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Author: Goldsite Team Publish Time: 2026-11-14 Origin: Site
Diabetes is one of the most common chronic metabolic diseases worldwide, and diabetic kidney disease (DKD) is its most serious microvascular complication. About one-third of people with type 1 diabetes and 50% of people with type 2 diabetes develop diabetic nephropathy during the course of the disease, and about 50% of those cases eventually progress to end-stage renal disease (ESRD). In China, the incidence of DKD among people with diabetes is as high as 30%–40%, and DKD has become a leading cause of ESRD.
“Diabetes–CKD co-management” has become a core consensus in nephrology and endocrinology in recent years. Both the KDIGO 2024 guideline and the ADA 2025 Standards of Care emphasize that people with diabetes and CKD need collaborative management by endocrinology and nephrology, moving from glucose control alone to combined cardio-renal protection: while controlling blood glucose, detect and intervene in kidney injury early, and slow the progression of CKD.
Core combined solution: HPLC HbA1c testing (reflecting mean glucose over 2–3 months, an etiological assessment) + specific-protein testing (UACR and tubular markers, reflecting the degree of kidney target-organ injury). The two are complementary and enable a two-dimensional assessment of diabetes and its kidney complications.
DKD incidence in people with diabetes 30–40% | Share of patients with early DKD 32.5% | CKD may already be present at T2DM diagnosis Yes | Recommended UACR screening frequency ≥1 / year |
UACR (urine albumin-to-creatinine ratio) is the ratio of urinary albumin concentration to urinary creatinine concentration, reported in mg/g (or mg/mmol). Because creatinine excretion is relatively constant, the ratio corrects for urine concentration or dilution, so a single spot urine can accurately reflect albumin excretion without a 24-hour collection.
| Category | UACR (mg/g) | UACR (mg/mmol) | Corresponding AER (mg/24h) | KDIGO albuminuria stage |
|---|---|---|---|---|
| Normal | < 30 | < 3 | < 30 | A1 (normal to mildly increased) |
| Microalbuminuria | 30–300 | 3–30 | 30–300 | A2 (moderately increased) |
| Macroalbuminuria | > 300 | > 30 | > 300 | A3 (severely increased) |
Optimal normal valueACR < 10 mg/g KDIGO clinical decision cut-points 30 and 300 mg/g
In a healthy kidney, the glomerular filtration barrier has three layers: the endothelial cell layer, the glomerular basement membrane (GBM), and the podocyte slit diaphragm. Under normal conditions, the GBM carries a strong negative charge (heparan sulfate proteoglycans) and effectively restricts the passage of negatively charged albumin (pI 4.8–5.2).
In the hyperglycemic state of diabetes, the glomerulus undergoes the following pathological changes:
Thus, the appearance of urinary albumin is a direct marker of glomerular filtration-barrier injury. Abnormalities can be detected before eGFR declines, making it one of the earliest biochemical markers of diabetic nephropathy.
Limitations of 24-hour urine: cumbersome collection, poor patient adherence, and large pre-analytical error (incomplete collection and laboratory error in urine-volume measurement).
Advantages of spot-urine UACR: it uses the relatively constant excretion of creatinine to correct for changes in urine volume; it correlates closely with the 24-hour albumin excretion rate (AER); first-morning ACR can even be more accurate than AER; and it requires only a single spot sample, which can be completed in clinic and is suitable for large-scale screening.
UACR is not only a kidney marker, but also a barometer of systemic vascular health:
| Guideline | Recommendation | Grade |
|---|---|---|
| ADA 2025 (11.1a) | In T1DM of ≥5 years’ duration and in all people with T2DM, assess UACR and eGFR annually | B |
| ADA 2025 (11.1b) | In people with confirmed CKD, monitor UACR and eGFR 1–4 times per year according to CKD stage | B |
| KDIGO 2024 | In people with CKD, measure albuminuria and eGFR at least once a year; twice a year in high risk, and ≥3 times a year in very high risk | 1B |
Clinical significance in brief: annual UACR screening is the core entry marker for diabetes–CKD co-management. It can detect early kidney injury before eGFR declines, guide the start of RAS blockade (ACEi/ARB is recommended when UACR is ≥30 mg/g), inform the indications for SGLT2 inhibitors and finerenone, and help predict cardiovascular and kidney outcomes. It is simple, low-cost and high-value — which is why it is a screening test that all people with diabetes should have at least once a year.
Glycated hemoglobin (HbA1c) is a stable product formed when the free amino group of the N-terminal valine on the β-chain of hemoglobin in red blood cells binds glucose in serum through a non-enzymatic reaction. The reaction is continuous, slow and irreversible. Red blood cells have a lifespan of about 120 days (three months), so HbA1c effectively reflects mean glucose over the past 8–12 weeks (2–3 months), expressed as a percentage of total hemoglobin.
