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Evaluation of the Renal Patient

By

Geetha Maddukuri

, MD, Saint Louis University

Last full review/revision Nov 2020| Content last modified Nov 2020
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In patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings can be local (eg, reflecting kidney inflammation or mass), result from the systemic effects of kidney dysfunction, or affect urination (eg, changes in urine itself or in urine production). (See also Evaluation of the Urologic Patient Evaluation of the Urologic Patient Urologic patients may have symptoms referable to the kidneys as well as to other parts of the genitourinary tract (GU) tract. (See also Evaluation of the Renal Patient.) Pain originating in... read more .)

History in the Renal Patient

History plays a limited role because symptoms are nonspecific.

  • Myoglobinuria

  • Hemoglobinuria

  • Porphyrinuria

  • Porphobilinuria

  • Food-induced urine coloring (some foods, eg, beets, rhubarb, sometimes food coloring, may make urine appear red)

  • Drug-induced urine coloring (some drugs, most commonly phenazopyridine, but sometimes cascara, diphenylhydantoin, rifampin, methyldopa, phenacetin, phenindione, phenolphthalein, phenothiazines, and senna may make urine appear dark yellow to orange or red)

High concentrations of urinary protein cause frothy or sudsy urine. Urinary frequency Urinary Frequency Urinary frequency is the need to urinate many times during the day, at night (nocturia), or both but in normal or less-than-normal volumes. Frequency may be accompanied by a sensation of an... read more (voiding more often) should be distinguished from polyuria Polyuria Polyuria is urine output of > 3 L/day; it must be distinguished from urinary frequency, which is the need to urinate many times during the day or night but in normal or less-than-normal volumes... read more (voiding a larger amount than normal) in patients who report excessive urination. Nocturia may be a feature of either but is often the result of excess fluid intake too close to bedtime, prostate enlargement Benign Prostatic Hyperplasia (BPH) Benign prostatic hyperplasia (BPH) is nonmalignant adenomatous overgrowth of the periurethral prostate gland. Symptoms are those of bladder outlet obstruction—weak stream, hesitancy, urinary... read more , or chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease . Family history is useful for identifying inheritance patterns and risk of polycystic kidney disease Autosomal Dominant Polycystic Kidney Disease(ADPKD) Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are... read more Autosomal Dominant Polycystic Kidney Disease(ADPKD) or other hereditary nephropathies (eg, hereditary nephritis, thin basement membrane disease Thin Basement Membrane Disease Thin basement membrane disease is diffuse thinning of the glomerular basement membrane from a width of 300 to 400 nm in normal subjects to 150 to 225 nm. (See also Overview of Nephritic Syndrome... read more Thin Basement Membrane Disease , nail-patella syndrome Nail-Patella Syndrome Nail-patella syndrome is a rare inherited disorder of mesenchymal tissue characterized by abnormalities of bones, joints, fingernails and toenails, and kidneys. Diagnosis is clinical. There... read more , cystinuria Cystinuria Cystinuria is an inherited defect of the renal tubules in which reabsorption of cystine (the homodimer of the amino acid cysteine) is impaired, urinary excretion is increased, and cystine stones... read more , hyperoxaluria).

Physical Examination of the Renal Patient

Chest examination

Pericardial and pleuritic friction rubs may be signs of uremia.

Abdominal examination

Pain elicited by mild striking of the back, flanks, and angle formed by the 12th rib and lumbar spine with a fist (costovertebral tenderness) may indicate pyelonephritis Acute pyelonephritis Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more or urinary tract obstruction Obstructive Uropathy Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more (eg, due to calculi). Normal kidneys are not usually palpable. However, in some women, the lower pole of the right kidney can occasionally be felt with palpation during deep inspiration, and large kidneys or masses can sometimes be felt without special maneuvers. In neonates, the kidneys can be felt with the thumbs when the thumbs are placed anterior and the fingers posterior to the costovertebral angle.

Transillumination can distinguish solid from cystic renal masses in some children < 1 year old if the kidney and mass are manipulated against the abdominal wall.

Skin examination

Chronic kidney disease can cause any of the following:

Uremic frost, the deposition of white-to-tan urea crystals on the skin after sweat evaporation, is rare.

