Renal Function Tests

Urine examination is one of the most important, simple, and non-invasive diagnostic tests in renal disease. Here are some key points:

• Urine should be examined fresh, preferably within 1 hour of voiding.
• If a delay is anticipated, it can be stored at 4°C in the refrigerator, adding a few drops of acetic acid.
• Methods of urine collection include:
  • Supra-pubic aspiration (SPA)
  • Mid-stream urine (MSU)
  • Clean catch
  • Catheter specimen
  • Bagging
  • Use of sterile nappies

Urine Microscopy

Urine microscopy involves examining the sediment of centrifuged urine under a microscope. Key points include:

• Urine is centrifuged at 3000 rpm for 3-5 minutes.
• The sediment is examined under the microscope.
• Items that can be seen include cells (erythrocytes, leukocytes, epithelial cells), casts (hyaline, granular, erythrocyte), crystals, and bacteria.
• Red cell casts are seen in glomerular diseases, while intact red cells indicate lower urinary tract diseases.
• More than 5 RBC/HPF (red blood cells per high-power field) indicate haematuria.
• More than 5 WBC/HPF (white blood cells per high-power field) indicate leucocyturia.
• For un-centrifuged urine, the presence of 1 bacterium indicates significant bacteriuria.

Urine pH

Urine pH measurement is useful for screening for Renal Tubular Acidosis. Key points include:

• Normal pH range is 4.5–7.0.
• pH varies with food intake, with lower pH observed with a high-protein diet.
• pH >7 may suggest defective acidification in the absence of infection and prolonged storage.

Sodium Excretion

Sodium excretion is assessed using the fractional excretion of sodium (FENa+), calculated from a random urine sample and a blood sample collected at the same time. Key points include:

• FENa+ < 1% indicates pre-renal conditions, while a value of 3% indicates intrinsic renal disease.
• This test is invalidated by prior administration of diuretics or sodium-containing fluids.

Proteinuria

Proteinuria testing involves various methods:

• Urine can be tested for protein using dipstick, sulpho-salicylic acid, and boiling.
• Normal value is less than 150mg/24 hours.
• For a random urine specimen, protein/creatinine should be less than 20mg/mmol or less than 0.2mg/mg.
• Protein/creatinine ratio is used in patients with proteinuria, such as those with nephrotic syndrome.

Specific Gravity

Specific gravity assessment indicates the patient's ability to concentrate urine:

• Normal range is 1.010 to 1.030.

Osmolality

Osmolality measures the number of solute particles per unit volume:

• Normal range is 40–1,500 mOsm/l.
• After an overnight fast, early morning urine osmolality should exceed 800mOsm/kg, and specific gravity should be greater than 1.015.

Glomerular function assessment centers around the glomerular filtration rate (GFR):

• The glomerular filtration rate (GFR) is the most comprehensive indicator of glomerular function.
• GFR measures the rate at which substances in plasma are filtered through the glomerulus and is usually expressed in milliliters per minute.
• An ideal marker or substance for GFR measurement possesses certain properties:
• It should be freely filtered at the glomerulus.
• It should achieve a stable plasma concentration.
• It should not be reabsorbed, secreted, or metabolized by the kidney.

Exogenous Markers of GFR

• Inulin: A polysaccharide considered the reference method for GFR estimation. It involves infusing inulin and measuring blood levels after a specified period to determine its clearance rate.
• Radioisotopes: Including Chromium-51 ethylene-diamine-tetra-acetic acid (51 Cr-EDTA), and Technetium-99-labeled diethylene-triamine-pentaacetate (99 Tc-DTPA).
  • Chromium-51 ethylene-diamine-tetra-acetic acid (51 Cr-EDTA)
  • Technetium-99-labeled diethylene-triamine-pentaacetate (99 Tc-DTPA)
• Non-radioactive contrast agent (Iohexol): Particularly useful in children.
• The use of exogenous markers requires testing in specialized centers and can be challenging to assay these substances.

Endogenous Markers of GFR

Endogenous markers commonly used for GFR assessment include:

• Creatinine
• Blood Urea Nitrogen (BUN)
• Cystatin C

Principles of GFR Calculation

• Amount of substance filtered = the amount excreted.
• Amount filtered = GFR × plasma concentration (P).
• The amount excreted = Urine concentration (U) × Urine flow rate.
• Thus, GFR × P = U × V.
• Therefore, GFR = (U × V) / P.

Normal Adult Values of GFR

Normal adult values of GFR are reached by 2 years of age:

• Neonate: 26 ± 2 ml/min/1.73 m²
• 1–2 weeks: 54 ± 8 ml/min/1.73 m²
• 6–12 months: 77 ± 14 ml/min/1.73 m²
• 1–2 years: 96 ± 22 ml/min/1.73 m²
• Adult: 118 ± 18 ml/min/1.73 m²

Estimation of GFR using formula

Schwartz Formula (Old Schwartz Formula) for Paediatrics

Estimation of GFR (eGFR) by using serum creatinine and height values:

K = 0.33 for low-birth-weight babies (<2.5 kg birth weight) in the first year of life

K = 0.45 for term, normal infants during the first year of life

K = 0.55 for children and adolescent girls

K = 0.70 for adolescent boys

Modified Schwartz Formula for Paediatrics

eGFR (ml/min × 1.73 m²) = 0.413 × Ht (cm) / Serum Cr (mg/dl).

