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Kidney Lect 4

Clinical Evaluation of Renal Function

QuestionAnswer
What are the (5) methods that allow a clinician to evaluate renal functions? • History and physical examination • Serum creatinine and calculation of GFR • Urinalysis (hematuria and/or proteinuria are abnormal) • Imaging to assess size and shape of kidneys and evaluate for obstruction. • Sometimes a kidney biopsy.
In clinical practice, measurement of “the kidney function” usually refers to... the measurement of the clearance of the metabolic end products (one of the most essential aspects of the kidney functions)
steady state The maintenance of stable body fluid composition requires that the appearance and disappearance rates of any substance in the body balance each other; balance when Ingested amount + produced amount = Excreted amount + consumed amount
Clearance the volume of plasma cleared entirely of a substance (i.e. creatinine) in a unit of time, and is represented by the formula UV/P
Glomerular filtration rate (GFR) rate at which fluid is filtered across the glomerular basement membrane into the tubules
GFR: how can it be measured? how does it correlate with kidney disease? GFR cannot be measured directly but can be estimated from the clearance of an “ideal” marker. GFR correlates well (but not perfectly) with complications of kidney disease
What are the normal GFR values of an adult man, adult woman, and newborns? Adults men 125 ± 15 ml/min/1.73 m2 women 110 ± 15 ml/min/1.73 m2 Newborns 50% of above (adjusted for body surface area)
How does GFR change with: age? time of day? exercise? With increasing age above 40 years, the GFR declines about 1%/yr. Changes in the GFR with time of day (highest in afternoon, lowest at night) and exercise (decreases). GFR corrected for BSA (important for children)
What are the few instances in which filtration (i.e. GFR) is above normal (called hyperfiltration)? • Pregnancy • Dietary protein load • Uncontrolled diabetes mellitus.
A decrease in filtration (GFR) represents... kidney failure
What is are the time differences between chronic, acute, and subacute kidney failure? • Chronic kidney disease (CKD): Kidney failure that occur over many months to years. • Acute kidney injury: over days. • Subacute: over weeks to months.
Glomerular filtration rate is measured by determining the plasma concentration and excretion of a marker substance that meets the following requirements: 1. The substance must be neither absorbed nor secreted by the renal tubules 2. The substance should be freely filterable across the glomerular membranes. 3. The substance is not metabolized or produced by the kidneys
How do you determine the filtered amount of inulin= excreted amount of inulin (equation) GFR x GFin = Uin x v. Where GFR is the glomerular filtration rate, GFin is the concentration of inulin in the filtrate, Uin is the concentration of inulin in urine, and V is the urine flow rate.
What is the ratio between concentration of inulin in the filtrate and the concentration of inulin in the plasma? Inulin is freely fitlrable, so its concentration in the filtrate and plasma are identical: Hence, Filtered amount of inulin = GFR x Pin, where Pin is the concentration of inulin in plasma.
What are the pros and cons of using inulin to measure GFR? It is completely filtered by the glomerulus and neither secreted nor reabsorbed nor any other way altered in the tubules (Thus, GFR=inulin clearance). However, need for inulin infusion-->inulin clearance is not clinically practical.
How could inulin be used to measure GFR? CIn is measured by infusing inulin intravenously to achieve a steady state blood level, then measuring plasma (PIn) and urine (UIn) levels of inulin and urine volume (V) simultaneously--> GFR = [In]clearance = ([In]urine * V)/Pin
Creatinine is derived from... the metabolism of creatine in skeletal muscle and from dietary meat intake.
Why is creatinine a good tool to measure GFR? • Creatinine release from muscle is constant (most conditions) • Completely filtered by the glomerulus. • Creatinine is not reabsorbed by the renal tubules. • Creatinine is secreted by the renal tubules. • Excretion is ~= creatinine filtered.
Why is creatinine not as ideal as inulin secretion to measure GFR? Approximately 10 to 40% of urinary creatinine is derived from tubular secretion. This is particularly important in advanced Stage of Chronic Kidney disease where filtration decreases and the percentage of creatinine from tubular secretion is higher.
