Laboratory Diagnosis of Renal Disease

OBJECTIVES

By the end of this session the reader should be able to:

  • Identify the most common non-protein nitrogenous substances in serum
  • Describe the influence of diet on serum urea-nitrogen
  • Discuss the use of serum urea-nitrogen, serum creatine, and glomerular filtration rate in the workup, diagnosis, and monitoring of renal disease and function
  • Calculate the creatinine clearance as an estimate of glomerular filtration rate
  • Describe physiological conditions in which the serum urea-nitrogen: creatinine ratio is increased
  • Describe physiological conditions in which the serum urea-nitrogen: creatinine ratio is decreased
  • Discuss the most common laboratory findings in acute pyelonephritis
  • Discuss the most common laboratory findings in nephrotic syndrome
  • Discuss the most common laboratory findings in acute glomerulonephritis
  • Discuss the most common laboratory findings in chronic glomerulonephritis
  • Calculate the selectivity ratio
  • Discuss the laboratory findings that differentiate prerenal from renal failure
  • Differentiate renal tubular dysfunction from glomerular dysfunction

KEY TERMS

Albuminuria - the presence of albumin in urine

Anuria - lack of urine output (< 50 mL per day)

Azotemia - an excess of urea, creatinine and other nitrogenous end products of amino acid metabolism in blood

Bowman’s capsule - a structure consisting of glomeruli and extended opening of proximal tubule

Casts - protein aggregates, outlined in the shape of renal tubules and excreted into the urine; the matrix is the Tamm-Horsfall protein

Creatinine - a spontaneous breakdown product of muscle creatine, used to monitor renal function

Creatinine clearance - an estimate of the glomerular filtration rate obtained by measurement of the amount of creatinine in the plasma and its rate of excretion into the urine

End-stage renal disease (ESRD) - a condition in which renal function is inadequate to support life

Glomerular filtration rate (GFR) - the rate in milliliters per minute that substances such as creatinine and urea are filtered through the kidney’s glomeruli (mL/min); a reflection of the number of functioning nephrons; estimated by the creatinine clearance (see above)

Glomerulonephritis - nephritis accompanied by inflammation of the capillary loops in the glomeruli of the kidney; occurs in acute, subacute, and chronic forms and may be secondary to hemolytic streptococcal infection; evidence suggesting possible immune or autoimmune mechanisms

Glomerulus - a tuft of blood vessels found in the nephron of the kidney that are involved in the filtration of the blood

Hematuria - blood in the urine

Hemodialysis - the exogenous removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane (for example, by means of a hemodialysis filter)

Isosthenuria - urine with a fixed specific gravity in range of 1.008 to 1.012

Microalbuminuria - low-grade, dipstick-negative increase in urine albumin excretion, useful in monitoring renal status of individuals prone to renal impairment from diseases such as diabetes

Nephritis - inflammation of the kidney with focal or diffuse proliferation or destructive processes that may involve the glomerulus, tubule, or interstitial renal tissue

Nephron - the anatomical and functional unit of the kidney, consisting of the renal corpuscle, proximal convoluted tubule, descending and ascending limbs of Henle’s loop, distal convoluted tubule, and collecting tubule

Nephrotic syndrome - general name for a group of diseases involving increased glomerular permeability, characterized by massive proteinuria and lipiduria with varying degrees of edema, hypoalbuminemia, and hyperlipidemia

Oliguria - decreased urine output (< 400 mL per day)

Peritoneal dialysis - hemodialysis through the peritoneum, the dialyzing solution being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure

Pyelonephritis - inflammation of the kidney and its pelvis

Pyuria - the presence of pus (an inflammation fluid with leukocytes and dead cells) in the urine

Renal threshold - the plasma concentration of a substance above which it will be excreted into the urine

Tamm-Horsfall protein - a mucoprotein produced by the ascending limb of the loop of Henle that is a normal constituent of urine and is the major protein constituent of urinary casts

Urea - major nitrogen containing product of protein metabolism, used to monitor renal function

Uremia - an excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acid metabolism; more correctly referred to as azotemia

BACKGROUND / SIGNIFICANCE

Most renal disease causes no symptoms until 50-75% of kidney function is destroyed. Lab tests often provide the initial recognition of renal impairment and can be used to direct further therapy. In therapeutics, knowledge of renal function is essential for recommending proper doses of prescription drugs. Many drugs are renally cleared and decreased renal clearance can lead to toxicity. Dose adjustments are based on assessments of renal function.