Neurologic examination

Patients with acute renal failure Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more may be drowsy, confused, or inattentive; speech may be slurred. Asterixis can be detected in handwriting or by observation of outstretched hands maximally extended at the wrists; after several seconds in this position, a hand flap in the flexor direction is asterixis. Asterixis suggests one of the following:

Testing of the Renal Patient

The initial steps in evaluation of renal disorders are:

  • Urinalysis

  • Serum creatinine level

Other urine, blood, and imaging tests (eg, ultrasonography, CT, MRI) are done in specific circumstances. Ideally, after the urethral meatus is cleaned, the urine specimen is collected midstream (clean-catch specimen) during the first void of the morning; the urine should be examined immediately because delays can lead to changes in test results. Bladder catheterization Bladder Catheterization Bladder catheterization is used to do the following: Obtain urine for examination Measure residual urine volume Relieve urinary retention or incontinence Deliver radiopaque contrast agents or... read more or suprapubic aspiration can be used for collection when urine cannot be obtained by spontaneous voiding or when vaginal material contaminates the urine specimen. However, the trauma of catheterization may falsely increase the number of red blood cells (RBCs) in the specimen, so catheterization is usually avoided if the outcome of interest is microscopic hematuria. A specimen from a catheter collection bag is not acceptable for microscopic or bacteriologic tests.

Urinalysis

A complete urinalysis includes the following:

  • Inspection for color, appearance, and odor

  • Measurement of pH, specific gravity, protein, glucose, RBCs, nitrites, and white blood cell (WBC) esterase by dipstick reagents

  • Microscopic analysis for casts, crystals, and cells (urine sediment)

Bilirubin and urobilinogen, although standard parts of many dipstick tests, no longer play significant roles in evaluation of renal or hepatic disorders.

Color is the most obvious of urine attributes, and observation of color is an integral part of urinalysis (see table Causes of Urine Color Changes Causes Of Urine Color Changes In patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings can be local (eg, reflecting kidney inflammation or mass), result... read more Causes Of Urine Color Changes ). Urine color may suggest possible causes and help direct additional testing.

Table
icon

pH is normally 5.0 to 6.0 (range 4.5 to 8.0). Measuring with a glass pH electrode is recommended when precise values are necessary for decision making, as when diagnosing renal tubular acidosis Renal Tubular Acidosis Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired bicarbonate resorption (type 2), or abnormal aldosterone... read more ; in these cases, a layer of mineral oil should be added to the urine specimen to prevent escape of carbon dioxide. Delay in processing a specimen may elevate pH because ammonia is released as bacteria break down urea. Infection with urease-producing pathogens can spuriously increase pH.

Specific gravity provides a rough measure of urine concentration (osmolality). Normal range is 1.001 to 1.035; values may be low in older patients or in those with impaired renal function, who are less able to concentrate urine. It is measured by hydrometer or refractometer or estimated with a dipstick. Accuracy of the dipstick test is controversial, but the test may be sufficient for patients who have calculi and are advised to self-monitor urine concentration to maintain dilute urine. Specific gravity by dipstick may be spuriously elevated when urine pH is < 6 or low when pH is >7. Hydrometer and refractometer measurements may be elevated by high levels of large molecules (eg, radiopaque contrast agent, albumin, glucose, carbenicillin) in the urine.

Protein, detected by standard dipstick tests, reflects mainly urinary albumin concentration, classified as negative (< 10 mg/dL), trace (15 to 30 mg/dL), or 1+ (30 to 100 mg/dL) through 4+ (> 500 mg/dL). Moderately increased albuminuria (formerly known as microalbuminuria), an important marker for renal complications in patients with diabetes, is not detected by standard dipsticks, but special microalbumin dipsticks are available. Light-chain proteins (eg, due to multiple myeloma) also are not detected. Significance of proteinuria Proteinuria Proteinuria is protein, usually albumin, in urine. High concentrations of protein cause frothy or sudsy urine. In many renal disorders, proteinuria occurs with other urinary abnormalities (eg... read more depends on total protein excretion rather than protein concentration estimated by dipstick; thus, when proteinuria is detected with dipstick testing, quantitative measures of urinary protein should be done. False-negative results can be caused by dilute urine. False-positive results can be caused by any of the following:

  • High pH (> 9)

  • Presence of cells

  • Radiopaque contrast agents

  • Concentrated urine

Glucose usually appears in the urine when serum glucose increases to > 180 mg/dL (> 10.0 mmol/L) and renal function is normal. Threshold for detection by urine dipstick is 50 mg/dL (2.8 mmol/L). Any amount is abnormal. Falsely low or negative results can result from any of the following:

  • Ascorbic acid

  • Ketones

  • Aspirin

  • Levodopa

  • Tetracycline

  • Very high urine pH

  • Dilute urine

Glucose can appear in the urine despite normal plasma glucose levels in Fanconi syndrome Fanconi Syndrome Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and bicarbonate wasting. It may be hereditary... read more (proximal tubule defect), and with use of sodium-glucose co-transporter 2 (SGLT2) inhibitor.

