Rubins - Kidney Questions

1. The answer is D: Renal dysplasia. Renal dysplasia is characterized by undifferentiated tubular structures surrounded by primitive mesenchyme, sometimes with heterotopic tissue such as smooth muscle and cartilage. Cysts often form from the abnormal tubules. Renal dysplasia results from an abnormality in metanephric differentiation. Variants of renal dysplasia include aplastic, multicystic (seen in this case), diffuse cystic, and obstructive forms. In most patients with multicystic renal dysplasia, a palpable flank mass is discovered shortly after birth. Unilateral multicystic renal dysplasia is the most common cause of an abdominal mass in newborns. Infantile polycystic disease (choice A) is invariably bilateral, and the kidneys are usually very large. Medullary sponge kidney (choice B) is characterized by multiple small cysts in the renal papillae. Wilms tumor (choice E) may contain heterologous elements but does not form large cysts. Diagnosis: Multicystic renal dysplasia

1. The mother of a 2-month-old child palpates a mass on the left side of the child's abdomen. Vital signs are normal. A CT-guided renal biopsy shows undifferentiated tubules surrounded by undifferentiated mesenchyme, smooth muscle, and islands of cartilage. The mass is removed (shown in the image) and displays variably sized cysts. Which of the following is the most likely diagnosis for this child's flank mass? (A) Infantile polycystic disease (B) Medullary sponge kidney (C) Neuroblastoma (D) Renaldysplasia (E) Wilms tumor

10. The answer is C: Minimal change disease, focal segmental glomerulosclerosis. Minimal change glomerulopathy causes 90% of the nephrotic syndrome in young children and 15% in adults. Proteinuria is generally more selective (albumin > globulins) than in the nephrotic syndrome caused by other diseases, but there is too much overlap for this selectivity to be used as a diagnostic criterion. This disease is characterized pathologically by fusion (effacement) of visceral epithelial foot processes; however, this can be visualized only by electron microscopy. Minimal change glomerulopathy is successfully treated with corticosteroids and does not progress to renal failure. Focal segmental glomerulosclerosis (FSGS) is the cause of nephrotic syndrome in 10% of children and 30% of adults. FSGS is the term applied to a heterogeneous group of glomerular diseases that have different causes, including mutations, viruses, drugs, and serum factors. Henoch-Schönlein purpura and lupus nephritis (choice A) generally present with nephritic syndrome and rash, among other signs and symptoms. Wilms tumor (choice E) is not a cause of nephrotic syndrome. Diagnosis: Minimal change nephrotic syndrome

10. A 12-year-old boy complains of swelling of his feet for the past 3 weeks. He is otherwise healthy, with no known previous illness. Vital signs are normal. Physical examination reveals pitting edema of the lower legs and a swollen abdomen. Urinalysis shows 4+ protein but no RBCs or WBCs. Which of the following are the most likely diagnoses to consider in your evaluation of this patient? (A) Henoch-Schönlein purpura, lupus nephritis (B) Malignant hypertension, renal vein thrombosis (C) Minimal change disease, focal segmental glomerulosclerosis (D) Pyelonephritis, acute tubular necrosis (E) Wilms tumor, renal cell carcinoma

11. The answer is C: Lipid droplets. The loss of protein in the urine in patients with nephrotic syndrome leads to hypoalbuminemia. A compensatory increase in lipoprotein secretion by the liver results in hyperlipidemia, which is reflected in the presence of lipid droplets in the urine. For this reason, minimal change disease is also referred to as lipoid nephrosis. Eosinophils (choice B) may be observed in allergic nephritis. White blood cell casts (choice E) are features of pyelonephritis. Diagnosis: Minimal change nephrotic syndrome

11. A 4-year-old girl presents with swelling of the legs and ankles. Physical examination reveals pitting edema of the lower extremities. Urinalysis show 2+ proteinuria. The urinary sediment contains no inflammatory cells or red blood cells. Serum levels of BUN and creatinine are normal. The patient recovers completely after a course of corticosteroids. Which of the following pathologic findings might be expected in the urine prior to treatment with corticosteroids? (A) Amyloidcasts (B) Eosinophils (C) Lipiddroplets (D) Red blood cell casts (E) White blood cells casts

12. The answer is D: Fusion of podocyte foot processes. The light microscopic appearance of glomeruli in minimal change glomerulopathy is essentially normal. However, electron microscopic examination of glomeruli reveals total effacement of visceral epithelial cell foot processes. This retraction presumably results from extensive cell swelling and occurs in virtually all cases of proteinuria in the nephrotic range. It is not a specific marker, but is characteristic of minimal change glomerulopathy. Minimal change disease is not characterized by deposits of immune complexes (choices B and C) and does not reflect changes in the basement membrane (choice A). Choice E is incorrect because minimal change disease involves changes in glomeruli, not renal tubules. Diagnosis: Minimal change nephrotic syndrome

12. For the patient described in Question 11, electron microscopy of a renal biopsy specimen prior to treatment would most likely demonstrate which of the following abnormalities? (A) Duplication of capillary basement membranes (B) Electron-dense immune deposits in the capillary base- ment membranes (C) Electron-dense immune deposits in the mesangium (D) Fusion of podocyte foot processes (E) Loss of microvilli by the tubular lining cells

13. The answer is D: Membranous glomerulopathy. Membranous glomerulopathy is a frequent cause of the nephrotic syndrome in adults and is caused by the accumulation of immune complexes in the subepithelial zone of glomerular capillaries. Immunofluorescence microscopy shows granular deposits of IgG outlining the glomerular capillary loops. The course of membranous glomerulopathy is highly variable, with a range of possible outcomes, including spontaneous remission (25%), persistent proteinuria and stable or only partial loss of renal function (50%), and renal failure (25%). Membrano-proliferative glomerulonephritis type I (choice C) is a chronic immune complex disease that features granular deposition of immunoglobulin and complement in glomerular capillary loops and mesangium. Diagnosis: Membranous glomerulopathy

13. A 44-year-old man complains of swelling of his legs and puffiness around his eyes. His abdomen has become protuberant and he feels short of breath. Physical examination reveals generalized edema and ascites. Total serum protein is 5.2g/dL (reference = 5.5 to 8.0 g/dL), and albumin is 1.9 g/dL (reference = 3.5 to 5.5g/dL). Serum cholesterol is elevated at 530 mg/dL. There are 5 g of protein in a 24-hour urine collection. The urinary sediment contains many hyalin casts but no RBCs or inflammatory cells. A renal biopsy stained by direct immunofluorescence for IgG is shown in the image. Which of the following is the most likely diagnosis? (A) Amyloid nephropathy (B) Focal segmental glomerulosclerosis (C) Membranoproliferative glomerulonephritis type I (D) Membranous glomerulopathy (E) Minimal change disease

14. The answer is E: Subepithelial deposits of immune complexes. Membranous glomerulopathy exhibits localization of immune complexes in the subepithelial zone (between the visceral epithelial cell and the glomerular basement membrane) as a result of immune complex formation in situ or the deposition of circulating immune complexes. Granular deposits of IgG outlining the glomerular capillary loops are identified by immunofluorescence microscopy. Deposition of antiglomerular basement membrane antibody (choice A) is a feature of Goodpasture syndrome. Deposition of IgA in the mesangium (choice B) occurs in Berger disease. Subendothelial deposits of immune complexes (choice D) are encountered in lupus nephritis and membranoproliferative glomerulonephritis. Diagnosis: Membranous nephropathy

14. The pathogenesis of nephrotic syndrome in the patient described in Question 13 is best characterized by which of the following mechanisms of disease? (A) Deposition of antiglomerular basement membrane antibody (B) Deposition of IgA in the mesangium (C) Expansion of the glomerular basement membrane with PAS-positive glycoproteins (D) Subendothelial deposits of immune complexes (E) Subepithelial deposits of immune complexes

15. The answer is D: Systemic lupus erythematosus. Immune complexes formed against DNA, RNA, and autologous proteins in patients with systemic lupus erythematosus may be deposited along the basement membrane of the glomeruli to form a pattern that may be indistinguishable from that of idiopathic membranous nephropathy. However, membranous nephropathy of lupus also features mesangial and subendothelial deposits of immunoglobulins. Immune complex deposition does not occur in the other choices. Diagnosis: Systemic lupus erythematosus

15. The glomerular changes in the patient described in Question 13 are frequently seen in patients with which of the following systemic diseases? (A) Amyloidnephropathy (B) Goodpasture syndrome (C) Scleroderma (D) Systemic lupus erythematosus (E) Wegener granulomatosis

16. The answer is A: Complement. In acute postinfectious glomerulonephritis, immune complexes localize in glomeruli by deposition from the circulation or by formation in situ as bacterial antigens bind circulating antibodies. The renal biopsy shows complement fixation. Complement activation is so extensive that over 90% of patients with postinfectious glomerulonephritis develop hypocomplementemia. Complement and other inflammatory mediators attract and activate neutrophils and monocytes, which stimulate the proliferation of mesangial and endothelial cells, resulting in diffuse proliferative glomerulonephritis. Typically, the level of serum C3 is depressed during the acute syndrome but returns to normal within 1 to 2 weeks. The other choices involve the coagulation system and are not components of immune complexes. Diagnosis: Postinfectious glomerulonephritis, nephritic syndrome

