Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function

Abstract Ammonium excretion is often estimated using urinary anion gap (UAG) and osmolality gap (UOG) when direct measurement is unavailable, particularly in patients with impaired kidney function. We aimed to examine how UAG and UOG vary across different levels of kidney function and their relation...

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Main Authors: Saeko Hatanaka Ito, Go Kanzaki, Hideaki Kuno, Takahito Niikura, Kosuke Honda, Yasuyuki Nakada, Nobuo Tsuboi, Takashi Hasegawa, Takashi Yokoo
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05249-w
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author Saeko Hatanaka Ito
Go Kanzaki
Hideaki Kuno
Takahito Niikura
Kosuke Honda
Yasuyuki Nakada
Nobuo Tsuboi
Takashi Hasegawa
Takashi Yokoo
author_facet Saeko Hatanaka Ito
Go Kanzaki
Hideaki Kuno
Takahito Niikura
Kosuke Honda
Yasuyuki Nakada
Nobuo Tsuboi
Takashi Hasegawa
Takashi Yokoo
author_sort Saeko Hatanaka Ito
collection DOAJ
description Abstract Ammonium excretion is often estimated using urinary anion gap (UAG) and osmolality gap (UOG) when direct measurement is unavailable, particularly in patients with impaired kidney function. We aimed to examine how UAG and UOG vary across different levels of kidney function and their relationships with acid–base parameters. This retrospective cohort study included 531 outpatients categorized by estimated glomerular filtration rate (eGFR: ≥ 90, 60–89, 45–59, 30–44, and < 30 mL/min/1.73 m2). UAG values increased significantly with declining eGFR (p = 0.002), whereas UOG showed no clear trend (p = 0.303). UAG correlated positively with serum pH (ρ = 0.135, p = 0.002) and urinary pH (ρ = 0.333, p < 0.001). UOG was strongly inversely correlated with urinary pH (ρ = -0.512, p < 0.001). Sensitivity analyses stratified by serum anion gap and bicarbonate substantiated UAG’s relationship with eGFR. Multivariate analyses confirmed UAG’s association with eGFR, serum pH, and urinary pH, whereas UOG was predominantly influenced by urinary pH and minimally by eGFR. Although UOG has traditionally been considered superior, our findings suggest that UAG demonstrated more consistent associations with kidney function parameters. However, direct NH₄⁺ measurements remain necessary for definitive clinical assessment.
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spelling doaj-art-7fbb1fc6744440f4874054a123c1ff832025-08-20T03:38:15ZengNature PortfolioScientific Reports2045-23222025-07-011511910.1038/s41598-025-05249-wUrine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney functionSaeko Hatanaka Ito0Go Kanzaki1Hideaki Kuno2Takahito Niikura3Kosuke Honda4Yasuyuki Nakada5Nobuo Tsuboi6Takashi Hasegawa7Takashi Yokoo8Division of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineDepartment of Internal Medicine, Atsugi City HospitalDivision of Nephrology and Hypertension Department of Internal Medicine, The Jikei University School of MedicineAbstract Ammonium excretion is often estimated using urinary anion gap (UAG) and osmolality gap (UOG) when direct measurement is unavailable, particularly in patients with impaired kidney function. We aimed to examine how UAG and UOG vary across different levels of kidney function and their relationships with acid–base parameters. This retrospective cohort study included 531 outpatients categorized by estimated glomerular filtration rate (eGFR: ≥ 90, 60–89, 45–59, 30–44, and < 30 mL/min/1.73 m2). UAG values increased significantly with declining eGFR (p = 0.002), whereas UOG showed no clear trend (p = 0.303). UAG correlated positively with serum pH (ρ = 0.135, p = 0.002) and urinary pH (ρ = 0.333, p < 0.001). UOG was strongly inversely correlated with urinary pH (ρ = -0.512, p < 0.001). Sensitivity analyses stratified by serum anion gap and bicarbonate substantiated UAG’s relationship with eGFR. Multivariate analyses confirmed UAG’s association with eGFR, serum pH, and urinary pH, whereas UOG was predominantly influenced by urinary pH and minimally by eGFR. Although UOG has traditionally been considered superior, our findings suggest that UAG demonstrated more consistent associations with kidney function parameters. However, direct NH₄⁺ measurements remain necessary for definitive clinical assessment.https://doi.org/10.1038/s41598-025-05249-wUrine anion gapUrine osmolality gapAcid–base balanceChronic kidney disease
spellingShingle Saeko Hatanaka Ito
Go Kanzaki
Hideaki Kuno
Takahito Niikura
Kosuke Honda
Yasuyuki Nakada
Nobuo Tsuboi
Takashi Hasegawa
Takashi Yokoo
Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
Scientific Reports
Urine anion gap
Urine osmolality gap
Acid–base balance
Chronic kidney disease
title Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
title_full Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
title_fullStr Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
title_full_unstemmed Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
title_short Urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
title_sort urine anion and osmolality gaps in the comprehensive evaluation of acid base balance across different levels of kidney function
topic Urine anion gap
Urine osmolality gap
Acid–base balance
Chronic kidney disease
url https://doi.org/10.1038/s41598-025-05249-w
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