INVESTIGATIONS IN RENAL MEDICINE

LEARNING OBJECTIVES

Students should be able to :  Basic and advance renal investigations  When, how, which and what type of investigation to be sent according to renal illness  The basics that how such investigation to be interpret  The significance of test in disease, its prognosis and monitoring.

How Useful Labs     

To identify renal dysfunction To diagnose renal disease To monitor disease progression To monitor response to therapy To assess changes in function that impact on therapy eg:chemotherapy

RENAL FUNCTIONS        

Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone Metabolites Regulation of water - electrolyte balances, body fluid osmolality Regulation of arterial pressure Regulation of acid-base balance Regulation of Erythrocyte Production

INVESTIGATIONS  Urinalysis  Blood analysis  GFR measurement and other special tests  Imaging  Renal biopsy

URINE ANALYSIS • • • • • • • • •

Physical examination Chemical examination Bacteriological and Microscopic examination 24 hour urinery out put [volume] Appearance, Colour, Turbidity pH Specific gravity Osmolality

 Dependent upon subject’s activity,hydration status, diet and body size  Temperate climates: output of 800-2500 ml urine per day is usual  Sudden changes in volume of urine can indicate problems with ability to concentrate urine.

INVESTIGATIONS – URINALYSIS APPEARANCE: o The normal urine is amber, however it has a little value in the diagnosis of renal disaeses.

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The abnormalities seen include:Bloody urine eg in Schistosomiasis infection. o Turbid urine eg in UTI o Dark or smoky urine eg in Cholestatic jaundice, haemoglobinuria. Drugs.

URINE APPEARANCE DISCOLOURATION

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Deep yellow - Concentrated urine, Jaundice Red urine - Haematuria, Haemoglobinuria Myoglobinuria, Porphyria, Beet root ingestion Drugs - rifampicin, pyridium Cloudy -Infection Milky – Chyluria, Pyuria, Phosphaturia Dark on standing –Porphyria, Alkaptonuria

INVESTIGATIONS – URINALYSIS pH:

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Normal Urinary pH is 4.0-8.0, Abnormalities in the pH may be helpful in the diagnosis and treatment of some urologic conditions. Alkaline urine in a patient with a urinary tract infection suggests the presence of Proteus mirabilis, Klebsiella, Pseudomonas, and Staphylococcus. Failure to acidify the urine below a pH of 4.0 despite a metabolic acidosis suggests a distal renal tubular acidosis.

INVESTIGATIONS – URINALYSIS SPECIFIC GRAVITY AND OSMOLALITY: S G measures the weight of the dissolved particles in the urine, while osmolality measures the no of the dissolved particles in the urine. The normal SG IS 1.001. when it is 1.010 it implies CRF, if it’s 1.025 it implies the pre renal phase of Acute Tubular Necrosis.

OSMOLALITY OF URINE      

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Measures urine concentrating ability Depends on # of particles, not size or charge Largely due to ADH (anti-diuretic hormone) Can reach maximum of 1200 mOsm/L Normal range: 300-900mOsm/L, plasma 285+10 prior to collection, fluid intake restricted, first void submitted for evaluation

PROTEIN: the normal daily urine protein output is < 30mg . Detection is primarily by urine dipstick, they are sensitive to 200 -300mg/L of protein and have almost superseded the more cumbersome suphosalicylate acid test. Heavy proteinuria is nearly almost of glomerular origin eg Nephrotic Syndrome, Diabetic Nephropathy, Hypertensive Nephropathy.

INVESTIGATIONS – URINALYSIS Proteinuria Score CONCENTRATION

SCORE

5-20mg/dl

TRACE

30mg/dl

+

100mg/dl

++

300mg/dl

+++

>2000mg/dl

++++

MICROALBUMINURIA

is the excretion of albumin by an individual

between 30mg-300mg/24hrs • Microalbuminuria signifies early stage of kidney damage in certain disease condition like DM,severe HT andCCF.

