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

Jeffrey William
Jeffrey WilliamCase Presenter | Beth Israel Deaconess Medical Center, Boston, MA, USA | No conflicts of interest reported
Johannes Schlondorff
Johannes Schlondorff Nephrology Discussant | Beth Israel Deaconess Medical Center, Boston, MA, USA | Conflict of interest reported: Partners Healthcare/BWH – Patent/IP

Case

A teenage male presents with worsening shortness of breath and lower extremity edema. Prior history of 3 gram proteinuria with similar presentation 1.5 years prior, which was never worked up, but identified as part of routine physical for a summer job.

Medical history:
None

Family history:
Unable to obtain

Physical Exam:
Hypertensive and > 140/70 mmHg.
3+ lower extremity edema.

Laboratory and other data:
Serum albumin 1.8 mg/dl
LDL 270 mg/dl, TG 340 mg/dl
ANA and ANCA negative
C3 low, at 30 mg/dl,
C4 low at 12 mg/dl
Dysmorphic RBCs in urine
Urinary albumin 7.5g/g

LE ultrasound without venous thrombosis
Chest X-ray with small left pleural effusion

Short term follow-up:
Despite initial therapy with angiotensin-converting-enzyme inhibitor and statin, proteinuria and nephrotic syndrome persists.
Furosemide was stopped few weeks after presentation, statin increased as tolerated, angiotensin-converting-enzyme inhibitor switched to angiotensin receptor blocker due to cough.  Recent initiation of every-other-day prednisone.

Kidney Pathology

Pathology images pending

Renal biopsy with extensive foot-process effacement, thickened glomerular basement membrane, and expansion of mesangium.  Severe and capillary luminal occlusive.  Extensive mesangial dense deposits, involving peripheral capillary loop basement membrane.

Questions posed & summary of key discussion points

1. Immunosuppression choice/course in C3 nephropathy?
2. What is the evidence?
3. Is it appropriate to embark on an extensive workup for an underlying etiology of C3 nephropathy, such as genetic testing if insurance does not provide any financial assistance?

Authors of case summary:

Dr. Nikhil Agrawal

Diagnosis
C3 glomerulonephritis (PMID: 24178974)

Differential diagnosis
Post streptococcal and staphylococcal-associated GN
Monoclonal gammopathy of renal significance
Dense deposit disease

Findings consistent with diagnosis:
Low serum C3
Biopsy IF with isolated C3 and no immunoglobulins
Young patient with nephrotic syndrome

Findings less consistent with diagnosis:
Low serum C4
Workup for underlying etiology not available

Therapeutic options:
MMF+ steroids (source: PMID 26221755 )
Eculizumab (source: PMID 22403278 )
Plasma exchange (source: PMID 21269585 )

Key points:
– Diagnosis of C3 Glomerulopathy is largely based on presence of C3 immunofluorescence in renal biopsy in absence of immunoglobulins.
– Clinical presentation can be very varied from indolent mild proteinuria to RPGN.
– Dense deposit disease (DDD) and C3 glomerulonephritis are the two types of C3 glomerulopathy.
– Diagnosis of DDD is based on dense basement membrane deposits on EM.
– One may look for C3 Nephritic factor mutation, factor H deficiency/mutations, CFHR mutations. These tests are done only in very specialized labs.
– Rule out monoclonal protein as the etiology of C3GN, specially in older patients.
– Treatment can be conservative (with ACE/ARB blockade) in mild disease.
– Treatment with Eculizumab has shown good response but is expensive.
– Treatment with plasma infusion or exchange can be tried if genetic deficiency or mutation in C3 or Factor H or if C3 nephritic factor is identified.
– Treatment with rituximab can be attempted but there is no good evidence to support that.