Renal Function Tests PDF

Renal function tests Clinical Biochemistry  Kidney structure and function Each kidney consists of one million functional units: Nephron, each nephron can be divided into: ○ A) The glomerulus (filtration). ○ B) Tubules (reabsorption and secretion). 1. Proximal tubule 2....

Renal function tests Clinical Biochemistry  Kidney structure and function Each kidney consists of one million functional units: Nephron, each nephron can be divided into: ○ A) The glomerulus (filtration). ○ B) Tubules (reabsorption and secretion). 1. Proximal tubule 2. Loop of Henle 3. Distal tubule 4. Collecting duct Functions of the kidney Excretory function ○ Removal of organic waste products from the body fluids (urea, creatinine and uric acid). ○ Kidneys function to get rid on undesirable waste products of metabolism and excess inroganic substances. ○ The maximal excretory rate is limited by their plasma concentration and rate of their filtration through the gomleruli. Functions of the kidney Regulatory function (Homeostasis) ○ Maintain constant optimal chemical composition of the body. ○ Retention of biologically active substances (glucose, amino acids, minerals and vitamins) by reabsorption in the tubules. ○ Regulation of the total water and electrolytes body content (Water-salt Balance). ○ Keeping constant pH of the blood by excreting H + ions and reabsorbing HCO3-. ○ Blood pressure regulation via renin-angiotensin system. Functions of the kidney Endocrine function ○ Kidneys act as endocrine gland, secreting variety of hormones (erythropoietin, renin, vit-D3), and are subject to control by others (ADH, Aldosterone and PTH). Urine formation Urine is a sterile fluid composed of: ○ Water (95%) ○ Nitrogen containing waste ○ Electrolytes Urine is formed in nephron by 3 processes: ○ Glomerular filtration: Cells and large proteins are filtered out of the blood to produced the ultrafiltrate → urine. ○ Tubular reabsorption: Transport of moleculed needed by the body into the blood (glucose and amino acids). ○ Tubular secretion: Reverse of reabsorption, in which molecules are transported directly from blood to the urine through the tubules. Urine formation Glomerular filtration ○ Filtration is a passive process in which cells and large proteins are filtered out of the blood to produce the ultrafiltrate that will eventually become urine. ○ Glomeruli act as seives (filters) that are permeable to water and low molecular weight substances but impermeable to macromolecules. ○ This impermeability is determined by size and charge with proteins smaller than albumin being filtered, and +ve charged molecules being filtered more readily than –ve charged. Urine formation Glomerular filtration ○ The volume of blood that is filtered through the glomeruli each minute is called the glomerular filtration rate (GFR). ○ It varies with body size so it is corrected to body surface area (BSA) of 1.73 m2. ○ In the normal adult, GFR is about 120 mL/min/1.73 m2 (about 180 L/day) and has similar composition to that of plasma except that it is almost free of protein. Urine formation Tubular reabsorption and secretion ○ Water and solute reabsorption occurs throughout the entire length of the tubule. Approximately 99% of water goes back into the body. Thus the 180 L that have been filtered become 1.5-2 L of urine per day. Renal Function Tests Collection of individual tests that help to determine if the kidneys are peforming their tasks adequately. Glomerular tests: ○ Urine analysis ○ Serum NPN (BUN, creatinine, uric acid) ○ Creatinine clearance ○ Cycstatin C ○ Urine albumin Renal Function Tests Collection of individual tests that help to determine if the kidneys are peforming their tasks adequately. Tubular tests: ○ Osmolality ○ Water deprivation test ○ Urine pH ○ Glycosuria ○ Aminoaciduria Glomerular Function Tests Urine analysis ○ Physical examinations: volume, color, odor, specific gravity (osmolality), reaction (pH) and aspect. ○ Chemical examinations: for constituents not normally found in urine such as proteins, glucose, ketone bodies, bile salts, bilirubin and blood. ○ Microscopic examination: Cells and casts: In case of glomerulonephrtits, urine will contain RBCs, pus cells and casts. Crystals: Urine may contain crystals of uric acid, calcium oxalate, phosphates and cysteine. Glomerular Function Tests Seum NPN compounds ○ Plasma concentrations of NPN (urea, creatinine, uric acid) are inversely related to GFR. ○ Creatinine is the most reliable test of GF. It is produced irreversibly from creatine and completely filtered from the blood by the glomerulus. It is not reabsorbed or secreted by renal tubules. ○ However, serum Cr is insensitive as GFR may decrease by 50% before Cr concentration rises beyond the normal range. ○ A normal plasma Cr does not necessarily imply normal renal function while raised Cr usually indicates impaired function. Glomerular Function Tests Seum NPN compounds ○ Endogenous creatinine production is directly proportional to muscle mass. i.e. Cr level in male > female. ○ Meat-rich diets can increase plasma Cr, so ideally blood samples should be collected after an overnight fasting. ○ Strenuous exercise can also cause transient slight increase in Cr concentrations. ○ N.B. Normal serum Cr is > 1.5 mg%. When reaches 8 mg% or more, patient will require renal dialysis. Glomerular