Diagnostic evaluation of the kidney and urinary tract

Diseases of the kidney and the urinary tract can present with a wide array of symptoms. In addition to flank or groin pain, referred pain may occur in other regions of the body, which can make diagnosis difficult. Therefore, acute abdominal pain requires consideration of the kidneys and urinary tract. Most chronic renal diseases are asymptomatic and are only detected through abnormal findings on urinalysis (erythrocytes, protein) or pathological changes of renal function parameters (increased serum creatinine, blood urea nitrogen). An ultrasound can be used for a quick evaluation of the kidney and urinary tract and is critical in diagnosing urinary tract obstructions and urinary retention.

• Changes in micturition (amount, appearance, discomfort)
• Flank pain
  • Colicky pain with radiation to the groin or genitals is more commonly seen in urolithiasis.
  • Persistent pain in inflammatory diseases
• Costovertebral angle tenderness (CVAT)
• Hematuria
• Hypertension: extrarenal manifestations that may indicate kidney injury
• Edema : See proteinuria.

Acute appendicitis should be differentiated from right-sided renal colic! Appendicitis often presents with nausea, fever, and pain at McBurney's point!

• Quantity of urine
  • Polyuria: urine output > 3 L/day in adults
  • Oliguria: urine output < 500 mL/day
  • Anuria: urine output < 50 mL/day
• Quality of urine
  • Isosthenuria: loss of the ability to concentrate or dilute urine → urine osmolality approaching that of plasma
  • Glycosuria: glucose in the urine
  • Proteinuria: > 150 mg protein/day in the urine
  • Leukocyturia/pyuria: white blood cells in the urine, sometimes with visible cloudiness
  • Bacteriuria: ≥ 10⁵ organisms/mL organisms (in midstream collection)
  • Hematuria (see below)
  • Hemoglobinuria: hemoglobin in the urine
  • Myoglobinuria: myoglobin in the urine

	Most likely diagnosis
Glycosuria	Diabetes mellitus
Bacteriuria	Urinary tract infection
Hematuria in the first or last part of micturition	Urethral damage
Persistent hematuria	Vesical or supravesical origin
Painless hematuria	Malignancy
Hemoglobinuria	Severe intravascular hemolysis
Myoglobinuria	Rhabdomyolysis
Polyuria	Diabetes mellitus, diabetes insipidus, drinking excessive amounts of water

References:^[1]

• Gross urine assessment
  • Turbidity (how cloudy the urine is)
  • Urine color
• Urine dipstick
  • pH (urine pH usually ranges from 4.5–8)
  • Specific gravity; : Large molecules such as glucose or radiocontrast media may increase the urine specific gravity despite a normal urine osmolality.
  • Heme: > 90% sensitivity for hematuria; however, always confirm with microscopy for the presence of RBCs, as a dipstick cannot differentiate between hematuria, hemoglobinuria, or myoglobinuria!
  • Leukocytes esterase; : enzyme produced by WBC that indicates a UTI
  • Protein (albumin)
  • Glucose, ketones, urobilinogen
  • Nitrites
• Urine sediment
  • Cells
    • Erythrocytes
    • Leukocytes
    • Acanthocytes
    • Urinary casts
      Tubular structures formed in the distal convoluted tubule and collecting duct of the kidneys
      • Hyaline casts: nonspecific finding; can also be found in healthy individuals, often after exercise
        • Structure: consist of a mucoprotein matrix of Tamm-Horsfall proteins
        • Microscopy: homogeneous, transparent, and eosinophilic
      • Granular casts: caused by degeneration of cells in RBC or WBC casts
        • Indicate stasis in the nephron
        • Seen in tubulointerstitial disease (glomerulonephritis, pyelonephritis, acute tubular necrosis)
        • Structure: composed of a hyaline matrix with cellular debris
        • Microscopy: usually bigger than hyaline casts; the droplets are refractive
      • Waxy casts: represent further degeneration of granular casts
        • Indicate renal stasis and severe renal disease
        • nonspecific and may be seen in both acute and chronic kidney diseases
        • Structure: degenerating granular cast
        • Microscopy: homogenous, sharp indentations; edges that appear more distinct and darker in color
      • Renal tubular epithelial cell casts; : indication of glomerulonephritis or interstitial nephritis; can occasionally be found in healthy individuals
        • Structure: consist of congregated tubular epithelial cells
        • Microscopy: tubular casts; can contain multiple layers of cells; sometimes hard to differentiate from WBC casts
      • White blood cell casts: strong indication of pyelonephritis; however, can also be seen in glomerulonephritis or interstitial nephritis
        • Structure: accumulated white blood cells contained within a protein matrix
        • Microscopy: Casts usually have sharp margins and the central nuclei are seen.
        • They can be hard to differentiate from renal tubular epithelial cell casts.
      • Red blood cells casts; : indication of glomerulonephritis
        • Structure: accumulated RBCs in a mucoprotein matric
        • Microscopy: Cluster of biconcave shaped RBCs with darkly-staining hemoglobin
      • Broad casts: usually seen with advanced chronic kidney disease; formed in dilated tubules with low flow

