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

Johannes Schlondorff Case Presenter | Beth Israel Deaconess Medical Center, Boston, USA | Conflict of interest reported: Partners Healthcare/BWH – Patent/IP

Isaac StillmanNephropathology Discussant | Beth Israel Deaconess Medical Center, Boston, USA | No conflicts of interest reported

Ali Poyan MehrNephrology Discussant | Beth Israel Deaconess Medical Center, Boston, MA, USA | Conflict of interest reported: Mallinckrodt - Glomerular Disease Consultant and Research Grant

Case

Elderly man with metabolic syndrome and recent hernia repair presents 2 weeks post-op with nausea, emesis and acute kidney injury (peak creatinine 4 mg/dl). He denies any recent nephrotoxic exposures.

Medical history:

No known kidney disease, no hematological disorders, no malignancies.

Physical exam:

Otherwise well appearing man, slightly elevated blood pressure, with mild abdominal obesity

Laboratory data:
Serum Alb 2.5 mg/dl
Serum protein-electrophoresis (SPEP) with hypogammaglobulinemia, and on repeat a few months later with trace IgG kappa monoclonal.
Normal complements, serologies negative.
Urine protein to creatinine ratio of 6.2 g/g.
Urine protein-electrophoresis (UPEP) with trace oligoclonal bands of IGG kappa.
Urine analysis notable for 4+ protein, 20-25 red blood cells per high power field with some acanthocytes, 15-20 white blood cells, few hyaline and moderate mixed cellular casts.

Kidney Pathology

Pathology images pending

Exudative endocapillary proliferative glomerulonephritis with monoclonal IgG2 kappa deposition.

IgG2 kappa deposition.

Questions posed & summary of key discussion points

1. How sensitive are serum and urine protein-electrophoresis in diagnosis of monoclonal gammopathy?
2. What are the patterns of renal involvement in monoclonal gammopathy?
3. How would you manage this case of monoclonal gammopathy of renal significance?

Author(s) of case summary:

Dr. Nikhil Agrawal

Diagnosis
Proliferative Glomerulonephritis with monoclonal Immunoglobulin deposits.
Monoclonal Gammopathy of Renal significance(MGRS)(PMID:23047823)

Differential diagnosis
Multiple Myeloma
Plasmacytoma
Monoclonal B cell lymphocytosis

Findings consistent with diagnosis
Monoclonal IgG2 kappa deposition on renal biopsy
SPEP with trace IgG kappa monoclonal

Findings less consistent with diagnosis
No Bone marrow biopsy studies
No imaging studies( CT or PET scan)

Therapeutic options
Rituximab monotherapy is recommended in cases of IgM-related disease (source:PMC4040895).
In non-IgM disorder, therapy should rely on antimyeloma agents (source:PMC4040895 ).

Key points:
– Diagnosis of MGRS requires exclusion of multiple myeloma or other lymphoproliferative disorders. Simplistically, it is MGUS with renal involvement.
– SPEP and IFE can detect a light chain clone at concentrations of >500 mg/l and >150 mg/l, respectively(PMC4863638).
– Urinary protein electrophoresis (UPEP) and urine IFE (UIFE) can identify an abnormal clone of light chain in the urine to a concentration of 10 mg/l (PMC4863638).
– Sensitivity of FLC for BJP was 98%. Use of FLC in addition to UPEP/UIFE increased the the number of MG detected by 7% (PMID:20961192).
– Serum or urine monoclonal protein may not be detected. Peripheral flow cytometry or PET scan can be useful in such cases to find an underlying lymphoproliferative disorder.
– If no monoclonal serum/urine protein and no lymphoproliferative disorder can be found, treatment options are not well defined and can be challenging. Rituximab(preferred for IgM) or Cytoxan therapy in addition to steroids can be used in severe or progressive disease.
– Besides proliferative glomerulonephritis, MGRS can present as other renal disorders similar to myeloma (other than cast nephropathy) such as immune deposition disease, amyloidosis, proximal tubular dysfunction.
– Treatment for MGRS should be considered even after ESRD if patient is a candidate for transplant due to high rate of recurrence(PMID:23047823).