A 15 year-old boy from Mexico presents with chronic renal failure. A careful history obtained from his uncle indicates that he has not been treated with dialysis. Radiography of the hand and forearm demonstrates erosion of the terminal phalanges and marked metaphyseal resorption of the ulna and radius. Excessive secretion of which of the following hormones most likely contributed to these problems?

A. Aldosterone

B. Calcitonin

C. Parathyroid hormone

D. Renin

E. Vitamin D

Explanation:

The correct answer is C. In renal failure, the ability of the kidney to secrete phosphate is impaired. The resultant hyperphosphatemia causes hypocalcemia and triggers excretion of large amounts of parathyroid hormone. The released parathyroid hormone is a major contributor to bony changes (e.g., osteitis fibrosa, a form of localized bone resorption) seen in some patients with chronic renal failure.

Aldosterone (choice A) is a regulator of serum sodium.

Calcitonin (choice B) levels are usually low in chronic renal failure, unless the parathyroids have so hypertrophied as to cause "tertiary hyperparathyroidism" with hypercalcemia.

Renin (choice D) is normally secreted by the kidney and may be either decreased or increased in varying stages and forms of kidney disease. Regardless, renin regulates blood pressure and aldosterone secretion, rather than bone metabolism.

The active form of Vitamin D (choice E), cholecalciferol, is formed in the kidney from Vitamin D absorbed from the gut and then processed by the liver. Uremia interrupts this pathway and consequently causes a functional Vitamin D deficiency. A child has been experiencing intermittent, short episodes of hematuria beginning shortly after a transient gastrointestinal infection. Which of the following renal biopsy findings would best establish the diagnosis of Berger's disease?

A. Crescent formation

B. Foot process effacement

C. Mesangial IgA deposits

D. Subepithelial humps

E. Tram tracking

Explanation:

The correct answer is C. The characteristic finding of Berger's disease is IgA deposition in the glomerular mesangium, which may also contain C3, properdin, IgG, and IgM. The disease is thought to be due to trapping of large IgA-antigen complexes in the glomeruli, leading to activation of the alternative complement pathway. Renal failure in these cases may take decades to develop.

Glomerular crescent formation (choice A) is due to proliferation of epithelial cells and infiltration by monocyte-macrophages. Crescents are an ominous sign, suggesting rapidly progressive glomerulonephritis.

Podocyte foot process effacement (choice B), when seen as the only finding or the principal finding, suggests minimal change disease, which is the major cause of the nephrotic syndrome in children.

Subepithelial humps (choice D) by electron microscopy suggests poststreptococcal glomerulonephritis. Immunofluorescence for IgG, IgM, and C3 yields a granular pattern.

Tram tracking (choice E), referring to a thickening of the walls of glomerular capillaries, suggests membranoproliferative glomerulonephritis.

A pathologist examining electron micrographs of glomeruli sees prominent deposits between the podocytes and the basement membrane of the glomerular capillaries. These findings are most likely related to prior infection with which of the following genera?

A. Escherichia

B. Klebsiella

C. Neisseria

D. Pseudomonas

E. Streptococcus

Explanation:

The correct answer is E. The disease is post-infectious glomerulonephritis, which is usually related to prior sore throat or skin infection by Streptococcal species; Staphylococcus also causes some cases. The prominent deposits are also known as subepithelial humps, and consist of immunoglobulin and complement.

Gram-negative rods such as Escherichia(choice A), Klebsiella (choice B), and Pseudomonas (choice D) have not been implicated as significant causes of post-infectious glomerulonephritis.

The gram-negative cocci Neisseria(choice C) have not been implicated in post-infectious glomerulonephritis.

A 30-year-old woman has had type 1 diabetes mellitus for 15 years. She develops proteinuria and acute renal failure. Which of the following would a renal biopsy most likely show?

A. Fusion of podocyte foot processes in otherwise normal-appearing glomeruli

B. Hyperplastic arteriolosclerosis ("onion-skinning")

C. Linear IgG deposits along the basement membrane

D. Ovoid hyaline masses in the periphery of the glomerulus

E. Periodic acid-Schiff (PAS)-positive, electron-dense deposits distributed along the epithelial side of the capillary basement membrane

Explanation:

The correct answer is D. Nodular glomerulosclerosis (Kimmelstiel-Wilson disease), as described above, is the most distinctive glomerular lesion associated with diabetes mellitus. Other glomerular findings in diabetes include widespread capillary basement membrane thickening and diffuse glomerulosclerosis.

Minimal change disease, the most common cause of nephrotic syndrome in children, is characterized by the podocyte changes described in choice A.

Hyperplastic arteriolitis (choice B) is associated with hypertensive damage to the kidneys. Other features include fibrinoid necrosis and necrotizing glomerulitis.

Goodpasture syndrome is associated with linear deposits of IgG along the basement membrane (choice C).

Membranous glomerulonephritis is characterized by PAS-positive, electron-dense deposits distributed principally along the epithelial side of the capillary basement membrane (choice E).

A 41-year-old man presents to his physician complaining of swollen ankles. He states that he has never had this problem before. Physical examination demonstrates marked lower extremity edema and periorbital swelling. His pulse is strong, and regular. Urine dipstick is 4+ positive for protein, but negative for blood and glucose. 24-hour urine collection demonstrates proteinuria of 6 grams per day. Which of the following is the most likely cause of this patient's disorder?

A. Berger's disease

B. Diabetic nephropathy

C. Membranoproliferative glomerulonephritis

D. Membranous glomerulonephritis

E. Minimal change disease

Explanation:

The correct answer is D. The patient has nephrotic syndrome, as evidenced by the presence of edema and massive proteinuria. The most common cause of nephrotic syndrome in adults is membranous glomerulonephritis, which is characterized by diffuse capillary thickening with a granular pattern on immunofluorescence.

Berger's disease (choice A) is characterized by IgA deposition in the glomerular mesangium. It does not usually cause nephrotic syndrome.

Diabetic nephropathy (choice B) can cause nephrotic syndrome, but there would likely be glucose in the urine.

Membranoproliferative glomerulonephritis (choice C) is an uncommon cause of nephrotic syndrome.

Minimal change disease (choice E) is the most important cause of nephrotic syndrome in children.

