Contributions
Abstract: PB2127
Type: Publication Only
Background
Multiple myeloma (MM) is a clonal B-cell disease of proliferating plasma cells. Renal disease is a common complication of MM that occurs in 20-25% of newly diagnosed patients. Cast nephropathy, amyloid light chain amyloidosis and monoclonal Ig deposition disease are the most common causes of chronic kidney disease in MM patients. Podocytes are unique cells with complex interdigitating foot processes that cover the outer surface of the glomerular basement membrane and thereby form an important layer of the glomerular filtration barrier. Podocyte injury is the hallmark of many glomerular diseases.
Aims
We have performed this study in order to investigate whether podocyte injury contributes to the pathogenesis of renal disease in MM patients and tried to detect correlations with treatment outcomes.
Methods
A total of 27 patients with newly diagnosed multiple myeloma and 20 healthy subjects were enrolled in the study and assessed concerning urinary podocytes and podocyte-associated molecules at bbaseline and end of the 6th month. Seven of the patients were lost due to death before the end of the study period. All the patients received bortezomib-based treatment. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Podocyn-mRNA (Pod), nephrin mRNA (Nep), and VEGF-A mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression of podocyte proteins were also corrected by urine Cr concentration., cDNA was produced and PCR was processed. Podocytes were identified by PCR tagging nephrin, podocyn and VEGF-A which are biomarkers of podocyte, was detected.
Results
Proteinuria was found in 74% and renal failure in 33% of the cases at diagnosis. Median proteinuria levels were significantly higher compared to controls (725 mg vs 45 mg, (P<0.001). Proteinuria significantly decreased at the end of sixth months of treatment (P=0.002). Podocyturia monitored by Pod-mRNA, VEGF-A mRNA and Nep-mRNA expression was unremarkable compared to healthy controls in newly diagnosed MM patients. However, although was insignificant, there was a tendency towards an increase in urinary podocyte proteins concomittantly with a significant increase in urinary podocyte proteins, Pod-mRNA:/Cr, Nep mRNA/Cr and VEGF-A mRNA/ Cr ratios after treatment as compared with the pretreatment levels (P=0.001; P:0.039 and P=0.001 respectively).
Conclusion
Podocyturia as a marker of glomerular injury is unremarkable in MM patients at diagnosis. However, increase in podocyturia and related proteins during treatment might indicate glomerular injury as a consequence of therapeutic drugs especially bortezomib which is known as an nonnephrotoxic agent except causing thrombotic angiopathy. Further studies with more patients and longer observation period are needed in order to understand the extent of glomerular injury in MM patients while on treatment with different and new agents.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Myeloma, Renal impairment
Abstract: PB2127
Type: Publication Only
Background
Multiple myeloma (MM) is a clonal B-cell disease of proliferating plasma cells. Renal disease is a common complication of MM that occurs in 20-25% of newly diagnosed patients. Cast nephropathy, amyloid light chain amyloidosis and monoclonal Ig deposition disease are the most common causes of chronic kidney disease in MM patients. Podocytes are unique cells with complex interdigitating foot processes that cover the outer surface of the glomerular basement membrane and thereby form an important layer of the glomerular filtration barrier. Podocyte injury is the hallmark of many glomerular diseases.
Aims
We have performed this study in order to investigate whether podocyte injury contributes to the pathogenesis of renal disease in MM patients and tried to detect correlations with treatment outcomes.
Methods
A total of 27 patients with newly diagnosed multiple myeloma and 20 healthy subjects were enrolled in the study and assessed concerning urinary podocytes and podocyte-associated molecules at bbaseline and end of the 6th month. Seven of the patients were lost due to death before the end of the study period. All the patients received bortezomib-based treatment. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Podocyn-mRNA (Pod), nephrin mRNA (Nep), and VEGF-A mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression of podocyte proteins were also corrected by urine Cr concentration., cDNA was produced and PCR was processed. Podocytes were identified by PCR tagging nephrin, podocyn and VEGF-A which are biomarkers of podocyte, was detected.
Results
Proteinuria was found in 74% and renal failure in 33% of the cases at diagnosis. Median proteinuria levels were significantly higher compared to controls (725 mg vs 45 mg, (P<0.001). Proteinuria significantly decreased at the end of sixth months of treatment (P=0.002). Podocyturia monitored by Pod-mRNA, VEGF-A mRNA and Nep-mRNA expression was unremarkable compared to healthy controls in newly diagnosed MM patients. However, although was insignificant, there was a tendency towards an increase in urinary podocyte proteins concomittantly with a significant increase in urinary podocyte proteins, Pod-mRNA:/Cr, Nep mRNA/Cr and VEGF-A mRNA/ Cr ratios after treatment as compared with the pretreatment levels (P=0.001; P:0.039 and P=0.001 respectively).
Conclusion
Podocyturia as a marker of glomerular injury is unremarkable in MM patients at diagnosis. However, increase in podocyturia and related proteins during treatment might indicate glomerular injury as a consequence of therapeutic drugs especially bortezomib which is known as an nonnephrotoxic agent except causing thrombotic angiopathy. Further studies with more patients and longer observation period are needed in order to understand the extent of glomerular injury in MM patients while on treatment with different and new agents.
Session topic: 13. Myeloma and other monoclonal gammopathies – Biology & Translational Research
Keyword(s): Myeloma, Renal impairment