To preserve patient privacy and for didactic purposes, case descriptions and pathology reports have been anonymized and partially fictionalized. The pathology images are representative images from a mixture of similar cases.

Invited Speakers

Samer Nasser
Samer NasserCase Presenter | Beth Israel Deaconess Medical Center, Boston, USA | No conflict of interest reported
Johannes Schlondorff
Johannes Schlondorff Nephrology Discussant | Beth Israel Deaconess Medical Center, Boston, USA | Conflict of interest reported: Partners Healthcare/BWH – Patent/IP


Patient is a 70 yrs. old male referred for elevated creatinine and proteinuria. He has had mildly elevated blood pressures which have been systolic in the 140-150 range and 80’s for diastolic but more recently in 165/95 range. He was taken off lisinopril because of hyperkalemia within the past year, with a creatinine of around 1.3-1.4 mg/dl. He denies any history of dysuria, hematuria, urgency, increased frequency, nocturia. He has foamy urine. For the past 2-3 months he has been having swelling in his legs. ROS otherwise negative.

Medical history:
As above

Furosemide daily, isosorbide daily, metoprolol twice daily, simvastatin every night, amlodipine daily.
He denies any NSAID or herbal medication use. He was recently started on isosorbide.

Physical Exam:
Right femoral bruit, 3+ edema

Laboratory and other data:
Microscopic examination of the urine reveals possible RBC casts. Dipstick shows 3+ protein and 2+ RBC.
The patient’s last creatinine values prior to this visit were:
Serum creatinine 1.38 mg/dl
Serum creatinine 1.32 mg/dl
Serum creatinine 1.28 mg/dl
Urinary protein/creatinine ratio of 8 g/g
ANA: 1:640
C3 78 low
C4 17 low normal
ANCA negative
Hep B and C negative
Rheumatoid Factor: negative
Cryoglobulin: pending
Serum and urine electrophoresis (SPEP and UPEP)): negative for monoclonal proteins.

Ultrasound: Left Kidney 12 cm and Right 11 cm with normal echogenicity.

Short term follow up:
After the biopsy, the patient was started on angiotensin receptor blocker, without noticeable improvement in proteinuria. In fact the kidney function worsened; creatinine increased to 1.5 mg/dl and serum potassium  increased to 6.1 mEq/l on two separate occasions. Baseline anemia is worsening.

Kidney Pathology

Pathology images pending

Membranoproliferative pattern glomerulonephritis with low-level IgM deposition. Approximately 50% of glomeruli are globally sclerotic. The remainder all show varying degrees of endocapillary proliferation with accompanying double contour formation. No crescents are noted. There is marked interstitial fibrosis and tubular atrophy. Chronic inflammation accompanies the scarring. Intact tubulo-interstitium shows minimal mononuclear inflammation. Arteries show marked intimal fibroplasia. Arterioles show marked mural thickening and hyaline change. Immunofluorescence: There is 0 to trace granular peripheral capillary loop staining for IgM and C3. IgG, IgA, kappa and lambda, and C1q are negative. 1+ IgM and 2+ C3 are seen in vessels. Electron Microscopy: Membranes show significant areas of thickening and wrinkling. No subepithelial electron dense deposits are noted. The mesangial matrix is increased, but deposits are inconspicuous. Endocapillary cellularity is variably increased and mesangial interposition is noted. Very rare subendothelial/endocapillary electron dense deposits are identified, with some showing vague cryoglobulin type substructure. These findings confirm a membranoproliferative pattern of injury but are difficult to precisely categorize. Deposits are quite limited, paralleling the findings on immunofluorescence. One option is that of a resolving (? circulating) immune complex glomerulonephritis. The patient is negative for Hepatitis B & C, but the possibility of a cryoglobulinemic or paraprotein related process should be considered. These findings must be taken into clinical context.

Questions posed & summary of key discussion points

1. What further work up should be done to elicit etiology?
2. What therapeutic options may one consider?

Author of case summary:

 Case summary pending

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