# Clinical Cases: Glomerular Filtration and Renal Blood Flow ## Case 1: NSAID-Induced Acute Kidney Injury ### Patient Presentation A 72-year-old male with osteoarthritis presents to his primary care physician with fatigue and decreased urine output over the past week. He has been taking ibuprofen 800 mg three times daily for the past 2 weeks for a flare of knee pain. ### History of Present Illness - Started high-dose ibuprofen 2 weeks ago - Noticed decreased urine output 5 days ago - Mild swelling in ankles - Currently taking lisinopril for hypertension and metformin for type 2 diabetes - Also recently started a low-sodium diet for blood pressure control ### Physical Examination - Blood pressure: 158/94 mmHg - Heart rate: 72 bpm - Weight: 2 kg increase from baseline - Trace bilateral pedal edema - Lungs clear to auscultation ### Workup **Laboratory Studies:** - Baseline creatinine (3 weeks ago): 1.2 mg/dL - Current creatinine: 2.8 mg/dL - BUN: 42 mg/dL - BUN:Creatinine ratio: 15:1 - Potassium: 5.4 mEq/L - Urinalysis: Specific gravity 1.025, no blood, no protein, no casts - Urine sodium: 8 mEq/L - Fractional excretion of sodium (FENa): 0.4% ### Diagnosis **NSAID-Induced Prerenal Acute Kidney Injury** ### Discussion This case illustrates the determinants of GFR from the lecture: - **Afferent Arteriolar Regulation**: Prostaglandins normally cause afferent arteriolar dilation, particularly important when renal perfusion is compromised. NSAIDs block prostaglandin synthesis, removing this protective vasodilation. - **Combined NSAID + ACE Inhibitor Effect**: The patient is also on lisinopril, which dilates the efferent arteriole. The combination creates a "perfect storm" - reduced inflow (blocked prostaglandin dilation) and reduced efferent constriction removes the ability to maintain glomerular capillary pressure. - **Low FENa**: The FENa <1% indicates intact tubular function with appropriate sodium conservation, confirming prerenal etiology rather than acute tubular necrosis. ### Starling Forces Analysis - Reduced renal perfusion (dehydration from low-sodium diet, reduced cardiac preload) - Blocked afferent dilation (NSAID effect) - Blocked efferent constriction (ACE inhibitor effect) - Net effect: Marked reduction in glomerular capillary hydrostatic pressure (PGC) and GFR ### Treatment - Discontinue ibuprofen immediately - Hold lisinopril temporarily - Gentle IV fluid resuscitation with normal saline - Monitor creatinine daily - Creatinine improved to 1.4 mg/dL after 5 days ### Clinical Pearl The "triple whammy" of NSAID + ACE inhibitor/ARB + diuretic or volume depletion is a common cause of prerenal AKI. All three factors reduce GFR: NSAIDs block afferent dilation, RAAS blockers remove efferent constriction, and volume depletion reduces perfusion pressure. --- ## Case 2: Bilateral Renal Artery Stenosis with ACE Inhibitor-Induced AKI ### Patient Presentation A 68-year-old female with a history of peripheral vascular disease and coronary artery disease presents for follow-up after starting ramipril 2 weeks ago for newly diagnosed heart failure with reduced ejection fraction. ### History of Present Illness - Started ramipril 5 mg daily 14 days ago - Routine labs today show markedly elevated creatinine - No symptoms of uremia - Mild dyspnea on exertion (unchanged from baseline) - No edema reduction since starting medication ### Physical Examination - Blood pressure: 136/82 mmHg (improved from 168/98) - Heart rate: 78 bpm - Bilateral abdominal bruits - 1+ bilateral pedal edema - JVP 10 cm H2O ### Workup **Laboratory Studies:** - Baseline creatinine (before ramipril): 1.3 mg/dL - Current creatinine: 3.1 mg/dL (>100% increase) - BUN: 58 mg/dL - Potassium: 5.8 mEq/L - Urine sodium: 12 mEq/L - FENa: 0.6% **Imaging:** - Renal Doppler ultrasound: Bilateral renal artery stenosis (>70% bilaterally) - Kidney sizes: Right 9.5 cm, Left 9.0 cm (mildly atrophic) ### Diagnosis **ACE Inhibitor-Induced AKI due to Bilateral Renal Artery Stenosis** ### Discussion This case demonstrates autoregulation and GFR maintenance: - **Autoregulation Limits**: The lecture describes autoregulation over MAP 80-180 mmHg. In renal artery stenosis, the post-stenotic pressure is already reduced, and GFR depends heavily on angiotensin II-mediated efferent constriction. - **Efferent Arteriolar Constriction**: Moderate efferent constriction increases PGC and maintains GFR despite reduced renal blood flow. ACE inhibitors remove this compensation. - **Filtration Fraction**: Normally ~20%, in