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    Add as FriendRenal Function Tests an overview.

    by: Mehmood

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    1 : Renal Function Tests an overview !!! Dr. S.M.H. DUHS
    2 : OBJECTIVES of RFTs: To detect possible renal damage Assessment of its severity. To observe the progress of renal disease To monitor the safe and effective use of drugs which are excreted in the urine
    3 : Tests usually included in the list Urine examination Tests of excretory functions Creatinine clearance Urinary acidification tests Urinary excretion of sodium and potassium Estimation of BUN and serum creatinine levels
    4 : Biochemical markers play an important role in accurate diagnosis and also for assessing risk and adopting therapy that improves clinical outcome. National Institute of Health (NIH) 2001 defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological, pathologic processes, or pharmacologic responses to a therapeutic intervention” As markers of renal function creatinine, urea, uric acid and electrolytes are for routine analysis whereas several studies have confirmed the usefulness of markers such as cystatin C, ß-Trace Protein.
    5 : Creatinine Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body depending on muscle mass Creatinine is a commonly used as measure of kidney function. The normal creatinine clearence test valve is 110-150ml/min in male and in female it is 100-130ml/min The creatinine clearance test is used to monitor the progression of renal disease. The diagnosis of renal failure is usually suspected when serum creatinine is greater than the upper limit of the "normal" interval.
    6 : In chronic renal failure and uremia, an eventual reduction occurs in the excretion of Creatinine by both the glomeruli and the tubules Creatinine values may alter as its generation may not be simply a product of muscle mass but influenced by muscle function, muscle composition, activity, diet and health status. The elevated values are also seen in muscular dystrophy paralysis, anemia, leukemia and hyperthyroidism. The decreased values are noticed with glomerulonephritis, congestive heart failure, acute tubular necrosis, shock, polycystic kidney disease, and dehydration. The increased tubular secretion of creatinine in some patients with kidney dysfunction could give false negative value .
    7 : Urea Urea is major nitrogenous end product of protein and amino acid catabolism, produced by liver and distributed throughout intracellular and extracellular fluid. urea is filtered out of blood by glomeruli and is partially being reabsorbed with water The most frequently determined clinical indices for estimating renal function depends upon concentration of urea in the serum. It is useful in differential diagnosis of acute renal failure and pre renal condition where blood urea nitrogen–creatinine ratio is increased
    8 : Increased blood urea nitrogen (BUN) is seen associated with kidney disease or failure, blockage of the urinary tract by a kidney stone, congestive heart failure, dehydration, fever, shock and bleeding in the digestive tract. The high BUN levels can sometimes occur during late pregnancy or result from eating large amounts of protein-rich foods. If the BUN level is higher than 100 mg/dL it points to severe kidney damage. Low levels are also seen in trauma, surgery, opioids, malnutrition, in fluid excess and anabolic steroid use.
    9 : Cystatin C The protease inhibitor Cystatin C is a non-glycosylated low molecular weight protein. Cystatin C has been proposed to be a marker as it is produced by all nucleated cells at a constant rate and is freely filtrated by the glomeruli and completely catabolized in the proximal tubules. The concentration of serum Cystatin C is mainly determined by glomerular filtration, which makes Cystatin C an endogenous marker of glomerular filtration rate Cystatin C was found to be an effective marker for glomerular filtration rate in patients with cirrhosis following liver transplantation Cystatin C has been found more useful for detecting early renal impairment in both type 1 and type 2 diabetic patients associated with mild kidney dysfunction with increased risk for cardiovascular events, peripheral arterial disease and heart failure
    10 : ß -Trace Protein (BTP) This protein is filtered at glomerulus and then reabsorbed in proximal tubule or excreted in urine and hence have potential to meet the criteria for use as a marker of glomerular filtration rate ß-Trace Protein is a low-molecular weight glycoprotein belonging to the lipocalin protein family with 168 amino acids and a molecular weight of 23000–29000, depending on the degree of glycosylation. It has been reported to be a better indicator of reduced glomerular filtration rate than serum creatinine . Serum ß -Trace Protein has been found to be elevated in patients with renal diseases . However, when compared, Cystatin C is still a better indicator than Serum ß-Trace Protein
    11 : Inulin Fructose polymer inulin (MW 5kDa) satisfies the criteria as an ideal marker of glomerular filtration rate. Rapid measurement of glomerular filtration rate by an inulin single-bolus technique would be practically useful
    12 : Iohexol A new technique of measuring iohexol clearance using timed dried capillary blood spots Blood spot iohexol clearance showed potential in estimating glomerular filtration rate accurately in large-scale epidemiological studies especially among individuals without established chronic kidney disease. Plasma clearance after single injection of iohexol gives a good estimate of glomerular filtration rate and is advantageous for the patients and clinicians. Iohexol clearance is also used to estimate residual renal function in hemodialysis patients .