In the 25th week of pregnancy, a G1P0 woman develops increased blood pressure (160/95) and proteinuria. Physical examination demonstrates generalized edema, and serum chemistries demonstrate hyperuricemia and increased concentrations of liver enzymes. Which of the following usually provides definitive therapy for this patient's medical condition

A. Anti-hypertensive medical therapy

B. Delivery

C. Low dose aspirin

D. Oxygen supplementation

E. Renal dialysis Explanation:

The correct answer is B. The woman has preeclampsia, the features of which include proteinuria and increased blood pressure. A wide variety of other features of preeclampsia can also be seen, including excessive weight gain, generalized edema, ascites, hyperuricemia, hypocalciuria, increased plasma concentration of von Willebrand factor and cellular fibronectin, reduced plasma concentration of anti-thrombin III, thrombocytopenia, increased hematocrit, increased liver enzymes, intrauterine growth retardation, and intrauterine hypoxia. Modern theories suggest that the true primary lesion may involve the endothelium, and that medical control of hypertension (choice A) actually only treats a small part of the syndrome. At present, the only definitive therapy is delivery of the baby, and obstetricians often play a delicate game trying to delay delivery for a premature baby's sake as long as possible while judging the severity of the preeclampsia and its immediate risks to mother and fetus.

Low dose aspirin (choice C) may have a modest effect in preventing pre-eclampsia, but this is not yet well established.

Oxygen supplementation (choice D) is used in some cases of cerebral hemorrhage secondary to preeclampsia,

but does not constitute definitive therapy.

Renal dialysis (choice E) is usually not necessary in preeclampsia, although both renal cortical necrosis and renal tubular necrosis can occasionally occur in this disorder.Renal biopsy demonstrates concentric, laminated thickening of arteriolar walls due to proliferation of smooth muscle cells. This process is best described by which of the following terms?

A. Atherosclerosis

B. Hyaline arteriolosclerosis

C. Hyperplastic arteriolosclerosis

D. Mönckeberg's arteriosclerosis

E. Polyarteritis nodosa

Explanation:

The correct answer is C. The "onion skinning" morphology of these arterioles is a feature of hyperplastic arteriolosclerosis. Affected vessels may also show necrotizing arteriolitis with acute vessel wall necrosis accompanied by fibrin deposition. This type of vessel change is a hallmark of severe (malignant) hypertension, and can damage arterioles throughout the body, notably in the kidneys, intestine, and gall bladder.

Atherosclerosis (choice A) would produce luminal narrowing by plaques.

Hyaline arteriolosclerosis (choice B) would produce partial replacement of arterial walls by homogeneous, pink material.

Mönckeberg's arteriosclerosis (choice D) is characterized by medial calcification of smaller arteries.

Polyarteritis nodosa (choice E) is characterized by focal acute inflammation of smaller arteries.

A 4 year-old child develops a large erythematous rash around the site of a mosquito bite. One month later, she is taken to a pediatrician because of a puffy face and swollen ankles. The scanty urine sample has a reddish-brown hue, and contains both red blood cells and protein. Which of the following distinctive features would be most likely to be seen on renal biopsy?

A. Fusion of podocyte foot processes

B. IgA in the mesangium

C. Linear IgG deposits

D. Onion-skinning of renal arterioles

E. Subepithelial electron dense humps

Explanation:

The correct answer is E. The disease is poststreptococcal glomerulonephritis, which can follow either streptococcal pharyngitis (one to two weeks after the infection) or skin infection (three to six weeks after the infection). The child is showing signs of both nephritis (hematuria) and nephrosis (puffy face and swollen ankles).The characteristic feature of this disease on renal biopsy is the presence of subepithelial humps, visible either by light or electron microscopy.

Fusion of podocyte foot processes (choice A) suggests minimal change disease.

IgA in the mesangium (choice B) suggests Berger's disease.

Linear IgG deposits (choice C) suggests anti-glomerular basement membrane disease, which is called Goodpasture's disease if it is accompanied by pulmonary damage.

Onion-skinning of renal arterioles (choice D) suggests malignant hypertension.

A 4-year-old girl is brought to the clinic by concerned parents. Physical examination is remarkable for extremity edema. Urinalysis shows significant proteinuria, but no red cells or casts. Electron microscopy performed on a kidney biopsy would be most likely to show which of the following findings?

A. Dense deposits

B. Fusion of epithelial foot processes

C. Mesangial deposits

D. Subendothelial deposits

E. Subepithelial spikes

Explanation:

The correct answer is B. The most frequent cause of nephrotic syndrome in children is minimal change disease (lipoid nephrosis), which is characterized by an absence of findings by light microscopy, and fusion of epithelial foot processes by electron microscopy.

Dense deposits (choice A) are seen in type II membranoproliferative glomerulonephritis.

Mesangial deposits (choice C) are a prominent feature of IgA nephropathy and are seen to a lesser degree in several other glomerulonephritides.

Subendothelial deposits (choice D) are seen in type I membranoproliferative glomerulonephritis.

Subepithelial spikes (choice E ) are a feature of membranous glomerulonephritis.

A 65-year-old man develops oliguria and peripheral edema over a period of weeks. Urinalysis reveals hematuria and proteinuria; examination of the urinary sediment reveals red cell casts. Radiologic and ultrasound studies fail to demonstrate an obstructive lesion. Renal biopsy shows many glomerular crescents. This presentation is most suggestive of which of the following conditions?

A. Anti-glomerular basement membrane disease

B. Diabetic nephropathy

C. Hypertensive nephropathy

D. Lupus nephritis

E. Minimal change disease

Explanation:

The correct answer is A. The two principal causes of rapidly progressive glomerulonephritis are anti-glomerular basement membrane (including both Goodpasture's syndrome and isolated anti-glomerular basement disease) and primary systemic vasculitis (including Wegener's granulomatosis, microscopic polyarteritis, idiopathic rapidly progressive glomerulonephritis, Churg-Strauss syndrome, polyarteritis nodosa, giant-cell arteritis, and Takayasu's arteritis). A very large variety of other systemic and primary glomerular disease may occasionally cause rapidly progressive glomerulonephritis, but this is usually not the typical presentation for these diseases.

Diabetic nephropathy (choice B) typically begins with microalbuminuria and hypertension and progresses over a 10 to 20 year period to renal failure.

