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.

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.

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.