    13 : Radioactive Markers In recent decade radioisotopes markers have been used to measure glomerular filtration rate. Some of them to mention are 125iodine (I)-iothalamate, 51CrEDTA ethylenediamine tetra acetic acid, 99mTc-DTPA (diethylene triamine penta acetic acid) and 99mTc mercapto acetyl triglycine. Renal 125iodine (I)-iothalamate clearance, is a simple and accurate test after a single subcutaneous injection, to measure glomerular filtration rate in adults Renal clearance of 125 iodine (I)-iothalamate was reproducible, simple, and practical in healthy children and those with mild and advanced renal disease. In one of the study the mean renal extraction of Cystatin C was equal to the mean renal extraction of 125 iodine (I)-iothalamate in hypertensive patients, suggesting tubular secretion of Cystatin C
    14 : Markers of tubular function Tubular function tests involve evaluation of functions of the proximal tubule (i.e. tubular handling of sodium, glucose, phosphate, calcium, bicarbonate and amino acids) and distal tubule (urinary acidification and concentration) Tsukahara H et al assessed the renal proximal tubular function in neonates by measuring urinary ß 2-microglobulin concentrations. Chen JY et al showed that in sick neonates the urinary ß 2-microglobulin and N-acetyl-ß-D-glucosaminidase were the early markers of renal tubular dysfunction. They concluded that the elevated levels of urinary ß 2-microglobulin and N-acetyl-ß-D-glucosaminidase in neonates born with meconium-stained amniotic fluid indicated the existence of tubular dysfunction, probably due to prenatal distress.
    15 : Serum osmolality was measured directly using osmometry, or estimated based on the direct measurement of the concentrations of the osmotically active substances (i.e. sodium, glucose, blood urea nitrogen, and ethanol). The difference between the measured osmolality and the calculated molarity is referred to as the osmole gap. Laloë PA et al observed severe hyponatraemia in some of the patients by measuring urine osmolality and urine sodium. According to Jeff MS there are some genes which are involved in urine concentration which may encode solute-transport proteins and the vasopressin receptors. These molecular mechanisms show the reduction in urine-concentrating ability with aging that predicts various changes in kidney function. While Landon S et al showed that aquaporin-1 has a physiologic role in renal function and is also essential for maximal urinary concentrating ability. In a complete deficiency of Aquaporin-1 there is defective urine concentrating ability.
    16 : Electrolyte The test for electrolytes includes the measurement of sodium, potassium, chloride, and bicarbonate for both diagnosis and management of renal, endocrine, acid-base, water balance, and many other conditions. Potassium used as a most convincing electrolyte marker of renal failure. The combination of decreased filtration and decreased secretion of potassium in distal tubule during renal failure cause increased plasma potassium. Hyperkalemia is the most significant and life-threatening complication of renal failure
    17 : Proteinuria Clinically the appearance of significant amount of protein in urine is one of the earliest sign of almost all renal diseases. Estimation of proteinuria helps in differentiating between tubulointerstitial and glomerular diseases and also to follow the progress of renal disease and to assess the response to therapy. Normally excretion in most healthy adults is between 20-150 mg of protein in urine over 24 hrs. Proteinuria more than 3.5 gm/day is taken to be diagnostic of nephrotic syndrome. Panels of protein measurement including albumin, a 2-macroglobulin, IgG and a 2- microglobulin have been employed in differential diagnosis of prerenal and postrenal disease.
