The presence of renal disease in a patient may be detected because of: 1. presentation with a symptom or clinical sign that indicates an underlying renal disorder; 2. the presence of a systemic disease known to involve the kidneys; 3. a family history of inherited renal disease; 4. the finding of asymptomatic urinary abnormalities or disordered renal function tests.
Asymptomatic urinary abnormalities • Asymptomatic proteinuria • Microalbuminuria • Microscopic haematuria
Asymptomatic proteinuria • Urinary protein excretion can amount to 150 mg daily in normal persons, consisting of albumin, Tamm–Horsfall protein and secretoryIgA. • An accurate 24-h urine collection is difficult to obtain, particularly in outpatients, and therefore it is frequently more convenient to estimate the urinary protein/creatinine ratio on a mid-morning sample of urine, a normal value would be less than 130 (as this is a ratio it is without units). Approximately half consists of low molecular weight proteins or protein fragments, with the rest being albumin.
The most common method of detecting proteinuria is by using dipstix. These paper strips are impregnated with tetrabromophenol blue which changes colour from yellow-green to blue-green in the presence of protein. • This test is very observer-dependent and it should be remembered that Bence-Jones protein will not be detected and that false-positive results can occur both in alkaline urine and in urine contaminated with antiseptics
Urinary protein excretion can increase during pyrexial illnesses, with strenuous exercise, congestive cardiac failure and hypertension. • In such patients the proteinuria is commonly mild (generally less than 1.5 g daily) and resolves with remission of the underlying cause. • If proteinuria is detected in these circumstances the test should be repeated once the potential cause has resolved. • If persistent proteinuria is detected then further investigation to determine the nature of the underlying disease is indicated.
Microalbuminuria • 'Microalbuminuria' is the term used for urinary protein excretion greater than normal but still less than that detectable by dipstix testing. • The excretion of more than 30 μg/min of albumin in an overnight collection or 70 μg/min in a 24-h collection in a patient with diabetes mellitus is indicative of early diabetic nephropathy. • It is, however, not specific for diabetes: microalbuminuria may also be present in hypertension, obesity, systemic lupus erythematosus, and following exercise. • Specifically designed stix tests are now available for screening purposes, but these remain only semiquantitative.
Microscopic haematuria • There is no agreed definition of microscopic haematuria as all urine samples contain some red blood cells. • The Scottish Intercollegiate Guideline Network (SIGN) has suggested the presence of a positive result on dipstix testing and/or the presence of more than five red blood cells per high-power field on urine microscopy. • Asymptomatic microscopic haematuria is occult haematuria, however detected and excludes haematuria visible to the naked eye or associated with urinary tract pain, infection or other symptom.
The further investigation of a patient found to have asymptomatic haematuria depends on a number of factors. • As haematuria can arise from any part of the urinary tract from the glomerulus to the urethra, the first issue is to determine whether further investigations should be urological or nephrological. • In men, particularly those over the age of 50 years, it is most likely that urological investigations will be required because of the increasing incidence of prostatic problems and urothelial malignancy and in such patients clinical examination must include a rectal examination to determine whether any prostatic abnormality can be detected. • By contrast, the presence of significant proteinuria, clinical evidence of renal disease and/or impaired renal function indicate the need for nephrological investigation.
Urine microscopy can be of value if performed on a fresh sample. Red cell casts are diagnostic of glomerular bleeding and do not arise from bleeding anywhere else in the renal tract. • Consideration of the morphology of red cells in the urine can also be useful: dysmorphic red cells, in particular those appearing as a ring form with bubbles, are probably the consequence of glomerular bleeding, whereas red cells of normal appearance are more likely to arise from a site in the lower urinary tract. • However, discrimination is not always straightforward, considerable interobserver variability is reported and the technique is not robust enough to be routinely applied in most centres.