Hematuria is detected when RBCs lyse on a dipstick test strip, releasing hemoglobin (Hb) and causing a color change. Range is from negative (0) to 4+. Trace blood (corresponding to 3 to 5 RBCs/high-power field [HPF]) is normal under some circumstances (eg, exercise) in some people. Because the test strip reagent reacts with Hb, free Hb (eg, due to intravascular hemolysis) or myoglobin (eg, due to rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more ) causes a positive result. Hemoglobinuria and myoglobinuria can be distinguished from hematuria by the absence of RBCs on microscopic examination and by the pattern of color change on the test strip. RBCs create a dotted or speckled pattern; free Hb and myoglobin create a uniform color change. Povidone iodine causes false-positive results (uniform coloring); ascorbic acid causes false-negative results.

Nitrites are produced when bacteria reduce urinary nitrates derived from amino acid metabolism. Nitrites are not normally present and signify bacteriuria. The test is either positive or negative. False-negative results may occur with any of the following:

  • Infection with certain pathogens that cannot convert nitrate to nitrite (eg, Enterococcus faecalis, Neisseria gonorrhoeae, Mycobacterium tuberculosis)

  • Urine that has not stayed long enough (< 4 hours) in the bladder

  • Low urinary excretion of nitrate

  • Enzymes (of certain bacteria) that reduce nitrates to nitrogen

  • High urine urobilinogen level

  • Presence of ascorbic acid

  • Urine pH < 6.0

Nitrites are used mainly with WBC esterase testing to monitor patients with recurrent urine infections, particularly children with vesicoureteral reflux Vesicoureteral Reflux (VUR) Vesicoureteral reflux is retrograde passage of urine from the bladder back into the ureter and sometimes also into the renal collecting system, depending on severity. Reflux predisposes to urinary... read more , and sometimes to confirm the diagnosis of uncomplicated urinary tract infection (UTI) in women of childbearing age.

WBC esterase is released by lysed neutrophils. Its presence in urine reflects acute inflammation, most commonly due to bacterial infection but sometimes due to interstitial nephritis Tubulointerstitial Nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more Tubulointerstitial Nephritis , nephrolithiasis Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more , or renal tuberculosis. Threshold for detection is about 5 WBCs/HPF, and test results range from negative to 4+. The test is not very sensitive for detection of infection. Contamination of a urine specimen with vaginal flora is the most common cause of false-positive results. False-negative results may result from any of the following:

  • Very dilute urine

  • Glycosuria

  • Urobilinogen

  • Use of phenazopyridine, nitrofurantoin, rifampin, or large amounts of vitamin C

WBC esterase is used mainly with nitrite testing to monitor patients with recurrent urine infections and sometimes to diagnose uncomplicated UTI Bacterial Urinary Tract Infections Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more in women of childbearing age. If both tests are negative, the likelihood of a positive urine culture is small.

Microscopic urine analysis

Detection of solid elements (cells, casts, crystals) requires microscopic analysis, ideally done immediately after voiding, and dipstick testing. The specimen is prepared by centrifuging 10 to 15 mL of urine at 1500 to 2500 rpm for 5 minutes. The supernatant is fully decanted; a small amount of urine remains with the residue at the bottom of the centrifuge tube. The residue can be mixed back into solution by gently agitating the tube or tapping the bottom. A single drop is pipetted onto a slide and covered with a coverslip. For routine microscopic analysis, staining is optional. The specimen is examined under reduced light with the low-power objective and under full-intensity light with the high-power objective; the latter is typically used for semiquantitative estimates (eg, 10 to 15 WBCs/high power field [HPF]). Polarized light is used to identify some crystals and lipids in the urine. Phase-contrast microscopy enhances identification of cells and casts.