    18 : It has been recommended the use of the protein/creatinine ratio as an Index of Quantitative Proteinuria in 24 hour urine collection . The prevalence of kidney diseases in people with diabetes was found to have proteinuria. The use of the clearance of haptoglobin, in particular provided valuable diagnostic information in cases in which the routine methods gave borderline values for the index of proteinuria During pregnancy proteinuria assay in 24 hour urine sample is performed. One of the investigations for proteinuria is semi-quantitative dipstick urinalysis as this method is relatively low cost and easily performed.
    19 : URINE EXAMINATION Urine examination is an extremely valuable and most easily performed test for the evaluation of renal functions. It includes physical or macroscopic examination, chemical examination and microscopic examination of the sediment.
    20 : Gross Examination The first part of the urinalysis is direct visual observation. Normal, fresh urine is clear and pale to dark yellow or amber in color. Cloudiness may be caused by excessive cellular material or protein in the urine or may reflect from crystallization or precipitation of salts upon standing at room temperature or in the refrigerator. A red or reddish-brown color could be from a food dye, consumption of beets, a drug, or the presence of either hemoglobin (from the breakdown of blood) or myoglobin (muscle breakdown). If the sample contains many red blood cells, it would be cloudy as well as red.
    21 : Acid/Base (pH) The dipstick yields the pH, a reflection of acid/base levels. The initial filtrate of blood plasma is usually acidified by the renal tubules and collecting ducts (microscopic structures in the kidneys of which there are millions) from a pH of 7.4 to about 6 in the final urine. in other words, the urine is acidified. However depending on the acid-base status, urinary pH may range from as low as 4.5 to as high as 8.0. One task nature has assigned to the kidneys is to rid the body of acid.
    22 : Specific Gravity Specific gravity measures urine density which reflects the ability of the kidney to concentrate or dilute the urine relative to the plasma from which it is filtered. Although dipsticks are available that also measure specific gravity in approximations, most laboratories measure specific gravity with a instrument call a refractometer. Specific gravity between 1.002 and 1.035 on a random sample should be considered normal if kidney function is normal. Any measurement below 1.007 to 1.010 indicates hydration and any measurement above it indicates relative dehydration. Urine having a specific gravity over 1.035 is either contaminated, contains very high levels of glucose, or the patient may have recently received high density radiopaque dyes intravenously for radiographic studies or low molecular weight dextran solutions.
    23 : Protein While the dipstick test has a protein measurement, more elaborate tests for urine protein should be performed since cells suspended in normal urine can produce a false high estimation of protein. Normal total protein excretion does not usually exceed 150 mg/24 hours or 10 mg/100 ml in any single specimen. More than 150 mg/day is considered proteinuria. Proteinuria greater than 3.5 gm/24 hours is severe and indicates the nephrotic syndrome.
    24 : Dipsticks detect protein by production of color with an indicator dye, Bromphenol blue, which is most sensitive to albumin but detects globulins and Bence-Jones protein poorly. Precipitation by heat is a better semi quantitative method, but overall, it is not a highly sensitive test. The sulfosalicylic acid test is a more sensitive precipitation test. It can detect albumin, globulins, and Bence-Jones protein at low concentrations. "Trace" protein is equivalent to 10 mg/100 ml or about 150 mg/24 hours (the upper limit of normal). 1+ corresponds to about 200-500 mg/24 hours; 2+ to 0.5-1.5 gm/24 hours, a 3+ to 2-5 gm/24 hours, and a 4+ represents 7 gm/24 hours or greater.
    25 : Glucose Glycosuria (excess sugar in urine) generally means diabetes mellitus.
    26 : Ketones Ketones (acetone, aceotacetic acid, beta-hydroxybutyric acid) may be present in diabetic ketosis or other forms of calorie deprivation (e.g. starvation). Ketones are easily detected using either dipsticks or test tablets containing sodium nitroprusside.
    27 : Nitrite A positive nitrite test indicates that bacteria may be present in significant numbers. Gram negative rods such as E. coli are more likely to give a positive test.
