Bp And Renal

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  • Bp And Renal

    1. 1. 24 hr BP control Renal aspects
    2. 2. Hypertension and Chronic Renal Disease: Hemodynamic Abnormalities Mean BP Total Systemic Vascular Resistance = X <ul><li>Increased Cardiac Output </li></ul><ul><li>Intravascular Volume </li></ul><ul><ul><li> Glomerular filtration </li></ul></ul><ul><ul><li> Sodium excretion </li></ul></ul><ul><ul><li> Extracellular Fluid </li></ul></ul><ul><ul><li> Renal Nerve Activity </li></ul></ul><ul><ul><li>Myocardial Performance </li></ul></ul><ul><ul><li> Adrenergic Activity </li></ul></ul>Increased Vasoconstriction  Adrenergic Stimuli  Angiotensin II  Endothelin  Endothelium-derived Contracting Factors  Thromboxane Cardiac Output Decreased Vasodilation  Prostacyclin  Nitric oxide  EDHF* Textor SC. Atlas of Diseases of the Kidney, 2001. *Endothelium-derived Hyperpolarizing Factors www.hypertensiononline.org
    3. 3. <ul><li>“ The inherent variability of the blood pressure has led </li></ul><ul><li>to problems in the diagnosis, treatment, and prognosis </li></ul><ul><li>of hypertension. Knowing how the blood pressure </li></ul><ul><li>fluctuates with the stresses and strains of everyday life </li></ul><ul><li>should help in assessing the severity of hypertension, </li></ul><ul><li>the response to treatment, and the prognosis in individual </li></ul><ul><li>cases” </li></ul><ul><li>Hinman et al; 1962 </li></ul>DIURNAL BLOOD PRESSURE VARIATION IS LONG RECOGNISED !
    4. 4. Diurnal blood pressure variation Am J Hypertens 2005; 18: 149-151.
    5. 5. Altered Circadian rhythm in CKD Nephrol Dial Transplant (1997) 12: 2301–2307
    6. 6. <ul><li>Consecutive patients referred for ambulatory blood pressure monitoring, Followed over 1 year </li></ul><ul><li>322 patients included: </li></ul><ul><ul><li>137 dippers, 185 non dippers </li></ul></ul><ul><li>Mean baseline GFRs </li></ul><ul><ul><li>Dippers: 80.5 mL/min per 1.73 m 2 </li></ul></ul><ul><ul><li>Non dippers: 76.4 mL/min per 1.73 m 2 </li></ul></ul>Arch Intern Med. 2006;166:846-852
    7. 7. Dippers vs Non dippers - only significantly different parameters shown - values in brackets are percentage of total Arch Intern Med. 2006;166:846-852 ACEI, BB Antihypertensive drugs 47 (25.4) 17 (12.4) Coronary artery disease 162 (87.6) 92 (67.2) Hypertension 32 (17.3) 9 (6.6) Diabetes mellitus 65.7 ± 12.2 61.3 ± 12.6 Age, y Non dippers (n = 185) Dippers (n = 137) Variable
    8. 8. Dippers vs Non dippers - only significantly different parameters shown - values in brackets are percentage of total Arch Intern Med. 2006;166:846-852 49.5 ± 15.2 55.8 ± 17.3 High-density lipoprotein 163.8 ± 93.7 129.4 ± 68.9 Triglyceride level, mg/dL 64.7 ± 26.6 81.0 ± 20.7 GFR at Follow-up 102.4 ± 28.5 95.7 ± 19.2 FBG, mg/dL Non dippers (n = 185) Dippers (n = 137) Variable
    9. 9. Dippers vs Non dippers Arch Intern Med. 2006;166:846-852
    10. 11. Non Dipping pattern – Cause or effect ? <ul><li>Fifteen healthy subjects (4 men, 11 women; aged 33 to 65 years;mean age 55±2 years) who underwent unilateral nephrectomy for kidney donation were studied </li></ul>Hypertens Res 2005; 28: 301–306 Results suggest that unilateral nephrectomy disturbs the circadian rhythm of BP as a function of renal dysfunction without affecting absolute levels of BP Non dipping of BP seems to be the consequence of the loss of renal function, rather than the cause
    11. 12. Am J Physiol Renal Physiol 2007 293:655-659
    12. 13. ABPM findings in a community <ul><li>The Spanish Society of Hypertension - 20000 patients - 17 219 analyzed </li></ul><ul><li>Remarkable discrepancy between office and ambulatory BP in high-risk hypertensive patients </li></ul><ul><li>The prevalence of a non-dipper BP pattern was almost 60% </li></ul>Journal of Hypertension 2007, 25:977–984
    13. 14. ABPM findings in a community Journal of Hypertension 2007, 25:977–984
    14. 15. Nocturnal BP Changes and CV Mortality: Ohasama study Extreme dippers Dippers Non-dippers Risers Risk of CV Mortality Ohkubo et al; AJH 1997; 10: 1201
    15. 16. Analysis of The Influence of the Morning Surge of BP on Stroke Incidence Cox regression analysis for clinical stroke events Covariates RR P value Age (10 yrs) 1.80 (1.21-2.69) 0.004 Male gender 1.42 (0.76-2.67) 0.266 BMI 0.98 (0.90-1.07) 0.663 24 hr SBP 1.37 (1.16-1.63) 0.003 Morning BP surge* 1.29 (1.10-1.51) 0.001 Nocturnal BP fall* 0.88 (0.73-1.06) 0.167 Lowest sleep BP 1.05 (0.65-1.71) 0.837 * per 10 mmHg Kario, Pickering et al, Circ 2003; 107:1401
