Kidney Diseases and Elevated Levels of Blood Urea, Uric Acid and Creatinine

There could be minimal to gross impairment of renal function during the onset and progression of a kidney disease or renal disorder. This impairment of renal function may range from subclinical to complete renal failure. Urine analysis and blood biochemistry have been of great help in the assessment of renal function. Simultaneous increase in the levels of blood urea and uric acid has been observed during a variety of renal disorders. Uric acid is an end product of purine (a component of nucleic acids and nucleoproteins) metabolism. The level of uric acid in the blood depends on its endogenous production through purine metabolism as well as from the exogenously taken purines in the food items. Normal range of uric acid in blood is 2 - 6mg/dl. Elevated level of uric acid is also observed in gout. Urea is an end product of protein metabolism and its normal range in blood is 20 - 40mg/dl.

Formation of Urea: The amino acids derived by the digestion of proteins of the food we eat are absorbed by the villi of the small intestine and brought to the liver through the portal vein. The essential amino acids required for the growth and repair of body tissues are passed on to the blood circulation by the liver and others are used to produce the blood proteins and useful proteins for the body. Useless proteins are broken down in the liver to form bioenergy composed of carbon, hydrogen and oxygen and a waste product urea. Urea is a water soluble substance and carried away buy the blood stream.

The uric acid level may increase earlier than the blood urea level during the course of renal disease. The serum uric acid could be found markedly increased from the normal level of 2 -6mg/dl to 10 - 30mg/dl with minimal impairment of renal function. The creatinine level in blood starts rising after 2 to 4 fold rise in the blood urea level. The level of urea may rise in a variety of conditions, but increased level of creatinine is considered more severe than the increased level of blood urea. The creatinine is derived from the creatine and is a waste product; on the other hand the creatine is necessary for the muscle contraction and is related to the phosphocreatine breakdown. The normal level of creatinine in the blood plasma or serum is 1 - 2mg/dl and its normal daily excretion ranges from 1 to 2 grams. The serum creatinine values of up to and even exceeding occasionally 20mg/dl have been seen in the later stages of renal failure. The major cause of increased levels of serum creatinine and blood urea is the poor clearance of these substances by the kidneys rather than excessive production. In acute glomerulonephritis values from normal to over 300mg/dl are generally observed. In conditions such as malignant hypertension, chronic pyelonephritis and heavy metal poisoning 10 to 15 fold increase in blood urea level may be detected. However, in cases of hypoadrenalism (Addison's disease) blood urea level of about 100mg/dl could be detected. Fifteen to 20 fold increase in the level of blood urea (i.e. a level of 600 - 800mg/dl) may lead to uremic coma in more than 80% cases of cases affected by severe renal disease or renal failure.

How Electrolyte Imbalance Causes Renal Disease Or Renal Disease Leads To Electrolyte Imbalance

Electrolytes or essential ions should always be in the state of homoeostasis. The Normal or standard range of electrolytes reflects the normal functional status of our kidneys. Our kidneys play a vital role in preserving the internal environment while excreting the waste products of metabolism, extra water and electrolytes. There is two way selectivity between the cause and effect between the electrolytes (essential ions) and renal disorder (kidney disease). Depletion of Sodium (Na⁺) or Potassium (K⁺) or Calcium (Ca⁺⁺) through excessive urinary excretion may cause renal failure or renal failure may lead to depletion of these ions or electrolytes in the blood plasma.

The renal tubules play a vital role in regulation and preservation of water and electrolytes. The function of tubular epithelium and tubular enzymes is under the control of hormones of some endocrine glands. Suboptimal response of tubular enzymes or over production of corresponding hormone may cause renal disorder (kidney disease). Anti-diuretic hormone of pituitary gland, aldosterone and parathyroid hormone affect the renal tubules to regulate and preserve the water and electrolytes. Potassium (K⁺) content of the cells plays a critical role in retention or excretion of potassium. The glomeruli of our kidneys excrete Potassium (K⁺) in glomerular filtrate and tubular epithelial cells also excrete Potassium (K⁺) by ion exchange in which Potassium (K⁺) of tubular cells is exchanged by Sodium (Na⁺) of glomerular filtrate. Re-absorption is controlled by proximal tubules whereas the excretion is controlled by distal tubules.

Low dietary intake, fever, trauma, or hemolysis leads to tissue catabolism in patients with anuria (no urine output) leading to release of more Potassium (K⁺) from the cells. In these patients Potassium (K⁺) concentration in blood may reach lethal level (more than 100 mEq/litre). Normal level of Potassium (K⁺) in serum is 5.5 mEq/litre. The clinical features of hyperkalemia (high level of Potassium in blood) could be mainly cardiac (bradycardia or arrhythmia) with significant changes in electrocardiogram (ECG). Potassium (K⁺) depletion may be renal or non-renal in origin and may be suspected when pronounced muscular weakness and lethargy is associated with electrolyte imbalance. Commonest cause of Potassium (K⁺) deficiency could be the uncontrolled use of diuretics for the treatment of congestive heart failure. Potassium (K⁺) deficiency leads to vacuolation of tubular epithelium in proximal tubules (known as clear cell nephropathy). The associated renal changes are reversible with correction in Potassium (K⁺) level in blood/serum. Aldosterone is Sodium (Na⁺) retaining adrenal corticoid secreted by adrenal cortex. Excessive secretion of this corticoid as in cases of adenoma of adrenal cortex may lead to increase in the level of Sodium (Na⁺) and extracellular fluid volume and altered function of Sodium pump. In usual Potassium (K⁺) losing nephropathies there is failure of hydrogen ion excretion in association with the failure of retention or conservation of Potassium (K⁺).

