Chapter 20
Kidney Learning Objectives: glomerular, tubular, and congenital anomalies
Glomerular Diseases (906-935)
1. What is azotemia? At what stage of renal failure does it occur?
 Azotemia is elevated BUN and creatinine caused by decreased GFR
 During unchecked renal failure, azotemia first appears in the insufficiency phase (20-50%)
2.
What is uremia? Secondary signs? At what stage of renal failure does it occur?
Uremia is a failure of renal excretory function as well as many metabolic and endocrine
alterations resulting from renal damage. Secondary gastroenteritis, peripheral neuropathy,
and uremic fibrinous pericarditis are common.
 chronic renal failure (5-20% of normal function)

3. What is the difference between nephritic syndrome and nephrotic syndrome?
 Nephritic syndrome is characterized by hematuria and mild proteinuria
i. Post-S. pyogenes infection
 Nephrotic syndrome is characterized by hyperlipidemia and heavy proteinuria
4. What symptoms result from renal tubular defects?
 Polyuria, nocturia, and electrolyte disorders (e.g. acidosis) result from renal tubular defects
5. Describe the immune deposition pattern in the glomerulus in Heymann nephritis:
 Under immunofluorescence microscopy, the pattern is that of granular deposition
 The culpable antibody reacts with an antigen complex located on the subepithelial aspect
(between epithelial cells and GBM) of the basement membrane
6. What antigen in collagen is responsible for the types of anti-GBM antibody-induced
glomerulonephritis, which may lead to Goodpasture syndrome?
 Part of the noncollagenous domain (NC1) of the a3 chain of type IV collagen triggers antiGBM glomerulonephritis
 These diseases exhibit linear deposition on immunofluorescence microscopy
7. When circulating antigen-antibody complexes lodge in the glomerulus, in which part do they
stick? How does this appear under immunofluorescence? Why might this occur?
 Circulating immune complex glomerulonephritis happens when these complexes lodge
subendothelially (between endothelium and GBM) or subepithelially (rare)
 These appear as granules, just like in Heymann nephritis
 SLE or viral hepatitis cause a “shower” of antigens & antibodies
8. What are the two major histologic characteristics of progressive renal damage?
 Focal segmental glomerulosclerosis is the first characteristic: it is initially an adaptive
enlarging response by surviving nephrons, but soon leads to sclerosis and proteinuria.
i. Hypertension and hypertrophy => cell injury, coagulation, and mesangial cell
hyperplasia=> sclerosis and proteinuria
 Tubulointerstitial fibrosis correlates best with decline in function. The process is kicked off
by proteinuria, which causes direct injury to and activation of tubular cells. This activation
consists of adhesion molecules, cytokines, chemokines, and growth factors, which cause
fibrosis
9. Which microbe causes glomerulonephritis? How does it appear under Light, Fluorescence, and
Electron microscopes? Clinical symptoms?
 Certain strains of group A, β-hemolytic streptococcus (pyogenes) can cause poststreptococcal
glomerulonephritis
 Diffuse swelling (L), granular IgG (F), in subepithelial humps (E);
i. like in #5? Immune interaction type is unknown
 Nephritic syndrome!
10. What is common to all three categories of rapidly progressive glomerulonephritis (RPGN)?
Describe them:
 Crescents are the most common histologic sign of rapidly progressive (crescenteric)
glomerulonephritis
 Goodpasture syndrome -- Anti-GBM linear deposition (see #6),
 Henoch-Schӧnlein purpura or lupus nephritis -- [Subendothelial] immune complex
deposition (#7)
 Pauci-immune type
i. usually AntiNeutrophil Cytoplasmic Antibodies (ANCAs) are present in the sera
ii. cases are usually isolated and idiopathic
11. What is most likely affecting a patient with (among other problems) sodium and water
retention, oval fat bodies in their urine, and renal vein thrombosis?
 These are all consequences of nephrotic syndrome, (along w/proteinuria and
hypoalbuminemia)
12. What are the most important causes of nephrotic syndrome (6)? Systemic + Primary
 Diseases that increase permeability of glomerular capillaries
 Systemic causes: diabetes, amyloidosis, and SLE
 Primary causes: minimal-change disease, membranous glomerulopathy, focal segmental
glomerulosclerosis
[My Clean Death Made God For Sure Glad]
13. A uniform and diffuse thickening of the glomerular capillary wall with subepithelial deposits and
no infection points to which disease?
 Membranous nephropathy is similar to postinfectious glomerulonephritis in appearance, but
without leukocyte infiltration. It is an autoimmune disorder (Heymann, see #5)
14. Which cause of nephrotic syndrome is more common in children than in adults?
 Minimal-change disease is most common between 2 and 6 years of age
15. How would you treat a patient with normal glomeruli but effacement of podocytes?
 Minimal change nephropathy features thinned and shortened podocytes, and it can be
treated with corticosteroids
16. Which kidney disease commmonly occurs in those with HIV, heroin addiction, sickle cell disease,
and mutations in the slit diaphragm proteins nephrin, podocin, α-actinin 4, or TRPC6?


focal segmental glomerulosclerosis (FSGS)
NPHS1 is the gene for nephrin, NPHS2 is the gene for podocin, both are autosomal recessives
17. How would you diagnose retraction and collapse of the entire glomerular tuft? Who commonly
gets this? What other signs would they have?
 This is collapsing glomerulopathy, a variant of FSGS
 common in the HIV+
 tuboreticular inclusions
18. What is a synonym for membranoproliferative glomerulonephritis (besides MPGN)? What
causes MPGN? What other disease does it resemble?
 mesangiocapillary glomerulonephritis
 autoimmune, idiopathic
 like RPGN but without their pathognomic sign
[just change one letter in the anagram]
19. How can you differentiate subtypes of MPGN?
 Type 1 will show subendothelial deposits on electron microscopy, caused by antibodyinduced complement activation (decreased C3)
 Type 2 will show dense deposits in the GBM, and it occurs in adults with α1-antitrypsin
deficiency and chronic immune complex disorders
20. What is another name for IgA nephropathy?
 IgA nephropathy is also known as Berger Disease
21. How does IgA nephrophathy differ from MPGN (2, histologic and clinical)?
 IgA nephropathy features widening and focal proliferation of mesangial cells only, instead of
MPGN’s splitting and mesangial & endocapillary proliferation
 IgA nephropathy usually results from a respiratory or GI infection, remits and relapses
22. Describe Alport syndrome:
 Usually X-linked, causes hematuria with progression to chronic renal failure, nerve deafness,
lens discoloration and posterior cataracts, basket-weave appearance microscopically
23. How would you diagnose a patient with thinning cortex, obliterated glomeruli, uremic
pericarditis, and hyperparathyroidism?
 These are all symptoms of chronic glomerulonephritis.
24. What is the most common cause of Chronic Glomerulonephritis?
 Rapidly progressive/crescenteric GN is the most common cause of chronic G.
25. A single disease is likely manifested by both Henoch-Schӧnlein purpura and which other
disease?
 IgA nephropathy seem to be manifestations of the same disease
26. What causes diabetic nephropathy (2)? What are the renal signs of diabetic nephropathy?
 Glycosylation and hemodynamic effects of diabetes contribute to diabetic nephropathy
 Sclerosis and Basement membrane thickening
27. Essential mixed cryoglobulinemia is associated with which microbe?
 Essential mixed cryoglobulinemia is associated with hepatitis C infection
Tubular and Interstitial Diseases (935-955)
28. What is the most common cause of renal failure, characterized by acute diminuation of renal
function which often includes morphologic evidence of injury? 4 causes?
 Acute Kidney Injury is the most common cause of acute renal failure
 Ischemia, toxic injury, acute tubulointerstitial nephritis, and urinary obstruction
29. What is the big early and reversible result of ischemic AKI?
 Loss of cell polarity occurs rapidly, due to transfer of Na+/K+ ATPases to the luminal surfaces
of tubular cells
 High Na+ causes vasoconstriction by tuboglomerlar feedback
 Which in turn decreases GFR
30. How can you differentiate ischemic and toxic AKI?
 Both share the feature of tubular necrosis, however:
 Ischemic AKI has patchy necrosis in tubules and Tamm-Horsfall protein casts
 Toxic AKI tends to necrose most of the proximal convoluted and proximal straight tubules
i. HgCl2: calcification; CCl4: fatty change & necrosis; ethylene glyc: calcium oxalate
31. What are the three stages of AKI? How does the first stage appear clinically?
 Initiation, maintenance, and recovery are the three stages of AKI
 AKI presents in the initiation phase as oliguria b/c lowered GFR, but frequently either does
not change or even increases urine output until the maintenance phase hits, at which time
urine output plummets
32. How can you identify tubulointerstitial nephritis? [Microbio 63 crossover] What bacteria besides
E. coli cause pyelonephritis? What bug affects the immunocompromised?
 subtle inability to concentrate urine, salt wasting, and metabolic acidosis
 Other enterobacteriae: Proteus mirabilis, Klebsiella, Enterobacter, Streptococcus faecalis,
and Staphylococci
 Polyomavirus in the immunosuppressed/compromised (transplants!)
33. What allows bacteria to ascend the ureter into the renal pelvis (vesicoureteral reflux)? What
parts of the kidney are most commonly affected in the resulting intrarenal reflux?
