Investigation of renaland urinary tract diseases

th
For 4 year medical student, 2016-2017 . College of Medicine, University of Baghdad
Dr. Mohammed Hannon Al Sodani ,
Consultant Nephrologist , C.A.B.M., F.I.B.M.

Objectives

- Know the main investigations used in renal and urinary tract disease.
- Understand the significance of each investigation
- Correlate between the investigations and the diseases
- Select specific investigations for specific diseases

Serum levels of endogenous compounds excreted by the kidney

Blood urea :- It increases in

- With high protein intake (+ GIT hemorrhage) & catabolic states, surgery, infection. Some drugs
corticosteroids and tetracycline.
- Tubular reabsorption of urea is increased when concentrated urine is produced, elevating blood
levels.
Its reduced in liver failure (low production from protein), anorexia or malnutrition (low protein intake),
and reduced catabolism (old age), Also in pregnancy it decreases Increase GFR (increase elimination)
Serum creatinine :- Reflects GFR (glomerular filteration rate) more reliably than urea,
It is produced from muscle at a constant rate , almost completely filtered at the glomerulus. If
muscle mass remains constant, changes in creatinine concentration reflect changes in GFR.
While in patients with low muscle mass (e.g. the elderly) serum creatinine may not be above normal until
GFR is reduced by > 50%. Serum creatinine and GFR. There is an inverse reciprocal relationship, a
GFR as low as 3040 mL/min without serum creatinine rising.

Important note :- serum urea and creatinine do

not rise above the normal range until there
is a reduction of 5060% in the GFR.
Serum creatinine 5-10% excreted by tubules
Measuring GFR
- Direct measurement using labelled EDTA or inulin. Most accurate but not in clinical practice.

- Creatinine clearance (CrCl) A more accurate measurement of GFR, Serum level is related to 24-hour
urinary creatinine excretion, but 24-hour urine collections are difficult and often inaccurate estimate
creatinine clearance or GFR from S.creatinine are available. Minor tubular secretion of creatinine causes
CrCl to exaggerate GFR when renal function is poor, and can be affected by drugs (e.g. trimethoprim,
cimetidine). Needs 24-hr urine collection (inconvenient and often unreliable)

CrCl (mL/min) = UV / ( P * 1440) =

Urine creatinine concentration (mol/L) Volume of urine (mL)

____________________________________________________
Plasma creatinine concentration (mol/L) time (min) ( 24 hours = 1440 min. )

Estimating GFR eGFR

Estimate creatinine clearance or GFR from S.creatinine are availabe with equations

Cockcroft and Gault (C&G) equation;- accurate at normal to moderately impaired

rena function Estimates CrCl, not GFR , Requires patient weight

CrCl (C&G) =
(140age in yrs) lean body wt (kg) (1.22 males or 1.04 females)
_________________________________________________________
serum creatinine (mol/L)

CrCl (C&G) =
(140age in yrs) lean body wt (kg)
___________________________________ ( x 0.85 for females)
72 * serum creatinine (mg/dl)

MDRD equation The Modification of Diet in Renal Disease study . Performs better than C&G at reduced
GFR. Requires knowledge of age and sex only .Can be reported automatically by laboratories

eGFR = 186* (creatinine in mol/L/88.4) 1.154 (age in yrs) 0.203 (0.742 if female) (1.21 if
black)
Limitations of eGFR-
Its estimation, least reliable at extremes of body composition (e.g. malnourished, amputees etc.) and
hospital inpatients , Creatinine level must be stable over days, underestimate normal or near-normal
function, Both need stable kidney function ( not normal or acute but stable) like CKD.
eGFR is not valid in under-18s or during pregnancy ,originally validated in US patients and eGFR for
any given creatinine was 21% higher in blacks estimate creatinine clearance or GFR from S.creatinine
are available. Normal GFR Normal ranges are 90140 mL/min in men and 80125 mL/min in women.
- Urinalysis detect abnormal constituents that indicate a pathological state.
- General characteristics of urine:
*Volume: normally 1.5 3 L / Day.
*Color: urochrome (amber yellow).
*Transparency: Clear transparent.
*Odor: faint aromatic odor (volatile organic acid)
*PH : slightly acidic 5.5 6.5.
*Physiological and normal constituents of urine: Normally 99 % water and 1% solids. Solids are:
organic substances: urea, uric acid, creatine, creatinine, amino acids, lactic acid , vitamins, pigments,
enzymes , inorganic substances: NH4, SO4, Ca+2, Cl-, PO4, Co3, Na+, K+, Mg+2, NO3, Fe, F, silicate.
The following parameters are normally not present in urine:
1) Glucose: (glucosurea) Dipsticks for glucose are very sensitive, might prompt consideration of
diabetes mellitus.
2) Protein: (proteinurea or albuminurea)
3) Blood: (hematurea or hemoglobinurea) Once found on dipstick, a midstream sample should be
examined for red cells or casts.
A) Dipstick that is strongly positive for haematuria with no red cells seen on microscopy might suggest
haemoglobinuria or myoglobinuria.
B) Red cells (usually 12 per highpower field) are described as dysmorphic if they originate from the early
nephron (glomerular bleeding), and may be accompanied by red-cell casts. Casts are cylindrical bodies,
moulded in the shape of the distal tubular lumen. Red-cell casts even if only single always indicate
renal disease.
NOTES on hematuria: -
*Bleeding may come from any site within the urinary tract.
* Overt bleeding from the urethra is suggested when blood is seen at the start of voiding and then the
urine becomes clear.
*Blood diffusely present throughout the urine comes from the bladder or above.
* Blood only at the end of micturition suggests bleeding from the prostate or bladder base.
*Women will commonly have dipstick-positive haematuria during a period; it is usually
worth repeating testing after menstruation

