2 Renal Flashcards
Functions of the kidney:
1 Excretion of water-soluble (Glomerular filtration & Tubular secretion)
2 ECF volume & BP (Salt, water excretion) & vasoacitive hormones)
3 Control of acid-base balance
(ECF volume, vasoactive hormones, sympathetic nervous system)
4 Hydroxylation of vitamin D
5 Control of RBC production
Cr is produced at a constant rate from?
Muscle turnover
6 measurements of kidney function
- Glomerular filtration rate (endogenous markers: Cr & Cystatin C, exogenous markers: Inulin)
- Tubular secretion(rare)
- ECF and BP
- Acid-base balance – serum [HCO3]
- Vit D hydroxylation – PTH measurement
- RBC production – Hb measurement
Cr production rate depends on…
Muscle mass therefore age, gender, ethnicity
Cr is secreted solely by
Glomerular filtration
What to think about with trimethoprim and cr?
Creatinine is a tiny bit excreted by tubular secretion. Important in very bad function. Simetadine and Trimethoprim inhibit tubular secretion.
CrCl is estimated using…. Formula…
Cockcroft and Gault
eGFR is calculated using the … Formula
MDRD
For CrCl use which type of body weight?
Ideal body weight
MDRD is less accurate for
Patients at extremes of weight
Other tests of kidney function 8
- Haematuria (blood in urine)
- Proteinuria (albumin/total protein)
- Abnormal cells or debris in the urine
- Laboratory measurement
- Acidification tests
- Radiology
- Microscopy
- Dipstick
Causes of chronic kidney disease
Diabetes Hypertension Glomerulonephritis Reflux nephropathy Polycystic disease Previous AKI Others: including nephrotoxicity
Causes of AKI?
Pre-renal – reduction in renal perfusion
(Hypovolaemia/sepsis/cardiogenic)
Renal – intrinsic kidney disease
• Prolonged pre-renal causing ‘acute tubular necrosis
• Specific causes e.g. vasculitis, glomerulonephritis, drugs
Post-renal – obstruction to urine flow.
(e.g. Prostatic bladder/malignancy)
Presentation of kidney disease
• CKD is often asymptomatic until stage 4 or even 5
• Late presentation of CKD5 = poor outcome
• So screening of at-risk populations is encouraged
• Anaemia is a common presenting problem
(Exclude alternative causes e.g. deficiency states, bone marrow disorders, haemolysis)
• Symptoms in advanced CKD often non-specific: fatigue, lethargy, loss of appetite, nausea, vomiting, nocturia and polyuria, muscle cramps, restless legs
Four treatments for kidney failure
1Conservative’ – drug treatment to minimise further loss of kidney function (antihypertensives, NaHCO3), plus symptomatic treatment (ESAs; antiemetics, etc)
2 Peritoneal dialysis
3 Haemodialysis
4 Kidney transplantation
Burden of dialysis 6
- Fluid/salt/potassium restriction
- Phosphate binders to reduce GI absorption of PO4
- Travel (to centre/restricted abroad)
- Continued symptoms
- Access problems
- Infectious problems
Why be careful with ACEI?
Restrict blood flow to the kidney, appears as failure… Is it?? I don’t know :/
MDRD is suitable for… And not suitable for…
Normalised GFR (ml/min/1.73m2) is appropriate for estimating how abnormal the kidney function is, but NOT for drug dose adjustment • At any given level of normalised GFR, bigger people would get smaller doses and smaller people larger doses.
Common maintenance drugs…
- BP-lowering drug treatment
- Lipid-lowering drug treatment
- Glucose-lowering drug treatment
- Phosphate binders
- Vitamin D analogues
- Sodium bicarbonate supplements
- Erythropoiesis stimulating agents
- Anti-platelet agents
- Water-soluble vitamin supplements
Criteria for acute kidney injury
Serum creatinine rises by ≥ 26µmol/L within 48 hours
- Serum creatinine rises ≥ 1.5 fold from the reference value, which is known or presumed to have occurred within one week
- urine output is < 0.5ml/kg/hr for >6 consecutive hours
Three drugs that reduce blood flow to the kidneys
Diuretic, NSAIDs, ACEi
5 drugs that contribute to intrinsic renal impairment in AKI
NSAIDs PPIs Antivirals Antibiotics (Direct toxic effect - ahminoglycosides)
2 drugs contributing to post-renal AKI
Methotrexate and aciclovir
Two normal responses of the kidney you reduced blood flow? What two drug classes are implicated?