Hypertensive nephropathy (choice C) due to essential hypertension typically presents with slowly rising BUN and creatinine; hypertensive nephropathy due to malignant hypertension presents with more rapidly rising BUN and creatinine.

Lupus nephritis (choice D) can have many presentations, but the most typical is proteinuria, which may be

severe enough to cause nephrotic syndrome. Also, 90% of cases of systemic lupus erythematosus occur in women, usually of child-bearing age.

Minimal change disease (choice E) typically presents with nephrotic syndrome and is not consistently associated with recognizable glomerular changes by light microscopy. Podocyte foot-process fusion can be seen by electron microscopy.

A 10-year-old boy is in a fire and sustains burns over 25% of his body. The next day, his serum urea nitrogen (BUN) is 30 mg/dL and his serum creatinine is 0.8 mg/dL. He receives intravenous fluids throughout his course and never has a significant drop in blood pressure or urine output. Which of the following most likely accounts for his BUN and creatinine values?

A. Decreased renal perfusion

B. Distal urinary tract obstruction

C. Increased synthesis of urea

D. Renal glomerular disease

E. Renal tubule interstitial disease

Explanation:

The correct answer is C. This patient has elevated BUN and normal serum creatinine. Raised BUN with normal creatinine can be seen in prerenal causes of azotemia, which can be subclassified into those due to decreased perfusion of the kidney and those due to increased synthesis of urea. In this case, the boy's blood pressure and urine output were maintained, so inadequate renal perfusion is unlikely. The burns themselves can cause significant urea production, since urea is the major nitrogen-containing end product of protein catabolism, which increases markedly in burn victims.

Decreased renal perfusion (choice A) also produces increased BUN with normal serum creatinine, but you would expect to see urine output decrease as a consequence of the inadequate perfusion.

Distal urinary tract obstruction (choice B), due to processes such as stones, cancer, or benign prostatic hyperplasia, causes both BUN and serum creatinine to rise, but the rise in serum urea is proportionally higher than that of serum creatinine.

In renal glomerular disease (choice D) of sufficient severity to cause acute or chronic renal failure, creatinine and urea usually rise in parallel.

In renal tubulointerstitial disease (choice E), notably in acute tubular necrosis, creatinine may rise disproportionately to urea.

A renal pathologist examining the day's kidney biopsies notes that one biopsy shows amorphous red nodules within the glomerular mesangium in hematoxylin and eosin stained material. Congo red stain of the biopsy demonstrates apple-green birefringence of these nodules. These nodules are most likely to be related to which of the following?

A. Acute urinary tract infection

B. Diabetes mellitus

C. Sarcoidosis

D. Systemic lupus erythematosus

E. Tuberculosis

Explanation:

The correct answer is E. Glomerular nodules may be either the Kimmelstiel-Wilson nodules of diabetes mellitus

or may be composed of amyloid. An amyloid origin can be confirmed by staining with Congo red, which causes the nodules to stain red with ordinary light but exhibit a distinctive "apple-green" birefringence when viewed with polarized light. The most common type of amyloid (type AA) is due to deposition of altered immunoglobulin light chains and is seen in diseases with chronic antigenic stimulation, such as tuberculosis.

Acute urinary tract infection (choice A) is an infection of too short a duration to cause amyloidosis.

Diabetic mellitus (choice B) is associated with glomerular nodules called Kimmelstiel-Wilson nodules, but these will not show apple-green birefringence when viewed with polarized light.

Sarcoidosis (choice C) typically involves the lymph nodes, lungs, spleen, and to a lesser extent, the skin and eye. It is unrelated to amyloidosis.

Systemic lupus erythematosus (choice D) can produce a wide range of renal lesions, but amyloid nodules are not among the likely manifestations.

At autopsy, a patient who had died with acute anuria and uremia is found to have ischemic necrosis of the cortex of both kidneys with relative sparing of the medulla. These pathological findings are most likely related to which of the following underlying conditions?

A. Disseminated intravascular coagulation

B. Multiple myeloma

C. Polycystic kidney disease

D. Pyelonephritis

E. Sickle cell anemia

Explanation:

The correct answer is A. Diffuse cortical necrosis, as described in this patient, is usually seen in the setting of disseminated intravascular coagulation, typically in the context of overwhelming sepsis. It can also be seen following hypotension combined with vasoconstriction.

Multiple myeloma (choice B) is associated with renal deposition of amyloid protein and damage to both glomeruli and tubules.

Adult polycystic kidney disease (choice C) would produce enlarged kidneys filled with cystic masses.

Pyelonephritis (choice D) would produce inflammation, often most severe in the renal pelvis.

Sickle cell anemia (choice E) usually affects the medulla most severely, and can cause papillary necrosis.

A renal biopsy is performed during a workup for renal insufficiency in a patient with a slightly reduced renal size. The biopsy incidentally samples one of the arcuate arteries, which shows reduplication of the elastic lamina and fibrosis of the media. These findings are most likely associated with which of the following?

A. Amyloidosis

B. Escherichia coli enterotoxin

C. Hypertension

D. Lipoid nephrosis

E. Sickle cell disease

Explanation:

The correct answer is C. The lesion described is called fibroelastic hyperplasia, and it can affect the media of larger interlobular and arcuate arteries. These changes are related to benign nephrosclerosis, usually in hypertensive patients. Other changes seen in benign nephrosclerosis include hyaline arteriolosclerosis and sometimes patchy ischemic atrophy.

Amyloidosis (choice A) can cause deposition of amyloid material (homogeneous eosinophilic extracellular deposits) around small blood vessels.

Escherichia coli enterotoxin (choice B) has been implicated in childhood hemolytic uremic syndrome with microangiopathic hemolytic anemia related to vascular intimal hyperplasia, fibrinoid necrosis, and thrombi.

Lipoid nephrosis (minimal change disease, choice D) has a normal or abnormal appearance by light microscopy.

Sickle cell disease (choice E) can cause focal occlusions of the vasa recta (the hypertonic, hypoxic milieu of the renal medulla favors sickling), leading to patchy papillary necrosis, proteinuria, and sometimes cortical scarring.

A patient comes to medical attention because of a kidney stone. During the clinical evaluation, the patient reveals that he has had a history of stomach ulcers. Which of the following diagnoses should the physician consider?

