Diagnostic evaluation of the kidney and urinary tract

This article covers important clinical findings of urological and renal conditions, including changes in micturition (e.g., dysuria, anuria) and changes in urine (e.g., hematuria, proteinuria) as well as the routine diagnostics for the initial evaluation of patients with urological and renal symptoms, including urinalysis and renal function testing. Urinalysis helps to evaluate urinary abnormalities and involves gross assessment of urine, dipstick, and microscopy of urine sediment. Dipstick is a diagnostic tool consisting of a urine test strip that allows for quick assessment of potentially pathological changes of various parameters (e.g., pH, glucose, protein). Urine sediment allows for microscopic detection of cells, urinary casts, urinary crystals, bacteria, and yeast in a urine sample. Renal function testing involves a panel of parameters to assess for renal dysfunction. Inulin clearance and creatinine clearance provide the most accurate calculation of the GFR while serum creatinine can be used together with demographic data to provide an estimated GFR. The BUN/creatinine ratio and fractional excretion of sodium can be used to evaluate the cause of acute kidney injury. The findings of these tests may be diagnostic or provide guidance for further diagnostic evaluation (e.g., renal biopsy, imaging)

For more on imaging and urodynamic tests, see “Diagnostic investigations in urology.” For more on urine culture, see “Laboratory tests” under diagnostics in “Urinary tract infections.” Current NBME laboratory reference values can be found under “Tips and Links” below.”

Clinical examination

• Changes in urine and micturition: evaluate amount, frequency, appearance, and discomfort (see table below for details)
• Flank pain
  • Colicky pain radiating to the groin or genitals is most commonly seen in urolithiasis
  • Persistent pain: indicative of inflammatory diseases (e.g., pyelonephritis)
• Costovertebral angle tenderness: : characteristic of pyelonephritis
• Nausea/vomiting: can be a sign of end-stage renal disease: or urolithiasis
• Hypertension: : can be an extrarenal manifestation of kidney injury
• Peripheral edema: : See “Proteinuria.”
• Pericardial friction rub: : See “Uremic pericarditis.”
• Pulmonary edema: can indicate volume overload due to renal injury with low urine output
• Skin changes: can be indicative of an underlying systemic disease
  • Allergic rash (e.g., tubulointerstitial nephritis, systemic lupus erythematosus)
  • Petechiae, purpura (e.g., Henoch-Schonlein purpura, thrombotic thrombocytopenic purpura)

Acute appendicitis should be differentiated from right-sided renal colic. Findings that suggest appendicitis include nausea, fever, and pain at McBurney point (see appendicitis signs).

Changes in micturition

Changes in urine

Urinalysis involves the gross examination of urine, chemical evaluation using urine dipstick, and microscopic assessment of urine sediment. Further tests include urine culture and urinary electrolyte levels. Indications for urinalysis include renal, urinary, and metabolic conditions.

Gross urine assessment

• Urine color
  • Normal: pale yellow to dark amber
  • Red urine: See “Hematuria.”
  • Black urine: alkaptonuria
• Turbidity: (cloudiness of the urine): cloudy urine suggests infection or chyluria

Certain drugs (e.g., rifampin, phenazopyridine), foods (e.g., beetroot), and types of porphyria cause red discoloration of urine.

Urine dipstick

A diagnostic tool consisting of a urine test strip that allows for quick assessment of potentially pathological changes of various parameters.

• pH (urine pH usually ranges from 4.5–8)
• Urine specific gravity: Measures the ratio of urine density over pure water density (normally 1.005–1.030)
  • High urine specific gravity: volume loss, heart failure, presence of large molecules (e.g., glucose, radiocontrast media)
  • Low urine specific gravity: renal failure, diabetes insipidus
• Heme: > 90% sensitivity for hematuria (low specificity)
• Leukocyte esterase: : enzyme produced by WBC that indicates a urinary tract infection
• Protein (albumin): See “Proteinuria.”
• Glucose: glycosuria is a key finding of diabetes mellitus
• Ketones: ketonuria can help diagnose diabetic ketoacidosis, a complication of type 1 diabetes mellitus
• Urobilinogen: See “Prehepatic jaundice” and “Intrahepatic jaundice.”
• Nitrite: : indicative of urinary tract infection caused by gram-negative bacteria (e.g., Enterobacteriaceae)

A urine dipstick cannot differentiate between hematuria, hemoglobinuria, or myoglobinuria!. Therefore, every positive test result for heme must be confirmed with the presence of RBCs on microscopy.

