Contributions
Abstract: PB2163
Type: Publication Only
Background
Renal involvement causing progressive proteinuric chronic kidney disease is present in 70% of patients with systemic AL amyloidosis at diagnosis. Patient and renal survival are dependent upon both successful free light chain suppression and degree of renal dysfunction at the time of diagnosis1. Urinary excretion of retinal binding protein (RBP), an indicator of renal tubular injury, has been used in detecting early renal involvement in multiple myeloma 2,3 Free light chains (FLC) are known to be toxic to the proximal tubule which contributes to a range of pathologies including cast nephropathy and Fanconi’s syndrome.4 Furthermore, treatment with systemic chemotherapy (often proteasome inhibitor based) to suppress FLC production can be associated with acute kidney injury (AKI).
Aims
We hypothesized that a significant proportion of patients with newly diagnosed renal AL amyloidosis have proximal tubular dysfunction and sought to determine whether this may predict renal outcomes.
Methods
All patients (n=158) who attended the National Amyloidosis Centre (NAC) from September 2016 to October 2017 and were enrolled into ‘ALchemy’, the centre’s prospective observational study for newly diagnosed patients with AL amyloidosis, underwent measurement of urinary RBP (uRBP) excretion in conjunction with routine clinical, biochemical and scintigraphy assessments.
Results
Median age was 69 yrs (44-90) with median serum creatinine of 89 umol/L and eGFR of 67 ml/min/1.73 m2. Median urinary protein creatinine ratio (uPCR) was 311 mg/mmol. Median uRBP was 285 μg/L. There was a significant correlation between uRBP and serum creatinine (Pearson correlation p<0.0001, R 0.6440) and uRBP and uPCR (Pearson correlation p<0.0001, R 0.5247) with a weaker correlation with uACR (Pearson correlation p<0.0001, R 0.3039). Despite this however, a markedly elevated uRBP/Creatinine (>1000mg/mmol) was detected in 35 patients including 9 who had an eGFR >30ml/min/1.7m2, and 8 who had uPCR <300 mg/mmol and ACR <50 mg/mmol. There was a strong correlation between altered fractional excretion of both phosphate and urate with uRBP (Pearson correlation, p<0.0001, R 0.6181).
Conclusion
Although there is a significant correlation between low molecular weight protein excretion indicating proximal tubular dysfunction with both serum creatinine and uPCR, there is a cohort of patients with both preserved renal excretory function and absence of significant proteinuria who have elevated uRBP excretion,. The association with fractional excretion of both phosphate and urate demonstrate that elevated uRBP excretion in patients with newly diagnosed untreated renal AL amyloidosis specifically indicates proximal tubular dysfunction. The analysis of whether uRBP predicts renal outcomes is underway and may be of relevance to other renal pathological lesions.
1. Merlini G, Comenzo RL, Seldin DC, Wechalekar A, Gertz MA. Immunoglobulin light chain amyloidosis. Expert review of hematology. 2014;7(1):143-156.
2.Gavrilov V, Yermiahu T, Gorodischer R. Urinary excretion of retinol in patients with multiple myeloma: a preliminary study. Am J Hematol. 2003;74(3):202-204.
3.Corso A, Serricchio G, Zappasodi P, et al. Assessment of renal function in patients with multiple myeloma: the role of urinary proteins. Annals of hematology. 1999;78(8):371-375.
4.Sanders PW. Mechanisms of light chain injury along the tubular nephron. Journal of the American Society of Nephrology : JASN. 2012;23(11):1777-1781.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, Myeloma, Renal failure
Abstract: PB2163
Type: Publication Only
Background
Renal involvement causing progressive proteinuric chronic kidney disease is present in 70% of patients with systemic AL amyloidosis at diagnosis. Patient and renal survival are dependent upon both successful free light chain suppression and degree of renal dysfunction at the time of diagnosis1. Urinary excretion of retinal binding protein (RBP), an indicator of renal tubular injury, has been used in detecting early renal involvement in multiple myeloma 2,3 Free light chains (FLC) are known to be toxic to the proximal tubule which contributes to a range of pathologies including cast nephropathy and Fanconi’s syndrome.4 Furthermore, treatment with systemic chemotherapy (often proteasome inhibitor based) to suppress FLC production can be associated with acute kidney injury (AKI).
Aims
We hypothesized that a significant proportion of patients with newly diagnosed renal AL amyloidosis have proximal tubular dysfunction and sought to determine whether this may predict renal outcomes.
Methods
All patients (n=158) who attended the National Amyloidosis Centre (NAC) from September 2016 to October 2017 and were enrolled into ‘ALchemy’, the centre’s prospective observational study for newly diagnosed patients with AL amyloidosis, underwent measurement of urinary RBP (uRBP) excretion in conjunction with routine clinical, biochemical and scintigraphy assessments.
Results
Median age was 69 yrs (44-90) with median serum creatinine of 89 umol/L and eGFR of 67 ml/min/1.73 m2. Median urinary protein creatinine ratio (uPCR) was 311 mg/mmol. Median uRBP was 285 μg/L. There was a significant correlation between uRBP and serum creatinine (Pearson correlation p<0.0001, R 0.6440) and uRBP and uPCR (Pearson correlation p<0.0001, R 0.5247) with a weaker correlation with uACR (Pearson correlation p<0.0001, R 0.3039). Despite this however, a markedly elevated uRBP/Creatinine (>1000mg/mmol) was detected in 35 patients including 9 who had an eGFR >30ml/min/1.7m2, and 8 who had uPCR <300 mg/mmol and ACR <50 mg/mmol. There was a strong correlation between altered fractional excretion of both phosphate and urate with uRBP (Pearson correlation, p<0.0001, R 0.6181).
Conclusion
Although there is a significant correlation between low molecular weight protein excretion indicating proximal tubular dysfunction with both serum creatinine and uPCR, there is a cohort of patients with both preserved renal excretory function and absence of significant proteinuria who have elevated uRBP excretion,. The association with fractional excretion of both phosphate and urate demonstrate that elevated uRBP excretion in patients with newly diagnosed untreated renal AL amyloidosis specifically indicates proximal tubular dysfunction. The analysis of whether uRBP predicts renal outcomes is underway and may be of relevance to other renal pathological lesions.
1. Merlini G, Comenzo RL, Seldin DC, Wechalekar A, Gertz MA. Immunoglobulin light chain amyloidosis. Expert review of hematology. 2014;7(1):143-156.
2.Gavrilov V, Yermiahu T, Gorodischer R. Urinary excretion of retinol in patients with multiple myeloma: a preliminary study. Am J Hematol. 2003;74(3):202-204.
3.Corso A, Serricchio G, Zappasodi P, et al. Assessment of renal function in patients with multiple myeloma: the role of urinary proteins. Annals of hematology. 1999;78(8):371-375.
4.Sanders PW. Mechanisms of light chain injury along the tubular nephron. Journal of the American Society of Nephrology : JASN. 2012;23(11):1777-1781.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Amyloidosis, Myeloma, Renal failure