A. Horner syndrome

B. Shy-Drager syndrome

C. Sipple syndrome

D. Turcot syndrome

E. Wermer syndrome

Explanation:

The correct answer is E. This patient may have Wermer syndrome (multiple endocrine neoplasia type I; MEN type I). In this disorder: 1) parathyroid hyperplasia or adenomas can cause hypercalcemia and kidney stones; 2) pancreatic neoplasms may secrete any of the islet hormones or may secrete gastrin, producing Zollinger-Ellison syndrome with multiple peptic ulcers; and 3) pituitary adenomas may occur rarely.

Horner's syndrome (choice A) is characterized by ptosis, miosis, and in many cases, hemianhidrosis. It is usually related to involvement of the cervical sympathetic plexus by tumor (usually lung cancer).

In Shy-Drager syndrome (choice B), there is autonomic nervous system failure, leading to orthostatic hypotension and parkinsonism.

Sipple syndrome (choice C) is MEN type II, characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid disease.

document.doc In the very rare Turcot syndrome (choice D), adenomas of the digestive tract and central nervous system gliomas (astrocytoma and medulloblastoma) occur.

Physical examination of a two-year-old child reveals a large abdominal mass. CT studies show that the mass arises in the kidney. Which of the following is most likely a distinctive feature of this lesion?

A. Abundant clear cells

B. Embryonic glomerular structures

C. Eosinophilic cells packed with mitochondria

D. Hamartomatous blood vessels

E. Necrotic bacterial forms in macrophages

Explanation:

The correct answer is B. A two-year-old with a tumor of the kidney most likely has Wilms tumor. This aggressive lesion (now with a 90% survival rate thanks to modern management) is microscopically interesting because it contains embryonic glomerular and tubular structures embedded in a spindle cell stroma which may also contain smooth muscle, striated muscle, bone, cartilage, fat, and fibrous tissue.

Abundant clear cells (choice A) are a feature of renal cell carcinoma.

Eosinophilic cells packed with mitochondria (choice C) suggests oncocytoma.

Hamartomatous blood vessels (choice D) suggest angiomyolipoma.

Necrotic bacterial forms in macrophages (choice E) suggest malakoplakia, which can cause mass lesions in the kidney without being a true tumor.

A concerned couple bring in a 2-year-old boy with gonadal dysgenesis to a clinic for a follow-up visit. The physician notices a large abdominal mass during his physical examination. Which of the following disorders does the patient most likely have?

A. Renal cell carcinoma

B. Renal hamartoma

C. Squamous cell carcinoma of the bladder

D. Transitional cell carcinoma of the bladder

E. Wilms' tumor

Explanation:

The correct answer is E. The only childhood malignancy listed is Wilms' tumor, which commonly presents in a toddler as a large abdominal mass. There is now a 90% survival rate for this tumor with combined therapy with surgery, chemotherapy, and radiotherapy.

Renal cell carcinoma (choice A), squamous cell carcinoma of the bladder (choice C), and transitional cell carcinoma of the bladder (choice D) are malignant tumors of adults.

Renal hamartoma (fibroma; choice B) causes a small, gray, benign module in the renal pyramids and is usually only identified as an incidental finding at autopsy.

An 8-year-old male with oliguria is sent by his pediatrician to the radiologist for a renal ultrasound. The ultrasound shows large, smooth kidneys with radial fusiform cysts in the cortex and medulla. Neither parent has a history of renal disease, but the father recalls a family history of "kidney problems." Which of the following is the correct diagnosis?

A. Glomerulocystic disease

B. Infantile polycystic disease

C. Medullary cystic disease

D. Segmental dysgenesis

E. Uremic medullary cystic disease

Explanation:

The correct answer is B. A disorder occurring in offspring of unaffected parents (in the context of a family history of the disease) suggests autosomal recessive inheritance. Infantile polycystic disease is the only disease listed in the choices with autosomal recessive inheritance. This disease affects both infants and

children and is usually bilateral. The cysts are fluid-filled and lined by cuboidal epithelium. It is thought to result from failure of communication between the nephron and pericaliceal system during development, leading to renal failure.

Glomerulocystic disease (choice A) is a rare disease without a recognized hereditary component that causes cortical cysts of the kidneys bilaterally, eventually producing renal failure. Grossly, the kidneys are enlarged with 1- to 8-mm cortical cysts that develop from dilated Bowman's spaces in the glomeruli. Newborns, infants, and children are affected.

Medullary cystic disease (choice C), or medullary sponge kidney, can affect all ages, but typically affects adults. It is not thought to be inherited and the cause is not known. The cysts are located at the tips of the papillae. It is usually asymptomatic, but can lead to defective sodium reabsorption in the tubule.

Segmental dysgenesis (choice D) is not inherited and affects all ages. The kidneys show irregular cysts with scarring. Symptoms depend upon the severity of disease. Patients may be asymptomatic if one kidney is spared.

Uremic medullary cystic disease (choice E) is a rare disease of children and young adults that causes multiple cysts of the medulla. There is also cortical tubular atrophy and intestinal fibrosis. Pathogenesis is unknown. Chronic renal failure occurs and mortality is high.

A 30-year-old woman undergoes her yearly gynecologic examination and is found to have microscopic hematuria. The hematuria is again documented on several more occasions when she is seen for other reasons. Because no etiology is obvious, renal biopsy is eventually performed; a photomicrograph of a hematoxylin and eosin-stained section is shown above. Immunofluorescent staining of histologic sections similar to the one shown demonstrates IgG, IgM, and complement in the glomerular mesangium. Which of the following is the most likely diagnosis?

A. Amyloidosis

B. Goodpasture syndrome

C. Henoch-Schönlein purpura

D. Lipoid nephrosis

E. Systemic lupus erythematosus

Explanation:

The correct answer is E. Systemic lupus erythematosus can produce a wide range of different glomerular lesions; in some cases, the presenting symptoms may be associated with renal disease. The pattern illustrated in the photomicrograph is mesangial expansion with cellular proliferation and occurs in approximately 25% of lupus patients. Granular mesangial deposits of immunoglobulin and complement are characteristically present and probably reflect the immune complex basis of the problem.

Amyloidosis (choice A) is not usually associated with immune complex deposition.

