In a previous article, we explored the possibilities for dried urine testing as an alternative to standard liquid urine testing, with a particular focus on patient convenience, sample stability, and accuracy. Here, we take a closer look at kidney function testing, specifically examining the key biomarkers that can be measured, the patient populations that benefit most, and how dried urine sampling could transform routine primary care screening through at-home sampling for patient-centric kidney health and chronic disease management.

Monitoring kidney health through blood and urine biomarkers

Kidney biomarkers can provide important clues about the severity and nature of kidney injury and disease to help doctors distinguish between different conditions to determine the best treatment plan. Reliable biomarkers also allow monitoring of disease progression, enable risk stratification to identify patients most likely to develop advanced disease, and can indicate an upcoming need for interventions such as dialysis or transplantation before kidney function deteriorates significantly.

The major biomarker for kidney disease is serum creatinine (SCr), which is measured in blood samples. Creatinine is a breakdown product of creatine and phosphocreatine, both of which are important energy sources in the kidney. This molecule is freely filtered by the glomerulus, which is the kidney’s specialized filtering unit. SCr levels are used to estimate glomerular filtration rate (eGFR) as an indicator of how well the kidneys can filter waste products from the blood, including creatinine and blood urea nitrogen (BUN). Elevated creatinine and/or BUN levels are used as indicators of reduced kidney function. According to the Mayo Clinic, the typical normal range for SCr is approximately 0.74-1.35 mg/dL for men and 0.59-1.04 mg/dL for women, although these values can vary between testing laboratories, as well as individual factors including age, sex, muscle mass (which may be related to age or fitness level), use of creatine supplements, hydration level, medications, and others.

Importantly, while blood tests remain the gold standard for assessing overall kidney function, urine tests can detect protein leakage and other early signs of kidney damage that are not detected in blood tests. One of the most widely used protein-based markers in urine is the albumin-to-creatinine ratio (uACR), which measures protein leakage into urine as an indicator of kidney damage. This ratio is used rather than measuring albumin alone because urine volume and concentration can vary dramatically throughout the day. By comparing albumin levels to creatinine, which is filtered consistently by the kidneys regardless of urine dilution, the uACR provides a standardized measure that accounts for natural variations in urine concentration. Detection of microalbuminuria, which is small amounts of albumin in the urine, by uACR is an important early indicator of kidney disease, especially in diabetes patients. According to the National Kidney Foundation (US), the cut-off for a normal uACR is less than 30 mg/g. Anything above 30 mg/g may indicate kidney disease, even if the estimated glomerular filtration (eGFR) number is above 60.

Alternative and emerging kidney biomarkers

Alternative or emerging blood and urine biomarkers include, but are not limited to, cystatin C, KIM-1, NGAL, and IGFBP7 x TIMP-2. Cystatin C, which is most often but not exclusively measured in the blood, is a small protein that regulates cysteine proteinase activity and is produced by all human nucleated cells. Like creatinine, cystatin C is filtered freely by the glomerulus. It has been explored as a more accurate measure of eGFR than SCr because it may correlate better with actual GFR in certain situations and is less influenced by non-kidney factors such as muscle mass, age, and sex. Additionally, cystatin C responds more rapidly to changes in kidney function due to its shorter half-life (1, 2).

KIM-1, a transmembrane protein, is an emerging urine biomarker that appears shortly after kidney injury and can help to predict both the risk of developing acute kidney injury (AKI) and disease severity, with elevated levels associated with worse outcomes including the need for dialysis and increased risk of death (3, 4).

NGAL is widely expressed and functions as a growth and differentiation factor in multiple cell types. Elevated NGAL levels are reported to be detectable in urine and plasma as early as 3 hours after ischemic or nephrotoxic kidney injury and persist for up to 5 days depending on the injury severity. NGAL has gained attention as an early predictive biomarker for AKI, and it may help to differentiate between different types of kidney damage (5, 6).

IGFBP7 and TIMP-2 are proteins that induce cell cycle arrest in renal tubular cells following kidney injury. When measured together as a urinary biomarker combination, they can predict the risk of developing moderate to severe AKI within 12 hours and they were FDA-approved in 2014 as a commercial test called NephroCheck for use in critically ill patients (7, 8).

From liquid urine collection and storage to dried urine sampling

In brief, traditional liquid urine testing involves collecting fresh urine in cups that are treated as biohazardous material requiring refrigeration and costly cold chain transport to testing laboratories. This sampling approach creates significant challenges including timing constraints, collection difficulties, and storage risks, particularly when repeat sampling is needed or when patients collect samples at home.

