MKSAP Review – Glomerular Diseases

1. MKSAP Review – Glomerular Diseases Patrick Cunningham M.D. Section of Nephrology University of Chicago

2. 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.

3. 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 patient’s management? A. Cystoscopy B. Kidney biopsy C. Spiral CT of the abdomen and pelvis D. Observation

4. RBC cast Hyaline cast

5. 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

6. dysmorphic RBCs muddy brown casts tubular cell casts oval fat body

7. 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

8. 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.

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

10. 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.

11. 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

12. 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

13. 18 • 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.

15. 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 complex–mediated glomerular nephritis D. Pigment nephropathy

16. 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 • Wegener’s • MPA • Churg-Strauss • IgA nepropathy • Anti-GBM/Goodpasture’s progress fast progress slow

17. 20 • A 48-year-old man is evaluated for an abnormal urinalysis discovered last week during an examination for a worker’s 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.

18. 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

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

20. 33 • 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.

21. 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

22. 39 • 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.

23. Urine immunoelectrophoresis shows a paraprotein λ 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

24. Albuminuric Amyloid – “Congo Red” Light chain deposition diseases Other rarer GNs Nonalbuminuric Cast neph-ropathy/myeloma kidney Hypercalcemia Uric acid nephropathy Paraprotein-assoc. renal diseases All may have light chains in urine

25. 27 • 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.

26. Kidney biopsy reveals diffuse mesangioproliferative 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 patient’s management? A. Azathioprine B. Cyclophosphamide C. Methylprednisolone D. Mycophenolate mofetil

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

28. 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.

29. 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

30. 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

31. 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.

32. 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 patient’s nephrotic syndrome? A. Focal segmental glomerulosclerosis B. IgA nephropathy C. Membranous glomerular nephropathy D. Minimal change disease

33. Nephrotic syndrome • Proteinuria > 3 g/24 h • Edema • Hypoalbuminemia • Hyperlipidemia • Hypercoaguability • Malnutrition, infection • Vitamin D deficiency

34. NSAIDs • Do not cause analgesic nephropathy • Most often prerenal azotemia, hypertension, fluid overload, hyperkalemia • Occasionally associated with membranous, FSGS • “Mixed lesion”: interstitial nephritis + MCD

35. 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

36. 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/Goodpasture’s

37. Glomerulus