RBCs < 3/HPF may be normal (< 5/HPF is sometimes normal, eg, after exercise), and any isolated hematuria Isolated Hematuria Hematuria is red blood cells (RBCs) in urine, specifically > 3 RBCs per high-power field on urine sediment examination. Urine may be red, bloody, or cola-colored (gross hematuria with oxidation... read more should be interpreted in clinical context. On microscopic analysis, glomerular RBCs are smaller and dysmorphic, with spicules, folding, and blebs; nonglomerular RBCs retain their normal shape and size.

WBCs < 5/HPF may be normal; special staining can distinguish eosinophils from neutrophils (see Other urine tests Other urine tests In patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings can be local (eg, reflecting kidney inflammation or mass), result... read more Other urine tests ). Pyuria is defined as > 5 WBCs /HPF in a sample of centrifuged urine.

Lipiduria is most characteristic of the nephrotic syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more ; renal tubular cells absorb filtered lipids, which appear microscopically as oval fat bodies, and cholesterol, which produces a Maltese cross pattern under polarized light. Lipids and cholesterol can also be free floating or incorporated into casts.

  • Urine concentration of crystal constituents

  • pH

  • Absence of crystallization inhibitors

Table
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Table
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Casts are made up of glycoprotein of unknown function (Tamm-Horsfall protein) secreted from the thick ascending loop of Henle. Casts are cylindrical and have regular margins. Their presence indicates renal origin, which may be helpful diagnostically. Types of casts differ in constituents and appearance (see table Urinary Casts Urinary Casts In patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings can be local (eg, reflecting kidney inflammation or mass), result... read more Urinary Casts ).

Table
icon

Other urine tests

Other tests are useful in specific instances.

Total protein excretion can be measured in a 24-hour collection or can be estimated by the protein/creatinine ratio, which, in a random urine sample, correlates well with values in g/1.73 m2 BSA from a 24-hour collection (eg, 400 mg/dL protein and 100 mg/dL creatinine in a random sample equal 4 g/1.73 m2 in a 24-hour collection). The protein/creatinine ratio is less accurate when creatinine excretion is significantly increased (eg, in muscular athletes) or decreased (eg, in cachexia).

Moderately increased albuminuria (formerly known as microalbuminuria) is albumin excretion persistently between 30 and 300 mg/day (20 to 200 micrograms [mcg]/min); lesser amounts are considered within the range of normal, and amounts > 300 mg/day (> 200 mcg/min) are considered overt proteinuria. Use of the urine albumin/urine creatinine ratio is a reliable and more convenient screening test because it avoids timed urine specimens and correlates well with 24-hour values. A value > 30 mg/g (> 0.03 mg/mg) suggests moderately increased albuminuria. The reliability of the test is best when a midmorning specimen is used, vigorous exercise is avoided before the test, because vigorous exercise can cause transient dipstick positivity for protein, and unusual creatinine production (in cachectic or very muscular patients) is not present. Moderately increased albuminuria can occur in all of the following:

Moderately increased albuminuria is an early stage of diabetic kidney disease in both type 1 and 2 diabetes; the progression of renal disease is more predictable in type 1 than 2 disease. moderately increased albuminuria is a risk factor for cardiovascular disorders and early cardiovascular mortality independent of diabetes or hypertension.

Sulfosalicylic acid (SSA) test strips can be used to detect protein other than albumin (eg, immunoglobulins in multiple myeloma) when dipstick urine tests are negative; urine supernatant mixed with SSA becomes turbid if protein is present. The test is semiquantitative with a scale of 0 (no turbidity) to 4+ (flocculent precipitates). Readings are falsely elevated by radiopaque contrast agents.

Ketones spill into urine with ketonemia, but use of test strips to measure urinary ketones is no longer widely recommended because they measure only acetoacetic acid and acetone, not beta-hydroxybutyric acid. Thus, a false-negative result is possible even without an exogenous cause (eg, vitamin C, phenazopyridine, N-acetylcysteine); direct measurement of serum ketones is more accurate. Ketonuria is caused by endocrine and metabolic disorders and does not reflect renal dysfunction.

