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The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice.<\/jats:p>","DOI":"10.1007\/s00467-022-05746-4","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T14:03:48Z","timestamp":1666188228000},"page":"2549-2562","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["How to define and assess the clinically significant causes of hematuria in childhood"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3812-2711","authenticated-orcid":false,"given":"Orsolya","family":"Horv\u00e1th","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7321-9861","authenticated-orcid":false,"given":"Attila J.","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-043X","authenticated-orcid":false,"given":"George S.","family":"Reusz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,19]]},"reference":[{"key":"5746_CR1","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/s0022-5347(17)40763-4","volume":"141","author":"AJ Mariani","year":"1989","unstructured":"Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A (1989) The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. 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