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Medicines in Kidney + Transplant - Coggle Diagram
Medicines in Kidney + Transplant
Kidney disease signs
Fluid Overload:
oedema and hypertension
Electrolyte imbalance:
hyperkaelemia, hyperphosphatemia and hypocalcaemia.
Acid-base imbalance:
acidosis
Impaired excretion:
uraemia (N/V), gout and protein/blood excretion
Impaired hormonal function:
anemia, hypocalcaemia and hyperthyroidism + impaired BP
Impaired drug excretion:
toxicities.
Classification
Acute Renal Failure:
rapid onset (with hours and days) + identifiable cause and potentially reversible.
Anything that can cause hypoperfusion (reduce blood supply to kidney), intrinsic damage (physical/immune damage to nephron) or kidney obstruction (kidney stones)
Chronic Renal Failure:
develops over months to years, a progressive irreversible decline in kidney function.
Anything that speeds up permanent damage.
Diagnosis
History + Physical examination (family history, dysuria/infection, nocturia)
Urinalysis and culture of fresh urine
Renal imaging: ultrasound or flowscan
Renal Biopsy
Renal function tests: Serum creatinine, urea, GFR.
Assessment of renal function:
Serum Creatine: useful for quick view on long term trend but SeCr changes only seen when >50% of kidney function is gone.
GFR: cockroft-gault formula or MDRD, simple calculations but requires height, weight and sex.
End Stage Renal Disease (GFR <15mL/min)
Treatment options:
Peritoneal Dialysis
Transplant
Haemodialysis
Haemodialysis:
removal of waste and solutes from the body by perfusing blood and dialysate across a semi-permeable membrane.
Takes 3-5 hours
Peritoneal dialysis:
Instil dialysis fluid (glucose solution) into peritoneal cavity. Removal of waste product via osmotic diffusion into the glucose solution.
Potential infection (glucose environment perfect for bacterial growth)
Better than haemodialysis as it portable.
Causes of death:
Cardiac (40%), Social factors (27%), infection, malignancy, vascular and others (33%)
Causes of ESRD
: - High BP and Protein in kidneys causes damage
Glomerulonephritiis (30%)
: Immune reaction causing inflammation of the glomeruli allowing proteins to leak through into kidneys and nephrons.
Diabetic Nephropathy (30%)
: Albumin in urine causing damage. Good diabetic control reduces albumin in the urine
Hypertension:
cause and sign of renal failure. Occurs due to compensatory mechanism to maintain GFR. Improving BP can improve outcome and progression targeting BP of 130/80
Diabetic Nephropathy:
Insulin (clearance is dependent in renal function)
Metformin (not recommended in GFR < 60mL/min)
Sulphonylureas: Gliclazide is safest (shorter t1/2 and no active metabolites)
DPP4i: sitagliptan (Januvia) is extensively cleared, use with caution.
Glomerulonephritis treatment:
Immunosuppressant (if immune reaction) - prednisolone, cyclophosphamide, cyclosporin.
Antiproteinuric therapy - ACEi/ARBs
Acid Suppression: PPI (due to high dose of steroids)
Antibacterial prophylaxis: Bactrim (during cytotoxic therapy) or Resprim
Statins: low albumin levels due to excretion - liver ramps up protein production which also ramps up lipid production.
Hypertension:
ACEi/ARB: careful of renal function, can reduce function but stables out
Beta-blockers and diuretics
CCBs (similar reduction in BP but less antiproteinuric properties, verapamil and ditiazem have similar effect)
Nephrolithiasis (Kidney Stones)
More than 90% due to calcium deposits and ammonium phosphate.
3% Uric acid
1 % Cystine
Treat with:
Increased fluid intake to increase solubility
More acidic to change solubility
Surgery to physically remove
Signs and Symptoms of CRF and Uraemia
GI Signs:
Nausea and vomiting, Weight loss
Fatigue and Lethargy:
Anaemia
Uraemic Pericarditis:
inflammation of the pericaridum in the heart
Cardiac:
Pulmonary Oedema, enlarged heart
Bones and Joints:
Bone pain and gout
Neurological:
Poor concentration and sleep
Skin:
Itchy and eruptions
Ususally asymptomatic until GFR is less than 15. Symptoms occur when there's a build up of uraemic toxins.
