INVESTIGATION OF RENAL DISEASE

Once renal disease is suspected, the purpose of investigation is to determine the cause and the presence or degree of renal dysfunction. Estimation of the glomerular filtration rate (eGFR, see below) is used to determine the degree of renal dysfunction. The clinical history and examination together with urine dipstick testing and microscopy of urine are the starting points for determin-ing the cause.

Blood tests

The serum urea or creatinine concentration represents the dynamic equilib-rium between production and elimination but levels do not rise above the normal range until there is a reduction of 50-60% in the GFR. The serum urea concentration is increased by a high-protein diet, increased tissue catabolism (surgery, trauma, infection) and gastrointestinal bleeding, whereas the level of creatinine is much less dependent on diet but is more related to age, sex and muscle mass. Once it is elevated, serum creatinine is a better guide to GFR than urea, although a normal level is not synonymous with a normal GFR.

Glomerular filtration rate

Measurement of the GFR is the best indicator of kidney function. Creatinine clearance is a reasonably accurate measure of GFR and is calculated using a 24-hour urine collection and a single plasma creatinine. In clinical practice the eGFR is calculated using formulae based on serum creatinine and demo-graphics e.g. the Cockroft-Gault equation.

Calculation of creatinine clearance using the Cockroft-Gault equation

Men

Women Use the same equation but multiply by 1.04 instead of 1.23.

The modification of diet in renal disease (MDRD) is more reliable than the Cockroft-Gault equation in ethnically diverse groups of individuals (www.nephron.com/MDRD_GFR.cgi). Neither are validated in AKI and preg-nancy. An eGFR < 60 mL/min/1.73 m2 body surface area for more than 3 months indicates CKD.

Urine dipstick testing

Urine dipstick testing detects the presence of blood, protein, glucose, ketones, bilirubin and urobilinogen in the urine and provides a semiquantita-tive assessment of the amount of substance present. Dipsticks can also be used to measure urine pH, which is useful in the investigation and manage-ment of renal tubular acidosis (p. 346). Each test is based on a colour change in a strip of absorbent cellulose impregnated with the appropriate reagent. The stick is dipped briefly into a fresh specimen of urine collected in a clean container and the colour changes compared with the manufacturer's colour charts on the reagent strip container. Haematuria or proteinuria suggests renal tract disease. Dipsticks are also available for testing for urinary nitrites and leucocyte elastase to identify UTIs (p. 370).

Proteinuria

This is an excess of protein in the urine. Under normal conditions the low molecular weight proteins and albumin that are filtered by the glomerulus are almost completely reabsorbed in the proximal renal tubule. This results in a normal urinary protein excretion of less than 150 mg/day of which only a small amount is albumin (<30 mg daily). Dipsticks are albumin specific and

Table 9.1 Causes of proteinuria

Type

Mechanism

Examples

Glomerular

Increased permeability

Glomerulopathies

Tubular*

Decreased reabsorption

Fanconi’s syndrome Tubulointerstitial disorders

Overflow

Plasma proteins produced

Multiple myeloma

in excess

Monoclonal gammopathy

Physiologicalt

Increased renal

Acute illness

haemodynamics

Fever

ntense activity

Upright posture

*Usually <1 g per day and may be associated with other defects of proximal tubular
function (e.g. glucosuria, phosphaturia, aminoaciduria).
†Mild proteinuria and not associated with underlying renal disease. Diagnosis is made
by the absence of proteinuria on subsequent urine examinations when the condition,
e.g. fever, resolves.

will detect albumin once urine levels exceed 200 mg/L (300 mg daily if urine volume is normal). Dipsticks do not detect abnormal proteins such as globu-lins and Bence Jones protein (immunoglobulin light chains) excreted in mul-tiple myeloma. The causes of proteinuria are listed in Table 9.1. Persistent proteinuria detected on dipstick testing requires full investigation and should be quantified and renal excretory function determined (by measurement of eGFR). Quantification of proteinuria is by measurement of protein and/or albumin concentration in a ‘spot' urine sample (ideally an early morning specimen) and normalizing to creatinine concentration to give a urine protein to urine creatinine ratio (PCR) or the more sensitive urine albumin to urine creatinine ratio (ACR). Normal protein excretion is less than 150 mg per day (PCR < 15 mg/mmol) and nephrotic range proteinuria (p. 365) is more than

3.5 g per day (PCR > 350 mg/mmol).

Microalbuminuria is an increase above the normal range in urinary albumin excretion that is undetectable by conventional dipsticks (i.e. 30-300 mg/ day). It is an early indicator of renal disease and is widely used as a predictor of the development of nephropathy in people with diabetes. An ACR of >2.5 mg/mmol in men and >3.5 mg/mmol in women indicates micro-albuminuria. Albumin excretion above 300 mg/day is overt proteinuria.

Haematuria

Haematuria is blood in the urine and is either visible (also called macroscopic or gross) or non-visible (also called microscopic), detected on urine dipstick (positive 1+ or greater).

Fig. 9.2 Sites and causes of bleeding from the urinary tract.

Haematuria can arise from several sites in the kidney or urinary tract (Fig. 9.2).

■ Blood only apparent at the start of micturition is usually due to urethral disease.

■ Blood at the end of micturition suggests bleeding from the prostate or bladder base.

■ Blood seen as an even discoloration throughout the urine suggests bleed-ing from a source in the bladder or above.