EXCRETORY FUNCTION OF KIDNEY

The excretory function of the kidney serves to rid the body of undesirable end products of metabolism. One of these groups, the non-protein nitrogenous (NPN) compounds, is listed in Table 1.

Table 1
Contributors Other Minor Contributors
Urea Nucleotides
Uric acid Purine
Creatinine Polypeptides
Creatine Glutathione
Amino acids
Ammonia

The two most popular screening tests for renal function are serum urea nitrogen and serum creatinine. Better measures of glomerular function are clearance tests. This is especially true in the aged, where serum creatinine measurements are less reliable due to decreasing muscle mass.

In uremia (kidney failure) the increase is mainly in urea, creatinine and uric acid. Uric acid and the other NPN-compounds are measured rarely in this context. Serum urea nitrogen (SUN) is normally ~45% of total NPN, but may be 80% of NPN in some disease states. In hepatic failure the ratio of non-urea/urea nitrogen increases, because of the inability of the liver to synthesize urea and to deaminate amino acids.

Urea Nitrogen

  • Major nitrogen-containing metabolic product of protein catabolism
  • Primarily synthesized by hepatocytes
  • Freely filtered by glomeruli, reabsorbed (amount varies) by tubules

Historically, urea was reported as blood urea nitrogen (BUN) and this terminology has been incorrectly carried over to the present. Urea nitrogen is now measured using serum and is reported as “serum urea nitrogen” (SUN). Urea is synthesized mostly in the liver as a by-product of the deamination of amino acids arising from protein catabolism.

Urea is filtered by the glomeruli; however, about 40-70% (amount depends on urine flow) is reabsorbed by passive diffusion into blood across the renal tubular epithelium. Thus, in conditions in which the glomerular filtration rate is decreased, SUN will be increased. For this reason, urea clearance tests are less informative than creatinine clearance tests and have been discontinued.

Reference Range for serum urea nitrogen: 8-18 mg/dL

The serum urea nitrogen level is greatly influenced by diet.

Table 2
Daily Protein Intake (g/kg body weight) Urea-N Average (mg/dL)
Low protein diet: 0.5 ~5
Average protein diet: 1 ~12
High protein diet: 2 ~22

SUN is not a sensitive indicator of renal dysfunction because renal function must be reduced by more than 50% to result in a rise of SUN.

Creatinine

  • Derived from spontaneous conversion of muscle creatine (about 1-2% of total muscle mass per day)
  • Daily excretion is fairly constant and independent of urinary volume. Thus, this measurement can be used to assess the relative completeness of a 24-hour urine collection.
    • Average men excrete: 1.5 g/d into the urine
      • Women: less
      • Athletes: more

Patients with hepatic disease, muscular dystrophy, paraplegia and poliomyelitis may excrete less creatinine due to decreased production. It should be noted that many laboratories use alkaline picrate (Jaffe) method for measuring creatinine.

Reference Range for serum creatinine
M 0.6-1.3 mg/dL
F 0.5-1.1 mg/dL

Note: Creatinine production is based on weight and gender that is generally related to muscle mass. Thus, be circumspect when treating individuals with a high normal creatinine when a low creatinine is appropriate due to small muscle mass. This would include children, elderly, women, paralyzed patients, and amputees.

Glomerular Filtration Rate

A useful assessment of renal function is the measurement of the glomerular filtration rate (GFR), especially in older people. The inulin clearance rate closely approximates the true GFR since inulin is freely filtered by the glomerulus with minimal tubular absorption or secretion. However, this test is difficult to perform routinely. Measuring the clearance of endogenous creatinine (clearance of creatinine produced by metabolic processes) is much more practical and convenient but less accurate. Creatinine, for the most part, is freely filtered; thus, clearance of endogenous creatinine is a reflection of GFR. Normally, only small amounts (< 6%) are reabsorbed by the tubules and an equal amount may be secreted by the tubules. The endogenous creatinine clearance rate is computed by the following formula:

(1)
\begin{align} {C}_{creat} \ = \ \frac{{U}_{creat}}{{P}_{creat}} \ \times \ \overline{V} \ \times \ \frac{1.73 {m}^{2}}{A} \end{align}
  • Ccreat = creatinine clearance rate in mL/min
  • Ucreat = urinary creatinine in mg/dL
  • V = urine flow in mL/min (volume of timed urine / collection time)
  • Pcreat = serum creatinine in mg/dL

Since creatinine clearance is related to patient size, a more accurate formula includes an estimation of body surface area in square meters obtained from a nomogram using the height and weight of the patient. A = body surface area in m2, and 1.73 m2 is the average body surface area. In essence this formula “normalizes” the clearance to that of a normal-sized person. Patients being tested for the GFR must be well hydrated to provide a urine flow of > 2 mL/ min.

