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
The ‘Liquid Renal Biopsy’!
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
WBC/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
Principally 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
 Salicylate intoxication
 Transplant rejection

12. Renal Tubular Cells

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

15. 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

16. 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.

17. HYALINE CASTS

18. Granular Casts
 Second-most common type of cast
 Result from the breakdown of cellular casts
or the inclusion of aggregates of plasma
proteins (e.g. albumin) or Ig light chains
 Classified as fine or coarse depending on
the size of inclusions
 Most often indicative of chronic renal
disease
 The "muddy brown cast" seen in acute
tubular necrosis is a type of granular cast.

19. Fine Granular Cast Coarse Granular Cast

20. Waxy Casts
• End 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

21. Broad Cast
Waxy Cast

22. 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

23. Pigment Cast
• So named due to discolouration
• Formed by the adhesion of metabolic
breakdown products or drug pigments
• Caused by:
 Hemoglobin in hemolytic anemia
 Myoglobin in rhabdomyolysis
 Bilirubin in liver disease.
 Drug pigments, such as phenazopyridine

24. RBC Cast
• Always 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

25. RBC Cast

26. WBC Cast
• Indicative of inflammation or infection
• Causes:
 Pyelonephritis (strong suggestion)
 Acute allergic interstitial nephritis
 Nephrotic syndrome
 Post-streptococcal acute
glomerulonephritis

27. WBC Cast

28. Bacterial Cast
• Found in pyelonephritis
• Seen in association with loose bacteria,
white blood cells, and white blood cell casts
• Discovery is rare, due to the infection-
fighting efficiency of neutrophils, and the
possibility of misidentification as a fine
granular cast.

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

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

31. CRYSTALS IN ACIDIC URINE

32. 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

33. Uric Acid Crystals

34. 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

35. Calcium Oxalate
Crystal

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

37. 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

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

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

40. CRYSTALS IN ALKALINE
URINE

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

42. Triple Phosphate Crystals

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

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

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

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

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

48. Microscopic hematuria D/D
contd..
Extra-glomerular:
Renal
• Malignancy
• Vascular disease (malignant hypertension, AVM,
nutcracker syndrome, renal vein thrombosis, sickle cell
trait/disease, papillary necrosis)
• Infection (pyelonephritis, TB, CMV, EBV)
• Hypercalciuria
• Hereditary disease (polycystic kidney disease,
medullary sponge kidney)

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

50. 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

51. Major causes of hematuria by age
and duration

54. Glomerular Hematuria with
active sediments
HISTORY:
• Early morning periorbital puffiness,
oliguria, dark colored urine, 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

55. • 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

56. 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

57. 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

58. 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

59. 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

60. Approach to a patient with pyuria
or WBC cast
Differential Diagnosis:
 Asymptomatic Bacteriuria
 Cystitis
 Pyelonephritis
 Prostatitis
 Complicated UTI

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

62. 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

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

64. 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

65. 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?

66. 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

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

68. 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

69. QUIZ BUGS

70. 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?

71. 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?

72. 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?