Du Quoc Minh QuanGroup 19 – Class Y12D

Ho Chi Minh City, 1st June

Approach a patient with kidney diseases

Urinalysis

Kidney function tests

The most accurate method of evaluating kidney function is a formal measurement of GFR with iothalamate, iohexol, or similar markers.

These tests are not recommended for routine clinical practice because they are too expensive and time-consuming.

For estimating GRF, serum creatinine is the most common choice.

Measuring kidney function

Serum creatinine is neither secreted nor reabsorbed => the rate of creatinine clearance is a reasonably close estimate of the GFR.

The change in serum creatinine overtime indicates the tempo of renal disease and can distinguish acute injury from chronic kidney disease.

Advantages of serum creatinin

Problems with the routine use of serum creatinine alone to infer GFR stem from the differing rates of creatinine production among individuals, mainly because of variations in muscle mass

Women and the elderly can have deceptively low serum creatinine levels despite significant declines in GFR.

The creatinine clearance overestimates GFR by about 10% owing to tubular secretion of creatinine. Calculation of creatinine clearance from a 24-hour urine collection can be cumbersome for patients and is prone to error because of inaccurate urine collection.

Disadvantages of serum creatinin

Creatinineurine: Urine creatinine concentration

V: urine flow rate

Creatinineplasma : Plasma creatinine concentration

Calculate creatinine clearance

urinecreatinin

plasma

Creatinin .VClearance

Creatinine

Because of the logistical and practical limitations of a 24-hour urine collection, several equations have been developed to estimate GFR on the basis of easily obtainable clinical data and laboratory results.

To date, the most widely used equations are Cockcroft-GaultModification of Diet in Renal Disease (MDRD) StudyChronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

Estimate GFR

Cockcroft-Gault equation

140 age xlean body wt kgCCr ml / min x0.85[iff emale]

SCr mg / dL x72

Adjust to body area surface:

CCr x1.73GFR

BSA Body weight kg xHeight cm

BSA3600

Cockcroft-Gault equation should not be used on patient with obesity (based on BMI), edema or pregnancy

GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black]

Where:Scr is serum creatinine in mg/dL,κ is 0.7 for females and 0.9 for males,α is -0.329 for females and -0.411 for males,min indicates the minimum of Scr /κ or 1max indicates the maximum of Scr /κ or 1

CKD-EPI single equation

Table 1: CKD EPI Equation for Estimating GFR Expressed for Specified Race, Sex and Serum Creatinine in mg/dL (From Ann Intern Med 2009;150:604-612, used with permission)

CKD – EPI Equation

MODIFICATION OF DIET IN RENAL DISEASE 1

GFR = 170 × SCr-0.999 × age-0,176 × BUN-0,170 × Albumin0,318 × 1.18 [if black] × 0.762 [if female]

MODIFICATION OF DIET IN RENAL DISEASE 2 (abbreviated)

GFR = 186 × SCr-1.154 × age-0.203 × 1.21 [if black] × 0.742 [if female]

MDRD

As shown in the figure, the CKD-EPI equation and the MDRD Study equation were equally accurate in a subgroup with estimated GFR (eGFR) less than 60 mL/min/1.73 m2. However, the CKD-EPI equation was more accurate in a subgroup with eGFR between 60 and 120 mL/min/1.73 m2.

CKD-EPI vs. MDRD

Cystatin C may provide a more accurate and prognostic measurement of GFR in patients whose creatinine levels are in the upper end of the normal range, but it does not replace estimated GFR measurements for most clinical purposes.

Urinalysis

Urinalysis is invaluable in the diagnosis of urologic conditions such as calculi, urinary tract infection (UTI), and malignancy.

It also can alert the physician to the presence of systemic disease affecting the kidneys.

Although urinalysis is not recommended as a routine screening tool except in women who may be pregnant, physicians should know how to interpret urinalysis results correctly.

The role of urinalysis

Specimen collection (as Ms. Anh has presented)

Physical properties: color and odor

Dipstick urinalysis

Microscopic Urinalysis (Mr. Minh will talk about)

Procedure of urinalysis

The normal color of the urine is derived from urochromes, which are pigments excreted in the urine.

Foods, medications, metabolic products,vand infection can cause abnormal urine colors

Abnormal color or appearance of the urine may be explained by many conditions (See table below).