Fig. 9.3 outlines an algorithm for the investigation of haematuria. Patients should be evaluated regardless of anticoagulant or antiplatelet therapy. Tran-sient causes such as urinary tract infection and contamination during men-struation are excluded by repeat testing. Urinary tract malignancy is more likely in patients with visible haematuria, urinary tract symptoms or those over 40 years of age; thus urological referral is usually indicated initially for appropriate imaging of the urinary tract (either ultrasound or computed

Cr, creatinine; eGFR, estimated glomerular filtration rate; ACR (PCR), albumin or protein: creatinine ratio

Fig. 9.3 Decision algorithm for the investigation of haematuria. Cr, creatinine; eGFR, estimated glomerular filtration rate; ACR (PCR), albumin (protein): creatinine ratio.

tomography [CT]) and cystoscopy. All other patients are more likely to have glomerular disease (often IgA nephropathy) and nephrology referral is indi-cated if initial or subsequent testing of renal function is abnormal.

Glycosuria

Diabetes mellitus must be excluded in any patients with a positive dipstick test for glucose.

Urine microscopy

This is performed on a fresh, clean-catch, mid-stream urine specimen in all patients suspected of having renal disease.

White cells

Ten or more white cells per cubic millimetre in fresh, unspun, mid-stream urine is abnormal, and indicates an inflammatory reaction within the urinary

tract, usually a UTI. Sterile pyuria (i.e. pus cells without bacterial infection) occurs in a partially treated UTI, urinary tract tuberculosis, calculi, bladder tumour, papillary necrosis and tubulointerstitial nephritis.

Red cells

One or more red cells per cubic millimetre is abnormal and must be inves-tigated (see haematuria).

Casts

Mucoprotein precipitated in the renal tubules results in the formation of hyaline casts, which on their own are a normal finding. The incorporation of red cells results in red cell casts, a finding pathognomonic of glomerulo-nephritis. White cell casts may be seen in acute pyelonephritis. Granular casts result from the disintegration of cellular debris and indicate glomerular or tubular disease.

Bacteria

Greater than 105 or 103 pathogenic organisms per mL of urine in a fresh midstream specimen in a symptomatic woman or man respectively indicates a UTI. In a woman, the diagnosis is also made with 102 coliform organisms per mL in the presence of pyuria (>10 white cells/mm3). Any growth of pathogenic organisms in urine by suprapubic aspiration is diagnostic of a UTI.

Imaging techniques

Plain X-ray is useful to identify renal calcification or radiodense calculi in the kidney, renal pelvis, line of the ureters or bladder.

Ultrasonography of the kidneys is the method of choice for assessing renal size, checking for pelvicalyceal dilatation as an indication of chronic renal obstruction, characterizing renal masses, diagnosing polycystic kidney disease, and detecting intrarenal and/or perinephric fluid (e.g. pus, blood). It has the advantage over X-ray techniques of avoiding ionizing radiation and the use of an intravascular contrast medium. Doppler ultrasonography is used to demonstrate renal artery perfusion and detect renal vein thrombosis. Bladder wall thickening can be detected in a distended bladder and an assessment of bladder emptying made by scanning after voiding.

CT is used as a first-line investigation in cases of suspected ureteric colic. It is also used to characterize renal masses that are indeterminate at ultra-sonography, to stage renal, bladder and prostate tumours, and to detect ‘lucent' calculi; low-density calculi which are lucent on plain films (e.g. uric acid stones) are well seen on CT. It is also used to look for retroperitoneal disease such as tumours and fibrosis, and CT angiography is used to visualize the renal arteries and veins.

Magnetic resonance imaging (MRI) is used to characterize renal masses as an alternative to CT, to stage renal, prostate and bladder cancer and also to image the renal arteries by MR angiography with gadolinium as contrast medium. In experienced hands, its sensitivity and specificity approaches renal angiography.

Excretion urography (also known as IVU or intravenous pyelography, IVP) has largely been replaced by ultrasonography and CT scanning.

Renal arteriography (angiography) is used in the diagnosis of renal artery disease but MR and spiral CT angiography are being used increasingly. The technique requires cannulation of the femoral artery and injection of a contrast medium. Complications include cholesterol embolizations and contrast-induced kidney damage.

Antegrade pyelography involves percutaneous puncture of a pelvicaly-ceal system with a needle and the injection of contrast medium to outline the pelvicalyceal system and ureter to the level of obstruction. It is used when ultrasonography has shown a dilated pelvicalyceal system in a patient with suspected obstruction. A catheter can then be placed percutaneously to drain the obstructed system (percutaneous nephrostomy) or a ureteric stent placed to relieve the obstruction.

Retrograde pyelography Following cystoscopy (endoscopic visualization of the bladder), contrast medium is introduced into the ureters via a catheter. Retrograde pyelography is used to investigate lesions of the ureter and to define the lower level of ureteral obstruction shown on other imaging studies. There is a small risk of introducing infection.

Renal scintigraphy Renal scintigraphy involves the intravenous injection of a radiopharmaceutical (e.g. diethylenetriaminepentaacetic acid [DPTA] labelled with technetium-99m) which is extracted from the blood-stream by the kidneys and subsequent imaging on a gamma camera with computer acquisition. It is used to detect anatomical or functional abnormali-ties of the kidneys or urinary tract. Dynamic renal scintigraphy is used to assess renal blood flow in suspected renal artery stenosis, renal function in obstruction, and in detection of vesicoureteric reflux. Static renal scintigraphy enables assessment of the size and position of the kidneys, differential func-tion of each kidney and parenchymal defects (scars, ischaemic areas, tumours).

Transcutaneous renal biopsy

Renal biopsy is carried out under ultrasound control. Microscopy is helpful in the investigation of the nephritic and nephrotic syndromes, AKI and CKD, haematuria after negative urological investigations and renal graft dysfunc-tion. Complications include haematuria, flank pain and perirenal haematoma formation.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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