Symptomatic presentations • Acute nephritic syndrome (haematoproteinuria syndrome) • Nephrotic syndrome • Disorders of micturition • Pain • Disorders of renal function
Disorders of micturition • Polakiuria • Nocturia • Dysuria • Polyuria • Olyguria and anuria
Polakiuria • Is the term applied when the bladder is emptied more often than normal, hence in obtaining a history it is therefore necessary to determine how often the patient passes urine. • This may be associated with a normal or increased 24-hour urine volume. • It is important to distinguish between these two situations as frequency in the presence of a normal output indicates a bladder (lower urinary tract) problem, whereas an increase in output is indicative of a disorder of urinary concentration or excessive fluid intake
Nocturia • Nocturia may arise from the many conditions that cause frequency. • On lying down there is an increase in renal perfusion resulting in increased urine flow, but ADH is secreted during sleep, thereby increasing urinary concentration and meaning that urine volume diminishes during sleep. In patients with sleep disturbance there is less ADH production and thus urine concentration is reduced, with increased urine volume such that nocturia may occur. • Enquiry should be made regarding sleep patterns in patients presenting with nocturia, in addition to considering those conditions that cause polyuria and frequenc
Dysuria • Dysuria is pain or discomfort on micturitionand one of the most frequent symptoms, accounting for about 2% of consultations in primary care. • It is more common in women and is usually described as a burning, scalding or tingling sensation in the urethra or at the urethral meatus occurring during or immediately after micturition. • Most commonly it is due to urinary infection, but it may also be caused by chemical irritation such as rarely occurs with cyclophosphamide. If associated with frequency and urgency of micturition it indicates bladder irritation such as cystitis. In young women this is usually associated with sexual activity, but in older persons it may indicate a lesion in the bladder or prostate. • Prostatic inflammation usually gives rise to perineal or rectal pain. • Very young children will be unable to complain of dysuria but urethral irritation may be inferred if the child cries during micturition.
Polyuria • Polyuria is an increase in the daily volume of urine and may arise from a number of different conditions. The normal daily urine volume varies considerably depending on fluid intake and insensible loss, but is normally in the range of 1 to 2 litres. • An increase in solute load, most commonly due to hyperglycaemia, reduces tubular reabsorption and increases urine production. Inadequate ADH secretion, such as following a head injury or associated with tumours or infection, result in an impaired urinary concentration and increased output (central diabetes insipidus). • Conditions that impair the tubular response to ADH, such as potassium depletion, lithium toxicity and some rare inherited diseases, also increase urine volume (nephrogenic diabetes insipidus), as do renal disorders that impair medullary concentration, such as analgesic nephropathy, papillary necrosis, medullary cystic disease and nephrocalcinosis.
Olyguria and anuria • Oliguria is a reduction in urine volume to such an extent that there is inability to excrete the residues of normal daily metabolic functions. • This normally means to a volume of less than 500 ml daily in an adult, usually indicating acute renal failure of whatever cause. • Anuria is the lack of any urine output and is indicative of obstruction, although it may occur in some forms of severe acute renal failure. • If anuria is present it is essential to perform a rectal examination to determine if there is any pelvic malignancy, such as a rectal or cervical carcinoma, to account for the obstruction.
Renal pain • Stretching of the capsule of the kidney causes renal pain that is felt in the loin ('renal angle'). • It can be produced by any condition that distends the kidney, such as inflammation, mass lesions or an obstruction. • The last is the most common cause, particularly obstruction of the pelviureteric junction, when the patient may give a history that anything that causes an acute increase in urine volume (for example, drinking a large quantity of water, beer, or lager or taking a diuretic) precipitates the pain.
Renal pain • Inflammatory pain, such as in pyelonephritis and (uncommonly) in glomerulonephritis, develops gradually, is usually constant in nature and is variable in severity. • A perirenal abscess, which may not always be associated with fever or tenderness, can give rise to symptoms and signs of diaphragmatic irritation and/or psoas irritation. • In the latter case, the patient usually prefers to rest with the hips flexed and reports that extension of the hips is accompanied by an increase in pain.