renal artery stenosis the filtration fraction increases as the kidney attempts to maintain GFR with reduced RBF. ACE inhibitors lower filtration fraction but at the cost of reduced GFR. ### Treatment - Discontinue ramipril immediately - Creatinine expected to improve (a >30% rise mandates stopping the drug) - Alternative heart failure management with hydralazine/nitrates - Cardiology and vascular surgery consultation for consideration of renal artery revascularization - In selected patients with bilateral stenosis and flash pulmonary edema, revascularization may be considered ### Clinical Pearl A creatinine rise >30% after ACE inhibitor or ARB initiation should prompt evaluation for bilateral renal artery stenosis or stenosis of a solitary kidney. However, a rise up to 30% is acceptable and reflects reduced intraglomerular pressure. --- ## Case 3: Contrast-Induced Nephropathy ### Patient Presentation A 64-year-old male with type 2 diabetes and chronic kidney disease (baseline creatinine 1.8 mg/dL, eGFR 38) undergoes cardiac catheterization for unstable angina. He returns 48 hours later with decreased urine output. ### History of Present Illness - Cardiac catheterization performed 2 days ago with 150 mL of iodinated contrast - Received inadequate pre-procedure hydration - Decreased urine output since the procedure - No chest pain - Taking metformin (was not held) ### Physical Examination - Blood pressure: 142/88 mmHg - Heart rate: 82 bpm - No peripheral edema - Lungs clear - Cardiac stent in place with good result ### Workup **Laboratory Studies:** - Baseline creatinine: 1.8 mg/dL - Current creatinine (48 hours post-procedure): 3.2 mg/dL - BUN: 48 mg/dL - Potassium: 5.1 mEq/L - Urinalysis: 1+ protein, rare muddy brown casts - FENa: 2.4% ### Diagnosis **Contrast-Induced Nephropathy (Contrast-Induced Acute Kidney Injury)** ### Discussion This case relates to GFR measurement and clinical applications: - **Creatinine as GFR Marker**: The lecture explains that creatinine clearance slightly overestimates GFR due to tubular secretion. The rise in creatinine 24-48 hours post-contrast is characteristic of contrast nephropathy. - **Risk Factors**: Pre-existing CKD (especially GFR <45) and diabetes are the strongest risk factors, as discussed in clinical applications. - **Mechanism**: Contrast causes both afferent vasoconstriction (reducing PGC) and direct tubular toxicity, transitioning from prerenal to intrinsic injury. ### Prevention (Should Have Been Done) - IV saline hydration before and after procedure - Hold metformin (lactic acidosis risk with AKI) - Minimize contrast volume - Consider alternatives to contrast (CO2 angiography) - Avoid concurrent nephrotoxins (NSAIDs) ### Treatment - Supportive care with IV fluids - Hold metformin until creatinine stabilizes - Monitor for recovery (typically peaks at 3-5 days, resolves by 7-14 days) - Patient's creatinine peaked at 3.8 mg/dL on day 4, then gradually improved to 2.2 mg/dL by day 10 ### Clinical Pearl Contrast nephropathy follows a predictable time course: creatinine begins rising within 24-48 hours, peaks at 3-5 days, and usually resolves within 7-14 days. Patients with pre-existing CKD may not return to baseline. --- ## Image Reference For visual reference of concepts in this lecture, see: - Radiopaedia: [Renal artery stenosis](https://radiopaedia.org/articles/renal-artery-stenosis) - Doppler and angiographic images - Wikimedia Commons: [Glomerulus](https://commons.wikimedia.org/wiki/Category:Glomerulus) - Histology images showing filtration structures - Radiopaedia: [Contrast-induced nephropathy](https://radiopaedia.org/articles/contrast-induced-nephropathy) - Clinical information and imaging --- ## Learning Points 1. **Autoregulation Limits**: Autoregulation maintains stable GFR over MAP 80-180 mmHg. Below this range, GFR falls proportionally with blood pressure. 2. **NSAIDs and Prostaglandins**: Prostaglandins provide protective afferent dilation during states of reduced renal perfusion; NSAIDs remove this protection. 3. **ACE Inhibitors and Efferent Tone**: ACE inhibitors dilate the efferent arteriole, reducing PGC and GFR. This is beneficial for proteinuria reduction but dangerous in bilateral renal artery stenosis. 4. **Creatinine Kinetics**: Serum creatinine is a lagging indicator - it reflects GFR changes from the previous days, not real-time kidney function. 5. **FENa Interpretation**: FENa <1% suggests prerenal etiology with intact tubular function; FENa >2% suggests intrinsic renal injury.