 Incompetence of the vesicoureteral valve is necessary
 Intrarenal reflux most commonly infects the upper and lower poles of the kidney
34. What are 3 complications of acute pyelonephritis?
 Papillary necrosis: in people with diabetes and obstructive UTIs (mostly men)
i. Papillary necrosis can also be caused by analgesic nephropathy, sickle cell trait
 Pyonephrosis = total obstruction by pus
 Perinephric abcesses
35. Which two conditions involve the calyx?
 Only chronic pyelonephritis and analgesic nephropathy affect the calyx
[“da chronic” is analgesic]
36. What is the most likely cause of chronic pyelonephritis? What are the gross hallmarks of chronic
pyelonephritis? How is it different from chronic glomerulonephritis? What bacteria causes
xanthogranulomatous pyelonephritis?
 Reflux
 Irregular scarring, which is coarse and discrete, overlying deformed calyces
 Contrast to diffuse and symmetric scarring of chronic glomerulonephritis
 Proteus
i. Can often be confused with renal cell carcinoma
37. What drugs cause drug-induced interstitial nephritis? What are the 5 signs of acute druginduced interstitial nephritis? What’s the timeline? (Also see #11)
 Synthetic penicillins, antiboiotics, thiazides, NSAIDs, and allopurinol & cimetidine
 This condition causes fever, eosinophilia, hematuria, proteinuria, and leukocyturia
i. glomeruli are normal microscopically (except for NSAID cases, see #39)
[F*** HELP, i don’t need any drugs]
 Symptoms occur about 15 days/2 weeks after the use of the above drugs
38. What are the 2 principal signs of analgesic nephropathy and how do they occur? How can you
differentiate it from diabetes?
 The oxidative metabolites of phenacetin & the vasoconstriction of aspirin cause papillary
necrosis, which leads to cortical interstitial nephritis when urine outflow stops
 Analgesic papillary necrosis affects almost all papillae at various stages, while diabetic
papillary necrosis will all appear to be at the same stage
39. What oddball signs does NSAID nephropathy present with?
 acute interstitial nephritis and minimal change disease => nephrotic syndrome
40. When does acute urate nephropathy occur? Describe the crystals that form in chronic urate
nephropathy:
 Chemotherapy increases the death of cancer cells, causing crystals of urate to form from
their discarded nucleotides
 The variably birefringent needle-like crystals in chronic urate nephropathy form tophi that
can clog tubules
41. How do nonrenal malignant tumors affect the kidneys (4)?
 Bence Jones proteins from multiple myeloma are toxic to renal epithelial cells and form
tubular casts
 Amyloidosis, light chain deposition, and hypercalcemia also occur
Vascular Diseases
42. What are the two arterial lesions which occur in benign nephrosclerosis?
 Medial and intimal thickening as a response to hemodynamic changes/aging/genetic defects
 Hyaline deposition due to extravasation of plasma through injured endothelium
i. Often w/fibroelastic hyperplasia
43. How does malignant hypertension develop? What does it do to renal vasculature?
 Malignant hypertension may be due to a vicious cycle of renin release and vasoconstriction,
all kicked off by some original vascular damage
 The two key histologic alterations in malignant hypertension are fibrinoid necrosis of
arterioles and “onion skinning,” hyperplasia which is caused by concentric layering of
collagen and proteoglycan layers
i. Permeability=> high protein kills vascular walls, kidney attempts compensation
with proteoglycan
44. What hormone will be elevated in most people with renal artery stenosis?
 Renin will be elevated in those with renovascular hypertension (so ACE inhibitors are useful)
45. What causes renal artery stenosis? How should it be diagnosed?
 Atheromatous plaques (70%) in old men
 Fibromuscular dysplasia in young females
 Arteriography must be used to diagnose stenosis because it resembles essential hypertension
46. What are the three causes of thrombotic microangiopathies, and in turn, what are their causes?
 Consumption of Shiga-like toxins (typical Hemolytic-Uremic Syndrome [HUS])
 Atypical HUS:
i. inherited mutations of complement
ii. postpartum HUS
iii. other causes of endothelial injury, such as antiphospholipid syndrome
 Thrombotic thromocytopenic purpura (TTP)
i. Due to deficiency in vWF regulator ADAMTS13
47. What bacteria is most likely to cause typical hemolytic-uremic syndrome
 E. Coli produces shiga-like toxin (not the bacteria that sounds like the toxin)
48. How does typical HUS present clinically?
 sudden onset of bleeding (e.g. hematemesis and melena), severe oliguria, hematuria,
neurologic changes, plus hemolytic anemia and thrombocytopenia (petechiae)