Renal pain • It can be difficult to distinguish renal pain from musculoskeletal pain, hence the history should enquire specifically about the relationship of pain to movement or position, neither of which greatly affects renal pain. • Clinical examination of the back and spine should determine any limitation of movement or localized point tenderness, which would suggest a musculoskeletal problem. • Some patients with polycystic renal disease complain of a constant dull loin ache. They may also suffer from the sudden onset of renal pain if there is bleeding into a cyst, or from pain of a more gradual onset if there is cyst infection.
Ureteric colic • Pain arising from an acute obstruction is frequently sudden in onset, severe, colicky and may radiate to the groin, scrotum, labia or upper thigh. • Many describe it as 'the worst pain that they have ever had' and the patient with ureteric colic typically thrashes about, unable to find comfort, looks pale and sweaty and often vomits, which can lead to diagnostic confusion. • The pain is due to acute distention of the pelvis of the kidney and the upper ureter and the associated increased peristalsis. If the obstruction is ureteric the pain resolves rapidly once the cause is extruded into the bladder, although when in the bladder it may result in bladder irritation with strangury or further obstruction if it becomes impacted at the urethral orifice.
Renal colic • Sudden onset • Very intense • Antalgic position • Unilateral • Lasts for minutes, hours, days (rare) • Precipitated by phisical effort, trepidations, wattery diet, heat • Accompanied by urinary , digestive, circulatory symptoms
Phisical exam • Anxiety • Agitated • Antalgic position • + Giordano
Causes • Nephrolithyasis • Cancer • Renal tuberculosis • Renal trauma • Sulphamide and cytostatics intake
Ureteric colic • The most common differential diagnoses of right-sided renal colic are biliary colic and appendicitis: diagnostic difficulty is less likely on the left side, although colonic pain requires consideration. • Chronic obstruction may be surprisingly asymptomatic. Retroperitoneal fibrosis is accompanied by a dull-aching back discomfort but is not associated with colic in spite of an obstruction.
Non-colicative lumbar pain(renal origin) • Acute – without irradiation, without disorders of micturition : APN, AGN • Chronic – lower intensity: CGN, renal tuberculosis • Differential diagnosis: muscular back pain (lumbago), hernia, spondilitis, spondilosis
Definition • This clinical syndrome typically presents with clinical findings of hematuria, proteinuria and dysmorphic red blood cells and/or red blood cell casts. • The proteinuria can range from 200 mg per day to heavy proteinuria (greater than 10 grams per day). <3.5 g/day • Clinically, it is accompanied by hypertension and edema.
Assessment • In cases in which the nephritic syndrome is the predominant clinical presentation, a search for systemic diseases is warranted. • The history and physical exam should particularly focus on the assessment of rashes, lung disease, neurologic abnormalities, evidence of viral or bacterial infections, and musculoskeletal and hematologic abnormalities. • Laboratory assessment should be tailored to the clinical findings in the history and physical examination.
Clinical findings • Not all four clinical features may be present simultaneously. • In some patients there is oedema due to salt and water retention in the oliguric phase. • Encephalopathy, particularly in children, may occur due to hypertension or electrolyte disorders such as hyponatraemia. • Hypertension is variable and oliguria depends to a large extent on the degree of glomerular involvement.
Urine exam • The urine typically appears 'smoky' due to the presence of red blood cell casts and rarely it will appear frankly red. • Proteinuria is variable in amount.
Causes • The 'classical' cause of acute nephritis is poststreptococcalglomerulonephritisand other infective causes . • However, these diseases are becoming less common, particularly in developed countries and it is more usual to see patients who have proteinuria and haematuria accompanied by variable hypertension and renal functional impairment in whom no identifiable preceding infection can be identified. • The presence of blood and protein in the urine is a sign of glomerular inflammation and is not indicative of any particular glomerular pathology. • On investigation such patients have a wide variety of glomerular appearances , hence renal biopsy is essential for precise diagnosis.