Ion-exchange high-performance liquid chromatography (IE-HPLC) separates different glycated forms of hemoglobin on a cation-exchange resin column by differences in charge. HbA1c carries more negative charge than non-glycated HbA and elutes before HbA under defined conditions. The result is calculated as the HbA1c peak area as a percentage of total hemoglobin peak area. Each sample produces a chromatogram, which can be used to judge whether a hemoglobin variant is present.
| Dimension | What it means |
|---|---|
| Precision | Inter-laboratory CV ≤3%; some methods reach 2% |
| Accuracy | NGSP reference method; highly correlated with the IFCC reference method (r=0.9940) |
| Resistance to interference | The chromatogram can identify hemoglobin variants (HbS, HbC and others) |
| Throughput | Fully automated, suitable for large clinical sample volumes |
| Traceability | DCCT/UKPDS data were established directly on HPLC methods |
| Comparison | HPLC (ion-exchange) | Immunoassay | Enzymatic method | Capillary electrophoresis |
|---|---|---|---|---|
| Precision | High (CV ≤3%) | High | High | High |
| Variant identification | Yes (visible on the chromatogram) | No | No | Yes |
| Variant interference | Some variant peaks may be masked | Not interfered with by HbS/HbC | Not interfered with | Less interference |
| Traceability | NGSP/DCCT | IFCC | IFCC | IFCC |
The DCCT (1983–1993): a landmark study led by the U.S. NIH, with 9 years of follow-up in people with type 1 diabetes. Bio-Rad HPLC was the sole comparison method. It established an HbA1c reference upper limit of 6.0% and a treatment threshold of ≥7%, and confirmed a strong association between HbA1c and retinopathy, nephropathy and neuropathy.
The UKPDS (1998): the United Kingdom Prospective Diabetes Study, with 10 years of follow-up in type 2 diabetes. It reproduced the DCCT conclusion — reductions in complications were directly related to reductions in HbA1c.
These two landmark trials established a causal relationship between glucose control (as measured by HbA1c) and diabetic complications, making HbA1c an irreplaceable core marker for long-term diabetes monitoring.
NGSP (National Glycohemoglobin Standardization Program): established in 1996, administered by the CDC, with Bio-Rad HPLC as the reference method.
IFCC (International Federation of Clinical Chemistry and Laboratory Medicine): the 2007 Milan consensus established IFCC as the only globally valid reference system. Conversion: NGSP (%) = 0.0915 × IFCC (mmol/mol) + 2.15
| Use | Criterion |
|---|---|
| Diagnosis of diabetes | HbA1c ≥ 6.5%（ADACriterion） |
| General adult treatment target | < 7.0% (53 mmol/mol) |
| More stringent glucose target | < 6.5% (48 mmol/mol) |
| When CKD is present | Individualized adjustment (consider hypoglycemia risk, anemia and other effects) |
Special considerations for HbA1c when CKD is present: insulin clearance falls in CKD, increasing hypoglycemia risk; anemia, shortened red-cell lifespan and EPO use can affect the accuracy of HbA1c measurement. ADA recommends that the HbA1c target be individualized when CKD is present.
| Assessment dimension | HbA1c alone | UACR alone | Combined testing |
|---|---|---|---|
| Glucose assessment | ✓ | ✗ | ✓ Complete |
| Kidney injury | ✗ | ✓ | ✓ Complete |
| Detection of early DKD | Indirect | Can detect microalbuminuria | Earlier |
| Risk stratification | Glucose dimension only | Kidney dimension only | Full stratification |
| Recognition of metabolic memory | ✗ | ✗ | ✓ HbA1c normal but UACR↑ |
Basic panel: HbA1c (HPLC) + UACR + eGFR → annual screening for all people with diabetes
Extended panel: basic panel + urinary α1-MG/RBP (tubular injury) + serum cystatin C (more precise GFR) → for people with a normal UACR but a high suspicion of early DKD, or with progressive CKD
Comprehensive panel: extended panel + urine transferrin (glomerular charge barrier) + urine IgG (pore-size barrier) → when the cause of CKD is unclear, or finer stratification is needed
Aristo Ur uses dual methodology (immunonephelometry and spectrophotometry), runs 200 tests per hour, and offers 48 assays. One instrument can complete the tests and automatically report ACR, as well as multiple urinary protein-to-creatinine ratios. Used together with the laboratory HPLC HbA1c line (HPLC HbA1c Analyzer), it forms the kidney side of this co-management solution: HbA1c is measured by ion-exchange HPLC, and ACR is calculated automatically after integrated testing of urine microalbumin and urine creatinine.