Other Formulae for eGFR

• Cockcroft–Gault equation
• Modified Diet in Renal Disease (MDRD) equation
• CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation

Radioisotope-Based Methods

Cystatin C-based equations, e.g., Filler’s formula:

The primary roles of the renal tubules are fluid and electrolytes re-absorption and urinary acidification.

• Water Excretion:
• Urine concentration
• Specific gravity (SG)
• Test of Glycosuria
• Excretion Rate of Electrolytes
• Renal Capacity to Acidify the Urine:
• Serial urine pH
• Bicarbonate excretion
• Titratable acid and ammonia excretion
• Ammonium chloride challenge test

• Plain Film of the Abdomen (Kidney, Ureters, and Bladder - KUB):
• Indicated for detection of nephrocalcinosis or renal stones that are radio-opaque
• Intravenous Urography (IVU):
• Shows kidney size and shape; excellent for demonstrating upper urinary tract anatomy
• Limited in detecting renal scars
• Indications include:
• When detailed calyceal anatomy is required (e.g., medullary necrosis)
• Renal calculi
• Suspected occult duplex kidney
• Provides detailed definition of the ureters
• Voiding Cysto-Urethrography (VCUG):
• Outlines the lower urinary tract; may also show upper urinary tract
• Contrast material is introduced via catheter into the bladder, and serial x-rays are taken before, during, and after voiding
• Useful in grading reflux (VUR)
• Indications include:
• Male infants with UTI
• Suspected ureteric dilatation
• Small contracted kidney
• Obstructive uropathy
• Antegrade Pyelography and Retrograde Pyelography
• Renal Arteriography:
• Used in suspected renovascular hypertension

• Abdominal Ultrasonography (US):
• A common imaging modality
• Non-invasive, absence of radiation, and easy accessibility
• Provides information on location, size, structure, and consistency of the kidney
• Useful in hydronephrosis, nephroblastoma, polycystic kidney disease, and neuroblastoma
• Limitations:
• Operator dependent
• Unreliable in detecting renal scarring, VUR, renal arterial abnormality, and mid-ureteric lesions
• Radioisotope Studies:
• Can be divided into:
• Dynamic renogram
• Static renal scan
• Cystography
• Dynamic Isotopic Renogram:
• Commonly used substances: Diethylene Triamine Penta-acetic Acid (DTPA) and Hippuran
• Provides information on the physiologic function of the kidney
• Static Renal Scan:
• Uses Dimercaptosuccinic Acid (DMSA) to detect renal scarring
• Most sensitive method for detecting renal scarring
• Indications include:
• Detection of focal parenchymal abnormalities
• Acute phase of pyelonephritis to demonstrate parenchymal involvement
• Detection of scar in the late phase
• Location of ectopic/absent kidneys
• Renovascular diseases and dribbling urinary incontinence

Other Imaging Techniques

• Computerized Tomography (CT):
• Provides clearer resolution of the kidney and surrounding structures
• Evaluation of renal tumors
• Magnetic Resonance Imaging (MRI):
• Indicated in children with neuropathic bladder
• Used for those with abnormal spinal radiograph

Various blood tests are done primarily to detect the presence of renal dysfunction and assess the degree of renal dysfunction.

Blood chemistry:

• Urea
• Creatinine
• Sodium
• Potassium
• Bicarbonate
• Calcium metabolism (calcium, phosphate, vitamin D, parathyroid hormone)

These tests assess the kidney's role in homeostasis.

Haematologic tests:

• FBC (Full Blood Count)
• Platelets
• Haematocrits
• ESR (Erythrocyte Sedimentation Rate)

Arterial blood gases:

Useful in assessing renal tubular acidosis.

Immunologic tests:

Evaluated in suspected immune-mediated renal diseases such as post-infectious acute glomerulonephritis and systemic vasculitidies.

• C3
• C4
• Anti-streptococcal antibodies
• Circulating immune complexes

Hormonal profiles:

• Parathyroid hormone

Indication:

• Nephrotic syndrome (steroid resistance, onset of NS in less than 1 year, atypical presentation-low serum complements)
• Acute renal failure with rapid deterioration, protracted course, or lack of response to treatment
• Acute nephritic syndrome with atypical course
• Systemic diseases with renal involvement
• In selected cases of chronic renal failure which is not associated with small, shrunken kidney

Contraindication:

• Single kidney
• Bleeding diathesis

Relative contraindication:

• Shrunken kidney
• Severe hypertension

Complications:

• Bleeding
• Haematuria
• Infection
• Transient hypotension
• Rarely arterio-venous fistula

Cystoscopy:

Evaluation of lower urinary tract.

Urodynamic Studies:

The study of pressure-volume relationship in the different compartments of urinary tract.