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: 8.56). 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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Available from: Fernando Fervenza, May 12, 2014
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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 · 2.89 Impact Factor
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    • "Most commonly, renal recovery correlates with reduction in SFLC load as noticed in our case; this association has been particularly reported in newly diagnosed MM [37] and biopsy proven MCN [47]—Leung et al. reported that renal response was not noticed unless there was a 50% or more reduction in SFLC load and suggested to consider plasmapheresis as a bridge or adjunctive therapy in biopsy proven MCN cases not responding immediately to chemotherapy as the chronicity of RF can affect the degree of recovery. Otherwise, there are no standard recommendations on when to resort to plasmapheresis in case of MM nonresponsive to chemotherapy. "
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    ABSTRACT: Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count-18,900/μL with no bandemia, hemoglobin 10.8 gm/dL, potassium-6.7 mEq/L, bicarbonate-15 mEq/L, blood urea nitrogen-62 mg/dL, SCr-5.6 mg/dL (baseline: 1.10), and corrected calcium-11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen.
    06/2014; 2014:940171. DOI:10.1155/2014/940171
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    • "In their study including patients with cast nephropathy, the combination of PE with high-dose dexamethasone-based chemotherapy induced an attenuation of kidney dysfunction in 45% and in 75% of patients in whom serum FLC levels decreased by >50% with treatment. In contrast, no correlation between renal response and reduction in serum FLC levels was observed in another study including patients without biopsy-proven cast nephropathy [18], indicating that pathological confirmation might influence therapeutic strategy and prognosis in MM with CKD. A treatment strategy was recently designed combining bortezomib-based therapy and PE in patients with biopsy-proven cast nephropathy or a high probability of cast nephropathy (>200 mg/dL of FLC) [58]. "
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    ABSTRACT: Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.
    The Scientific World Journal 10/2013; 2013:487285. DOI:10.1155/2013/487285 · 1.73 Impact Factor
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