Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney

Basnayake, Kolitha; Cheung, Chee Kay; Sheaff, Michael; Fuggle, W. J.; Kamel, Dia; Nakoinz, Sandra; Hutchison, Colin A.; Cook, Mark; Stoves, John; Bradwell, Arthur R.; Cockwell, Paul

doi:10.1136/jcp.2010.079236

Cited by 33 publications

(37 citation statements)

References 33 publications

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“…The increased production of light chains by neoplastic plasma cell populations overwhelms the proximal tubular capacity to perform this function, and excess light chains bind to Tamm-Horsfall protein in the distal tubule, causing obstruction and a reduction in GFR. Factors that promote cast formation include a heavy load of serum-free light chains (SFLC) delivered to the distal tubule, acidic urine, concurrent treatment with furosemide or nonsteroidal anti-inflammatory drugs, dehydration, intravenous contrast, and hypercalcemia (28).…”

Section: Intrinsic Causesmentioning

confidence: 99%

Onco-Nephrology

Lam

Humphreys

2012

Clinical Journal of the American Society of Nephrology

111

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SummaryAKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology.

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Section: Intrinsic Causesmentioning

confidence: 99%

Onco-Nephrology

Lam

Humphreys

2012

Clinical Journal of the American Society of Nephrology

111

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“…Однако у большинства больных (68%) с диализ-зависимой ПН к моменту начала лечения был выявлен в нефробиоптате распространенный тубулоинтерстици-альный фиброз, который может сформироваться в тече-ние 2-3 мес от первых проявлений КН. Следует также учесть возможность его прогрессирования в процессе терапии, пока сохраняется секреция моноклональных ЛЦ [23]. Наличие выраженного тубулоинтерстициально-го фиброза объясняет низкую частоту ПочО у больных с тяжелой ПН.…”

Section: Discussionunclassified

“…Внутриканальцевых цилиндров не обнаружено, однако сохранялись исходные признаки тубулоинтерстициального фиброза. Получен-ные данные, как и результаты других исследований, под-тверждают возможность регрессии внутриканальцевых цилиндров при прекращении или значительном сниже-нии экскреции с мочой белка BJ [23]. Таким образом, морфологические изменения в почках при диализзависи-мой ПН определяют вероятность ПочО после лечения.…”

Section: морфологические изменения в почках как предикторы почо на прunclassified

“…Противоопухолевую тера-пию проводили по содержащим бортезомиб протоколам. Крайне важным является тот факт, что улучшение функ-ции почек наблюдалось лишь у пациентов с гематологиче-ским ответом на лечение [23,25]. Подобный подход к те-рапии представляется перспективным, так как он позво-ляет увеличить степень и скорость редукции ЛЦ, не усугу-бляя токсичность терапии.…”

Section: таблица 1 вариант нефропатии и частота почо у больных с диаunclassified

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Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors

Рехтина¹,

Mendeleeva²,

Biryukova³

2015

Ter. arkh.

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“…27 Cast nephropathy Excess SFLC filtered through the glomerulus into the proximal tubule of the nephron binds the multiligand receptors, megalin and cubulin, resulting in endocytosis by the clathrin-dependent endosomal-lysosomal pathway in the proximal tubule cells, and if the concentration of the light chains overwhelms this lysosomal degradation pathway, then proximal tubular cell necrosis and apoptosis can occur. [28][29][30] Renal failure in cast nephropathy (also known as myeloma kidney) is associated with the level of light chain. 28 When the FLC exceed the endocytosis capacity of the proximal tubule cells, the FLC enter the distal tubule, in which they bind to a 9-amino acid-binding domain on the Tamm-Horsfall glycoprotein by the third complementarity determining region causing obstruction and reduction in glomerular filtration and interstitial blood flow and eventually interstitial nephritis from tubular rupture.…”

Section: Pathogenesis Of Renal Failure In Plasma Cell Myelomamentioning

confidence: 99%

Renal failure in multiple myeloma: a medical emergency

Wirk

2011

Bone Marrow Transplant

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Up to 50% of newly diagnosed plasma cell myeloma (PCM) patients can present with renal insufficiency, 20% with severe renal impairment and 10% requiring dialysis. PCM patients account for 2% of the dialysis population, adding 5000 new patients each year worldwide. Dialysisdependent PCM patients have a 2.77 higher risk of death compared with other dialysis-dependent patients without this diagnosis. Renal failure and especially dialysis dependency is an independent poor prognostic factor in PCM, with the majority unable to achieve dialysis independence. Renal failure in PCM is a medical emergency with the need for rapid accurate diagnosis and prompt institution of supportive care and PCM-directed therapy, because reversal of renal impairment and recovery from dialysis dependency can occur in up to half the patients early in the course of disease and can lead to enormous survival benefits. Recently, the serum free light chain (SFLC) assay and serum b-2-microglobulin free heavy chain (SFHC) assay have been used to rapidly diagnose PCM in renal failure and provide prognostic information in the setting of renal failure where the Durie-Salmon and International Staging Systems do not. A renal biopsy early in the course of renal impairment can provide diagnostic and prognostic information. A new generation of dialyzers with larger pores than routine dialyzers can be used with extended hemodialysis to remove SFLC more efficiently than plasmapheresis, allowing for greater renal recovery. Novel chemotherapy agents such as bortezomib are associated with an improved renal response and have moved to the front line of therapy. Successful use of high-dose therapy and autologous hematopoietic cell transplantation (HCT) in PCM with renal failure and even dialysis dependency has been associated with late renal recovery and also allowed for the subsequent use of renal transplantation to provide even greater survival benefits. Combined non-myeloablative allogeneic HCT with renal transplant in PCM patients with end-stage renal disease on dialysis is now being studied in prospective trials.

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Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney

Cited by 33 publications

References 33 publications

Onco-Nephrology

Onco-Nephrology

Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors

Renal failure in multiple myeloma: a medical emergency

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