What are the limitations of using creatinine clearance (clinically)? 1) An incomplete urine collection, 2) Increasing creatinine secretion
How is the adequacy of 24-hour urine collection checked? The adequacy of a 24-hour urine collection is checked by comparing the measured amount of creatinine excretion to the expected amount based on weight, gender, and age
What are normal values of creatinine excretion for adult women, men, the elderly, and children? women 15-25 mg/kg/d men 20-30 mg/kg/d elderly, muscle wasting 10 mg/kg/d children 14.7 + (0.45xage) mg/kg/d
How does muscle mass affect creatinine excretion? Muscle mass and, therefore, creatinine production (so, excretion) decreases with age beyond the 40's. Muscle mass decreases in any patient who is bed-fast, is physically inactive, has major amputation or is on chronic corticosteroids.
How would renal failure make estimating GFR more difficult? As the GFR falls, the rise in the SCr is partially opposed by the enhanced tubular secretion. Thus in advanced CKD, creatinine excretion is much greater than the filtered load, resulting in a potentially large overestimation of the GFR
What information does serum creatinine tell you? Serum creatinine concentration varies inversely with GFR. The higher the serum creatinine, the worse the kidney function. Serum creatinine reflects both creatinine production and clearance
What is the normal serum creatinine level in adults? In children? How do you covert from mg/dL to international units (μmol/L)? 0.6 to 1.2 mg/dl; lower in children. The value is lower in children. (To convert from mg/dl to international units, μmol/L, multiply by 88).
What physiological / pathological changes can change creatinine levels? Serum creatinine is affected by muscle mass, diet, creatine supplements, malnutrition, and amputations
What are some of the limitations of using serum creatinine to measure GFR? Production of creatinine differs among individuals depending on muscle mass. For example patients with amputation, muscle wasting or malnutrition will have low muscle mass so the serum creatinine level may appear normal but in fact could represent low G
How will glomerular injury affect GFR or serum creatinine measurements? Glomerular injury may not initially lead to changes in GFR or serum creatinine. As a result, if this is suspected, you should look for other signs of kidney disease such as protein or blood in urine or abnormal Renal imaging studies.
Cockroft –Gault formula based on demographics, serum creatinine and lean body weight: (140-age) x weight{kg}/(72 x serum creatinine); multiply times 0.85 for women; use lean body weight in obsese patients
What are the advantages of the Cockroft –Gault formula? Disadvantages? Avoids need for 24 hour urine collection; Does not take into account actual muscularity but is a population estimate of such;
MDRD Modification of Diet in Renal Disease, which was a study evaluating the effect of dietary protein restriction and BP control on the progression of renal disease. Data from this study were used to develop an equation, predicting GFR from serum creatinine
MDRD formula (do not need to memorize) requires age, race, and gender, but NOT weight: GFR= 170 x Scr^(-0.999) x age^(-0.176) x 0.762 if female x 1.180 if black x BUN^(-0.170) x albumin^(0.318)
What is a limitation in using the results from the MDRD formula? The MDRD formula tends to underestimate GFR, when creatinine is normal or “near-normal”. That is why laboratories report GFRs as > 60ml/min, when it is expected to be close to normal.
What value does the Cockcroft-Gault formula tend to overestimate? Why (what factor does it not include)? Cockcroft-Gault tends to over-estimate GFR due to tubular secretion.
Cockcrof-Gault formula: pros,cons Avoids 24 collection As it is an estimate of creatinine clearance, it tends to overestimate GFR Commonly used in prescribing information for dose adjustments
Estimated GFR using MDRD: pros,cons Avoids urine 24 hr collection Better estimation of GFR than serum creatinine alone Commonly reported on clinical laboratory results
Plasma creatinine: pros, cons Easy to obtain Varies with muscle mass and is inaccurate in extreme muscle mass Affected by some drugs
Creatinine clearance: pros,cons Urine collection can be unreliable. If it is an inadequate collection, it will give you false results. Can overestimate GFR secondary to increased creatinine secretion in advanced CKD
BUN: what is it? What are normal values? How do you convert to international units? Blood urea nitrogen (BUN, normal 7-21 mg/dl); To convert from mg/dl to international units [mM/L], divide by 2.8
What is BUN dependent on? • Protein intake (+ correlation) • Catabolism (+ correlation). • Liver function • Volume status: urea reabsorption is increased along the renal tubules in volume depletion and low urine flow rates and is decreased at high urine flow rates.