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BLOOD : Using the dipstick in urine, blood should not be present in the urine. Stix tests for blood are very sensitive. It is +ve if there are 2 or more cells. False positives are due to:

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Menstrual blood Dehydration (raised sp gravity) Exercise (bladder contusions)

DIPSTICK URINE DIPSTICKS

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Strip impregnated with reagents for the substances in question within a urine sample Substance level can be altered in the setting of pathology within the urinary tract Measured substances: Modern dipsticks with multiplied zones:

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Protein, hemoglobin, glucose, urobilinogen, nitrite, leukocytes, specific gravity, and pH.

FORMED ELEMENTS • • • • •

Epithelia, red cells, white cells Crystals Mucus Renal casts Microorganisms

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Usually of no clinical significance 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 URINALYSIS – MICROSCOPY

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White cells: they are not expected to be more than 5/hpf. If it is, then it indicates an inflammatory reaction within the tract. Red cells: the presence of >1-2rbc/hpf in male and 2-3rbc/hpf in female indicates microscopic haematuria. Casts: it could be granular, hyaline or cellular. Granular cast is seen in CRF and the recovery phase of ARF.

LEUKOCYTES • • •

Pus, or pyuria May indicate urinary tract infection UTI if more than 10/HPF Glitter cells in dilute alkaline urine

ERYTHROCYTES • • •

Hematuria may indicate renal damage Menstrual contamination May be crenated or ghost cells

URINE SEDIMENTS • •

CASTS Cylindrical bodies formed by coagulation of Tomm-Horsfall glycoprotein within the tubules hallmark of renal parenchymal disease often seen normally after exercise Pseudocasts :Are composed of clumped urates, leucocytes and bacteria.

URINALYSIS – MICROSCOPY • • •

Hyaline cast is seen in normal urine or after exercise. Red blood cell cast is seen in glomerular disease esp glomerulonephritis White cell casts are found in acute pyelonephritis

URINE SEDIMENTS

URINE SEDIMENTS Common Crystals in Acid pH •

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Amorphous Urate

– Orange powder – May clear with warming or saline Uric Acid

– Brown lemon shaped or star shaped – Birefringent with polarized light Calcium Oxalate

– Envelope

URINE SEDIMENTS

URINE SEDIMENTS Common Crystals in Alkaline pH

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Amorphous Phosphate

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White powder May clear with saline

Triple Phosphate

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Coffin lid

Ammonium Biurate

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Thorn apple

Calcium Carbonate

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Effervesce with SSA

BLOOD CHEMISTRY Impairment of renal function leads to elevation of end products of protein metabolism thus increased accumulation of urea,BUN, & creatinine in blood & azotemia Results.

Clinical Assessment of Renal Function: Glomerular Filtration Rate(GFR) •

Parameters used Blood urea nitrogen Serum creatinine Endogenous creatinine clearance

GFR •

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The glomerular filtration rate (GFR) provides a useful index of overall renal function; Daily GFR in normal individuals is variable depending on the gender, with a range of 90-130 mL/min/ 1.73 m2 of body surface area. GFR can be measured indirectly by determining the renal clearance of plasma substances which are not bound to plasma proteins, are freely filterable across the glomerulus, and are neither secreted nor reabsorbed along the renal tubules, such as Inulin or Evans blue.

