📄 nephrology

Association between the hemoglobin albumin lymphocyte and platelet score and chronic kidney disease: insights from patient data and animal models

This study demonstrates that lower HALP scores are independently associated with an increased risk of chronic kidney disease and albuminuria, identifying a protective threshold effect and validating these clinical findings through superior discriminative ability compared to other biomarkers and consistent results in a rat nephrectomy model.

Original authors: Zhang, w., Wang, Y., Ye, W., Wang, Y., Chen, X., Zhao, B., Zhang, X., Chen, z.

Published 2026-06-23

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CC BY 4.0

Original authors: Zhang, w., Wang, Y., Ye, W., Wang, Y., Chen, X., Zhao, B., Zhang, X., Chen, z.

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

The Big Picture: A "Health Report Card" for Your Kidneys

Imagine your body is a busy city. Your kidneys are the water treatment plants that filter out trash and keep the water clean. Sometimes, these plants get clogged or damaged, leading to a problem called Chronic Kidney Disease (CKD). The trouble is, the plants often keep working quietly even when they are broken, so the city doesn't realize there's a problem until it's too late.

This study is like a team of detectives trying to find a new, easy way to spot these broken plants early. They looked at a specific "report card" called the HALP score.

What is the HALP Score?

Think of the HALP score as a four-ingredient smoothie that tells you how well your body is doing two big jobs:

Nutrition: How well you are fed and fueled.
Inflammation: How much your body is fighting a low-level fire (swelling or irritation).

The smoothie is made of four ingredients found in a standard blood test:

Hemoglobin (The oxygen carriers, like delivery trucks).
Albumin (The protein, like the construction workers fixing the city).
Lymphocytes (The immune soldiers, like the police force).
Platelets (The clotting agents, like the emergency repair crews).

The Formula: You take the "good guys" (Hemoglobin, Albumin, Lymphocytes), multiply them together, and divide by the "repair crew" (Platelets).

High HALP Score: A strong smoothie. It means you have plenty of fuel, good construction workers, and a strong police force, with just enough repair crews to handle minor issues.
Low HALP Score: A weak smoothie. It suggests your body is running low on fuel, the construction workers are tired, and the police force is shrinking, while the repair crews are overwhelmed.

What Did the Researchers Find?

The team did two things: they looked at data from 25,000 real people (from a massive US health survey) and they tested this theory on rats with kidney damage.

1. The Human Detective Work (The Survey)
They found a clear pattern: People with a lower HALP score were much more likely to have kidney disease or protein leaking into their urine.

The "Sweet Spot": They discovered a "tipping point" (a threshold) at a score of 52.43.
- If your score was below this, every tiny increase in your score made your risk of kidney disease drop significantly.
- Once your score went above 52.43, the risk stopped dropping. It was like climbing a hill; once you reach the top, going higher doesn't make you any safer.
The Comparison: They compared the HALP score to other known health markers (like PNI, SII, LMR, and PLR). The HALP score was the best detective of the bunch. It was better at spotting kidney trouble than any of the other single markers they tested.
The Catch: While the HALP score was great at spotting early signs of trouble (like protein in the urine), it wasn't as good at predicting severe kidney failure (where the filtration rate drops very low) once the disease was already advanced.

2. The Rat Experiment (The Lab Test)
To make sure this wasn't just a coincidence in humans, they created a group of rats with damaged kidneys (by surgically removing most of their kidney tissue).

The Result: The rats with damaged kidneys had much lower HALP scores than the healthy rats.
The Connection: The lower the rat's HALP score, the worse their kidney damage was. The score dropped as the "trash" in their blood (creatinine and urea) went up.
The Best Match: The HALP score correlated most strongly with the amount of protein leaking into the rats' urine, confirming the human findings.

Why Does This Matter?

The paper suggests that the HALP score is a simple, cheap, and powerful tool.

It combines four things that doctors already measure in a standard blood test.
It acts like a "canary in the coal mine," potentially warning us about kidney stress before the damage becomes irreversible.
It works across different groups of people (men, women, young, old, with or without diabetes).

What the Paper Doesn't Say

It is important to stick to what the paper actually claims:

It is not a cure: The paper does not say that eating more protein or taking vitamins will fix your kidneys. It only says the score reflects the current state of health.
It is not a crystal ball: Because the study looked at a snapshot in time (a single survey), it cannot prove that a low score causes kidney disease, or that raising the score will stop the disease. It only shows they are linked.
It needs more testing: The "magic number" of 52.43 is a discovery from this specific study. The authors say this number needs to be tested on other groups of people before doctors can use it as a strict rule.

The Bottom Line

This study suggests that if you look at a simple "smoothie" made of four common blood numbers (Hemoglobin, Albumin, Lymphocytes, and Platelets), you can get a surprisingly accurate picture of your kidney health. A low score is a red flag that your kidneys might be under stress, and this score seems to be a better warning system than other similar tools currently in use.