    16. 18. Cause of Circadian Rhythms - Role of the Autonomic system <ul><li>212 patients with progressive autonomic failure due to familial amyloid polyneuropathy </li></ul><ul><li>Group I </li></ul><ul><ul><li>No evidence yet of impairment of their ANS </li></ul></ul><ul><ul><li>Circadian BP and HR variations indistinguishable from controls </li></ul></ul><ul><li>Group II </li></ul><ul><ul><li>Variable parasympathetic, intact sympathetic </li></ul></ul><ul><ul><li>24 hour HR was higher vs Controls but maintained </li></ul></ul><ul><ul><li>Circadian BP variation diminished - attenuation of the nocturnal BP decline </li></ul></ul>Hypertension 2000;35;892-897
    17. 19. Role of the Autonomic system <ul><li>Group III </li></ul><ul><ul><li>parasympathetic failure and intermediate sympathetic dysfunction </li></ul></ul><ul><ul><li>Blunted diurnal BP variation </li></ul></ul><ul><li>Group IV </li></ul><ul><ul><li>parasympathetic failure and severe sympathetic dysfunction </li></ul></ul><ul><ul><li>Absent diurnal BP variation </li></ul></ul>Hypertension 2000;35;892-897
    18. 20. How to tackle the variations Pharmacodynamic Pharmacokinetic maintain blood concentration of a drug for longer periods longer acting drugs <ul><li>Sympatholytic drugs </li></ul><ul><li>RAAS system </li></ul>
    19. 21. Diuretics Convert Non-Dippers to Dippers Systolic pressure mmHg Day Night No Rx HCTZ No Rx HCTZ Dippers Non-Dippers Uzu & Kimura Circ 1999; 100:1635
    20. 22. Diuretics Convert Non-Dippers to Dippers Systolic pressure mmHg Day Night No Rx HCTZ No Rx HCTZ Dippers Non-Dippers Uzu & Kimura Circ 1999; 100:1635
    21. 23. Effects of Alpha-Blockade on the Morning Surge of Blood Pressure Kario, Pickering, et al Am J Hypertens 2004;17; 668 Doxazosin No Rx
    22. 24. Role of alpha blockers <ul><li>Type 2 DM with hypertension and nephropathy </li></ul><ul><li>Effects of antihypertensive therapy of combinations of angiotensin converting enzyme (ACE) inhibitor, calcium antagonists (CCB), diuretics (DU), and α blocker (AB) </li></ul><ul><li>At the end of the study </li></ul><ul><ul><li>Significant associations among </li></ul></ul><ul><ul><li>decline of 24-hr creatinine clearance and the levels of systolic blood pressure </li></ul></ul><ul><ul><li>levels of systolic blood pressure and the urine excretion of protein-creatinine ratio in the morning </li></ul></ul><ul><ul><li>Analysis of patients who had systolic blood pressure in the morning less than 140 mmHg revealed that 65% of these patients received doxazosin-averaged doses of 4.8 ± 1.5 mg daily </li></ul></ul>Clinical and Experimental Hypertension, 2005; 27:129 - 138
    23. 25. Pre Tx(n = 30) – CCB/DU + ARB Tx (n = 27) – Pre Tx + AB at bedtime
    24. 26. Changing the timing of dosing helps <ul><li>Setting & Participants </li></ul><ul><ul><li>32 CKD patients with CKD , eGFR > 90 mL/min/1.73 m2 and ABP night-day ratio greater than 0.9 </li></ul></ul><ul><ul><li>normal daytime ABP (<135/85 mm Hg) </li></ul></ul><ul><li>Intervention </li></ul><ul><ul><li>Shifting 1 antihypertensive drug from morning to evening </li></ul></ul><ul><li>Outcomes </li></ul><ul><ul><li>Percentage of patients changing the night-day ratio of mean ABP from greater than 0.9 to 0.9 or less 8 weeks after the shift </li></ul></ul><ul><li>Measurements </li></ul><ul><ul><li>Office blood pressure/ABP and proteinuria at baseline and after the shift </li></ul></ul>AJKD, 2007;50(6):908-17
    25. 27. Changing the timing of dosing helps <ul><li>Results </li></ul><ul><li>After shift: </li></ul><ul><ul><li>ABP N/D ratio decreased in 93.7% of patients, with normal circadian rhythm restored in 87.5% </li></ul></ul><ul><ul><li>Was not associated with an increase in diurnal ABP and was independent from number and class of shifted drug </li></ul></ul><ul><ul><li>Office blood pressure in the morning also decreased (from 136 ± 16/77 ± 10 to 131 ± 13/75 ± 8 mm Hg; P = 0.02) </li></ul></ul><ul><ul><li>Urinary protein excretion decreased from 235 ± 259 to 167 ± 206 mg/dl ( P < 0.001) </li></ul></ul>AJKD, 2007;50(6):908-17
    26. 28. Question: If you were allowed just one reading over 24 hours to predict morbidity, which would you choose? Gosse et al, J Hum Hypertens 2001; 15: 413 Awake Awake Sleep Going to bed Arising Evening BP Lowest BP Preawake BP Morning BP
    27. 29. <ul><li>Masked hypertension = ↑ risk of ESRD in CKD </li></ul><ul><li>White coat hypertension = better outcome </li></ul><ul><li>AMBP = Home BP >> Clinic BP </li></ul><ul><li>BP obtained in triplicate twice daily for 3 days every 3 months appears appropriate </li></ul><ul><li>Alternatively, blood pressure obtained thrice daily for 1 week can be used </li></ul>Curr Opin Nephrol Hypertens, 2006 15:309–313

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