The pathogenesis of diabetic kidney disease (DKD) involves the combined action of two pathways: glomerular injury and tubulointerstitial fibrosis. In recent years the research paradigm has shifted from a glomerulus-centered view to a tubule-centered view, recognizing that tubular injury may play an earlier and more central role in the onset of DKD.
Key insight: thickening of the tubular basement membrane (TBM) is among the earliest quantitatively detectable structural changes in the diabetic kidney, and can be observed even in patients with normoalbuminuria. Interstitial fibrosis and tubular atrophy (IFTA) are the most reliable histological predictors of DKD prognosis — together they can explain 94% of GFR variance in people with diabetes. This means that monitoring UACR alone (which reflects glomerular injury) may miss early tubulointerstitial injury, and that tubular markers (α1-MG, RBP, cystatin C and others) are needed as a complement.
In addition to UACR, the following laboratory markers can be used for early prediction and management of diabetes-related CKD. From different angles — the glomerular charge barrier, the pore-size barrier, tubular reabsorption, and more precise GFR estimation — they fill blind spots left by UACR. Combined testing can substantially improve the detection of early DKD.
| Molecular weight | About 77,000–81,000 Da (intermediate-molecular-weight protein) |
| Isoelectric point (pI) | 5.5–6.6 (higher than albumin, 4.8–5.2) |
| Mechanism of injury | Transferrin carries less negative charge, so charge repulsion at the GBM is weaker; it leaks more readily than albumin when the charge barrier is injured early |
| Reference range | 0–2.0 mg/L (measured value in normal controls about 0.6±0.2 mg/L) |
| Abnormal values | DM with normoalbuminuria: 2.4±0.9 mg/L (P<0.001); DM with microalbuminuria: 4.4±1.5 mg/L |
| Assay methods | ELISA, immunoturbidimetry |
Core value: a rise in urine transferrin appears earlier than microalbuminuria. In people with diabetes who still have a normal urine microalbumin, urine transferrin excretion is already significantly elevated. A 24-month prospective study by Narita T et al. (Diabetes Care, 2006) showed that transferrin can predict progression to microalbuminuria in patients with normal urinary albumin. UTRF is an independent risk factor for diabetic nephropathy (OR=16.138, P<0.001).
| Molecular weight | About 150,000–170,000 Da (high-molecular-weight protein) |
| Mechanism of injury | A normal glomerulus is almost impermeable to IgG; IgG in urine indicates severe pore-size barrier injury, and a shift from selective to non-selective proteinuria |
| Reference range | < 5.0 mg/L |
| Selectivity proteinuria index (SPI) | SPI = (urine IgG × serum transferrin) / (serum IgG × urine transferrin); SPI ≥0.21 = non-selective proteinuria (poor prognosis) |
| FEIgG cut-off | 0.043% (values above this predict ESRD, HR=37.1) |
| Assay methods | Immunoturbidimetry, immunonephelometry, ELISA |
Core value: urine IgG is a stronger indicator of diabetic nephropathy than microalbuminuria (Mohan S et al., 2012). The fractional excretion of IgG (FEIgG) is a strong independent predictor of ESRD (HR=37.1). If α1-microglobulin excretion is also increased, this suggests combined glomerular and tubulointerstitial injury and a worse prognosis.
| Molecular weight | About 33,000 Da (low-molecular-weight protein) |
| Mechanism of injury | Free α1-MG is freely filtered at the glomerulus, and 95–99% is reabsorbed in the proximal tubule; urinary excretion rises when the tubule is injured |
| Reference range | < 12 mg/L (morning urine); normal excretion 5–50 mg/day |
| Advantage vs β2-MG | Retains 86.4% of activity after 4 days at room temperature in acidic urine; higher excretion (less measurement error); not affected by malignancy; immunoturbidimetric methods can be automated |
| Assay methods | Immunoturbidimetry (preferred), immunonephelometry, ELISA |
Core value: in people with diabetes who are still in the normoalbuminuric stage, urinary α1-MG is already significantly higher than normal. Early tubular injury in diabetic nephropathy may precede glomerular injury, and urinary α1-MG can serve as a sensitive marker at this stage. After contrast exposure, urinary α1-MG rises in about 10–15% of patients, about 24–48 hours before a rise in serum creatinine, giving it early-warning value. It is increasingly regarded as a preferred low-molecular-weight protein marker over β2-MG.
