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RENAL GROUP E

RENAL GROUP E. ACEI. ACEI inhibit angiotensin converting enzyme in the body. Enzyme maintains balance between: -Angiotensin 2 -Bradykinin -vasoconstrictive -vasodilatory -salt retentive -naturiretic. RAS SYSTEM. ACEIs action in CHF.

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RENAL GROUP E

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  1. RENAL GROUP E

  2. ACEI • ACEI inhibit angiotensin converting enzyme in the body. • Enzyme maintains balance between: • -Angiotensin 2 -Bradykinin -vasoconstrictive -vasodilatory -salt retentive -naturiretic

  3. RAS SYSTEM

  4. ACEIs action in CHF • Relaxation of blood vessels leading to a decreased force of cardiac contraction. • Decrease in systemic vascular resistance with minimal increase in heart rate. • Reduction in blood volume causing a fall in blood pressure • Overall reduction in heart workload.

  5. MONITORING RENAL FUNCTION • Monitor at baseline and 1-2 weeks after initiating treatment. • Regular monitoring throughout treatment especially when there is a dose increase. • ACEIs have the potential to cause a rapid, severe decline in renal function

  6. SEVERE RENAL FAILURE • Occurs in certain disease states characterized by decreased perfusion across the glomerular. • ACEIs are contraindicated in these groups. These include: -angioedema -cardiac outflow obst. -aortic stenosis -renal artery stenosis

  7. DECREASED GFR

  8. WHY MONITOR RF? • Many ACEIs are almost 100% renally cleared, a renally impaired patient may not adequately clear drug • Renal function declines with age and may be effected my certain medications • The reduced clearance may lead to adverse effects of the drug

  9. ACEI ADVERSE EFFECTS -Hypotension -dizziness -headache -palpitations -hyperkalemia -further RI • Dose reduction may be needed to avoid these effects in the renally impaired

  10. HYPERKALEMIA • Decreased aldosterone production increases sodium excretion. • Sodium crosses tubules via Na+/K+ATPase pump in the tubular lumen. • As Na is excreted K+ is absorbed.

  11. TOO MUCH K+? • High potassium levels interferes with depolarizing mechanism and lowers resting potential. • A concentration >7mmol/L may cause cardiac arrest. • Hyperkalemia symptoms include: nausea, diarrhoea, muscle weakness

  12. CALCULATION • ABSORBANCE UNKNOWN ABSORBANCE STANDARD * 100 = • MG PREFORMED CREATININE/100ML

  13. CALCULATION • mg total creatinine/100mg – mg preformed creatinine/100mL EQUALS mg creatinine formed/100mL

  14. ADVANTAGES • Inexpensive • Simple method • Results not affected by dietary intake

  15. DISADVANTAGES • Poor sensitivity • Poor specificity • Interactions with pseudocreatinine substances

  16. ACCURACY • Jaffe Assay lacks specificity for detection of serum picrate-creatinine complex formed by reaction. • Positive interference (endogenous compounds, clinical conditions, drugs) • Negative interference (bilirubin, haemoglobin)

  17. ACCURACY CONT... • Literature indicates Jaffe reports falsely elevated serum Cr by >26% compared to MEKC method • Variation in upper limit of normal (0.2 - 0.4mg/dl) between labs due to different assay calibration. • Urine Cr Clearance lacks chromogen interference but needs timed collection, special storage and is subject to errors and daily variations

  18. Picrate-Creatinine Complex

  19. IMPLICATIONS FOR GFR • GFR indicates total functioning renal mass but no direct way to measure • Inulin ideal compound but impractical • Serum Cr insensitive to marked ↓ in GFR so not a good indicator alone (due to extra-renal compensation)

  20. MORE IMPLICATIONS... • Prediction equation’s transform serum Cr to CrCl and estimate GFR via consideration of age, sex, body size and ethnicity variables; assume patient steady-state and average Cr production rate • Accuracy needs low bias and high precision • Cockcroft-Gault equation extensively used but still overestimates GFR by 23%

  21. CREATININE CLEARANCE • CrCl via urine is composite of secretion and GFR; ↓ GFR masked by secretion compensation; not a better estimate of GFR than serum Cr but more cumbersome • CrCl useful to estimate GFR in patients with abnormal diet and muscle mass

  22. CLINICAL IMPLICATIONS • GFR estimates are accurate enough in most clinical settings • Serum Cr based GFR estimates problematic in renal impairment due to extra-renal and secretion compensation that keeps serum Cr stable despite ↓ GFR; can obscure early damage and impairment progression.

  23. CHILDREN AND THE ELDERLY • Children are a special case due to changing muscle mass (growth and maturation) • Elderly need additional markers of kidney disease if low GFR i.e. proteinuria and hypertension • Medication dosing/selection with narrow therapeutic index and high toxicity

  24. The End

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