Reference Range: male = 117 ± 20 mL/min; female = 95 ± 20 mL/min


The relationship between serum creatinine and creatinine clearance is logarithmic (see Figure 1). Thus, initially, for small numeric changes in serum creatinine, there are significant numeric changes for creatinine clearance. In later stages of uremia, small numeric changes in the clearance are associated with significant changes in serum creatinine. Note the decrease in the number of nephrons with decrease of clearance and increase in serum creatinine.
Fig1.jpg

Figure 1: Correlation of Plasma Creatinine and Creatinine Clearance. Relationship between serum creatinine, creatinine clearance and number of remaining nephrons.

The endogenous creatinine clearance rate is primarily an estimate of GFR; however, a small amount of tubular secretion augments glomerular filtration. Therefore, total urinary creatinine is slightly higher than the amount actually filtered by the glomeruli. The amount of urinary creatinine derived from tubular secretion rises proportionally in renal failure with an increase in serum creatinine. With advancing renal failure and increase in serum creatinine, the tubular secretion proportionally increases up to 40-60%. From an interpretation standpoint this is important. With normal or early renal failure creatinine clearance approximates true GFR. With advanced renal failure creatinine clearance overestimates true GFR, which is because of the increased amount of creatinine in urine due to tubular secretion, which in turn is caused by the high concentration of creatinine in circulation.

Alternatively, more accurate isotopic methods for measuring GFR can be utilized, e.g. the clearance of injected 51Cr-labelled EDTA from the blood. This compound is completely filtered by the glomeruli and is not secreted or reabsorbed by the tubules. However, this method requires a special laboratory equipped to handle and measure radioactive isotopes.

An alternative to measuring GFR is to use the Cockroft and Gault equation[1] to estimate creatinine clearance based on a single measurement of serum creatinine. Where Screat is serum creatinine (mg/dL) and weight is in kilograms.

(2)
\begin{align} {C}_{creat} \left( males\right) \ = \ \frac{(140 - age)(Weight)}{({ S}_{creat})(72)} \end{align}
(3)
\begin{align} {C}_{creat} \left( females\right) \ = \ \frac{(140 - age)(Weight)}{({ S}_{creat})(72)} \ (0.85) \end{align}

TUBULAR FUNCTION

The most often used function tests are renal concentrating power and the ability to produce an acid urine (in suspected renal tubular acidosis).

Urine Osmolality and Renal Concentrating Ability

Osmolality refers to the concentration of osmotically active particles (osmolutes) in solution, expressed in mOsm/kg of water. Urine osmolality varies widely in health, between about 60 and 1250 mOsm/kg. The failing kidney loses its capacity to concentrate urine. A patient with polyuria due to chronic renal failure (CRF) is unable to produce either a dilute or a concentrated urine. Instead, urine osmolality in these patients is generally within 50 mOsm/kg of the plasma osmolality (i.e., between about 240 and 350 mOsm/kg).

Urine osmolality is a measure of concentrating power of the kidney. Urine specific gravity is usually directly proportional to osmolality. Both give misleadingly high results if there is significant glycosuria or proteinuria. The error can be mathematically corrected. Measurement of osmolality with an osmometer is more accurate, but also more difficult than specific gravity measurements.

Random testing of either specific gravity or osmolality is not very informative, due to the effect of fluid intake. Repeated measurements, or measurements under controlled fluid intake are more reliable. Specific gravity values of more than 1.025 or osmolality values more than 875 mOsm/kg indicate adequate renal concentrating ability. Recurring values of 1.010 (1.008-1.012) indicate isosthenuria (fixed specific gravity). This finding suggests loss of tubular concentrating and diluting ability and is frequently a prelude to anuria.

