Skip to main content

Advertisement

Log in

Tubular PAH transport capacity in human kidney tissue and in renal cell carcinoma: correlation with various clinical and morphological parameters of the tumor

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

In vitro accumulation ofp-aminohippurate (PAH) was investigated in “intact” human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pTl PAH uptake is lowest, perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of “intact” tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Berlion M, Arvelo F, Leonce S, Bourgeois Y, Rigaudy P, Bizzari JP, Poupon MF (1993) Antitumor activity of the new vinca-alkaloid S 12363 alone or in combination with verapamil on a human multidrug resistant renal carcinoma xenograft. In Vivo 7:399–405

    PubMed  Google Scholar 

  2. Bratton AC, Marshall EK (1939) A new coupling component for sulfonamide determination. J Biol Chem 128:537–550

    Google Scholar 

  3. Bräunlich H (1981) Excretion of drugs during postnatal development. Pharmacol Ther 12:299–320

    PubMed  Google Scholar 

  4. Braunlich H, Pils W (1992) Synergistic effect of triiodothyronine and dexamethasone on renal tubular transport ofp-aminohippurate in rats of different ages. Dev Pharmacol Ther 19:50–56

    PubMed  Google Scholar 

  5. Bräunlich H, Meinig T, Grosch U (1993) Postnatal development of sex differences in renal tubular transport ofp-aminohippurate (PAH) in rats. Exp Toxicol Pathol 45:309–313

    PubMed  Google Scholar 

  6. Broxterman HJ, Pinedo HM, Kuiper CM, van der Hoeven JJ, de Lange P, Quak JJ, Scheper RJ, Keizer HG, Schuurhuis GJ, Lankelma J (1989) Immunohistochemical detection of P-glycoprotein in human tumor cells with a low degree of drug resistance. Int J Cancer 43:340–343

    PubMed  Google Scholar 

  7. Chapman AE, Goldstein LJ (1995) Multiple drug resistance: Biologic basis and clinical significance in renal-cell carcinoma. Semin Oncol 22:17–28

    Google Scholar 

  8. Efferth T, Lohrke H, Volm M (1989) Reciprocal correlation between expression of P-glycoprotein and accumulation of rhodamine 123 in human tumors. Anticancer Res 9:1633–1637

    PubMed  Google Scholar 

  9. Eliason JF, Ramuz H, Yoshikubo T, Ishikawa T, Yamamoto T, Tsuruo T (1995) Novel dithiane analogues of tiapamil with high activity to overcome multidrug resistance in vitro. Biochem Pharmacol 50:187–196

    PubMed  Google Scholar 

  10. Fisher RL, Sanuik JT, Gandolfi AJ, Brendel K (1994) Toxicity of cisplatin and mercuric chloride in human kidney cortical slices. Hum Exp Toxicol 13:517–523

    PubMed  Google Scholar 

  11. Fleck C, Kunze C, Braunlich H (1987) Relation between renal and hepatic excretion of drugs: V. Factors influencing accumulation of phenol red in kidney and liver tissue from rats of different ages. Exp Pathol 32:99–110

    PubMed  Google Scholar 

  12. Fleck C, Haubold D, Hillmann T, Möckel H, Möckel M, Bräunlich H (1993) Evaluation of methods indicating higher susceptibility of immature rats to renal ischemia. Exp Toxicol Pathol 45:155–160

    PubMed  Google Scholar 

  13. Focan C (1995) Circadian rhythms and cancer chemotherapy. Pharmacol Ther 67:1–52

    PubMed  Google Scholar 

  14. Gottesman MM, Hrycyna CA, Schoenlein PV, German UA, Pastan I (1995) Genetic analysis of the multidrug transporter. Ann Rev Genetics 29:607–649

    Google Scholar 

  15. Hermanek P, Schrott KM (1990) Evaluation of the new tumor, nodes and metastases classification of renal cell carcinoma. J Urol 144:238–242