Goodpasture syndrome (choice B) is characterized by linear IgG deposition along basement membranes.

Henoch-Schönlein purpura (choice C) characteristically shows IgA deposits.

The glomeruli in lipoid nephrosis (choice D), also known as minimal change disease, appear normal or very nearly normal.

A 55-year-old man with a history of recurrent calcium-containing renal stones presents to the emergency room with excruciating flank pain and blood in the urine. This patient is likely to have which of the following underlying disorders?

A. Anemia of chronic disease

B. Chronic Proteus infection

C. Factor VIII deficiency

D. Hyperaldosteronism

E. Hyperparathyroidism

Explanation:

The correct answer is E. This patient is experiencing the very painful passage of a renal stone, which is often accompanied by hematuria. His history of recurrent urolithiasis with calcium-containing stones implies a disorder in the regulation of calcium concentration. Hyperparathyroidism is associated with increased parathormone (PTH) levels, which can produce hypercalcemia, hypercalciuria, and, ultimately, renal stones.

Anemia of chronic disease (choice A) does not produce calcium stones. It is an attractive distracter because the patient presents with a chronic condition and hematuria. Note that urinary blood loss is not usually significant enough to produce an anemic state.

Chronic Proteus infection (choice B) would produce struvite (magnesium-ammonium phosphate), not calcium stones. Staghorn calculi are also seen.

Factor VIII deficiency (choice C) occurs in hemophilia, a hereditary clotting disorder. It is not associated with calcium stones.

Hyperaldosteronism (choice D) results in potassium depletion, sodium retention, and hypertension. Primary hyperaldosteronism (Conn's syndrome) is associated with adrenocortical adenomas in 90% of patients and is characterized by decreased renin. Secondary hyperaldosteronism results from excessive stimulation by angiotensin II that is caused by excess renin production (plasma renin-angiotensin levels are high). Neither condition is associated with renal stones.

A pediatrician discovers a large mass in the abdomen of a 3-year-old child. Ultrasound examination demonstrates that the mass appears to arise from the right kidney. Which of the following tumors is most likely present?

A. Cortical adenoma

B. Hemangioma

C. Nephroblastoma

D. Oncocytoma

E. Renal cell carcinoma

Explanation:

The correct answer is C. Nephroblastoma (Wilms tumor) characteristically affects children between 2 and 4 years of age and can form large spherical masses composed of variegated tissues including primitive renal epithelial elements, a sarcomatous-appearing stroma, abortive glomeruli and tubules, and heterologous tissues such as muscle, cartilage, fat, and bone.

Cortical adenoma (choice A) is a small (under 2 cm) benign tumor that is usually found incidentally at autopsy.

Hemangiomas (choice B) can occur in the kidney, but would not usually produce a large mass.

Oncocytomas (choice D) are benign tumors that can be large but do not usually affect young children.

Renal cell carcinoma (choice E) is usually a disease of older adults.

During a routine physical examination, a 45-year-old woman is noted to have a ruddy complexion. Her hematocrit is 52%. Her lungs are clear and she does not smoke. Serum erythropoietin levels are elevated. Cancer of which of the following organs is the most likely cause of her increased hematocrit?

A. Breast

B. Colon

C. Kidney

D. Stomach

E. Thyroid

Explanation:

The correct answer is C. The kidney normally produces erythropoietin, which stimulates the erythroid cell line in the bone marrow. Renal cell carcinoma can lead to overproduction of erythropoietin and thereby cause secondary polycythemia. Other causes of secondary polycythemia are diseases that impair oxygenation, including pulmonary diseases (including smoking) and congestive heart failure.

Breast cancer (choice A) can present as an axillary mass or as Paget's disease of the nipple.

Colon cancer (choice B) and stomach cancer (choice D) can present with anemia secondary to blood loss.

Thyroid cancer (choice E) can present with hypothyroidism.

A 42-year-old paraplegic woman has a neurogenic bladder and requires an indwelling urinary catheter. She develops a urinary tract infection and is seen by a urologist, who orders abdominal x-rays and an intravenous pyelogram. The radiographic studies demonstrate a very large stone that fills and follows the contours of the renal pelvis. The stone is most likely composed of which of the following?

A. Calcium salts

B. Cholesterol

C. Cystine

D. Magnesium ammonium phosphate

E. Uric acid

Explanation:

The correct answer is D. Staghorn calculi, such as described in the question, are associated with infection by urea-splitting bacteria (notably Proteus species) and are composed of magnesium ammonium phosphate (struvite). They are more common in women than men, and are far more common in patients requiring chronic bladder catheterization.

Calcium-containing stones (choice A) are typically seen in patients with hypercalcinuria without hypercalcemia; one-fifth of patients with this type of stone have hyperuricosuria.

Cholesterol (choice B) is found in gall stones, not kidney stones.

Cystine stones (choice C) are rare; they may be seen in patients with cystinuria, an autosomal recessive disorder of amino acid metabolism.

Uric acid stones (choice E) are seen in gout, leukemia, and in patients with acidic urine.

A 35-year-old man develops oliguria, peripheral edema, and shortness of breath over a two week period. Serum chemistries show markedly elevated BUN and creatinine. Renal biopsy shows many glomerular crescents, and fluorescent antibody studies demonstrate linear deposits of IgG along the glomerular basement membrane. This patient is also at increased risk for developing

A. bladder carcinoma

B. meningioma

C. pulmonary hemorrhage

D. rheumatoid arthritis

E. testicular carcinoma

Explanation:

The correct answer is C. The clinical scenario is that of rapidly progressive glomerulonephritis. Linear deposits of IgG along the basement membrane make the diagnosis of anti-glomerular basement membrane disease, which may either occur as an isolated finding or as part of Goodpasture's syndrome, which also features prominent pulmonary hemorrhage as a result of antibody attack on the alveolar capillary basement membrane. Formerly, the prognosis of patients with these conditions was dismal (most dying within 6 months of either renal failure or pulmonary hemorrhage), but the patients can now often be successfully treated with aggressive management including plasma exchange, renal dialysis, and high-dose immunosuppression.

Predisposing factors for bladder carcinoma (choice A) include industrial chemical exposure, cigarette smoking, and infection with Schistosoma haematobium. There is no link between bladder carcinoma and glomerulonephritis.

