What You Will Learn
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- The kidneys are retroperitoneal organs with various roles in the body.
- They are highly perfused organs, receiving 20-25% of cardiac output.
- The structural and functional unit of the kidneys is the nephron, which has various segments/parts:
- Renal corpuscle - Bowmanâs capsule and the glomerular capillary tuft.
- The tubules.
- The collecting systems.
- The kidneys are almost completely silent in health and remain so until their functions are severely impaired.
- Renal function tests (RFT) are a group of tests that evaluate kidney functions.
Excretory and Regulatory Functions
- Removal of water-soluble nitrogenous waste products of metabolism (urea, creatinine, urate) and catabolic turnover of cells, and the elimination of drugs and toxins;
- Maintenance of water, electrolyte (ion concentrations), and acidâbase balance (pH of body fluids);
- Regulation of extracellular fluid volume;
- Maintenance of body fluid composition;
- Maintenance of blood pressure.
Metabolic Function
- Gluconeogenesis.
Endocrine Functions
- Renin production;
- Erythropoietin production: control of erythropoiesis;
- Synthesis of 1,25-dihydroxycholecalciferol;
- Catabolism of polypeptide hormones (e.g., parathyroid hormone, insulin).
The list of investigations of the renal system is extensive and includes:
- Simple urinalysis
- Imaging studies such as MRI and DMSA
The reasons for ordering these investigations include:
- To confirm the clinical diagnosis
- To assess structural and/or functional integrity of the urinary tract
- To assess the severity and extent of disease or the degree of dysfunction
- To obtain data necessary for prognostication
- In anticipation of treatment, e.g., to have "baseline values before nephrotoxic drugs that could further compromise the kidney
- To exclude or eliminate other differentials
Classification of Investigations for Renal System
Investigations for the renal system can be grouped into 7 broad categories:
- Urine Examinations: These tests involve analyzing urine samples to assess kidney function and detect abnormalities.
- Blood Tests/Chemistry: These tests analyze blood samples to evaluate kidney function, electrolyte balance, and other biochemical parameters.
- Estimation of Glomerular Filtration Rate (GFR): GFR tests measure the rate at which the kidneys filter waste products from the blood.
- Assessment of Tubular Function: These tests evaluate the ability of the renal tubules to reabsorb and secrete substances.
- Imaging Studies: Imaging techniques such as MRI, ultrasound, and DMSA scans provide visual information about the structure and function of the kidneys and urinary tract.
- Renal Biopsy: A renal biopsy involves obtaining a tissue sample from the kidney for microscopic examination to diagnose kidney diseases.
- Miscellaneous/Others: This category includes various other specialized tests and procedures related to kidney assessment.
Urine Examinations
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 4.5â7.0.
- 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 40â1,500 mOsm/l.
- After an overnight fast, early morning urine osmolality should exceed 800mOsm/kg, and specific gravity should be greater than 1.015.
Assessment of Glomerular Functions
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 Ă plasma concentration (P).
- The amount excreted = Urine concentration (U) Ă Urine flow rate.
- Thus, GFR Ă P = U Ă V.
- Therefore, GFR = (U Ă 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 mÂČ
- 1â2 weeks: 54 ± 8 ml/min/1.73 mÂČ
- 6â12 months: 77 ± 14 ml/min/1.73 mÂČ
- 1â2 years: 96 ± 22 ml/min/1.73 mÂČ
- Adult: 118 ± 18 ml/min/1.73 mÂČ
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 Ă 1.73 mÂČ) = 0.413 Ă Ht (cm) / Serum Cr (mg/dl).
Other Formulae for eGFR
- CockcroftâGault 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., Fillerâs formula:
Assessment of Renal Tubular Functions
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
Imaging Studies/Radiological Evaluation
- 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
Blood Tests
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
Renal Biopsy
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
Miscellaneous Investigations
Cystoscopy:
Evaluation of lower urinary tract.
Urodynamic Studies:
The study of pressure-volume relationship in the different compartments of urinary tract.
Evaluation of the renal system is an integral component of managing renal diseases. Simple investigations, such as urinalysis, can be highly reliable when conducted correctly, providing valuable information for identifying various renal disorders. The estimated glomerular filtration rate (eGFR) stands out as the premier indicator of kidney function in clinical practice. Furthermore, it's crucial to customize renal investigations based on the individual patient's clinical condition.
Practice Questions
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