Kidney Diseases: Diagnostic Terms and Features

The genetic, environmental, chemical and biological factors are known to influence the bio-physiology and microanatomy of kidneys. A possible clinical diagnosis of kidney diseases or renal disorders could be achieved through ultrasonography, biochemical investigations of blood and urine analysis. The pathological diagnosis of non-neoplastic and neoplastic kidney diseases needs light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) study of the kidney biopsy. Narrowing down at the appropriate and accurate diagnosis of a kidney disease needs expertise in the evaluation of LM, IFM and EM features. The light microcopy has its limitations in the exploration of microanatomy of renal lesions due to its low resolution power. The initial task in the pathological diagnosis of a kidney disease is to decide the renal compartments associated with the primary lesion or initial site of injury. The glomeruli, tubules, interstitium, extraglomerular vessels or podocytes may be affected primarily in various combinations in various renal diseases. The history of hypertension or diabetes in addition to chronic inflammatory disease like rheumatoid arthritis, osteomyelitis, tonsillitis and tuberculosis has its own implications in renal disorders. In some kidney diseases multiple components may be affected simultaneously by the pathogenic process. The glomeruli and blood vessels are found affected in certain forms of vasculitis. Immunological findings are mandatory to achieve an accurate diagnosis of vasculitis associated kidney diseases. Tubules and interstitium are found affected in tubulointerstitial nephritis. The role of EM and ultrastructural morphometry is implicit in achieving a diagnosis of thin basement membrane disease (TBMD), Alport's syndrome (hereditary nephropathy), minimal change disease (MCD), amyloidosis and evaluation of podocyte injury. The thickness and texture of glomerular basement membrane (GBM), reorganization of foot processes of podocytes and podocyte injury are directly associated with the biophysiology of proteinuria (excretion of protein in urine) and hematuria in some kidney diseases. The histopathologic lesions in the affected kidneys could only be explained with a thorough knowledge of universally accepted appropriate terms which could be understood by a clinician. The term focal is used when <50% of glomeruli are involved and the term diffuse refers to the involvement of 50% or more glomeruli. The term segmental is used when a part of a glomerular tuft is affected and the term global is used when entire glomerular tuft is affected. The term mesangial hypercellularity means >4 nuclei in the matrix of a peripheral mesangial segment. The term sclerosis refers to increased collagenous extracellular matrix causing mesangial expansion, obliterating capillary lumen or forming contact to Bowman's capsule. Some of the important diagnostic features of kidney biopsy evaluation have been cited below in a tabulated form: (For a full view of the Table - Just click on the image below)

The neoplastic kidney disease are renal cell carcinoma, juxta glomerular cell tumor, renal adenoma, oncocytoma and metastatic tumors which need immunohistochemical (IHC) and EM study for an accurate diagnosis.

Urinary Deposits in Health and Disease

The water and salt balance of our body is taken care by our kidneys through excretion of water and salts under the strict regulatory control of various hormones. The chemical and microscopic examination of urine for the evaluation of health status is a routine procedure at health centers. The abnormal excretion of biochemical substances on physical and chemical analysis of urine and presence of chemical crystals, various cell types and casts in the urine is the first alarming point about many diseases. The microscopic examination of urinary deposits would yield a valuable information about a positive or negative character. The components of the urinary deposit can be classified into three groups: 1) Chemicals as crystals or amorphous deposits, 2) Cells from the blood or urinary tract, and 3) Casts

1. Chemical substances as crystals or amorphous deposits: Some of the inorganic and organic chemical substances could be appreciated in the urine of normal people of all age groups, but some other chemicals are always associated with pathological conditions. The presence of crystals of chemical substances in the urinary deposits is influenced by acidic or alkaline reaction of the urine. Phosphates (ammonium magnesium phosphate, Calcium hydrogen phosphate and magnesium phosphate), Calcium oxalate, uric acid and urates (of Ammonium, Sodium, Potassium, Calcium and Magnesium) are most commonly detected in the urinary deposits. Other chemical substances viewed in the urinary deposits may be Calcium carbonate, Calcium sulphate, amino acids (cystine, tyrosine and leucine), hippuric acid, cholesterol, xanthine, Sulphonamide drugs and pigments like bilirubin. Phosphates are deposited in alkaline urine and get dissolved in dilute acetic acid. Calcium oxalate crystals are soluble in hydrochloric acid but uric acid crystals are not soluble in acetic acid or hydrochloric acid. Presence of red blood cells(RBCs) in the urine may give color to the deposits. The crystals of chemical substance have very typical shapes. Microscopic examination of urinary deposits by an experienced medical technologist or pathologist is needed for an accurate assessment of chemicals, cells or casts excreted in the urine. Calcium oxalate is present in some fruits and vegetables and notable among them are strawberries, rhubarb and spinach. The crystals of Tyrosine appear like tufts of needles and those of Leucine are in spherical shape. Crystals of tyrosine and leucine are seen very rarely in the cases of severe liver disease and cirrhosis. Crystals of cholesterol appear as rectangular or rhomboid plates with notched corners and occur the urine form the patients affected by some kidney disease. Sulphonamide crystals could be found in urinary deposits during treatment with such drugs. These are formed from acetyl derivatives in the urinary tract.
2. Cells: Red blood cells (RBCs) could be detected in the urinary deposits during macrohematuria (>1000 RBCs/ml of urine) as well as microhematuria (<1000 RBCs/ml of urine). Pus cells: Less than 10 leucocytes or pus cells per microlitre (µl) of urine may occur in normal urine. An increase in the number of pus cells is called pyuria and is indicative of some inflammatory disease in the urinary tract. Urine culture may help to establish the causative agent of urinary tract infection. The cells present during the acute inflammation are mainly polymorphonuclear cells. Microscopic examination of the urinary deposit is the only satisfactory test to establish the presence of pus cells. Epithelial Cells: Epithelial cells may be detected normally in urine from female patients but an increased number could be due to pathological reasons. Epithelial cells in the urine of males are normally very few in number. Epithelial cells could be from the squamous epithelium, transitional epithelium (from the bladder, prostate, ureters and pelvis of kidneys), and basal or parabasal cells. Abnormal cells such as tumor cells may also be detected in the urinary deposits. Sometimes spermatozoa may also be present in the normal urine of males.
3. Casts: Casts are formed in renal tubules whose shape these take. Subsequently the casts are pushed by the fluid along the tubules and appear in the urine. These are seen on microscopic examination of urinary deposits. The casts could be classified on the basis of their appearance under the microscope as: 1) Hyaline casts: are simplest, pale transparent and homogenous structures with cylindrical shape and do not contain cells or granules. 2) Epithelial casts: When there is tubular damage, cells from the tubular epithelium could be trapped into casts and give rise to epithelial casts. 3) Granular casts: Casts containing closely packed granules of various size and shape are generally formed due to degeneration of tubular epithelial cells and are indicative of renal disease. 4) Fatty casts: are derived from epithelial cells when fat granules are present along with granular material. Such casts are found in tubulopathy and are indicative of degeneration of tubular epithelium.

