MKSAP Review – Glomerular Diseases

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MKSAP Review Glomerular Diseases

• Patrick Cunningham M.D.
• Section of Nephrology
• University of Chicago

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1

• A 35-year-old woman is evaluated for a 1-month
  history of progressive bilateral lower-extremity
  edema. She was diagnosed with type 1 diabetes
  mellitus 10 years ago. At her last office visit 4
  months ago, the urine albumin-creatinine ratio
  was 100 mg/g. Medications are enalapril, insulin
  glargine, insulin aspart, and low-dose aspirin.
• On physical examination, vital signs are normal
  except for a blood pressure of 162/90 mm Hg.
  Cardiopulmonary and funduscopic examinations are
  normal. There is 3 pitting edema of the lower
  extremities to the level of the thighs
  bilaterally.

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On kidney ultrasound, the right kidney is 12.2 cm
and the left kidney is 12.7 cm. There is no
hydronephrosis, and no kidney masses are seen.
Which of the following is the most appropriate
next step in this patients management? A.
Cystoscopy B. Kidney biopsy C. Spiral CT of the
abdomen and pelvis D. Observation
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RBC cast Hyaline cast
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Casts

• RBC casts glomerulonephritis
• Dysmorphic RBCs - glomerulonephritis
• WBC casts interstitial nephritis, pyelo
• Tubular cell casts ATN
• Granular casts nonspecific many ATN
• Muddy brown casts ATN
• Hyaline casts normal more with dehydration
• Oval fat bodies heavy proteinuria

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dysmorphic RBCs
muddy brown casts
tubular cell casts
oval fat body
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Diabetic Nephropathy

• Requires 10 years of diabetes before abnormal
  proteinuria, decreased GFR
• Near perfect correlation with retinopathy in type
  I, 67 in class II
• Heavy proteinuria, occasionally mild hematuria
• Goal BP 130/80, emphasize ACEI/ARB

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71

• A 33-year-old man comes for a follow-up
  evaluation. Two weeks ago, he underwent living
  unrelated kidney transplantation for end-stage
  kidney disease secondary to focal segmental
  glomerulosclerosis. Before kidney
  transplantation, he had been anuric and underwent
  dialysis. Current medications are tacrolimus,
  mycophenolate mofetil, prednisone, fluconazole,
  valganciclovir, and trimethoprim-sulfamethoxazole.
  
• On physical examination, temperature is normal,
  blood pressure is 138/98 mm Hg, pulse rate is
  80/min, and respiration rate is 15/min. BMI is
  29. Cardiopulmonary and funduscopic examinations
  are normal. There are staples at the kidney
  transplantation incision site in the lower right
  quadrant of the abdomen. There is 1 bilateral
  peripheral edema.

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Which of the following is the most likely
diagnosis? A. Diabetic nephropathy B. IgA
nephropathy C. Membranous nephropathy D.
Recurrent focal segmental glomerulosclerosis
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4

• A 25-year-old black man is evaluated in the
  emergency department for swelling of the feet and
  legs. He has a 5-year history of HIV infection
  for which he has refused treatment.
• On physical examination, temperature is normal,
  blood pressure is 128/74 mm Hg, pulse rate is
  88/min, and respiration rate is 12/min. BMI is
  23. Cardiopulmonary examination is normal.
  Abdominal examination is normal. There is 2
  presacral and 3 bilateral lower-extremity edema.

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Kidney ultrasound reveals bilaterally enlarged
kidneys with patchy areas of increased density.
The renal veins are patent. Kidney biopsy is
performed, and results are pending. Which of the
following is the most likely diagnosis? A.
Collapsing focal segmental glomerulosclerosis B.
IgA nephropathy C. Membranous nephropathy D.
Postinfectious glomerulonephritis
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Focal Segmental Glomerulosclerosis

• Nephrotic syndrome and CKD
• Much more common in African-Americans
• Can be associated with morbid obesity
• Immune complex negative
• Poor prognosis, some may respond to steroids
• A subset is collapsing glomerulopathy, seen with
  HIV
• May recur rapidly after transplant

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• A 45-year-old man with a 10-year history of HIV
  infection is evaluated in the hospital for an
  elevated serum creatinine level and abnormal
  urinalysis 5 days after admission for
  cytomegalovirus retinitis and latent syphilis. He
  has previously refused treatment with highly
  active antiretroviral therapy. Medications are
  ganciclovir, trimethoprim-sulfamethoxazole,
  metoprolol, intramuscular penicillin G
  benzathine, and low-molecular-weight heparin.
• On physical examination, temperature is normal,
  blood pressure is 150/88 mm Hg, pulse rate is
  88/min, and respiration rate is 16/min. BMI is
  22. Funduscopic examination reveals yellow-white,
  fluffy retinal lesions adjacent to retinal
  vessels. Cardiopulmonary examination is normal.
  Cutaneous and neurologic examinations are normal.
  There is trace bilateral lower-extremity edema.