4) Bile salts: in patients with Jaundice.

5) Ketone bodies or Acetone: could appear in urine in late stages of diabetes mellitus.
6) Bacteria and pus cells: Dipstick tests for bacteriuria are based on the detection of nitrite produced from the reduction
of urinary nitrate by bacteria, and also on the detection of leucocyte esterase, an enzyme specific for neutrophils.
Where positive, a mid-stream sample sent for microscopy, culture and sensitivities (MC&S).
* A measurement of 10 WBCs (pus) /mL in fresh mid-stream urine samples is abnormal and suggests
urinary tract infection (UTI).
*Note:- Not all pyuria is UTI, though; pus cells are seen with renal stones, tubule-interstitial nephritis,
papillary necrosis, tuberculosis and interstitial cystitis. White cell casts may be seen with (and are more
characteristic of) acute pyelonephritis.

Screening for the presence of blood, protein, glucose, ketones, nitrates and leucocytes and to assess pH and
osmolality of urine can be achieved by dipstick testing. Urine microscopy or flow cytometry can detect
erythrocytes, which are indicative of bleeding from the urogenital tract (anywhere from kidney to tip of
penis); dysmorphic erythrocytes, which suggest the presence of nephritis; red cell casts, indicative of
glomerular disease; and crystals, which may be observed in patients with renal stone disease. It should be
noted that calcium oxalate and urate crystals can sometimes be found in normal urine that has been left to
stand, due to crystal formation ex vivo.
The presence of leucocytes and bacteria in urine is indicative of renal tract infection. White cell casts are
strongly suggestive of pyelonephritis.

7) Urine pH can provide diagnostic information in the assessment of renal tubular acidosis.

Other things to examine in urine :-

Appearance :- Unless urine is visibly bloody (or cola-coloured, in cases of myoglobinuria or
haemoglobinuria), inspection of the urine is not helpful. Cloudy, offensive-smelling urine may
denote infection, but this should be further tested by dipsticks.
Volume :- High daily volumes are also seen with glycosuria or increased protein catabolism following
surgery, as the solute load requiring excretion is higher.
Specific gravity and osmolality :- can be helpful in confirming loss of concentrating ability (as might
be seen when tubular function fails in acute tubular necrosis or CKD). It can also be helpful in oliguric
patients, when a high SG might suggest pre-renal AKI, as opposed to established acute tubular
necrosis.
* Urine specific gravity (SG, where <1.008 is dilute and >1.020 is concentrated) is a measure of
the weight of dissolved particles in urine, whereas urine osmolality reflects the number of such particles.

Urine collection over a 24-hour period can be performed to measure excretion of solutes, such as calcium,
oxalateand urate, in patients with recurrent renal stone disease. Proteinuria can also be measured on 24-
hour collections but is usually now quantified by protein/ creatinine ratio on spot urine samples.
Others, including concentrating ability , and calculation of fractional calcium, phosphate or sodium
excretion, stone analysis.
Imaging Techniques

Plain X-rays: renal outlines - opaque calculi (radiodense) - calcification within the renal tract.