Hypercalcemia (high level of Calcium in blood) as seen in primary hyperparathyroidism, sarcoidosis, excessive vitamin D intake or idiopathic hypercalcemia of infants, may also result in renal damage. Hypercalcemia is also a feature of acute osteoporosis of multiple myeloma and matastatic carcinomatosis of bone. Hypercalcemia could be a lethal complication associated with sarcoidosis but may successfully be reversed with timely steroid therapy. The serum level of Calcium (Ca⁺⁺) may return to normal in a few weeks but the reversal of renal insufficiency may take a year or longer. Calcium (Ca⁺⁺) is retained in our body in the form of Calcium phosphate. The hormone like action of vitamin D during excessive intake, causes increased excretion of phosphorus in urine, unsaturation of serum Calcium phosphate, demineralization of bone leading to increased level of Calcium in blood and increased loss of Calcium in urine. Hypercalcemia could cause nephrocalcinosis leading to renal insufficiency.

Renal Biopsy Procedure: Complications

Pathological lesions in affected kidneys of patients with renal disorder (kidney disease) could only be evaluated through histological, immunofluorescence and ultrastructural examination of renal biopsy. The renal biopsy (kidney biopsy) procedure as percutaneous needle biopsy was established long back in 1949 and has undergone a great refinement. At present, a large number of medical centers have been performing ultrasound guided percutaneous renal biopsy procedure for the diagnostic and prognostic evaluation of renal tissue. However, majority of the centers lack the facility of electron microscopy for ultrastructural examination of renal biopsies. Cases with microscopic hematuria (blood in urine) and hereditary nephropathies need ultrastructural examination of renal biopsy (kidney biopsy) for an accurate diagnosis. In expert hands the procedure is as safe as incision biopsy or percutaneous biopsy of liver, but post biopsy complications in rare cases could not be avoided. Hematuria (blood in urine) is a common complication and could rarely necessitate blood transfusion. There are 0.01 percent (1 in 10,000) chances of severe hemorrhage secondary to puncture leading to compulsive nephrectomy (surgical removal of kidney). Uncommon complications could be sepsis and hypertension due to perirenal hematoma. Renal biopsy (kidney biopsy) procedure is not advisable for patients with only one functional kidney.

Albumin & Casts in Urine and Associated Renal Lesions

Urine analysis is the cheapest and routine investigation which could be of great help to the clinician to reach at a diagnosis of a complex renal disorder. Albuminuria (excretion of albumin in urine) detected on heat test of the urine and the casts detected on microscopic examination of first morning specimen of urine reveal a lot about the associated renal lesions (pathological changes in kidney). Albuminuria we know definitely to be glomerular origin, although the tubules may also play their part in its production. It seems probable that this is mainly due to the glomerular basement membrane (GBM) which separates the epithelium of the tuft from the endothelium lining the capillaries, with increase of its permeability.

Casts are the microscopic accumulations of cells or coagulated proteins or lipids. Casts if present could be detected on microscopic examination of deposit obtained after centrifugation of urine. The casts must also be traced to the glomerulus, at least the essential hyaline matrix of the cast composed of coagulated albumin. Again the tubules add their contribution in the shape of epithelial cells and fatty and granular detritus which give to the casts their characteristic appearance. Careful examination casts is as informative as blood biochemistry investigations in cases of kidney disease. The cast gives a picture of the degenerative changes in the tubules. A hyaline cast indicates slight glomerular leakage without active tubular degeneration. Cellular casts denote marked activity of the morbid process. Granular casts denote moderate activity. The admixture of red blood cells (RBCs) is a sign of glomerular hemorrhage. We find that the study of casts is of remarkable importance in assessing the prognosis of a renal disorder. As long as there is considerable activity there is a scope for improvement. For such a study to be of value, the urine should be fresh. If the urine is alkaline or has been allowed to stand for long time, the casts may largely disappear. The absence of casts in an alkaline urine has not the same significance as when the urine is acidic. The acidity of the urine assists in the formation of casts. Deposition of casts in the tubules may lead to oliguria (low output of urine) leading to edema.

Kidney Biopsy and Its Diagnostic Relevance

The entire focus of the modern medicine is to find a rational treatment for various ailments. The accurate diagnosis is the key to specific therapy for a disease. Kidney biopsy evaluation is of paramount importance to assess the pathological lesions associated with the disordered renal function and for deciding the course of a particular treatment regimen. Percutaneous needle biopsy of kidney was introduced by Iversen in 1949. Kidney biopsy, need not to be performed in every case with symptoms of renal disease. For kidney biopsy procedure, the patients must be selected carefully, excluding cases with only one functional kidney. Patient is briefly hospitalized for taking kidney biopsy. The blood coagulation parameters of the patient must be within normal limits. Needle biopsy of kidney is performed by the Nephrologist under ultrasound guidance, preserved in the suitable fixatives and immediately rushed to the Pathology Laboratory for histological, immunofluorescence and ultrastructural examination. Composite study of the kidney biopsy by the three methods mentioned above is essential to establish an accurate diagnosis of renal disorder or kidney disease and evolution of a particular renal disorder. A renal biopsy (kidney biopsy) must contain glomeruli to be considered adequate for achieving a diagnosis. Generally, the specimen is considered adequate when atleast 5 glomeruli with corresponding tubules are present. Many pathologists believe that interpretation of renal biopsies is extremely difficult. Obviously it has become more complex over the years because of changing approaches to the classification of glomerular diseases. A thorough knowledge of normal histology and ultrastructure of renal components is essential to recognize any alteration in various components of the kidney. An accurate diagnosis could only be achieved through clinicopathological correlation and consideration of family history of patient in cases of congenital and hereditary glomerular diseases.