Urine sediment

• Indications: can help identify acute and chronic kidney diseases, classify renal calculi, and diagnose UTIs
• Method: Urine is centrifuged and the pellets are examined under the microscope (supernatant is discarded).
• Assessment: provides valuable information about the underlying cause of kidney damage
  • Cells
    • Erythrocytes
    • Leukocytes
    • Acanthocytes
  • Urinary casts: Tubular structures formed in the distal convoluted tubule and collecting duct of the kidneys that are indicative of a disease affecting the renal tubules and/or glomeruli
    • See table below for details.
  • Crystals: See overview of urinary calculi.
  • Bacteria
  • Yeast

Further laboratory tests

• Urine osmolality
  • Can be used to evaluate urine concentration
  • More accurate than the dipstick measurement for specific gravity
• Urine osmolar gap (UOG): The difference between measured urine osmolality and calculated urine osmolality, used to estimate urine NH₄⁺ concentration in metabolic acidosis.
• Urine electrolytes
  • Urine sodium (Na⁺): e.g., low urine sodium indicates that the kidneys are trying to retain free water by reabsorbing Na⁺ (e.g., due to dehydration)
  • Fractional excretion of sodium: can help determine the cause of acute kidney injury
• Urine creatinine: used to calculate creatinine clearance
• Urine culture: see diagnosis of UTIs

Overview

• Parameters of renal function allow for the evaluation of changes in renal function.
• Inulin clearance and creatinine clearance (with 24-hour urine collection): allow for the most accurate calculation of the glomerular filtration rate
• Serum creatinine and serum cystatin C allow for indirect measurement of the glomerular filtration rate (see estimated GFR).
• Urea (BUN) and uric acid are largely dependent on renal excretion; however, they only provide an inaccurate assessment of renal function.
• Fractional excretion of urine is used to establish the cause of acute kidney injury.
• Current NBME laboratory reference values can be found under “Tips and Links” below.”

Glomerular filtration rate (GFR) ^[3][4]

• Defined as the 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
• 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 10 years.
• GFR can be calculated or estimated using various methods (e.g., estimated GFR).

Serum creatinine

• Indirect indicator of renal function
  • Creatinine is a metabolite of creatine in the muscle (creatine + ATP ⇄ phosphocreatine + ADP).
  • Creatinine is entirely removed by glomerular filtration.
  • Because creatinine is produced at a relatively constant rate and freely filtered by the glomeruli, it can be used to estimate GFR.
• Creatinine-blind range
  • Serum creatinine levels do not start rising until the GFR is reduced by approx. 50%.
  • If the GFR is > 60 mL/min, serum creatinine cannot be used to assess kidney function.
• Additional interfering factors:
  • Increased creatinine levels
    • High-protein diet
    • High muscle mass
    • Rigorous exercise
  • Decreased creatinine levels: low muscle mass

Serum creatinine levels do not start rising until the GFR is reduced by approx. 50%.

Creatinine clearance

• Used in clinical settings to approximate the glomerular filtration rate (GFR)
• Slightly overestimates GFR because of minimal creatinine secretion in the proximal tubules ^[5]
• A precise evaluation of creatinine clearance requires measuring creatinine in the urine over a 24-hour period.

• Creatinine clearance = (Crea_Urine x V) / Crea_Plasma ≈ GFR
  • Crea_Urine = creatinine concentration in urine
  • V = rate of urine flow in mL/min (volume/time)
  • Crea_Plasma = creatinine concentration in plasma

Creatinine clearance can be used to approximate the GFR.

Estimated GFR (eGFR)

• Calculated using serum creatinine concentration and demographic data
• Several prediction equations can be used in clinical practice.
  • Cockcroft-Gault equation
    • Creatinine clearance = [(140 – age) x weight (kg) x constant] / Constant = serum creatinine (mmol/L)
  • Modification of Diet in Renal Disease (MDRD) study equation
  • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

Serum cystatin C

• A more precise indicator of the GFR than serum creatinine
• Cystatin C is a small protein that inhibits cysteine proteinases and is produced by all nucleated cells.
• Analysis is more complex and expensive; therefore, not routinely ordered.
• Lower “blind range” than serum creatinine: used particularly when urine sampling is not feasible (e.g., in infants)

Blood urea nitrogen (BUN)

• A waste product produced by the liver in the urea cycle after protein degradation
• Filtered and excreted by the kidneys
• Elevated with
  • Reduced GFR
  • High protein diet
  • Protein catabolism

BUN/creatinine ratio

• Can help diagnose the underlying cause in acute kidney injury
  • 10:1–20:1 can be normal or may indicate a postrenal cause.
  • ≥ 20:1 indicates prerenal cause: Urea reabsorption is increased, which is typical in patients with dehydration or hypoperfusion.
  • ≤ 15:1 indicates intrarenal cause: Renal damage causes decreased urea reabsorption.

