Azotemia and Urinary abnormalities .pptx

Azotemia, initial assessment, approach to patient with protienuria

1. AZOTEMIA AND URINARY ABNORMALITIES DR. ARSHAD MAHMOOD DNB GENERAL MEDICINE RESIDENT

2. ( azot , "nitrogen" + - emia , "blood condition") is a medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds) in the blood AZOTEMIA

3. Nephrologic syndromes consist of specific sets of clinical and laboratory findings that help in diagnosis and management Reduction in GFR indicates impaired kidney function Urine sediment analysis can reveal red blood cells (RBCs), white blood cells (WBCs), casts, and crystals Proteinuria, or abnormal excretion of serum proteins , suggests glomerular dysfunction Urine output disturbances - (low urine output), anuria (absence of urine), or polyuria (excess urine

4. GFR : Essential for evaluating kidney function in both hospital and outpatient settings. Direct Measurement: Uses radioactive isotopes (e.g., inulin, iothalamate) that are filtered but not reabsorbed or secreted Plasma creatinine (P Cr) is widely used but has limitations due to muscle metabolism variations and tubular secretion. A fall in GFR leads to azotemia (buildup of nitrogenous waste) and affects drug clearance, necessitating careful dosage adjustments. Creatinine Clearance ( CrCl ) : Measured from plasma and urine creatinine over 24 hours; formulas like Cockcroft-Gault and MDRD are commonly used for estimation. Limitations of Creatinine-Based Estimates: Requires a steady-state assumption; affected by diet, muscle mass, and chronic illnesses, potentially masking true GFR changes. ASSESSMENT OF GFR

5. ADVANCES & LIMITATIONS IN GFR ESTIMATION Race Modifier Controversy: CKD-EPI equation previously adjusted GFR for black individuals; many centers now exclude race-based adjustments for equity in care. Implications of Race Modifier Removal: Positive: Earlier access to kidney transplant waitlists. Negative: Possible CKD overdiagnosis, inaccurate drug dosing, reduced imaging access, and fewer living kidney donations. Cystatin C as an Alternative Marker: Produced at a constant rate by nucleated cells, less influenced by muscle mass than creatinine. Advantages of Cystatin C: More sensitive in detecting early GFR decline, independent of race and muscle mass. Challenges with Cystatin C: Levels influenced by diabetes, inflammation, and smoking, requiring further validation. Future Direction: Combining creatinine and cystatin C to improve GFR estimation for better clinical decision-making.

6. PRERENAL FAILURE: Accounts for 40–80% of ARF cases; reversible if treated early. Causes: Hypovolemia, cardiac output reduction, NSAIDs/ACE inhibitors. Severe hypoperfusion can cause Acute Tubular Necrosis (ATN). POSTRENAL AZOTEMIA: Accounts for <5% of ARF cases; caused by urinary tract obstruction. Diagnosis: Ultrasound shows ureteral/pelvic dilation; further imaging may be required. Early intervention ensures reversibility. INTRINSIC RENAL DISEASE: Causes: ATN, interstitial nephritis, glomerular diseases, vascular causes. Excludes prerenal and postrenal causes.

7. ACUTE TUBULAR NECROSIS (ATN): Ischemic ATN: Seen in major surgery, trauma, sepsis. Nephrotoxic ATN: Caused by medications, toxins. Urinalysis findings: Muddy brown granular casts, tubular epithelial cell casts.

8. Oliguria: Urine output <400 mL/day . Anuria: Urine output <100 mL/day. Causes: Complete obstruction, vascular occlusion, severe ATN, NSAID/ACE inhibitor/ARB combination therapy. Urinalysis & Biomarkers: Helps differentiate prerenal azotemia from ATN. Prerenal: Concentrated urine, low sodium excretion. ATN: Dilute urine, cellular debris, muddy brown casts.

9. APPROACH TO AZOTEMIA

10. ABNORMALITIES OF THE URINE PROTIENURIA Presence of excess protein in urine. Detected via dipstick (detects albumin only) but can give false results in certain conditions (pH >7, blood contamination, dilution). Quantification: Albumin-to-Creatinine Ratio (ACR) estimates Albumin Excretion Rate (AER). Spot urine protein/creatinine ratio helps approximate daily protein loss. 24-hour urine collection - gold standard Normal kidneys excrete <150 mg/day total protein , <30 mg/day albumin. Disruptions in glomerular barrier (charge & size selectivity) lead to protein leakage. Glomerular proteinuria : Due to basement membrane disruption (e.g., immune complex deposition). Tubular proteinuria : Due to defective proximal tubule reabsorption. Overflow proteinuria : Excessive protein production (e.g., multiple myeloma).