There is not official GFR
Renal Anaemia
Reduced RBC production:
Reduced EPO production in the kidney causing iron and folate deficiency.
Increased RBC loss:
RBC fragility and acute blood loss.
Treatment:
Treat underlying cause first.
Erythropoietin (ESAs)
- Stimulates production of RBC. Erythropoietin Beta has less injection pain.
Check other potential causes such as bleeding before use
Iron Supplement
- IV is preferred, quick effect and no absorption limit and GIT upset.
Vitamin B, C and Folate
- due to overall reduced intake of food
Transfusion in serious cases
- rapidly correct Hb but increases risk of antibody formation , increasing risk of kidney rejection
Immunosuppression cover in transfusions: Cyclsporins, azathioprine or mycophenolate
Aim to correct haemoglobin and not restore to baseline/normal range to prevent overshooting and minimise rapid Hb rise.
CKD Mineral and Bone Disorder
Hyperphosphatemia and PTH build up
Renal failure reduces conversion of vitamin D into active form, thus reducing calcium absorption and increasing PTH levels.
Increased PTH
causes breakdown of bone to maintain calcium levels in the blood.
Thus
renal osteodystrophy
occurs
High phosphate levels can cause extraskeletal calcification. Calcium and Phosphate complex in the blood causes vascular calcification, hardening the blood vessels = increasing CVD risk and complications.
Build up of phosphate also increases PTH to reduce phosphate absorption, but that also increases calcium reabsorption from the bone.
Treatment
Phosphate management: Restriction in phosphate intake from diet and provide adequate dialysis to flush phosphate out.
Phosphate binders with meals
calcium carbonate (cheap and accessible)
aluminium phosphate binders (potent but expensive and potential aluminium build up toxicity)
renagel (low potentcy and expensive but works)
lanthanum (rare earth element = expensive, high potency and not absorbed)
velphoro (well tolerated but some mild diarrhoea and dark stools)
Vitamin D/analogs: to reduce phosphate levels due of vitamin D deficiency
given active form of vitamin D (calcitriol)
Calcium supplement and calcimimetics (cinacalcet)
Parathyroidectomy
Calciphylaxis:
Soft tissue calcification cuasing pain and requires amputation.
Treatment: oxygen tank
Administer
sodium thiosulphate
to reverse precipitation
Stopping warfarin to prevent worsening, due to warfarin promoting calcium deposition leading to calciphylaxis
Hyperkalemia
Treatment:
Modify diet to reduce K intake
Modify drugs (ACEi/ARBs and spironolactone)
Binding resin (Resonium 15-30g oral)
IV Insulin + Dextrose (shift glucose to shift K),
Salbutamol (shifts K intracellularly)
Dialysis (physical filtering)
Acid Base Imbalance
Body produces 1mmol/kig of metabolic acid daily and buffered by kidney's by producing bicarbonate.
- Imbalance treatment
= Sodibic (Sodium bicarbonate 840mg) 1-2 sachets tds OR add to dialysis filtrate
Bleeding and Anticoagulation
CKD patients have higher risk of bleeding.
LMWH accumulate in CKD thus use with care
Standard Heparin, Warfarin and Antiplatelets are dosed as normal initially.
Gout and Hyperuricemia
Renal Impairment builds up uric acid = increase potential for gout attacks
Allopurinol
100-200mg daily recommended due to active metabolite uses renal clearance.
Probenecid - for gout and hyperuricemia may require higher doses to get into kidney.
Caution with colchine (renally cleared) and Avoid NSAIDs
Restless Leg Syndrome
Distrubs sleep
Treatment:
BZD (Clonazepam 0.5mg nocte) or Levo/carbidopa (100/25mg nocte)
Oedema and fluid overload
Reduced urine output and low albumin levels
Treatment
Loop diuretics (Frusemide)
GI Problems
Commonly experience anorexia, nausea, vomiting and constipation
Treatment
Dialysis
Antacids
PPIs
Coloxyl Senna or Sorbitol
Transplantation
Immune response to the antigens on the donated organ triggers T and B cell response. Matching blood type, HLA and cross-matching essential in minimising major rejection.