Predisposing factors for meningiomas (choice B) include von Recklinghausen's neurofibromatosis and probably small, inconsequential trauma to the meninges. There is no link between meningiomas and glomerulonephritis.

Glomerulonephritis was previously considered to be almost nonexistent in rheumatoid arthritis (choice D); it is now acknowledged that rheumatoid arthritis may occasionally be associated with mesangial proliferation, membranous nephropathy, and rarely, rapidly progressive glomerulonephritis.

Testicular carcinoma (choice E) is unrelated to glomerulonephritis. Predisposing factors for testicular carcinoma include a failure of testicular descent.

A 35-year-old woman has had type 1 diabetes mellitus for 20 years. She is now developing advanced disease with visual complaints, foot ulcers, and renal disease. Which of the following features that might be seen on renal biopsy is most specific for diabetic glomerulosclerosis?

A. Mesangial IgA deposits

B. Necrotic epithelial cells in tubules

C. Nests of cells with abundant clear cytoplasm

D. Numerous neutrophils in tubules

E. Ovoid, periodic acid-Schiff (PAS)-positive, hyaline masses

Explanation:

The correct answer is E. The most specific lesion of diabetic glomerulosclerosis for the purposes of the USMLE is the Kimmelstiel-Wilson nodule. These are ovoid, hyaline, PAS-positive structures found in the mesangial core at the edge of the glomerulus. Although this lesion is the most distinctive (pathognomonic) for diabetes, it is not seen in all renal biopsies from diabetic patients. Other changes that may be present include glomerular capillary basement membrane thickening, diffuse glomerulosclerosis, hyaline thickening of arteriolar walls, tubular atrophy, interstitial fibrosis, and PAS-positive capsular drops in the parietal layer of Bowman capsule.

Mesangial IgA deposits (choice A) are a feature of Berger disease (IgA nephropathy).

Necrotic epithelial cells in tubules (choice B) are a feature of acute tubular necrosis.

Nests of cells with abundant clear cytoplasm (choice C) are a feature of renal cell carcinoma.

Numerous neutrophils in tubules (choice D) are a feature of acute pyelonephritis.

A 3-year-old child develops headaches and is brought to the family doctor. Funduscopic examination reveals papilledema; one retina also shows a very vascular tumor. CT of the head demonstrates a cystic tumor of the cerebellum. This child has a high likelihood of later developing which of the following?

A. Berry aneurysm of the basilar system

B. Bilateral renal cell carcinoma

C. Cancer of a peripheral nerve

D. Choreiform movements related to decreased GABA and acetylcholine

E. Serum cholesterol of greater than 700 mg/dL

Explanation:

The correct answer is B. The disease is von Hippel-Landau disease, which is associated with a deletion involving the VHL gene on chromosome 3 (3p). Affected individuals develop vascular tumors (hemangioblastomas) of the retina, cerebellum, and/or medulla. Roughly half of the affected individuals later develop multiple, bilateral renal cell carcinomas.

Berry aneurysms (choice A) are unrelated to hemangioblastomas, but are instead associated with adult polycystic disease.

Peripheral nerve cancers (choice C) are a feature of von Recklinghausen's disease (neurofibromatosis type I).

Choreiform movements, related to decreased GABA and acetylcholine (choice D), are a feature of Huntington's disease.

Extremely high serum cholesterol (choice E) suggests the homozygous form of familial hypercholesterolemia.

A 2-year-old child with leukemia develops nephrotic syndrome. Light microscopic studies are normal. Electron microscopic studies demonstrate fusion of epithelial foot processes. The current hypothesis for the pathogenesis of this change is that it is secondary to which of the following?

A. Consumption of complement factors

B. IgG directed against basement membrane

C. Immune complex deposition

D. Lymphokine production by T cells

E. Mesangial IgA deposition

Explanation:

The correct answer is D. The child is suffering from minimal change or nil disease (lipoid nephrosis), which has a peak incidence at 2-3 years of age. Minimal change disease can be associated with food allergies, medications, or hematologic malignancies, or it can occur idiopathically. The pathology does not appear to involve complement, immunoglobulins, or immune complex deposition. Rather, an altered cell-mediated immunologic response with abnormal secretion of lymphokines by T cells is thought to reduce the production of anions in the glomerular basement membrane, thereby increasing the glomerular permeability to plasma albumin through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to favor foot process fusion. Some authors have noted that other conditions associated with T-cell abnormalities, such as Hodgkin's disease and T-cell lymphoma, are sometimes associated with minimal change disease.

Consumption of complement factors (choice A) is observed in many conditions in which complement activation occurs, for example, membranoproliferative glomerulonephritis.

IgG directed against renal and pulmonary basement membranes (choice B) is found in Goodpasture's syndrome, a cause of rapidly progressive glomerulonephritis and hemoptysis.

Immune complex deposition (choice C) is associated with type III hypersensitivity reactions, including postinfectious glomerulonephritis, lupus nephritis, Henoch-Schönlein purpura, cryoglobulinemia, and bacterial endocarditis.

Mesangial IgA deposition (choice E) is associated with Berger's disease, or IgA nephropathy, a cause of glomerulonephritis.

A patient who is being treated for leukemia develops unilateral flank pain. Radiologic studies demonstrate a

dilated renal pelvis and dilation of the upper one-third of the corresponding ureter. A stone with which of the following compositions is most likely causing this patient's problems?

A. Calcium salts

B. Cholesterol

C. Cystine

D. Struvite

E. Uric acid

Explanation:

The correct answer is E. Patients prone to develop uric acid stones include those with gout, leukemia (particularly during chemotherapy, which releases large amounts of nucleic acids from dying leukemia cells), and acidic urine.

Calcium-containing stones (choice A) are the most common kind in the general population.

Cholesterol stones (choice B) are found in the gall bladder.

Cystine stones (choice C) are a rare form of renal stone seen in patients with cystinuria.

Struvite (magnesium-ammonium phosphate) stones (choice D) are known for producing massive staghorn stones that fill the renal pelvis.

A 46-year-old female with rheumatoid arthritis develops progressively worsening renal failure. She undergoes diagnostic renal biopsy, revealing thickening of the mesangial matrix and widened capillary basement membranes due to deposition of an amorphous, eosinophilic material that stains with Congo red. The material is shown to be composed of AA (amyloid-associated) protein fibrils. In which of the following locations is this protein synthesized?