16. A 14-year-old girl presents with a 5-day history of hypertension, oliguria, and hematuria. She was seen 2 weeks earlier for a severe throat infection with group A (β-hemolytic) streptococci. A kidney biopsy displays glomerulonephritis. Immunofluorescence staining for which of the following proteins would provide the strongest evidence that this patient's glomerulonephritis is mediated by immune complexes? (A) Complement (B) Fibrinogen (C) Hageman factor (clotting factor XII) (D) Plasminogen (E) Thrombin

17. The answer is E: Wegener granulomatosis. Wegener granulomatosis is a systemic necrotizing vasculitis of unknown etiology that is characterized by granulomatous lesions of the nose, sinuses, and lungs and is associated with renal glomerular disease. Lesions associated with this condition feature parenchymal necrosis, vasculitis, and a granulomatous inflammation composed of neutrophils, plasma cells, and macrophages. More than 90% of patients with Wegener granulomatosis exhibit ANCA, of whom 75% have C-ANCA. ANCA glomerulonephritis is an aggressive, neutrophil- mediated disease that is characterized by glomerular necrosis and crescents. Goodpasture syndrome (choice B) is characterized by both kidney and pulmonary involvement but does not display ANCA. Churg-Strauss syndrome (choice A) features eosinophilia and asthma. Diagnosis: Wegener granulomatosis

17. A 28-year-old man complains of nasal obstruction, bloody nose, cough, and bloody sputum. A chest X-ray displays cavi- tated lesions and multiple nodules within both lung fields. Urinalysis reveals 3+ hematuria and red blood cell casts. Laboratory studies show anemia and elevated serum levels of C-ANCA (antineutrophil cytoplasmic antibody). Peripheral eosinophils are not increased. A renal biopsy exhibits focal glomerular necrosis with crescents and vasculitis affecting arterioles and venules. What is the appropriate diagnosis? (A) Churg-Strausssyndrome (B) Goodpasture syndrome (C) Hypersensitivityvasculitis (D) Polyarteritisnodosa (E) Wegener granulomatosis

18. The answer is C: Rapidly progressive glomerulonephritis (RPGN). Focal necrotizing glomerulonephritis is one of the early features of Wegener granulomatosis. The pathogenesis of this renal disease is not known, but it is thought to be immune mediated because most patients have antibodies to neutrophils (ANCA). These autoantibodies activate neutrophils and cause them to adhere to endothelial cells, release toxic oxygen metabolites, degranulate, and kill the endothelial cells. Exudation of inflammatory cells through the disrupted, segmentally necrotic basement membrane leads to the formation of crescents. Clinically, the disease presents as RPGN, a clinical term that is used to denote the rapid onset of renal failure caused by severe glomerular injury. Wegener granulomatosis does not cause membranoproliferative glomerulonephritis (choices D and E). Diagnosis: Wegener granulomatosis, crescentic glomerulonephritis

18. Which of the following best describes the renal disease of the patient described in Question 17? (A) Chronic nephritic syndrome (B) Nephrotic syndrome (C) Rapidly progressive glomerulonephritis (D) Type I membranoproliferative glomerulonephritis (E) Type II membranoproliferative glomerulonephritis

19. The answer is E: Focal segmental glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is characterized by glomerular scarring (sclerosis) that affects some (focal), but not all, glomeruli and initially involves only part of an affected glomerular tuft (segmental). By light microscopy, varying numbers of glomeruli show segmental obliteration of capillary loops by increased collagen and the accumulation of lipid or proteinaceous material. FSGS is the cause of the nephrotic syndrome in 30% of adults and 10% of children. It is also the most common renal complication of intravenous drug abuse. Clinically, it presents with proteinuria, which occasionally may be so massive as to produce nephrotic syndrome. Nephropathy associated with HIV infection is a severe and rapidly progressive collapsing form of FSGS. Patients typically progress to end-stage renal disease in less than a year. The other choices involve glomeruli diffusely. Crescents (choice C) are not observed in the photomicrograph shown. Diagnosis: Focal segmental glomerulosclerosis

19. A 30-year-old man with a history of drug addiction presents with a 6-month history of progressive swelling in his ankles and abdomen. Urinalysis shows heavy proteinuria (>4 g per 24 hours) but no evidence of inflammatory cells or RBCs. Laboratory studies reveal hyperlipidemia and hypoalbuminemia. Serum creatinine level is normal. The blood test for ANCA is negative. The patient responds well to treatment with corticosteroids, but edema and proteinuria recur the following year. The steroid treatment is repeated with the same results. Upon the third recurrence of edema and proteinuria, the patient becomes steroid resistant. A renal biopsy is shown in the image. Which of the following is the most likely diagnosis for this patient's glomerulopathy? (A) Acute glomerulonephritis (B) Amyloidosis (C) Crescentic glomerulonephritis (D) Diffuse proliferative glomerulonephritis (E) Focal segmental glomerulosclerosis

2. The answer is A: Autosomal dominant polycystic kidney disease. Autosomal dominant polycystic kidney disease, which is characterized by enlarged multicystic kidneys, is the most common of a group of congenital diseases that are characterized by numerous cysts within the renal parenchyma. Most cases are caused by mutations in the polycystic kidney disease 1 gene, which encodes polycystin (function unknown). Half of all patients eventually develop end-stage renal failure. Most patients develop clinical manifestations in the fourth decade of life, which is why this condition was also called adult polycystic kidney disease. Symptoms include a sense of heaviness in the loins, bilateral flank and abdominal masses, and passage of blood clots in the urine. Azotemia is common and, in half of patients, progresses to uremia (clinical renal failure) over a period of several years. Autosomal recessive polycystic kidney disease (choice B) occurs in infants. Hydronephrosis (choice C) does not feature multiple cysts. Medullary sponge kidney (choice D) consists of multiple small cysts. Multicystic renal dysplasia (choice E) is usually unilateral. Diagnosis: Autosomal dominant polycystic kidney disease

2. A 38-year-old man presents with vague flank pain and describes the passage of blood clots in his urine. Physical examination reveals bilateral flank and abdominal masses. Laboratory studies show elevated blood urea nitrogen and creatinine. Urinalysis reveals hematuria, proteinuria, and oliguria. A CT scan discloses bilaterally, massively enlarged kidneys. The patient subsequently develops end-stage kidney disease and receives a renal transplant. The patient's kidneys are removed during surgery (shown in the image). What is the most likely diagnosis? (A) Autosomal dominant polycystic kidney disease (B) Autosomal recessive polycystic kidney disease (C) Hydronephrosis (D) Medullary sponge kidney (E) Multicystic renal dysplasia

20. The answer is D: Erythropoietin. Erythropoietin is released by the interstitial peritubular cells of the kidney in response to hypoxia and activates specific receptors on the cell membrane of erythroid progenitor cells in the bone marrow. This effect rescues progenitor cells from programmed cell death, promotes colony growth, and restores normal red blood cell mass. Renin (choice E) is released by the juxtaglomerular apparatus. Diagnosis: Anemia, hypoxia

20. A 20-year-old woman is involved in an automobile accident and loses a large amount of blood. In response to hypoxia, interstitial peritubular cells of the kidney would be expected to release which of the following hormones? (A) Aldosterone (B) Angiotensin (C) Angiotensinogen (D) Erythropoietin (E) Renin

21. The answer is B: Berger disease (IgA nephropathy). Berger disease is the most common form of glomerulonephritis in adults. Deposition of IgA-dominant immune complexes is the cause of the nephropathy, but the constituent antigens and the mechanism of accumulation have not been determined. Exacerbations of IgA nephropathy are often initiated by infections of the respiratory or gastrointestinal tracts. The diagnostic finding on renal biopsy is intense mesangial staining for IgA, which is almost always accompanied by staining for C3. IgA nephropathy manifests a continuum of glomerulopathies, ranging from no discernible light microscopic changes to chronic sclerosing glomerulonephritis. Patients frequently present with hematuria and proteinuria, and 20% of patients develop renal failure after 10 years. Neither amyloid nephropathy (choice A) nor membranous nephropathy (choice D) features RBC casts. Hereditary nephritis (Alport syndrome; choice C) reflects abnormal type IV collagen in the glomerular basement membrane. Hematuria is present early in life; proteinuria, progressive renal failure, and hypertension develop later in the course of the disease. Wegener granulomatosis (choice E) is usually positive for ANCA. Diagnosis: Berger disease, IgA nephropathy

21. A 32-year-old man complains of recurrent hematuria since his youth. The hematuria typically occurs following upper respiratory tract infections. Vital signs are normal. Urinalysis shows proteinuria, hematuria, and a few red blood cell casts. Laboratory studies disclose normal levels of BUN and creatinine. The ANA and ANCA tests are negative. Which of the following is the most likely diagnosis? (A) Amyloid nephropathy (B) Berger disease (IgA nephropathy) (C) Hereditary nephritis (Alport syndrome) (D) Membranous glomerulopathy (E) Wegener granulomatosis

22. The answer is C: Mesangial deposition. IgA nephropathy (Berger disease) is caused by immune complexes of IgA, which are located within the mesangium, where they most likely activate complement through the alternative pathway. The diagnostic finding is mesangial staining that is more intense for IgA than for IgG or IgM. Diagnosis: Berger disease, IgA nephropathy

22. For the patient described in Question 21, which of the following patterns of IgA immunofluorescence would be expected in the renal biopsy? (A) Granular capillary membrane deposition (B) Linear basement membrane staining (C) Mesangial deposition (D) Perivascular location (E) Subepithelial deposits

23. The answer is C: Focal proliferative glomerulonephritis. Focal proliferative glomerulonephritis typically presents with pathologic changes in some glomeruli, whereas others remain normal. This group of diseases includes lupus nephritis, nephritis that accompanies several vasculitides, Henoch-Schönlein purpura, and several other disorders. It also includes IgA nephropathy (Berger disease), which, as in this case, presents with mesangial deposits of IgA and mesangial cell proliferation. The clinical presentation is variable, which reflects the varied pathologic severity of disease. Diagnosis: Berger disease, IgA nephropathy

23. A 25-year-old man complains of intermittent hematuria over the past 8 years. Urinalysis shows microscopic hematuria. Urine cultures are negative. A renal biopsy (shown in the image) displays mesangial proliferation within some glomeruli, whereas others appear normal. Immunofluorescence staining discloses mesangial deposition of IgA. Which of the following is the appropriate pathologic diagnosis? (A) Amyloid nephropathy (B) Crescentic glomerulonephritis (C) Focal proliferative glomerulonephritis (D) Membranous nephropathy (E) Nodular diabetic glomerulosclerosis

24. The answer is E: Subepithelial and subendothelial deposits. The most distinctive ultrastructural features of acute postinfectious glomerulonephritis are subepithelial dense deposits that are shaped like "humps." These deposits are invariably accompanied by mesangial and subendothelial deposits, which may be more difficult to find but are probably more important in pathogenesis because of their proximity to inflammatory mediator systems in the blood. Choices A, B, and C describe limited deposition of immune complexes, whereas choice D is a feature of antiglomerular basement membrane disease (Goodpasture syndrome). Diagnosis: Postinfectious glomerulonephritis, nephritic syndrome

24. An 8-year-old boy presents with headaches, dizziness, and malaise approximately 2 weeks after a severe sore throat. His mother describes puffiness of his face and darkening of his urine. She also notes that her son is passing less urine and that he is becoming increasingly short of breath. On physical exam- ination, there is anasarca, hypertension (190/130 mm Hg), and tachycardia. The urine is scanty and brownish red. Urinalysis shows 3+ proteinuria. Microscopic examination of the urine discloses numerous RBCs, as well as occasional granular and red cell casts. A renal biopsy is stained by direct immunofluorescence microscopy for complement C3, and the results are shown. Which of the following best describes the pattern of immunofluorescence observed in this renal biopsy? (A) Dense deposits in glomerular crescents between epithelial cells (B) Deposits limited to the mesangium (C) Granular deposits along the perimesangial reflections (D) Linear staining along the glomerular basement membranes (E) Subepithelial and subendothelial deposits

25. The answer is C: Group A (b-hemolytic) streptococci. Acute postinfectious glomerulonephritis is an immune complex disease of childhood, which occurs after an infection with group A (β-hemolytic) streptococci and is caused by the deposition of immune complexes in glomeruli. Occasional examples are caused by staphylococcal infection (e.g., acute staphylococcal endocarditis, staphylococcal abscess), and rare cases result from viral (e.g., hepatitis B) or parasitic (e.g., malaria) infections. The primary infection involves the pharynx or, in hot and humid environments, the skin. In recent years, the proportion of cases of acute postinfectious glomerulonephritis caused by staphylococcal infection (choice E) has been increasing. Diagnosis: Nephritic syndrome, acute postinfectious glomerulonephritis

25. Which of the following is the most likely cause of acute postinfectious glomerulonephritis in the patient described in Question 24? (A) Escherichia coli (B) Epstein-Barr virus (C) Group A (β-hemolytic) streptococci (D) Klebsiellasp. (E) Staphylococcus sp.

26. The answer is D: Recovery without serious consequences. Overt nephritis after postinfectious glomerulonephritis usually resolves after several weeks, although hematuria and especially proteinuria may persist for several months. Diagnosis: Nephritic syndrome, acute postinfectious glomerulonephritis

26. Which of the following is the most likely outcome of glomerulonephritis in the patient described in Question 24? (A) Bilateral cortical necrosis (B) Development of nephrotic syndrome (C) Membranoproliferative glomerulonephritis (D) Recovery without serious consequences (E) Transition into crescentic glomerulonephritis

27. The answer is E: Proliferative glomerulonephritis. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a generalized dysregulation and hyperactivity of B cells, with production of autoantibodies to a variety of nuclear and nonnuclear antigens. Nephritis is one of the most common complications of SLE. Immune complexes may localize in glomeruli by deposition from the circulation, formation in situ, or both. Diffuse proliferative glomerulonephritis is a severe form of lupus nephritis, characterized by widespread involvement of glomeruli and diffuse proliferation of mesangial and endothelial cells and even of epithelial cells. Deposits of immune complexes, visible by electron microscopy or immunofluorescence microscopy, are present on both sides of the basement membrane, in the mesangial areas, and even inside the capillary loops. The thickened basement membranes of the glomeruli are colloquially known as "wire loop" lesions. Membranous nephropathy (choice D) may occur in SLE, but the current biopsy displays hypercellularity. SLE is not a cause of membranoproliferative glomerulonephritis, type II (choice C). Diagnosis: Systemic lupus erythematosus

27. A 30-year-old woman with systemic lupus erythematosus presents with oliguria. Laboratory studies show elevated serum levels of creatinine and BUN. Urinalysis reveals 4+ proteinuria and hematuria. The renal biopsy (shown in the image) exhibits segmental endocapillary hypercellularity and thickening of capillary walls, and 90% of the glomeruli appear hypercellular. Which of the following is the appropriate pathologic diagnosis? (A) Crescentic glomerulonephritis (B) Focal segmental glomerulosclerosis (C) Membranoproliferative glomerulonephritis, type II (D) Membranous nephropathy (E) Proliferative glomerulonephritis

28. The answer is C: Linear along the glomerular basement membrane (GBM). Anti-GBM antibody glomerulonephritis is an uncommon but aggressive form of glomerulonephritis that occurs as a renal limited disease or is combined with pulmonary hemorrhage (Goodpasture syndrome). The disease is mediated by an autoimmune response against a component of the GBM that is located within the noncollagenous domain of type IV collagen. A characteristic feature of anti-GBM glomerulonephritis is the presence of diffuse linear staining of GBMs for IgG, which indicates autoantibodies bound to the basement membrane. By light microscopy, over 90% of patients with anti-GBM glomerulonephritis have glomerular crescents (crescentic glomerulonephritis). Linear immunofluorescence for IgG is seen along the GBM. Anti-GBM glomerulonephritis typically presents with rapidly progressive renal failure and nephritic signs and symptoms. Diagnosis: Goodpasture syndrome

28. A 35-year-old man with a history of smoking presents with hematuria and bloody sputum. Over the next 2 days, he develops oliguria and renal failure, after which he is placed on dialysis. A renal biopsy is stained with fluorescein-conjugated goat antihuman IgG, and the results are shown. Which of the following best describes the pattern of direct immunofluorescence observed on this photomicrograph? (A) Discontinuous and peripheral (B) Finely granular along the perimesangial reflections (C) Linear along the glomerular basement membrane (D) Mesangial with a stalk predominance (E) Peripheral granular humps

29. The answer is C: Membranous glomerulopathy. Many malignant neoplasms may be accompanied by a variety of paraneoplastic syndromes, among which is membranous nephropathy. Other causes of secondary membranous nephropathy include autoimmune diseases (e.g., systemic lupus erythematosus), infectious diseases (e.g., hepatitis B), and therapeutic agents (e.g., penicillamine). Immune complex deposition is found in all of these conditions. IgA nephropathy and Goodpasture syndrome (choices A and B) are not paraneoplastic disorders. Minimal change glomerulopathy (choice D) is usually found in children and is not a paraneoplastic disorder. Nodular glomerulosclerosis (choice E) reflects diabetic lesions. Diagnosis: Membranous nephropathy, paraneoplastic syndrome

29. A 54-year-old woman with squamous cell carcinoma of the lung develops bilateral pitting edema of the lower extremi- ties. Laboratory studies show hyperlipidemia, hypoal- buminemia, and 4+ proteinuria. Urinalysis reveals no inflammatory cells or RBCs. Renal biopsy in this patient would most likely show which of the following patterns of glomerulopathy? (A) Berger disease (IgA nephropathy) (B) Goodpasture syndrome (C) Membranous glomerulopathy (D) Minimal change glomerulopathy (E) Nodular glomerulosclerosis

3. The answer is A: Hepatic cysts. One third of patients with autosomal dominant polycystic kidney disease (ADPKD) also have hepatic cysts, whose lining resembles bile duct epithelium. The other choices do not arise in ADPKD. Diagnosis: Autosomal dominant polycystic kidney disease

3. The patient described in Question 2 carries an increased risk for which of the following abnormalities? (A) Hepaticcysts (B) Horseshoe kidney (C) Pulmonarycysts (D) Renal cell carcinoma (E) Transitional cell carcinoma of the bladder

30. The answer is A: Crescents in the urinary space. Crescentic glomerulonephritis is the morphologic equivalent of acute renal failure, which may develop in rapidly progressive glomerulonephritis of Goodpasture syndrome. This disease is mediated by antibodies to collagen type IV, which attack the GBM. The same antibodies attack the lung and cause hemoptysis. Rupture of the GBM and extravasation of blood and inflammatory cells into the urinary space (i.e., the space between Bowman capsule and the glomerular capillary tufts) leads to the appearance of hypercellular, crescent-like tissue. These structures are composed of proliferating parietal epithelial cells, as well as visceral epithelial cells and macrophages. Crescentic glomerulonephritis can be caused by other diseases, such as Wegener granulomatosis or polyarteritis nodosa, which are also diseases that damage the capillary loops of the glomeruli and allow an inflammatory exudate to accumulate in the urinary space. The other choices are not representative of epithelial crescents. Diagnosis: Goodpasture syndrome

