Multiple Myeloma as a Potential Cause of Low Complements in Patients With Acute Kidney Injury.

Multiple myeloma (MM) is a plasma cell malignancy belonging to the class of monoclonal gammopathies that leads to end-organ damage myeloma events that encompass anemia, the presence of lytic bone lesions, hypercalcemia, and renal insufficiency. However, there are very few reported cases of patients with low complements in the context of MM and renal failure. Traditionally, low complements in glomerular disease are associated with conditions such as membranoproliferative glomerulonephritis, cryoglobulinemia, systemic lupus erythematous, and post-infectious glomerulonephritis. Despite its rarity, physicians should maintain a high degree of suspicion and consider MM as a potential cause of low complements in patients with renal injury. In this case report, we present a patient with a history of MM associated with acute kidney injury with hypocomplementemia, an atypical presentation of myeloma in MM.

Renal outcome in multiple myeloma patients with cast nephropathy: a retrospective analysis of potential predictive values on clinical and renal outcome.

OBJECTIVE: Cast nephropathy (CN) is the leading cause of acute kidney injury (AKI) in multiple myeloma (MM). Since it is sparsely documented why some patients with CN do achieve a renal response while others do not, we describe a single-center cohort of patients with multiple myeloma and biopsy-confirmed CN to evaluate potential markers of renal response. METHODS: The data was collected as a retrospective, single-center analysis of CN-patients treated at the Medical University Vienna between 01/01/2004 and 01/01/2022. Baseline parameters and clinical outcome was compared between renal responders and non-responders. RESULTS: Among 28 patients with CN, n = 23 were assessed for renal response (14 responders; 9 non-responders). Renal responders were younger (median age: 61 years; 77 years, p = 0.039), showed higher overall survival (153months; 58months, p = 0.044) and achieved hematologic response (≥PR) to first-line therapy (p = 0.029), and complete hematologic response (CR) at any time (p = 0.025) significantly more often. Further, we could show that rapid initiation of anti-myeloma therapy after initial presentation correlated significantly with renal response (median 9 days; 27 days, p = 0.016). Analyses of kidney biopsy specimens revealed that patients with a high IF/TA score showed end stage renal disease (dialysis ≥ 3 months) significantly more often (p = <0.001). DISCUSSION: In summary, our data suggests, that a rapid start with systemic hematologic treatment in patients with MM and CN is crucial and achieving an early hematologic response is important for renal recovery. Moreover, achieving a deep hematologic response and subsequent renal recovery improves clinical outcome as reflected by an overall survival benefit.

Procollagen C-proteinase enhancer-1 and renal failure in multiple myeloma.

BACKGROUND: Renal involvement is present in approximately 50% of multiple myeloma (MM) cases and is associated with a poor prognosis. Procollagen C-Proteinase Enhancer 1 (PCPE-1) is an extracellular matrix glycoprotein that has been shown to increase collagen production by enhancing the activity of Procollagen C-Proteinase (PCP) involved in collagen fibrillogenesis and contribute to the fibrotic process. This study investigates the relationship between PCPE-1 and renal function in myeloma patients. METHODS: Eighty-one adults, consisting of 61 patients diagnosed with MM and 20 healthy controls, were included in this cross-sectional study. The MM patients with renal injury (RI) were classified as "MM-RI( +)" and those with no RI as "MM-RI(-)". RESULTS: The median serum PCPE-1 level was 10.7 (5.0-39.4) ng/mL for the entire study population, 9.9 (5.0-13.6) ng/mL for the control group, 10.0 (6.4-22.5) ng/mL for the MM-RI(-) group, and 11.4 (8.1-39.4) ng/mL for the MM-RI( +) group. The difference between the control group and MM-RI( +) group was statistically significant (p < 0.013). PCPE-1 levels negatively correlated with estimated glomerular filtration rate (eGFR), serum albumin, and hemoglobin levels but positively correlated with serum creatinine and CRP levels in the entire study population. Among MM patients, only serum phosphorus and beta-2-microglobulin (ß2M) were positively correlated with PCPE-1. PCPE-1 levels was not affected by other parameters in the entire study population and in the MM group. CONCLUSIONS: Although serum PCPE-1 was higher in the MM-RI( +) group, it was thought to be associated with low GFR reflecting non-specific kidney injury rather than myeloma-related kidney injury.

Outcomes of kidney transplantation in patients with myeloma and amyloidosis in the USA.

BACKGROUND: Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. METHODS: We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. RESULTS: Among 168 369 adult first kidney transplant recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67-2.99] and aHR 1.40 [95% CI 1.08-1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37-2.53) versus aHR 1.16 (95% CI 0.89-1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91-2.56) and aHR 1.30 (95% CI 1.03-1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. CONCLUSION: The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD.

Multiple Myeloma and Renal Failure: Mechanisms, Diagnosis, and Management.

