Azotemia and Urinary Abnormalities

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 _mol/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). CLcr overestimates glomerular

filtration rate (GFR),particularly at lower levels. A formula that allows 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:

(140 _ age) _ lean body weight (kg)

Creatinine clearance (mL/min) _ 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. Isotopic markers (e.g.,

iothalamate) provide more accurate estimates of GFR.

Manifestations of impaired renal function include: volume overload,hypertension,

electrolyte abnormalities (e.g., hyperkalemia, hypocalcemia, hyperphosphatemia),

metabolic acidosis, hormonal disturbances (e.g., insulin resistance,

functional vitamin D deficiency, secondary hyperparathyroidism), and,

when severe,“uremia” (one or more of the following: anorexia, lethargy, confusion,

asterixis, pleuritis,pericarditis,enteritis,pruritus, sleep and taste disturbance,

nitrogenous fetor).

An approach to the patient with azotemia is shown in Fig. 56-1.

ABNORMALITIES OF URINE VOLUME

OLIGURIA This refers to sparse urine output,usually defined as _400

mL/d. Oligoanuria refers to a more marked reduction in urine output,i.e., _100

mL/d. Anuria indicates the absence of urine output. Oliguria most often occurs

in the setting of volume depletion and/or renal hypoperfusion,resulting in “prerenal

azotemia” and acute renal failure (Chap. 140). Anuria can be caused by

complete bilateral urinary tract obstruction; a vascular catastrophe (dissection

or arterial occlusion); renal vein thrombosis; and hypovolemic,cardiogenic, or

septic shock. Oliguria is never normal,since at least 400 mL of maximally

concentrated urine must be produced to excrete the obligate daily osmolar load.

POLYURIA Polyuria is defined as a urine output _3 L/d. It is often accompanied

by nocturia and urinary frequency and must be differentiated from other more common conditions associated with lower urinary tract pathology

and urinary urgency or frequency (e.g.,cystitis, prostatism). It is often accompanied

by hypernatremia (Chap. 3). Polyuria (Table 56-1) can occur as a response

to a solute load (e.g.,hyperglycemia) or to an abnormality in antidiuretic

hormone (ADH) action. Diabetes insipidus is termed central if due to the insufficient hypothalmic production of ADH and nephrogenic if the result of renal

insensitivity to the action of ADH. Excess fluid intake can lead to polyuria,but

primary polydipsia rarely results in changes in plasma osmolality unless urinary

diluting capacity is impaired,as with chronic renal failure. Tubulointerstitial

diseases and urinary tract obstruction can be associated with nephrogenic diabetes

insipidus. The approach to the pt with polyuria is shown in Fig. 56-2.

Major Causes of Hematuria

LOWER URINARY TRACT

Bacterial cystitis

Intestitial cystitis

Urethritis (infectious or inflammatory)

Passed or passing kidney stone

Transitional cell carcinoma of bladder or structures proximal to it

Squamous cell carcinoma of bladder (e.g.,following schistosomiasis)

UPPER URINARY TRACT

Renal cell carcinoma

Age-related renal cysts

Other neoplasms (e.g.,oncocytoma, hamartoma)

Acquired renal cystic disease

Congenital cystic disease,including autosomal dominant form

Glomerular diseases

Interstitial renal diseases

Nephrolithiasis

Pyelonephritis

Renal infarction

ABNORMALITIES OF URINE COMPOSITION

PROTEINURIA This is the hallmark of glomerular disease. Levels up to

150 mg/d are considered within normal limits. Typical measurements are semiquantitative, using a moderately sensitive dipstick that estimates protein concentration; therefore,the degree of hydration may influence the dipstick protein

determination. Most commercially available urine dipsticks detect albumin and

do not detect smaller proteins,such as light chains, that require testing with

sulfosalicylic acid. More sensitive assays can be used to detect microalbuminuria

in diabetes mellitus. A urine albumin to creatinine ratio _30 mg/g defines

the presence of micoalbuminuria.

Urinary protein excretion rates between 500 mg/d and 3 g/d are nonspecific

and can be seen in a variety of renal diseases (including hypertensive nephrosclerosis, interstitial nephritis,vascular disease,and other primary renal diseases with little or no glomerular involvement). Lesser degrees of proteinuria (500 mg/d to 1.5 g/d) may be seen after vigorous exercise,changes in body position, fever,or congestive heart failure. Protein excretion rates _3 g/d are termed

nephrotic range proteinuria and are accompanied by hypoalbuminemia, hypercholesterolemia, and edema in the nephrotic syndrome. Massive degrees of proteinuria (_10 g/d) can be seen with minimal change disease,primary focal

segmental sclerosis,membranous nephropathy, collapsing glomerulopathy, and

HIV-associated nephropathy and can be associated with a variety of extrarenal

complications (Chap. 144).

Pharmacologic inhibition of ACE or blockade of angiotensin II or aldosterone

receptors may reduce proteinuria in some pts,particularly those with diabetic

nephropathy. Specific therapy for a variety of causes of nephrotic syndrome

is discussed in Chap. 144.

HEMATURIA Gross hematuria refers to the presence of frank blood in

the urine and is more characteristic of lower urinary tract disease and/or bleeding

diatheses than intrinsic renal disease (Table 56-2). Cyst rupture in polycystic

kidney disease and flares of IgA nephropathy are exceptions. Microscopic hematuria (_1–2 RBC/high powered field) accompanied by proteinuria,hypertension, and an active urinary sediment (the “nephritic syndrome”) is most likely related to an inflammatory glomerulonephritis (Chap. 144). Free hemoglobin and myoglobin are detected by dipstick; a negative urinary

sediment with strongly heme-positive dipstick are characteristic of either hemolysis or rhabdomyolysis,which can be differentiated by clinical history and

laboratory testing. Red blood cell casts are not commonly seen but are highly

specific for glomerulonephritis.

The approach to the pt with hematuria is shown in Fig. 56-3.

PYURIA This may accompany hematuria in inflammatory glomerular diseases.

Isolated pyuria is most commonly observed in association with an infection

of the upper or lower urinary tract. Pyuria may also occur with allergic

interstitial nephritis (often with a preponderance of eosinophils),transplant rejection, and noninfectious,nonallergic tubulointerstitial diseases. The finding of

“sterile” pyuria (i.e.,urinary white blood cells without bacteria) in the appropriate

clinical setting should raise suspicion of renal tuberculosis.