EASIER DIKD PDF

I. Tubular Epithelial Cell Damage A. Acute Tubular Injury/Necrosis 1. Aminoglycoside Nephrotoxicity ○ Mechanism: Accumulates in the proximal tubules, causing oxidative stress and cellular necrosis. The drug enters through endocytosis due to its cationic nature,...

I. Tubular Epithelial Cell Damage A. Acute Tubular Injury/Necrosis 1. Aminoglycoside Nephrotoxicity ○ Mechanism: Accumulates in the proximal tubules, causing oxidative stress and cellular necrosis. The drug enters through endocytosis due to its cationic nature, leading to tubular obstruction. ○ Clinical Presentation: Gradual increase in serum creatinine (SCr), decreased urine output, seen 5-7 days after treatment. ○ Diagnostics: Rising SCr and BUN, decreased creatinine clearance. ○ Management: Discontinue therapy, use alternative antibiotics like penicillin. ○ Mnemonic: "AGNs cause Acute Glomerular Nephritis slowly" 2. Radiographic Contrast Media Nephrotoxicity ○ Mechanism: Causes renal vasoconstriction via the release of adenosine and endothelin, leading to ischemia and reduced renal blood flow. ○ Clinical Presentation: Non-oliguric AKI, with SCr peaking 3-4 days after exposure. ○ Management: Avoid nephrotoxic agents, hydrate, use low-osmolar contrast. 3. Mnemonic: "Contrast = Constricts renal flow" 4. Cisplatin Nephrotoxicity ○ Mechanism: Cisplatin accumulates in proximal tubular cells, causing oxidative damage and necrosis. ○ Clinical Presentation: Polyuria, decreased serum magnesium (hypomagnesemia), hypokalemia, and hypocalcemia. ○ Management: Adjust doses, manage electrolyte disturbances. ○ Mnemonic: "Cisplatin Cells Plunder Mg and Ca" 5. Amphotericin B Nephrotoxicity ○ Mechanism: Binds to ergosterol in the kidney’s cell membrane, causing increased permeability and necrosis. It also induces vasoconstriction in afferent arterioles. ○ Clinical Presentation: Nonoliguric AKI, electrolyte wasting. ○ Management: Switch to liposomal Amphotericin, replace electrolytes. ○ Mnemonic: "Ampho tears membranes, spills electrolytes" B. Osmotic Nephropathy ○ Drugs involved: Mannitol, intravenous immunoglobulin (IVIG) containing sucrose. ○ Mechanism: High osmolar drugs cause cellular swelling and vacuolization in proximal tubular cells. ○ Presentation: Oliguria 2-4 days after exposure; cellular swelling is evident. ○ Management: Discontinue the offending agent. II. Hemodynamically Mediated Kidney Injury This results from drugs that impair kidney blood flow, affecting renal hemodynamics. 1. ACEIs and ARBs ○ Mechanism: These drugs dilate efferent arterioles, reducing glomerular pressure and thereby lowering glomerular filtration rate (GFR). ○ Risk Factors: Patients with renal artery stenosis, CHF, or pre-existing kidney disease.  ○ Clinical Presentation: AKI with rise in serum creatinine. ○ Management: Monitor SCr, discontinue if creatinine rises >30%. INITIATE LOW DOSE ○ Mnemonic: "ACE/ARB Arrest Efferent pressure" 2. NSAIDs and COX-2 Inhibitors ○ Mechanism: Inhibit prostaglandin synthesis, reducing afferent arteriolar dilation, which leads to ischemia in conditions of reduced renal blood flow. ○ Clinical Presentation: : AKI within 2-7 days, weight gain, diminished urine output, elevated BUN, SCr, and blood pressure. ○ Management: Stop NSAIDs and provide supportive care. Kidney function typically recovers in 3-5 days. ○ Mnemonic: "NSAIDs & Cox inh. Narrow Prostaglandin flow" 3. Cyclosporine & Tacrolimus ○ Mechanism: Causes vasoconstriction of afferent arterioles through increased thromboxane A2 and endothelin production, leading to reduced renal plasma flow and GFR. ○ Clinical Presentation: Hypertension, hyperkalemia, decreased GFR. ○ Management: Dose reduction, calcium channel blockers. ○ Mnemonic: "Cyclic pressure on afferents" 4. SGLT-2 ○ Mechanism: SGLT-2 inhibitors can cause volume depletion and reduce renal perfusion. They lead to prerenal AKI by reducing glomerular filtration through vasoconstriction of the afferent arteriole via tubuloglomerular feedback. ○ Clinical Presentation: AKI, volume depletion, and prerenal azotemia. ○ Diagnostics: Elevated serum creatinine and decreased GFR, urinalysis for dehydration markers. ○ Management: Discontinue the drug, ensure hydration, treat electrolyte imbalances, provide IV fluids for volume depletion. ○ Mnemonic: "SGLT Sends Glomerular Flow Low" 5. Chimeric Antigen Receptor (CAR) T-Cell Therapy ○ Mechanism: CAR T-cells trigger a cytokine release syndrome (CRS) leading to systemic inflammation, hypotension, and multi-organ toxicity, including AKI. Prerenal injury is common due to systemic hypotension, and direct tubular damage may occur due to cytokine storm. ○ Clinical Presentation: High fever, hypotension, hypoxia, multi-organ failure, and AKI, typically within days to weeks of treatment. ○ Diagnostics: AKI with rapid rise in serum creatinine, urinalysis, and signs of systemic inflammation. ○ Management: Supportive care, including vasopressors and IV fluids. Anti-interleukin-6 (IL-6) therapy (tocilizumab) and corticosteroids are used to manage severe CRS. ○ Mnemonic: "CAR-T Cells Cause Cytokine Chaos" III. Obstructive Nephropathy 1. Crystal Nephropathy ○ Drugs involved: Acyclovir, Sulfonamides, Indinavir, Methotrexate. ○ Mechanism: Precipitation of drug crystals in the renal tubules due to supersaturation or pH changes in urine. ○ Clinical Presentation: Hematuria, flank pain. ○ Management: Hydration, adjust urine pH. ○ Mnemonic: "Crystals Clog kidneys" and "Crystals Stop Inflow" Crystal nephropathy, Sulfonamides, Indinavir. 2. Vancomycin Cast Nephropathy  ○ Mechanism: Vancomycin forms obstructive tubular casts, leading to nephrotoxicity.. ○ Clinical Presentation: Sudden AKI, electrolyte imbalances. ○ Management: Discontinue vancomycin, hydrate. ○ Mnemonic: "Vancomycin Volume Casts in tubules" 3. Acute Phosphate Nephropathy Mechanism: Caused by oral sodium phosphate solutions (used for bowel cleansing) leading to calcium-phosphate precipitation in the renal tubules, which results in tubular calcification and nephrocalcinosis. Clinical Presentation: AKI developing days to months after exposure. Commonly presents with normocalcemia, low-grade proteinuria, and bland urinary sediment. Diagnostics: Elevated serum phosphate, urinalysis (low-grade proteinuria), renal biopsy shows calcium-phosphate crystals. Management: Discontinue phosphate-containing agents, aggressive hydration, and electrolyte management. Dialysis may be needed in severe cases. Mnemonic: "Phosphate Packs Kidneys with Crystals" 4. Nephrolithiasis ○ Mechanism: Formation of kidney stones due to the precipitation of drugs or their metabolites in the urinary tract, often caused by sulfonamides, triamterene, and protease inhibitors. ○ Clinical Presentation: Flank pain, hematuria, and possible urinary tract obstruction without a decrease in GFR. ○ Diagnostics: Imaging (CT or ultrasound) to identify stones, urinalysis showing hematuria and crystals. ○ Management: Hydration to maintain urine output, discontinuation of the offending drug, alkalinization of urine (for certain drugs), thiazide diuretics for calcium stones, or surgical interventions (e.g., lithotripsy) for large stones. ○ Mnemonic: "Stones Stop the Flow" IV. Glomerular Disease 1. Minimal Change Disease (MCD) ○ Drugs involved: NSAIDs, Lithium, Interferons. ○ Mechanism: T-cell dysfunction leads to cytokine release, damaging the glomerular filtration barrier and causing proteinuria. ○ Clinical Presentation: Nephrotic syndrome with proteinuria, edema, and hypoalbuminemia. ○ Management: Corticosteroids, ACE inhibitors, and ARBs to control symptoms. ○ Mnemonic: "Minimal Cells Disappear (MCD)" 2. Focal Segmental Glomerulosclerosis (FSGS) ○ Drugs involved: NSAIDs, Lithium, Sirolimus. ○ Mechanism: Podocyte injury causes glomerular scarring, leading to proteinuria and nephrotic syndrome. ○ Clinical Presentation: Proteinuria, hypertension. ○ Management: ACEIs/ARBs, immunosuppressants. ○ Mnemonic: "FSGS = Focal Scars Glomeruli" 3. Membranous Nephropathy ○ Mechanism: Immune complexes deposit in the glomerular membrane, causing proteinuria and nephrotic syndrome. Triggered by autoimmune diseases or drugs like NSAIDs and gold salts. ○ Clinical Presentation: Proteinuria (foamy urine), edema, weight gain, hypoalbuminemia.  ○ Diagnostics: Urinalysis (proteinuria), blood tests (low albumin), kidney biopsy (immune complex deposits). ○ Management: ACEIs/ARBs, diuretics, corticosteroids, immunosuppressants, statins for hyperlipidemia. ○ Mnemonic: "Membrane Mess by Immune Complexes" V. Tubulointerstitial Nephritis 1. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) ○ Mechanism: NSAIDs reduce prostaglandin synthesis, causing decreased blood flow to the renal interstitium and leading to inflammation. ○ Clinical Presentation: AKI, fever, rash, eosinophilia, oliguria. ○ Diagnostics: Elevated serum creatinine, kidney biopsy showing inflammation. ○ Management: Discontinue NSAIDs, corticosteroids if needed. ○ Mnemonic: "NSAIDs Narrow Flow to Nephrons" 2. Proton Pump Inhibitors (PPIs) ○ Mechanism: PPIs cause a hypersensitivity reaction, resulting in acute interstitial nephritis (AIN). ○ Clinical Presentation: AIN symptoms occur weeks to months after PPI exposure, often without typical signs like fever or rash. ○ Diagnostics: Kidney biopsy confirms AIN. ○ Management: Discontinue PPI, corticosteroid therapy. ○ Mnemonic: "PPIs Prick the Kidneys" 3. Immune Checkpoint Inhibitors Mechanism: Immune-related adverse effects from these drugs can trigger AIN by attacking kidney tissues. Clinical Presentation: AKI, may lack typical AIN symptoms like rash and eosinophilia. Diagnostics: Kidney biopsy required for confirmation. Management: Discontinue offending drug, corticosteroids for severe cases. Mnemonic: "Checkpoint Inhibitors Challenge the Kidneys" A. Chronic Interstitial Nephritis 1. Lithium Mechanism: Long-term lithium use damages renal tubular cells, leading to chronic inflammation and nephrogenic diabetes insipidus. Clinical Presentation: Polyuria, polydipsia, increased BUN and creatinine, bland urine sediment. Diagnostics: Kidney biopsy, routine kidney function tests. Management: Discontinue lithium, consider using amiloride to prevent nephrogenic diabetes insipidus. Mnemonic: "Lithium Loves Tubular Damage" 2. Cyclosporine and Tacrolimus  Mechanism: Calcineurin inhibitors cause vasoconstriction, leading to chronic ischemic damage in the renal interstitium. Clinical Presentation: Hypertension, hyperkalemia, decreased GFR, renal biopsy shows fibrosis. Management: Reduce dosage, switch to alternative immunosuppressants, use calcium channel blockers for vasoconstriction. Mnemonic: "Calcineurin Constricts and Causes Chronic Damage" 3. Aristolochic Acid Mechanism: Herbal products containing aristolochic acid form mutagenic compounds, causing interstitial fibrosis and tubular atrophy. Clinical Presentation: Hypertension, mild proteinuria, increased creatinine, rapid progression to end-stage kidney disease (ESKD). Management: Avoid aristolochic acid, corticosteroids may help in managing nephropathy. Mnemonic: "Aristolochic Acid Attacks Interstitium" B. Papillary Necrosis 1. Analgesic Nephropathy Mechanism: Chronic analgesic use (especially phenacetin, aspirin) depletes renal glutathione, causing papillary necrosis and interstitial nephritis. Clinical Presentation: Asymptomatic early, progressing to hematuria, proteinuria, hypertension, and renal failure. Management: Discontinue analgesics, monitor kidney function closely. Mnemonic: "Pain Pills Poison Papillae" VI. Renal Vasculitis, Thrombosis, and Cholesterol Emboli 1. Renal Vasculitis ○ Mechanism: Autoimmune attack on kidney blood vessels. ○ Management: Immunosuppressants. ○ Mnemonic: "Vasculitis Violates vessels" 2. Thrombotic Microangiopathy ○ Mechanism: Blood clot formation obstructs capillaries. ○ Management: Anticoagulants. ○ Mnemonic: "Tiny Thrombi Trouble kidneys" 3. Cholesterol Emboli ○ Mechanism: Plaque rupture leads to embolization. ○ Management: Statins, surgery. ○ Mnemonic: "Cholesterol Clots create chaos"