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Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
Kidney International (Impact Factor: 8.52). 07/2008; 73(11):1282-8. DOI: 10.1038/ki.2008.108
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ABSTRACT Cast nephropathy is the most common cause of renal disease in multiple myeloma, however, treatment with plasma exchange remains controversial even after 3 randomized controlled studies. We sought to determine the importance of diagnostic confirmation and goal directed therapy in the treatment of cast nephropathy in forty patients with confirmed multiple myeloma and renal failure who underwent plasma exchange. A positive renal response was defined as a decrease by half in the presenting serum creatinine and dialysis independence. No baseline differences were noted between eventual renal responders and non-responders. Three quarters of the patients with biopsy proven cast nephropathy resolved their renal disease when the free light chains present in the serum were reduced by half or more but there was no significant response when the reduction was less. The median time to a response was about 2 months. In patients without cast nephropathy, renal recovery occurred despite reductions in free light chain levels of the serum. No association was found between free light chains in the serum, urinary monoclonal proteins, overall proteinuria and cast nephropathy. We found that the relationship between renal recovery and free light chain reduction was present only in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease.

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    • "The large distribution volume of light chains probably explains the low efficiency of the plasma exchange procedure [7] [23] [24]. The removal of greater quantities of serum free light chains has been demonstrated with the use of high cut-off dialyzers (pore sizes of 25 to 50 kDa) and two clinical trials in Europe are currently underway to investigate whether this can improve the renal prognosis independently of chemotherapy (European Trial of Free Light Chain Removal by Extended Hemodialysis in Cast Nephropathy [EuLITE] and Studies in Patients With Multiple Myeloma and Renal Failure Due to Myeloma Cast Nephropathy [MYRE]) [25]. "
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    ABSTRACT: Background Patients with multiple myeloma (MM) manifesting acute kidney injury (AKI) and who later recover renal function and independence from renal replacement therapy (RRT) are considered to have a better outcome. The aim of this work was to study the factors associated with renal function recovery (independence of hemodialysis) and longer survival in these patients. Methods A retrospective single center study including patients with a diagnosis of MM and severe AKI, defined as stage 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) criteria: 3.0 times baseline increase in serum creatinine (sCr) or increase in sCr to ≥ 4.0 mg/dL or initiation of RRT, was conducted. Data was registry-based and collected between January 2000 and December 2011. We examined demographic and laboratorial data, presenting clinical features, precipitating factors, need for RRT and chemotherapy. Death was considered the primary endpoint. Results Lower serum β2-microglobulin was the only independent factor associated with recovery of renal function and independence of RRT (OR 0.95, 95% CI: 0.91–0.99, P = 0.02). The median survival after AKI was 10.7 ± 12.1 months. The factors associated with longer survival were independence of RRT (HR 2.21; 95% CI: 1.08–4.49; P = 0.02), lower CRP (HR 1.07; 95% CI: 1.03–1.12; P = 0.001) and younger age (HR 1.03; 95% CI: 1.01–1.06; P = 0.005). Conclusions Our study suggests that MM patients with lower serum β2-microglobulin have a higher likelihood of recovering renal function after severe AKI. Independence of RRT, lower CRP and younger age are associated with longer survival.
    European Journal of Internal Medicine 09/2014; 25(7). DOI:10.1016/j.ejim.2014.06.023 · 2.30 Impact Factor
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    • "Extracorporeal removal of nephrotoxic light chains from the blood seems to be a reasonable approach in cast nephropathy and plasma exchange has been widely used in clinical practice to decrease serum FLC concentrations. However, there is no convincing evidence about the benefit of plasmapheresis in acute renal failure in multiple myeloma and conflicting outcomes have been reported by many studies ((Zuchelli P,et al,1988, Clark WF,et al,2005, Leung N,et al,2008) . "
    Multiple Myeloma - An Overview, 01/2012; , ISBN: 978-953-307-768-0
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    • "Kidney failure in patients with a presumptive diagnosis of multiple myeloma may also be a result of light chain amyloidosis (AL), light chain deposition disease (LCDD), monoclonal immunoglobulin deposition disease (MIDD), or acute tubular necrosis (ATN) from the use of nephrotoxic agents in the setting of monoclonal gammopathy. (Leung et al., 2008) Although renal disease in patients with multiple myeloma is heterogeneous, careful attention must be paid when selecting an appropriate treatment to decrease progression to ESRD and dialysis, which are associated with shortened overall survival. (Blade et al., 1998; Blade & Rosinol, 2005). "
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    ABSTRACT: Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.
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