Urea •

End-product of protein metabolism chiefly excreted through the kidney • It is filtered by the glomeruli and variably reabsorbed in the tubules • The normal plasma concentration is 20-40 mg/dl • Blood urea concentration is about 14% less than plasma concentration

CREATININE • • • •

Formed at a constant rate by dehydration of muscle creatine Normally 1–2% of muscle creatine is broken into creatinine Mol. Wt. 113 Creatinine is freely filtered by the glomerulii and is not reabsorbed 10–15% is secreted into proximal tubule

CREATININE • • •

Normal serum level 1–2 mg/dl 24 hour creatinine excretion 20 mg/kg/day for males 15 mg/kg/day for females Children, females, elderly, spinal cord injured have low serum and urine creatinine

BUN •

Normal BUN range is 8-25 mg/dL

BUN/CREATININE RATIO 10:1 • •

Normal Chronic renal failure

RENAL CLEARANCE TESTS •

To assess GFR & renal blood flow “renal clearance of a substance is the volume of plasma that is completely cleared of the substance by the

kidneys per unit time”

Urea clearance test •

No need of IV infusion • Less sensitivity test because plasma concentration of urea is affected by number of factors • Like dietary protein,fluid intake, inflammation, trauma, surgery, corticosteroids • Partly reabsorbed from tubules CREATININE CLEARANCE TEST Does not require intravenous infusion. Method is much more widely used than inulin clearance for estimating GFR clinically. Creatinine clearance is not a perfect marker of GFR because a small amount of it is secreted by the tubules.

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normally 90-130 ml/min in an adult of normal Size approx- 100 mL/min/1.73 m2 in healthy young women 120 mL/min/1.73 m2 in healthy young men. The Ccr declines by an average of 0.8 mL/min/yr after age 40 years as part of the aging process.

INVESTIGATIONS – IMAGING

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Plain X-ray Cystoscopy Excretion urography Ultrasonography Computed tomography (CT) Magnetic resonance imaging (MRI)

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Antegrade pyelography Retrograde pyelography Micturating cystourethrography (MCU)

Aortography or renal arteriography Renal scintigraphy – dynamic and static

INVESTIGATIONS – IMAGING •

Plain X-ray: A plain abdominal X-ray mainly identifies renal calcification or radiodense calculi in the kidney, renal pelvis,line of the ureters or the bladder.

INVESTIGATIONS – IMAGING •

Cystoscopy: this involves direct inspection of the bladder interior using an instrument called cystoscope. It can show exactly where the problem is in the bladder and biopsies can be taken while in there. It is cheap but unpleasant for the patient.

INTRAVENOUS UROGRAPHY:

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It has been for many years the standard imaging procedure for evaluating the urinary tract since it provides an assessment of the kidneys, ureters, and bladder. The dye`is filtered and secreted by the renal tubules in normal kidneys, resulting in a nephrogram formed by opacification of the renal parenchyma.

INVESTIGATIONS – IMAGING •

It is performed to obtain a detailed view of the pelvicaliceal system, assess renal size and shape, detect and localize renal stones, and assess renal function. It is particularly useful in diagnosing certain disorders such as medullary sponge kidney and papillary necrosis.

INVESTIGATIONS – IMAGING

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Ultrasonography: It has an advantage over X-ray techniques of avoiding ionising radiation and IV contrast medium, it uses high frequency sound waves. In renal diagnosis, it is the method of choice for

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Measure sizes of parts of renal system. Check for blood vessel diameter. Checking whether masses are cysts or solid/textured. Measure perfusion, check for clots (uses Doppler shift in signal). Check bladder wall thickness, stones or emptying.

Disadvantages are:

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Lack of details Relies on the expertise of the operator May miss small stones or those in the ureter It has poor specificity and sensitivity

INVESTIGATIONS – IMAGING •

CT Scan: it is a 3D imaging and it’s used mainly as a second line imaging method in the urinary tract, but first line investigation in cases of suspected ureteric colic. It helps to stage renal tumor, to visualise

arteries and veins and also useful for finding structural abnormalities.