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On kidney ultrasound, the right kidney is 11.6 cm
and the left kidney is 11.8 cm. The echotexture
of the renal parenchyma is diffusely increased.
There is no hydronephrosis, and no calculi or
solid masses are seen. Which of the following
is the most likely diagnosis? A. Acute
interstitial nephritis B. Collapsing focal
segmental glomerulosclerosis C. Immune
complexmediated glomerular nephritis D. Pigment
nephropathy
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Glomerulonephritis
Nephritic urine RBCs, RBC casts Low mod
proteinuria
Nephrotic urine No casts, few RBCs Heavy
proteinuria

• Diabetes
• Amyloid
• Membranous Nephropathy
• FSGS
• Minimal Change Disease
• Sometimes MPGN

C3, C4
Low
Normal

• Postinfectious
• Lupus nephritis
• MPGN (often Hep C)

ANCA ()
ANCA (-)

• Vasculitis
• Wegeners
• MPA
• Churg-Strauss

• IgA nepropathy
• Anti-GBM/Goodpastures

progress fast
progress slow
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• A 48-year-old man is evaluated for an abnormal
  urinalysis discovered last week during an
  examination for a workers compensation claim.
  Four months ago, he injured his back lifting a
  box at work. Since then, he has had chronic low
  back pain for which he takes acetaminophen daily.
  He has not worked for 3 months. He has no other
  symptoms or medical problems and takes no
  additional medications.
• On physical examination, temperature is normal,
  blood pressure is 145/88 mm Hg, pulse rate is
  92/min, and respiration rate is 12/min. BMI is
  33. The chest is clear to auscultation. He has
  full range of motion of the back without evidence
  of point tenderness. Neurologic examination is
  normal. There is 1 bilateral peripheral edema.
• Imaging studies of the lumbosacral spine and
  pelvis obtained last week are normal.

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Kidney biopsy is performed. Electron microscopy
of a kidney biopsy specimen reveals subepithelial
deposition of immune complexes. In addition to
adding a statin agent, which of the following is
the most appropriate management for this
patient? A. Lisinopril B. Mycophenolate
mofetil C. Plasmapheresis D. Prednisone and
cyclophosphamide
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Membranous Nephropathy

• Nephrotic syndrome and CKD
• Subepithelial immune complexes
• Decent response to immunosuppressives
• May be associated with solid tumors
• Associated with renal vein thrombosis

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• A 72-year-old man is admitted to the hospital
  with a 3-month history of progressive dyspnea,
  bilateral lower-extremity edema, and nonradiating
  pain in the right flank. He has gained 3.2 kg (7
  lb). He was diagnosed with benign prostatic
  hyperplasia 3 years ago. He has a 30-year history
  of hypertension. Medications are lisinopril and
  terazosin.
• On physical examination, temperature is 36.5 C
  (97.8 F), blood pressure is 158/92 mm Hg, pulse
  rate is 82/min, and respiration rate is 12/min.
  BMI is 31. Jugular venous pressure is normal.
  Cardiopulmonary examination reveals decreased
  breath sounds at both lung bases. Abdominal and
  neurologic examinations are normal.

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Serum and urine protein electrophoreses are
normal. A chest radiograph shows normal heart
size and bilateral pleural effusions. On kidney
ultrasound, the right kidney is 13.5 cm and the
left kidney is 12.0 cm. There is increased
echogenicity and no hydronephrosis. Doppler
ultrasound shows possible right renal vein
thrombosis. Which of the following is the most
likely diagnosis? A. IgA nephropathy B.
Membranous nephropathy C. Multiple myeloma D.
Obstructive nephropathy
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• A 68-year-old man is evaluated for a 3-month
  history of peripheral edema. He has recently
  noticed exertional dyspnea but has not had chest
  pain. He has no history of liver or kidney
  disease or deep venous thrombosis. He does not
  drink alcoholic beverages or smoke cigarettes.
  His only medication is a multivitamin.
• On physical examination, temperature is normal,
  blood pressure is 132/77 mm Hg, pulse rate is
  80/min, and respiration rate is 18/min. BMI is
  29. Funduscopic examination is normal. Cardiac
  examination reveals an S3 and a grade 2/6
  holosystolic murmur at the left sternal border
  that radiates to the cardiac apex. Pulmonary
  examination reveals bilateral basilar crackles.
  Tongue is enlarged. There are ecchymoses on the
  arms and legs. Hepatomegaly is present. There is
  2 bilateral peripheral edema and normal
  sensation in the extremities.