| Molecular weight | 11,800 Da (99 amino acids) |
| Mechanism of injury | Freely filtered at the glomerulus, with 99.9% reabsorbed and degraded in the proximal tubule; a 10% fall in reabsorption can increase excretion about 30-fold |
| Reference range | < 0.2 mg/L (370 μg/24h) |
| Main limitation | Degrades rapidly at pH <5.5 (cathepsin D activation); urine must be alkalinized before testing; affected by malignancy |
| vs α1-MG | α1-MG is superior to β2-MG in acid stability, excretion amount, measurement accuracy and resistance to interference from malignancy |
| Assay methods | RIA, ELISA, immunoturbidimetry, latex-enhanced immunoturbidimetry |
Caution: β2-MG is a classic tubular-injury marker with very high sensitivity, but it is highly unstable in acidic urine (it degrades rapidly at pH <5.5), which is its main clinical limitation. Samples must be fresh and alkalinized (pH >5.5) before testing. Because of this limitation, RBP and α1-MG are considered more practical and reliable in clinical use.
| Molecular weight | About 21,000 Da |
| Mechanism of injury | A vitamin A transport protein synthesized in the liver; free RBP is rapidly filtered at the glomerulus and almost completely reabsorbed in the proximal convoluted tubule; urinary levels rise when the tubule is injured |
| Reference range | < 0.7 mg/L |
| Core advantages | Not affected by pH or proteolytic enzymes (stable in acidic urine); not affected by sex, posture or diurnal variation; urinary RBP excretion correlates clearly with the degree of tubulointerstitial injury |
| vs β2-MG | Far more stable than β2-MG, and more practical and reliable in use |
| Assay methods | ELISA, rapid latex immunonephelometry, immunoturbidimetry |
Core value: urinary RBP can detect tubular dysfunction early, sensitively reflects the degree of proximal tubular injury, and can serve as a sensitive biochemical marker for monitoring the course of disease, guiding treatment and judging prognosis. In 2023, Zhou et al. (BMC Nephrology) evaluated urinary RBP as an early diagnostic marker of diabetic nephropathy. It has an important place in the reliable monitoring of tubular injury in DKD.
| Molecular weight | 13,300 Da (122 amino acids) |
| Production | Produced at a constant rate by all nucleated cells (housekeeping gene); not affected by age, sex, body weight, muscle mass or inflammation |
| Metabolism | Freely filtered at the glomerulus → completely reabsorbed and degraded in the proximal convoluted tubule → does not return to blood → no tubular secretion |
| Determinants of serum concentration | Determined only by GFR (concentration is constant from age 1 to about 60) |
| Reference range | 0.51–1.09 mg/L; >1.0 mg/L suggests impaired kidney function |
| Assay methods | PETIA (particle-enhanced immunoturbidimetry), PENIA (particle-enhanced immunonephelometry) |
Core advantages — why it is superior to serum creatinine:
A specific KDIGO 2024 recommendation: when cystatin C is available, estimate eGFR with the combined creatinine–cystatin C equation (eGFRcr-cys), because the combined formula is closest to measured GFR. Cystatin C should be measured when eGFR is <60, or when muscle mass is abnormal, in liver disease or heart failure, or when drug doses need to be adjusted.
Value of combined diagnosis: cystatin C together with urine transferrin (UTRF) has the greatest diagnostic value for diabetic nephropathy (AUC=0.909, sensitivity 0.917, specificity 0.760).