30. A 30-year-old man with a history of smoking suddenly develops oliguria, hematuria, and hemoptysis. Serologic studies reveal antibodies to the glomerular basement membrane (GBM). A renal biopsy is shown. Which of the following pathologic changes is visible by light microscopy in this biopsy specimen? (A) Crescents in the urinary space (B) Leukocytic infiltrates in the glomeruli (C) Mesangial cell proliferation (D) Thickening of the GBM (E) Thrombi in glomerular capillaries

31. The answer is A: Acute pyelonephritis. Pyelonephritis refers to bacterial infection of the kidney parenchyma. Gram-negative bacteria, most commonly Escherichia coli, cause 80% of acute pyelonephritis. The infection reaches the kidney by ascending through the urinary tract, a process that depends on the following several factors: (1) bacterial infection of the urine, (2) reflux of the infected urine up the ureters into the renal pelves and calyces, and (3) entry of the bacteria through the papillae into the renal parenchyma. Bacteriuria is a typical finding in patients with acute pyelonephritis. Diabetic patients with glucosuria are at increased risk for developing acute pyelonephritis. Acute bacterial infection is not a typical feature of the other choices. Diagnosis: Acute pyelonephritis

31. A 52-year-old woman who suffers from diabetes mellitus and frequent urinary tract infections presents with a 3-day history of flank pain, undulating fever, and general malaise. A CBC shows neutrophilic leukocytosis (16,000/μL). Urine cultures reveal more than 100,000 bacterial colonies, composed predominantly of Gram-negative microorganisms. Blood pressure is 170/100mmHg, BUN is 30mg/dL, and creatinine is 2.0 mg/dL. Fasting serum glucose is 190 mg/dL. Urinalysis shows 2+ sugar and 1+ protein. Microscopic examination of the urine sediment reveals neutrophils and occasional leukocyte casts. Which of the following is the most likely diagnosis? (A) Acute pyelonephritis (B) Acute tubular necrosis (C) Diabetic nephropathy (D) Postinfectious glomerulonephritis (E) Nephrolithiasis

32. The answer is D: Pyelonephritis. Symptoms of pyelonephritis include fever, chills, malaise, and flank pain. There is an increased incidence of pyelonephritis in pregnancy. On gross examination, the kidneys of acute pyelonephritis may have small white abscesses on the subcapsular surface. The urothe- lium of the pelvices and calyces may be hyperemic and cov- ered by a purulent exudate. Acute pyelonephritis is often a focal disease, and much of the kidney often appears normal. Renal biopsy shows an extensive infiltrate of neutrophils in the collecting tubules and interstitial tissue. Cystitis (choice A) and urethritis (choice E) are incorrect because the finding of leukocyte casts in urine supports the diagnosis of an upper urinary tract infection. Diagnosis: Acute pyelonephritis

32. A 22-year-old woman in the second trimester of pregnancy presents with flank pain, fever of 38.7°C (103°F), and chills. Hemoglobin is 13.4 g/dL, WBCs are elevated (13,500/μL with 78% neutrophils), and there are 265,000 platelets/μL. Physical examination reveals costovertebral angle tenderness. The urine shows numerous WBCs and WBC casts. Which of the following is the most likely diagnosis? (A) Cystitis (B) Endometritis (C) Glomerulonephritis (D) Pyelonephritis (E) Urethritis

33. The answer is A: Gram-negative bacteria. Acute pyelonephritis and chronic pyelonephritis are bacterial diseases that usually develop from ascending infections related to the reflux of infected urine from the lower urinary tract. Gram-negative bacteria from the feces, most commonly E. coli, cause 80% of cases of acute pyelonephritis. Infection of the bladder often precedes acute pyelonephritis. Bladder infection is more common in females because of a short urethra, lack of antibacterial prostatic secretions, and facilitation of bacterial migration by sexual intercourse. Hematogenous dissemination of organisms may lead to urosepsis. Infection with Gram-positive bacteria (choice B) can occur but is not common. Viruses (choice C) and mycobacteria (choice E) do not ordinarily cause renal disease. Choice D (immune complex deposition) is associated with glomerular disease. Diagnosis: Acute pyelonephritis

33. Which of the following is the most likely cause of the renal disease in the patient described in Question 32? (A) Gram-negativebacteria (B) Gram-positive bacteria (C) Humanpapillomavirus (D) Immune complex deposition (E) Mycobacteria

34. Patients with chronic pyelonephritis suffer episodic manifestations of urinary tract infection or acute pyelonephritis, such as recurrent fever and flank pain. Urinalysis demonstrates leukocytes, and imaging studies reveal cortical scarring. The microscopic appearance of chronic pyelonephritis is nonspecific. In this case, the biopsy shows tubular dilation and atrophy. Many tubules contain eosinophilic hyaline casts resembling the colloid of thyroid follicles (so-called thyroidization). The interstitium is scarred and contains a chronic inflammatory cell infiltrate (see photomicrograph). With the exception of acute pyelonephritis, the other choices are not related to bacterial infections. Acute pyelonephritis (choice A) is not characterized by scarred and shrunken kidneys. Diagnosis: Chronic pyelonephritis

34. A 50-year-old woman complains of severe headaches and dizziness. The patient has a history of repeated urinary tract infections. The blood pressure is 180/110mmHg. Laboratory studies show elevated levels of BUN (38 mg/dL) and creatinine (2.8mg/dL). A CT scan of the lower abdomen reveals small, irregularly shaped kidneys with deep coarse scars. A percutaneous renal biopsy is shown. Which of the following is the appropriate diagnosis? (A) Acute pyelonephritis (B) Acute tubular necrosis (C) Chronic pyelonephritis (D) Nephrosclerosis (E) Tubulointerstitial nephritis

35. The answer is E: Repeated bouts of acute pyelonephritis. Chronic pyelonephritis is caused by recurrent and persistent bacterial infection secondary to urinary tract obstruction, urine reflux, or both. Choices A, B, and C cause glomerular disease, and choice D (hypertension) is a vascular disorder that is not associated with deep cortical scarring. Diagnosis: Chronic pyelonephritis

35. The pathogenesis of the renal disease in the patient described in Question 34 is related to which of the following conditions? (A) Amyloidosis (B) Antiglomerular basement membrane disease (C) Chronic hepatitis B infection (D) Hypertension (E) Repeated bouts of acute pyelonephritis

36. The answer is C: Diabetic glomerulosclerosis. Diabetes mellitus, a complex metabolic disease associated with glucosuria and polyuria, is the leading cause of end-stage renal disease in the United States, accounting for a third of all patients with chronic renal failure. Diabetic glomerulosclerosis is a component of the vascular sclerosis that involves many small vessels throughout the body. In this condition, the glomeruli show diffuse mesangial matrix expansion with focal, segmental, nodular, and sclerotic lesions. Nodular widening of the mesangial areas is associated with hyalinization of arterioles and focal hyaline changes of Bowman capsule. Diabetic glomerulosclerosis eventually results in progressive renal failure. The other choices are not associated with diabetes and glucosuria. Diagnosis: Diabetic nephropathy, diabetes mellitus

36. A 52-year-old woman presents with swelling of her ankles of 6 weeks in duration. Physical examination reveals an obese woman (BMI = 32kg/m2) with pitting edema of the lower extremities and periorbital edema. Laboratory studies show hyperlipidemia and hypoalbuminemia. Urinalysis discloses 3+ proteinuria and 3+ glucosuria but no evidence of inflammatory cells or RBCs. A kidney biopsy stained with PAS (shown in the image) displays a prominent increase in the mesangial matrix, forming nodular lesions, and thickening of capillary basement membranes. Which of the following is the most likely pathologic diagnosis? (A) Acute glomerulonephritis (B) Amyloid nephropathy (C) Diabetic glomerulosclerosis (D) Malignant nephrosclerosis (E) Membranoproliferative glomerulonephritis

37. The answer is C: Hyperglycemia. The cardinal sign of diabetes mellitus is increased levels of blood glucose (hyperglycemia). Abnormal nonenzymatic glycosylation of serum and matrix proteins, including those of the glomerular basement membrane and mesangial matrix, may induce binding of plasma proteins, such as immunoglobulins and, thereby, stimulate excessive matrix production. As a result, the GBMs are thickened and hyperpermeable to albumin, which leads to proteinuria. Overt proteinuria occurs 10 to 15 years after the onset of diabetes and often becomes severe enough to cause nephrotic syndrome. The other choices are not characteristic of diabetes. Diagnosis: Diabetes mellitus, diabetic glomerulosclerosis

37. Which of the following serum abnormalities is expected in the patient described in Question 36? (A) Hyperbilirubinemia (B) Hypergammaglobulinemia (C) Hyperglycemia (D) Hyperuricemia (E) Hypobilirubinemia

38. The answer is D: Renal papillary necrosis. Glucosuria of diabetes predisposes to acute pyelonephritis by providing a rich medium for bacterial growth. Necrosis of the papillary tips may occur in severe cases. Symptoms include fever, urinary colic, and severe groin and flank pain. The other choices are not complications of pyelonephritits. Diagnosis: Papillary necrosis, diabetes mellitus

