Serine

Your kidneys help make serine and control how much leaves in urine. Studies have linked urinary serine patterns with kidney disease, but a standalone result cannot yet diagnose early kidney damage or show whether preventive treatment is working.

Urine amino acid profiles have established clinical uses in evaluating selected inherited metabolic disorders and problems with kidney amino acid transport. Using urinary serine by itself to assess hypertension-related kidney damage, diabetic kidney disease, or longevity remains research-stage. Laboratories may provide comparison ranges, but those are different from validated kidney-risk thresholds or treatment targets.

What Serine Does

Serine comes from food, the breakdown of existing proteins, and production inside your body. Human studies show that the kidneys release serine into the circulation and that this release falls in chronic kidney disease. That does not establish how much serine your whole body makes, or allow a urine measurement to quantify kidney production.

Cells use serine to build proteins and certain fats in cell membranes, including those surrounding nerves. Serine also supplies carbon for reactions involving folate that help make DNA building blocks. It contributes to the production of glutathione. Glutathione helps protect cells from damage caused by reactive chemicals.

Serine exists in two mirror-image forms. The L form is used to build proteins. The D form participates in nerve signaling, and the kidneys handle it differently. Studies that specifically measure D-serine address a different measurement from urinary serine without a stated distinction between the two forms.

What the Urine Number Reflects

Urinary serine depends on the amount circulating in blood, kidney filtration, and how much the kidney tubules reclaim. The tubules normally return filtered amino acids to the bloodstream. Kidney production and use of serine can also influence this system, but a urine result cannot separate these processes. It is not a direct measure of serine production or a reliable substitute for a blood serine measurement.

This test measures serine in urine using LC-MS and reports mg/g. Urine amino acid results are often expressed per gram of creatinine, but the unit mg/g alone does not identify the denominator. Check the full unit on your laboratory report. If it is creatinine-normalized, the ratio reduces the effect of urine dilution; it does not measure the total amount lost over a day.

LC-MS combines liquid chromatography with mass spectrometry. It separates compounds and detects characteristic signals from charged molecules. The method name alone does not establish whether L-serine and D-serine were measured separately. That requires a validated separation step, so this result should not be interpreted as a D-serine result unless the laboratory explicitly identifies it that way.

Kidney Disease Associated With High Blood Pressure

A study compared urine from 62 people with clinically defined hypertensive nephrosclerosis and 33 healthy controls. Hypertensive nephrosclerosis involves kidney scarring associated with longstanding high blood pressure. Using LC-MS and creatinine normalization, researchers found a different distribution of urinary serine values in the kidney disease group. Its median was about 55% lower, although the comparison of medians alone was not statistically conclusive.

A second cohort found a median about 70% lower in the kidney disease group. A separate biopsy analysis found altered activity of genes involved in serine metabolism. These findings support a biological association, but the participants already had kidney disease. The study did not establish that a low result predicts future damage, identifies its cause, or improves decisions beyond established kidney tests. The reported percentages are group comparisons, not targets for your result. The original study also describes the assay and population differences that limit direct comparison with a commercial report.

Diabetic Kidney Disease and D-Serine

A study of 388 participants examined D-serine in paired plasma and urine samples using specialized two-dimensional chromatography. It calculated fractional excretion. This is the proportion of filtered D-serine that ends up in urine. Calculating it requires blood and urine measurements, including creatinine; a standalone urinary serine concentration cannot provide it.

In the study's validation group, a model combining the D-serine profile with age, sex, eGFR, and urine albumin identified about 91% of diabetic nephropathy cases and correctly classified about 79% of participants without that diagnosis. The comparison included selected biopsy-confirmed kidney diseases and participants without kidney disease. These results do not establish screening performance in the general population or in people with prediabetes, and they do not validate this urine LC-MS test.

Research in living kidney donors and transplant recipients also found that combining D-serine clearance with creatinine clearance improved agreement with a reference measurement of filtration. That approach used paired blood measurements and timed urine collections. It was a different procedure from measuring serine in an individual urine sample.

Other Urinary Findings

In a study of 133 children with Mycoplasma pneumonia, an untargeted LC-MS analysis reported a higher signal identified as L-serine in the 48 severe cases than in milder cases. The study measured relative signals across many compounds and did not establish a concentration threshold for this test. It suggests that acute illness can affect urinary serine, but the mechanism and relevance to an otherwise well adult remain uncertain.

A cross-sectional study of 234 adults found that urinary serine was part of a six-compound pattern distinguishing cardiovascular risk groups among adults aged 30 to 50. The work used an initial magnetic-resonance analysis followed by targeted mass spectrometry. Serine alone did not significantly correlate with the calculated lifetime risk score. The study did not follow participants to determine whether their urine results predicted future heart attacks.

What Blood Studies Add

The main long-term studies measured serine in plasma or serum. Those measurements describe circulating serine, and their findings cannot be transferred to a urine result.

The mortality findings differ across populations, and the studies do not establish why. Differences in health, measurement methods, and other factors may contribute. These associations provide no validated direction to aim for in urine and do not show that changing serine levels improves survival.

Low circulating serine has also been linked to macular telangiectasia type 2. This rare retinal disease affects central vision. Human observations, mouse experiments, and experiments in human retinal tissue grown in the laboratory connect altered serine metabolism with abnormal fats that can damage retinal and peripheral nerve cells. These findings do not establish urinary serine as a test for eye disease, nerve damage, or serine deficiency.

When Results Can Be Misleading

• Bacterial growth: in experiments growing bacteria in human urine outside the body, E. coli, Klebsiella pneumoniae, and Proteus mirabilis consumed 90% to 98% of the available serine. This supports concern about infection and sample contamination, but it does not mean every urinary infection lowers serine by that amount or that a low result diagnoses infection.
• Storage and transport: prolonged storage at room temperature can reduce urinary serine. Stability depends on the assay and handling conditions. Refrigeration does not automatically invalidate a sample, and the claim that a second freeze-thaw cycle necessarily destroys serine is unsupported.
• Urine dilution and creatinine: if the result is creatinine-normalized, unusually dilute urine or differences in creatinine production can affect the ratio. Muscle mass influences creatinine production, so normalization does not remove every source of variation.
• Illness and metabolic changes: acute illness and changes in metabolic state can alter amino acid excretion. A result obtained during illness may not represent your usual state.
• LC-MS interference: other compounds in urine can suppress or enhance the measured signal, and inadequate separation can cause interference. Sample preparation, calibration, and whether the method separates L-serine from D-serine also matter. Results from different assays should not be treated as interchangeable.

What a Trend Can Establish

Repeated measurements can document variation in urinary serine. There is no validated size or direction of change that proves kidney recovery, worsening kidney disease, or a successful longevity intervention. Using the same laboratory and comparable collection conditions improves consistency, but it does not establish clinical meaning.

Established kidney assessment uses filtration estimates and urine albumin together, as described in the KDIGO kidney disease guideline. Urinary serine remains an exploratory addition to that assessment.