Imagine facing a heart attack only to discover your kidneys are at serious risk too—it's a double blow that affects thousands, and new research is shining a light on how to spot trouble early. In this study, we dive into how a simple blood marker called serum angiotensinogen could be the key to predicting kidney problems in heart attack survivors, potentially changing how doctors manage these intertwined heart-kidney crises.
Serum Angiotensinogen: A Potential Game-Changer for Kidney Health After Heart Attacks – Insights and Real-World Applications
- Research Article *
- Open Access (check out the basics at https://www.springernature.com/gp/open-science/about/the-fundamentals-of-open-access-and-open-research) *
Release Date: November 19, 2025 *
Authors: Xiaoqin Zhang¹, Haoyong Zhang¹, Xi Liu¹, and Chen Yu¹ (and collaborators) *
Published in BMC Nephrology (visit https://bmcnephrol.biomedcentral.com/) – Volume 26, Article 651 (2025). Be sure to cite this work properly.
Summary
Background and Goals
When someone suffers an acute myocardial infarction (AMI)—that's a heart attack in plain terms—their kidneys can take a hit too. This condition, known as acute kidney injury (AKI) or type 1 cardiorenal syndrome (CRS), shows up in 9.6% to 43.2% of these cases, according to various studies. For beginners, think of AKI as a sudden drop in kidney function, like your body's filters getting clogged unexpectedly. This not only complicates recovery but also boosts the chances of long-term issues like chronic kidney disease (CKD), where kidneys gradually lose their filtering power over time. The exact rate of CKD following this in heart attack patients? Still a bit of a mystery, but it's a big concern.
Previous work has pointed to promising signs in the blood, such as angiotensinogen (a protein involved in blood pressure regulation) and α-Klotho (a protective factor for kidneys and aging), that might help catch type 1 CRS early. But do these hold up as predictors for kidney troubles years down the line in heart attack patients? That's what this research sets out to explore, aiming to give doctors tools for better prevention and care.
Approach
We ran a forward-looking observational study with 149 AMI patients admitted to Shanghai Tongji Hospital from November 2018 to August 2019. To keep it simple, this means we followed real patients over time without changing their treatment—just watching and measuring. We split them into groups: 103 without AKI (non-AKI) and 21 with AKI. Right at admission, we used a technique called enzyme-linked immunosorbent assay (ELISA)—essentially a high-tech blood test—to check levels of serum angiotensinogen, α-Klotho, and fibroblast growth factor 23 (FGF-23, a hormone that helps balance minerals like phosphorus).
We tracked them for an average of 36 months, noting who developed CKD. Then, we crunched the numbers to see how these biomarkers linked to kidney outcomes. For example, imagine using these tests like an early warning system for your car's engine—catching issues before they lead to a breakdown.
Findings
Out of 149 participants, 21 (about 14%) ended up with AKI, and the hospital death rate was low at 0.02%. Fast-forward three years: 22 patients (17.6%) had progressed to CKD. Here's the exciting part—only serum angiotensinogen levels showed a clear connection to both AKI and CKD development. The other biomarkers didn't stand out in this group.
We tested three prediction models for spotting AKI and CKD. For AKI, the areas under the curve (AUC, a measure of how well a test predicts—think of it as a score from 0 to 1, where higher is better) were 0.811 (95% CI: 0.565–0.733, p < 0.001), and for CKD, 0.700 (95% CI: 0.579–0.821, p < 0.001). The best threshold for angiotensinogen was 1541.40 pg/ml for AKI and 1332.88 pg/ml for CKD. Adding factors like age, serum creatinine (Scr, a waste product that builds up if kidneys falter), and estimated glomerular filtration rate (eGFR, a calculation of how well kidneys filter blood) supercharged these models, making predictions even sharper. In everyday terms, it's like upgrading from a basic weather app to one with radar for storms ahead.
Key Takeaway
Bottom line: Serum angiotensinogen looks like a reliable blood marker to forecast AKI and CKD risks in AMI patients, offering a straightforward way for clinicians to intervene early and improve lives.
Expert Review Notes (available at https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7/peer-review)
Opening Discussion
Type 1 cardiorenal syndrome (CRS1) happens when a sudden heart problem, like in AMI, triggers AKI—a tough combo with sky-high rates of illness and death [1]. For those new to this, picture the heart and kidneys as partners: if the heart stumbles, it can starve the kidneys of blood flow, leading to damage. AKI isn't just a short-term worry; it's a stepping stone to CKD and even end-stage kidney disease (ESRD), where dialysis might become necessary. But how often does AKI turn into CKD in CRS1? The numbers are fuzzy, and the shift involves tangled biological processes—like inflammation, scarring, and hormonal imbalances—that scientists are still untangling.
Spotting reliable early signals is vital for stepping in before things worsen. Enter angiotensinogen: this liver-made protein kicks off the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluids but can go haywire in stress [2]. In AKI, RAAS ramps up, flooding the kidneys with angiotensin II, a constrictor that squeezes blood vessels. Urinary angiotensinogen (measured in urine) is steadier than direct angiotensin checks and flags AKI worsening, especially in heart failure flare-ups [3]. Ongoing RAAS overdrive, shown by high urinary levels, can fuel lasting kidney harm and CKD [4]. In severe cases, it even predicts needs for dialysis or death.
But here's where it gets controversial: High angiotensinogen might amp up RAAS, spiking angiotensin II, blood pressure, and heart strain—yet some argue RAAS blockers (common meds like ACE inhibitors) could help or hurt in acute settings. Does blocking it too soon risk low blood pressure? We'll circle back to that. Angiotensin II teams with aldosterone in high blood pressure and heart issues. In CRS1, poor kidney blood flow activates RAAS, feeding a vicious cycle. Urinary angiotensinogen surges on arrival, strongly signaling AKI [3,5,6]. It could be a top marker for acute heart-kidney links, revealing kidney status and CKD risks—but is serum (blood) version as good? More studies needed to confirm.
And this is the part most people miss: FGF23 and Klotho duo. FGF23, from bones, manages phosphorus and vitamin D; it needs Klotho (mostly kidney-based) as a partner to keep minerals balanced [7]. High FGF23 ties to artery hardening in CKD stages, worsening heart disease. Klotho, an anti-aging hero, boosts FGF23's phosphate-dumping and fights fibrosis via pathways like Wnt/β-catenin [8,9]. Low Klotho means phosphate buildup (hyperphosphatemia) and more injury.
Even without kidney tissue, Klotho shields the heart from excess FGF23's damage. High FGF23 and low Klotho signal kidney woes and heart risks, prime for early CRS1 alerts [6,10]. But do they predict AKI-to-CKD shifts in AMI? That's our quest.
This work probes serum angiotensinogen, FGF23, and α-Klotho for forecasting AKI progression post-AMI. We did a prospective, one-site study with 149 AMI adults in the Cardiac Care Unit (CCU), testing these at diagnosis to predict CRS1 kidney slides.
Study Setup and Methods
Design Overview
We included adults (18+) with AMI admitted to Tongji Hospital's CCU in Shanghai, China, from November 2018 to August 2019. We skipped those dying in the first 48 hours, or with liver cirrhosis, active cancer, or bad infections—to focus on clear cases.
AMI covers ST-elevation (STEMI, full blockage) and non-ST (NSTEMI, partial). Diagnosis followed the Fourth Universal Definition, backed by artery scans [11]. AKI used KDIGO rules: Scr up by ≥0.3 mg/dL (26.5 µmol/L) or 50% from baseline in 48 hours. We skipped urine output (low flow for 6 hours) since diuretics muddied it. CRS1: AKI within 48 hours of AMI [13]. All data from hospital electronic files; labs at Tongji's facility.
Ethics and Participation
Everyone signed informed consent. Approved by Tongji's Ethics Committee (KYSB-2017-116), following Helsinki standards.
