Kidney Damage

Question 1

What is Acute kidney Injury?

Answer 1

Occurs over short time-days to weeks

Question 2

What is chronic kidney damage?

Answer 2

months to years of damage

Question 3

How is AKI diagnosed?

Answer 3

Serum creatinine and/or urine output

Question 4

Creatinine levels for AKI

Answer 4

Stage 1 AKI: Rise of ≥26 µmol/L within 48 hours or 1.5–2 times the baseline creatinine.

Stage 2 AKI: Rise to 2–3 times the baseline creatinine.

Stage 3 AKI: Rise to ≥3 times baseline or above 354 µmol/L, or the need for dialysis.

Question 5

Urine output

Answer 5

Urine Output Criteria:

Stage 1 AKI: <0.5 mL/kg/hr for 6 hours.

Stage 2 AKI: <0.5 mL/kg/hr for 12 hours.

Stage 3 AKI: <0.3 mL/kg/hr for 24 hours or no urine (anuria) for 12 hours.

Question 6

What are the three categories of kidney injury

Answer 6

Prerenal – due to reduced blood flow to the kidney.

Intrinsic Renal – due to damage within the kidney itself.

Postrenal – due to obstruction of urine flow after it leaves the kidney.

Question 7

AKI causes

Answer 7

Intrinisic renal causes are majority,
Prerenal one third
post renal, one quarter

Question 8

Prerenal kidney injury

Answer 8

reduced perfusion to the kidneys.
Shock-sepsis, heart failure, fluid loss/haemorrhage
Without shock intravascular volume depletion-reduced fluid intake, increased fluid loss, oedema causing fluid redistribution
stenosis of renal artery, thrombosis of vein or artery, cancer affecting blood flow

Question 9

Glomerulus and GFR regulation

Answer 9

GFR (Glomerular Filtration Rate) is regulated by the tone of the afferent and efferent arterioles.

Increased afferent arteriolar tone or decreased afferent arteriolar tone reduces GFR.

Drugs affecting vascular tone and GFR include:

NSAIDs: constrict the afferent arteriole, reducing GFR.

Calcineurin inhibitors: affect renal blood flow and reduce GFR.

ACE inhibitors: dilate the efferent arteriole, reducing GFR.

Question 10

Proximal Convoluted Tubule (PCT)

Answer 10

SGLT2 inhibitors (e.g., Dapagliflozin) inhibit glucose reabsorption and promote glucosuria, helping to lower blood glucose in diabetes.

Uricosuric drugs (e.g., Probenecid, Losartan) inhibit organic anion transporters, increasing uric acid excretion and benefiting patients with gout.

Carbonic anhydrase inhibitors (e.g., Acetazolamide, Topiramate) interfere with bicarbonate reabsorption, causing proximal renal tubular acidosis.

Mitochondrial toxins (e.g., Tenofovir, Adefovir, Dimethyl fumarate) damage proximal tubular cells due to their high energy demands, leading to Fanconi syndrome or acute tubular necrosis

Question 11

Loop of henle

Answer 11

The NKCC2 (Na⁺-K⁺-2Cl⁻ cotransporter) is the primary salt transporter in the thick ascending limb.

Loop diuretics (e.g., Furosemide, Bumetanide, Torasemide) inhibit NKCC2, mimicking Bartter syndrome.

Effects of loop diuretics and Bartter syndrome:

Diuresis and decreased blood pressure.

Hypokalemia (potassium loss).

Metabolic alkalosis (due to sodium delivery to the collecting duct).

Hypercalciuria (impaired calcium reabsorption via paracellular route).

Question 12

DCT

Answer 12

The NCC (Na⁺-Cl⁻ cotransporter) is the main transporter in the DCT.

Thiazide diuretics (e.g., Bendroflumethiazide, Hydrochlorothiazide, Metolazone) inhibit NCC, mimicking Gitelman syndrome.

Effects of thiazides and Gitelman syndrome:

Diuresis and reduced blood pressure.

Hypokalemia and metabolic alkalosis.

Hypocalciuria (enhanced calcium reabsorption via transcellular route).

Question 13

Colecting duct

Answer 13

Principal Cells – Sodium and Water Handling
Sodium is reabsorbed via ENaC (epithelial sodium channel).

ENaC inhibition (e.g., by Amiloride) or PHA1 (pseudohypoaldosteronism type 1):

Causes diuresis, hyperkalemia, and metabolic acidosis.

Liddle syndrome and mineralocorticoid agonists (e.g., aldosterone) upregulate ENaC:

Cause hypertension, hypokalemia, and metabolic alkalosis (opposite effects of ENaC inhibition).

Water reabsorption occurs via aquaporins, controlled by vasopressin (ADH).

NDI (nephrogenic diabetes insipidus) results from disruption in aquaporin or vasopressin pathways.

Vaptans (e.g., Tolvaptan) inhibit vasopressin receptors (V2), causing aquaresis and hypernatremia due to free water loss.

Intercalated Cells – Acid/Base Regulation
Alpha intercalated cells secrete acid (H⁺) into urine.

Beta intercalated cells secrete bicarbonate (HCO₃⁻).

Carbonic anhydrase inhibitors (e.g., Acetazolamide, Topiramate):

Disrupt function of alpha cells, causing distal renal tubular acidosis.

Lead to metabolic acidosis, hypokalemia, and hypercalciuria.

Also impairs proximal tubular bicarbonate reabsorption, thus cause both proximal and distal RTA.