STEPTRACKERPHARMACOLOGY | RENAL | HIGH-YIELD REVIEW

RAAS & Other Renal Drugs

The renin-angiotensin-aldosterone chain can be cut at four points; beyond it sit drugs for electrolytes, stones, bladder and kidney protection, plus the drugs that harm kidneys.

FOCUS ON
RAAS blockade: aliskiren (direct renin inhibitor) → ACE inhibitors (block AT I → AT II and bradykinin breakdown) → ARBs (AT1 block) → MRAs (aldosterone receptor). All: ↑ K⁺, ↓ GFR acutely, teratogenic; contraindicated in bilateral renal artery stenosis. ACEi only: cough, angioedema (bradykinin; also hereditary C1-INH deficiency is a contraindication). SGLT2 inhibitors slow CKD. Hyperkalemia: calcium gluconate (stabilize membrane) → insulin + glucose, β2 agonist, bicarbonate (shift) → loop diuretic, patiromer, sodium zirconium cyclosilicate, dialysis (remove). CKD-mineral: phosphate binders (sevelamer, calcium acetate, lanthanum), calcitriol, cinacalcet (calcimimetic). Anemia of CKD: erythropoietin (↑ BP, thrombosis). Stones: thiazide (Ca²⁺), potassium citrate (Ca²⁺, uric acid, cystine), allopurinol (urate). Nephrotoxins: NSAIDs, aminoglycosides, amphotericin B, IV contrast, cisplatin, vancomycin, calcineurin inhibitors, acyclovir, lithium.
DRUG · GROUP
MECHANISM
USE
KEY POINTS
Aliskiren
Direct renin inhibitor → ↓ angiotensin I
Hypertension
Not with ACEi/ARB (diabetes) · ↑ K⁺, teratogenic
ACE inhibitors
Block ACE → ↓ AT II, ↓ aldosterone, ↑ bradykinin; ↑ renin (loss of feedback)
HTN, HFrEF, diabetic nephropathy, post-MI
Cough, angioedema, ↑ K⁺, ↑ creatinine, fetal renal damage
ARBs
AT1 receptor antagonist; ↑ AT II and renin
Same as ACEi
No bradykinin effects; losartan uricosuric
Mineralocorticoid antagonists
Block aldosterone at collecting duct
Hyperaldosteronism, HF, ascites
↑ K⁺, antiandrogen (spironolactone)
Hyperkalemia — stabilize
IV calcium gluconate/chloride
ECG changes (peaked T, wide QRS)
Doesn't lower K⁺; works in minutes
Hyperkalemia — shift
Insulin (+ glucose), albuterol, sodium bicarbonate
Temporary K⁺ entry into cells (Na⁺/K⁺-ATPase)
Watch hypoglycemia
Hyperkalemia — remove
Loop diuretic, patiromer, sodium zirconium cyclosilicate, sodium polystyrene sulfonate, dialysis
Total-body K⁺ elimination
Binders work in hours; dialysis definitive
Phosphate binders
Sevelamer, calcium acetate/carbonate, lanthanum
Hyperphosphatemia of CKD
Calcium binders → hypercalcemia, vascular calcification
Calcitriol · cinacalcet
Active vitamin D · ↑ Ca²⁺-sensing receptor sensitivity → ↓ PTH
Secondary hyperparathyroidism
Cinacalcet → hypocalcemia
Erythropoiesis-stimulating agents
Epoetin, darbepoetin
Anemia of CKD (give iron too)
Hypertension, thrombosis; target Hb ≤ 11–12
Potassium citrate
Alkalinizes urine; citrate chelates Ca²⁺
Calcium oxalate, uric acid and cystine stones
Hyperkalemia in CKD
Nephrotoxic drugs
Hemodynamic: NSAIDs, ACEi, calcineurin inhibitors · tubular: aminoglycosides, amphotericin, cisplatin, contrast · interstitial: penicillins, PPIs · crystals: acyclovir, methotrexate, indinavir
—
Hydrate, dose by GFR, avoid combinations

Mechanism — where RAAS can be blocked

Angiotensinogen
→
ReninAliskiren
→
ACE-prils (also stops bradykinin breakdown)
→
AT1 receptor-sartans
→
Aldosterone receptorSpironolactone, eplerenone

Triple whammy AKI

DRUG
GLOMERULAR EFFECT
RESULT
NSAID
Afferent constriction (↓ PGs)
↓ Inflow
ACEi / ARB
Efferent dilation
↓ Filtration pressure
Diuretic
↓ Volume
↓ Perfusion

How it's tested

COMMON CONFUSIONACE inhibitors and ARBs raise renin (lost negative feedback); only aliskiren lowers renin activity.
THE TRAPIn hyperkalemia with ECG changes, calcium comes first — it protects the heart but doesn't lower potassium.
YOUR APPROACHHyperkalemia: stabilize → shift → remove. CKD: BP + proteinuria (ACEi/ARB, SGLT2i) → anemia → bone-mineral.

If you see… think…

Angioedema on ACEi → bradykinin; switch class (ARB with caution)
Peaked T waves → IV calcium gluconate first
Drug that lowers K⁺ by shifting it into cells → insulin + glucose, albuterol
Secondary hyperparathyroidism in CKD → cinacalcet, calcitriol, phosphate binder
Non-calcium phosphate binder → sevelamer
Hypertension after EPO in CKD → erythropoietin effect
AKI after NSAID + ACEi + diuretic → triple whammy
Direct renin inhibitor → aliskiren
Stone prevention for uric acid or cystine → potassium citrate
Rising creatinine with crystals after IV antiviral → acyclovir