Kidneys normal response to a reduction in renal blood flow is :
• Vasodilation of afferent blood vessels – prostaglandins
• Vasoconstriction of efferent blood vessels – renin angiotensin system
Therefore ACEi and NSAIDs prevent body from achieving normal response
Consider acute nephrotoxic drug action
- C - Contrast media
- A - Angiotensin converting enzyme inhibitor
- N - Non steroidal anti-inflammatory drugs
- D - Diuretics
- A - Angiotensin II receptor blockers
Role of the pharmacist in AKI (6)
- Preventing AKI – Education / Risk assessment
- Recognising AKI
- Identify possible drug causes
- Stop nephrotoxic drugs
- Review drugs that may worsen biochemistry e.g. cause hyperkalaemia
- Review doses of other medication that may accumulate
Some general info on CDK
- Abnormal kidney function and/or structure
- Common, frequently unrecognised
- Often co-exists with other conditions
- Diabetes, Cardiovascular disease
- Risk of developing increases with age
- Often asymptomatic – 30% of patients with advanced kidney disease are referred late
- Treatment can prevent or delay progression of CKD and reduce or prevent development of complication
Nine complications of CKD
- Anaemia
- Hyperphosphataemia
- Renal Bone Disease
- Oedema
- Hypertension
- Itching
- Nausea
- Electrolyte Imbalances
- Restless Legs/Cramps
How do we treat anaemia in AKI?
erythropoietin (SC or IV) and iron (IV) - sometimes straight into the dialysis machine
How to treat hyperphosphatemia?
Phosphate binders
What vitamin supplement is mainly used in kidney disease?
Alfacalcidol
How to treat itching? (2)
Antihistamines and moisturisers
How to treat cramps?
Quinine and stretching
How to treat restless legs
Clonazepam
Phosphate binders may chelate other drugs such as (2)
quinolone antibiotics, levothyroxine
Four effects on adsorption
- Reduced compliance (due to uremic symptoms/polypharmacy)
- Gastric oedema
- Phosphate binders (bind quinolones, levothyroxine)
- PPI and H2 receptor antagonists reduce gastric acidity
Effects on distribution
• Low albumin reduces the amount of protein binding
• Uraemia causes displacement from protein binding sites
> Increased free drug… Therapeutic drug monitoring
Which drugs should be theraputic monitored… 5
- Low albumin reduces the amount of protein binding
- Uraemia causes displacement from protein binding sites
- Increased free drug -
- Phenytoin Sodium valporate
- Diazepam Warfarin
- Digoxin
- Therapeutic drug monitoring…. Due to their changes free levels as a result of reduced protein binding in renal disease
Effects of metabolism on CDK
- Vitamin D – Kidney hydroxylation at 1-alfa position
- In CKD need to give activated vitamin D
- Insulin
Effects on excretion
- Significant for drugs which are >25% excreted unchanged in the urine
- Remember metabolites
- Drugs with a narrow therapeutic index
Five drugs to consider due to half life changes as renally excreted
- Aciclovir – Half life extended from 3-20 hours
- Gabapentin – 100% excreted in kidneys
- Methotrexate – 80-90% excreted in urine
- Digoxin 76-85% excreted unchanged in urine
- Opiates –morphine
- Half life of 6 glucoronide increased from 3-5 hours to 50hours
Haemodialsysis or haemofitration require anticoagulants?
Dialysis
Ideal renal drug (7) features
- Less than 25% excreted in the urine
- No active metabolites
- Disposition unaffected by fluid balance changes
- Disposition unaffected by protein binding
- Disposition unaffected by tissue sensitivity
- Wide therapeutic index
- Not nephrotoxic
Decrease dose or decrease frequency in kidney disease?
Antibiotics – where you want to maintain peak increase dose interval
- Decreasing dose smoother profile e.g. allopurinol
- Consider formulations available
- Consider renal replacement therapy
- Example
- Digoxin reduce loading dose and reduce maintenance dose
- Meropenem give od post dialysis
Pharmacists role in CLD
Stop nephrotoxic drugs if patient has function
- Review drugs that may worsen biochemistry e.g. cause hyperkalaemia, increase sodium
- Advice on minimum volumes for IV’s if patient fluid restricted
- Review doses of other medication that may accumulate
- eGFR or cockcroft and gault
- Consider adjusting medication around dialysis
- Patient education
- Supply of hospital only medication
Pharmacists role in transplants
• Avoid nephrotoxic drugs • Ensure medication is adjusted for level of renal function • Ensure transplant medication is continued • Ensure appropriate brand is supplied • Consider drug interactions • Macrolides • Antifungals
Four OTC problems in renal patients
- Caution antacids
- Na, Ca, Mg, Al content
- Caution Cough/Cold remedies
- Sympathomimetics
- Products with electrolytes in them
- Na - Andrews Liver Salts
- K - Losalt
- Citrate - Cystemme (UTI symptom relief)
- Travel medicine
Reduction in renal blood flow (perrennial cause of AKI) results in (2)
Ischemia and tubular necrosis
Increased production if wastes by… (3) Can result in pre renal cause for AKI
Waste products such as urea
By infection, upper GI bleeding, steroid therapy
Interstitial nephritis is …
Interstitial damage mediated by hypersensitivity reaction to neurotoxins, results in inflammation affecting those cells lying between the nephrons
Most common cause Intra-renal AKI?