    28 : MICROSCOPIC URINALYSIS A sample of well-mixed urine (usually 10-15 ml) is centrifuged in a test tube at relatively low speed (about 2000-3,000 rpm) for 5-10 minutes which produces a concentration of sediment (cellular matter) at the bottom of the tube. The fluid on top is poured off to a volume of 0.2 ml to 0.5 ml left inside the tube. The sediment is resuspended in the remaining urine by flicking the bottom of the tube several times. A drop of resuspended sediment is poured onto a glass slide and a thin slice of glass (a coverslip) is place over it. The sediment is first examined under low power to identify crystals, casts, squamous cells, and other large objects. "Casts" are plugs of material which came from individual tubules. The numbers of casts seen are usually reported as number of each type found per low power field (LPF). For an example: "5-10 hyaline casts/L casts/LPF." Since the number of elements found in each field may vary considerably from one field to the next, several fields are averaged. Then, examination is carried out at high power to identify crystals, cells, and bacteria. The various types of cells are usually described as the number of each type found per average high power field (HPF). For example: "1-5 WBC/HPF."
    29 : Red Blood Cells Hematuria is the presence of abnormal numbers of red cells in urine due to any of several possible causes, e.g. glomerular damage, tumors which erode the urinary tract anywhere along its length, kidney trauma, urinary tract stones, renal infarcts, acute tubular necrosis, upper and lower urinary tract infections, nephrotoxins, and physical stress (like a contact sport, or long distance running for example). Theoretically, no red cells should be found, but that is not true because some are present even in healthy individuals. However, if one or more red cells can be found in every high power field, and if contamination is ruled out, the specimen reflects some abnormality.
    30 : RBC's may appear normally shaped, swollen by dilute urine (in fact, only cell ghosts and free hemoglobin may remain), or crenated (deflated and wrinkled up) by concentrated urine. Both swollen, partly hemolyzed RBC's and crenated RBC's are sometimes difficult to distinguish from WBC's in the urine. In addition, red cell ghosts may simulate yeast. The presence of poorly shaped (dysmorphic) RBC's in urine suggests glomerulonephritis. Dysmorphic RBC's have odd shapes as a consequence of being distorted via passage through the abnormal glomerular drainage structures.
    31 : White Blood Cells Pyuria refers to abnormal numbers of leukocytes (white cells) that may appear with infection in either the upper or lower urinary tract or with acute glomerulonephritis. Usually, the WBC's are granulocytes. White cells from the vagina, in the presence of vaginal and cervical infections, or the external urethral meatus (opening) in men and women may contaminate the urine. If two or more leukocytes per each high power field appear in non-contaminated urine, the specimen is probably abnormal. Leukocytes have lobed nuclei and granular cytoplasm.
    32 : Epithelial Cells Renal tubular epithelial cells which are usually larger than granulocytes contain a large round or oval nucleus and normally appear in the urine in small numbers. However, with nephrotic syndrome and in conditions leading to tubular degeneration, the number sloughed into the urine is increased. When lipiduria ("fat in the urine") occurs, these cells contain endogenous fats.
    33 : Epithelial cells from the large drainage structures (the renal pelvis, ureter, or bladder) have more regular cell borders, larger nuclei, and smaller overall size than squamous epithelium. Renal tubular (from the microscopic tubules in the kidneys) epithelial cells are smaller and rounder than transitional epithelium, and their nuclei occupy more of the total cell volume. Squamous epithelial cells from the skin surface or from the outer urethra can appear in urine. They represent possible contamination of the specimen with skin bacteria.
    34 : Casts Urinary casts are formed only in the distal convoluted tubule (DCT) or the collecting duct (distal nephron). The proximal convoluted tubule (PCT) and loop of Henle do not produce casts. Hyaline casts are composed primarily of a mucoprotein (Tamm-Horsfall protein) secreted by tubule cells. Even with injury causing increased glomerular permeability to plasma proteins with resulting proteinuria, most of the matrix that cements urinary casts together is Tamm-Horsfall mucoprotein, albumin and some globulins. Low flow rate, high salt concentration, and low pH, all lead to protein denaturation and precipitation, particularly that of the Tamm-Horsfall protein.
    35 : Protein casts with long, thin tails are formed at the junction of Henle's loop and the distal convoluted tubule and are known as cylindroids. Red blood cells may stick together and form red blood cell casts. Such casts are indicative of glomerulonephritis, with leakage of RBC's from glomeruli, or severe tubular damage. White blood cell casts are most typical for acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates inflammation of the kidney.
