Diuretics
| Class | Drugs | Site of Action | Mechanism | Key Electrolyte Effects | Clinical Use |
|---|---|---|---|---|---|
| Loop diuretics | Furosemide (Lasix), torsemide, bumetanide, ethacrynic acid | Thick ascending loop of Henle | Inhibit Na-K-2Cl cotransporter (NKCC2) → block Na/K/Cl reabsorption → massive water/electrolyte loss | ↓K+, ↓Mg2+, ↓Ca2+, ↓Na+, metabolic alkalosis; ototoxicity (high IV doses or with aminoglycosides) | AKI (oliguric phase), CHF (acute decompensation), pulmonary edema, hypercalcemia, hyperkalemia, CKD; most potent diuretics |
| Thiazide diuretics | Hydrochlorothiazide (HCTZ), chlorthalidone (preferred), metolazone | Distal convoluted tubule (DCT) | Inhibit Na-Cl cotransporter (NCC) → moderate Na/water excretion | ↓K+, ↓Na+, ↓Mg2+, ↑Ca2+ (unique — reabsorb calcium!), hyperuricemia, hyperglycemia; metabolic alkalosis | Hypertension (1st-line per JNC), CHF, edema, nephrolithiasis (calcium stones — reduces urinary calcium), nephrogenic DI (paradoxical); ineffective when GFR <30 |
| Potassium-sparing | Spironolactone, eplerenone (MRAs); triamterene, amiloride (ENaC blockers) | Collecting duct | MRAs: block aldosterone receptor → block Na reabsorption + K excretion. ENaC blockers: directly block Na channels | ↑K+, mild ↓Na+, acidosis; gynecomastia (spironolactone — anti-androgen effect) | Ascites/CHF (spironolactone); hypokalemia prevention; primary hyperaldosteronism (spironolactone); Liddle syndrome (amiloride) |
| Carbonic anhydrase inhibitors | Acetazolamide (Diamox) | Proximal tubule | Inhibit carbonic anhydrase → reduce HCO3- reabsorption → bicarbonaturia, diuresis, metabolic acidosis | ↓K+, metabolic acidosis, ↓HCO3- | Altitude sickness, glaucoma (reduces aqueous humor), metabolic alkalosis (short-term), pseudotumor cerebri |
| Osmotic diuretics | Mannitol | Entire nephron | Non-reabsorbable solute → osmotic water retention in tubule → increased urine output | Initial hypernatremia, then dilutional hyponatremia; ↑K+ transiently | Cerebral edema (ICP reduction), acute glaucoma, drug overdose, oliguric AKI (prevent tubular obstruction); contraindicated in anuria, HF, pulmonary edema |
🧠 Mnemonic — Diuretic Sites: The LOOP Goes Thick, THIAZIDE Distal, SPIRO CollectsLoop → Thick ascending limb. Thiazide → Distal convoluted tubule. Spironolactone/amiloride → Collecting duct. Acetazolamide → Proximal tubule.
ACE Inhibitors, ARBs & ARNi
| Class | Examples | Mechanism | Adverse Effects | Key Indications & Contraindications |
|---|---|---|---|---|
| ACE Inhibitors (ACE-I) | Lisinopril, enalapril, ramipril, captopril, benazepril | Inhibit ACE → block angiotensin I → angiotensin II conversion → vasodilation, ↓aldosterone, ↓Na/water retention; also block bradykinin degradation → accumulation | Dry cough (10–15%, from bradykinin accumulation — switch to ARB), angioedema (rare but dangerous, especially Black patients), hyperkalemia, AKI (in bilateral RAS), teratogenic (fetal toxicity — contraindicated in pregnancy) | HFrEF, post-MI, diabetic nephropathy, proteinuria reduction, HTN. Contraindicated: bilateral RAS, pregnancy, prior ACE-I angioedema, hyperkalemia K+ >5.5 |
| ARBs (Angiotensin Receptor Blockers) | Losartan, valsartan, irbesartan, olmesartan, candesartan, telmisartan | Block AT1 receptor for angiotensin II → similar effects to ACE-I; NO bradykinin accumulation → no cough | Hyperkalemia, AKI (bilateral RAS), teratogenic; NO cough; angioedema extremely rare | Same indications as ACE-I; preferred when ACE-I causes cough. Do NOT use ACE-I + ARB together (dual RAAS blockade → worse outcomes — ONTARGET trial) |
| ARNi (Angiotensin Receptor-Neprilysin Inhibitor) | Sacubitril/valsartan (Entresto) | Sacubitril (neprilysin inhibitor) → increases natriuretic peptides (ANP, BNP) → vasodilation, natriuresis; + ARB (valsartan) component | Hypotension, hyperkalemia, angioedema (risk if switching from ACE-I — wait 36 hours); do NOT use with ACE-I | HFrEF (EF ≤40%): PARADIGM-HF trial showed superior to enalapril in reducing CV death/HHF; replace ACE-I or ARB in GDMT |
🎯 Boards PearlACE-I cough: due to bradykinin accumulation (ACE also degrades bradykinin). Switch to ARB — no cough. Lisinopril-induced angioedema: do NOT re-challenge with ACE-I; can use ARB cautiously (different mechanism, very rarely cross-reacts). Both ACE-I and ARBs reduce intraglomerular pressure (dilate efferent arteriole more than afferent) → INCREASE serum creatinine slightly at initiation (acceptable up to 30% rise) → reduce long-term progression of CKD and diabetic nephropathy.