| Marker | Site of injury reflected | Molecular weight | Reference range | Core advantage | Main limitation |
|---|---|---|---|---|---|
| UACR | Glomerular filtration barrier | — | <30 mg/g | Internationally recognized gold standard; simple | Appears later; does not reflect tubular injury |
| Urine transferrin | Glomerular charge barrier | ~79 kDa | <2.0 mg/L | Appears earlier than microalbuminuria | No unified international standard |
| Urine IgG | Glomerular pore-size barrier | ~150 kDa | <5.0 mg/L | Predicts ESRD (HR=37.1) | Reflects later-stage injury |
| Urine α1-MG | Proximal tubule | ~33 kDa | <12 mg/L | Good acid stability; not affected by malignancy | Standardized local reagent kits still to be resolved |
| Urine β2-MG | Proximal tubule | ~11.8 kDa | <0.2 mg/L | Very high sensitivity (10% fall in reabsorption ≈ 30-fold rise in excretion) | Unstable in acidic urine |
| Urine RBP | Proximal tubule | ~21 kDa | <0.7 mg/L | Not affected by pH; more reliable than β2-MG | Specificity is only moderate |
| Serum cystatin C | GFR (glomerular filtration function) | ~13.3 kDa | 0.51–1.09 mg/L | Not affected by muscle mass; sensitive to a mild fall in GFR | Affected by inflammation, smoking and thyroid status |
| Recommendation no. | Content | Grade |
|---|---|---|
| 1.1.2.1 | In adults at risk of CKD, use eGFRcr; when cystatin C is available, use the combined eGFRcr-cys estimate | 1B |
| 3.6.3 | In CKD with diabetes and A2/A3 proteinuria → start a RASi (ACEi or ARB) | 1B |
| 3.7.1 | In T2D with CKD and eGFR ≥20 → recommend an SGLT2 inhibitor | 1A |
| 3.8.1 | In T2D with eGFR >25, normal serum potassium, and persistent proteinuria after a max-tolerated RASi → a nonsteroidal MRA | 2A |
| 3.9.1 | In T2D + CKD with inadequate glucose control on metformin + an SGLT2 inhibitor → a long-acting GLP-1 RA | 1B |
| Recommendation no. | Content | Grade |
|---|---|---|
| 11.1a | T1DM of ≥5 years’ duration and all T2DM → assess UACR and eGFR annually | B |
| 11.1b | Confirmed CKD → monitor UACR and eGFR 1–4 times per year | B |
| 11.2 | Optimize glucose management to reduce CKD risk or slow progression | A |
| 11.4a | UACR ≥30 mg/g and/or eGFR <60 → strongly recommend an ACEi or ARB | A |
| 11.5a | T2D + CKD + eGFR ≥20 → an SGLT2 inhibitor | A |
| 11.5b | T2D + CKD → a GLP-1 RA to reduce cardiovascular risk and slow kidney disease | A |
| 11.5c | eGFR ≥25 + albuminuria → a nonsteroidal MRA | A |
| 11.9 | Persistently rising albuminuria and/or a persistent fall in eGFR and/or eGFR <30 → refer to nephrology | A |
| eGFR \ ACR | A1 (<30 mg/g) | A2 (30–300 mg/g) | A3 (>300 mg/g) |
|---|---|---|---|
| G1 (≥90) | Low risk | Moderate risk | High risk |
| G2 (60–89) | Low risk | Moderate risk | High risk |
| G3a (45–59) | Moderate risk | High risk | Very high risk |
| G3b (30–44) | High risk | Very high risk | Very high risk |
| G4 (15–29) | Very high risk | Very high risk | Very high risk |
| G5 (<15) | Very high risk | Very high risk | Very high risk |
| Risk level | Monitoring frequency | Applicable group |
|---|---|---|
| Low risk | Once a year | G1-G2 + A1 |
| Moderate risk | Once a year | G3a + A1 or G1-G2 + A2 |
| High risk | Twice a year | G3b + A1 or G3a + A2 or G1-G2 + A3 |
| Very high risk | ≥3 times a year (up to 4) | G4-G5 or G3b-G4 + A2-A3 |
All people with diabetes (annual basic screening):
Normal UACR but a high suspicion of early DKD, or progressive CKD:
When the cause of CKD is unclear, or finer stratification is needed:
A World Diabetes Day call: the key to diabetes–CKD co-management is acting early. Annual UACR screening is the simplest and most efficient way to find injury early. An HbA1c at target does not mean the kidney is safe — “metabolic memory” may continue to injure the kidney after glucose has normalized. Combined testing and integrated management are what make both glucose control and kidney protection possible.
See the HPLC HbA1c line (GSH-50, GSH-60 and GSH-120), Specific Protein (Aristo, GPP-100) and point-of-care HbA1c (A1c Go) at MEDICA 2026, 16 to 19 November, Messe Düsseldorf, Hall 1 · Stand B56. GSH-120 will have its world premiere at the show. Distributors and laboratory customers are welcome to book a booth meeting, and to ask at the stand about Aristo Ur and the diabetes and kidney co-management pairing.
Focusing on In Vitro Diagnostics R&D and Manufacturing Since 1999.
Goldsite Diagnostics Inc., founded in 1999, specializes in in-vitro diagnostics devices and reagents. For more than 27 years, the company has been developing and producing IVD products, from China’s first specific protein analyzer to today’s nephelometry, HPLC HbA1c, POCT, hematology and biochemistry lines, as well as laboratory automation (TLA Lab Automation). Its market currently covers China and more than 100 countries.
Learn more: https://en.goldsite.com.cn/
This report is based on the KDIGO 2024 Clinical Practice Guideline for CKD, the ADA Standards of Care in Diabetes 2025, and related evidence.
Research date: 13 November 2026 · World Diabetes Day (14 November) feature
For medical professionals only. This is not a clinical practice recommendation.