    36 : When cellular casts remain in the nephron for some time before they are flushed into the bladder urine, the cells may degenerate to present as a coarsely granular cast, later a finely granular cast, and ultimately, a waxy cast. Granular and waxy casts are be believed to come from renal tubular cell casts. Broad casts come from damaged and dilated tubules and are therefore seen in end-stage chronic renal disease.
    37 : The so-called telescoped urinary sediment is one in which red cells, white cells, oval fat bodies, and all types of casts are found in more or less equal profusion. The conditions which may lead to a telescoped sediment are: (1) malignant hypertension (2) lupus nephritis, (3) diabetic glomerulosclerosis, and (4) rapidly progressive glomerulonephritis. (5) In end-stage kidney disease of any cause, the urinary sediment often becomes very scant because few remaining nephrons produce dilute urine.
    38 : Bacteria Bacteria are common in urine specimens ? Therefore, microbial organisms found in all but the most scrupulously collected urines should be interpreted and correlated with the condition of the patient. Diagnosis of bacteriuria in a case of suspected urinary tract infection requires culture. A colony count may also be done to see if significant numbers of bacteria are present. Generally, more than 100,000/ml of one organism reflects significant bacteriuria. The presence of multiple organisms reflect contamination. However, the presence of any organism in catheterized or suprapubic tap (needle directly into the bladder) specimens should be considered significant.
    39 : Yeast Yeast cells may be contaminants or represent a yeast infection. They are often difficult to distinguish from red cells and amorphous crystals but are distinguished by their tendency to form buds. Most often they are Candida, which can colonize bladder, urethra, or vagina.
    40 : Crystals Common crystals seen even in healthy patients include calcium oxalate, triple phosphate crystals and amorphous phosphates cystine tyrosine crystals with congenital tyrosinosis leucine crystals in patients with severe liver disease or with maple syrup urine disease.
    41 : Miscellaneous Findings Unidentifiable objects (referred to as "crud") may find their way into a specimen, particularly those that patients bring from home. Spermatozoa can sometimes be seen. Rarely, pinworm ova may be seen the urine. Malignant cells
    42 : ESTIMATION OF BLOOD UREA NITROGEN (BUN) & SERUM CREATININE In renal failure all non-protein nitrogen constituents of the plasma are retained. Blood urea Nitrogen estimations are frequently performed as a test of renal function, but the causes of a raised BUN are many such as; Hemorrhage in the gut or body tissues Severe infections Burns Muscle injury High gluco corticoid dosage Tetracycline therapy (with the exception of doxycycline)
    43 : The estimation is most useful for the assessment of the severity and progress of renal failure in; Acute tubular necrosis Acute glomerulonephritis Chronic renal disease Post-renal obstruction Decrease in BUN level may be caused by; Low protein diet Liver damage Dialysis
    44 : Under these conditions plasma creatinine clearance (or even plasma creatinine) will be a true measure of the renal damage because endogenous creatinine production remains relatively constant. Other plasma analyses, such as measurement of uric acid, electrolytes and acid base state, or of proteins, although valuable and often necessary in the assessment of known renal disease, show alterations in a wide variety of other disorders. Normal Plasma values of BUN and creatinine are as follows; BUN = 8-25 mg/dl Creatinine = 0.6-1.6 mg/dl
    45 : TESTS OF EXCRETORY FUNCTIONS If the clinical findings or simple urine examination indicate that renal damage is present, renal function can be assessed by tests of excretory function. Following tests can be performed for this purpose; Urine concentration test Vasopressin test Urine dilution or water load test Dye excretion tests
    46 : 1. URINE CONCENTRATION TEST The ability of the kidney to concentrate urine is a test of tubular function that can be carried out readily with only minor inconvenience to the patient. This test requires a water deprivation for 14 hrs and has replaced the previous 24 hrs water deprivation test. The test should not be performed on a dehydrated patient.
    47 : 2. VASOPRESSIN TEST This is more pleasant for the patient than full water deprivation, and depends only on renal tubular function. METHOD The patient has nothing to drink after 6 p.m. At 8 p.m. five units of vasopressin tannate is injected subcutaneously. All urine samples are collected separately until 9 a.m. the next morning. INTERPRETATION Satisfactory concentration is shown by at least one sample having a specific gravity above 1.020, or an osmolality above 800 m osm/kg. The test may be combined with measurements of plasma osmolality. The urine/plasma osmolality ratio should reach 3 and values less than 2 are abnormal. If this test or the water deprivation test gives a normal result, and there is no protein in the urine, then it is unlikely that standard clearance tests will show functional damage in diffuse renal disease. This test will often detect impaired function when creatinine clearance is normal, as in hypertension or potassium deficiency.