38. A 70-year-old diabetic woman presents with sudden onset of excruciating groin and flank pain. Physical examination shows pitting edema of the lower extremities. Laboratory studies reveal decreased serum albumin and increased serum lipids. Urine cultures reveal more than 100,000 bacterial colonies composed predominantly of Gram-negative microorganisms. Which of the following is the most likely diagnosis? (A) Acute tubular necrosis (B) Crescentic glomerulonephritis (C) Diabetic glomerulosclerosis (D) Renal papillary necrosis (E) Renal vein thrombosis

39. The answer is A: Collagen. Hereditary nephritis (Alport syndrome) reflects abnormal type IV collagen in the glomerular basement membrane. The syndrome is a proliferative and sclerosing glomerular disease, often accompanied by defects of the ear or the eyes, which is caused by a genetic abnormality in type IV collagen. Hematuria is present early in life in males with X-linked disease and in both sexes with autosomal recessive disease. Proteinuria, progressive renal failure, and hypertension develop later in the course of the disease. Virtually all men with the X-linked syndrome and both sexes with autosomal recessive disease develop end-stage renal disease by ages 40 to 50 years. Patients with Marfan syndrome have mutations in the fibrillin gene (choice C). Diagnosis: Hereditary nephritis, Alport syndrome

39. A 40-year-old man with Alport syndrome presents with a 3-month history of headaches. His blood pressure is 165/100mmHg. A urinalysis shows 3+ proteinuria and 2+ hematuria. Laboratory studies disclose elevated levels of BUN (48mg/dL) and creatinine (3.6mg/dL). This patient's renal disease is caused by mutation in a gene that encodes which of the following extracellular matrix proteins? (A) Collagen (B) Entactin (C) Fibrillin (D) Fibronectin (E) Laminin

4. The answer is D: Pelvis. Most ectopic kidneys are located along the pathway of renal migration during fetal development and are caudal to their normal lumbar position. During fetal life, the kidneys are initially located in the lower abdomen. As development progresses, they normally move upward toward their permanent position. Kidneys that do not reach the lumbar area but remain in the pelvis or presacral area are considered ectopic. Fusion of both kidneys results in so-called "horseshoe" kidney. Diagnosis: Ectopic kidney

4. A 46-year-old woman presents with a 6-month history of vague upper abdominal pain after fatty meals, some abdominal distension, and frequent indigestion. Physical examination shows an obese woman (BMI = 32kg/m2) with right upper quadrant tenderness. A CT scan discloses gallstones and an ectopic kidney. Which of the following is the expected location of the ectopic kidney? (A) Adjacent to gallbladder (B) Attached to the left adrenal gland (C) Fused laterally with the contralateral kidney (D) Pelvis (E) Posterior epigastrium

40. The answer is A: Acute tubulointerstitial nephritis. Drug- induced (hypersensitivity) acute tubulointerstitial nephritis reflects a cell-mediated immune response. It is characterized histologically by infiltrates of activated lymphocytes (T lymphocytes) and admixed eosinophils, a pattern that indicates a type IV cell-mediated immune reaction. Although eosinophils may be present, they are not essential for the diagnosis of drug- induced nephropathy. Acute tubulointerstitial nephritis typically presents as rapidly progressive renal failure, beginning approximately 2 weeks after drug administration is started. Most patients recover fully if the drug is discontinued. The other choices are not associated with an eosinophilic response and are not related to drug hypersensitivity. Diagnosis: Acute tubulointerstitial nephritis

40. A 35-year-old man presents with fever and rash after beginning treatment with penicillin 2 weeks earlier for a sinus infection. Urinalysis shows 3+ hematuria, as well as mononuclear cells, neutrophils, and eosinophils. A percutaneous renal biopsy is shown. Which of the following is the most likely diagnosis? (A) Acute tubulointerstitial nephritis (B) Chronic pyelonephritis (C) Crescenticglomerulonephritis (D) Focal necrotizing glomerulonephritis (E) Focal segmental glomerulosclerosis

41. The answer is D: Cortical infarct. Renal cortical infarcts are, for the most part, caused by arterial obstruction, and most represent embolization to the interlobar or larger branches of the renal artery. Common sources of emboli include mural thrombi, infected valves, and complicated atherosclerotic plaques. A cross section of the kidney shows a peripheral infarct, char- acterized by marked pallor extending to the subcapsular surface. Choices A and E (benign and malignant nephrosclerosis) are vascular disorders that are general rather than localized. Choices B and C do not cause ischemic lesions. Diagnosis: Renal cortical infarct

41. A 58-year-old man with a history of coronary artery disease, peripheral vascular disease, and a recent heart attack suddenly develops painless hematuria. He subsequently suffers a massive stroke and expires. The patient's kidney at autopsy is shown. Which of the following is the most likely diagnosis? (A) Benign nephrosclerosis (B) Chronic pyelonephritis (C) Cortical abscess (D) Cortical infarct (E) Malignant nephrosclerosis

42. The answer is B: Bilateral renal cortical necrosis. Bilateral renal cortical necrosis is a syndrome characterized by massive tubular necrosis involving large portions of the cortex of both kidneys. Massive bilateral renal cortical necrosis typically occurs in the setting of hypovolemia and endotoxic shock. The term infarct is used when there is one area (or a few areas) of necrosis caused by occlusion of arteries, whereas cortical necrosis implies more widespread ischemic necrosis. The other choices are not associated with grossly visible cortical necrosis. Diagnosis: Renal cortical necrosis

42.A 36-year-old woman in the third trimester of pregnancy (gravida II, para I) presents to the emergency room with the sudden onset of severe vaginal bleeding. Ultrasound examination of the abdomen discloses abruptio placentae. A healthy neonate is delivered; however, the mother's blood loss is uncontrollable. She becomes hypotensive and obtunded and subsequently dies of hypovolemic shock. The kidneys at autopsy are shown. Which of the following is the most likely diagnosis? (A) Acute tubulointerstitial nephritis (B) Bilateral renal cortical necrosis (C) Crescentic glomerulonephritis (D) Necrotizing glomerulonephritis (E) Renal papillary necrosis

43. The answer is C: Eclampsia. Preeclampsia, which is characterized by the triad of hypertension, proteinuria, and edema, complicates the third trimester of pregnancy (choice E). When these features are complicated by convulsions, the term eclampsia is applied. On histologic examination, the glomeruli are uniformly enlarged and the endothelial cells are swollen, an appearance that results in an apparently bloodless glomerular tuft. The other choices are not ordinarily seen as complications of pregnancy. Diagnosis: Eclampsia

43. A 33-year-old woman in her third trimester of pregnancy (gravida I, para 0) is rushed to the emergency room after suffering a seizure. The patient is hypertensive and laboratory studies show that the patient manifests nephritic syndrome. What is the appropriate diagnosis? (A) Acute tubular necrosis (B) Crescentic glomerulonephritis (C) Eclampsia (D) Malignantnephrosclerosis (E) Preeclampsia

44. The answer is B: Acute tubular necrosis (ATN). ATN is a severe, but potentially reversible, impairment of tubular epithelial function caused by ischemia or toxic injury, which results in acute renal failure. Ischemic ATN results from reduced renal perfusion, usually associated with hypotension. Tubular epithelial cells, with their high rate of energy-consuming metabolic activity and numerous organelles, are particularly sensitive to hypoxia and anoxia. Ischemic ATN is characterized by swollen kidneys that have a pale cortex and a congested medulla. No pathologic changes are seen in the glomeruli or blood vessels. Necrosis of individual tubular epithelial cells is evident both from focal denudation of the tubular basement membrane and from the individual necrotic epithelial cells present in some tubular lumina. Acute intersti- tial nephritis (choice A) and eosinophilic interstitial nephritis (choice C) feature interstitial inflammation, which is not seen in this case. Diagnosis: Acute tubular necrosis

44. A 60-year-old man undergoes resection of an abdominal aneurysm, which is complicated by massive hemorrhage. Two days after surgery, the patient develops acute renal insufficiency. He is placed on dialysis but suffers a massive heart attack and dies. Microscopic examination of the kidneys at autopsy reveals necrotic epithelial cells within the lumina of some tubules (shown in the image). The arrows identify enlarged, regenerative epithelial cells. What is the appropriate diagnosis? (A) Acute interstitial nephritis (B) Acute tubular necrosis (C) Eosinophilic interstitial nephritis (D) Fanconi syndrome (E) Polyarteritis nodosa

46. The answer is A: Acute tubular necrosis (ATN). Nephrotoxic ATNis caused by chemically induced injury to epithelial cells. Because they absorb and concentrate the chemicals, tubular epithelial cells are preferred targets for certain toxins, including some antibiotics, radiographic contrast agents, heavy metals (e.g., mercury), and organic solvents. The photomicrograph shows widespread necrosis of proximal tubular epithelial cells with sparing of distal and collecting tubules. Tubulointerstitial nephritis (choice E) may be a response to certain drugs but features interstitial inflammation. Diagnosis: Acute tubular necrosis

46. A 60-year-old man presents with acute renal insufficiency. He treated his garden last week with a number of herbicides and insecticides, some of which may have contained heavy metals. Laboratory studies confirm oliguria and increased levels of BUN (54 mg/dL) and creatinine (3.7 mg/dL). A renal biopsy is shown. What is the most likely diagnosis? (A) Acute tubular necrosis (ATN) (B) Bilateral cortical necrosis (C) Papillary necrosis (D) Rapidly progressive glomerulonephritis (E) Tubulointerstitial nephritis