Ultrasound: This quick, non-invasive is the first and often the only.
In renal diagnosis, it is the imaging method of choice for:-
A) Assessing renal size and symmetry (normal-sized kidneys with abnormal function suggest an acute cause, as kidneys
scar (chronic) as they fail, and may shrink in length and volume cortico-medullary differentiation is low and
hyperechoic renal cortex), and allowing directed renal biopsy.
B) Ruling out obstruction, either of the bladder and ureters with unilateral or by lateral hydronephrosis, or kidney itself
(where plevicalyceal may suggest ureteric or pelvic disease),,
C) Characterizing renal masses as cystic (either simple cysts or polycystic kidneys) or complex and solid (benign and
malignant renal tumours, and infected collection).
D) Guiding intervention aimed at relieving obstruction (percutaneous nephrostomy).
E) Confirming renal vein patency, and suggesting (but not proving) renal artery disease Doppler ultrasonography (duplex).
F) Looking for bladder tumours or stones. A scan obtained after voiding (post- micturition) allows bladder emptiness to
be assessed

- Renal size and position, detect dilatation of the collecting system ( obstruction) , distinguish tumors
and cysts,the prostate and bladder, and estimate completeness of emptying, with other abdominal,
pelvic and retroperitoneal pathology.

Hydronephrosis is "water inside the kidney refers to distension and dilation of the renal pelvis and calyces,
usually caused by obstruction of the free flow of urine from the kidney.
 - In Chronic Kidney Disease, U/S density (echogenicity) of the renal cortex is increased and cortico-
medullary differentiation is lost Normal kidney ;-The normal cortex is less echo-dense (blacker) than the
adjacent liver.

A simple cyst occupies the upper pole of an otherwise normal kidney.

The renal pelvis and calyces are dilated by a chronic obstructionto urinary outflow. The thinness
and increased density of the remaining renal cortex indicate chronic changes
Doppler techniques show blood flow in extra renal & larger intrarenal vessels.
However, renal ultrasound is:- operator-dependent, stored images convey only a fraction of the
information and it is often less clear in obese patients
Intravenous urography (IVU) ;- X-rays taken at intervals following administration of an IV bolus of an
iodine-containing compound that is excreted by the kidney. An early image (1 minute after injection)
demonstrates the nephrogram phase of renal perfusion followed by contrast filling the collecting
system, ureters& bladder. An excellent definition of the collecting system and ureters.
Superior to U/S for examining renal papillae, stones & urothelial malignancy. The disadvantages of
this technique are the injection of a contrast medium, exposure to irradiation, time requirement,
dependence on adequate renal function,

Intravenous urography (IVU).

A Normal nephrogram phase at 1 minute.
B Normal collecting system at 5 minutes.
C Bilateral reflux

Pyelography direct injection of contrast medium into the collecting system (pelvicalyceal system) from
above or below. Best views of the collecting system and upper tract, used to identify the cause of urinary
tract obstruction. Antegrade pyelography requires the insertion of a fine needle into the pelvicalyceal
system under ultrasound or radiographic control, difficult and hazardous in a non-obstructed kidney. In
the presence of obstruction, percutaneous nephrostomy drainage can be established, and often stents can
be passed through any obstruction. Retrograde pyelography can be performed by inserting catheters into
the ureteric orifices at cystoscopy allowing contrast study of the ureter from the bladder.
Renal arteriography and venography to investigate suspected renal artery stenosis or haemorrhage.
Therapeutic balloon dilatation and stenting of the renal artery bleeding vessels or arteriovenous
fistulae occluded.
Renal arteriography remains the gold standard in the diagnosis of renal artery stenosis.

Computed tomography (CT)

A) Characterizing masses & cystic lesions within the kidney that are indeterminate at ultrasonography.
B) Clear definition of retroperitoneal anatomy regardless of obesity. (retroperitoneum for tumours,
retroperitoneal fibrosis)
C) Even without contrast medium it is better than IVU for demonstrating renal stones.
D) Stage renal and bladder tumours.
E) visualize the renal arteries and veins by CT angiography
DISADVANTAGES radiation and contrast nephrotoxicity.

CT, the Rt kidney is expanded by a low-density tumour which fails to take up contrast
material. Tumour is shown extending into the renal vein and inferior vena cava
CT arteriograms are reconstructed using a rapid sequence technique in which images are obtained
immediately following a large bolus injection of intravenouscontrast medium. This produces high-quality
images of the main renal vessels and is of value in trauma, renal haemorrhage and the investigation of
possible renal artery stenosis. Enables functional assessment of vascular structures, e.g. angiomyolipomas.

Magnetic resonance imaging (MRI) excellent resolution and distinction between different tissues (and
stage the prostate) and the use of MRA in good hands equals to renal angio.
Normal Polycystic kidneys

Magnetic resonanceangiography (MRA) ;- uses gadolinium-based contrast media, which may carry risks for
patients with very low GFR . Good images of main renal vessels but may miss branch artery stenosis

The Food and Drug Administration (FDA) advises not

using gadolinium in patients with renal insufficiency
because of the development of nephrogenic systemic
fibrosis.

