Measurement of TmP/GFR
Introduction
The ratio of tubular maximum reabsorption of phosphate (TmP) to glomerular filtration rate (GFR) is used to evaluate renal phosphate transport. Renal tubular phosphate reabsorption is mainly controlled by dietary phosphate, and hormones, e.g. PTH, FGF23, and insulin-like growth factor 1.
TmP/GFR
This essentially corresponds to the theoretical lower limit of serum phosphate (Pi) below which all filtered phosphate would be reabsorbed. Calculation of TmP/GFR assumes that serum Pi concentration is equal to its concentration in the glomerular filtrate, and that creatinine clearance is a close approximation to GFR.
Fractional Tubular Reabsorption of Phosphate (TRP)
The fraction of Pi in the glomerular filtrate that is reabsorbed in the renal tubules. If TRP is low in hypophosphatemia this usually points to a renal tubule defect.
Indications
Assessment of renal phosphate handling may be indicated in a variety of pathological conditions associated with hypophosphatemia. Impaired renal phosphate reabsorption may be due to elevated levels of phosphaturic hormones, i.e. FGF23 and PTH, or due to primary or acquired renal tubular phosphate wasting. It is also recommended to monitor the response to burosumab in X-linked hypophosphatemia [1].
Procedure
TmP/GFR can be calculated, using a second morning spot urine and serum sample taken at the same time point [2-5]. Similarly, serum Pi, TmP/GFR are highest in early childhood and constantly decrease with age, reaching adult values after completion of pubertal growth. A commonly used formula to calculate TmP/GFR, which is applicable in both the fasting and non-fasting child, age-dependent reference values and an online calculator, are given below. It is important to use the same units for phosphate and creatinine values in the urine and serum samples, respectively.
Although calculation of the percentage of tubular reabsorption of phosphate (TRP) can easily be done, this method is not reliable in order to exclude renal phosphate wasting. Indeed, TRP may be falsely normal, despite renal phosphate wasting, as, in contrast to TmP/GFR, it does not correct for the amount of filtered phosphate. Thus, in cases of low serum Pi levels, the remaining phosphate reabsorption capacity may still be enough to maintain a normal TRP, whereas TmP/GFR, which corrects for GFR and thus for the amount of filtered phosphate, is already clearly reduced.
CALCULATOR
TRP and TmP/GFR are calculated by entering the fasting urine and plasma concentrations, in the same concentration units
Reference values:
TRP: 85 – 95 % [6]
TmP/GFR:
| Age | Range (mmol/L) | Range (mg/dL) | n | Reference |
|---|---|---|---|---|
| 0 – 5 m |
1.02 – 2.00 |
3.16 – 6.19 |
41 |
[3, 4] |
| 6 – 12 m |
1.13 – 1.88 |
3.50 – 5.82 |
10 |
[3, 4] |
| 1 – 5 y |
1.05 – 1.78 |
3.25 – 5.51 |
54 |
[3, 4] |
| 6 – 12 y |
0.97 – 1.64 |
3.00 – 5.08 |
62 |
[3, 4] |
| 13 – 15 y |
0.91 – 1.68 |
2.82 – 5.20 |
27 |
[3, 4] |
| ≥ 16 y and adults |
0.84 – 1.23 |
2.60 – 3.80 |
16 |
[7] |
m: months; y: years
Conversion factor for phosphate: mmol/L x 3.097 = mg/dL.
NOTE. SI Units x Conversion Factor = Metric Units
FORMULA
TRP = 1- ((Up/Pp) x (Pcr/Ucr));
TmP/GFR = Pp – (Up/ Ucr) x Pcr [2, 5]
P: Plasma; p: phosphate; U: urine; cr: creatinine
Interpretation
Low levels suggest renal phosphate wasting.
© for this presentation:
Prof. Dr. Dieter Haffner, Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany, and
Dr. Dirk Schnabel, Center for Chronic Sick Children, Pediatric Endocrinology, Charité, University Medicine Berlin, Berlin, Germany, 2021.
References
1. Haffner D, Emma F, Eastwood DM, Duplan MB, Bacchetta J, Schnabel D, Wicart P, Bockenhauer D, Santos F, Levtchenko E, Harvengt P, Kirchhoff M, Di Rocco F, Chaussain C, Brandi ML, Savendahl L, Briot K, Kamenicky P, Rejnmark L, & Linglart A (2019) Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol 15: 435-455.
2. Brodehl J, Krause A, & Hoyer PF (1988) Assessment of maximal tubular phosphate reabsorption: Comparison of direct measurement with the nomogram of bijvoet. Pediatr Nephrol 2: 183-189.
3. Brodehl J (1994) Assessment and interpretation of the tubular threshold for phosphate in infants and children. Pediatr Nephrol 8: 645.
4. Brodehl J, Gellissen K, & Weber HP (1982) Postnatal development of tubular phosphate reabsorption. Clin Nephrol 17: 163-171.
5. Alon U, & Hellerstein S (1994) Assessment and interpretation of the tubular threshold for phosphate in infants and children. Pediatr Nephrol 8: 250-251.
6. Kruse K, Kracht U, & Göpfert G (1982) Renal threshold phosphate concentration (TmPO4/GFR). Arch Dis Child 57: 217-223.
7. Stark H, Eisenstein B, Tieder M, Rachmel A, & Alpert G (1986) Direct measurement of TP/GFR: A simple and reliable parameter of renal phosphate handling. Nephron 44: 125-128.