49. What is the pentad of signs associated with TTP? When does it present?
 1) neurologic symptoms, 2) fever, 3) microangiopathic hemolytic anemia, 4)
thrombocytopenia, 5) renal failure
 usually presents in adults under 40
50. How would thrombotic microangiopathies look under the microscope?
 Splitting or reduplication of the basement membrane (“double countours”/”tram tracks”)
 “Onion-skinning” hyperplasia in the arterioles
[little onion thormbi on tram tracks]
51. Problems due to sickle cell (4):
 1) Hematuria, 2) diminished concentrating ability (hyposthenuria), 3) papillary necrosis,
4) proteinuria
52. What are the causes of diffuse cortical necrosis? What are the signs?
 Uncommon, but occurs after obstetric emergencies sucha as abrutio placenta, septic shock,
or extensive surgery
 Micro-thrombi cause ischemic necrosis and cortical destruction
Congenital Anomalies (955-967)
53. How can you identify a truly hypoplastic kidney (not due to disease)?
 A hypoplastic kidney shows no scars and has a reduced number of lobes a pyramids
i. This fun word: oligomeganephronia describes a subtype of hypoplastic kidney
54. What would you suspect if you saw islands of undifferentiated mesenchyme, with cartilage and
immature collecting ducts?
 These are characteristic signs of multicystic renal dysplasia, which can be uni- or bi-lateral
55. Which mutation causing autosomal dominant (adult) polycystic kidney disease would you
rather have?
 PKD2 is the milder (and rarer) mutation. Its gene product polycystin-2 serves as part of the
mechanosensory apparatus of tubular cells. (specifically, it’s a Ca++ channel)
56. What are some extrarenal complications of polycystic kidney disease?
 Many with polycystic kidney disease will also develop liver cysts, mitral valve prolapse, or
most worryingly get berry aneurysms and subarachnoid hemorrhages
57. How is autosomal recessive (childhood) polycystic kidney disease different?
 Besides the obvious, Cysts are smaller and radially arranged
 PKHD1: codes for fibrocystin, which is another component of tubule mechanosensation
58. Diagnose dilated papillary ducts in the medulla and small cysts lined by cuboidal/transitional
epithelium:
 This is medullary sponge kidney, which is benign
59. What is the most common cause of end stage renal disease in young people?
 Medullary cystic disease/nephronopthisis kills children and young people.
i. In contrast, ARPKD appears around the time of birth
60. How are congenital kidney defects inherited?
 Except for Alport syndrome (X-linked), kidney defects are autosomal recessive when they
appear in childhood, and autosomal dominant when they show up in adults
i. For adults, deletion or inactivation of the good allele takes time
61. Acquired/Dialysis-associated cystic disease predisposes patients towards what disease?
 Renal cell carcinoma
62. How can you tell cysts apart from tumors?
 Cysts have smooth contours and give fluid rather than solid signals on radiography
63. When do uric acid calculi form? How does uric acid influence the formation of other types
kidney stones?
 They are rare! Usually need low pH
 Uric acid crystals can cause “nucleation” and formation of calcium oxalate kidney stones even
without hypercalciuria
64. When do magnesium ammonium phosphate stones form?
 Magnesium ammonium phosphate stones are large and form as a result of infection by
microbes that convert urea to ammonia, like Proteus
65. How can hyperoxaluria occur?
 Vegetarians, enteric diseases (overabsorption), and people with hereditary primary oxaluria
are more prone to forming calcium oxalate renal calculi
66. What should you do about small adenomas in the kidneys?
 All renal adenomas should be regarded as potentially malignant until proven otherwise
67. How does Oncocytoma appear? Is it dangerous?
 Will have eosinophillic cells with many mitochondria. They are usually benign.
68. Name the major risk factors for renal cell carcinoma:
 Tobacco
 Von Hippel-Lindau (VHL) syndrome
 Hereditary/familial clear cell carcinoma
 Hereditary papillary carcinoma
 Acquired cystic disease
69. What does the VHL gene do?
 normally suppresses cancer by targeting hypoxia-inducible factor-1 for degredation.
Unchecked HIF-1 increases transcription of VEGF, TGF-α, and friends.
i. Mutated in clear cell carcinoma
70. Name and differentiate the three types of renal carcinoma:
 Clear cell carcinomas are usually well-differentiated and have delicate branching vasculature
 Papillary is what it sounds like
 chromophobe ditto
71. Why is renal cell carcinoma one of the great mimics of medicine?
 In order of likelihood: polycythemia, hypercalcemia, hypertension (renin), hepatic
dysfunction, feminization/masculinization, Cushing syndrome, eosinophilia, and amyloidosis