Renal artery stenosis. MRA following injection of contrast. The abdominal aorta is severely irregular and
atheromatous. The left renal artery is stenosed.

Radionuclide studies;- A functional studies requiring the injection of gamma ray-emitting

radiopharmaceuticals which are taken up and excreted by the kidney, monitored by an external gamma
camera. (99mTc-DTPA) Diethylenetriamine-Pentaacetic Acid labelled with technetium is excreted by
glomerular filtration. Provides information regarding the arterial perfusion of each kidney. Delayed peak
activity and reduced excretion is seen in RAS. In patients with significant obstruction of the outflow
tract, DTPA persists in the renal pelvis, and a loop diuretic fails to accelerate its disappearance.
*In patients with unilateral renal artery stenosis, there is, typically, a slowed and reduced uptake
of tracer with a delay in reaching a peak.

Following intravenous injection, images of the renal cortex show the shape, size and relative function
of each kidney. Sensitive method for showing cortical scarring that is of particular value in
children with vesico-ureteric reflux and pyelonephritis.

Renal complications of radiological investigations;-

Contrast nephrotoxicity ;- An acute deterioration in renal function, commencing < 48 hrs after of i.v.
radiographic contrast media. Risk factors include (Pre-existing renal impairment , use of high-osmolality,
ionic contrast media and repetitive dosing in short time periods ,diabetes mellitus , myeloma , dehydration
Drugs- ACEI ARBs NSAIDs-

Prevention , If the risks are high, consider alternative methods of imaging, Hydration, e.g. free oral
fluids plus i.v. isotonic saline 500 mL then 250 mL/hr during procedure. Avoid nephrotoxic drugs;
withhold (NSAIDs). Omit metformin for 48 hrs after procedure in case renal impairment occurs, N-acetyl
cysteine may provide weak additional protection
Cholesterol atheroembolism Days to weeks after intra-arterial investigations or interventions. Caused
by showers of cholesterol-containing microemboli, arising in atheromatous plaques in major arteries. In
patients with widespread atheromatous disease, usually after interventions such as surgery or
arteriography but sometimes after anticoagulation, loss of renal function, haematuria, proteinuria,
eosinophilia and inflammatory features ( mimic a small-vessel vasculitis.) Accompanying signs of
microvascular occlusion in the lower limbs (e.g. ischaemic toes, livedo reticularis) are common. There
is no specific treatment but anticoagulation may be detrimental.
The foot of a patient who suffered extensive atheroembolism following coronary artery stenting.

Nephrogenic sclerosing fibrosis after MRI contrast agents. Chronic progressive sclerosis of skin, deeper
tissues and other organs, associated with gadolinium-based contrast agents. Only reported in patients
with renal impairment, typically on dialysis or with GFR < 1mL/min/1.73m2. Caution is advised in
patients with GFR < 30 mL/min/1.73m2
Renal biopsy; is used to establish the nature and extent of renal disease in order to judge need for
treatment & the prognosis. Transcutaneous, with U/S or contrast radiography guidance to ensure accurate
needle placement into a renal pole. Specimens are divided into 3 samples for light & electron microscopy
and for immunofluorescence.
Renal Biopsy ;- Indications
1- ARF , not adequately explained (after exclusion of obstruction, reduced renal perfusion
and ATN) .
2. CKD with normal-sized kidneys or unexplained , may be diagnostic, (e.g., identify
IgA nephropathy )

3.
Nephrotic syndrome or glomerular proteinuria in adults
4. Nephrotic syndrome in children with atypical features (hematuria and increased HTN)
or is not responding to treatment
5. Isolated hematuria.

6. Non Nephrotic range proteinuria >1g/24hr with renal characteristics or associated
abnormalities

7.
Familial Renal Disease Biopsy of one non affected member
8. Renal Transplant Dysfunction
Contraindications
Patient related ;- coagulation disorder or thrombocytopenia. Aspirin and other
antiplatelet agents, Uncontrolled hypertension, Uremia, Obesity, Uncooperative patient.
Kidney related Kidneys < 60% predicted size, Solitary kidney (except transplants) (relative
contraindication), Acute pyelonephritis/ perinephric abscess and Renal neoplasm
Most contraindications are relative rather than absolute; when clinical
circumstances necessitate urgent biopsy, they may be overridden, EXCEPT (apart
form) uncontrolled bleeding diathesis.
Complications;- Pain, usually mild, Bleeding into urine hematuria , usually minor / clot
colic and obstruction ,Bleeding around the kidney hematoma, occasionally massive and
requiring angiography with intervention, or surgery and arteriovenous fistula, rarely
significant clinically.

*Normal kidney size = 3 vertebrae.