P0498CLINICAL PRESENTATION AND RENAL HISTOPATHOLOGICAL FINDINGS IN PATIENTS WITH MONOCLONAL GAMMOPATHY
Authors: Alfano Gaetano , Delrio Alice , Fontana Francesco , Ferrari Annachiara , Solazzo Andrea , Mori Giacomo , Cappelli Gianni 
Published: June 2020

Abstract

Background and Aims
Monoclonal gammopathy is associated with renal lesions due to the toxic effect of M-protein. The aim of our study was to evaluate the prevalence and the clinical presentation of monoclonal gammopathy in patients who underwent kidney biopsy for renal impairment.

Method
We conducted a retrospective study at the Nephrology and Dialysis Unit of the University Hospital of Modena from 2005 to 2017. The diagnosis of renal disease was proved histologically.

Results
Monoclonal gammopathy was found in 179 out of 1334 patients (13.4%). Mean age was 66.1±13.4 years with a predominance of males (63.7%). There was no differences (P=0.16) between the age of patients with benign (64.9±14.3) and malignant lymphoproliferative diseases (67.6±12). The hematologic disorders involved in the production of M-protein were MGUS (51.9%), myeloma multiple (MM) (25.7%), amyloidosis (8.9%) smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%).
The prevalence of MGUS was estimated to be 6.97% (93/1334). Mean serum creatinine was 2.68±2.12 mg/dl (eGFR of 35.24±29.32 ml/min) and urine protein/creatinine ratio of 5.1±6.5. None of the study subjects progressed to MM or other lymphoproliferative diseases. The most common kidney disease was membranoproliferative (GN) (19.3%). MGRS has been identified in five patients (5.4%).
Mean age of MM was 66.84±13 years. Serum concentration M-protein was 1.47±0.98. Among patients with AKI (89.1%), 13 patients (28.2%) required urgent hemodialysis.
Histological evaluation showed cast nephropathy (71.7%), MM-associated AL amyloidosis (15.2%), MM-associated-light chain deposition disease (4.3%) and interstitial nephritis (8.7%).
Nine patients had a diagnosis of smoldering MM. Average age was 69.17±10.8 years old. At presentation, creatinine was 2.31±2.6 mg/dl (GFR of 41.35 ml/min). Evaluation of renal biopsies allowed us to identify different patterns of glomerular diseases, expression of an aspecific renal involvement of this hematological disease.
AL amyloidosis was secondary to MGUS (75%) and smoldering MM (33%). Mean age was 66.04±11.7 years old. At presentation mean urine protein/creatinine ratio was 8.33±3.2 concomitant to a serum albumin level of 2.74±0.84 gr/dl. Mean creatinine was 1.4 mg/dl corresponding to eGFR= 56.5 ml/min.
Average age of NHL patients was 72.6±9.6 years. Renal function was extremely variable at presentation; mean creatinine was 2.4±1.6 mg/dl (eGFR of 30.4±22.7 ml/min). Histological evaluation of biopsy specimen revealed amyloidosis (25%), cryoglobulinemic GN (25%), LCDD (16.6%), cast-nephropathy (8.3%), LCDD (8.3%) and other renal diseases (16.8%).
Three patients (1.12%) had a diagnosis of HL at mean age of 69.04±5.3 years. At presentation, renal function was normal in all patients with a creatinine of 0.93±0.07mg/dl (eGFR of 62.7.3±7.4 ml/min). Urine protein/creatinine ratio was 0.3±0.2. Kidney biopsy revealed cryoglobulinemic GN (75%) and hypertensive nephrosclerosis (25%).
ANOVA analysis did not found statistically significant differences in age (p=0.11) and serum concentration of M-protein (P=0.42) between groups. The differences in mean serum creatinine and mean urine protein/creatinine ratio were statistically significant between groups, (P&lt;0.0001) and (P=0.003), respectively. A post hoc Tukey test showed that proteinuria was higher in AL amyloidosis compared to MM and HL, whereas renal function was worse in MM patients compared to the others.

Conclusion
MGUS was the most common monoclonal gammopathy. Surprisingly, it is frequently associated with membranoproliferative glomerulonephritis. MGRS is a rare histopathological entity (5.4%). MM manifests frequently with AKI whereas AL amyloidosis with nephrotic syndrome. Renal function was extremely variable in NHL patients; on the other hand, the limited number of HL patients with renal involvement in our cohort does not allow generalization of our findings.