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Harald Mischak, Opponent's comments, Nephrology Dialysis Transplantation, Volume 30, Issue 4, April 2015, Pages 531–532, https://doi.org/10.1093/ndt/gfv044a
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Richard Glassock soundly discussed the historical development of kidney biopsy with its undeniable contribution to nephrology. He appreciates its further improvement by applying additional evaluation tools like immunofluorescence and electron microscopy and accredits the value of ‘traditional’ biomarkers like urinary albumin or eGFR for e.g. prognosis. Kidney biopsy has resulted in the definition of multiple new disease entities and subclassifications, but treatment of these different diseases is very similar; the impact of these morphology-based definitions on therapy appears very limited. Further, kidney biopsy is an invasive procedure associated with the risk of severe complications exceeding 1%, including, in rare cases, death [1, 2]. In contrast to urine sampling, kidney biopsy is not a ‘safe procedure’.
While biopsy was referred to as ‘gold standard’, this standard is not ‘golden’: Substantial interobserver differences and differences due to sampling clearly reduce the value of the biopsy-based assessment [3].
Repetitive sampling to unmask the evolution of a disease and/or assess treatment response is only possible non-invasively, e.g. urine-based. Apparently the abilities of urinary proteomic biomarkers for improving patient management are underestimated. These biomarkers enable differentiating between different renal diseases, and, more important, enable assessment on a molecular level. Glassock rightly states that a single biomarker is not sufficient to replace biopsy, but multidimensional biomarker panels have been developed, demonstrating excellent diagnostic accuracy. One example is CKD273, a classifier based on 273 urinary peptides, demonstrated to be well suitable for the early detection of CKD and for prognosis of progression [4]. As outlined in my article, today urinary proteome analysis can replace kidney biopsies in many cases and it will lead to changes in diagnosis, prognosis and therapy of CKD patients by assessing disease on a molecular level, as kidney biopsies did in the past by assessing CKD on a histomorphological level. The definition of CKD on a molecular, proteome level will enable identification of more appropriate therapeutic targets and development of new treatment regiments. Nephrology is privileged of having urine as an easy to access, abundant outflow product of the kidneys, reliable reflecting their status, an unsurpassed diagnostic opportunity not available for other organs.
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