Approach to a patient with active urinary sediments

Diagnostic approach to patients with incidental findings of active urinary sediments

1. APPROACH TO A PATIENT WITH ACTIVE URINARY SEDIMENTS Dr. Sayan Chakraborty First Year PGT-MD Tropical Medicine School of Tropical Medicine, Kolkata

2. Urine Microscopy T he ‘Liquid R enal B iopsy ’! INDICATIONS: Suspected urinary tract infection Suspected acute glomerulonephritis. Suspected acute interstitial nephritis (requires staining for eosinophils ). Unexplained acute or chronic renal failure. Haematuria (with or without proteinuria) on urine dipstick test. Suspected urinary tract malignancy.

3. Classification of Urinary Sediments Cells Renal casts Crystals Microorganisms Mucus Miscellaneous

4. Cells- Erythrocytes Description Size : 7-8 µm in diameter Pale or yellowish, smooth biconcave disk No nucleus or cytoplasmic granules Normal : Less than 2 RBC/HPF Can originate from any part of the urinary tract Associated Conditions Glomerulonephritis Calculi BHP/ Prostatitis Carcinoma of bladder/kidney Trauma IgA nephropathy Urinary Schistosomiasis etc.

5. Hematuria

6. Leucocytes Description Typically neutrophils (PMN) Larger than RBC, 10-12 µm in diameter Contain nucleus and cytoplasmic granules Brownian movement  (“glitter cells”) Normal : no more than 2 W BC/HPF Associated Conditions Can originate from any part of the urinary tract (glomerulus to urethra) Increased In inflammatory processes of the urinary tract ( pyuria )

7. PYURIA BACTERIURIA

8. EPITHELIA Squamous epithelia Large flat cell with central oval nucleus Transitional (bladder) epithelia Spindle shaped with large oval nucleus Maybe in sheet Renal tubular epithelia Small cell with large oval nucleus Most clinically significant

9. Squamous Epithelial Cells Large, flat, irregular-shaped cells P rincipally from the urethra and vagina

10. Transistional Epithelial Cells  2-4 times larger than leukocytes Round, pear-shaped, tail-like projections Large round nucleus

11. Renal Tubular Epithelial Cells Description Slightly larger than WBC Flat , cuboidal or columnar One large round nucleus Associated conditions Tubular damage Pyelonephritis ATN S alicylate intoxication T ransplant rejection

12. Renal Tubular Cells

13. Urinary Casts F irst described by  Henry Bence Jones  (1813-1873 ) C ylindrical structures Formed in the  distal convoluted tubule  and  collecting ducts  of  nephrons F orm via precipitation of  Tamm- Horsfall   mucoprotein  which is secreted by  renal tubule  cells, and sometimes also by albumin in conditions of proteinuria

14. Classification of Casts Acellular casts Hyaline casts Granular casts Waxy casts Fatty casts Pigment casts Crystal casts Cellular casts Red blood cell casts White blood cell casts Bacterial casts Epithelial cell casts

15. Hyaline Cast   Most common type of cast   Solidified   Tamm- Horsfall mucoprotein  secreted from the tubular epithelial cells. CAUSES: Low urine flow, concentrated urine, acidic environment, dehydration or vigorous exercise.   Phase contrast microscopy leads to easier identification.

16. HYALINE CASTS

17. Granular Casts S econd-most common type of cast R esult from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g . albumin) or I g light chains C lassified as fine or coarse d epending on the size of inclusions M ost often indicative of chronic renal disease The "muddy brown cast" seen in  acute tubular necrosis  is a type of granular cast.

18. Fine Granular Cast Coarse Granular Cast

19. Waxy Casts E nd product of cast evolution Waxy casts fall under the umbrella of “broad” casts Suggest very low urine flow associated with severe, longstanding kidney disease such as chronic renal failure.  Formed in diseased, dilated ducts

20. Broad Cast Waxy Cast

21. Fatty Cast Hyaline casts with fat globule inclusions Formed by the breakdown of lipid-rich epithelial cells If cholesterol or cholesterol esters are present - “Maltese cross” sign under polarized light   Pathognomonic for high urinary protein nephrotic syndrome

22. Pigment Cast So named due to discolouration Formed by the adhesion of metabolic breakdown products or drug pigments Caused by: H emoglobin in  hemolytic anemia Myoglobin in  rhabdomyolysis B ilirubin  in liver disease. Drug pigments, such as  phenazopyridine