Dried urine sampling offers an attractive alternative that addresses the aforementioned drawbacks. This method requires patients to saturate a filter card with urine, which is then dried and sent directly to a testing lab. Dried urine samples are highly stable and do not support microbial growth, eliminating biohazard concerns and removing the need for refrigeration, cold chain logistics, and the general hassle of storing fresh urine. Recent studies continue to validate dried urine sampling for clinical applications. Earlier this year, researchers in the Czech Republic demonstrated that dried urine spot sampling is a useful microsampling technique for creatinine and neopterin (a biomarker of inflammation). Using just 10 μL of urine from 12 healthy volunteers, 12 cancer patients, and 12 SARS-CoV-2 infected patients, they achieved results that were comparable to testing with 100 μL of fresh liquid urine. They reported that dried urine samples remained stable for up to 5 days at 40°C and 4 months at room temperature, allowing cost-effective transport via standard mail (9).

Primary care & preventive applications

The possibility to perform kidney function testing on dried urine samples has many attractive benefits for healthcare systems and importantly also for patients. These include cost-effectiveness through early detection programs; by preventing the incidence of costly late-stage kidney disease through affordable screening, the overall burden on healthcare systems can be reduced, by detecting and addressing kidney problems before dialysis or transplantation becomes necessary. 

The simplicity of dried urine sampling should make it feasible to integrate kidney function screening into annual health checkups, workplace wellness programs, and preventive health visits, making kidney testing as routine as cholesterol or blood pressure checks. The possibility to post dried urine samples by regular mail also increases access to better kidney healthcare for rural populations and for those who cannot travel for regular healthcare checks.

Of note, uACR testing is often performed as a complementary analysis alongside other routine tests for several chronic conditions including diabetes and cardiovascular conditions, for which at-home monitoring solutions already exist. A complete home testing solution could eliminate the need for hospital visits that might otherwise be necessary just to collect a urine sample. For example, diabetes patients already have access to home HbA1c testing and continuous glucose monitoring (CGM) systems; adding dried urine uACR testing would enable comprehensive at-home diabetes management and regular monitoring to detect diabetic nephropathy early and track disease progression. Similarly, hypertension patients routinely monitor blood pressure at home, and incorporating kidney function testing through dried urine sampling would provide a more complete picture of cardiovascular-kidney health without requiring clinic visits, while enabling ongoing monitoring of disease progression and treatment optimization.

Patient-centric chronic kidney disease management

Beyond the chronic disease patient benefits outlined above, dried urine testing could improve healthcare for elderly patients who require regular screening for age-related kidney decline as well as post-transplant patients who require continuous monitoring for transplant rejection. Through at-home monitoring, patients can become more actively involved in their healthcare management, possibly leading to better compliance and earlier detection of disease progression. Integration with digital health platforms and telemedicine applications could further enhance patient-centric care, allowing real-time monitoring and immediate intervention when biomarker changes indicate deteriorating kidney function.

Something new is coming!

As dried urine sampling continues to gain clinical validation, we anticipate broader adoption in primary care and chronic kidney disease management settings. We look forward to sharing our upcoming development in dried urine sampling that will make kidney health monitoring more accessible and patient-friendly.

References

1. Delanaye P, Cavalier E, Morel J, et al. Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine. BMC Nephrol. 2014 Jan 13;15:9.
2. Lima RM, Navarro LH, Nakamura G, et al. Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery. Clinics (Sao Paulo). 2014 Jun;69(6):378-83.
3. Humphreys BD. Mechanisms of Renal Fibrosis. Annu Rev Physiol. 2018 Feb 10;80:309-326.
4. Steubl D, Block M, Herbst V, et al. Urinary uromodulin independently predicts end-stage renal disease and rapid kidney function decline in a cohort of chronic kidney disease patients. Medicine (Baltimore). 2019 May;98(21):e15808.
5. Schmidt IM, Srivastava A, Sabbisetti V, et al. Chronic Kidney Disease Biomarkers Consortium and the CRIC Study Investigators. Plasma Kidney Injury Molecule 1 in CKD: Findings From the Boston Kidney Biopsy Cohort and CRIC Studies. Am J Kidney Dis. 2022 Feb;79(2):231-243.e1.
6. Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet. 1999 Jul 31;354(9176):359-64.
7. Endre ZH, Pickering JW. Acute kidney injury: cell cycle arrest biomarkers win race for AKI diagnosis. Nat Rev Nephrol. 2014 Dec;10(12):683-5.
8. Nalesso F, Cattarin L, Gobbi L, et al. Evaluating Nephrocheck® as a Predictive Tool for Acute Kidney Injury. Int J Nephrol Renovasc Dis. 2020 Apr 24;13:85-96.
9. Suwanvecho C, Vyleťalová L, Přívratská N, et al. Dried urine spot as a stable, green, and practical microsampling tool in clinical practice for quantification of neopterin and creatinine. Green Chem. 2025.