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Neue Einblicke in die Pathogenese der Nierensteine

New insights into the pathogenesis of renal stone disease

  • Leitthema
  • Published:
Der Nephrologe Aims and scope

Zusammenfassung

Hintergrund

Nierensteine sind eine häufige und weltweit verbreitete Ursache von Nierenerkrankungen mit einem meist chronischen Verlauf. Kalziumhaltige Steine stellen dabei den größten Anteil dar.

Fragestellung

Ein Verständnis der Pathogenese der Steinbildung ist von therapeutischer Bedeutung, insbesondere um das Wiederauftreten der Erkrankung zu vermindern.

Material und Methoden

Als Grundlage dieses Übersichtsartikels dienen eine selektive Literaturrecherche und eigene Arbeiten zum Thema.

Ergebnisse

Die Steinanalyse und ein 24-Stunden-Sammelurin zur Bestimmung lithogener und litholytischer Substanzen stehen im Zentrum der Diagnostik. Hierbei liefern die ermittelten Konzentrationen von Kalzium, Oxalat, Harnsäure und Zitrat sowie die Bestimmung des pH-Werts und insbesondere die des Harnvolumens wichtige Informationen.

Schlussfolgerungen

Neue Erkenntnisse – erworben in Mausmodellen – sprechen für eine Rolle des Inflammasoms bei der durch Kalziumoxalatkristalle ausgelösten Entzündungsreaktion. In Zukunft könnten sich daraus neue therapeutische Ansatzpunkte ergeben.

Abstract

Background

Renal stones are a common and chronic problem worldwide. The majority of patients with nephrolithiasis form calcium stones.

Objectives

An understanding of the pathogenesis of kidney stones is essential to establish therapeutic approaches and in particular to reduce recurrence.

Methods

This review article is based on a selective literature research and own work.

Results

A stone analysis and 24-hour urine collection for determination of lithogenic and litholytic risk factors provide important information to identify causes for stone formation. The concentration of calcium, oxalate, uric acid, citrate, determination of urine pH and urine volume are essential to define risks for renal stone disease. New findings in mouse models have identified the inflammasomes as a key factor that triggers inflammation in the kidneys secondary to calcium oxalate crystals.

Conclusion

Further understanding of how to modulate the inflammasome response may provide new insights into the pathogenesis of nephrolithiasis and allow the development of novel therapeutic agents to treat renal stone disease in humans.

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Literatur

  1. Aronson PS (2006) Essential roles of CFEX-mediated Cl(-)-oxalate exchange in proximal tubule NaCl transport and prevention of urolithiasis. Kidney Int 70:1207–1213

    Article  CAS  PubMed  Google Scholar 

  2. Bobulescu IA, Maalouf N, Capolongo G et al (2013) Renal ammonium excretion after an acute acid load: blunted response in uric acid stone formers but not in patients with type 2 diabetes. Am J Physiol Renal Physiol 305:F1498–F1503

    Article  CAS  PubMed  Google Scholar 

  3. Coe FE, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115:2598–2608

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Coe F, Parks L, Moore E (1979) Familial idiopathic hypercalciuria. N Engl J Med 300:337–340

    Article  CAS  PubMed  Google Scholar 

  5. Curhan GC, Taylor EN (2008) 24-h uric acid excretion and the risk of kidney stones. Kidney Int 73:489–496

    Article  CAS  PubMed  Google Scholar 

  6. Evan A, Lingmann A, Coe F et al (2003) Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle. J Clin Invest 111:607–616

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Gillen DL, Worcester EM, Coe FL (2005) Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III. Kidney Int 67:685–690

    Article  PubMed  Google Scholar 

  8. Hesse A, Brändle E, Wilbert D et al (2003) Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. Eur Urol 44:709–713

    Article  CAS  PubMed  Google Scholar 

  9. Kim S, Coe F, Tinouth F et al (2005) Stone formation is proportional to papillary surface coverage by Randall’s plaque. J Urol 173:117–119

    Article  CAS  PubMed  Google Scholar 

  10. Knauf F, Ko N, Jiang Z et al (2011) Net intestinal transport of oxalate reflects passive absorption and SLC26A6-mediated secretion. J Am Soc Nephrol 22:2247–2255

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Knauf F, Asplin J, Granja J et al (2013) NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int 84:895–901

    Article  CAS  PubMed  Google Scholar 

  12. Kuo RL, Evans J, Paterson A et al (2003) Urine calcium and volume predict coverage of renal papilla by Randall’s plaque. Kidney Int 64:2150–2154

    Article  PubMed  Google Scholar 

  13. Moe O (2006) Kidney stones: pathophysiology and medical management. Lancet 367:333–344

    Article  CAS  PubMed  Google Scholar 

  14. Mulay S, Rupanagudi O, Khader M et al (2013) Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J Clin Invest 123:236–246

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Pak CY, Huet A, Pointdexter B et al (2004) Rapid communication: relative effect of urinary calcium and oxalate on saturation of calcium oxalate. Kidney Int 66:2032–2037

    Article  CAS  PubMed  Google Scholar 

  16. Randall A (1937) The origin and growth of renal calculi. Ann Surg 105:1009–1027

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Reddy SW, Sakhaee CY, Brinkley K et al (2002) Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 40:265–274

    Article  CAS  PubMed  Google Scholar 

  18. Rule AR, Melton V, Bergstralh LJ et al (2010) Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol 21:1641–1644

    Article  PubMed Central  PubMed  Google Scholar 

  19. Saigal CJ, Anga GT (2005) Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int 68:1808–1814

    Article  PubMed  Google Scholar 

  20. Sakhaee K, Maalouf NM, Sinnott B (2012) Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management. J Clin Endocrinol Metab 97:1847–1860

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Singh AS, Sarkar S (2007) Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase inhibitor. Am J Kidney Dis 49:153–157

    Article  CAS  PubMed  Google Scholar 

  22. Strowig T, Henao Mejia J, Elinav E et al (2012) Inflammasomes in health and disease. Nature 481:278–286

    Article  CAS  PubMed  Google Scholar 

  23. Wagner C, Mohebbi N (2010) Urinary pH and stone formation. J Nephrol 23(Suppl 16):S165–S169

    PubMed  Google Scholar 

  24. Worcester EM, Coe FL (2008) Nephrolithiasis. Prim Care 35:369–391

    Article  PubMed Central  PubMed  Google Scholar 

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Danksagung

Der Autor dankt Professor Andrew Evan, Indiana University School of Medicine, USA, für die Bereitstellung der Abbildung 1.

Einhaltung ethischer Richtlinien

Interessenkonflikt. F. Knauf gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Medizinische Klinik 4, Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen und Klinikum Nürnberg, Ulmenweg 18, 91054, Erlangen, Deutschland

    F. Knauf

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Correspondence to F. Knauf.

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Knauf, F. Neue Einblicke in die Pathogenese der Nierensteine. Nephrologe 9, 196–203 (2014). https://doi.org/10.1007/s11560-013-0850-0

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  • DOI: https://doi.org/10.1007/s11560-013-0850-0

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