SGLT-2 Inhibitors in CKD
| Drug | CKD Indication | Trial Evidence | Notes |
|---|---|---|---|
| Dapagliflozin (Farxiga) | CKD with or without T2DM (eGFR 25–75) | DAPA-CKD: 39% reduction in composite of worsening kidney function, ESRD, or death | FDA-approved for CKD. Continue down to eGFR 25; stop when <20 (drug ineffective). HbA1c lowering is less important at low GFR |
| Empagliflozin (Jardiance) | CKD with or without T2DM | EMPA-KIDNEY: benefit across wide range of CKD; reduced kidney disease progression and CV death | FDA-approved for CKD (2023). Broad CKD indication including non-diabetic CKD |
🏥 KDIGO 2022 CKD GuidelinesFor T2DM + CKD: metformin + SGLT-2 inhibitor is the cornerstone combination. SGLT-2 inhibitors should be offered to all T2DM + CKD patients if eGFR ≥20 and tolerated — regardless of whether diabetes is controlled. GLP-1 agonists as add-on for CV/obesity benefit. RAAS blockade (ACE-I or ARB): max tolerated dose for proteinuria reduction and BP control. Target BP <130/80 for most CKD patients.
Phosphate Binders (CKD-Mineral Bone Disease)
| Drug | Type | Notes |
|---|---|---|
| Calcium carbonate (Tums), calcium acetate (PhosLo) | Calcium-based binders | Inexpensive; effective; risk of hypercalcemia and vascular calcification with long-term use — limit if calcium >10.2 or history of vascular calcification |
| Sevelamer carbonate/HCl (Renvela/Renagel) | Non-calcium, non-absorbed polymer | Preferred in dialysis patients; also lowers LDL; no calcium load; may cause GI side effects; more expensive |
| Lanthanum carbonate (Fosrenol) | Non-calcium, non-absorbed metal | Chewable; effective; lanthanum accumulation in bones (theoretical concern with very long-term use) |
| Sucroferric oxyhydroxide (Velphoro) | Iron-based binder | Low phosphorus dose needed; may also treat iron deficiency; GI side effects; stool discoloration (black) |
Erythropoiesis-Stimulating Agents (ESAs)
| Drug | Indication | Target Hgb | Key Points |
|---|---|---|---|
| Epoetin alfa (Epogen, Procrit) | Anemia of CKD (decreased EPO production), anemia of chemotherapy, HIV-related anemia | 10–11.5 g/dL (CKD not on dialysis: <11 g/dL per KDIGO) | SQ injection. Assess iron stores before starting (ESA resistance with iron deficiency). Black box warning: avoid targeting Hgb >11 → increased CV events, stroke, VTE, tumor progression |
| Darbepoetin alfa (Aranesp) | Same as epoetin; longer half-life → less frequent dosing | 10–11.5 g/dL | Once every 1–4 weeks dosing vs. epoetin 1–3×/week; same risks |
🎯 Boards PearlBefore ESA therapy: replete iron (ferritin >200 mcg/L, TSAT >20% preferred). Pure red cell aplasia (PRCA): rare but serious complication of epoetin — anti-EPO antibodies → treat by stopping ESA, possible immunosuppression. ESA use in CKD not on dialysis: only initiate Hgb <10 g/dL and clinical scenario warrants it. Do NOT target Hgb >13 g/dL with ESAs (increased CV events — TREAT trial).
Potassium Binders
| Drug | Mechanism | Key Points |
|---|---|---|
| Patiromer (Veltassa) | Non-absorbed polymer binds K+ in GI tract → fecal excretion | Works in colon; onset 7+ hours; do NOT give within 3 hours of other oral medications (reduces absorption); safe long-term; preferred for chronic hyperkalemia. Can allow continuation/initiation of RAAS therapy |
| Sodium zirconium cyclosilicate (Lokelma) | Microporous crystal selective for K+ → traps K+ in GI tract | Faster onset than patiromer (onset ~1 hour); can be used for acute hyperkalemia management; contains sodium (caution in HF, CKD with volume overload) |
| Sodium polystyrene sulfonate (Kayexalate) | Ion exchange resin binds K+ in gut | AVOID — associated with intestinal necrosis (especially with sorbitol); limited evidence; rarely used now; sodium load |
Sodium Bicarbonate in CKD
| Indication | Goal | Notes |
|---|---|---|
| Metabolic acidosis in CKD (serum HCO3- <22 mEq/L) | Maintain serum HCO3- >22 mEq/L | Oral sodium bicarbonate (650mg tablets); protects against bone disease, muscle wasting, progression of CKD. Caution with sodium load in volume-overloaded or hypertensive patients. Monitor BP and edema. Alternate: sodium citrate (Bicitra) |