Fractional excretion of sodium (Fe_Na)

• Definition: percentage of the glomerular filtered sodium (Na_Filtered) that is eventually excreted in the urine (Na_Excreted)
• Usage
  • Can help establish the cause of acute kidney injury
  • Can help distinguish between renal and extrarenal etiology in hypotonic hyponatremia (see “Diagnostic approach to hyponatremia”)
• Calculation
  • Filtered Na = Na_Plasma x GFR
  • Excretion rate of Na = Na_Urine x V
  • Fe_Na = Na_Excreted / Na_Filtered
  • Fe_Na = (Na_Urine x V) / (Na_Plasma x GFR)
  • Fe_Na = (Na_Urine x V) / (Na_Plasmax [Crea_Urine x V / Crea_Plasma])
  • Fe_Na = (Na_Urine x Crea_Plasma) / (Na_Plasmax Crea_Urine)
• Interpretation
  • In acute kidney injury
    • Low Fe_Na (< 1%): indicates a prerenal cause (renal hypoperfusion)
    • High Fe_Na (> 2%): indicates an intrarenal etiology (e.g., acute tubular necrosis)
    • Inconclusive Fe_Na (1–2%): can be seen with either disorder
  • In hypotonic hyponatremia
    • Low Fe_Na (< 1%): extrarenal cause
    • High Fe_Na (> 1%): renal cause

Additional blood tests

• Autoantibodies: : particularly antinuclear antibodies (ANCA) as an indication of glomerulonephritis
• Uric acid: a metabolite of purine bases
  • Uric acid crystals can form in the joints, where they can trigger inflammatory reactions and pain (i.e., gout attack).
  • Hyperuricosuria can lead to uric acid nephropathy.
• Other parameters that should be evaluated in renal disease (particularly in chronic renal failure) are serum electrolytes (Na⁺, K⁺, Ca²⁺, phosphate), vitamin D, and parathyroid hormone (PTH).
  • See the Diagnostics section of CKD for details.

Renal parameter changes

Overview

• Usually performed percutaneously under local anesthesia and with ultrasound guidance.
• Examination of the tissue sample includes light, immunofluorescence, and electron microscopy.
• The most common complication is bleeding.

Indications

• Nephritic and/or nephrotic syndrome with no apparent underlying disease: allows diagnosing type of glomerulonephritis
• Suspected lupus nephritis
• Rapidly progressive glomerulonephritis
• Renal transplant rejection or dysfunction
• Unexplained acute kidney injury

Contraindications

• Solitary kidney (relative contraindication)
• Infection of the kidneys
• Coagulation disorders (e.g., thrombocytopenia, disorders of the platelet function, bleeding diathesis)
• Uncontrolled hypertension
• Anatomic abnormalities
  • Abnormal position of the kidneys
  • Atrophic kidneys
  • Vascular malformations in the kidney region
• Hydronephrosis
• Multiple, bilateral renal cysts
• Renal tumor

• One-Minute Telegram 14-2020-3/3: GFR formulas are just estimates, but can we estimate better?

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2. Urinalysis. https://library.med.utah.edu/WebPath/TUTORIAL/URINE/URINE.html. Updated: January 1, 2017. Accessed: April 16, 2018.
3. Redal-Baigorri B, Rasmussen K, Heaf JG. Indexing glomerular filtration rate to body Surface area: clinical consequences. J Clin Lab Anal. 2013; 28 (2): p.83-90. doi: 10.1002/jcla.21648 . | Open in Read by QxMD
4. GFR. https://www.kidney.org/kidneydisease/siemens_hcp_gfr. . Accessed: May 31, 2018.
5. Lin Y, Bansal N, Vittinghoff E, Go AS, Hsu C. Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study. BMC Nephrol. 2013; 14 (1). doi: 10.1186/1471-2369-14-268 . | Open in Read by QxMD
6. Fischbach FT, Dunning MB. A Manual of Laboratory and Diagnostic Tests. Lippincott Williams & Wilkins ; 2009