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Urine immunoelectrophoresis shows a paraprotein ?
spike. Chest radiograph shows an enlarged cardiac
silhouette. On kidney ultrasound, the kidneys are
12.5 cm bilaterally. Which of the following
diagnostic studies should be performed next? A.
Abdominal fat pad biopsy B. Bone marrow
biopsy C. Kidney biopsy D. Liver biopsy
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Paraprotein-assoc. renal diseases

• Albuminuric
• Amyloid Congo Red
• Light chain deposition diseases
• Other rarer GNs

• Nonalbuminuric
• Cast neph-ropathy/myeloma kidney
• Hypercalcemia
• Uric acid nephropathy

All may have light chains in urine
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• A 33-year-old man comes for a follow-up
  evaluation for persistent microscopic hematuria
  and proteinuria. He feels well and is otherwise
  asymptomatic. He has no history of edema or gross
  hematuria. There is no family history of kidney
  disease.
• On physical examination, temperature is normal,
  blood pressure is 142/96 mm Hg, pulse rate is
  72/min, and respiration rate is 14/min. BMI is
  29. The remainder of the examination, including
  cutaneous and neurologic examinations, is normal.

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Kidney biopsy reveals diffuse mesangioproliferativ
e lesions throughout all glomeruli with cellular
proliferation. Immunofluorescence testing reveals
significant IgA deposition and IgG, C3, and C4
deposition. In addition to enalapril, which of
the following is the most appropriate next step
in this patients management? A.
Azathioprine B. Cyclophosphamide C.
Methylprednisolone D. Mycophenolate mofetil
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IgA Nephropathy

• Classic gross hematuria after UTIs
• Glomerulonephritis, may progress to CKD in some
• Incidence Asian gt white gt black
• Prognosis usually good, rarely given immunologic
  therapies
• No helpful serologies do NOT check IgA level!

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6

• A 19-year-old woman is evaluated for a 3-month
  history of periorbital edema, ankle edema that
  worsens towards the end of the day, and foamy
  urine. Medical history is unremarkable, and she
  takes no medications.
• On physical examination, temperature is normal,
  blood pressure is 112/70 mm Hg, pulse rate is
  60/min, and respiration rate is 12/min. BMI is
  24. Funduscopic examination is normal. There is
  2 bilateral pedal edema.

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Kidney biopsy is performed. Electron microscopy
of the specimen reveals diffuse foot process
effacement. Light microscopy is normal.
Immunofluorescence testing shows no immune
complex deposits. Which of the following is the
most appropriate treatment for this patient? A.
Cyclophosphamide B. Cyclosporine C.
Prednisone D. Tacrolimus
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Minimal Change Disease

• Pure nephrotic syndrome without hematuria,
  hypertension, or change in creatinine
• Much more common in children
• Can be associated with hematologic malignancies,
  NSAIDs
• Light microscopy normal, foot process effacement
  on electron microscopy
• Good response to steroids

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15

• A 42-year-old woman is evaluated for a 3-month
  history of progressive cervical lymphadenopathy,
  fatigue, night sweats, bilateral lower-extremity
  and abdominal wall edema, and a 4.5-kg (10.0-lb)
  weight gain. History is significant for three
  episodes of weight gain and facial and
  lower-extremity edema lasting 4 weeks in her 20s
  and 30s. Her only current medication is a
  multivitamin.
• After an evaluation and lymph node biopsy, she is
  diagnosed with stage IIIB Hodgkin lymphoma.

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On kidney ultrasound, the kidneys are 13.5 cm
bilaterally and edematous. The corticomedullary
junction is apparent, and there is no
hydronephrosis. Which of the following is the
most likely cause of this patients nephrotic
syndrome? A. Focal segmental glomerulosclerosis
B. IgA nephropathy C. Membranous glomerular
nephropathy D. Minimal change disease
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Nephrotic syndrome

• Proteinuria gt 3 g/24 h
• Edema
• Hypoalbuminemia
• Hyperlipidemia
• Hypercoaguability
• Malnutrition, infection
• Vitamin D deficiency

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NSAIDs

• Do not cause analgesic nephropathy
• Most often prerenal azotemia, hypertension, fluid
  overload, hyperkalemia
• Occasionally associated with membranous, FSGS
• Mixed lesion interstitial nephritis MCD

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Membranoproliferative Glomerulonephritis

• Mixed nephritic/nephrotic picture and CKD
• Often associated with Hep C and/or
  cryoglobulinemia
• May respond to plasmapheresis, Hep C treatment
• Low serum complement levels, positive cryos,
  maybe positive RF

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Serologies

• ANA in lupus but not specific for kidney disease
  and titers not helpful
• Anti-dsDNA titers correlate with SLE nephritis
• Anti-GBM in antiGBM disease/Goodpastures

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Glomerulus