Chapter 48: Azotemia and Urinary Abnormalities

Chapter 48: Azotemia and Urinary Abnormalities is a topic covered in the Harrison's Manual of Medicine.

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ABNORMALITIES OF RENAL FUNCTION, AZOTEMIA

Azotemia is the retention of nitrogenous waste products excreted by the kidney. Increased levels of blood urea nitrogen (BUN) (>10.7 mmol/L [>30 mg/dL]) and creatinine (>133 µmol/L [>1.5 mg/dL]) are ordinarily indicative of impaired renal function. Renal function can be estimated by determining the clearance of creatinine (CLcr) (normal >100 mL/min); this can be directly measured from a 24-h urine collection using the following equation:

Creatinine clearance (mL/min) = (uCr × uV)/(sCr × 1440)

  1. Where uCr is urine creatinine in mg/dL
  2. Where sCr is serum creatinine in mg/dL
  3. Where uV is 24-h urine volume in mL
  4. Where 1440 represents number of minutes in 24 h

The “adequacy” or “completeness” of the collection is estimated by the urinary volume and creatinine content; creatinine is produced from muscle and excreted at a relatively constant rate. For a 20- to 50-year-old man, creatinine excretion should be 18.5–25.0 mg/kg body weight; for a woman of the same age, it should be 16.5–22.4 mg/kg body weight. For example, an 80-kg man should excrete between ∼1500 and 2000 mg of creatinine in an “adequate” collection. Creatinine excretion is also influenced by age and muscle mass. Notably, creatinine is an imperfect measure of glomerular filtration rate (GFR), because it is both filtered by glomeruli and secreted by proximal tubular cells; the relative contribution of tubular secretion increases with advancing renal dysfunction, such that creatinine clearance will provide an overestimate of the “true” GFR in pts with chronic kidney disease. Isotopic markers that are filtered and not secreted (e.g., iothalamate) provide more accurate estimates of GFR.

A formula that allows for an estimate of creatinine clearance in men that accounts for age-related decreases in GFR, body weight, and sex has been derived by Cockcroft-Gault:

Creatinine clearance (mL/min) = (140-age) × lean body weight (kg)/plasma creatinine (mg/dL) × 72

This value should be multiplied by 0.85 for women.

GFR may also be estimated using serum creatinine–based equations derived from the Modification of Diet in Renal Disease Study. This “eGFR” (estimated glomerular filtration rate) is now reported with serum creatinine by most clinical laboratories in the United States and is the basis for the National Kidney Foundation classification of chronic kidney disease (Table 48-1).

TABLE 48-1: The Classification of Chronic Kidney Disease
KIDNEY DAMAGE STAGEDESCRIPTIONEGFR (ml/min PER 1.73 m2)
0With risk factors for CKDa>90
1With evidence of kidney damageb>90
2Mild decrease in GFR60–89

3a

3b

Moderate decrease in GFR

45–59

30-44

4Severe decrease in GFR15–29
5Kidney failure<15
aDiabetes, high blood pressure, family history, older age, African ancestry.
bAbnormal urinalysis, hematuria, proteinuria, albuminuria.
Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

More recently, estimation of GFR using measurement of an alternative circulating marker, cystatin C, has been incorporated into clinical practice. Cystatin C, a member of the cystatin superfamily of cysteine protease inhibitors, is produced at a relatively constant rate from all nucleated cells; as with creatinine, measurement of cystatin C generates an estimated GFR (eGFR). Serum cystatin C has been proposed to be a more sensitive marker of early GFR decline than is Cr, with lesser effects of muscle mass on circulating levels; however, like serum creatinine, cystatin C is influenced by the pt’s age, race, and sex.

Manifestations of impaired renal function include volume overload, hypertension, electrolyte abnormalities (e.g., hyperkalemia, hypocalcemia, hyperphosphatemia), metabolic acidosis, and hormonal disturbances (e.g., insulin resistance, functional vitamin D deficiency, secondary hyperparathyroidism). When severe, the symptom complex of “uremia” may develop, encompassing one or more of the following symptoms and signs: anorexia, dysgeusia, nausea, vomiting, lethargy, confusion, asterixis, pleuritis, pericarditis, enteritis, pruritus, sleep and taste disturbance, hiccups, and nitrogenous fetor.

An approach to the pt with azotemia is shown in Fig. 48-1.

FIGURE 48-1
hmom20_ch48_f001.png

Approach to the pt with azotemia. FeNa, fractional excretion of sodium; GBM, glomerular basement membrane. (From Lin J, Denker BM: Azotemia and urinary abnormalities, in Kasper DL et al (eds). Harrison’s Principles of Internal Medicine, 19th ed. New York, NY: McGraw-Hill; 2014.)