Important Points:

• Collection of urine from each kidney by ureteric catheterization and from urinary bladder may be used to locate the site of pus formation.
• Cytological examination of the first morning urine for three consecutive days should be performed to rule out any malignancy in doubtful case.
• If large number of pus cells are detected in the urine, a urine culture is advisable to rule out the infectious organism.

Types and Causes of Proteinuria

Proteinuria means the excretion of protein in the urine. A healthy person does not excrete proteins in the urine or the excretion of proteins is less than 150 mg per day. The proteins most commonly found in the urine are those derived from the plasma of blood and consist of a mixture of albumin and globulin. Predominantly albuminuria (excretion of albumin in urine) is detectable on routine urine analysis during a medical examination. Albuminuria could be organic (due to involvement of kidneys or other organs) or functional (due to physiological or biological stress on kidneys). The functional albuminuria is usually intermittent and not accompanied by any symptoms or evidence of kidney disease. Renal function tests and urinary deposits are found to be normal during the functional albuminuria. It may be connected with posture; being absent when the person is lying down and present when standing. The functional albuminuria usually clears up in early adult life and seems to be associated with the growth and development of kidneys. Any severe stress may also lead to transient albuminuria. Exposure to severe cold and excessive exercise or physical activity may cause functional or transient proteinuria. However, there is nothing to worry about as the functional albuminuria is self limiting with respect to the cause. Mild to moderate functional albuminuria may also be detected during last two months of pregnancy due to pressure on kidneys.

Organic albuminuria is of three types: 1) Renal Albuminuria - When the cause is the kidney disease. 2) Pre-renal Albuminuria - When the kidneys are affected secondarily to some other disease. Post-renal Albuminuria - When the protein is added to the urine after it has left the renal tubules.

1. Renal Albuminuria: It is found in all forms of kidney disease. The cause of renal disorder or kidney disease may be inflammatory (infectious), degenerative (immunological) or destructive (toxic or malignant). The plasma globulin and red blood cells (RBCs) may also be excreted along with albumin during some renal disorders. The urine would be smoky in color if macroscopic hematuria (blood in urine) is also associated with proteinuria. The cases of acute glomerulonephritis may excrete 0.5 to 2.0 percent (0.5 g to 2.0 g/dl) protein in the urine, whereas the cases affected by chronic glomerulonephritis generally excrete less than 0.5 percent (0.5 g/dl) protein in the urine. The amount of protein excreted daily would vary depending on the volume of urine voided daily. The ratio of albumin to globulin excreted in the urine may vary from 10:1 to 5:1. A routine and quantitative urine analysis is required to evaluate the extent of excretion of proteins in the urine.

2. Pre-renal Albuminuria: It is found in a variety of conditions exerting stress on the kidneys. The pre-renal albuminuria usually disappears when the primary disease is cured. Impairment of renal circulation due to dehydration, diarrhea or vomiting, blood loss due to accidental injuries or anemia are the most common conditions, which could lead to pre-renal albuminuria.

3. Post-renal Albuminuria: The proteinuria or albuminuria is termed as post-renal albuminuria if protein is possibly added to the urine as it passes along the urinary tract after leaving the urinary tubules of the kidneys. The major causes of the post-renal albuminuria are the lesions of the renal pelvis or urinary bladder. Lesions of the prostate (in male patients) and urethra also lead to post-renal albuminuria. Admixture of discharges from the vagina (in female patients) and semen (in male patients) may also give positive tests for protein.