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ACEI inhibit angiotensin converting ACEI inhibit angiotensin converting enzyme in the body.enzyme in the body.

Enzyme maintains balance between:Enzyme maintains balance between: -Angiotensin 2-Angiotensin 2 -Bradykinin-Bradykinin

-vasoconstrictive-vasoconstrictive -vasodilatory-vasodilatory

-salt retentive-salt retentive -naturiretic-naturiretic

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Relaxation of blood vessels leading to Relaxation of blood vessels leading to a decreased force of cardiac a decreased force of cardiac contraction.contraction.

Decrease in systemic vascular Decrease in systemic vascular resistance with minimal increase in resistance with minimal increase in heart rate.heart rate.

Reduction in blood volume causing a Reduction in blood volume causing a fall in blood pressurefall in blood pressure

Overall reduction in heart workload.Overall reduction in heart workload.

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Monitor at baseline and 1-2 weeks Monitor at baseline and 1-2 weeks after initiating treatment.after initiating treatment.

Regular monitoring throughout Regular monitoring throughout treatment especially when there is a treatment especially when there is a dose increase.dose increase.

ACEIs have the potential to cause a ACEIs have the potential to cause a rapid, severe decline in renal rapid, severe decline in renal functionfunction

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Occurs in certain disease states Occurs in certain disease states characterized by decreased perfusion characterized by decreased perfusion across the glomerular.across the glomerular.

ACEIs are contraindicated in these ACEIs are contraindicated in these groups. These include:groups. These include:

-angioedema-angioedema -cardiac outflow -cardiac outflow obst.obst.

-aortic stenosis-aortic stenosis -renal artery -renal artery stenosisstenosis

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Many ACEIs are almost 100% Many ACEIs are almost 100% renally cleared, a renally impaired renally cleared, a renally impaired patient may not adequately clear patient may not adequately clear drugdrug

Renal function declines with age and Renal function declines with age and may be effected my certain may be effected my certain medicationsmedications

The reduced clearance may lead to The reduced clearance may lead to adverse effects of the drugadverse effects of the drug

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-Hypotension-Hypotension -dizziness-dizziness

-headache-headache -palpitations-palpitations

-hyperkalemia-hyperkalemia -further RI-further RI

Dose reduction may be needed to Dose reduction may be needed to avoid these effects in the renally avoid these effects in the renally impaired impaired

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Decreased aldosterone production Decreased aldosterone production increases sodium excretion.increases sodium excretion.

Sodium crosses tubules via Sodium crosses tubules via Na+/K+ATPase pump in the tubular Na+/K+ATPase pump in the tubular lumen.lumen.

As Na is excreted K+ is absorbed.As Na is excreted K+ is absorbed.

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High potassium levels interferes High potassium levels interferes with depolarizing mechanism and with depolarizing mechanism and lowers resting potential.lowers resting potential.

A concentration >7mmol/L may A concentration >7mmol/L may cause cardiac arrest.cause cardiac arrest.

Hyperkalemia symptoms include: Hyperkalemia symptoms include: nausea, diarrhoea, muscle weaknessnausea, diarrhoea, muscle weakness

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ABSORBANCE UNKNOWNABSORBANCE UNKNOWN ABSORBANCE STANDARD * 100 =ABSORBANCE STANDARD * 100 =

MG PREFORMED MG PREFORMED CREATININE/100MLCREATININE/100ML

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mg total creatinine/100mg – mg mg total creatinine/100mg – mg preformed creatinine/100mLpreformed creatinine/100mL

EQUALSEQUALS

mg creatinine formed/100mLmg creatinine formed/100mL

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InexpensiveInexpensive Simple methodSimple method Results not affected by dietary Results not affected by dietary

intakeintake

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Poor sensitivityPoor sensitivity Poor specificityPoor specificity Interactions with pseudocreatinine Interactions with pseudocreatinine

substancessubstances

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Jaffe Assay lacks specificity for Jaffe Assay lacks specificity for detection of serum picrate-creatinine detection of serum picrate-creatinine complex formed by reaction.complex formed by reaction.

Positive interference (endogenous Positive interference (endogenous compounds, clinical conditions, compounds, clinical conditions, drugs)drugs)

Negative interference (bilirubin, Negative interference (bilirubin, haemoglobin)haemoglobin)

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Literature indicates Jaffe reports falsely Literature indicates Jaffe reports falsely elevated serum Cr by >26% compared to elevated serum Cr by >26% compared to MEKC methodMEKC method

Variation in upper limit of normal (0.2 - Variation in upper limit of normal (0.2 - 0.4mg/dl) between labs due to different 0.4mg/dl) between labs due to different assay calibration.assay calibration.

Urine Cr Clearance lacks chromogen Urine Cr Clearance lacks chromogen interference but needs timed collection, interference but needs timed collection, special storage and is subject to errors special storage and is subject to errors and daily variationsand daily variations

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GFR indicates total functioning renal GFR indicates total functioning renal mass but no direct way to measuremass but no direct way to measure

Inulin ideal compound but Inulin ideal compound but impracticalimpractical

Serum Cr insensitive to marked ↓ in Serum Cr insensitive to marked ↓ in GFR so not a good indicator alone GFR so not a good indicator alone (due to extra-renal compensation)(due to extra-renal compensation)

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Prediction equation’s transform serum Cr Prediction equation’s transform serum Cr to CrCl and estimate GFR via to CrCl and estimate GFR via consideration of age, sex, body size and consideration of age, sex, body size and ethnicity variables; assume patient ethnicity variables; assume patient steady-state and average Cr production steady-state and average Cr production rate rate

Accuracy needs low bias and high Accuracy needs low bias and high precisionprecision

Cockcroft-Gault equation extensively Cockcroft-Gault equation extensively used but still overestimates GFR by 23%used but still overestimates GFR by 23%

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CrCl via urine is composite of CrCl via urine is composite of secretion and GFR; ↓ GFR masked secretion and GFR; ↓ GFR masked by secretion compensation; not a by secretion compensation; not a better estimate of GFR than serum better estimate of GFR than serum Cr but more cumbersomeCr but more cumbersome

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

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GFR estimates are accurate enough GFR estimates are accurate enough in most clinical settingsin most clinical settings

Serum Cr based GFR estimates Serum Cr based GFR estimates problematic in renal impairment due problematic in renal impairment due to extra-renal and secretion to extra-renal and secretion compensation that keeps serum Cr compensation that keeps serum Cr stable despite ↓ GFR; can obscure stable despite ↓ GFR; can obscure early damage and impairment early damage and impairment progression.progression.

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Children are a special case due to Children are a special case due to changing muscle mass (growth and changing muscle mass (growth and maturation)maturation)

Elderly need additional markers of Elderly need additional markers of kidney disease if low GFR i.e. kidney disease if low GFR i.e. proteinuria and hypertensionproteinuria and hypertension

Medication dosing/selection with Medication dosing/selection with narrow therapeutic index and high narrow therapeutic index and high toxicitytoxicity

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