Urine Protein Selectivity Index Calculator
Urine Protein Selectivity Index Calculator
Calculate the IgG-to-transferrin clearance ratio that classifies proteinuria as selective or non-selective — a 1960s test, largely displaced by biopsy and genetic testing, with a recent and narrow revival.
Urine Protein Selectivity Index
IgG clearance ÷ transferrin clearanceUrine IgG 12 mg/L, serum IgG 8 g/L, urine transferrin 45 mg/L, serum transferrin 1.8 g/L
Formula
= (urine IgG × serum transferrin) ÷ (serum IgG × urine transferrin)
≤ 0.10 highly selective · 0.11–0.20 moderately selective · > 0.20 non-selective
- why a clearance ratio
- each protein’s clearance is its urine concentration divided by its serum concentration, and the urine volume term is identical for both, so it cancels. That is what lets the index be calculated from a spot sample with no timed collection
- units
- the four concentrations must be paired consistently — both urine proteins in the same unit, both serum proteins in the same unit — and the index is then dimensionless. This page takes urine in mg/L and serum in g/L
- IgG, 150 kDa
- the large molecule. It should be almost entirely retained by an intact filter, so its appearance in urine signals larger defects
- transferrin, 76 kDa
- the intermediate molecule, and roughly the size of albumin at 67 kDa. It leaks in any glomerular proteinuria, which makes it the reference denominator
- 0.20
- the conventional cutoff between selective and non-selective, with 0.10 dividing highly from moderately selective. The distributions across histological diagnoses overlap, so these are probabilistic boundaries and not diagnostic ones
Worked example
Urine IgG 12 mg/L, serum IgG 8 g/L, urine transferrin 45 mg/L, serum transferrin 1.8 g/L
IgG clearance ∝ 12 ÷ 8 = 1.5
Transferrin clearance ∝ 45 ÷ 1.8 = 25
1.5 ÷ 25 = 0.06
0.10 or below → highly selective proteinuria
Historically associated with minimal change disease and steroid responsiveness — supportive, not diagnostic
What the index was used for, and what replaced it
| Question | Then (1960s–1980s) | Now |
|---|---|---|
| Which child with nephrotic syndrome will respond to steroids? | Selectivity index, with a selective result favouring minimal change disease | An empirical steroid trial. Most childhood nephrotic syndrome is steroid-sensitive minimal change disease, so steroids are started without a biopsy and the response is the test |
| What is the histological diagnosis? | Selectivity index as a non-invasive proxy | Renal biopsy, with immunofluorescence, electron microscopy and PLA2R serology for membranous nephropathy |
| Why is this child steroid-resistant? | Non-selective proteinuria implying a structural lesion | Genetic testing — NPHS1, NPHS2, WT1, INF2 and others — which changes management because monogenic disease does not respond to immunosuppression |
| Can we avoid a biopsy in this pregnant patient? | Not an established role | The one setting where selectivity has been argued to retain value, since biopsy carries added risk in pregnancy |
Why the index is noisy
| Problem | Effect on the index |
|---|---|
| Serum IgG falls in nephrotic syndrome because it is lost in the urine | A lower denominator term for IgG clearance raises the index, independently of the filter |
| Serum transferrin falls in nephrotic syndrome and rises in iron deficiency | Moves the index in either direction for reasons unrelated to glomerular permeability |
| Tubular reabsorption of filtered protein differs between the two proteins | The urine concentrations are not pure filtration signals |
| Urine transferrin is not a routine assay in many laboratories | Long turnaround, method differences between laboratories, and thresholds that were derived on older assays |
| Substitute numerators (alpha-2-macroglobulin, IgM) have been proposed as better discriminators | Published cutoffs do not transfer between numerators |
A historical test, honestly described
Proteinuria selectivity asks a physical question about the glomerular filter: is it leaking only intermediate-sized proteins, or has it developed defects large enough to pass immunoglobulin G as well? The index operationalises that as the ratio of IgG clearance to transferrin clearance, which reduces to urine IgG times serum transferrin over serum IgG times urine transferrin. Because both clearances share the same urine volume term, it cancels, and the index can be computed from a single untimed sample. A value of 0.10 or below is called highly selective, 0.11 to 0.20 moderately selective, and above 0.20 non-selective.
