Tests of renal function 3
- 1. Tests of Renal Function Cyrus Cryst MD FASN VMMC
- 2. Estimates of Glomerular function • Serum Creatinine • BUN • eGFR • Cockroft-Gault Formula or MDRD • 24 hour Creatinine Clearance • Iothalamate Clearance
- 3. Plasma Creatinine • Creatinine is derived from metabolism of creatine in skeletal muscle and in dietary meat protein • It is released constantly into the circulation • It is freely filtered at the glomerulus and is neither absorbed nor metabolized by the kidney • 15% of urinary creatinine is derived from tubular secretion
- 4. Plasma Creatinine • GFR x PCr = Ucr x Volume • GFR = Ucr x Volume / PCr • This formula overestimates the true GFR by 10-15% (due to tubular secretion of creatinine) and that is balanced by the error in creatinine measurement.
- 5. Calculation of CCR • If : PCr = 1.2 GFR = U V/P • Ucr = 100 mg/dl • V = 1.2 Liters per day • GFR = 100 mg/dl x 1.2mg/dl /1.2L/day= 100 L/day • This must be multiplied by 1000 ml/liter and again by 1/1440 (minutes per day) To yield conventional units: 70 ml/min Normal is 130 ml/min in men and 120 ml/min in women
- 6. Limitations of eGFR • Only applies in “steady state” • Only for those with impaired GFR < 60 • Only for those under 65 • Depends on accurate measurement of creat • CKD-EPI formula for “normal population”
- 7. Plasma Creatinine • Is the most useful blood test to monitor change in renal function. • Change in plasma creatinine means a change in rate of production OR a change in GFR • Don’t neglect conditions that cause increase in plasma creatinine production: – Rhabdomyalysis – Protein ingestion • Drugs affect creatinine secretion can raise creat 10% (trimethaprim)
- 9. eGFR and Creatinine • Nomogram – takes creat and ‘assigns’ an estimate of GFR • No account of age, muscle mass, prior condition – two values for race. • Very concerning for patients to be told “stage 3 kidney failure” • No context can go up and down • At extremes of age, weight, muscle mass may be inaccurate
- 10. Heat map: stages of renal impairment
- 11. When Creatinine Elevation is Misleading • Pts who have lost or donated a kidney • People taking sulfa-TRIMETHOPRIM • Volume depletion – ‘fasting’ • ACEI and ARB – lead to ~30% decline in eGFR that is reversible with discontinuation of the drug
- 12. Clinical tips • A plasma creatinine rising 1.0 mg/dl/24 hours reflects GFR = 0 • RAAS inhibitors can raise serum creat by 0.2-0.6 depending on volume depletion • Getting a complete 24 hour urine for Creat Clearance in the hospital is very difficult.
- 13. Urinalysis in renal disease • Color • Specific Gravity • Leucocyte Esterase • Protein • pH • Osmolality • Glucose • Part 2 – Sediment – Patterns of injury • Part 3 – Urine electrolytes – Settings where useful
- 14. Urine Color • Usually clear, light yellow • Lighter when dilute, darker when concentrated • White due to phosphate crystals or pyuria • Green due to methylene blue dye, propofol • Black due to malignancy • Red or brown due to Heme or pigments • Turbidity may indicate infection, crystals or phosphates
- 15. Red urine • Hematuria - the sediment is red, supernatent is clear • If supernatent is RED, test for heme. – Heme Positive - RHABDOMYALYSIS – Heme Negative? - RARE- Porphyuria, Beets, phenazopyridine.