Electrolyte measurements help diagnose specific disorders. Sodium (Na) level can help distinguish whether volume depletion (urine Na < 10 mEq/L [10 mmol/L]) or acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more Acute Tubular Necrosis (ATN) (urine Na > 40 mEq/L [40 mmol/L]) is the cause of acute renal insufficiency or failure. The fractional excretion of Na (FENa) is the percentage of filtered Na that is excreted. It is calculated as the ratio of excreted to filtered Na, which can be simplified to the following:

equation

where UNa is urine Na, PNa is plasma Na, PCr is plasma creatinine, and UCr is urine creatinine.

This ratio is a more reliable measure than UNa alone because UNa levels between 10 and 40 mEq/L (or 10 and 40 mmol/L) are nonspecific. FENa< 1% suggests prerenal causes, such as volume depletion; however, acute glomerulonephritis or certain types of acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more Acute Tubular Necrosis (ATN) (eg, rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is a clinical syndrome involving the breakdown of skeletal muscle tissue. Symptoms and signs include muscle weakness, myalgias, and reddish-brown urine, although this triad is... read more , radiocontrast-induced renal failure Contrast Nephropathy Contrast nephropathy is worsening of renal function after IV administration of radiocontrast and is usually temporary. Diagnosis is based on a progressive rise in serum creatinine 24 to 48 hours... read more ) and acute partial obstruction can result in FENa< 1%. A value > 1% suggests intrarenal causes such as acute tubular necrosis Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more Acute Tubular Necrosis (ATN) or acute interstitial nephritis Acute tubulointerstitial nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more Acute tubulointerstitial nephritis .

Other useful measurements include the following:

Eosinophils, cells that stain bright red or pink-white with Wright or Hansel staining, most commonly indicate one of the following:

Cytology is used for the following:

  • To screen for cancer in high-risk populations (eg, petrochemical workers)

  • To evaluate persistent painless hematuria of unclear etiology after cystoscopy in the absence of glomerular disease (suggested by the absence of dysmorphic RBCs, proteinuria, and renal failure) in patients with irritative voiding symptoms

Sensitivity is about 90% for carcinoma in situ; however, sensitivity is considerably lower for low-grade transitional cell carcinomas. Inflammatory or reactive hyperplastic lesions or cytotoxic drugs for carcinoma may produce false-positive results. Accuracy for detecting bladder tumors may be increased by vigorous bladder lavage with a small volume of 0.9% saline solution (50 mL pushed in and then aspirated by syringe through a catheter). Cells collected in the saline are concentrated and examined.

Blood tests

Blood tests are useful in evaluation of renal disorders.

Serum creatinine values > 1.3 mg/dL (> 114 micromol/L) in men and > 1 mg/dL (> 88.4 micromol/L) in women are usually abnormal. Serum creatinine depends on creatinine generation as well as renal creatinine excretion. Because creatinine turnover increases with higher muscle mass, muscular people have higher serum creatinine levels and older and undernourished people have lower levels.

Serum creatinine may also be increased in the following conditions:

ACE inhibitors and ARBs reversibly decrease glomerular filtration rate (GFR) and increase serum creatinine because they vasodilate efferent more than afferent glomerular arterioles, mainly in people who are dehydrated or are receiving diuretics. In general, serum creatinine alone is not a good indicator of kidney function. The Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) formula estimate GFR based on serum creatinine and other parameters and more reliably evaluate kidney function.

Blood urea nitrogen (BUN)/creatinine ratio is used to distinguish prerenal from renal or postrenal (obstructive) azotemia; a value > 15 is considered abnormal and may occur in prerenal and postrenal azotemia. However, BUN is affected by protein intake and by several nonrenal processes (eg, trauma, infection, gastrointestinal [GI] bleeding, corticosteroid use) and, although suggestive, is generally inconclusive as evidence of renal dysfunction.

Cystatin C, a serine proteinase inhibitor that is produced by all nucleated cells and filtered by the kidneys, can also be used to evaluate kidney function. Its plasma concentration is independent of sex, age, and body weight. Testing is not always available, and values are not standardized across laboratories. Measurement of cystatin C is used to confirm chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease in specific circumstances when eGFR calculations based on serum creatinine are less accurate and/or when eGFR is 45 to 59 mL/min with no markers of kidney damage present.

Serum electrolytes (eg, sodium [Na], potassium [K], bicarbonate [HCO3]) may become abnormal and the anion gap (Na – [Cl +HCO3]) may increase in acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more and chronic kidney disease. Serum electrolytes should be monitored periodically in patients with renal disorders.