SUN/CREATININE RATIOS IN VARIOUS CONDITIONS

Normal ratio: ~12-20 (or 10-18 with less specific methods)

In practice, the greatest increase in the ratio may be seen in prerenal azotemia, where ratios of 30/1 or 35/1 may be observed. However, other conditions may also change the ratio, depending on the rate of urea synthesis, kidney blood flow, or glomerular filtration rate. When evaluating SUN/creatinine ratios realize that SUN production is dependent on available protein (increased protein intake increases the ratio) and liver function (decreased liver function lowers the ratio). In addition, the ratio is affected by the specificity of the creatinine method. (Less specific methods give higher creatinine values.)

The ratio is increased in conditions in which there is increased urea synthesis, as observed in the presence of blood in the GI tract, in muscle wasting disease, and in severe tissue trauma, all of which provide proteins that are catabolized into their constituent amino acids, which are then deaminated and converted into urea. Other conditions such as intraperitoneal extravasation of urine and urinary enteric fistulas lead to greater urea reabsorption. Increased tubular reabsorption of urea occurs with decreased tubular flow as a result of dehydration, decreased cardiac output, or shock (= prerenal azotemia), or due to renal disease, such as early acute glomerulonephritis, malignant nephrosclerosis, or postrenal obstruction.

Decreased ratios are seen in the presence of decreased urea synthesis (chronic glomerulonephritis with protein deficiency, severe hepatic insufficiency, and starvation) and decreased urea reabsorption (overhydration and rapid hydration). The decrease in ratio due to hemodialysis is caused by the more efficient dialysis of urea vs. creatinine. In acute tubular necrosis, urea and creatinine are equally and passively returned to the tubular blood. Therefore, the ratio is decreased.

RENAL FAILURE

Acute renal failure occurs rapidly and is potentially reversible if the initial illness or insult is survived (60% survival rate). Chronic renal failure usually develops over years in an insidious manner leading to endstage renal disease requiring lifelong dialysis or renal transplant.

Azotemia (increase of urea or other non-protein nitrogenous - compounds) is divided into 3 categories:

  1. Prerenal azotemia is caused by a decrease in renal blood flow, e.g. due to decreased cardiac output
  2. Renal azotemia results from damage to the kidney
  3. Postrenal azotemia is due to obstruction of urine flow, e.g. by prostatic hypertrophy or tumor

Laboratory Findings in Acute Glomerulonephritis

Acute diffuse inflammatory changes in the glomeruli with hematuria, RBC casts, mild proteinuria, and often hypertension, edema, and azotemia.

Serum chemistries

  • Elevated SUN
  • Elevated creatinine
  • Elevated uric acid
  • Elevated SUN/creatinine (> 20:1)
  • Decreased creatinine clearance
  • GFR decreased
  • Metabolic acidosis due to retention of phosphate, sulfate, amino acids, and other metabolic acids

Urinalysis

  • Red cells in urine
    • Microscopic hematuria (Smoky urine)
    • Macroscopic hematuria (Red urine)
  • Casts: Red cell casts (Blood casts)
  • Proteinuria, mild to moderate

Selectivity ratio

The ratio of the clearances of a high and a low molecular weight protein (IgG and albumin, respectively) gives an indication of the nature of glomerular damage in glomerular proteinuria (selective vs. non-selective).

(4)
\begin{align} Selectivity \ ratio \ = \frac{IgG \ clearance}{albumin \ clearance} \end{align}
  • High selectivity < 0.15; e.g., minimal change glomerulonephritis
  • Poor selectivity > 0.30; other than minimal change disease
  • The selectivity index is identical to the ratio, except that it is expressed in percent, (i.e., it is multiplied times 100).

Laboratory Findings in Chronic Glomerulonephritis

Slowly progressive glomerular disease. The syndrome is due to several diseases of different etiology. The disease is characterized by diffuse sclerosis of glomeruli, loss of nephrons, and loss of protein into the urine.

Serum chemistry values

  • Uremia (Elevated SUN, creatinine and uric acid)
    • Elevated SUN may not be as much as in acute glomerulonephritis, due to loss of protein in the urine
  • Hyponatremia
  • Hyperkalemia (Secondary to potassium retention)
  • Hypocalcemia (Secondary to loss of albumin into the urine and phosphate retention)
  • Hyperphosphatemia (Secondary to phosphate retention)
  • Decreased creatinine clearance
  • Metabolic acidosis (Secondary to retention of hydrogen ion)
  • Elevated alkaline phosphatase (Secondary to hypocalcemia stimulating secretion of parathyroid hormone)
  • Decreased SUN/creatinine ratio (<10:1)
  • GFR decreased

Urinalysis

  • Proteinuria (Massive)
  • Cylindruria (Tubular casts in the urine)
  • Episodic hematuria (Red cells in urine)
  • Isosthenuria (Low specific gravity fixed between 1.008 and 1.012)
  • GFR decreased

Anemia of chronic disorders

Laboratory Findings in Nephrosis (Nephrotic Syndrome)

Complex condition that follows prolonged increase in glomerular permeability for proteins. It may follow various insults to the kidney, including heavy metal, parasites, infections, etc.)