Actute tubular necrosis, where the proximal tubule is highly active and therefore more susceptible to ischaemia or toxins… Common cause of this is renal hypo fusion.
Post renal causes of AKI result from… Such as… 4
Obstruction to the urinary tract
Urinary stones, constipation, neoplasm, benign prostatic hypertrophy?
Cockroft-Gault not appropriate for use in….
ARF in a patient with previously normal function as serum cr rises by only 10-20 micromol/l per day.
AND
paediatrics or highly muscle developed patients (athletes)
AND
pt with extensive burns
AND
pt with fluid overload
How to assess cr clearance in AKI…
24 hour urine collection
ACR
Albumin:creatinine ratio
NICE recommends using this to retention protein in urea rather than other methods
Proteininuria is an important indicator or…
Kidney disease and the risk of its progression
Functions of the kidney
Excretion of water-soluble waste products: Glomerular filtration, tubular secretion
MDRD eqution
Does not require body weight as an input variable, provides a normalised estimate
What will happen to the C&G and MDRD estimate is a person puts on weight
C&G will stay the same because the rise in serum creatinine will be cancelled out by the rise in weight.
eGFR
= % Kidney function
Tests for kidney function
Blood in the urine
Causes of chronic kidney disease
Diabetes, hypertension, glomerularphritis, reflux nephropathym polycycstic disease, previous acute KI, nephrotoxicity
Clinical presentation of chronic kidney disease
Often asymptomatic until stage 4 or 5, sos creeping of at risk populations is encouraged. Anaemia is a common presenting problem.
Treatments for kidney failure
Conservative - drug treatment to minimise further loss of kidney function (antihypertensives, NaHCO3), plus symptomatic treatment (anti emetics etc)
Burdens of dialysis
Fluid restriction, restriction of salt intake, restriction of potassium intake, phosphate binders to reduce GI absorption of PO4, travel, restriction in travel within the UK (and abroad), continued symptoms, access problems, infectious problems
Normalised GFR
appropriate for estimating ho normal the kidney function is, but not for dose adjustment
Acute kidney injury
Clinically, characterised by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homeostasis.
5-20%
Estimated amount of critically ill patients that experience an episode of AKI.
more than or equal to 26micromol/L within 48 hours
Amount serum creatinine has to rise by to indicate AKI (within 48 hours)
more than or equal to 1.5 fold from the reference value, occurring within one week
Amount serum creatinine has to rise by to indicate AKI (within one week)
less than 0.5ml/kg/hr for >6 consecutive hours
Urine output amount to indicate AKI
Affect on distribution in kidney failure
Low albumin decreases amount of protein binding
Vitamin D
Is hydroxylated in the kidney at the 1 alpha position to it’s activated form. So in kidney failure need to give the activated form, e.g. alficalcidol, not calcichew D3
Excretion in kidney failure
Is significant for drugs which are >25% excreted unchanged in urine, and drugs with a narrow therapeutic index.
Aciclovir
Half life is extended from 3 to 20 hours in kidney failure
Gabapentin
100 % excreted in the kidneys
Methotrexate
80-90% excreted unchanged
Digoxin
76-85% excreted unchanged in urine
Opiates - morphine
half life of 6 glucuronide increased from 3-5 hours to 50 hours.
Properties of the ideal renal failure drug
less than 25% excreted in urine, no active metabolites, disposition unaffected by fluid balance changes, disposition unaffected by protein binding, disposition unaffected by tissue sensitivity, wide therapeutic index, not nephrotoxic.
Cockcroft - gault is not appropriate for use in
acute renal failure with previously normal renal function/paediatrics/extensive burns/fluid overload
How to measure renal func in AKI
24h urine sample
variables in MDRD
age sex ethnicity and serum creatanin
test to detect proteininurea
ACR (albumin creatanin ratio)
Normally the kidney ….. K
filters
with decreasing GFR K levels
rise (unless dietary intake reduced)
Diet avoiding K
avoid orange juice, nuts, crisps, baked beans
Medication that causes K retention (caution in renal failure)
spironoloctone
ACE-I
Used to treat high K levels?