The clinical claim, made by Cameron and Blandford in 1966, was that selective proteinuria predicted steroid responsiveness, because selectivity tracked with minimal change disease while non-selective proteinuria tracked with proliferative and sclerosing lesions. That claim was broadly reproducible at the level of groups. It was never reliable at the level of a patient, because the distributions for minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy overlap substantially around the cutoff.
It should be said plainly that this test is not part of current practice. Childhood nephrotic syndrome is now managed with an empirical course of corticosteroids, because most of it is steroid-sensitive minimal change disease and the response to treatment is a better and faster answer than any index; where steroids fail, biopsy and genetic testing — NPHS1, NPHS2, WT1 and others — give information the selectivity index cannot, and monogenic disease changes management by removing the case for immunosuppression. In adults the biopsy is the diagnostic test, with PLA2R serology for membranous nephropathy. KDIGO guidance contains almost nothing on proteinuria selectivity, and it is not widely measured anywhere.
There is a narrow revival worth knowing about. The index has been reported to predict response to rituximab in adults with minimal change disease and focal segmental glomerulosclerosis, to predict remission in IgA nephropathy, and it has been argued for in pregnancy, where biopsy carries added risk. Substituting alpha-2-macroglobulin or IgM for IgG as the large-molecule numerator discriminates better in some series, but published cutoffs do not transfer between numerators. Treat a result from this calculator as one descriptive observation about a filter, useful for teaching and for research, and not as a guide to whether to give a patient steroids. This calculator supports a clinician’s assessment and does not replace it.
Frequently asked questions
What selectivity index counts as selective proteinuria?
An index of 0.20 or below is conventionally called selective, subdivided into highly selective at 0.10 or below and moderately selective from 0.11 to 0.20. Above 0.20 is non-selective. The boundaries separate groups better than they separate individual patients.
How is the protein selectivity index calculated?
It is IgG clearance divided by transferrin clearance, which works out as (urine IgG x serum transferrin) divided by (serum IgG x urine transferrin). The urine volume term cancels between the two clearances, so no timed collection is needed — only paired urine and serum concentrations.
Is the selectivity index still used clinically?
Rarely. Childhood nephrotic syndrome is treated with an empirical steroid course, and where that fails, biopsy and genetic testing give answers the index cannot. KDIGO guidance says almost nothing about proteinuria selectivity and it is not routinely measured in most countries. Recent interest is confined to predicting rituximab response and to pregnancy, where biopsy is riskier.
Does a selective index mean minimal change disease?
It favours it but does not establish it. Selectivity was historically associated with minimal change disease and with steroid responsiveness, but the distributions for minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy overlap around the cutoff. The diagnosis in an adult is made on biopsy.
Why do serum protein levels distort the index?
Because they are the denominators of the two clearances. Serum IgG falls in nephrotic syndrome as it is lost in urine, which raises the index without any change in the filter, and serum transferrin falls in nephrotic syndrome but rises in iron deficiency. Differential tubular reabsorption of the two filtered proteins adds further noise.
Related calculators
References
- Cameron JS, Blandford G. The simple assessment of selectivity in heavy proteinuria. Lancet. 1966;2(7460):242–247.
- Bazzi C, Petrini C, Rizza V, et al. Characterization of proteinuria in primary glomerulonephritides: SDS-PAGE patterns and selectivity index. Nephron. 1997;77(1):1–9.
- Ishikura K, Hamada R, Sakai T, et al. Proteinuria selectivity index predicts response to rituximab in adults with minimal change disease and focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2022;37(4):789–795.
- Rovin BH, Adler SG, Barratt J, et al. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1–S276.
Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.