23. RBC Cast A lways pathological, and is strongly indicative of glomerular damage Causes: Glomerulonephritis from various causes Wegener's granulomatosus Systemic lupus erythematosus Goodpasture’s syndrome Renal   infarction Subacute  bacterial endocarditis

24. RBC Cast

25. WBC Cast Indicative of inflammation or  infection Causes: Pyelonephritis (strong suggestion) A cute allergic interstitial nephritis N ephrotic syndrome P ost-streptococcal acute glomerulonephritis

26. WBC Cast

27. Bacterial Cast Found in   pyelonephritis S een in association with loose bacteria, white blood cells, and white blood cell casts D iscovery is rare, due to the infection-fighting efficiency of  neutrophils, and the possibility of misidentification as a fine granular cast.

28. Epithelial Cell Cast Stasis and desquamation of renal tubular epithelial cells following tubular damage and necrosis.

29. Crystals In Acidic Urine Uric Acid Calcium Oxalate Cystine Leucine Cholesterol Tyrosine Sulfonamide In Alkaline Urine Triple phosphate Ammonium biurate Calcium phosphate

30. Crystals in acidic urine

31. Uric Acid Crystal Description Many different shapes, diamond, rhombic prism or rosette Yellow or brown in colour Associated conditions Very common Can be normal occurence Associated with increased purine metabolism

32. Uric Acid Crystals

33. Calcium oxalate crystal Description Colorless , octahedral or envelope Associated Conditions Ingestion of oxalate-rich foods: spinach, rhubarb, tomatoes, garlic, oranges, asparagus High intake of ascorbic acid Ethylene glycol poisoning

34. Calcium Oxalate Crystal

35. Cystine Crystal Colorless , refractile , hexagonal plates Found in Congenital cystinosis or cystinuria

36. Leucine Crystal Description Oily, highly refractile , yellow or brown spheroids and concentric striations Associated Conditions Clinically significant Maple syrup urine disease, Oasthouse urine disease, severe liver disease Seen with tyrosine in liver disease

37. Cholesterol Crystal Description Large, flat, transparent Notched corners Associated Conditions Excessive tissue breakdown Obstructed lymphatic flow Nephritis and nephrotic conditions

38. Tyrosine Crystal Description Very fine, highly refractile needles Black , yellow In sheaves or clusters Associated Conditions Severe liver disease Tyrosinosis  

39. Crystals in alkaline urine

40. Triple Phosphate Crystal Description Colorless prisms 3-6 sides , oblique ends Coffin lids Associated Condition Can be found in normal urines Chronic urinary inflammation

41. Triple Phosphate Crystals

42. Ammonium Biurate Crystal Yellow brown spherical bodies with long irregular spicules

43. Calcium Phosphate Crystal Long thin, colorless needles One pointed end Arranged as rosettes or star Can be found normally

44. Active Urinary Sediments I ndicates inflammation in the glomerular capillary wall The sediments are: • Red blood cells/casts • White cells/casts

45. Approach to a patient with RBCs or RBC casts in urine HEMATURIA

46. Microscopic hematuria D/D Glomerular Primary nephritis (post streptococcal glomerulonephritis, Ig A nephropathy, Anti-GBM disease) 2 nd nephritis ( SLE, Goodpasture’s syndrome, ANCA related vasculitis ) Alport’s syndrome (hereditary nephritis) Thin basement membrane nephropathy (benign familial hematuria )

47. Microscopic hematuria D/D contd.. Extra-glomerular : Renal M alignancy V ascular disease ( malignant hypertension, AVM, nutcracker syndrome, renal vein thrombosis, sickle cell trait/disease, papillary necrosis) I nfection (pyelonephritis, TB, CMV, EBV) H ypercalciuria H ereditary disease (polycystic kidney disease, medullary sponge kidney )

48. Microscopic hematuria D/D contd.. Extra-renal malignancy (prostate, ureter, bladder) BPH Nephrolithiasis Coagulopathy Trauma

49. Extraglomerular vs Glomerular Hematuria in Urine Analysis Extraglomerular Glomerular Color (if macroscopic) Red or pink Red, smoky brown, or "Coca-Cola" Clots May be present Absent Proteinuria <500 mg/day May be >500 mg/day RBC morphology Normal Dysmorphic RBC casts Absent May be present

