Simple Blood Ratio HRR Emerges as a New Clue for Detecting Diabetic Kidney Disease

Diabetic kidney disease remains one of the most feared complications of type 2 diabetes, quietly damaging the filters of the kidney in millions of patients long before symptoms become obvious. Now, a team of researchers in China has reported that a remarkably simple calculation, performed on two numbers that already appear in every routine complete blood count, may help flag which critically ill patients with diabetes are carrying this hidden burden. The measure, known as the hemoglobin-to-red cell distribution width ratio, or HRR, was linked in a large retrospective study to the presence of diabetic kidney disease among hospitalized patients with type 2 diabetes.

The research, published in BMC Endocrine Disorders, drew on the MIMIC-IV database, a vast, de-identified repository of intensive care unit records maintained through PhysioNet and approved by the institutional review boards of the Massachusetts Institute of Technology and Beth Israel Deaconess Medical Center. After applying strict inclusion and exclusion criteria, the investigators identified 8,201 patients who had been diagnosed with type 2 diabetes mellitus during an ICU stay. Because the data were fully anonymized and the design was retrospective, individual informed consent was not required, and the study was conducted in accordance with the Declaration of Helsinki.

To understand why this ratio matters, it helps to unpack its two components. Hemoglobin is the iron-containing protein inside red blood cells that carries oxygen from the lungs to every tissue in the body, including the delicate capillary networks of the kidney. Red cell distribution width, or RDW, is a measure of how much the sizes of circulating red blood cells vary from one another. A high RDW signals anisocytosis, a heterogeneity in cell size that has been associated in numerous studies with inflammation, oxidative stress, nutritional deficiencies, and disturbed red blood cell production in the bone marrow. Both hemoglobin levels and RDW have previously been shown to correlate with diabetic kidney disease, which is precisely why the authors reasoned that combining them into a single ratio might capture more information than either marker alone.

The logic behind the combination is straightforward. Hemoglobin tends to fall as diabetic kidney disease progresses, in part because damaged kidneys produce less erythropoietin, the hormone that stimulates red blood cell production, and in part because of the chronic inflammatory state that accompanies renal decline. RDW, meanwhile, tends to rise as the marrow responds unevenly to these stresses, releasing red cells of increasingly disparate sizes. Dividing hemoglobin by RDW therefore creates an index that moves downward when both abnormalities are present, potentially offering a single integrated signal of the physiological turbulence that diabetic kidney disease generates.

To test that idea rigorously, the team used stratified random sampling by diabetic kidney disease status to split their cohort into a training set of 5,741 cases and a validation set of 2,460 cases, in a seven-to-three ratio. This division matters because it allows a finding discovered in one portion of the data to be checked against an independent portion, guarding against the statistical flattery that can arise when researchers analyze and validate on the same patients. The stratification by disease status ensured that both sets contained comparable proportions of patients with and without diabetic kidney disease, preserving the balance needed for fair comparison.

The analytical toolkit combined three complementary techniques. Multivariate logistic regression, which estimates the association between an exposure and an outcome while adjusting for other variables, showed that elevated HRR was negatively correlated with the risk of diabetic kidney disease, a relationship that reached statistical significance. In other words, patients with higher ratios were less likely to have the disease, and those with lower ratios were more likely to have it, exactly the direction the underlying biology would predict.

Next, the researchers turned to receiver operating characteristic curve analysis, a standard method for quantifying how well a continuous marker discriminates between two groups. The area under the ROC curve reflects this discriminatory power, with a value of 0.5 indicating performance no better than a coin flip and a value of 1.0 indicating perfect separation. When the team compared HRR against hemoglobin alone and RDW alone, the ratio demonstrated slightly better discriminatory performance for diabetic kidney disease than either single indicator, in both the training and the validation sets, with the differences reaching statistical significance. This is a meaningful, if modest, advantage: it suggests that the integrated ratio genuinely carries information that neither component captures on its own, rather than simply repackaging the same signal.

Perhaps the most intriguing result came from restricted cubic splines, a flexible regression technique that allows researchers to map out nonlinear dose-response relationships without imposing a predetermined straight line. The spline analysis confirmed that the relationship between HRR and diabetic kidney disease risk was not linear but curved, with a turning point identified at an HRR value of 6.9492. Below that threshold, the association between the ratio and disease risk behaved differently than above it, hinting that the marker may be most informative within a specific physiological range. Nonlinear findings of this kind are increasingly recognized as important in biomarker research, because they can reveal thresholds at which risk accelerates or plateaus, information that a simple linear model would smooth over and obscure.

The clinical appeal of HRR lies in its accessibility. Unlike specialized renal markers or imaging studies, the ratio requires no additional blood draw, no extra cost, and no laboratory beyond the standard complete blood count that virtually every hospitalized patient already receives. For patients with type 2 diabetes admitted to intensive care, a low HRR could serve as an inexpensive red flag prompting clinicians to look more closely at kidney function, tighten glycemic management, or consider nephroprotective strategies earlier in the hospitalization. The authors caution, however, that the discriminatory advantage of HRR over its individual components was slight, and that a cross-sectional design captures a single moment in time rather than tracking disease development, so the ratio cannot establish that low HRR precedes or causes kidney damage.

Those caveats frame the study as a promising observational association rather than a ready-made diagnostic test. The team, led by Feng Li, Yali Li, Hongsheng Ren, Lujing Meng, and corresponding author Jiefang Zhang, based at Heze Municipal Hospital, the Provincial Hospital of the First Medical University of Shandong Province, and Qingdao Municipal Hospital, acknowledges that prospective studies will be needed to determine whether HRR can predict the future onset or progression of diabetic kidney disease, and whether it adds value beyond established measures such as estimated glomerular filtration rate and urinary albumin. Still, the findings add to a growing body of evidence that routine hematological indices, examined with modern statistical tools, can illuminate the inflammatory and hematological fingerprints of diabetic complications. In a disease that affects more than half a billion people worldwide and quietly destroys kidneys along the way, even a slightly sharper, essentially free early warning signal could prove valuable. The work was supported by the Key Medical and Health Discipline of Shandong Province, and the full open-access article is available under a Creative Commons license for clinicians and researchers who wish to examine the methods in detail.

Subject of Research: Association between the hemoglobin-to-red cell distribution width ratio and diabetic kidney disease in patients with type 2 diabetes

Article Title: Association between hemoglobin-to-red cell distribution width ratio (HRR) and diabetic kidney disease: a cross-sectional study based on the MIMIC-IV database

Article References: Li, F., Li, Y., Ren, H., Meng, L., & Zhang, J. (2026). Association between hemoglobin-to-red cell distribution width ratio (HRR) and diabetic kidney disease: a cross-sectional study based on the MIMIC-IV database. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02588-1

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02588-1

Keywords: diabetic kidney disease, type 2 diabetes, hemoglobin, red cell distribution width, HRR, MIMIC-IV, biomarker, ICU, cross-sectional study, logistic regression, restricted cubic splines, nephrology