Procedures
Scr measured on day one and twice in first three days. eGFR via 2021 CKD-EPI formula (a math tool estimating kidney filter speed). We checked deaths and CKD via records.
Sample Collection and Testing
Blood drawn day one, spun down, frozen at -80°C. Thawed for ELISA kits (Enzyme-linked Biotechnology, Shanghai) per instructions for α-Klotho, FGF23, angiotensinogen.
What We Measured
Main goal: In-hospital AKI and death. Secondary: AKI leading to CKD in three years.
Data Crunching
Categories as counts (percentages); continuous as medians (IQR) or means ± SD. Compared with t-tests, Mann-Whitney, or chi-square (two-tailed, p<0.05 significant). ROC for AUC; best cutoff via Youden's index (sensitivity + specificity -1). Correlations: Pearson for normal, Spearman otherwise. Logistic regression for links; univariate p<0.05 to multivariate. Used SPSS 21.0.
Participant Details
149 AMI patients (see Fig. 1 flowchart: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Fig1). Excluded 25 missing data/samples; 21 (14.09%) got AKI.
Group Profiles
Table 1 summarizes (https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Tab1). Mean age 64.33 ± 12.62 (33-89); more men (female:male 0.35, p=0.050). Common histories: hypertension (59.68%), diabetes (23.38%), stroke (16.13%), drinking (12.1%). No group differences in histories or RAAS inhibitor use (p>0.05).
Median systolic BP 124 mmHg (IQR 112-150); no big gaps vs. non-AKI (p=0.940). Diastolic and heart rate similar (p=0.533, 0.062).
Labs alike for potassium, cholesterol, LDH, HDL/LDL, glucose, HbA1c. But AKI group had higher CRP (inflammation marker), lower hemoglobin/albumin; big differences in BUN, UA, Scr, eGFR, hsTnI (all p<0.001 or 0.005)—showing worse kidney start and heart damage.
Killip classes (heart failure severity): I 79%, II 10.5%, III 4.8%, IV 5.7%; AKI higher severity (p=0.001). Contrast dye volumes same (148 vs. 135 mL, p=0.369; Supplemental Table 1).
Biomarker Links to AKI in AMI
Day-one levels: α-Klotho and FGF23 no difference; angiotensinogen higher in AKI (median 1761.67 pg/mL [IQR 1655.69–1848.07] vs. 1418.90 [1305.83–1677.93], p=0.001; Fig. 2: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Fig2—comparisons A-C).
AKI vs. Non-AKI Profiles
AKI folks had poorer baseline kidneys (higher Scr, lower eGFR). They faced higher in-hospital death risk and more post-discharge CKD (Table 2: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Tab2). For instance, AKI survivors were twice as likely to hit CKD, underlining the long shadow of acute hits.
AKI Risk Factors in AMI
Nine factors tied to AKI: age, angiotensinogen, hsTnI, Hb, CRP, albumin, BUN, Scr, eGFR. Multivariate: age, angiotensinogen, admission Scr key independents (Table 3: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Tab3). Older age means frailer kidneys; high angiotensinogen signals RAAS storm.
CKD Predictors Post-AMI
Univariate: ten factors (age, angiotensinogen, etc.; Table 4). Dropped BUN/UA (high overlap), Scr (tied to eGFR) to avoid stats bias. Multivariate: only angiotensinogen and admission eGFR independent for CKD (Table 4). Sustained high angiotensinogen might drive fibrosis, turning acute to chronic.
Angiotensinogen's Diagnostic Power for AKI/CKD in AMI
Three models: 1 (angiotensinogen solo), 2 (+Scr), 3 (+age/Scr). ROC AUC for AKI: 0.811 (0.565–0.733, p<0.001), 0.935 (0.882–0.988, p<0.001), 0.955 (0.914–0.996, p<0.001). For CKD: 0.700 (0.579–0.821, p=0.003), 0.814 (0.701–0.928, p<0.001), 0.955 (0.921–0.990, p<0.001). Cutoffs: AKI 1541.40 pg/ml (sens 95.2%, spec 61.17%); CKD 1332.88 pg/ml (95.5%, 55.3%). Adding vars boosted accuracy (Fig. 3: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-025-04573-7#Fig3—A/B ROCs). But here's the controversy: High sensitivity means it catches most at-risk, but moderate specificity might flag false alarms—worth the extra tests?