Immunosuppressant Therapy
Calcineurin Inhibitor:
prevents NFAT translation thus prevent T-cell proliferation
Cyclosporin - used in very low/low risk transplant
Side effects: nephrotoxicity, aesthetic changes (hair growth), HTN and hyperlipidaemia
Tacrolimus - used in moderate to high risk transplant
Nephrotoxicity, HTN, Diabetes, Hyperlipidaemia
Antiproliferative agents:
inhibits proliferation by blocking or disruptiing DNA base chains
Azathioprine - replaced with mycophenoate but used if cost is an issue for patient.
Side effects: skin photosensitivty, haematological reduction
Mycophenoate - IMPDH inhibitor selective of T and B cells, better ADRs than Azathiopurine and used in low to high risk patients.
Side effects: GI and Haemto effects
Steroids:
to reduce inflammation and use its immunosuppresant side effect
Prednisolone - used in all approach of transplant
Switch from CNI in 4 months for very low risk patients
Fast taper for low risk patients
Slow taper for moderate to high risk.
Anti-body Induction:
Anti-IL2 antibodies to prevent T-cell proliferation. Used in high risk patient to prevent rejection not treat.
Basiliximab - Dose given 2hr before surgery and 4 days post-op.
Effect lasts for 4-6 weeks used in low to moderate risk.
Anti-thymocyte globulin - used in high risk.
mTOR inhibitors:
blocks the signals after IL-2 activation
Sirolimus - once daily for long term maintenance
Everolimus - BD dosing
switch from CNI in 4-6 months for very low to moderate risk and 12 months for high risk
Less malignancy vs CNI and doesn't increase BP.
Side effects: delayed wound healing, hyperlipidaemia and haematological effects
General immunosuppressed side effects
Infection: increase risk and reduced ability to fight infection.
Most common in weeks/months of therapy with UTIs, wounds and respiratory being most common.
Malignanacy: All cancers but prostate and breast increased risk.
Sun cancers can be prevented with sunscreen.
Acute Rejection
Methylprednisolone:
Short IV course (1g IV daily for 3 days) to help swelling and inflammation
Polyclonal antibodies:
ATG, antibodies against T-cells. Will feel trash for first few days.
Drug Interactions and TDM
P-GP and 3A4 alterations
Especially for mTOR inhibitors due to low bioavailability
Changes to 3A4 = many folds of increases or decreases in drug concentration
TDM
Most fit the criteria for TDM
Narrow TPI
Poor relationship with dose and blood concentration
potential DDIs
Generally AUC is used for TDM
Compliance
Important as body never forgets and will attack new kidney as foreign object
Cost may drive non-compliance = may switch to generic BUT don't switch if stable already.
Missed doses = take within 6-8 hours of missed dose, or skip until next dose.
Monitoring for Cytomegalovirus Disease (CMV)
Normally suppresed by immune system
With immune compromised = nasty infection
Treatment: Valcyte (prodrug to ganciclovir) for 3-6 months prophylaxis
Dosing in Renal Impairment
Assess degree of kidney damage and impairment
Assess stability: any big changes in GFR and serum creatinine
Clearance mechanism of the drug
any active metabolites (may need to reduce parent drug)
non active and non toxic metabolites may not require dose change
If Fe is low = no dose change
If Fe is high = dose change
Wide TI = No change
Narrow TI = dose change
Avoiding nephotoxic drugs if possible
PPIs and NSAIDs = Idiosyncratic reactions
Antivirals and Statins induced myopathy = block urine flow
Drugs aggravate metabolic changes
Hyperkalemia: ACEi/ARBs, K sparring diuretics and Eplerenone
Catabloic effects: Tetracycline
Sodium retention, fluid retention and anaemia
Changing doses
Dose method: reduce dose size with same intervals
Interval method: reduce intervals with same dose
Combination method: reduce dose size and increase intervals
1 - Fe(1- % renal function) = % dose reduction
Changes must be practical
Pain relief:
Avoid NSAIDs
Avoid Morphine and pethidine
Use oxycodone or fentanyl
Diuretics
Avoid thiazides (less effective in low GFR)
Avoid K sparring diuretics
Use frusemide (loop diuretics)