Table 3: Triad
Proteinuria, > 3.5 g/day SUN/creatinine ~12 (normal)
Hypoalbuminemia GFR normal
Hyperlipidemia
In addition, edema is generally present

The loss of protein leads to a decrease in oncotic pressure, resulting in edema. The decreased oncotic pressure stimulates a compensatory increase in hepatic lipoprotein synthesis, and, thus, hyperlipidemia is often seen in this condition. Increase in lipoproteins is also caused by loss of factors regulating lipoprotein synthesis. In the nephrotic syndrome there is a loss of a variety of proteins, such as transferrin, cortisol-binding globulin, thyroxine-binding globulin, and some coagulation factors. However, some coagulation factors are increased, e.g. Factor V and VIII, leading to thrombosis.

Major diagnostic findings

  • Low serum albumin, 1-2.5 g/dL (Normal: 3.4-4.8 g/dL)
  • Normal: SUN, serum creatinine, serum SUN/creatinine ratio, creatinine clearance
  • Increase in serum lipids (Triglycerides, cholesterol, lipoproteins)

Less specific findings

  • Increase in serum phospholipids
  • Decreased serum globulins (e.g. serum ceruplasmin, complement, transferrin)
  • A/G ratio reversed, or decreased (A/G = albumin / globulin)

Urinalysis

  • Reduced volume (From low urine output)
  • Large amounts of protein, usually 3.5-10 g/d; values up to 50 g/24 h are possible
  • Excretion of red and white cells is common
  • Casts: many hyaline and finely granular casts due to low urine flow
  • Oval fat-body casts in the urine (Fat is doubly refractile)
  • Oval fat bodies (Epithelial cells and macrophages loaded with fat)

Serum

Thyroxine-binding globulin may be decreased; accordingly, total T4 (thyroxine) may be decreased; thyroid function, however, is normal (normal free thyroxine). Total globulin concentration may be normal, but α2-globulins are increased (alpha-2 macroglobulin and low-density lipoprotein), and γ-globulins may be low (see serum protein section). Hence, serum protein electrophoresis typically demonstrates diminished albumin and elevated alpha-2 globulin fraction.

Laboratory Findings in Acute Pyelonephritis

Acute infective tubulo-interstitial nephritis; acute pyogenic infection of the kidney - one of the most common diseases of the kidney

Serum chemistry values

  • Normal: Urea N, serum creatinine, SUN, serum SUN/creatinine ratio (~12), creatinine clearance, GFR, and uric acid

Urinalysis

  • Pyuria (Pus in urine)
  • Microhematuria (Few red cells in urine)
  • White cells and white cell casts
  • Bacteriuria (Bacteria in urine)

Hematology

  • Peripheral leukocytosis

Laboratory Findings for Differentiating Prerenal and Renal Failure

Table 4
Prerenal failure Renal failure
Urine osmolality (mOsmol / kg) >500 <350
Urine: plasma ratio of urea concentration >10:1 <3:1
Urine: plasma ratio of osmolality >1.5:1 <1.1:1
Serum urea / creatinine ratio >20:1 variable

URINALYSIS

The routine urinalysis is carried out in three phases: macroscopic, chemical, and microscopic analysis.

Macroscopic Examination (Gross Examination)

  • Color
  • Turbidity

Chemical Examination

  • Specific gravity (Normal, 24 hours: 1.010-1.025)
  • Protein
  • Glucose
  • Ketone bodies
  • Hemoglobin (Occult blood)
    • Note: Myoglobin also reacts
  • Bile (Direct or conjugated bilirubin reacts, but not unconjugated)
  • Urobilinogen

Microscopic Examination

  • Larger elements are: casts, mucous threads, parasites, ova, foreign bodies, etc. (low power)
  • Casts, if present, are also examined under the high power field to determine their types
  • The numbers of red cells, white cells, epithelial cells, bacteria, yeast, trichomonas, and crystals are also counted and an average count for each is recorded

Urine Casts

Casts are found in the urine sediment. They are formed in two ways, by precipitation and gelling of proteins in tubular fluid, and by clumping of cells in tubules. Casts are molded in the lumen of the distal renal tubules or collecting ducts. The matrix of all casts is a specific mucoprotein common to all casts, namely Tamm-Horsfall protein. The classification of casts is based on appearance, physical properties, and type of cellular components. Cells within the matrix can degenerate into coarse and finely granular casts and to waxy casts.