What clinical information does the BUN value give you? The BUN level help assess dietary protein intake, presence of catabolism, volume status, and renal perfusion as well as GFR
Azotemia Elevation of BUN and serum creatinine
Acute Kidney Injury GFR is falling rapidly: Creatinine excretion decreases and the Serum creatinine and BUN rise rapidly. The patient is not in a steady state.
Why does the 24-hour collection of urine to determine creatinine clearnace NOT reflect the GFR? In such a setting, a 24-hour collection to obtain creatinine clearance is not a reflection of GFR, since the patient is not in a steady state condition. Nor can the formulas to determine creatinine clearance apply.
General definition of AKI • Loss of renal function over hours to days • Expressed clinically as the retention of nitrogenous waste products in the blood (azotemia: rising serum BUN and creatinine)
What are the key facts necessary to remember about interpreting lab results in suspected cases of acute kidney injury? • Formulas for creatinine clearance are not applicable (not in steady state) • BUN and serum creatinine rise and are followed serially. • BUN:creatinine ratio help to determine location of kidney problem (prekidney, intrinsic kidney, or obstruction).
The specific gravity (the weight of urine compared to distilled water) is dependent on the... number and size and density of particles in the urine
Urine osmolality is dependent only on the... number of particles in the urine.
The range of specific gravity in people is between... 50 to 1200 mOsm/kg.
How would Glucosuria and radiographic contrast excreted in the urine affect the specific gravity? Increased
How is the chemical composition of urine determined? Chemical composition as determined by dipstick
What is the range of urine pH? 4.5 to 8.0
What clinical information does urine pH tell you? Renal stone disease: uric acid stones may be associated with a persistently LOW pH while calcium phosphate stones with a relatively HIGH pH. Urinary tract infection with urea splitting organisms will result in a HIGH (alkaline) pH.
How can proteinuria be confirmed? The presence of protein in a urine specimen can be confirmed by adding 20% sulfasalicyclic acid to the urine, which precipitates the protein, making the urine appear cloudy.
How is proteinuria quantified? What are higher levels suggestive of? Abnormal degrees of proteinuria (using the dipstick) are categorized as trace to 4+ with the higher amounts suggestive of glomerular (as opposed to tubular) disease.
With patients with proteinuria, how can you use creatinine levels to estimate daily protein excretion? Dividing the albumin or protein concentration by the urine creatinine concentration provides a protein to creatinine ratio-->estimate creatinine excretion in 24 hours-->multiply by ratio
What are normal protein levels in the urine? Normally, in a 24-hour collection there is less than 100 mg/d of protein, most of which is Tamm-Horsfall protein secreted by the tubules.
What may cause abnormal proteinuria? • leaking of protein through an abnormal basement membrane (esp. albumin) • from the tubules (uncommon) • "overflow" protein in multiple myeloma (Bence-Jones protein) or other disorders with increased production of immunoglobulin.
macroalbuminuria: definition? how do you detect it? Albuminuria greater than or equal of 300 mg/d; dipstick
microalbuminuria: definition? common etiology? Albuminuria greater than 30 mg/d creatinine but less than 300 mg/d; measured to detect early diabetic nephropathy
How useful are urine dipsticks in analysis of blood in the urine? Urine dipsticks for blood will not discriminate between red blood cells, hemoglobinuria and myoglobinuria
How do you determine if there are blood cells present in the urine? microscopic examination
If you see blood in the urine, what anatomical sites could it come from? Blood in the urine may be from any site along the urinary system—kidney, ureter, bladder, prostate (in men), urethra, vaginal contamination (in women).
What do RBCs in urine AND proteinuria suggest? underlying intrinsic renal problem
What are normal levels of glucose in the urine? At normal levels of serum glucose, all of the glucose (which is freely filtered at the glomerulus) is reabsorbed.