Technical Summary: Association between the HALP Score and Chronic Kidney Disease

Problem Statement
Chronic kidney disease (CKD) represents a significant global public health burden, yet early detection remains challenging due to the asymptomatic nature of the disease in its initial stages. By the time clinical symptoms manifest, renal injury is often irreversible. Current literature suggests that CKD progression is driven by a bidirectional "inflammation-malnutrition" interaction. While composite biomarkers integrating nutritional and inflammatory status have shown promise in specific renal subtypes (e.g., diabetic nephropathy, IgA nephropathy) and dialysis populations, evidence regarding the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score in the general adult population remains scarce. Furthermore, the biological pathways linking the HALP score to CKD lack experimental validation.

Methodology
This study employed a dual-approach design combining a large-scale human cohort analysis with an animal model validation.

Human Cohort Analysis:
- Data Source: The study analyzed data from 25,160 adult participants (aged ≥20) drawn from the National Health and Nutrition Examination Survey (NHANES) cycles spanning 2009–2018.
- Exposure: The HALP score was calculated as: $[Hemoglobin (g/L) \times Albumin (g/L) \times Lymphocyte (10^9/L)] / Platelet (10^9/L)$ .
- Outcomes: The primary outcomes were CKD (defined as albuminuria ≥30 mg/g or eGFR <60 mL/min/1.73 m²), albuminuria, and low-eGFR.
- Statistical Analysis: Weighted multivariable logistic regression was used to assess associations across three models (crude, demographic-adjusted, and fully adjusted for lifestyle, comorbidities, and laboratory parameters). Generalized additive models (GAMs) and two-piecewise linear regression were utilized to identify non-linear relationships and threshold effects. Subgroup, interaction, and sensitivity analyses were conducted to ensure robustness. Receiver operating characteristic (ROC) curve analysis compared the discriminative capacity of the HALP score against the Prognostic Nutritional Index (PNI), Systemic Immune-Inflammation Index (SII), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR).
Animal Model Validation:
- Model: A 5/6 nephrectomy rat model (Platt's method) was established in male Sprague-Dawley rats to induce CKD.
- Procedure: Rats underwent a two-step surgical procedure (left renal partial resection followed by right total nephrectomy).
- Assessment: Renal function (BUN, Scr, UACR) and HALP components were measured. Histopathological analysis (H&E and Masson trichrome staining) confirmed renal injury. Pearson correlation analysis examined the relationship between HALP scores and renal function markers.

Key Results

Inverse Association: After adjusting for multiple confounders, higher HALP scores were significantly inversely associated with the prevalence of CKD (OR = 0.97, 95% CI: 0.94–0.99) and albuminuria (OR = 0.97, 95% CI: 0.93–0.99).
Threshold Effect: Non-linear analysis revealed a threshold effect for CKD risk. The risk declined as the HALP score increased up to an inflection point of 52.43. Beyond this threshold, no further protective effect was observed. A similar threshold pattern was identified for albuminuria (inflection point at 49.82).
Low-eGFR Association: While an inverse association was observed in crude and demographic-adjusted models, the association between HALP score and low-eGFR lost statistical significance after full adjustment for all covariates.
Discriminative Ability: ROC analysis demonstrated that the HALP score possessed superior discriminative ability for identifying CKD and albuminuria compared to PNI, SII, LMR, and PLR.
Animal Validation: CKD model rats exhibited significantly lower HALP scores compared to controls, accompanied by reduced hemoglobin, albumin, and lymphocytes, and elevated platelets. The HALP score showed a strong negative correlation with serum creatinine, BUN, and urinary albumin-to-creatinine ratio (UACR), with UACR showing the strongest correlation ( $r = -0.771$ ). Histology confirmed typical CKD pathology in the model group.

Significance and Claims
The authors claim that this study provides the first comprehensive evidence linking the HALP score to CKD in a general, nationally representative population, extending beyond previous research limited to specific renal subtypes or dialysis patients. The study highlights the HALP score as an affordable, readily measurable biomarker that integrates both inflammatory and nutritional dimensions, potentially offering a more comprehensive assessment of renal injury risk than single-axis indices.

The identification of a specific threshold (52.43) suggests a potential clinical utility for stratifying risk and identifying individuals who may benefit from nutritional intervention or inflammatory monitoring. The inclusion of the 5/6 nephrectomy rat model serves to validate the clinical findings experimentally, reinforcing the biological plausibility of the association.

The authors maintain a modest stance, acknowledging that the cross-sectional nature of the NHANES data precludes causal inference and that the proposed mechanisms (inflammation, malnutrition, platelet activation) remain speculative without further mechanistic study. They conclude that while the HALP score is a promising indicator for CKD risk assessment, longitudinal and interventional studies are necessary to establish its predictive utility and confirm whether modulating the HALP score can alter disease progression.