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Proximal renal tubular dysfunction in primary distal renal tubular acidosis

Abstract

Low-molecular-weight (LMW) proteinuria has been described in patients with primary distal renal tubular acidosis (dRTA). However, other proximal renal tubular dysfunctions have rarely been reported. In this report we describe reversible and multiple proximal renal tubular cell dysfunctions in a patient with dRTA. A 4-year-old girl was admitted to our hospital for investigation of short stature and proteinuria. Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria. The patient was diagnosed as having dRTA with multiple proximal renal tubular dysfunctions. All proximal renal tubular dysfunction subsided 1.5 years after starting alkali therapy. The precise pathogenic mechanisms underlying the development of multiple proximal renal tubular dysfunctions in dRTA remained unclear. However, proximal renal tubular endosomal dysfunction resulting from a profound intracellular acidosis caused by vacuolar H+-ATPase dysfunction or hypokalemic nephropathy might contribute to the development of proximal renal tubular dysfunctions in patients with dRTA.

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References

  1. 1.

    Rodríguez-Soriano J (2002) Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13:2160–2170

    PubMed  Google Scholar 

  2. 2.

    Karet FE (2002) Inherited distal renal tubular acidosis. J Am Soc Nephrol 13:2178–2184

    CAS  PubMed  Google Scholar 

  3. 3.

    Stover EH, Borthwick KJ, Bavalia C, Eady N, Fritz DM, Rungroj N, Giersch ABS, Morton CC, Axon PR, Akil I, Al-Sabban EA, Baguley DM, Bianca S, Bakkaloglu A, Bircan Z, Chauveau D, Clermont MJ, Guala A, Hulton SA, Kroes H, Li Volti G, Mir S, Mocan H, Nayir A, Ozen S, Rodriguez Soriano J, Sanjad SA, Tasic V, Taylor CM, Topaloglu R, Smith AN, Karet FE (2002) Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J Med Genet 39:796–803

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Igarashi T, Kawato H, Kamoshita S (1990) Reversible low-molecular-weight proteinuria in patients with distal renal tubular acidosis. Pediatr Nephrol 4:593–596

    CAS  PubMed  Google Scholar 

  5. 5.

    Onigata K, Yagi H, Takeuchi K, Yutani S, Nagashima K (1994) A case of distal renal tubular acidosis with short stature and arthralgia (in Japanese). Shonika Rinsho 47:517–521

    Google Scholar 

  6. 6.

    Kikuta Y, Kasetani H, Ito T (2003) A boy with distal renal tubular acidosis (in Japanese). Shonika Rinsho 56:1539–1545

    Google Scholar 

  7. 7.

    Yamamoto K, Cox JPDT, Friedrich T, Christie PT, Bald M, Houtman PN, Lapsley MJ, Patzer L, Tsimaratos M, Hoff WGV, Yamaoka K, Jentsch TJ Thakker RV (2000) Characterization of renal chloride channel (CLCN5) mutations in Dent’s disease. J Am Soc Nephrol 11:1460–1468

    Google Scholar 

  8. 8.

    Norden AGW, Lapsley M, Igarashi T, Kelleher CL, Lee PJ, Matsuyama T, Scheinman SJ, Shiraga H, Sundin DP, Thakker RV, Unwin RJ, Verroust P, Moestrup SK (2002) Urinary megalin deficiency implicates abnormal tubular endocytic function in Fanconi syndrome. J Am Soc Nephrol 13:125–133

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Marshansky V, Ausiello DA, Brown D (2002) Physiological importance of endosomal acidification: potential role in proximal tubulopathies. Curr Opin Nephrol Hypertens 11:527–537

    Google Scholar 

  10. 10.

    Schwartz MM (1998) Hypokalemic nephropathy. In: Jennette JC, Olson JL, Schwartz MM, Silva FG (eds) Heptinstall’s pathology of the kidney, 5th edn. Lippincott-Raven, Philadelphia, pp 662–665

  11. 11.

    Emery C, Young RM, Morgan DB, Hay AW, Tele-Donker D, Rubython J (1984) Tubular damage in patients with hypokalemia. Clin Chim Acta 140:231–238

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Alpern RJ, Toto RD (1990) Hypokalemic nephropathy—a clue to cystogenesis? N Engl J Med 322:398–399

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The author would like to thank Dr. Takashi Igarashi of the Department of Pediatrics, Faculty of Medicine, University of Tokyo, for his valuable comments about the patient in this report.

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Correspondence to Toru Watanabe.

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Watanabe, T. Proximal renal tubular dysfunction in primary distal renal tubular acidosis. Pediatr Nephrol 20, 86–88 (2005). https://doi.org/10.1007/s00467-004-1693-8

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Keywords

  • Low-molecular-weight proteinuria
  • Endosome
  • Endosomal dysfunction
  • Megalin
  • Hypokalemic nephropathy