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Future research directions in nocturia

Future research directions in nocturia. Charlotte Graugaard-Jensen MD, PhD Department of Urology Aarhus University Hospital, Skejby Denmark 2012. Once upon a time, nocturia was…. The disease of old men. Associated with BPH. Symptom of getting older. Treated with TUR-P.

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Future research directions in nocturia

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  1. Future research directions in nocturia Charlotte Graugaard-Jensen MD, PhD Department of Urology Aarhus University Hospital, Skejby Denmark 2012

  2. Once upon a time, nocturia was… The disease of old men Associated with BPH Symptom of getting older Treated with TUR-P TUR-P = transurethral resection of the prostate

  3. Today … Europen=845 USAn=934 26% 12% 74% 88% Nocturnal polyuria Without nocturnal polyuria Abrams et al. Neurourol Urodyn 2004;23:466 Weiss et al. J Urol 2011;186: 1358-63

  4. Agenda BP ? Sodium Water Sleep

  5. Water Renal sensitivity Diurnal rhythm Gender differences • Arginine VasoPressin

  6. Attenuated nocturnal increase Nocturnal polyurics had no nocturnal increase in AVP One oral dose of dDAVP restored the diurnal rhythm Hvistendahl GM et al, J Urol 2007, 178,2671

  7. AVP and nocturnal voiding 18 elderly males 36 h admission Diurnal rhythm attenuated in nocturics Graugaard-Jensen et al. J Urol 2006;176:1034

  8. Water Renal sensitivity Diurnal rhythm Gender differences • Arginine VasoPressin

  9. Impaired renal sensitivity • Nocturnal polyuria – impaired renal sensitivity to AVP? • 174 patients • 4 groups • UAVP/Ucr equal between groups • Nocturnal urine volume different between groups Tani et al. Int J Urol 2008;15:151

  10. Water Renal sensitivity Diurnal rhythm Gender differences • Arginine VasoPressin

  11. Gender differences Female rats have a greater sensitivity to endogenously secreted AVP (2.7x) Females may be more susceptible to the development of dilutional hyponatraemia Liu J et al. Am J Physiol Renal Physiol 2011;300:F433

  12. Gender differences in AVP Desmopressin Relative sensitivity women/men: 2.7 Juul K V et al. Am J Physiol Renal Physiol 2011;300:F1116

  13. Oestrogen and AVP P-osm P-Na Stachenfeld et al. Am J Physiol 2003;562:869 Forsling. J Endocrinol 1981;89:263 Graugaard-Jensen. BMC Urology 2008;8:16 Oestrogen

  14. Testosterone and AVP Lower renal sensitivity to AVP in men Stachenfeld et al. Am J Appl Physiol 2001;91:1893

  15. Water Renal sensitivity Diurnal rhythm Gender differences • Arginine VasoPressin

  16. Sodium ProstaGlandinE2 Natriuresis

  17. PGE2 and natriuresis Increased sodium excretion increased PGE2 excretion Kamperis K et al. Am J Physiol Renal Physiol 2006;291:F1232

  18. NSAIDs and natriuresis Ibuprofen: FENa Uvol similar Lauridsen et al. BMC Nephrology 2010;11:28

  19. PGE2 • 37 healthy young men/women • 24 h admission • Gender difference in PGE2 excretion • No gender difference in urine • output or sodium excretion PhD thesis. 2008. Graugaard-Jensen

  20. PGE2 • 37 healthy young men/women • 24 h admission • Gender difference in PGE2-excretion • No gender difference in urine • output or sodium excretion PhD-thesis; 2008: Graugaard-Jensen

  21. Blood pressure Nurse, get on the internet. Go to SURGERY.COM Scroll down and click on the “Are you totally lost?” icon Is nocturia of cardiovascularorigin?

  22. BP and nocturia in elderly men • 18 healthy elderly males • 36 h admission • Nocturia BP Graugaard-Jensen et al. J Urol 2006;176:1034

  23. BP and nocturnal Uvol correlation in men • 17 men with nocturia • 10 controls • 36 h admission • Nocturnal diuresis BP Matthiesen TB. J Urol 1996;156:1292

  24. BP and nocturnal Uvol correlation in both genders • 17 men and 6 women • 24 h admission • Nocturnal diuresis BP Asplund R. Neth J Med 2002 Aug;60(7):276

  25. Autonomic imbalance? • Enuretic children have too much sympathetic activity at night … • Parasympathetic hypoactivity in enuretics relative to healthy children • The enuretic children had parasympathetic hyperfunction, which was normalised post-treatment Dündaröz MR et al. Int Urol Nephr 2001;32:393 Dündaröz MR et al. Int Urol Nephr 2009;41:231 Fujiwara J et Scand. J Urol Nephrol 2001;35:350

  26. Agenda BP ? Sodium Water Sleep

  27. Sleep deprivation (SD) • 20 young adults • One normal night and one night with SD • Acute SD markedly increased diuresis and sodium output Kamperis K et al. Am J Physiol Renal Physiol 2010;299:F404

  28. Sleep deprivation Renin-angiotensin-aldosterone system Attenuated night-dipping in BP AVP and ANP unaffected by SD Kamperis K et al. Am J Physiol Renal Physiol 2010;299:F404

  29. Sleep deprivation in children 20 children 2 x 24 h admission 1 night with SD Mahler B et al. Am J Physiol Renal Physiol 2012;302:F236

  30. Sleep apnoea • Leads to natriuresis diuresis • Atrial natriuretic peptide Data represent mean ±SEM calculated from nine animals. Renal function was measured for one 15 minute clearance period before (pre-) and two 15 minute periods after a 10 minute period of increased inspiratory resistance (Post-1 and Post-2). *P < 0.05 vs pre value GFR, glomular filtration rate; UV, urine volume; cGMP, cyclic guanosine monophosphate Yalkut D et al. J Lab Clin Med 1996;28:323

  31. Sleep apnoea and hypertension AVP BP Pressure-natriuresis Gjørup Ph. Scand J Clin Lab Invest 2008;68(1):11

  32. Autonomic imbalance Patients with severe obstructive sleep apnoea have an increased LF/HF ratio increased sympathetic activity Noda et al. Clin Cardiol 1998;21:271

  33. Conclusion BP ? Sodium Water Sleep

  34. Which way? • Water • No nocturnal increase in AVP • Sensitivity to AVP • Sodium • PGE2 • Blood pressure • ‘Hypertension’ • Dipping • Sleep • Deprivation • Apnoea Autonomic imbalance

  35. THANK YOU

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