Renin, a proteolytic enzyme, is stored in the juxtaglomerular cells of the kidneys. Renin secretion is stimulated by reduced blood volume and renal blood flow and is inhibited by sodium and water retention. Plasma renin is assayed by measuring renin activity as the amount of angiotensin I generated per hour. Specimens should be drawn from well-hydrated, sodium- and potassium-replete patients. Plasma renin, aldosterone, cortisol, and adrenocorticotropic hormone (ACTH) should be measured in evaluation of all of the following:

The plasma aldosterone/renin ratio calculated from measurements obtained with the patient in an upright posture is the best screening test for hyperaldosteronism, provided that plasma renin activity is < 0.5 ng/mL/h (< 0.5 mcg/L/h) and aldosterone is > 12 to 15 ng/dL (333 to 416 pmol/L).

Evaluating Kidney Function

Kidney function is evaluated using values calculated from formulas based on results of blood and urine tests.

GFR

Glomerular filtration rate (GFR), the volume of blood filtered through the kidney per minute, is the best overall measure of kidney function; it is expressed in mL/min. Because normal GFR increases with increasing body size, a correction factor using body surface area (BSA) typically is applied. This correction is necessary to compare a patient’s GFR to normal and to define different stages of chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease . Given the mean normal BSA of 1.73 m2, the correction factor is 1.73/patient BSA; adjusted GFR results are then expressed as mL/min/1.73 m2.

Normal GFR in young, healthy adults is about 120 to 130 mL/min/1.73 m2 and declines with age to about 75 mL/min/1.73 m2 at age 70. Chronic kidney disease is defined by a GFR < 60 mL/min/1.73 m2 for > 3 months. The standard for GFR measurement is inulin clearance. Inulin is neither absorbed nor secreted by the renal tubule and therefore it is the ideal marker for evaluation of kidney function. However, its measurement is cumbersome and, therefore, is mostly used in research settings. GFR is most accurately estimated by combining CKD-EPI equations based on creatinine and cystatin C, than by equations that use creatinine or cystatin C alone (1 Evaluation reference In patients with renal disorders, symptoms and signs may be nonspecific, absent until the disorder is severe, or both. Findings can be local (eg, reflecting kidney inflammation or mass), result... read more Evaluation reference ).

Creatinine clearance

Creatinine is produced at a constant rate by muscle metabolism and is freely filtered by the glomeruli and also is secreted by the renal tubules. Because creatinine is secreted, creatinine clearance (CrCl) overestimates GFR by about 10 to 20% in people with normal kidney function and by up to 50% in patients with advanced renal failure; thus, use of CrCl to estimate GFR in chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease is discouraged.

Using a timed (usually 24-hour) urine collection, CrCl can be calculated as

equation

where UCr is urine creatinine in mg/mL, UVol is urine volume in mL/min of collection (1440 minutes for a full 24-hour collection), and PCr is plasma creatinine in mg/mL.

Creatinine Clearance Calculators

Estimating creatinine clearance

Because serum creatinine by itself is inadequate for evaluation of kidney function, several formulas have been devised to estimate CrCl using serum creatinine and other factors.

The Cockcroft-Gault formula can be used to estimate CrCl. It uses age, lean body weight, and serum creatinine level. It is based on the premise that daily creatinine production is 28 mg/kg/day with a decrease of 0.2 mg/year of age.

equation

The Modification of Diet in Renal Disease (MDRD) study formula (current 4-factor formula) can also be used, although it requires a calculator or computer:

equation

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula provides a lower sensitivity but a higher specificity for detecting a GFR less than 60 mL/min per 1.73 m2, and may be more useful in evaluating patients with normal or near-normal kidney function. Like the Cockcroft-Gault and MDRD equations, it is also based on the serum creatinine level.

equation

where SCr is serum creatinine in mg/dL, kappa (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 1, and max indicates the maximum of SCr /κ or 1.

A calculator is available from the National Kidney Foundation.

Evaluation reference

Drugs Mentioned In This Article

Drug Name Select Trade
No US brand name
ACETADOTE
PROVAYBLUE
FURADANTIN, MACROBID, MACRODANTIN
ACHROMYCIN V
ANCOBON
TAGAMET
No brand name
ZOVIRAX
CRIXIVAN
MEFOXIN
DIPRIVAN
Levodopa
RIFADIN, RIMACTANE
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