Kidney Function Testing

The Function of Kidneys A) Excretion & Elimination: removal of organic wastes products from body fluids (urea, creatinine, uric acid) Homeostatic regulation: Water -Salt Balance Acid - base Balance Enocrine function: Hormones B) C)

Most types of renal diseases cause destruction of complete nephron. Many diseases affect renal function. In some, several functions are affected. In others, there is selective impairment of glomerular function or one or more tubular function . Most types of renal diseases cause destruction of complete nephron.

Biochemical Tests of Renal Function Measurement of GFR Clearance tests Plasma creatinine Urea, uric acid There are variety of investigations done to assess different functions of the kideneys

Renal Tubular Function Tests Osmolality measurements Specific proteinuria Aminoaciduria Urinalysis Complete urine analysis

Biochemical Tests of Renal Function Measurement of GFR Clearance tests Plasma creatinine Urea, uric acid and β2-microglobulin

Glomerular Filtration Rate The amount of filtrate that flows out of all the renal corpuscles of both kidneys every minute is called the glomerular filtration rate (GFR). In the normal adult, this rate is about 120 ml/min; about 180 liters/Day

Glomerular Filtration Rate (Cont’d) The glomerular filtration rate (GFR) provides a useful index of the number of functioning glomeruli. It gives an estimation of the degree of renal impairment by disease.

Accurate measurement of GRF is by clearance tests that requires determination of the concentration in plasma and urine of a substance that is: Freely filtered at glomeruli. Neither reabsorbed nor secreted by tubules. Its concentration in plasma needs to remains constant throughout the period of urine collection.  Better if the substance is present endogenously. Easily measured.

What is Clearance test used for measurement of glomerular filtration rate Clearance is defined as the (hypothetical) quantity of blood or plasma completely cleared of a substance per unit of time. V is not urine volume, it is urine flow rate GFR can be estimated by measuring the urinary excretion of a substance that is completely filtered from the blood by the glomeruli and it is not secreted, reabsorbed or metabolized by the renal tubules Inulin (ref . method) Inulin an exogenous compound that meets the criteria of clearance was used but it requires the infusion of inulin into the blood and is not suitable for routine clinical use

Creatinine 1 to 2% of muscle creatine spontaneously converts to creatinine daily and released into body fluids at a constant rate. Creatinine released into body fluids at a constant rate and its plasma levels maintained within narrow limits  Creatinine clearance may be measured as an indicator of GFR. Creatinine is endogenous compound that meets most of the criteria for clearance As you know :

Creatinine clearance and clinical utility Small quantity of creatinine is reabsorbed by the tubules and other quantities are actively secreted by the renal tubules  So creatinine clearance is approximately 7% greater than inulin clearance. The difference is not significant when GFR is normal but when the GFR is low (less 10 ml/min), tubular secretion makes the major contribution to creatinine excretion and the creatinine clearance significantly overestimates the GFR.

Creatinine (Cont’d) Creatinine clearance is usually about 110 ml/min in the 20-40 year old adults. It falls slowly but progressively to about 70 ml/min in individuals over 8o years of age. In children, the GFR should be related to surface area, when this is done, results are similar to those found in young adults.

Creatinine clearance is only recommended in the following conditions: Patients with early ( minor ) renal disease. Assessment of possible kidney donors. Detection of renal toxicity of some nephrotoxic drugs.

Plasma Creatinine is a better than Creatinine Clearance as indicator of kidney function test Plasma Creatinine correlates with GFR as does creatinine clearance in patients with renal disease Measurments of plasma creatinine are as effective in detecting early renal disease as creatinine clearance Plasma creatinine remains fairly constant throughout adult life while creatinine clearance decreases with aging Plasma creatinine measurements enable the progress of renal disease to be followed with better precision than creatinine clearance

Use of Formulae to Predict Clearance Formulae have been derived to predict Creatinine Clearance (CC) from Plasma creatinine. Plasma creatinine derived from muscle mass which is related to body mass, age, sex. Cockcroft & Gault Formula CC = k[(140-Age) x weight(Kg))] / serum Creatinine (µmol/L) k = 1.224 for males & 1.04 for females Modifications required for children & obese subjects Can be modified to use Surface area

Biochemical Tests of Renal Function Measurement of GFR Clearance tests Plasma creatinine Urea, uric acid

Measurement of non-protein nitrogen-containing compounds Catabolism of proteins and nucleic acids results in formation of so called non-protein nitrogenous compounds.

