Article

Paraproteinemic renal diseases that involve the tubulo-interstitium.

Department of Pathology, St. Louis University, St. Louis, Mo., USA.
Contributions to nephrology (Impact Factor: 1.49). 02/2007; 153:105-15. DOI:10.1159/000096763
Source: PubMed

ABSTRACT The renal response to deposition of monoclonal light chains represents a spectrum of pathologic changes that can be divided into glomerular or tubulo-interstitial processes. Involvement of the tubulo-interstitium can include activation of the proximal tubule, proximal tubule injury/cell death, and cast nephropathy. In these diseases, the culprit is not the intact immunoglobulin protein but instead the immunoglobulin light chain. Recent noninvasive tests, including immunofixation electrophoresis or quantification of serum free light chains, have increased the sensitivity for detection of an abnormality in circulating free light chains and are invaluable ancillary tools, but short of renal biopsy, the diagnosis of these diseases can prove challenging. A description of the pathobiology and overview of the approach to management of these light chain-mediated renal lesions is provided.

0 0
 · 
0 Bookmarks
 · 
102 Views
  • [show abstract] [hide abstract]
    ABSTRACT: Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma.
    Nature Reviews Nephrology 11/2011; 8(1):43-51. · 7.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Multiple myeloma (MM) is the most frequent monoclonal gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal gammopathy of undetermined significance (MGUS) than with MM. Unfortunately due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Since treatment is not recommended for MGUS, appropriate treatment is commonly withheld. In addition to end stage renal disease and the persistence of the monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function is possible upon successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We feel the term monoclonal gammopathy of renal significance (MGRS) is most helpful to indicate a causal relationship between the monoclonal gammopathy and the renal damage and since the significance of the monoclonal gammopathy is no longer undetermined.
    Blood 10/2012; · 9.06 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Myeloma kidney is a tubulointerstitial pathology that accounts for approximately 80-90% of severe acute kidney injury in patients with multiple myeloma. Unless there is rapid intervention, progressive irreversible damage from interstitial fibrosis and tubular atrophy occurs. Work over the past decade has demonstrated that an early sustained reduction in serum concentrations of pathogenic monoclonal free light chains (FLCs) leads to improved renal recovery rates. In turn, an early improvement in renal function is associated with improved patient survival. An early reduction in FLC levels should therefore become standard of care, although the optimum mechanisms to achieve this depletion of FLCs remain to be determined. To provide a coordinated, cross-disciplinary approach to research in this disease, the International Kidney and Monoclonal Gammopathy Research Group was formed. In this Review, we address the current state of knowledge in the management of myeloma kidney.
    Nature Reviews Nephrology 02/2012; 8(4):234-43. · 7.94 Impact Factor

Full-text (2 Sources)

View
78 Downloads
Available from
Dec 18, 2012