Push K back into cells:
Calcium glucuronate
Then: 50% dextrose + insulin infusion
OR salbutamol neb/IV
OR NaHCO3 (sodium bicarb)
AND K resin exchange mechanism OR dialysis
Problems resulting from high K
fatal arrhythmias
K resin exchange mechanism
Calcium resonium
Function of bicarbonate
buffer H ions
Bicarbonate is regenerated where?
in the tubular cells - then passed back into plasma
Renal failure effect on bicarb
reduced regeneration (and the reduced GFR means kidneys don't filter other potential buffers such as phosphate - accumulates - acidosis)
Result of low bicarbonate
hypokaleamia (low K) & hypernatraemia (high Na)
fluid overload
Treatments for decreased bicarb
oral bicarbonate (contravertial - alkalinisation)
OR
titrate contiunous line against plasma pH
As GFR decreases phosphate … and calcium ….
phosphate accumulates
calcium decreases
Renal bone disease
mixture of oesteomalacia & hyperparathyroidism
*as a result of accumulated phosphate and Ca decrease
Phosphate binders can cause
HYPERcalcaemia > renal damage
Essential to maintain normal fluid volume
sodium reabsorption in the tubule (back into the blood stream) - this ability is lost in kidney damage - fluid overlaod
Haemodialysis
& 3 disadvantages
several hours 3/week via fisula into vein
Risk of infection/ischemia of the hand, pt feels worse between sessions,
At what CrCl is dialysis needed
<15
Peritoneal dialysis
Catheter puts solution in, diffuses over membrane 6 hours, drain and replace.
Can be done at home. More stable condition.
Risk of infection - scarring
Weight gain as glucose moves
Constipation can reduce efficacy
Haemofiltration
In ICU - continuous against semipermiable membrane but putting in replacement fluid to prevent deydration
Factors to consider for medication & dialysis
Excreted or metabolised?
Severity of renal fuction?
Stop nephrotoxics
Does it matter if the drug accumulates? (narrow therapeutic index)
Is the drug cleared by peritoneal/heamofilration? - alter dose
Heamodialysis - alter timeing?
How phosphate binders work?
Form insoluble non-absorbable complexes
4 phosphate binders
Aluminium hydroxide (tox problems) Calcium carbonate (corrects concurrent hypocalciumia but needs high dose) Calcium acetate (lower doses) Sevelamer (decreases likelyhood of hypercacimia - expensive)
Problems with dihydropyridine CCBs (nifedipine)
less cardiac depression BUT only dilate efferent arterioles which may result in glomerular damage
If using ACEi to lower BP
monitor potassium (as they are potassium sparing)
Choice of betablockers
Atenolol - well tolerated but requires adjustment in renal failure
Metoprolol - not need for adjustment
Should not use CCBs with
b blockers
ACEi have advantage that
they may reduce thirst
Choices for oedema
Furosemide (limited to a loop diuretic)
+/-
Metazolone works synergistically with furosemide
Thiazides are not used becuase
ineffective in renal failure
Potassium sparing diuretics are not used because
hyperkalemia risk
Hydroxylation of vitamin D occurs
at alpha one position - in the kidney
Impairment in renal failure > defective bone militarization > oesteomalacia
When using Alfacacidol monitor
serum calcium
+ correct hyperphosphatemia before initiating therapy (or results in soft tissue calcification)
Anaemia is noticable when GFR <
30ml/min (shorten RBC survival, bone marrow supression, poor dietary uptake of folate/iron)
Treat aneamia with
EPO +/- iron ( may want to check ferratin stores to see if iron is being absorbed and if not administer IV)
80% of AKI is
pre-renal
MDRD tends to over/underestimate
underestimate
Cockroft Gault tends to under/overestimate
overestimate
MDRD assumes
levels constant over past few days… therefore do not use to assess AKI
Itching as a result of
uremic symptoms (high K & low K may contribute)
- Micropercipitation of divalent ions elevated by PTH & increase in dermal mast cell activity.
elcetrolyte correction may help but might not improve until dialyis
Nausea and loss of appetite a result of
uremic symptoms
Muscle weakness and cramp due to
toxin build
or sudden drop in electrolytes from dialysis
Ankle swelling caused by
fluid build up - (also maybe amlodipine)
Nocturia caused by
kidney not concentrating urine enough and not producing ADH for nighttime
instead of weigh MDRD uses
standardised body s.a
HCO3
bicarbonate
PO4
Phosphate
PTH levels increase from
low calcium (PTH increases production of Ca through bone reacbsorption)
How to treat high PTH
activated vitamin D