47. The answer is E: Malignant hypertension. The term malignant hypertension refers to a severely elevated blood pressure that results in rapidly progressive vascular disease, affecting the brain, heart, and kidney. Malignant hypertension injuries endothelial cells and causes increased vascular permeability, which leads to the insudation of plasma proteins into the vessel wall and morphologic evidence of fibrinoid necrosis. Acute injury is rapidly followed by smooth muscle proliferation and a concentric increase in the number of layers of smooth muscle cells, yielding the so-called "onion skin" appearance. This form of smooth muscle cell hyperplasia may be a response to the release of growth factors derived from platelets and other inflammatory cells at the site of vascular injury. Amyloid nephropathy (choice A) is ruled out by the absence of Congo red staining. The other choices do not cause malignant nephrosclerosis. Diagnosis: Malignant hypertension

47. A 45-year-old man undergoes renal biopsy for evaluation of chronic renal failure. The patient is obese (BMI = 37 kg/m2) and admits to smoking two packs per day for 30 years. Physical examination reveals a blood pressure of 190/110 mm Hg. An echocardiogram shows conspicuous left ventricular hypertrophy. A renal biopsy discloses pathologic changes in small renal arteries, including "onion-skinning" and fibrinoid necrosis. The Congo red stain is negative. Laboratory studies show hematocrit of 40%, hemoglobin of 18.7 g/dL, serum cholesterol of 250 mg/dL, BUN of 45 mg/dL, and serum creatinine of 5.5mg/dL. Which of the following is the most likely underlying cause of chronic renal failure in this patient? (A) Amyloid nephropathy (B) Chronic pyelonephritis (C) Congestive heart failure (D) Cushingsyndrome (E) Malignant hypertension

48. The answer is E: Renin. Renal artery stenosis causes cells of the juxtaglomerular apparatus to release renin, which induces aldosterone-mediated retention of sodium and water by the kidney (renovascular hypertension). In cases of unilateral renal artery stenosis, the level of renin in the renal vein of the ischemic kidney is elevated, whereas it is normal in the contralateral kidney. Renal artery stenosis is caused by atherosclerosis in adults, but in children it reflects fibromuscular dysplasia of the renal artery. Aldosterone (choice A), angiotensin (choice B), and plasminogen (choice D) are not synthesized in the kidney. Erythropoietin (choice C) influences the production of red blood cells. Diagnosis: Renovascular hypertension

48. A 58-year-old man with a history of hyperlipidemia and high blood pressure presents to the emergency room for evaluation of headaches and blurred vision. His blood pressure is 200/115mmHg, and pulse is 95 per minute. Funduscopic examination reveals several small retinal microaneurysms and cotton-like zones of retinal edema and necrosis. Intravenous pyelography discloses small kidneys bilaterally. Renal arteriography shows stenoses of both renal arteries. Hypertension in this patient is caused by the renal release of which of the following hormones? (A) Aldosterone (B) Angiotensin (C) Erythropoietin (D) Plasminogen (E) Renin

49. The answer is C: Hemolytic uremic syndrome (HUS). HUS features microangiopathic hemolytic anemia and acute renal failure, with little or no evidence for significant vascular dis- ease outside the kidneys. It is the most common cause of acute renal failure in children. Major causes for HUS are Shiga tox- in-producing strains of Escherichia coli, which are ingested in contaminated food. The toxin injures endothelial cells, thereby setting in motion the sequence of events that produces thrombotic microangiopathy. Patients present with hemorrhagic diarrhea and rapidly progressive renal failure. Postinfectious glomerulonephritis (choice A) follows streptococcal infections and is not characterized by acute renal failure. Diagnosis: Hemolytic uremic syndrome

49. A 6-year-old child develops fever, abdominal pain, and bloody diarrhea. Several other children in the neighborhood had similar symptoms. The common feature was traced to eating hamburgers at a fast food restaurant. The clinical course is complicated by the development of acute renal failure. Which of the following is the most likely diagnosis? (A) Acute postinfectious glomerulonephritis (B) Churg-Strauss syndrome (C) Hemolytic uremic syndrome (D) Malignanthypertension (E) Polyarteritis nodosa

5. The answer is E: Nephrotic syndrome. This patient has minimal change glomerulopathy with nephrotic syndrome. The nephrotic syndrome is characterized by heavy proteinuria (>3.5g protein per 24 hours), hypoalbuminemia, hyperlipidemia, and edema. In minimal change glomerulopathy, there is effacement of visceral epithelial cell (podocyte) foot processes, which allows protein to be lost from the plasma into the urine (proteinuria). The other choices are characterized by morphologic changes in glomeruli. Diagnosis: Nephrotic syndrome, minimal change disease

5. A 12-year-old girl complains of swelling of her eyelids, abdomen, and ankles. She had been in good health until several months ago, when she gained some weight and noted swelling of her lower legs. An X-ray film of the chest shows bilateral pleural effusions, without evidence of lung disease. Urinalysis reveals heavy proteinuria (8 g per 24 hours) without hematuria. A percutaneous needle biopsy of the kidney discloses no morphologic abnormalities by light microscopy. Which of the following best describes this patient's medical condition? (A) Amyloid nephropathy (B) Focal segmental glomerulosclerosis (C) Hereditary nephritis (D) Membranous glomerulopathy (E) Nephrotic syndrome

50. The answer is D: Henoch-Schönlein purpura. Henoch- Schönlein purpura is the most common type of childhood vasculitis and is caused by vascular localization of immune complexes containing predominantly IgA. The glomerular lesion is identical with that of IgA nephropathy. Hemolytic uremic syndrome (choice C) is caused by exposure to Shiga toxin-producing strains of Escherichia coli and is not associated with angiopathy outside of the kidney. The other choices are not typically associated with rash. Diagnosis: Henoch-Schönlein purpura

50. A 5-year-old girl presents with the sudden onset of diffuse arthralgias and skin rash. Physical examination shows a violaceous maculopapular rash on the lower torso. Urinalysis discloses oliguria and 2+ hematuria. Urine cultures are negative. This child's clinical presentation is commonly associated with which of the following diseases? (A) Bergerdisease (B) Goodpasture syndrome (C) Hemolytic uremic syndrome (D) Henoch-Schönleinpurpura (E) Polyarteritis nodosa

51. The answer is D: Renal carcinoma (RCC). RCC is the most common cancer of the kidney, accounting for 90% of kidney cancers. Most cases of RCC are sporadic, but about 5% are inher- ited. The 5-year survival is 90% if the RCC has not extended beyond the renal capsule; survival drops to 30% if there are dis- tant metastases. The tumor spreads most frequently to the lung and the bones. Oncocytoma and angiomyolipoma (choice A) are often difficult to differentiate from RCC by imaging techniques. Tumors such as nephroblastoma (choice C) and Wilms tumor (choice E) occur in the pediatric age group. Diagnosis: Renal cell carcinoma

51. A 50-year-old man is found to have blood in his urine during a routine checkup. He is otherwise in excellent health, except for a mild microcytic, hypochromic anemia. An enlarged right kidney is found on X-ray examination, and CT scan reveals a renal mass of irregular shape, measuring 6cm in diameter. Which of the following is the most likely diagnosis? (A) Angiomyolipoma (B) Metastatic carcinoma (C) Nephroblastoma (D) Renal cell carcinoma (E) Wilms tumor

52. The answer is D: VHL. Clear cell carcinoma is the most common type of RCC. The cytoplasm appears clear because it is rich in glycogen and fat, which are washed out during histo- logic processing of the tissue. Loss of one allele of the VHL gene occurs in virtually all (98%) of sporadic clear cell RCC, and mutations in the gene are found in more than half of these tumors. Thus, the evidence strongly suggests that loss of the tumor suppressor function of the VHL gene product is an important event in the genesis of clear cell RCC. WT1 is also a tumor suppressor gene, but it is implicated in the develop- ment of Wilms tumor (choice E). Diagnosis: Renal cell carcinoma

52. For the patient described in Questions 51, a fine-needle aspiration of the renal mass shows glycogen-rich tumor cells. Molecular studies would most likely identify mutations in which of the following growth regulatory genes? (A) ADPKD (B) IGF-2 (C) PAX6 (D) VHL (E) WT1

53. The answer is E: Wilms tumor. This malignant neoplasm of embryonal nephrogenic elements is composed of elements that resemble normal fetal tissue, including (1) metanephric blastema, (2) immature stroma (mesenchymal tissue), and (3) immature epithelial elements. It is the most frequent abdominal solid tumor in children, with a prevalence of 1 in 10,000. Wilms tumor usually presents between 1 and 3 years of age, and 98% occur before 10 years of age. In most instances of Wilms tumor, the neoplasm is sporadic and unilateral. How- ever, in 5% of cases, it arises in the context of several congenital syndromes. Choices A, B, and D are not renal tumors. Renal cell carcinoma (choice C) is a tumor of adults. Diagnosis: Wilms tumor

53. The mother of a 12-month-old boy palpates a mass on the right side of the infant's abdomen. The surgical specimen is shown. Microscopically, the tumor is composed of multiple elements, including blastemal, stromal, and epithelial tissues. Which of the following is the most likely diagnosis? (A) Ganglioneuroma (B) Neuroblastoma (C) Renal cell carcinoma (D) Teratocarcinoma (E) Wilms tumor

