What is the significance of a sharp rise in Albumin-to-Creatinine Ratio (ACR) with a stable estimated Glomerular Filtration Rate (eGFR)?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

A sharp rise in albumin-to-creatinine ratio (ACR) despite stable estimated glomerular filtration rate (eGFR) is a significant indicator of early kidney damage and requires prompt medical attention, likely warranting referral to a nephrologist. This pattern suggests that protein is leaking into the urine while kidney filtration function remains intact. The most recent and highest quality study 1 recommends optimizing blood pressure control, aiming for targets below 130/80 mmHg using medications like ACE inhibitors (such as lisinopril 10-40 mg daily) or angiotensin receptor blockers (such as losartan 25-100 mg daily), which specifically reduce proteinuria.

Key Recommendations

  • Improve glycemic control if diabetic, targeting HbA1c below 7% as suggested by 1 and 1
  • Reduce dietary sodium to less than 2 grams daily and consider moderate protein restriction (0.8 g/kg/day) as recommended by 1
  • Lifestyle modifications including weight loss if overweight, regular exercise, and smoking cessation are essential

Rationale

The elevated ACR indicates damage to the glomerular filtration barrier allowing albumin to leak into urine, which is both a marker of kidney damage and can itself contribute to further kidney injury through tubular toxicity. The combination of rising ACR with stable eGFR often represents a critical window for intervention before irreversible kidney damage occurs. According to 1, an increase in ACR above normal is associated with increased risk for adverse outcomes, and this increased risk is a continuum.

Monitoring and Referral

The frequency of monitoring should be guided by the severity of CKD and the risk for progression, as recommended by 1 and 1. Referral to a nephrologist may be considered for individuals with eGFR below 45 mL/min per 1.73 m2 or those with rapidly progressing disease. Timely identification and treatment of acute kidney injury (AKI) is also important, as AKI is associated with increased risks of progressive CKD and other poor health outcomes 1.

From the Research

Significance of a Sharp Rise in Albumin-to-Creatinine Ratio (ACR) with a Stable estimated Glomerular Filtration Rate (eGFR)

  • A sharp rise in ACR with a stable eGFR is associated with an increased risk of adverse renal events, including end-stage renal disease (ESRD) and mortality 2.
  • The combination of an increase in ACR and a decrease in eGFR is strongly associated with the risk of advanced CKD, with a hazard ratio of 15.15 (95% CI, 12.43-18.46) compared to stable values of both 3.
  • Changes in ACR are strongly and consistently associated with the risk of ESRD, with a 4-fold increase in ACR associated with a 3.08-times higher risk of ESRD 2.
  • A high ACR level is a strong risk factor for renal tubular impairment in patients with type 2 diabetes, with a baseline ACR > 63.10 mg/g associated with a strong risk of A1MCR rising from normal to >15 mg/g (odds ratio = 11.12, P = 0.001) 4.

Key Findings

  • The risk of ESRD and mortality is higher in patients with a sharp rise in ACR, even with a stable eGFR 2, 3.
  • The combination of changes in ACR and eGFR predicts kidney outcomes better than either alone 3.
  • A high ACR level is associated with an increased risk of developing renal tubular injury in patients with type 2 diabetes 4.
  • Changes in eGFR category accompanied by ≥25% decline (certain drop) is associated with increased ESRD risk, but this elevated risk is captured by patient characteristics and eGFR at the last visit 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Changes in GFR and Albuminuria in Routine Clinical Practice and the Risk of Kidney Disease Progression.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2021

Research

Short-term change in kidney function and risk of end-stage renal disease.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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