Function Tests Creatinine clearance (CrCl) ○ It is the amount of blood completely cleared of creatinine per minute. ○ It is the best measurment of GFR. ○ Normal value is about 120 mL/min. ○ Minimum level of CrCl needed to maintain life without need of renal dialysis is 10 ml/min. ○ The test is done by comparing serum Cr levels and amount of excreted Cr in 24 hrs urine. Glomerular Function Tests Creatinine clearance (CrCl) CrCl = (U x V) / P ○ Normal CrCl in adult is 120 mL/min, corrected to a standard BSA of 1.73 m2. ○ Accurate measurment of CrCl is difficult especially in outpatients as it it necessary to obtain a complete and accurately timed sample of urine. ○ Measurments of CrCl has become potentially unreliable and no longer recommended in practice. ○ Estimated GFR (eGFR) can be used as it reliable, not requiring urine collection. ○ MDRD formula (Four variable Formula): Cr, Age, Sex, Race. ○ A six-variable formula includes serum urea and albumin in addition. Glomerular Function Tests Cystatin C ○ Low Mwt peptide produced by nucleated cells. ○ Cleared from plasma by GF and its plasma concentration reflects the GFR more accurately than Cr as it is not affected by gender or muscle mass. ○ Measurement may have a role in detection of early renal impairment. Albumin in urine ○ Small amount of albumin is found in urine (< 25 mg/day). When exceeds 250 mg/day, this indicates severe damage of glomerular membrane. Tubular Function Tests Renal tubular dysfunctions are less common than that of glomerulus. It may affect the ability of the renal tubules to concentrate urine, excrete acidic urine or impaired reabsorption of amino acids, glucose, ….. It is difficult to be measure the tubular function quantitatevly (unlike GFR). Tests rely on the detection of increased conc. of substances in urine that are normally reabsorbed by tubules. Tubular Function Tests Osmolality (plasma and urine) ○ Urine osmolality is a general marker of tubular function. ○ Normal plasma osmolality is 280-295 mOsml/kg. ○ A 24-hr urine osmolality should be 2-3 times the plasma osmolality. i.e. Urine/Plasma osmolality ratio = 2-3. ○ If ratio < 2, tubules are not reabsorbing H2O. Tubular Function Tests Water deprivation test ○ The normal physiological response to water deprivation is water retention, which minimizes the rise in plasma osmolality. ○ The body achieves this water retention by means of vasopressin (ADH) and its the action on the renal tubules. ○ Fluid is restricted overnight (8 pm–10 am) and measure the osmolality of urine voided in the morning. Normally, urine osmolality should be raised. ○ If the urine osmolality fails to rise in response to water deprivation, suspect Diabetes insipidus. ○ In case of central (neurogenic) diabetes insipidus; the renal tubules respond normally to the desmopressin (vasopressin synthetic analogue) and the urine osmolality rises. ○ Nephrogenic diabetes insipidus is characterized by failure of the tubules to respond; the urine osmolality response remains flat. Tubular Function Tests Urine pH ○ Normal urine pH is slightly acidic (pH = 5). ○ Only fresh sample should be used. ○ Normal response to metabolic acidosis (induced by NH4Cl) is to increase H+ excretion and urine pH will be around 5.3. ○ If pH > 5.3 -> The cause of metabolic acidosis is tubular dysfunction (Renal Tubular Acidosis or RTA). Tubular Function Tests 1 and 2 microglobulins in urine ○ Small proteins that are normally filtered through the glomeruli and reabsorbed by the tubules. ○ Increased conc. in urine is a sensitive indicator of renal tubular damage. Glycosuria ○ Renal threshold is the capacity of the renal tubules to reabsorb a substance. ○ Presence of glucose in urine when blood glucose is normal usually reflects the inability of renal tubules to reabsorb glucose (Renal Glycosuria). Aminoaciduria ○ Amino acids may be present in urine in excessive amount either because the plasma concentration exceeds the renal threshold or because of renal tubular damage. Renal failure Acute Renal Failure (AKI) ○ Failure of renal function over a period of hours or days identified by a rising serum urea and creatinine. ○ Urine output falls to less than 400 mL/24 hours, and the patient is oliguric. ○ The patient may pass no urine at all and be anuric. Chronic Renal Failure (CRF) ○ Failure of kidney over a period of months or years. ○ Leads to end stage renal failure (ESRF). CRF is irreversible. Acute renal failure Pre-renal failure ○ Reduced blood supply due to blood loss, burns, prolonged vomiting or diarrhea, CHF, hepatic failure. Post-renal failure ○ Renal stones or cancer of prostate or bladder. Renal failure Acute renal failure Biochemical findings ○ Decreased GFR. ○ Increased serum urea and creatinine. ○ Metabolic acidosis. ○ Hyperkalaemia. ○ Low urine output (oliguria or anuria) with high osmolality. ○ Increased AVP and aldosterone secretion. Chronic renal failure Aetiology involves any kidney diseases leading to loss of functioning nephrons. CRF patients may have no symptoms until GFR falls below 15 mL/min. If CRF not treated by dialysis or transplant, death will happen. Consequences of CRF include disordered water and sodium metabolism, hyperkalaemia, abnormal calcium (hypocalcaemia) and phosphate metabolism, and anemia (due to erythropoietin decrease), increase in PTH secretion and metabolic acidosis. Thanks