54. The answer is D: Neuroblastoma. Abdominal masses in children include Wilms tumor (choice E), neuroblastoma, and multicystic renal dysplasia. Of these, only neuroblastoma secretes catecholamines and causes elevation of vanillyl mandelic acid in the urine. Diagnosis: Neuroblastoma

54. The parents of a 6-month-old girl palpate a mass on the left side of the child's abdomen. Urinalysis shows high levels of vanillyl-mandelic acid. A CT scan reveals an abdominal tumor and bony metastases. Which of the following is the most likely diagnosis? (A) Dysgerminoma (B) Ganglioneuroma (C) Immature teratoma (D) Neuroblastoma (E) Wilms tumor

55. The answer is E: Renal tubules. Renal cell carcinoma originates from renal tubules or ductal epithelial cells. The tumor is composed of cuboidal cells that form either tubules or solid nests. It accounts for 90% of all renal cancers and more than 11,000 cases a year in the United States. Most of these tumors are of the clear cell type and almost all show loss of one allele of the von Hipple-Lindau (VHL) gene. Diagnosis: Renal cell carcinoma

55. A 50-year-old man is found to have blood in his urine during a routine checkup .A CBC shows microcytic, hypochromic anemia. An enlarged right kidney is found on X-ray examination. A CT scan reveals a renal mass of irregular shape measuring 5cm in diameter. The nephrectomy specimen is shown. This malignant neoplasm most likely originates from which of the following tissues in the kidney? (A) Glomeruli (B) Juxtaglomerular cells (C) Lymphatics (D) Renalpapillae (E) Renal tubules

56. The answer is B: Leukemia. Any condition associated with elevated levels of uric acid in the blood may cause tubular deposits of uric acid crystals (see photomicrograph). The classic chronic disease in this category is primary gout. Chronic urate nephropathy caused by gout is characterized by tubular and interstitial deposition of crystalline monosodium urate. Acute urate nephropathy can also be caused by increased cell turnover. For example, leukemic patients who undergo chemotherapy develop hyperuricemia due to the increased formation of uric acid from nucleic acids released from destroyed leukemic cells. This oversupply of urates may cause renal changes similar to those of gout or other forms of hyperuricemia. The other choices are not associated with hyperuricemia. Diagnosis: Acute renal failure, urate nephropathy

56. A 56-year-old woman presents with acute renal failure. A frozen section of a renal biopsy demonstrates birefringent, intratubular deposits of uric acid crystals (shown in the image). This finding suggests that the patient has been treated recently for which of the following underlying conditions? (A) Chronic hepatitis B (B) Leukemia (C) Porphyria (D) Rheumatoid arthritis (E) Ulcerative colitis

57. The answer is A: Calcium oxalate. Nephrolithiasis and urolithiasis are stones within the collecting system of the kidney (nephrolithiasis) or elsewhere in the collecting system of the urinary tract (urolithiasis). The pelves and calyces of the kidney are common sites for the formation and accumulation of calculi. Calcium oxalate stones are the most common (80%) form of kidney stones in the United States, whereas calcium phosphate stones (choice B) are more common in England. Both are usually related to idiopathic calciuria and increased absorption of calcium in the intestine. Magnesium ammonium phosphate stones (choice D) are typically formed in urine made alkaline by urea splitting bacteria. Uric acid stones, found in 25% of patients with gout, are smooth, yellow, hard, and radiolucent. Cystine stones (choice C) occur in children with hereditary cystinuria, an inborn error of amino acid metabolism marked by an excess of cystine in the urine. Diagnosis: Nephrolithiasis

57. A 46-year-old man with no past medical history presents with excruciating episodic (colicky) right flank pain. A renal stone is passed. In the United States, this stone is most likely composed of which of the following? (A) Calcium oxalate (B) Calcium phosphate (C) Cystine (D) Magnesium ammonium phosphate (E) Uric acid

58. The answer is E: Urinary tract obstruction. Obstructive uropathy is caused by structural or functional abnormalities in the urinary tract that impede urine flow, which may cause renal dysfunction (obstructive nephropathy) and dilation of the collecting system (hydronephrosis). In this neglected patient, severe prostatic hyperplasia caused urinary tract obstruction. In early hydronephrosis, the most prominent microscopic finding is dilation of the collecting ducts, followed by dilation of the proximal and distal convoluted tubules. Grossly, progressive dilation of the renal pelves and calyces occurs, and atrophy of the renal parenchyma ensues. The other choices do not cause bilateral hydronephrosis. Diagnosis: Hydronephrosis

58. A 75-year-old homeless man is brought to the emergency room in a coma. Upon admission to the hospital, the BUN is 74 mg/ dL, and the creatinine is 6.5 mg/dL. He dies thereafter, and an autopsy reveals abnormal kidneys (shown in the image). The pathogenesis of this disease is most likely related to which of the following? (A) Acutepyelonephritis (B) Amyloidosis (C) Polycystic kidney disease (D) Systemichypertension (E) Urinary tract obstruction

59. The answer is E: Infection. In most cases, the presence of a urinary stone is associated with an increased blood level and urinary excretion of its principal component. Most kidney stones contain calcium complexed with oxalate or phosphate, or a mixture of these anions. However, some 15% of stones result from infection. In the presence of urea-splitting bacteria, the resulting alkaline urine favors the precipitation of magnesium ammonium phosphate (struvite) and calcium phosphate (apa- tite). They form the so-called staghorn calculi that fill the entire pelvis and calices. Whereas the other choices may by associated with nephrolithiasis; they do not appear as staghorn calculi. Diagnosis: Nephrolithiasis

59. A 55-year-old man dies of chronic renal failure. Examination of his kidneys at autopsy reveals a "staghorn" calculus. Which of the following best describes the pathogenesis of this renal stone? (A) Gout (B) Hereditary cystinuria (C) Hypercalcemia (D) Hyperparathyroidism (E) Infection

6. The answer is D: Postinfectious glomerulonephritis. This case is illustrative of nephritic syndrome in the setting of poststreptococcal glomerulonephritis. Nephritic syndrome is characterized by hematuria (either microscopic or visible grossly), variable degrees of proteinuria, and decreased glomerular filtratio. It results in elevations of serum blood urea nitrogen and creatinine, as well as oliguria, salt and water retention, edema, and hypertension. Glomerular diseases associated with the nephritic syndrome are caused by inflammatory changes in glomeruli, such as infiltration by leukocytes, hyperplasia of glomerular cells, and, in severe lesions, necrosis. The other choices are not related to streptococcal pharyngitis. Choices B, C, and E do not present with hematuria. Diagnosis: Postinfectious glomerulonephritis, nephritic syndrome

6. An 8-year-old boy presents with headaches, dizziness, and malaise. He was seen for a severe sore throat 2 weeks ago. Physical examination reveals facial edema. The blood pressure is 180/110 mm Hg. A 24-hour urine collection demonstrates oliguria, and urinalysis shows hematuria. Which of the following best describes this patient's medical condition? (A) Hereditary nephritis (B) Membranous glomerulonephritis (C) Minimal change nephritic syndrome (D) Postinfectious glomerulonephritis (E) Thin glomerular basement membrane nephropathy

60. The answer is B: Hydronephrosis. Obstructive uropathy is caused by structural or functional abnormalities in the urinary tract that impede urine flow, which may cause renal dysfunction (obstructive nephropathy) and dilation of the collecting system (hydronephrosis). Metastatic cervical cancer is a frequent cause of bilateral ureteral obstruction and resulting hydronephrosis. Polycystic kidney disease (choice C) is a congenital disease. The other choices are not related to obstruction of the lower urinary tract. Diagnosis: Hydronephrosis

60. A 36-year-old woman presents with advanced cervical carcinoma, and a CT scan shows widespread pelvic spread. If this condition is not surgically corrected, the patient's kidneys will most likely develop which of the following conditions? (A) Acute vasculitis (B) Hydronephrosis (C) Polycystic kidney disease (D) Staghorncalculi (E) Tubulointerstitial nephritis

61. The answer is E: Thrombotic microangiopathy. Thrombotic microangiopathy has a variety of causes, all of which cause endothelial damage that initiates a final common pathway of vascular changes. Injured endothelial surfaces promote thrombosis, which may cause focal ischemic necrosis. Pathologic changes in the kidney are comparable to those seen in malignant hypertensive nephropathy. These lesions include arteriolar fibrinoid necrosis, arterial edematous intimal expansion, glomerular congestion, and vascular thrombosis. Patients typically present with thrombocytopenia, hypertension, and renal failure. The causes of thrombotic microangiopathy include infections, drugs (e.g., cisplatin chemotherapy), autoimmune diseases, malignant hypertension, and pregnancy. Alterations in blood flow lead to mechanical fragmentation of erythrocytes (schistocytes). Henoch-Schönlein purpura (choice B) does not have microan- giopathic features that lead to anemia or thrombocytopenia. Diagnosis: Thrombotic microangiopathy

61. A 34-year-old man undergoing cisplatin-based chemotherapy complains of a 1-week history of increasing fatigue and headaches. He also reports seeing blood in his urine. Blood pressure is 150/100mmHg. Physical examination reveals diffuse purpura over his upper trunk and arms. Laboratory studies show elevated levels of BUN and creatinine, and 24-hour urinalysis reveals hematuria and oliguria. Urine cultures are negative. A CBC demonstrates severe anemia (hematocrit 28%) and thrombocytopenia (50,000/μL). The direct Coombs test is negative. A peripheral blood smear reveals schistocytes. Which of the following is the most likely cause of acute renal failure in this patient? (A) ANCA glomerulonephritis (B) Henoch-Schönlein purpura (C) Nephrotoxic acute tubular necrosis (D) Polyarteritisnodosa (E) Thrombotic microangiopathy