- 17. Urine Specific Gravity • Surrogate for urine osmolality • Indicates dilute or concentrated urine • SG of 1.010 is about isosomolar • Highest in extreme vol depletion 1.030 • May be falsely high in cases of contrast excretion or glucose • Cannot be falsely low
- 18. Leucocyte Esterase • Enzyme released by neutrophils – marker for leucocytes in urine. • False positive if urine is VERY dilute or concentrated • False Negative if urine is very concentrated • Nitrates- test for presence of nitrate reductase – Also has false pos, negs and not elaborated by all bugs
- 19. Leucocyte Esterase • Leukocyte estrase and nitrite - surrogate markers for pyuria and enterobacteriaceae • Postive results may be an important clue: – May detect WBC or bacteria not associated with UTI! – “sterile pyuria?” • TB, • Interstitial nephritis, • Stones
- 20. Urine Protein • Patients usually only excrete 150 mg protein /day or less • Dipstick usually only picks up ALBUMIN • Dipstick usually positive only for >300 mg/day • Scores 1-2-3+ • Sulfosalicylic acid test - for light chains
- 21. Microalbuminuria • Screening test for diabetic nephropathy • Risk factor for cardiac disease • Also used with microalbumin/creat ratio
- 22. Quantitative protein excretion • 24 hour collection determines if patient has “nephrotic range” proteinuria - evidence of glomerular disease - >3.5 gm/1.73 M2 • Alternative method is to use a spot Protein- to-creatinine ratio in mg/mg which correlates with g/1.73 M2 protein excretion.
- 23. Urine pH • Range is 4.5-8.0 • Best use is in Metabolic acidosis - normally patients should excrete an acid urine pH <5 – If urine pH is >5 In a patient with ACIDOSIS suspect a renal tubular acidosis – If urine pH is > 7.0 - 9.0 - suspect a urease producing organism such as P. miriabilis (associated with staghorn calculi)
- 24. Urine Osmolality • Plasma osmolality is maintained in a narrow range normally by the kidney’s ability to elaborate urine that varies widely in osmolality. • Urine osmolality measurements are key to unraveling the DDX of • hypernatremia, • hyponatremia, • polyuria
- 25. Urine Glucose • Indicates High plasma glucose levels (but is insensitive) • Can indicate a proximal tubular reabsorptive problem - Fanconi’s syndrome • Urinary glucose measurements reflect mean glucose levels, not peak concentrations.
- 26. PART II • The Urine Sediment Exam
- 28. Sediment • Crystals • Cells – Heme – Wbc – epithelial • Bacteria • Casts • Patterns
- 29. Crystals • Uric Acid • Calcium • Cystine • Struvite - magnesium/ammonium/phosphate
- 31. Crystals
- 33. Sediment - Cells • Pyuria – May reflect infection – Usually accompanies any renal disease – May be stained for eosinophils • Tubular epithelial cells – In casts reflect ATN – Individually are seen in many situations
- 35. Sediment - Cells • Hematuria - – Always abnormal in older men – Can be transient in younger patients – RBC morphology can reflect upper or lower tract bleeding – Persistent heme needs to be evaluated – Always present if foley in place
- 38. Urine sediment - Casts • Hyaline • Red Cell Casts • WBC casts • Epithelial cell casts • Fatty casts • Granular cell casts – Muddy brown casts • Waxy casts • Broad casts
- 43. Urine sediment patterns • Hematuria, >3.5 grams of protein a day, RBC casts, dysmorphic red cells, and Lipiduria – Any of these findings singly or in combination reflect glomerular disease, or vasculitis
- 44. Urine sediment patterns • Multiple granular and epithelial cell casts with free epithelial cells. – Coarse granular casts in “dirty” background – Signifies ATN - acute toxic or ischemic injury – Beware of hyperbilirubinemia
- 46. Urine sediment patterns • Pyuria with WBC and Granular or waxy casts and no proteinuria – Suggests interstitial disease or Obstruction – Can be seen with other signs of glomerular disease
- 47. Urine sediment patterns • Hematuria alone – Variable significance - depends on the setting • Stone? Flank pain • Tumor? Age, imaging studies • Mild glomerular disease - IgA, thin basement membrane disease, Alport’s, • PCKD
- 48. Urine sediment patterns • Hematuria and Pyuria with no or variable casts-can be seen with any of the following: – Interstitial nephritis – Glomerular disease – Vasculitis – Obstruction – Renal infarction
- 49. Urine sediment patterns • Pyuria alone? • Usually a UTI • Sterile pyuria suggests TB, analgesic nephropathy
- 51. Tests of renal function Part 3 - Urine Electrolytes • Sodium excretion • FENa • Chloride excretion • Potassium excretion • Urine osmolality and pH