INVESTIGATIONS – IMAGING •

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MAGNETIC RESONANCE IMAGING: this is not usually used except to view renal massses not identified by the previous methods. It does the following; Stage renal, prostate and bladder Ca. Demonstrates the main vessels and their blood flow. It is however expensive

Magnetic Resonance Imaging INVESTIGATIONS – IMAGING

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ANTEGRADE PYELOGRAPHY: this involves percutaneous injection with needle at the level of renal pelvis (junction between kidney and ureter). Inject contrast medium to show where obstruction in tract occurs. Often used after ultrasound has shown there is a problem. Focuses on renal pelvis and ureters

INVESTIGATIONS – IMAGING •

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Retrograde Pyelography:

this is done following cystoscopy, inject contrast medium at the bottom of the ureter. It is mainly used to investigate lesions of the ureter and to locate the level of the ureteral obstruction. It is invasive, requires a GA and may result in the introduction of

infection.

INVESTIGATIONS – IMAGING • •

Renal Angiography: This is mainly used to define extrarenal or intrarenal arterial disease. Convectional or digital subtraction angiography is used. It is the Gold standard of renal artery imaging. Usually indicated prior to renal transplant in the donor.Complication include cholesterol embolizations and contrast induced kidney damage.

INVESTIGATIONS – IMAGING •

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Micturating Cystourethrography – MCU: This involves catherization and the instillation of contrast medium into the bladder. The catheter is then removed and the px is screened during voiding to check for vesicoureteric reflux and to study the urethra and bladder emptying. it is invasive.

INVESTIGATIONS – IMAGING Aortography or Renal Arteriography: the 2 typesare Conventional and Digital Subtraction Angiography. DSA is commonly used because it allows for the use of small doses of contrast medium. Inject it into larger artery or vein near kidneys. • Mainly used to monitor extrarenal or intrarenal arterial disease. • Invasive, but becoming more routine. • Less discomfort for px, (Usually insert catheter through small incision in groin – (e.g. femoral vein).

AORTOGRAPHY OR RENAL ARTERIOGRAPHY INVESTIGATIONS – IMAGING

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Renal Scintigraphy: This uses gamma camera and can be divided into: Dynamic studies where kidney function monitored serially over period of time, most often by using a radiopharmaceutical excreted by glomerular filtration. Static studies involving imaging of tracer that is taken up and reained by the renal tubule.

INVESTIGATIONS – IMAGING

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Dynamic Scintigraphy: Here, radiopharmaceutical technetiumlabelled diethlenetriaminepentaacetic acid ; 99Tcm-DTPA excreted by glomerular filtration. 123

I labelled ortho- iodohippuric acid (Hippuran ) is both filtered and excreted by tubules.Following venous injection with tracer, emissions from kidney recorded and computer analyses time-activity curves. Allows examination of renal blood perfusion, glomerular filtration, transit through kidney and outflow from urinary tract. It can however give false-positive or false-negative results. Less invasive and can give a lot of information about whole urinary system over time. Can monitor more realistic physiological conditions.

INVESTIGATIONS – IMAGING

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STATIC SCINTIGRAPHY: Performed using 99TcmDMSA, which is taken up by tubular cells.Uptake is proportional to renal function. The Function is evenly divided between kidneys. This technique good for looking for problems that only

affect one kidney as can detect imbalances in function.Normal kidneys show uniform uptake with smooth renal outline.

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Again, less invasive and tells us about actual function, but only gives us a snapshot of what is going on and poor anatomical resolution. RENAL BIOPSY

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This is ultimate in the diagnosis and assessment of most chronic kidney disease. It is done percutaneous under ultrasound guidance. There are indications,contraindications and complications for this procedure.

INDICATIONS FOR RENAL BIOPSY

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Investigation of proteinuria of unknown cause or suspected glomerular disease. Microscopic hematuria Diagnosis of rejection in renal transplant Further investigation of prolonged acute renal failure Unexplained chronic renal failure Systemic disease with proteinuria

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TAKE HOME MESSAGE So at the end we are able to send appropriate lab investigation according to individual patient We are now Able to know, interpret basics of urinalysis Able to understand advance lab investigations in renal medicine When ,how and which lab is suitable for which patient.

THANKS