50. Major causes of hematuria by age and duration

51. Glomerular Hematuria with active sediments HISTORY: Early morning periorbital puffiness, oliguria , dark colored u rine, edema or hypertension Recent throat or skin infection may suggest postinfectious glomerulonephritis Joint pains, skin rashes, and prolonged fever in adolescents suggest a collagen vascular disorder

52. Skin rashes and arthritis can occur in Henoch-Schönlein purpura and systemic lupus erythematosus A family history that is suggestive of Alport syndrome, collagen vascular diseases, urolithiasis , or polycystic kidney disease is important Passage of clots in urine suggests an extra-glomerular cause

53. Physical Examination Measurement of the blood pressure (with an appropriately sized cuff) Evaluation for the presence of periorbital puffiness or peripheral edema Detailed skin examination to look for purpura . Abdominal examination to look for palpable kidneys

54. Initial Work up CBC, PT, INR, electrolytes, kidney function UA and microscopy to determine the number and morphology of RBC, crystal and casts Consider urine C/S Repeat UA in a few days

55. Further Work up Throat swab C/S, ASO titre, complement levels for PSGN ANA, dsDNA for SLE Skin biopsy showing IgA deposition s/o HSP ANCA for systemic vasculitis Imaging: USG, CT, Radionuclide studies

56. Renal Biopsy Indications: Significant proteinuria Abnormal renal function Recurrent persistent hematuria Serologic abnormalities (abnormal complement, ANA, or dsDNA levels) Recurrent gross hematuria A family history of end stage renal disease

57. Approach to a patient with pyuria or WBC cast Differential Diagnosis : Asymptomatic Bacteriuria Cystitis Pyelone phritis Prostatitis Complicated UTI

58. CASE 1 A 40 year old female patient presented with Dysuria Frequency Urgency What is the approach for management?

59. Diagnostic Approach Patient profile Management 1. Otherwise healthy woman, not pregnant, clear history Uncomplicated cystitis: No Urine c/s needed OPD management 2. Woman with unclear history or risk factors for STD Uncomplicated cystitis or STD: Dipstick, Urinalysis STD evaluation, pelvic examination 3. Male with pelvic, perineal or prostatic pain Acute prostatitis: Urinalysis and C/S Urologic evaluation 4. Indwelling urinary catheter CAUTI: Change or remove catheter Urinalysis , C/S Blood C/S if fever 5. All other patients Complicated UTI; Urinalysis, C/S Modify functional or anatomic abnormality

60. Case 2 A patient presented with acute onset of: Back pain Nausea/vomiting Fever Possible cystitis symptoms Approach?

61. Diagnostic Approach Patient profile Management Otherwise healthy woman, not pregnant Uncomplicated pyelonephritis: Urine Culture OPD management All other patients Pyelonephritis: Urine Culture Blood Culture Patients with non-localizing systemic symptoms like fever, altered mental status along with leucocytosis: Consider Complicated UTI or Pyelonephritis :- Look for other potential etiologies Urine Culture Blood Culture

62. Case 3 30 year old second gravida lady in her third trimester presented with a positive urine culture in the absence of any symptom. What should be her ideal management?

63. Diagnostic Approach Patient profile Management Pregnant or renal transplant recipient or planned to undergo an invasive urologic procedure Asymptomatic Bacteriuria (ABU) Screening and treatment warranted All other patients Consider ABU No additional treatment and workup needed Patient with urinary catheter Consider CA-ABU No additional treatment and workup needed Remove unnecessary catheters

64. Case 4 68 year old gentleman presented with recurrent acute urinary symptoms. Approach to management?

65. Diagnostic Approach Patient Profile Management Male Consider chronic bacterial prostatitis: Meares-Stamey 4-glass test Urology consultation Otherwise healthy female not pregnant Consider reucurrent cystitis: Urine Culture Consider prophylaxis or patient initiated management

66. QUIZ BUGS

67. Carrot no. 1 A 10 year old male child presented with hearing loss, dimness in vision and persistent hematuria . Gene study showed COL4A4 mutation. What is your diagnosis?

68. Carrot no. 2 21 Year old female visited ophthalmology clinic with complaints of pain in eyes and difficulty in adjusting to dark. She was found to have iliac horns and gave history of passage of reddish urine. What is your diagnosis?

69. Carrot no. 3 30 year old lady presented with pain in left lower quadrant along with hematuria . The figure beside shows the etiology . What is your diagnosis?