Deeper Insights
AKI hit 14.09% here, matching lit [14], and it's a major drag: longer stays, higher deaths, CKD/ESRD risks [15,16]. Causes? Unstable blood flow, swelling, drug/contrast toxins [17]. Early catch via biomarkers like NGAL, KIM-1, IL-18 helps [18,19,20-27]. Urine angiotensinogen predicts in heart failure [5]; our serum version shone, hinting RAAS role in AKI squeeze [28,29-32]. But counterpoint: In some views, RAAS activation protects short-term—blocking it early could backfire. What do you think?
Klotho/FGF23 promising elsewhere [33,34], but flat here—maybe small group or one-time check missed dynamics. AKI in AMI mixes ischemia, toxins; not all fit one mold.
Risks like age/angiotensinogen/Scr make sense: elders more vulnerable, baseline kidneys matter. For CKD, angiotensinogen/eGFR flag ongoing harm.
Models show angiotensinogen's strength, amped by basics—could slot into apps for quick risk scores.
Limits: Small size might miss subtle diffs (e.g., contrast as AKI trigger [35-37]); single measure ignores changes; high sens/low spec for screening, not diagnosis; no urine markers; spotty albuminuria data. Larger trials needed.
This flags angiotensinogen for early alerts in AMI—prompt fluid tweaks, kidney watches, safe meds. Next: Bigger studies, RAAS therapy trials.
Wrapping Up
Serum angiotensinogen stands out for predicting AKI/CKD post-AMI, boosting models for better care. More work on its biology and treatments ahead.
Data Access
Request from corresponding author (Dr. Yu); privacy limits full share.
Key Terms
AKI: Sudden kidney failure
CRS1: Heart-triggered kidney issue
AMI: Heart attack
CKD: Long-term kidney disease
FGF-23: Mineral hormone
ELISA: Blood test method
Scr: Creatinine in blood
eGFR: Kidney filter estimate
ESRD: Kidney failure end-stage
RAAS: Blood pressure system
CCU: Heart unit
STEMI/NSTEMI: Heart attack types
TC/LDH/HDL/LDL/BG/CRP/BUN/UA/hsTnI: Various blood measures
Sources (full list with DOIs, etc., as in original—e.g., 1. Ronco et al., J Am Coll Cardiol 2012; up to 37. Jentzer et al., J Am Coll Cardiol 2020).
Thanks
Gratitude to patients and team.
Support
Funded by China NSF (82300769), Shanghai Rising-Star (23YF1440600), Tongji projects (ITJ(ZD)2201, etc.), Putuo Consortium (YLT2403).
Author Details
¹Nephrology, Tongji Hospital, Tongji University, Shanghai 200065, China
Xiaoqin Zhang: Data, analysis, writing
Haoyong Zhang: Data help
Xi Liu: Experiments, analysis
Chen Yu: Oversight, writing
Contact: Xi Liu or Chen Yu
Ethics
Tongji approved (KYSB-2017-116); consent given; Helsinki compliant. No conflicts.
Publisher Note
Springer neutral on claims.
Rights
CC BY-NC-ND 4.0: Share non-commercially, credit source.
About This Piece
Zhang et al., BMC Nephrol 26, 651 (2025). DOI: 10.1186/s12882-025-04573-7
Received May 15, 2025; Accepted Oct 21, 2025; Published Nov 19, 2025.
Keywords:
Now, a thought-provoker: While angiotensinogen seems promising, why didn't Klotho/FGF23 pan out here—sample size or something deeper in AMI? And should we rush RAAS blockers in acute cases, or hold off? Agree this changes practice, or too early? Share in comments—your take could spark the next breakthrough!