    PubMed  Google Scholar 

  16. Klinger W, Müller D, Kleeberg U, Barth A (1983) Extrapolation von Tierversuchen auf Reaktionen beim Menschen. Pharmazie 38:621–623

    PubMed  Google Scholar 

  17. Lai T, Collins CM, Hall P, Morgan AP, Smith PJ, Stonebridge BR, Symes MO (1993) Verapamil enhances doxorubicin activity in cultured human renal carcinoma cells. Eur J Cancer 29A:378–383

    PubMed  Google Scholar 

  18. Licht T, Gottesman, MM, Pastan I (1995) Transfer of the MDR 1 (multidrug resistance) gene: Protection of hematopoietic cells from cytotoxic chemotherapy, and selection of transduced cells in vivo. Cytokin Mol Ther 1:11–20

    Google Scholar 

  19. Mickisch GH (1994a) Therapie des Nierenzellkarzinoms — Eine Aktualisierung notwendig? Akta Urol 25:77–83

    Google Scholar 

  20. Mickisch GH (1994b) Multidrug Resistance des Nierenzellkarzinoms — Von der Laborkuriosität zur klinischen Realität. Akta Urol 25:327–337

    Google Scholar 

  21. Mickisch GH, Merlino GT, Aiken PM, Gottesman MM, Pastan I (1991) New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene. J Urol 146:447–453

    PubMed  Google Scholar 

  22. Naito S, Sakamoto N, Kotoh S, Goto K, Matsumoto T, Kumazawa J (1993) Expression of P-glycoprotein and multidrug resistance in renal cell carcinoma. Eur Urol 24:156–160

    PubMed  Google Scholar 

  23. Nishiyama K, Shirahama T, Yoshimura A, Sumizawa T, Furukawa T, Ichikawa-Haraguchi M, Akiyama S, Ohi Y (1993) Expression of the multidrug transporter, P-glycoprotein, in renal and transitional cell carcinomas. Cancer 71:3611–3619

    PubMed  Google Scholar 

  24. Okada S, Hamazaki S, Ebina Y, Li JL, Midorikawa O (1987) Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation. Biochem Biophys Acta 922:28–33

    PubMed  Google Scholar 

  25. Palmer BF, Levi M (1996) Effect of aging on renal function and disease. In: Brenner BM (ed) The kidney, 5th edn. WB Saunders, Philadelphia, pp 2274–2298

    Google Scholar 

  26. Robsen CJ, Churchill BM, Anderson W (1969) The results of radical nephrectomy for renal cell carcinoma. J Urol 101:297–301

    PubMed  Google Scholar 

  27. Skinner DG, Calvin RB, Vermillion CD, Pfister RC, Leadbetter WF (1971) Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer 28:1165–1177

    PubMed  Google Scholar 

  28. Stopp M, Bräunlich H (1975) Die Akkumulation vonp-Aminohippursäure und Zyklopenthiazid in Nierenrindenschnitten verschieden alter Ratten und ihre Abhängigkeit von der Energiebereitstellung. Acta Biol Med Germ 34:89–98

    PubMed  Google Scholar 

  29. Stopp M, Bräunlich H (1980) In vitro analysis of drug-induced stimulation of renal tubularp-aminohippurate (PAH) transport in rats. Biochem Pharmacol 29:983–986

    PubMed  Google Scholar 

  30. Volm M, Pommerenke EW, Efferth T, Lohrke H, Mattern J (1991) Circumvention of multi-drug resistance in human kidney and kidney carcinoma in vitro. Cancer 67:2484–2489

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fleck, C., Göckeritz, S. & Schubert, J. Tubular PAH transport capacity in human kidney tissue and in renal cell carcinoma: correlation with various clinical and morphological parameters of the tumor. Urol. Res. 25, 167–171 (1997). https://doi.org/10.1007/BF00941977

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00941977

Key words

Navigation