Types of urine casts

Hyaline casts.
The casts consist only of Tamm-Horsfall protein. They are excreted by the normal kidney in small amounts. Excretion of numerous casts is seen in all renal diseases associated with benign essential hypertension, and nephrotic syndrome.

White blood cell (leukocyte) casts.
These casts are formed when WBC's are incorporated into the protein matrix. They enter the urine stream by ameboid movement through and between tubular epithelial cells and sometimes they cross the glomerular capillary lumen. These casts are associated with diseases with leukocytic exudation and interstitial inflammation. Example: pyelonephritis.

Red cell (erythrocyte) casts.
Presence of these casts indicates severe injury to the glomerular basement membrane. The reddish orange color is secondary to hemoglobin pigmentation. Erythrocytes (RBC’s) are biconcave disks packed in fibrin meshwork within the cast matrix. These casts are associated with acute glomerulonephritis (most common), lupus nephritis, Goodpasture’s syndrome, and subacute bacterial endocarditis (SBE).

Renal epithelial casts.
These casts are due to constant desquamation and renewal of the renal epithelium. Their presence points to a pathological process occurring in the kidney and affecting the tubular portion of the nephron (tubular damage). Epithelial casts are associated with exposure to nephrotoxic agents and exposure to some viruses.

Granular casts.
These casts are formed from breakdown products of cellular casts and immunoglobulins. There is a progression from coarsely granular to finely granular casts.

Waxy casts.
These are the result of progressive degenerative changes occurring in cellular casts and they are associated with severe chronic renal disease and amyloidosis.

Fatty casts.
These casts are probably due to leakage of lipoproteins through the glomerular filter and are associated with nephrotic syndrome, diabetes mellitus, and damaged renal tubular epithelial cells.

Mixed cell casts.

Table 5: Some Commonly Seen Urinary Crystals
Crystal Appearance Urine pH
Calcium oxalates "Envelopes" acid
Sodium urates "Whetstones" acid
Triple phosphates (magnesium ammonium phosphate) "Coffin lids" alkaline
Ammonium biurates "Thorn apples" alkaline
Amorphous phosphates Amorphous debris alkaline
Tyrosine Needles in rosettes acid
Leucine Spheres acid
Sulfonamides Sheaves acid
Cystine Hexagons acid

Drug crystals (e.g., ampicillin needles, primidone hexagons) are formed from drugs that are present in relatively high concentrations and that are relatively insoluble in water at the urinary pH.

CASE STUDIES

Case 1

(Ann. Pharmacother. 36(9):1380-1382, 2002)

A 73-year-old white man, with a medical history of non-small-cell lung cancer and idiopathic myelofibrosis with myeloid metaplasia, was prescribed levofloxacin 500 mg/d orally because of a lower urinary tract infection. Three days after starting treatment with levofloxacin, the patient was admitted to the hospital with palpable purpura and erythematous skin lesions over the lower limbs and trunk, with a markedly diminished urine output. His vital signs were BP 155/70 mmHg, HR 92 beats/min, RR 14 breaths/min, and (axillary) Temp 37.1°C.

Initial patient labs (2 weeks prior to levofloxacin): creatinine 1.0 mg/dL, urea 38 mg/dL.

On admission the patient’s serum creatinine concentration was 6.4 mg/dL and serum urea nitrogen 190 mg/dL. Serum electrolytes were normal. Hemoglobin and hematocrit were 8.4 g/dL and 24%. Bilirubin, aminotransferase enzymes, and alkaline phosphatase were normal; lactate dehydrogenase was also normal. Urinalysis disclosed 3+ proteinuria, with no casts or crystals, an acidic pH (5.0), and a reduced specific gravity (1.007). The daily urinary output was 0.6, 0.5, and 0.8 L over the first 3 days of the hospital stay, respectively. Cultures of peripheral blood and urine grew no pathogens.