	Glomerular hematuria	Nonglomerular hematuria
Color (macroscopic)	Red, smoky brown, “Coca-Cola”	Red or pink urine
Clots	Absent	Sometimes present
RBC morphology	Dysmorphic	Normal (isomorphic)
RBC Casts	Sometimes present	Absent
Proteinuria	> 500 mg/day	< 500 mg/day

References:^[1][2]

Diagnostics

• Physical exam
  • Initial hematuria typically suggests a urethral cause.
  • Terminal hematuria suggests damage to the bladder, prostate, or trigonal area.
  • Total hematuria suggests damage in the kidneys or ureter.
  • Microhematuria: hematuria that is not grossly visible
  • Macrohematuria: hematuria that is grossly visible (see also red urine)
• Urinalysis: > 3 erythrocytes/HPF or > 5 erythrocytes/ μL
  • If normal → evaluate for coagulation disorders, kidney stones, and malignancy (see bladder cancer)
  • If pyuria → urine culture (see urinary tract infection)
  • If RBC casts and proteinuria → evaluate for glomerular diseases

Differential diagnosis

• Nephritic syndrome
• Infection
  • Cystitis
  • Urethritis
  • Prostatitis
• If asymptomatic, consider malignancy.
  • Urothelial cancer
  • Renal cell carcinoma
  • Prostate cancer
  • In children, Wilms tumor
• Urolithiasis
• Coagulation disorder (e.g., hemophilia)
• Polycystic kidney disease
• Myoglobinuria in professional athletes or crush syndrome
• Medication side effect
• Porphyrias

References:^[1][3][3]

• Urinary metabolites
  • Serum creatinine: used as an indirect indicator of the glomerular filtration rate
    • Serum creatinine levels do not start rising until the GFR is reduced by at least 50% → If the GFR is > 60 mL/min, serum creatinine cannot be used to assess kidney function = "creatinine-blind" range!
    • Additional interfering factors:
      • Falsely elevated values: high-protein diet, high muscle mass, rigorous exercise
      • Falsely decreased values: low muscle mass
  • Blood urea nitrogen (BUN): metabolite of ammonia and proteins (also elevated in catabolic states)
    • BUN/creatinine ratio
      • ≥ 20:1: Prerenal cause; urea reabsorption is increased. Typical for dehydration or hypoperfusion.
      • ≤ 10:1: Intrarenal cause; renal damage causes decreased urea reabsorption.
      • 10:1–20:1: Normal or postrenal cause.
  • Uric acid: metabolite of purine bases
  • Serum cystatin C : a more precise indicator of the glomerular filtration rate, though the analysis is more complex and expensive. Not routinely ordered.
• Creatinine clearance: equates approximately to the glomerular filtration rate (GFR)
  • A more precise evaluation of creatinine clearance requires measuring creatinine in the urine over a 24-hour period (urine creatinine concentration x urine volume over 24 hours).
  • Creatinine clearance or GFR can be estimated using the Cockcroft-Gault equation.
    • Equation: CCr (mL/min) = ((140-age) x lean body weight(kg)) / (72 x serum creatinine (mg/dL))
    • For women, the result should be multiplied by 0.85.
• Glomerular filtration rate (GFR): volume of primary urine that is filtrated by the kidneys over a certain amount of time per standardized body surface area (1.73 m²)
  • Normal GFR: ≥ 90 mL/min/1.73m² is considered normal.
  • GFR is ∼ 120 mL/min/1.73m² in young adults, decreases with age, and varies considerably between males and females.
  • After the age of 29, a physiological decrease in the GFR of about 10 mL/min/1.73m² occurs every ten years.
  • The GFR can be estimated using the Cockcroft-Gault equation.
  • Creatinine clearance approximates GFR but slightly overestimates it because of minimal creatinine secretion at the proximal tubule.
• Other parameters that should be evaluated in renal disease (particularly in chronic renal failure) are Na⁺, K⁺, Ca²⁺, phosphate, vitamin D, and parathyroid hormone (PTH).
• Autoantibodies (particularly antinuclear antibodies as an indication of glomerulonephritis)

References:^[4][5][6]