A. Bone marrow

B. Brain

C. Liver

D. Synovium

E. Thyroid

Explanation:

The correct answer is C. AA protein represents an enzymatically degraded form of SAA (serum amyloid-associated) protein, which is synthesized in the liver. SAA is produced in response to cytokines that are released in a number of inflammatory conditions, including chronic infections, connective tissue disorders, and inflammatory bowel disease. It is not known why only a minority of people with these conditions develop amyloidosis.

Bone marrow (choice A) and lymph nodes are the source of the AL (amyloid light chain) proteins, which cause amyloidosis in plasma cell and B-cell proliferations (e.g., multiple myeloma). This is the most common form of amyloidosis in the U.S. today.

Beta 2-amyloid protein (Aβ2) is found in the brain (choice B) and forms the core of the plaques in Alzheimer's disease.

The synovium (choice D) may be the site of chronic inflammation and pannus formation in rheumatoid arthritis, but amyloid is not synthesized here.

In medullary carcinoma, excess calcitonin production leads to heavy amyloid deposition within the thyroid gland (choice E), but this amyloid is not derived from AA protein.

A 34-year-old man develops pulmonary hemorrhage and glomerulonephritis. Lung biopsy withimmunofluorescence demonstrates IgG deposition along the basement membrane. These antibodies are most likely directed against which of the following types of collagen?

A. Type I

B. Type II

C. Type III

D. Type IV

E. Type XExplanation:The correct answer is D. The disease described is Goodpasture's syndrome, in which autoantibodies tobasement membrane proteins cause damage to the lungs and kidneys. Pulmonary hemorrhage (especially in smokers) and rapidly progressive glomerulonephritis are common. The characteristic autoantibody present is directed against Type IV collagen, a component of the basement membrane.Type I collagen (choice A) is found in bone, skin, tendon, dentin, fascia, and late wound repair.Type II collagen (choice B) is found in cartilage (including hyaline cartilage), the vitreous body of the eye, and the nucleus pulposus of the intervertebral disk. Type III collagen (choice C) is found in skin, blood vessels, uterus, fetal tissue, and granulation tissue.Type X collagen (choice E) is found in epiphyseal plates.

A 42-year-old woman is noted to have mildly elevated creatinine and blood urea nitrogen on routine physicalexam. She recalls that her father also had kidney trouble and died in kidney failure. Workup reveals persistentazotemia and microscopic hematuria without evidence of urinary tract infection. An ultrasound of the kidneysidentifies bilaterally enlarged and multicystic kidneys. In addition to chronic renal failure, the clinician should alsobe concerned about her risk of

A. liver failure

B. pancreatic insufficiency

C. portal hypertension

D. renal cell carcinoma

E. subarachnoid hemorrhage

Explanation:

The correct answer is E. Multicystic kidneys, slowly progressive renal failure, and a positive family history arecharacteristics of autosomal dominant (adult) polycystic kidney disease (APKD). This disease typically presentsin the 40s to 60s and is characterized by marked renal enlargement due to numerous fluid-filled cysts, whichdevelop between the normally functioning nephrons. APKD is highly associated with hepatic cysts, and berryaneurysms in the circle of Willis that may rupture, producing spontaneous subarachnoid hemorrhage.Infrequently, APKD also produces cysts in the pancreas, spleen, or lungs, but these are not clinically relevant.

Hepatic cysts in adult polycystic disease do not ordinarily produce symptoms of hepatic failure (choice A).

Pancreatic cyst formation in APKD is not generally associated with pancreatic insufficiency (choice B).

Children with autosomal recessive polycystic kidney disease may develop congenital hepatic fibrosis withhypertension and splenomegaly, but this is not part of APKD (choice C).

APKD is not considered a risk factor for renal cell carcinoma or any other type of cancer (choice D).

A 3-year-old child develops severe generalized edema following a viral infection. On the basis of clinicalchemistry tests, a renal biopsy is performed, with normal light microscopic findings. Which of the followingabnormal laboratory values might be expected in this individual?

A. Decreased alpha globulin levels

B. Decreased fibrinogen

C. Increased serum calcium levels

D. Low serum albumin levels

E. Red blood cell casts in the urine

Explanation:

The correct answer is D. This child has minimal change disease, which is the major cause (over 90% of cases)of nephrotic syndrome in children aged 2 to 6 years. The most prominent clinical chemistry finding in thesepatients is massive proteinuria. The urinary protein in minimal change disease, in contrast to other causes ofnephrotic syndrome, is often composed predominantly of albumin. Many other clinical chemistry changes mayalso be seen, including decreased serum albumin levels, hyperlipidemia, increased serum levels of alpha2- andbeta-globulins, decreased IgG, and increased fibrinogen. Minimal change disease characteristically showsnormal or near normal appearance of the glomeruli by light microscopy and extensive fusion of foot processesof the glomerular podocytes by electron microscopy. A point not always recognized by beginners is that thepodocyte alterations may represent a reaction to, rather than a cause of, the proteinuria (e.g., an attempt to"seal the holes" in the glomerulus), since varying degrees of foot process fusion (together with more specificfeatures) may sometimes be seen in other glomerular diseases associated with the nephrotic syndrome.

Alpha-globulin levels (choice A) would be increased, rather than decreased, in minimal change disease.

Fibrinogen levels are increased, rather than decreased (choice B).

Serum calcium levels (choice C) are typically decreased in the nephrotic syndrome, possibly due to renal lossof vitamin D binding protein.

Red blood cell casts in the urine (choice E) are indicative of glomerulonephritis, rather than the nephroticsyndrome.

Following a respiratory infection, a 20-year-old man goes to his physician for a follow-up visit. Physicalexamination is unremarkable, but dipstick analysis of his urine reveals marked proteinuria and microscopic hematuria. The young man is referred to a specialist, who performs a renal biopsy. Immunofluorescencebmicroscopy of the biopsy tissue demonstrates IgA deposition in the glomerular mesangium. These results are most consistent with which of the following disorders?

