clinical detection of urinary casts and dysmorphic red blood cells accompanying either macroscopic or microscopic hematuria clearly indicate that urinary

tract bleeding is glomerular in origin, but they do not accurately indicate disease activity. Immunohistochemical analysis of renal biopsy specimens is the gold standard for diagnosing and evaluating IgAN activity. However, over the prolonged clinical course of IgAN (approximately 20 years) the histological phenotype is dependent on the timing of renal biopsy [11]. In many countries, abnormalities found during urinalysis may be overlooked or purposely not followed up by further examination until renal function impairment is evident [6]. This raises a controversial issue among nephrologists of whether to perform renal biopsy in circumstances without renal function impairment or nephritic range proteinuria because of a perception that a specific MK-1775 purchase treatment is not yet available. Routine screening for urinary abnormalities is performed for all school-aged children in Japan [5, 12, 13]. Furthermore, symptom-free individuals with microscopic hematuria are more likely to undergo renal biopsy, leading to increased diagnosis

of IgAN in Japan. However, it is a common practice not to recommend renal biopsy for patients presenting with isolated hematuria or mild proteinuria in the UK, Canada, and the USA, where renal biopsy is reserved for those who develop increasing proteinuria or worsening renal function [6]. Differences in the pathological Liothyronine Sodium variables used for renal prognosis in the Japanese and Oxford classifications may partly account for the timing of renal biopsy [14, 15]. Renal biopsies cannot be performed frequently because of the risks involved with the procedure and for socioeconomic reasons. Therefore, renal biopsy is still a snapshot evaluation method and is not a practical method for determining disease activity. New sensitive and adequately specific noninvasive tests are developing that may guide therapeutic strategies applicable to all IgAN stages. Multivariable pathophysiological processes may mediate IgAN initiation and progression, although IgAN is attributable to mesangial IgA or IgA immune complex (IC) deposition.