  1. How do you interpret the initial creatinine and urea results?
  2. How do you interpret the admission creatinine and urea results?
  3. How do you interpret the hemoglobin and hematocrit?
  4. How do you interpret the bilirubin, aminotransferase and alkaline phosphatase?
  5. How do you interpret the urinalysis results?
  6. What is a probable mechanism for these findings?
  7. What medication recommendations would you have for treating this patient?

Case 2

(Clin. Infect. Dis. 36(8):1082-1085, 2003)

A 49-year-old AIDS patient with multiple drug-resistant HIV gets tenofovir added to his drug regimen. His medical history was also notable for adrenal insufficiency, hypogonadism, anemia, peripheral neuropathy, asthma, and large B cell lymphoma of the thoracic spine. His serum creatinine level had ranged from 1.9 to 2.8 mg/dL, and it was 2.3 mg/dL just before he started receiving tenofovir. The patient had received enteric-coated didanosine formulation (400 mg/day) several months before tenofovir therapy was started.

The patient returned for a follow-up visit 2 weeks after he started the new regimen, at which time the creatinine level was 2.0 mg/dL, bicarbonate 21 mmol/L and albumin 3.0 g/dL. Due to lower extremity edema he was prescribed furosemide.

Six weeks after starting tenofovir the patient was brought to the emergency department with a 4-day history of progressive fatigue, weakness, confusion, oliguria, and myalgia. At admission to the emergency department, the patient was noted to be hypotensive (blood pressure, 90/50 mmHg), and laboratory studies included:

BUN 78 mg/dL, creatinine 7.6 mg/dL, arterial blood gas pH 6.93, bicarbonate of 5 mmol/L and lactate of 5.5 mmol/L (normal 0.5-2.2 mmol/L). No evidence of infection was found with blood culture.

  1. If the patient weighed 74.6 kg calculate his estimated GFR based on the creatinine of 2.3 mg/dL.
  2. Based on this creatinine are dose adjustments required for tenofovir?
  3. How do you interpret the lab values at the 2 week follow-up?
  4. How do you interpret the lab values at the 6 week follow-up?
  5. Calculate the patients estimated GFR at six weeks post therapy.
  6. Discuss the importance of knowing the renal status in patients dosed with tenofovir.
  7. What is this patient’s prognosis?

Case 3

An 87-year-old retired tailor appears in his physician’s office complaining of the slow onset of ankle and shin swelling, mild shortness of breath, and fatigue. Urinalysis performed in the office reveals marked proteinuria, and the patient is seen for further evaluation and work-up. The serum urea-N was 35 mg/dL, creatinine 3.8 mg/dL, sodium 136 mmol/L, potassium 5.6 mmol/L, chloride 104 mmol/L, and bicarbonate 20 mmol/L. Total serum protein was 4.3 g/dL with albumin 1.4 g/dL.

  1. Given a serum creatinine of 3.8 mg/dL, a urine creatinine concentration of 210 mg/dL and a 24 hour urine volume of 288 mL, calculate the creatinine clearance in this patient.
  2. Interpret the creatinine clearance you have obtained for this patient.
  3. What other blood/serum tests may be abnormal?
  4. What further studies should be performed on the urine of this patient? What type of casts may be present in urine?
  5. What is the differential diagnosis for this patient?
  6. Are the increased SUN and creatinine values typical for this disease?

Case 4

A 5-year-old girl develops swelling of her ankles and feet. Her anxious mother brings her daughter to the pediatrician. A urinalysis is performed revealing large amounts of protein. The girl is admitted in acutely ill condition to a local pediatric intensive care unit. Admission laboratory studies reveal: serum urea-N 15 mg/dL, creatinine 1.2 mg/dL, serum sodium 133 mmol/L, potassium 4.6 mmol/L, chloride 101 mmol/L, bicarbonate 23 mmol/L and calcium 7.4 mg/dL. Her serum cholesterol is found to be 350 mg/dL. The urine contained hyaline, granular, and fatty casts.

  1. What is the probable diagnosis for this patient?
  2. Describe the probable gross appearance of this patient’s serum.
  3. What would you expect the patient’s serum albumin to be (high, normal, or low)? Which other serum proteins are likely to be abnormal?
  4. Describe the mechanism for hyperlipidemia in this patient.
  5. Explain the low serum calcium (7.4 mg/dL) found in this patient.
  6. Describe the serum electrophoresis pattern.
  7. What type of urinary sediments would you expect?
Bibliography
1. Tietz Textbook of Clinical Chemistry, 3rd edition, 1999, p 1242

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