62. The answer is B: Papillary necrosis. Patients with sickle cell disease develop painful, episodic crises. The rigidity of sick- led erythrocytes results in obstruction of the microcirculation, with subsequent hypoxia and ischemic injury in many organs. Patients experience severe pain, especially in the chest, abdomen, and bones. Sickle cell nephropathy is the most common organ manifestation of sickle cell disease. The interstitial tissue in which the vasa recta course has a low oxygen tension. As a result, in patients with sickle cell disease, erythrocytes in the vasa recta tend to sickle and occlude the lumina. Infarcts in the medulla and papillae ensue, sometimes severe enough to cause renal papillary necrosis. The glomeruli are conspicuously congested with sickle cells. None of the other choices are direct complications of sickle cell anemia. Choices C, D, and E do not cause papillary necrosis, and acute pyelonephritis (choice A) does so only rarely. Diagnosis: Sickle cell disease, papillary necrosis

62. A 16-year-old black girl with sickle cell anemia presents to the emergency room because she is experiencing severe bone pain (avascular necrosis). An abdominal CT scan shows evidence of splenic infarcts. Which of the following renal diseases is a direct complication of this patient's vasoocclusive disease? (A) Acutepyelonephritis (B) Papillary necrosis (C) Polycystic kidney disease (D) Urate nephropathy (E) Urolithiasis

63. The answer is A: ABO antigens. Incompatible ABO histo-blood group antigens, which are expressed on endothelial cells and erythrocytes, are absolute barriers to a successful transplant. ABO-incompatible grafts encounter preformed circulating antibodies, which bind to endothelial cells and cause immediate (hyperacute) rejection. By contrast, the most common patterns of acute and chronic rejection are caused primarily by donor-recipient differences in HLA molecules encoded by the major histocompatibility complex. These molecules are expressed on most cell surface membranes. Other causes of transplant rejection tend to be chronic, because they do not involve preformed antibodies. None of the other choices mediates hyperacute graft rejection. Diagnosis: Graft-versus-host disease

63. A 35-year-old woman with end-stage renal disease of unknown etiology is transplanted with a cadaver kidney. The patient develops oliguia shortly after transplantation and a renal biopsy shows immediate (hyperacute) rejection. Immunosuppression improves renal function. Which of the following represents the principle target for immune attack directed against this patient's allograft? (A) ABO antigens (B) Bacterial antigens (C) Glomerular basement membrane antigens (D) β2-Microglobulin (E) Urothelium

64. The answer is B: Fibromuscular dysplasia. The most frequent cause of renovascular hypertension in children is fibromuscular dysplasia. This disease is characterized by fibrous and muscular stenosis of the renal artery. Areas of medial thick- ening alternate with areas of atrophy producing a "string of beads" pattern in angiograms. Stenosis or total occlusion of a main renal artery produces hypertension that is potentially curable by reconstitution of the arterial lumen. Buerger disease (choice A) and Kawasaki disease (choice D) do not typically affect the renal arteries. Giant cell arteritis (choice C) and Takayasu arteritis (choice E) may cause secondary hypertension by producing sclerotic thickening of the renal arteries; however, these vascular diseases are distinctly uncommon in children. Diagnosis: Fibromuscular dysplasia

64. A 12-year-old girl complains of headaches and blurred vision. She has a history of high blood pressure, but is not currently taking medication. Her blood pressure is 160/95mmHg and pulse is 95 per minute. Funduscopic examination reveals small retinal microaneurysms and cotton-like zones of retinal edema and necrosis. She is hospitalized for further evaluation. Renal arteriography shows segmental stenoses forming multiple ridges that project into the lumen. What is the most likely cause of secondary hypertension in this young patient? (A) Buergerdisease (B) Fibromuscular dysplasia (C) Giant cell arteritis (D) Kawasakidisease (E) Takayasu arteritis

7. The answer is D: Red blood cell casts. Injury to the glomerular capillaries results in spillage of protein and blood cells into the urine. Hematuria is also seen in patients with bleeding from the lower urinary tract. However, RBC casts in the urine sediment originate from erythrocytes compacted during pas- sage through the renal tubules and denote a renal origin of hematuria. Diagnosis: Postinfectious glomerulonephritis, nephritic syndrome

7. What finding on microscopic urinalysis indicates that hematuria in the patient described in Question 6 is caused by a renal process, rather than bleeding from another site in the urinary tract? (A) Bloodclots (B) Hemoglobin crystals (C) Phagocytosedhemoglobin (D) Red blood cell casts (E) White blood cell casts

8. The answer is A: Amyloid nephropathy. The clinicopathologic findings establish a diagnosis of multiple myeloma. The neoplastic plasma cells typically secrete a homogeneous immunoglobulin chain, which can be detected in serum or urine by electrophoresis. Amyloid nephropathy is caused by the deposition of secreted lambda or kappa light chains in the glomerular basement membranes and mesangial matrix. Amorphous acellular material expands the mesangium and obstructs the glomerular capillaries. Deposits of AL amyloid may also appear in the tubular basement membranes and in the walls of renal vessels. Renal amyloidosis usually presents with nephrotic syndrome. The deposits of amyloid may take on a nodular appearance, reminiscent of the Kimmelstiel-Wilson lesion of diabetic glomerulosclerosis (choice E). However, amyloid deposits are not PAS positive and are identifiable by Congo red staining with characteristic apple-green birefringence. IgA nephropathy (choice C) and membranous glomerulonephritis (choice D) are unrelated to light-chain disease. Diagnosis: Amyloid nephropathy, multiple myeloma

8. A 60-year-old man complains of chronic back pain and fatigue, excessive urination, and increased thirst. X-ray examination reveals numerous lytic lesions in the lumbar vertebral bodies. Laboratory studies show hypoalbuminemia, mild anemia, and thrombocytopenia. Urinalysis displays 4+ proteinuria. A monoclonal immunoglobulin light-chain peak is demonstrated by serum electrophoresis. A bone marrow biopsy discloses foci of plasma cells, which account for 20% of all hematopoietic cells. A kidney biopsy is obtained (shown in the image). Which of the following is the most likely cause of nephrotic syndrome in this patient? (A) Amyloid nephropathy (B) Crescentic glomerulonephritis (C) IgA nephropathy (Berger disease) (D) Membranous glomerulonephritis (E) Nodular glomerulosclerosis (Kimmelstiel-Wilson disease)

9. The answer is A: Amyloid nephropathy. Amyloidosis is a well- known complication of chronic inflammatory disorders, such as chronic suppurative bronchiectasis, rheumatoid arthritis, or osteomyelitis. These conditions stimulate the production of amyloid from the serum amyloid A (SAA) protein, an acute- phase reactant secreted by the liver. The kidneys, liver, spleen, and adrenals are the most common organs involved. Renal amyloidosis leads to nephrotic syndrome (as in this case) and renal failure. Nephrotic syndrome caused by deposition of SAA amyloid is clinically indistinguishable from that related to AL amyloid. The other choices have not been linked to chronic inflammatory conditions. Wegener granulomatosis (choice E) affects the lungs and kidneys, but bronchiectasis is not a feature of this disease. Diagnosis: Amyloid nephropathy, bronchiectasis

9. A 49-year-old man with a history of heavy smoking presents with a 5-year history of shortness of breath and cough and production of abundant foul-smelling sputum. A pulmonary work-up demonstrates chronic bronchiectasis. Laboratory studies reveal hypoalbuminemia and hyperlipidemia. Urinalysis shows heavy proteinuria (>4 g per day). Which of the following is the appropriate diagnosis? (A) Amyloid nephropathy (B) Berger disease (IgA nephropathy) (C) Focal segmental glomerulosclerosis (D) Minimal change glomerulopathy (E) Wegener granulomatosis

45. The answer is D: Nephrosclerosis. Hypertensive nephrosclerosis (so-called benign nephrosclerosis) leads to obliteration of glomeruli and may lead to end-stage kidney disease. Hypertensive nephrosclerosis is identified in approximately 15% of patients with benign hypertension. Even mild-to-moderate hypertension causes hypertensive nephrosclerosis. On histologic examination, most glomeruli are hyalinized, and the tubules are either atrophic or replaced by fibrous tissue. Arterioles exhibit concentric hyaline thickening of the wall, often with the loss of smooth muscle cells or their displacement to the periphery. This arteriolar change is termed hyaline arteriolosclerosis. The other choices are not related to hypertension. Diagnosis: Nephrosclerosis, benign; systemic hypertension

A 70-year-old obese woman (BMI = 34 kg/m2) presents with a 3-month history of progressive renal insufficiency. She has a longstanding history of hypertension. An intravenous pyelogram shows that both kidneys are small, and the pelves and calyces appear dilated. The patient subsequently suffers a massive stroke and expires. Examination of the kidneys at autopsy reveals symmetrically shrunken small kidneys, with a uniformly finely granular surface (shown in the image). Which of the following is the appropriate diagnosis? (A) Amyloidosis (B) Hydronephrosis (C) Ischemic acute tubular necrosis (D) Nephrosclerosis (E) Tubulointerstitial nephritis