Investigation of tubular reabsorption of phosphates in patients with chronic kidney disease

Česká verzia

Authors: Miroslava Horáčková ¹; Otto Schück ^1,2; Ivo Sotorník ²; Janka Franková ²; Milena Štollová ²; Irena Látová ²; Hana Malinská ²; Jana Urbanová ²
Authors place of work: Interní klinika 2. LF UK a FN Motol, Praha, přednosta prof. MUDr. Milan Kvapil CSc., MBA ¹; Klinika nefrologie IKEM Praha, přednosta prof. MUDr. Ondřej Viklický, CSc. ²
Published in the journal: Vnitř Lék 2015; 61(12): 1034-1038
Category: Original Contributions

Summary

Introduction:
Moderate to medium decrease in glomerular filtration (GFR) in individuals with chronic kidney disease (CKD) does not need to be associated with hyperphosphatemia due to an adaptive decrease in tubular reabsorption of phosphates (TR_Pi) in residual nephrons. The clinical assessment of this function is performed based on the measurement of fractional phosphate excretion (FE_Pi), which is a quantity specifying the proportion of the filtered amount of phosphates which is excreted in the urine. This quantity may provide useful information about the involvement of kidneys in phosphate homeostasis of the internal environment. This study focuses on the comparison of a kr(FE_Pi) value examined based on a ratio of a phosphate clearance (C_Pi) and a creatinine clearance (C_Kr) marked kr(FE_Pi), and a value calculated based on a ratio of C_Pi and an exactly measured GFR as an inulin clearance (C_in), marked as in(FE_Pi).

The goal of comparing the two methods of examining FE_Pi was to establish to what extent it is possible to evaluate the degree of inhibition of tubular phosphate transport in residual nephrons based on a simple examination of kr(FE_Pi) .

Methodology:
The examination of in(FE_Pi) and kr(FE_Pi) was carried out for 53 patients with CKD. The values of the examined quantities were as follows: S_Kr 199 ± 45 µmol/l; S_Pi 1.41 ± 0.29 mmol/l; C_Kr 0,95 ± 0.36 ml/s/1.73 m²; C_in 0.71 ± 0.25 ml/s/1.73 m². For the purpose of comparison a cohort of 18 healthy volunteers was examined.

Results:
For individuals with CKD an average value of kr(FE_Pi) equalled 29.1 ± 10.9 % and in(FE_Pi) 52.4 ± 4.3 %. The values of in(FE_Pi) were higher than kr(FE_Pi) (p < 0.001) for all patients, although an average C_Pi value for patients with CKD did not significantly differ from the control cohort (0.22 vs 0.21 ml/s/1.73 m²). The values of in(FE_Pi) increased proportionally to S_Kr values and at higher values S_Kr (> 300 µmol/l) they gradually approached 100 % (indicating the complete inhibition of tubular reabsorption of phosphates in residual nephrons). The values of in(FE_Pi) were higher in all patients with CKD than kr(FE_Pi) as expected, likely because the value C_Kr decreases at a slower rate than C_in (GFR) in individuals with CKD as a result of increased tubular secretion of creatinine in residual nephrons.

Conclusion:
The results of this study support the assumption that, provided the values of kr(FE_Pi) which are easily measurable in clinical practice have reached 50-60 %, almost complete inhibition of tubular reabsorption of phosphates in residual nephrons must be assumed and no favourable effect of phosphatonins on renal phosphate excretion can be expected. When looking for new possibilities of inhibition of tubular phosphate reabsorption, potential adverse effects of phosphatonins on organs must be considered.

Key words:
hyperphosphatemia – chronic renal disease – tubular phosphate reabsorption

Zdroje

1. Slatopolsky E, Rondon AM, Elkan I et al. Control of phosphate excretion in uremic man. J Clin Invest 1968; 47(8): 1865–1874.

2. Prié D, Beck L, Urena P et al. Recent findings in phosphate homeostasis. Curr Opin Nephrol Hypertens 2005; 14(4): 318–324.

3. Prié D, Beck L, Urena P et al. Recent findings in phosphate homeostasis. Curr Opin Nephrol Hypertens 2005; 13(6): 675–681.

4. Sotorník I, Kutílek Š et al. Kostní minerály a skelet při chronickém onemocnění ledvin. Galén: Praha 2011. ISBN 9788072627691.

5. Jabor A et al. Vnitřní prostředí. Grada: Praha 2008. ISBN 978–80–247–1221–5.

6. Llach F, Massry SG. On the mechanism of secondary hyperparathyroidism in moderate renal insufficiency. J Clin Endocrinol Metab 1985; 61(4): 601–606.

7. Llach F, Velasquez Forero F. Secondary hyperparathyroidism in chronic renal failure: pathogenic and clinical aspects. Am J Kidney Dis 2001; 38(5 Suppl 5): S20-S33.

8. Sulková S. Renální osteopatie. Maxdorf: Praha 2007. ISBN 978–80–7345–119–6.

9. Schück O. Examination of kidney function. Martinus Nijhoff: Boston-Hague-Dodrecht-Lancaster: 1984.

10. Teplan V et al. Metabolismus a ledviny. Grada: Praha 2000. ISBN 80–7169–731–1.

11. Schiavi SG, Moe OW. Phosphatonins: a new phase of phosphate regulating proteins. Curr Opin Nephrol Hypertens 2002; 11(4):423–430.

12. Saito H, Kusano K, Kinosaki M et al. Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate cotransport activity and 1 alfa, 25-dihydroxyvitamin D3 production. J Biol Chem 2003; 278: 2206–2211.

13. Imanishi A, Inaba M, Nakatsuka K et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 2004; 65(5):1943–1946.

14. Lasson T, Nisbeth U, Ljunggren O et al. Circulating concentration of FG-23 increases as renal function declines in patients with chronic kidney disease but does not change in response to variation of phosphate intake in healthy volunteers. Kidney Int 2003; 64(6): 2272–2279.

15. Shigematsu TKJ, Yamashita T, Fukumoto S et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis 2004; 44(2): 250–256.

16. Yamazaki Y, Okazaki R, Shibata M et al. Increased circulatory level of biologically active full-length FGF-23 in hyperphosphatemia rickets/osteomalacia. J Clin Endocrinol Metab 2002; 87(11): 4957–4960.

17. Quarles LD. FGF-23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab 2003; 285(1):E1-E9.

18. Gutierrez O, Isakova T, Rhee E et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16(17): 2205–2215.

19. Schück O, Kašlíková J, Skibová J. Močové vylučování fosforu a reziduální funkce ledvin u jedinců v pravidelném dialyzačním léčení. Klin Biochem Metab 1998; 6(1): 3–5.

20. Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold of phosphate concentration. Lancet 1975; 2(7929): 309–310.

21. Shemesh O, Goldbertz H, Kriss J et al. Limitations of creatinine clearance as a filtration marker of glomerulopathic patients. Kidney Int 1985; 28(5): 830–838.

22. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3(1): 1–150. Dostupné z WWW: http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf.

23. White RP, Samson FE. Determination of inulin in plasma and urine by use of anthrone. J Lab Clin Med 1954; 43(3):475–478.

24. Goldberg H, Fernandez A. Simplified Method for the estimation of inorganic phosphorus in body fluids. Clin Chem 1966; 12(12): 871–882.

25. Bland JM, Altman DG. Statistical methods assessing agreement between methods of clinical measurement. Lancet 1986; 1(8476): 307–310.