How should you interpret a normal serum glucose level in a patient with renal disease? In some renal diseases the threshold for glucose absorption is lowered, resulting in glucosuria at normal serum glucose levels.
What do ketones in the urine indicate? May be present with diabetic ketoacidosis or states of starvation
Urobilinogen produced in the gut from metabolism of bilirubin, then some is reabsorbed and excreted in the urine
What etiologies explain changes in urobilinogen? In obstructive jaundice, since bilirubin does not reach the gut, urinary urobilinogen is decreased. If jaundice is not from obstruction, then urinary urobilinogen is increased
What is the use of bilirubin in urinary analysis? Urine only obtains unconjugated bilirubin
Nitrite: if present in the urine, what does it signify? This is a screening test for Gram negative bacteria, which convert urinary nitrate to nitrite. Will not detect infections due to enterococcus or organisms that do not produce nitrite. Ascorbate in the urine causes false negative.
Leukocytes in the urine: what is the threshold? The threshold is 5-15 WBC/HPF and false negative tests may be seen with glycosuria, high specific gravity, cephalexin, tetracycline therapy
Hyaline casts may form in increased numbers with fever and exercise. Patients with prerenal azotemia or obstruction may also have little in the way of formed elements in their urine.
A normal urine has a ___ sediment, with very few cells or casts bland
Acute tubular necrosis sediment the most common cause of acute renal failure, classically has tubular cells, granular debris, and pigmented granular casts.
Nephritic sedimen has red blood cells, often dysmorphic and acanthocytes, (with protein on dipstick) with granular and red blood cell casts.
What diseases can cause nephritic sediment? Red blood cell casts indicate that hematuria is glomerular in origin. A nephritic sediment is present in proliferative glomerulonephritis and renal vasculitis.
Nephrotic sediment 4+ protein, fatty casts, and oval fat bodies (lipid filled cells). This is seen in patients with glomerulonephritis with nephrotic range proteinuria. Nonproliferative glomerulonephritis with heavy proteinuria will have a nephrotic sediment.
what does the urine in patients with pyelonephritis and acute interstitial nephritis look like? contains many white blood cells and white blood cell casts. The culture will be positive in pyelonephritis (generally >105 organisms) but not in acute interstitial nephritis.
Broad casts Broad casts are characteristic of chronic renal failure in which the tubules of the functioning nephrons have dilated.
Telescoped urine has elements of chronicity (that is, broad casts) and more acute disease (granular casts and RBC casts). This is characteristic but not specific for rapidly progressive glomerulonephritis
Calcium oxalate crystals are found in acid urine, may occur in the absence of disease, and look like envelopes. Ethylene gylcol overdose results in a marked increase in calcium oxalate crystalluria.
Uric acid crystals occur in acid urine and have a varied appearance
Cystine crystals are hexagons, always pathologic, and occur in acid urine. Presence may be confirmed by nitroprusside test.
Triple (magnesium ammonium) phosphate crystals occur in alkaline urine and are associated with urea splitting bacteruria and infection. These look like coffins.
Calcium carbonate crystals (granular masses or dumbbells) occur in alkaline urine
Renal ultrasound: pros? very good for renal size, renal masses,echogenicity, renal cysts and obstruction. It is a safe procedure. It doesn’t involve IV dye. Doppler imaging of renal vessels can be used to assess for renal artery stenosis or thrombosis.
Computer assisted tomography and magnetic resonance imaging: pros? are also used to visualize the kidneys but are seldom the first imaging study ordered. Used to evaluate renal masses and complex cyst and renal blood vessels.
Renal arteriogram primarily used to confirm the presence of renal artery stenosis or to complete the evaluation of a renal tumor. Renal arteriogram is also the last step in evaluating a potential living related renal transplant donor.
Intravenous pyelogram not commonly used
Radioisotopic imaging of the kidney It evaluates the function of the kidney; when enalaprilat is used, this technique can be useful in diagnosing renal artery stenosis
Created by: karkis77