Laboratory • A complete blood count (CBC), electrolyte panel, 24-hour urine collection for protein and creatinine clearance, and liver function tests should be obtained initially. Serum complement (C3) levels are often clinically helpful to assist in the diagnosis of a specific renal disease (Table 9-5).
Immunology • Further laboratory assessment may be performed based on these findings, and may include an anti-streptolysin (ASO) titer, antinuclear antibody (ANA), antineutrophilcytoplasmic antibodies (ANCA), cryoglobulins, and/or an anti-GBM antibody. These early assessments may provide a presumptive diagnosis and should lead the clinician to an appropriate therapeutic intervention while awaiting renal biopsy results.
Renal biopsy • tissue diagnosis confirms the clinical findings and provides information regarding the acuity and chronicity of the disease process can a glomerular disease can be properly managed
Acute glomerulonephritis • inflammatory process causing renal dysfunction over days to weeks that may or may not resolve • If the inflammatory process is severe, the glomerulonephritis may lead to a greater than 50% loss of nephron function over the course of just weeks to months. • Such a process, called rapidly progressive glomerulonephritis, can cause permanent damage to glomeruli if not identified and treated rapidly. • Prolonged inflammatory changes can result in chronic glomerulonephritis with persistent renal abnormalities that progress to ESRD.
Symptoms and Signs • Edema is first seen in regions of low tissue pressure such as the periorbital and scrotal areas. • Hypertension, if present, is due to volume overload rather than vasoactive substances such as angiotensin II, whose levels are low.
Laboratory Findings • Serum chemistries • Urinalysis • Biopsy
Serum chemistries • There are no serum chemistries characteristic of nephritic syndrome, but certain special tests are often performed depending on the history and the results of the preliminary evaluation. • These include complement levels, antinuclear antibodies (ANA), cryoglobulins, hepatitis serologies, ANCA, anti-GBM antibodies, antistreptolysin O (ASO) titers and C3 nephritic factor.
Urinalysis • The urinalysis shows red blood cells. These may be misshapen from traversing a damaged capillary membrane—so-called dysmorphic red blood cells. • Red blood cell casts and moderate degrees of proteinuria are also characteristic of the urinary sediment. • Placing the patient in a lordotic position for an hour increases sensitivity for finding red cell casts in the next urine specimen.
Biopsy • Renal biopsy should be considered if there are no other contraindications to biopsy (eg, bleeding disorders, thrombocytopenia, uncontrolled hypertension). • Rapidly progressive glomerulonephritis is likely when over 50% of glomeruli contain crescents. • The type of disease can be categorized according to the immunofluorescent pattern and appearance on electron microscopy
Essentials of Diagnosis • Edema. • Hypertension. • Hematuria (with or without dysmorphic red cells, red blood cell casts).
Definition • Another major cause of edema is nephrotic syndrome, the clinical hallmarks of which include proteinuria (>3.5 gm per day), hypoalbuminemia, hypercholesterolemia and edema. • The degree of the edema may range from pedal edema to total body anasarca, including ascites and pleural effusions. • The lower the plasma albumin concentration, the more likely the occurrence of anasarca; the degree of sodium intake is, however, also a determinant of the degree of edema.
Causes • Systemic causes include diabetes mellitus, lupus erythematosus, drugs (e.g., phenytoin, heavy metals, NSAIDs), carcinomas and Hodgkin's disease • Primary renal diseases such as minimal change nephropathy, membranous nephropathy, focal glomerulosclerosis and membranoproliferativeglomerulonephritis.
Pathogenesis • Traditionally, ECF volume expansion in nephrotic syndrome was believed to depend on hypoalbuminemia and underfilling of the arterial circulation. Several observations have raised questions about this hypothesis