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Early diagnosis and intervention are key to improve outcomes. Single-nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR), or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after the loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin\u2013angiotensin system blockers to mineralocorticoid receptor blockers to sodium\u2013glucose co-transporter 2 inhibitors to tolvaptan, induce an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predate current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single-nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.<\/jats:p>","DOI":"10.1093\/ndt\/gfae027","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T04:33:12Z","timestamp":1706934792000},"page":"1228-1238","source":"Crossref","is-referenced-by-count":84,"title":["Glomerular hyperfiltration as a therapeutic target for CKD"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-0675","authenticated-orcid":false,"given":"Mehmet","family":"Kanbay","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Koc University School of Medicine , Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidar","family":"Copur","sequence":"additional","affiliation":[{"name":"Department of Medicine, Koc University School of Medicine , Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cicek N","family":"Bakir","sequence":"additional","affiliation":[{"name":"Department of Medicine, Koc University School of Medicine , Istanbul ,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Covic","sequence":"additional","affiliation":[{"name":"Nephrology Clinic, Dialysis and Renal Transplant Center \u2013 \u2018C.I. Parhon\u2019 University Hospital \u00a0 , Iasi ,","place":["Romania"]},{"name":"and \u2018Grigore T. Popa\u2019 University of Medicine \u00a0 , Iasi ,","place":["Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-9523","authenticated-orcid":false,"given":"Alberto","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz UAM , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine R","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Washington , Seattle, WA ,","place":["USA"]},{"name":"Providence Medical Research Center, Providence Health Care , WA 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