    48 : 3. URINE DILUTION (WATER LOAD) TEST This test is very simple, but because it is less sensitive than the water deprivation test as test of renal damage its use is not often required. METHOD After an overnight fast the patient (who is not allowed to smoke) empties his bladder completely and is given 1000 ml of water to drink. Urine specimens are collected for the next 4 hours, the patient emptying bladder completely on each occasion. INTERPRETATION Unless there is renal functional impairment, the patient will excrete at least 700 ml of urine in the 4 hours, and at least one specimen will have a specific gravity less than 1.004. Kidneys which are severely damaged cannot excrete a urine of lower specific gravity than 1.010 or a volume above 400 ml in this time. There is a delayed diuresis. Abnormal results are also found if there is delayed water absorption or adrenal cortical hypofunction. The test should not be done if there is oedema or renal failure; water intoxication may result.
    49 : 4. DYE EXCRETION TESTS Many dyes are excreted by the kidneys, and measurement of their concentration in the urine after parenteral injection can be used as a measure of renal function. Phenolsulphonphthalein (phenol red) is filtered by the glomeruli and secreted by the tubules. Its excretion essentially tests for renal plasma flow and is therefore impaired early in conditions such as heart failure. After intramuscular or intravenous injection of 6 mg of dye to a normal subject, 40-60 percent of the dose will be excreted in the first hour, and another 20-25 percent in the second hour; less than 50 percent excreted over two hours is abnormal. Indigo-carmine is sometimes used in surgical practice. During cystoscopy both ureteric orifices may be observed, and after intravenous injection of 100 mg dye, colour should be seen issuing from both ureters, in about equal concentration, in 15 minutes. Maximum excretion is normally reached in 45 minutes.
    50 : CREATININE CLEARANCE TEST The value of this test is that of a roughly quantitative measure of glomerular damage when simpler tests have already demonstrated renal impairment. Due to lack of sensitivity it is not considered the first line test for the diagnosis of renal function impairment. The creatinine clearance may be normal when early renal damage has been demonstrated by urine concentration test and by the presence of proteinuria as in hypertension. This test may be done over two separate hourly periods or over 4 hours, but a 24 hour period for measurement of endogenous creatinine clearance is recommended. The results are independent of the rate of urine flow.
    51 : METHOD A careful and accurate 24 hour collection of urine is made. At some time during the day (but not within 1-3 hours after a large meal) a blood sample is taken for plasma creatinine analysis; this and the whole 24 hours urinary collection are sent to the laboratory. Calculation of creatinine clearance is made with the help of formula (U x V)/P x 1.73/A where U = Urine creatinine concentration P = Plasma creatinine concentration V = Urine flow in ml/min A = Body surface area in m2 and 1.73 is the standard body surface area Body surface area can be measured with the help of height and weight charts or with the help of following formula. log A = 0.425 log W + 0.725 log H - 2.144 Where A = Body surface area in m2 W = Weight in Kg H = Height in cm
    52 : INTERPRETATION Endogenous creatinine clearance is a rough measure of the glomerular filtration rate normally 100-130 ml/min in an adult of normal size. Correction is necessary for surface area in children, or in adults of abnormal build. Values below 90 ml/min (corrected to normal surface area) are indicative of diminished glomerular filtration rate. The test has particular value in the general assessment of renal function in cases when plasma analyses are invalid, such as after dialysis, or when the BUN (but not the plasma creatinine) has been lowered by a low protein diet. Errors in 24 hours urine collection lead to the incorrect values for creatinine clearance. The formula of Cock Croft and Gaut is a very helpful tool to avoid this complication. According to this formula Creatinine clearance = 140-Age x Weight (Kg) Plasma Creatinine x 72 For females the estimated GFR is 15% less than the calculation because of less muscle mass.
