Mechanism and prevention of acute kidney injury from cast nephropathy in a rodent model

Ying, Wei‐Zhong; Allen, Colin; Curtis, Lisa M.; Aaron, Kristal J.; Sanders, Paul W.

doi:10.1172/jci46490

Cited by 77 publications

(58 citation statements)

References 41 publications

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“…Other possible roles for uromodulin include a defensive role against urinary tract infection and possible roles in innate immunity (1). In disease, interactions between monoclonal free light chains and uromodulin are thought to be critical for cast formation and AKI in cast nephropathy associated with multiple myeloma (101).…”

Section: Uromodulinmentioning

confidence: 99%

Thick Ascending Limb of the Loop of Henle

Mount

2014

Clinical Journal of the American Society of Nephrology

146

106

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The thick ascending limb occupies a central anatomic and functional position in human renal physiology, with critical roles in the defense of the extracellular fluid volume, the urinary concentrating mechanism, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition. The last decade has witnessed tremendous progress in the understanding of the molecular physiology and pathophysiology of this nephron segment. These advances are the subject of this review, with emphasis on particularly recent developments.

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Section: Uromodulinmentioning

confidence: 99%

Thick Ascending Limb of the Loop of Henle

Mount

2014

Clinical Journal of the American Society of Nephrology

146

106

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“…However, it is not currently in clinical use. Therefore, the principles of the treatment of myeloma cast nephropathy are the elimination of FLCs and restriction of FLC production using chemotherapy [12]. Patients with multiple myeloma with kidney dysfunction are very likely to develop end-stage renal disease, and the survival rate is quite poor in untreated patients [13].…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy plus selective plasma exchange

et al. 2016

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Myeloma cast nephropathy is a major complication of multiple myeloma. Recent evidence has demonstrated that the earlier induction of bortezomibbased chemotherapy with plasma exchange (PE) provides better results for kidney function and patient survival. Due to its non-selectivity, PE with albumin replacement carries the risk of fibrinogen loss, leading to bleeding. We herein report a case of successful treatment of myeloma cast nephropathy using bortezomib-based chemotherapy and selective PE. A 61-year-old woman who had a 20-year history of type II diabetes mellitus was admitted to our hospital for the evaluation of hypercalcemia, severe kidney dysfunction, and anemia. Subsequent bone marrow evaluation and renal biopsy revealed that she had multiple myeloma (IgG-j) and myeloma cast nephropathy. Ten days after admission, bortezomib-based chemotherapy with selective PE achieved rapid and thorough free light-chain (FLC) reduction; within a month, her kidney function had been recovered (creatinine level, 1.2 mg/dl). Her serum fibrinogen level was not reduced, and no bleeding complication occurred. Five months later, autologous hematopoietic stem-cell transplantation was performed successfully, and the patient's kidney function was stable (creatinine level, 1.1 mg/dl) thereafter. This case report demonstrates the importance of early induction therapy with bortezomib-based chemotherapy and PE in a patient with myeloma cast nephropathy, which is especially applicable in patients aged \65 years. In addition, it shows that selective PE is a safe and effective method of FLC removal.

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“…These findings allowed the development of an inhibiting cyclized competitor peptide, which inhibits cast precipitation (34).…”

Section: Light Chain Cast Nephropathymentioning

confidence: 99%

“…This process is prevented by a competitive inhibitor peptide that stops binding of light chains to THP, decreasing intratubular cast formation and preventing AKI in an animal model (34). Another contributing factor to THP binding and predisposing to cast nephropathy may be the isoelectric point (pI) of the light chain (18).…”

Section: Light Chain Cast Nephropathymentioning

confidence: 99%