Physical properties: Color

APPEARANCE CAUSE

Milky Acid urine: urate crystalsAlkaline urine: insoluble phosphatesInfection: pusSpermatozoaChyluria

Smoky pink Hematuria ( >0.54 ml blood/L urine)

Foamy Proteinuria

Blue or green Pseudomonas urinary tract infectionBilirubinMethylene blue

Orange Drugs: anthraquinones (laxatives), rifampicin, Urobilinogenuria

Pink or red Aniline dyes in sweetsPorphyrins (on standing)Blood, hemoglobin, myoglobinDrugs: phenindione, phenolphthaleinAnthocyaninuria (beetroot, “beeturia”)

APPEARANCE CAUSE

Yellow MepacrineConjugated bilirubinPhenacetinRiboflavin

Brown or black Melanin (on standing)Myoglobin (on standing)Alkaptonuria

Green or black PhenolLysol

Brown Drugs: phenazopyridine, furazolidone, L-dopa, niridazoleHemoglobin and myoglobin (on standing)Bilirubin

From Forbes CD, Jackson WF. Color Atlas and Text of Clinical Medicine. 3rd ed. London: Mosby; 2003.

The normal odor of urine is described as urinoid; this odor can be strong in concentrated specimens but does not imply infection.

Diabetic ketoacidosis can cause urine to have a fruity or sweet odor, and alkaline fermentation can cause an ammoniacal odor after prolonged bladder retention.

Persons with UTIs often have urine with a pungent odor.

Other causes of abnormal odors include astrointestinal-bladder fistulas (associated with a fecal smell), cystine decomposition (associated with a sulfuric smell), and medications and diet (e.g., asparagus).

Physical properties: Odor

Ketonuria

Nitrites

Leukucyte Esterase

Bilirubin

Urobilinogen

Specific gravity

Urinary pH

Hematuria

Proteinuria

Gycosuria

Dipstick urinalysis

Dipstick urinalysis

Urinary specific gravity (USG) correlates with urine osmolality and gives important insight into the patient’s hydration status.

It also reflects the concentrating ability of the kidneys.

Normal USG can range from 1.003 to 1.030

Specific gravity (SG)

Indicate relative dehydration.

Associated with diuretic use, diabetes insipidus, adrenal insufficiency, aldosteronism, and impaired renal function

SG > 1.020

Indicates relative hydration.

associated with glycosuria and the syndrome of inappropriate antidiuretic hormone

SG < 1.010

Specific gravity

In patients with intrinsic renal insufficiency, USG is fixed at 1.010—the specific gravity of the glomerular filtrate

Urinary pH can range from 4.5 to 8 but normally is slightly acidic (i.e., 5.5 to 6.5) because of metabolic activity.

Ingestion of proteins and acidic fruits (e.g., cranberries) can cause acidic urine, and diets high in citrate can cause alkaline urine.

Urinary pH generally reflects the serum pH, except in patients with renal tubular acidosis (RTA)

Urinary pH

Urinary pH of a healthy individual

The inability to acidify urine to a pH of less than 5.5 despite an overnight fast and administration of an acid load is the hallmark of RTA.

In type I (distal) RTA, the serum is acidic but the urine is alkaline, secondary to an inability to secrete protons into the urine.

Type II (proximal) RTA is characterized by an inability to reabsorb bicarbonate. This situation initially results in alkaline urine, but as the filtered load of bicarbonate decreases, the urine becomes more acidic.

Renal tubular acidosis

Type I RTA

Type II RTA

Determination of urinary pH is useful in the diagnosis and management of UTIs and calculi.

Alkaline urine in a patient with a UTI suggests the presence of a urea-splitting organism, which may be associated with magnesium-ammonium phosphate crystals and can form staghorn calculi.

Uric acid calculi are associated with acidic urine.

Urinary pH

According to the American Urological Association, the presence of three or more red blood cells (RBCs) per high-powered field (HPF) in two of three urine samples is the generally accepted definition of hematuria.

The dipstick test for blood detects the peroxidase activity of erythrocytes. However, myoglobin and hemoglobin also will catalyze this reaction, so a positive test result may indicate hematuria, myoglobinuria, or hemoglobinuria

=> the role of microscopic examination

Hematuria

Glomerular hematuria typically is associated with significant proteinuria, erythrocyte casts, and dysmorphic RBCs.

However, 20 percent of patients with biopsy-proven glomerulonephritis present with hematuria alone.

IgA nephropathy (i.e., Berger’s disease) is the most common cause of glomerular hematuria.

Glomerular Hematuria

Nonglomerular hematuria is secondary to tubulointerstitial, renovascular, or metabolic disorders.

Like glomerular hematuria, it often is associated with significant proteinuria; however, there are no associated dysmorphic RBCs or erythrocyte casts.

Further evaluation of patients with glomerular and nonglomerular hematuria should include determination of renal function and 24-hour urinary protein or spot urinary protein-creatinine ratio.

Renal (nonglomerular) hematuria

Urologic causes of hematuria include tumors, calculi, and infections. Urologic hematuria is distinguished from other etiologies by the absence of proteinuria, dysmorphic RBCs, and erythrocyte casts. Even significant hematuria will not elevate the protein concentration to the 2+ to 3+ range on the dipstick test. Up to 20 percent of patients with gross hematuria have urinary tract malignancy; a full work-up with cystoscopy and upper-tract imaging is indicated in patients with this condition.