A. Berger's disease

B. Goodpasture's syndrome

C. Minimal change disease

D. Poststreptococcal glomerulonephritis

E. Systemic lupus erythematosus

Explanation:

The correct answer is A. Berger's disease, or Ig A nephropathy, may develop after a respiratory infection. It is amajor cause of recurrent microscopic hematuria, and may progress to renal failure in a number of cases. (Note:don't confuse Berger's disease with Buerger's disease-a vasculitis that occurs in smokers.)

Questions about Goodpasture's syndrome (choice B) often contain a clue about linear deposition of IgGanti-basement membrane antibodies.

You should associate fusion of podocyte foot processes with minimal change disease (choice C).

Classic poststreptococcal glomerulonephritis (choice D) may follow pharyngitis caused by group Astreptococcus. This type of glomerulonephritis is associated with granular immunofluorescence and

subepithelial humps by electron microscopy.

Renal involvement in lupus (choice E) can have many manifestations, but there will usually be evidence of asystemic inflammatory disease.

An abdominal x-ray performed on a 54-year-old man demonstrates a large, irregular, calcified mass with multiplebroad projections filling one renal pelvis. Which of the following laboratory findings might be expected in thispatient?

A. Decreased urine pH

B. Hypercalcemia

C. Hyperuricemia

D. Increased ammonia concentration in the urine

E. Increased cystine concentration in the urine

Explanation:

The correct answer is D. The patient has a stag-horn calculus. These very large calculi are almost alwayscomposed principally of magnesium ammonium phosphate (often with enough calcium to be radio-opaque) andform in the setting of infection by urea-splitting bacteria such as Proteus.

Increased urine ammonia concentrations are a byproduct of the bacterial metabolism of urea, and tend toincrease urine pH (compare with choice A).

Hypercalciuria, with or without hypercalcemia (choice B), is a cause of calcium oxalate stones.

Uric acid stones can be seen in patients with hyperuricemia (choice C) secondary to gout, or in conditions inwhich a very rapid cell turnover occurs (e.g., leukemias).

Genetically determined defects in the renal transport of amino acids are associated with cystine stones (choiceE).

During a routine physical examination, a 45-year-old woman is noted to have a ruddy complexion. Her hematocrit is 52%. Her lungs are clear and she does not smoke. Serum erythropoietin levels are elevated. Cancer of which of the following organs is the most likely cause of her increased hematocrit?

A. Breast

B. Colon

C. Kidney

D. Stomach

E. Thyroid

Explanation:

The correct answer is C. The kidney normally produces erythropoietin, which stimulates the erythroid cell line in the bone marrow. Renal cell carcinoma can lead to overproduction of erythropoietin and thereby cause secondary polycythemia. Other causes of secondary polycythemia are diseases that impair oxygenation, including pulmonary diseases (including smoking) and congestive heart failure.

Breast cancer (choice A) can present as an axillary mass or as Paget's disease of the nipple.

Colon cancer (choice B) and stomach cancer (choice D) can present with anemia secondary to blood loss.

Thyroid cancer (choice E) can present with hypothyroidism.

A pathologist examining electron micrographs of glomeruli sees prominent deposits between the podocytes and the basement membrane of the glomerular capillaries. These findings are most likely related to prior infection with which of the following genera?

A. Escherichia

B. Klebsiella

C. Neisseria

D. Pseudomonas

E. Streptococcus

Explanation:

The correct answer is E. The disease is post-infectious glomerulonephritis, which is usually related to prior sore throat or skin infection by Streptococcal species; Staphylococcus also causes some cases. The prominent deposits are also known as subepithelial humps, and consist of immunoglobulin and complement.

Gram-negative rods such as Escherichia(choice A), Klebsiella (choice B), and Pseudomonas (choice D) have not been implicated as significant causes of post-infectious glomerulonephritis.

The gram-negative cocci Neisseria(choice C) have not been implicated in post-infectious glomerulonephritis.

A 43-year-old man presents to his physician with complaints of fatigue. Physical examination is remarkable for hypertension. Laboratory examination reveals anemia, elevated blood urea nitrogen (BUN), and elevated creatinine. Which of the following conditions would best account for this presentation?

A. Adult polycystic kidney disease

B. Lipoid nephrosis

C. Poststreptococcal glomerulonephritis

D. Renal cell carcinoma

E. Wilms' tumor

Explanation:

The correct answer is A. Adult polycystic disease is characterized by kidneys that progressively enlarge as a consequence of multiple renal cysts. Presenting signs (typically beginning when patients are in their 40s), include hypertension (secondary to renin production), renal failure (with elevated BUN and creatinine), and anemia (secondary to a failure of renal erythropoietin production). This autosomal dominant condition also causes cysts in other organs (liver, pancreas, spleen, gonads), berry aneurysms (the rupture of which may cause death), and abnormalities of cardiac valves.

Lipoid nephrosis (choice B), or minimal change disease, is the most common cause of nephrotic syndrome in children, and is not usually associated with renal failure.

Poststreptococcal glomerulonephritis (choice C) usually presents with hematuria following a bout of streptococcal pharyngitis.

Renal tumors typically present either as a mass or with hematuria. Renal cell carcinoma (choice D) generally affects adults, while Wilms' tumor (choice E) is an early childhood tumor.

A concerned mother brings her 6-year-old son to the pediatrician because he has developed a "puffy face." On

examination, the child has a blood pressure of 90/60, marked periorbital edema, and pitting edema of both the hands and feet. His cardiac exam is unremarkable and he has no splenomegaly or signs of liver disease. Laboratory values are notable for decreased serum albumin and increased total cholesterol. A urinalysis reveals 4+ proteinuria but no red blood cells, white blood cells, or casts. The most likely cause of this child's disease is

A. Goodpasture's syndrome

B. minimal change nephropathy

C. poststreptococcal glomerulonephritis

D. systemic lupus erythematosus

E. Wegener's granulomatosis

Explanation:

The correct answer is B. This boy has nephrotic syndrome: edema, heavy proteinuria with a benign urinary sediment, hypoalbuminemia, and hypercholesterolemia. Of the choices listed, only minimal change nephropathy is a recognized cause of nephrotic syndrome. It is the most common cause of nephrotic syndrome in children.

All the other choices are not consistent with the clinical history and are causes of nephritis, not nephrosis. Remember that nephritic patients present with hypertension, moderate proteinuria, hematuria, and an active urinary sediment with red blood cell casts.