Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury

Activin A is known to impede tubular repair following renal ischemia, whereas exogenous follistatin, an activin A antagonist, has been shown to ameliorate kidney damage in rats. Despite these findings, the precise role of endogenous follistatin in the kidney has yet to be elucidated. In this study,...

Full description

Bibliographic Details
Main Authors: Izumi Nagayama, Kaori Takayanagi, Daisuke Nagata, Hajime Hasegawa, Akito Maeshima
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/13/6/525
_version_ 1797241696424034304
author Izumi Nagayama
Kaori Takayanagi
Daisuke Nagata
Hajime Hasegawa
Akito Maeshima
author_facet Izumi Nagayama
Kaori Takayanagi
Daisuke Nagata
Hajime Hasegawa
Akito Maeshima
author_sort Izumi Nagayama
collection DOAJ
description Activin A is known to impede tubular repair following renal ischemia, whereas exogenous follistatin, an activin A antagonist, has been shown to ameliorate kidney damage in rats. Despite these findings, the precise role of endogenous follistatin in the kidney has yet to be elucidated. In this study, we investigated the localization of follistatin in the normal human kidney and its potential utility as a marker for acute kidney injury (AKI). In a total of 118 AKI patients and 16 healthy adults, follistatin levels in serum and urine were quantified using ELISA, and correlations with clinical parameters were analyzed. Follistatin-producing cells were positive for Na-Cl co-transporter and uromodulin, but negative for aquaporin 1 and aquaporin 2. Unlike healthy adults, urinary follistatin significantly increased in AKI patients, correlating positively with AKI severity. Urinary follistatin levels were notably higher in patients needing renal replacement therapy. Significant correlations were observed with urinary protein, α1 microglobulin, and urinary NGAL, but not with urinary KIM-1, urinary L-FABP, urinary NAG, urinary β2 microglobulin, or serum creatinine. Interestingly, no correlation between urinary and serum follistatin levels was identified, indicating a renal origin for urinary follistatin. In conclusion, follistatin, produced by distal tubules, is detectable in the urine of AKI patients, suggesting its potential as a valuable marker for monitoring acute tubular damage severity in AKI.
first_indexed 2024-04-24T18:27:26Z
format Article
id doaj.art-f166ca40669945c48dd6f6381c05bf95
institution Directory Open Access Journal
issn 2073-4409
language English
last_indexed 2024-04-24T18:27:26Z
publishDate 2024-03-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj.art-f166ca40669945c48dd6f6381c05bf952024-03-27T13:30:39ZengMDPI AGCells2073-44092024-03-0113652510.3390/cells13060525Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney InjuryIzumi Nagayama0Kaori Takayanagi1Daisuke Nagata2Hajime Hasegawa3Akito Maeshima4Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, JapanDepartment of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke 329-0431, JapanDepartment of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, JapanDepartment of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe 350-8550, JapanActivin A is known to impede tubular repair following renal ischemia, whereas exogenous follistatin, an activin A antagonist, has been shown to ameliorate kidney damage in rats. Despite these findings, the precise role of endogenous follistatin in the kidney has yet to be elucidated. In this study, we investigated the localization of follistatin in the normal human kidney and its potential utility as a marker for acute kidney injury (AKI). In a total of 118 AKI patients and 16 healthy adults, follistatin levels in serum and urine were quantified using ELISA, and correlations with clinical parameters were analyzed. Follistatin-producing cells were positive for Na-Cl co-transporter and uromodulin, but negative for aquaporin 1 and aquaporin 2. Unlike healthy adults, urinary follistatin significantly increased in AKI patients, correlating positively with AKI severity. Urinary follistatin levels were notably higher in patients needing renal replacement therapy. Significant correlations were observed with urinary protein, α1 microglobulin, and urinary NGAL, but not with urinary KIM-1, urinary L-FABP, urinary NAG, urinary β2 microglobulin, or serum creatinine. Interestingly, no correlation between urinary and serum follistatin levels was identified, indicating a renal origin for urinary follistatin. In conclusion, follistatin, produced by distal tubules, is detectable in the urine of AKI patients, suggesting its potential as a valuable marker for monitoring acute tubular damage severity in AKI.https://www.mdpi.com/2073-4409/13/6/525follistatinacute kidney injuryurinary biomarker
spellingShingle Izumi Nagayama
Kaori Takayanagi
Daisuke Nagata
Hajime Hasegawa
Akito Maeshima
Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
Cells
follistatin
acute kidney injury
urinary biomarker
title Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
title_full Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
title_fullStr Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
title_full_unstemmed Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
title_short Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury
title_sort potential utility of urinary follistatin as a non invasive indicator of acute tubular damage in patients with acute kidney injury
topic follistatin
acute kidney injury
urinary biomarker
url https://www.mdpi.com/2073-4409/13/6/525
work_keys_str_mv AT izuminagayama potentialutilityofurinaryfollistatinasanoninvasiveindicatorofacutetubulardamageinpatientswithacutekidneyinjury
AT kaoritakayanagi potentialutilityofurinaryfollistatinasanoninvasiveindicatorofacutetubulardamageinpatientswithacutekidneyinjury
AT daisukenagata potentialutilityofurinaryfollistatinasanoninvasiveindicatorofacutetubulardamageinpatientswithacutekidneyinjury
AT hajimehasegawa potentialutilityofurinaryfollistatinasanoninvasiveindicatorofacutetubulardamageinpatientswithacutekidneyinjury
AT akitomaeshima potentialutilityofurinaryfollistatinasanoninvasiveindicatorofacutetubulardamageinpatientswithacutekidneyinjury