Urologic Hematuria

In patients with asymptomatic microscopic hematuria (without proteinuria or pyuria), 5 to 22 percent have serious urologic disease, and 0.5 to 5 percent have a genitourinary malignancy.

Exercise-induced hematuria is a relatively common, benign condition that often is associated with longdistance running. Results of repeat urinalysis after 48 to 72 hours should be

negative in patients with this condition.

Causes of Hematuria and their relationship with age

Proteinuria is defined as urinary protein excretion of more than 150 mg per day (10 to 20 mg per dL) and is the hallmark of renal disease.

Microalbuminuria is defined as the excretion of 30 to 150 mg of protein per day and is a sign of early renal disease, particularly in diabetic patients.

Proteinuria

The reagent on most dipstick tests is sensitive to albumin but may not detect low concentrations of γ-globulins and Bence Jones proteins.

Dipstick tests for trace amounts of protein yield positive results at concentrations of 5 to 10 mg per dL—lower than the threshold for clinically significant proteinuria.

A result of 1+ corresponds to approximately 30 mg of protein per dL and is considered positive; 2+ corresponds to 100 mg per dL, 3+ to 300 mg per dL, and 4+ to 1,000 mg per dL.

Dipstick urinalysis reliably can predict albuminuria with sensitivities and specificities of greater than 99 percent.

Asymptomatic proteinuria is associated with significant renal disease in less than 1.5 percent of patients.

Causes of proteinuria

Glucose normally is filtered by the glomerulus, but it is almost completely reabsorbed in the proximal tubule.

Glycosuria occurs when the filtered load of glucose exceeds the ability of the tubule to reabsorb it (i.e., 180 to 200 mg per dL).

Etiologies include diabetes mellitus, Cushing’s syndrome, liver and pancreatic disease, and Fanconi’s syndrome.

Glycosuria

Ketones, products of body fat metabolism, normally are not found in urine.

Dipstick reagents detect acetic acid through a reaction with sodium nitroprusside or nitroferricyanide and glycine.

Ketonuria most commonly is associated with uncontrolled diabetes, but it also can occur during pregnancy, carbohydrate-free diets, and starvation.

Nitrites normally are not found in urine but result when bacteria reduce urinary nitrates to nitrites.

Many gramnegative and some gram-positive organisms are capable of this conversion, and a positive dipstick nitrite test indicates that these organisms are present in significant numbers (i.e., more than 10,000 per mL).

This test is specific but not highly sensitive. Thus, a positive result is helpful, but a negative result does not rule out UTI.

The nitrite dipstick reagent is sensitive to air exposure, so containers should be closed immediately after removing a strip.

Nitrites

Leukocyte esterase is produced by neutrophils and may signal pyuria associated with UTI.

To detect significant pyuria accurately, five minutes should be allowed for the dipstick reagent strip to change color.

Leukocyte casts in the urinary sediment can help localize the area of inflammation to the kidney.

Leukocyte esterase

Urine normally does not contain detectable amounts of bilirubin.

Unconjugated bilirubin is water insoluble and cannot pass through the glomerulus; conjugated bilirubin is water soluble and indicates further evaluation for liver dysfunction and biliary obstruction when it is detected in the urine.

Normal urine contains only small amounts of urobilinogen, the end product of conjugated bilirubin after it has passed through the bile ducts and been metabolized in the intestine.

Urobilinogen is reabsorbed into the portal circulation, and a small amount eventually is filtered by the glomerulus. Hemolysis and hepatocellular disease can elevate urobilinogen levels, and antibiotic use and bile duct obstruction can decrease urobilinogen levels.

Bilirubin and urobilinogen

Donald W. Landry, Hasan Bazari. Approach to the patient with renal disease, Goldman Cecil Medicine 25th e. ELSEVIER 2016

Estimating GFR, National Kidney Disease Education Program, U.S. Department of Health and Human services

Rossini Botev, Jean-Pierre Mallié, Cecilé Couchoud, Otto Schück, Jean-Pierre Fauvel, Jack F.M. Wetzels, Nelson Lee, Natale G. De Santo, and Massimo Cirillo. Estimating Glomerular Filtration Rate: Cockcroft–Gault and Modification of Diet in Renal Disease Formulas Compared to Renal Inulin Clearance, Clin J Am Soc Nephrol. 2009 May; 4(5): 899–906

References

Forbes CD, Jackson WF. Color Atlas and Text of Clinical Medicine. 3rd ed. London: Mosby; 2003

Jeff A. Simerville, M.D., William C. Maxted, M.D., And JOHN J. Pahira, M.D. Urinalysis: A Comprehensive Review. Georgetown University School of Medicine, Washington, D.C.