Abstract
Background
Monoclonal gammopathy of renal significance (MGRS) is a recently defined entity. It is a group of renal diseases due to paraprotein deposition from a small B lymphocyte or plasma cell clon, not meeting the criteria for an overt gammopathy-associated neoplasm. Despite this feature, the secondary kidney damage may be severe and irreversible; therefore, its early recognition and treatment are crucial. There are few studies on MGRS in the international literature, and no reported data from Latin America (LA).
Aims
To describe epidemiological and clinical characteristics of patients diagnosed with MGRS in LA.
To evaluate patients outcomes.
Material and methods
This is an international multicentric retrospective case series study.
All members of GELAMM (Grupo de estudio latinoamericano de Mieloma Múltiple) were invited to participate.
Patients with diagnosis of MGRS according to the IMWG definition were included. All cases had pathological diagnosis provided by a renal biopsy.
Epidemiological and clinical data were collected from clinical records in a standardized report form.
Renal response was arbitrarily defined as the partial or total recovery of renal failure or renal symtoms at the end of treatment.
Statistical analysis was performed by descriptive statistics using STATA 12.
Results
We received data from 18 patients, from centers in Chile, Argentina and Uruguay. Median follow up was 22,5 months.
The patients characteristics are shown in table 1. The median age was 58 years (36 to 78 years). Male to female ratio was 1:1,25. Twelve had history of hypertension and one patient of renal transplantation. Anemia was present in 78% of cases (mean 10,7g/dL +/-2,3), hypoalbuminemia in 72% (mean 2,8g/dL +/-0,7), renal failure in 83% (mean creatinine of 4,6mg/dL +/- 4,8) with 47% of these (7 patients) requiring renal replacement therapy (RRT). Proteinuria was measured in 16 patients. Its average was 4,4gr (range 0,12 - 11,5gr/24hrs). LDH and calcemia were normal in all cases.
Half of the patients presented as a nephrotic syndrome. Regarding histological subtypes, the most frequently diagnosed was the proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). The paraprotein most frequently found was Kappa, and in the renal biopsy was IgG Kappa deposition (table 1).
Serum protein electrophoresis (sPEP) was performed in all cases. Only 8 out 18 patients underwent urine protein electrophoresis (uPEP) and 14 had urine and serum immunofixation (IFX) done. Serum free light chain (sFLC) were performed in 94% of the patients. The paraprotein identification according to each of this exams is shown in figure 1.
Seventeen patients received treatment; 13 received an anti-plasma cell drug, 7 a thalidomide based regimen and 6 a bortezomib based regimen. The patient with IgM MGRS was treated with a rituximab based regimen. Regarding renal responses, there were no data in 5 patients. Nine out 13 of the patients achieved renal response: 3 achieved partial recovery and 9 complete recovery. Three patients become RRT independent. There was no mortality in our cohort. No patient relapsed, but 3 progressed: 1 to multiple myeloma (MM), 1 to systemic amyloidosis and another to systemic light chain deposition disease (LCDD).
Discussion
Only 18 cases from 3 South American countries were collected. The lack of hematologists in some countries, difficulties in achieving a renal biopsy, non-availability of immunofluorescence in the histological studies and few experienced pathologists could be some of the problems in our region.
Our cohort is of rather young patients, which is probably related to the fact that these patients are mostly undergoing renal biopsy. We believe, however, that the incidence of MGRS (similar to what happens with MGUS), increases with age, which could mean a problem of underdiagnoses.
As expected, nephropathies frequently associated with MM were found: AL amyloidosis and LCDD. However, the most common renal pathology was PGNMID, a rare entity. This data must be corroborated with a larger study.
The high sensitivity of sFLC to identify the paraprotein was corroborated and highlighted the importance of this test in the follow up.
Half of patients achieved a renal response, which reinforces the fact that they must be promptly treated.
Conclusion
According to our knowledge, this is the larger cases series study in LA, and we hope it will be a contribution to the knowledge of this pathology.
Disclosures
No relevant conflicts of interest to declare.
Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis