PHAR3911 - Kidneys

outline the excretory functions of the kidneys

excretion of metabolic waste (urea, creatine), bioactive substances (hormones, drugs) and toxins

outline the endocrine functions of the kidneys

erythropoietin (RBC production)

Renin (RAAS BP regulation)

Prostaglandins

outline the regulatory functions of the kidneys

water balance (urine)

electrolyte balance

outline the metabolic functions of the kidneys

activation of vitamin D

what is the anatomy of the kidney?

what is the filtration process of the kidneys?

occurs at glomerulus filter

small molecules able to pass through membrane

GFR indicates renal function

blood in urine indicates glomerular damage

how are prostaglandins and Ang-II involved in filtration?

PG control size of afferent arteriole

AT-II control size of efferent arteriole

example: less salt = PG widens afferent Ang-II closes efferent

what are the THREE endogenous markers for kidney function?

Creatine

Urea

Albumin and blood (glomerular -ve -> disease/ damage can neutralise -> -ve albumin normally rapelled now pass thru -> 3m = damage often CKD)

what are the main factors influencing serum creatinine?

age (old have lower)

gender (female have lower)

malnutrition (lower)

medications (trimethoprim increases)

what is acute kidney injury?

abrupt decline in renal function leading to increase in serum concs of urea, creatine, and other substances

reversible if identified early

what are the THREE ways of acquiring AKI?

Community-acquired (elderly)

Hospital-acquired (surgery or drug-induced)

ICU-acquired (septic shock)

what is the main biomarker and mortality risk of AKI?

biomarker is GFR

24-48 hours delay between damage/cell death to see increased serum creatine from reduced GFR

what is the Dx criteria for AKI?

increase serum creatine >25umol/L within 48 hours

OR

increase 1.5x baseline 7days prior

OR

significant reduction in output

what are the THREE categories of AKI?

1. pre-renal (organ before kidney e.g heart not enough blood)

2. intra-renal (direct kidney tissue damage)

3. post-renal (obstruction of urethra)

how does ACEI + NSAID combination affected patients with kidney stress?

NSAIDS block action of PG

ACE1/ARB block action of Ang-II

can lead to renal failure

what are the clinical manifestations of AKI?

hypertension, oedema, n/v, dark urine

what are the key aspects of AKI prevention?

identify high-risk patients

fluid therapy

stop nephrotoxic drug therapy until kidneys are normal (SADMAN)

monitor renal function

adjust doses

what are they key steps to treatment of pre-, intra-, and post- renal AKI?

Pre-renal: remove offending medication

Intra-renal: fluids, remove medication, wait for recovery

pot: relieve obstruction

what are the THREE steps Hyperkalaemia (K+>6.5mmol/L) Tx?

1. calcium gluconate to stabilize

2. insulin (carry K+ back into cells)

3. ion exchange resin hemodialysis

define Chronic Kidney Disease (CKD)

kidney damage

GFR <60ml/min for 3 months

long term preventable health condition

typically asymptomatic until most of function lost

what are NINE risk factors for CKD?

1. diabetes

2. uncontrolled hypertension

3. CVD

4. Family Hx

5. obesity

6. smoking

7. >60

8. ATSI

9. AKI Hx

what are the TWO main causes of CKD?

Diabetes (T2D)

Hypertension

how is CKD linked to CVD?

causes vasoconstriction -> exacerbate hypertension

pressure on heart -> CVD

what are FIVE non-pharmacological management strategies for CKD?

1. smoking cessation

2. diet (limit salt)

3. alcohol limit

4. physical activity

5. weight management

how to preserve renal function in CKD patients?

manage hypertension with ACE or ARB (Ramipril) and or CCB (amlodipine)

what is the Tx and link between lipids and CKD?

CKD can alter lipid metabolism -> increase LDL, TG, VLDL

Tx: if pt >50 years old + GFR >60 = statin OR <60 = statin + ezetimibe

if pt <50 = statin

how to manage Na+ balance in CKD patients?

diuretics -> inhibit sodium reabsorption -> reduce risk of retention -> oedema

thiazides (idapamide) or loop (frusemide) or K+ sparing (spironolactone) risky

limit salt intake

how to manage metabolic acidosis in CKD patients?

acid-base balance hindered by CKD

sodium bicarbonate (SodiBic)

how to manage pruritis in CKD patients?

often in stage 4 and 5

emollients

avoid soaps

primrose oil

UVB therapy

how to manage vit D and phosphorus metabolism issues in CKD patients?

kidney involved in bone metabolism (phosphate excretion, vit D activation) -> risk of bone diseases (osteoporosis)

Tx:

1. phosphate (diet + binding agents)

2. calcium

3. vitamin D

how to manage anemia in CKD patients?

caused by reduced EPO synthesis and iron absorption

Tx: iron supplement -> target Hb 100-115g/L -> decrease morbidity

SE: increase blood viscosity -> increase BP -> CV risk

what are the THREE Tx options for End-Stage Kidney Disease (ESKD)?

1. Renal Replacement Therapy (dialysis)

2. Transplant

3. supportive care

how to determine whether dialysis should be initiated?

A - acidosis

E - electrolyte imbalance (K+)

I - intoxicants

O - overload

U - uremia (sickness)

GFR 15mL/min or less

what are the two processes that make up dialysis?

diffusion and convection

what are the TWO modalities of dialysis?

1. peritoneal dialysis (PD) - catheter in abdomen multiple times a day

2. hemodialysis (HD) - blood through machine multiple times a week (4-6h at least 3 times)

what is an AV fistula in hemodialysis?

surgical connection of veins in the arm

allows blood flow >400 mL/min

high pressure fast flow facilitates dialysis

what are the pros and cons of hemodialysis?

pros: 3 treatments per week, no at home equipment

cons: travel, restricted diet, infection risk

what are the TWO methods of peritoneal dialysis?

CAPD

APD (overnight)

what is the process of peritoneal dialysis?

drain

flush

fill

dwell

what are the pros and cons of peritoneal dialysis?

pros: flexible with lifestyle, can be asleep, can travel

cons: permanent catheter, infection risk, weight gain

how is drug dosing affected by dialysis?

drugs that are likely to be cleared by the dialysis should be dose afterwards to avoid Tx failure

what are the benefits and side effects of renal transplantation?

benefit: extend life, improve QOL

side effects: immunosuppression, infection risk, long term cancer risk

what are the THREE risk factors of drug-induced kidney disease (DIKD)?

1. CKD Hx

2. Elderly

3. Infection/ critical illness

what are the FOUR classes of drugs that can worsen renal function?

1. Diuretics

2. ACE/ARB

3. NSAIDs

4. Antihypertensives

what are THREE classes of drugs that cause direct nephrotoxicity?

1. antimicrobials (amp-B, gentamicin)

2. anticancer (methotrexate)

3. Immunosuppressants (cyclosporin)