11. Severe Proteinuria (>3.5 g/day) Nephrotic Syndrome: Characterized by: Hypoalbuminemia (due to urinary loss & proximal tubule catabolism). Edema (sodium retention & reduced oncotic pressure). Hyperlipidemia (increased hepatic lipoprotein synthesis). Hypercoagulability (loss of antithrombin III, proteins C & S). Infection Risk (loss of immunoglobulins). Non-Nephrotic Causes: o Diabetes, various renal diseases. Pathophysiology: Loss of albumin → reduced plasma oncotic pressure → fluid shifts → edema. Renin-Angiotensin System (RAAS), AVP, and Sympathetic Activation → worsens sodium & water retention. Hypercoagulability due to loss of clotting regulators. NEPHROTIC SYNDROME & SEVERE PROTEINURIA

12. Minimal Change Disease (MCD): Podocyte foot process fusion → Selective albuminuria. Glomerular Diseases: Basement membrane & slit diaphragm disruptions → Non-selective proteinuria. Multiple Myeloma: Excess light chains (Bence-Jones proteins) → Cast nephropathy, Amyloidosis, Light Chain Deposition Disease. Drugs & Diseases: Many medications & systemic diseases can induce nephrotic syndrome. Diagnostic Approach: Dipstick Test → Spot Urine ACR/Protein-Creatinine Ratio. 24-Hour Urine Collection Electrophoresis for Light Chains Renal Biopsy SPECIAL CONDITIONS:

13. APPROACH TO THE PATIENT WITH PROTIENURIA

14. Hematuria : Presence of ≥2-5 RBCs/HPF in urine. Detected via dipstick test (false positives with myoglobinuria, e.g., rhabdomyolysis). Microscopic Hematuria : Found in urinalysis, requires evaluation if persistent or significant (>3 RBCs/HPF in 3 samples). Gross Hematuria with Clots: Suggests postrenal causes (urinary collecting system pathology). Causes of Hematuria : 1) Non-Glomerular (Postrenal or Urologic): Stones, Tumors , Tuberculosis, Trauma, Prostatitis. Hypercalciuria/Hyperuricosuria → May resolve with dietary changes. Infections (Cystitis, Urethritis, Pyelonephritis). 2) Glomerular Causes (Renal): Dysmorphic RBCs & RBC Casts → Glomerulonephritis. Common Diseases: IgA Nephropathy: Episodic gross hematuria . Hereditary Nephritis: Family history of renal failure. Thin Basement Membrane Disease: Familial microscopic hematuria . HEMATURIA, PYURIA, AND CASTS

15. Presence of WBCs in urine (>5 WBCs/HPF). WBC Casts indicate renal (not lower urinary tract) inflammation. Causes of Pyuria: Infectious: Bacteria present: UTI (cystitis, pyelonephritis). Sterile Pyuria (no bacteria on culture): Tuberculosis, STIs, interstitial nephritis. Non-Infectious: Glomerulonephritis (alongside RBC casts). Tubulointerstitial Nephritis (e.g., drug-induced, transplant rejection). PYURIA – CAUSES & CLINICAL SIGNIFICANCE

16. RBC Casts : Diagnostic of  glomerulonephritis. WBC Casts : Seen in  pyelonephritis, interstitial nephritis, glomerulonephritis . Hyaline Casts:  Nonspecific, seen in dehydration or exercise. Granular Casts : Indicate  acute tubular necrosis. Waxy & Broad Casts : Found in  chronic kidney disease (CKD) due to tubular atrophy & dilation . Key Diagnostic Approach: Microscopy: Identify RBC shape, WBCs, and casts. Dipstick & Urinalysis: Check for proteinuria, pyuria, and hematuria . Renal Biopsy & Serology (if needed): Evaluate glomerular diseases. CASTS IN URINE

17. APPROACH TO THE PATIENT WITH HEMATURIA

18. Polyuria: Urine output >3 L/day. Must differentiate from urinary frequency (small volumes). Confirm with 24-hour urine collection. Two Mechanisms of Polyuria: Solute Diuresis (excretion of nonabsorbable solutes)- Urine osmolality >300 mosmol /L  Glucose (Diabetes Mellitus) – Most common cause Mannitol, radiocontrast agents, high-protein feedings Sodium-wasting disorders (e.g., Bartter’s syndrome, resolving ATN) Water Diuresis (excess water excretion)- Urine osmolality <250 mosmol /L  Polydipsia (habitual, psychiatric, neurologic) Diabetes Insipidus (DI): Central DI: ↓ AVP secretion Nephrogenic DI: Tubular resistance to AVP POLYURIA

19. Key Diagnostic Tests: Plasma AVP or Copeptin (AVP precursor) → Distinguishes Central vs. Nephrogenic DI Water Deprivation Test: Differentiates Primary Polydipsia vs. DI Central DI → Urine concentrates after AVP administration Nephrogenic DI → No response to AVP Hypertonic Saline-Stimulated Copeptin Test (Alternative to water deprivation test) Clinical Approach: Confirm Polyuria (>3 L/day) with 24-hour urine collection Check urine osmolality → Solute or Water diuresis? Measure AVP or copeptin → Central or Nephrogenic DI? Consider Water Deprivation Test if needed DIAGNOSIS & EVALUATION OF POLYURIA

20. APPROACH TO THE PATIENT WITH POLYURIA

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