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ABNORMALITIES OF RENAL FUNCTION, AZOTEMIA

Azotemia is the retention of nitrogenous waste products excreted by the kidney. Increased levels of blood urea nitrogen (BUN) (>10.7 mmol/L [>30 mg/dL]) and creatinine (>133 µmol/L [>1.5 mg/dL]) are ordinarily indicative of impaired renal function. Renal function can be estimated by determining the clearance of creatinine (CLcr) (normal >100 mL/min); this can be directly measured from a 24-h urine collection using the following equation:

Creatinine clearance (mL/min) = (uCr × uV)/(sCr × 1440)

  1. Where uCr is urine creatinine in mg/dL
  2. Where sCr is serum creatinine in mg/dL
  3. Where uV is 24-h urine volume in mL
  4. Where 1440 represents number of minutes in 24 h

The “adequacy” or “completeness” of the collection is estimated by the urinary volume and creatinine content; creatinine is produced from muscle and excreted at a relatively constant rate. For a 20- to 50-year-old man, creatinine excretion should be 18.5–25.0 mg/kg body weight; for a woman of the same age, it should be 16.5–22.4 mg/kg body weight. For example, an 80-kg man should excrete between ∼1500 and 2000 mg of creatinine in an “adequate” collection. Creatinine excretion is also influenced by age and muscle mass. Notably, creatinine is an imperfect measure of glomerular filtration rate (GFR), because it is both filtered by glomeruli and secreted by proximal tubular cells; the relative contribution of tubular secretion increases with advancing renal dysfunction, such that creatinine clearance will provide an overestimate of the “true” GFR in pts with chronic kidney disease. Isotopic markers that are filtered and not secreted (e.g., iothalamate) provide more accurate estimates of GFR.

A formula that allows for an estimate of creatinine clearance in men that accounts for age-related decreases in GFR, body weight, and sex has been derived by Cockcroft-Gault:

Creatinine clearance (mL/min) = (140-age) × lean body weight (kg)/plasma creatinine (mg/dL) × 72

This value should be multiplied by 0.85 for women.

GFR may also be estimated using serum creatinine–based equations derived from the Modification of Diet in Renal Disease Study. This “eGFR” (estimated glomerular filtration rate) is now reported with serum creatinine by most clinical laboratories in the United States and is the basis for the National Kidney Foundation classification of chronic kidney disease (Table 48-1).

TABLE 48-1: The Classification of Chronic Kidney Disease
KIDNEY DAMAGE STAGEDESCRIPTIONEGFR (ml/min PER 1.73 m2)
0With risk factors for CKDa>90
1With evidence of kidney damageb>90
2Mild decrease in GFR60–89

3a

3b

Moderate decrease in GFR

45–59

30-44

4Severe decrease in GFR15–29
5Kidney failure<15
aDiabetes, high blood pressure, family history, older age, African ancestry.
bAbnormal urinalysis, hematuria, proteinuria, albuminuria.
Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

More recently, estimation of GFR using measurement of an alternative circulating marker, cystatin C, has been incorporated into clinical practice. Cystatin C, a member of the cystatin superfamily of cysteine protease inhibitors, is produced at a relatively constant rate from all nucleated cells; as with creatinine, measurement of cystatin C generates an estimated GFR (eGFR). Serum cystatin C has been proposed to be a more sensitive marker of early GFR decline than is Cr, with lesser effects of muscle mass on circulating levels; however, like serum creatinine, cystatin C is influenced by the pt’s age, race, and sex.

Manifestations of impaired renal function include volume overload, hypertension, electrolyte abnormalities (e.g., hyperkalemia, hypocalcemia, hyperphosphatemia), metabolic acidosis, and hormonal disturbances (e.g., insulin resistance, functional vitamin D deficiency, secondary hyperparathyroidism). When severe, the symptom complex of “uremia” may develop, encompassing one or more of the following symptoms and signs: anorexia, dysgeusia, nausea, vomiting, lethargy, confusion, asterixis, pleuritis, pericarditis, enteritis, pruritus, sleep and taste disturbance, hiccups, and nitrogenous fetor.

An approach to the pt with azotemia is shown in Fig. 48-1.

FIGURE 48-1
hmom20_ch48_f001.png

Approach to the pt with azotemia. FeNa, fractional excretion of sodium; GBM, glomerular basement membrane. (From Lin J, Denker BM: Azotemia and urinary abnormalities, in Kasper DL et al (eds). Harrison’s Principles of Internal Medicine, 19th ed. New York, NY: McGraw-Hill; 2014.)

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