    53 : URINARY ACIDIFICATION TEST This procedure tests the ability of the renal tubules to form an acidic urine and to excrete ammonia. It is useful if there is doubt whether a patient's acidosis (confirmed by plasma analyses) is due to a pre-renal cause, or to kidney damage as in renal tubular acidosis. METHOD The patient fasts from midnight until the conclusion of the test, zero time. The patient empties his bladder completely. The urine is collected. The patient takes 0.1 g (1.9 m mol) of ammonium chloride/kg body weight and drinks a liter of water. A standard dose of 5 g is sometimes used. In children the dose should be proportional to the body surface area. At 2 hours, 4 hours, and 6 hours; complete urine specimens are collected.
    54 : INTERPRETATION In a normal subject the urine will be acidified to pH 5.3 or less, and will contain more than 1.5 m mol of ammonia per hour, in at least one of the specimens. If there is marked damage to the renal acidifying power, the pH of the later specimens of urine will be unaltered from that of the resting specimen, and less than 0.5 m mol of ammonia per hour will be excreted. The pH results are more significant than the ammonia results, as 3 days are needed for full development of extra ammonium ion excretion.
    55 : URINARY EXCRETION OF SODIUM AND POTASSIUM ? SODIUM EXCRETION The kidney normally excretes sodium and can conserve sodium very efficiently if dietary sodium is reduced. In chronic renal failure, however, the capacity of the kidney to adapt to changes in sodium intake is reduced. In most patients with chronic renal failure it is possible to maintain adequate sodium balance provided large changes in sodium intake are avoided. When the ability of the diseased kidneys, to adapt to changes in sodium intake is exceeded, there is a tendency to retain sodium and water and oedema develops when dietary sodium is increased. On the other hand, if dietary sodium is restricted, the diseased kidneys may fail to conserve sodium and water, and the consequent depletion may, in turn, reduce the GFR even further.
    56 : Occasionally, in chronic pyelonephritis or other disorders affecting primarily the renal tubules, large amounts of sodium are lost in the urine and severe sodium depletion can occur. It is possible to test the ability of the kidney to conserve sodium by giving a diet containing 20 m mol sodium/day. Normally the urinary sodium excretion should fall to the amount present in the diet within a week. This test should always be monitored with great care by daily measurement of plasma [sodium] and [urea], since severe sodium depletion may be induced. Measurement of urinary sodium should form part of the overall assessment of fluid and electrolyte balance in patients on fluid replacement therapy. It is important to collect all the urine passed. In these patients it is also important to assess all other losses of fluid and electrolytes, and relate losses to the patient's intake, dietary and parenteral.
    57 : POTASSIUM EXCRETION This is largely independent of GFR since potassium is completely reabsorbed from the glomerular filtrate in the proximal tubules and secreted by the distal tubules. The rate of secretion of potassium is influenced by the transtubular potential and by the tubular cell [potassium]. It is usually maintained adequately provided the urine flow rate is greater than one liter per day. Retention of potassium tends to occur late in the progress of renal disease, when oliguria and anuria supervene. However, in patients with oliguria due to acute or chronic renal failure, hyperkalemia and potassium retention can develop rapidly. Dangerous hyperkalemia can follow the ingestion of potassium containing foods.
    58 : Excessive renal losses of potassium only rarely occur in chronic renal disease. However, the sodium depletion, which sometimes occurs in renal disease, may be associated with secondary aldosteronism. This in turn, causes excessive loss of potassium. Acid-base disturbances markedly affect renal output of potassium. Excessive losses occur particularly when there is a metabolic alkalosis, since the kidney is unable to conserve potassium efficiently in the presence of an alkalosis. Some of the primary tubular disorders are also associated with excessive losses of potassium, and treatment with diuretics commonly causes potassium depletion. Measurement of urinary potassium output may provide valuable data in patients suspected of having abnormal losses. If dietary potassium is reduced to 20 m mol/day, urinary output should fall to this value within one week (occasionally this takes two weeks) in healthy individuals. The persistence of a relatively high urinary potassium output in the presence of hypokalemia strongly suggests that the kidney is not able to conserve potassium adequately.
    59 : Clinical manifestations of renal disease Nephrotic syndrome Rapidly progressive glomerulonephritis Nephrotic syndrome Hematuria Acute renal failure Chronic renal failure Urinary tract infection Urinary tract obstruction nephrolithiasis

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