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

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

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

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

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

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

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

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

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

13 mg total creatinine/100mg – mg preformed creatinine/100mL mg total creatinine/100mg – mg preformed creatinine/100mLEQUALS mg creatinine formed/100mL

14 Inexpensive Inexpensive Simple method Simple method Results not affected by dietary intake Results not affected by dietary intake

15 Poor sensitivity Poor sensitivity Poor specificity Poor specificity Interactions with pseudocreatinine substances Interactions with pseudocreatinine substances

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

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

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

20 Prediction equations 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 Prediction equations 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 Accuracy needs low bias and high precision Cockcroft-Gault equation extensively used but still overestimates GFR by 23% Cockcroft-Gault equation extensively used but still overestimates GFR by 23%

21 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 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 CrCl useful to estimate GFR in patients with abnormal diet and muscle mass

22 GFR estimates are accurate enough in most clinical settings 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. 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 are a special case due to changing muscle mass (growth and maturation) 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 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 Medication dosing/selection with narrow therapeutic index and high toxicity

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