Plasma Urea Urea is the major nitrogen-containing metabolic product of protein catabolism in humans, Urea is filtered freely by the glomeruli Plasma urea concentration is often used as an index of renal glomerular function (50 % or more of urea filtered at the glomerulus is passively reabsorbed by the renal tubules.This fraction increases if urine flow rate decreases , such dehydration)

Plasma Urea (2.5-6.6 mmol/L) Non renal factors can affect the urea level (normal adults is level 5-39 mg/dl) like: Mild dehydration, high protein diet, increased protein catabolism, Measurement of plasma creatinine provides a more accurate assessment than urea because there are many factors that affect urea level.

Uric acid (0.12-0.42mmol/L males) In human, uric acid is the major product of the catabolism of the purine nucleosides, adenosine and guanosine. Overproduction of uric acid may result from increased synthesis of purine precursors. In humans, approximately 75% of uric acid excreted is lost in the urine; most of the reminder is secreted into the GIT Purines are derived from catabolism of dietary nucleic acid (nucleated cells, like meat) and from degradation of endogenous nucleic acids

Uric acid (cont’d) Renal handling of uric acid is complex and involves four sequential steps: Glomerular filtration of virtually all the uric acid in capillary plasma entering the glomerulus. Reabsorption in the proximal convoluted tubule of about 98 to 100% of filtered uric acid. Subsequent secretion of uric acid into the lumen of the distal portion of the proximal tubule. Further reabsorption in the distal tubule. Hyperuricemia is defined by serum or plasma uric acid concentrations higher than 7.0 mg/dl (0.42mmol/L) in men or greater than 6.0 mg/dl (0.36mmol/L) in women

Uric acid (cont’d) The handling of kidney for urate can be affected by diseases or drugs: When GFR becomes reduced for any reasons, urate retention occurs. Lactic acid compete with the urate for the and some diuretics (thiazide)compete with the urate for the excretory pathway Most uricosuric acid act by decreasing tubular reabsorption

Osmolality measurements Specific proteinuri Aminoaciduria

Renal tubular function tests The healthy kidney has a considerable reserve capacity for reabsorbing water, and for excreting H+ and other ions Tubular function tests, are not often used unless there is a reason to suspect that a specific abnormality is present. The functions tested most often are renal concentrating power and ability to produce an acid urine

Urinalysis: Osmolality measurements in plasma and urine Osmolality serves as general marker of tubular function. Because the ability to concentrate the urine is highly affected by renal diseases. This is conveniently done by determining the osmolality, and then comparing this to the plasma. If the urine osmolality is 600mosm/kg or more, tubular function is usually regarded as intact When the urine osmolality does not differ greatly from plasma (urine: plasma osmolality ratio=1), the renal tubules are not reabsorbing water Osmolality : is the osmotic presssure exerted by a solution across a membrane. It is proportional to the number of solute particles per unit weight of water. The units are mmol/kg

A patient with polyuria due to chronic renal failure is unable to produce either a dilute or concentrated urine. Instead urine osmolality is generally within 50mmol/kg of the plasma osmolality

MAJOR CAUSES OF KIDNEY DISEASE

Major Causes of Kidney Diseases Prenal causes : (leading to hypoperfusion) Glomerular diseases Tubular diseases Obstructive uropathy diseases:

Glomerular Disease: Two general patterns (with considerable overlap in some diseases) are seen: A nephritic pattern, : which is associated with inflammation on histologic examination and produces an active urine sediment with red cells, white cells, granular and often red cell and other cellular casts, and a variable degree of proteinuria.

A nephrotic pattern: Is not associated with inflammation on histologic examination Is associated with proteinuria, often in the nephrotic range, and an inactive urine sediment with few cells or casts.

Nephrotic syndrome

Nephrotic Syndrome The nephrotic syndrome is caused by renal diseases that increase the permeability across the glomerular filtration barrier. It is classically characterized by four clinical features, (but the first two are used diagnostically because the last two may not be seen in all patients): Nephrotic range proteinuria — Urinary protein excretion greater than 50 mg/kg per day Hypoalbuminemia — Serum albumin concentration less than 3 g/dL (30 g/L) Edema Hyperlipidemia