Multiple myeloma (MM) is the second most common hematologic malignancy that involves monoclonal immunoglobulin (Ig)-producing plasma cells. Due to its multifaceted clinical manifestations and complications, it draws attention to various medical specialties like neurology, nephrology, orthopedics, cardiology, etc. Renal failure (RF) is one of the most common and most serious complications of MM that can be caused either by excess immunoglobulins that are nephrotoxic or some other causes like hypercalcemia, infection, etc. In this review article, we have discussed the pathogenesis of RF in MM, described the different diagnostic tools to diagnose RF in MM, and explained different treatment modalities to treat RF in MM, including certain general measures (i.e., hydration, withholding any nephrotoxic agents), renal replacement therapy, serum free light chain (SFLC) removal by plasma exchange and high cut-off dialyzer (HCO-HD), chemotherapy, hematopoietic stem cell transplantation (HSCT), and renal transplantation.

A New Reality for Multiple Myeloma Renal Failure: US Data Report on Kidney Transplant Outcomes.

INTRODUCTION: Describe graft and overall survival outcomes in multiple myeloma (MM) patients who underwent kidney transplant (KT) compared to the general KT population. PATIENTS AND METHODS: The Organ Procurement and Transplantation Network/National United Network for Organ Sharing (OPTON/UNOS) database was analyzed from 1988 to 2019 with R 4.00 and the 2013-2017 United States Renal Data System (USRDS) was surveyed for incidence and mortality of MM ESRD. RESULTS: USRDS analysis revealed 961 patients diagnosed with ESRD due to MM on average annually, accounting for 0.8% of the ESRD population. Without KT, 44.4% of MM patients died in the first year of renal replacement initiation. OPTON/UNOS analysis identified 218 MM KT patients, compared to 490,089 patients without MM. There was no difference in graft survival between MM KT and the general population (P-value = .13, HR = 1.19 [0.95, 1.49], 95% CI). Median graft survival in MM KT was 2683 days (7.4 years). KT patients with MM had a higher risk for death (P-value = <.0001, HR = 1.83 [1.41, 2.37], 95% CI), and median overall survival was 3076 days (8.4 years). Survival difference was lost when comparing patients ≥50 years (P-value = .42, HR = 1.14 [0.83, 1.56], 95% CI). CONCLUSION: Patients with MM renal failure who underwent KT had equivalent graft and age-matched overall survival compared to the general KT population. Therefore select patients with MM renal failure have potential for excellent KT outcomes, should be considered for transplantation when feasible, and should not be excluded from KT based on a history of MM.

A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment.

Acute kidney injury (AKI) is a common presentation which can result from a number of different underlying pathological processes. Haematological malignancies, particularly multiple myeloma (MM), are known to frequently present with AKI. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare condition which can cause crescentic glomerulonephritis (GN), resulting in AKI. We present the case of a 60-year-old man who presented with clinical features suggestive of AAV in the context of blood tests which demonstrated AKI and positive perinuclear ANCA (p-ANCA) and anti-myeloperoxidase (anti-MPO) titres. Further investigations demonstrated an underlying diagnosis of MM. A renal biopsy was ultimately required to determine the cause of AKI, a cast nephropathy. This case is the first to our knowledge which demonstrates a rare situation in which myeloma kidney is associated with positive p-ANCA and anti-MPO titres, without any evidence of a crescentic GN. It highlights the importance of following up on all investigations sent in the context of AKI, even when a potential diagnosis seems evident. Furthermore, it demonstrates the role of renal biopsy in confirming a diagnosis in the context of AKI with multiple differential diagnoses.

Crystals, crystals everywhere but not a clue till late Light chain crystalline proximal tubulopathy with concomitant myeloma cast nephropathy.

The renal diseases commonly associated with myeloma include primary amyloidosis, cast nephropathy, and light chain deposition disease. Less frequent forms of renal involvement encountered in the course of myeloma are crystalline and non-crystalline proximal tubulopathies, neoplastic plasma cell infiltration, and immunoglobulin crystallization in interstitial histiocytes and glomerular cells including podocytes. Light chain proximal tubulopathy (LCPT) caused by aggregation of non-crystalline and rarely crystalline deposits of monoclonal light chains in the cytoplasm of proximal tubular epithelial cells, accounts for less than 5% of monoclonal gammopathy-associated kidney diseases. We report the case of a 48-year-old Indian woman with multiple myeloma, who presented with acute kidney injury and nephrotic syndrome, in whom the renal biopsy revealed widespread crystalline inclusions in extraglomerular and glomerular compartments. We present illustrative light microscopic (LM) and diagnostic electron microscopic (EM) findings of this case which enabled a diagnosis of crystalline LCPT, crystal storing histiocytosis, and crystalline podocytopathy occurring synchronously with myeloma cast nephropathy. While documenting this unique juxtapositioning of multicompartmental paraproteinemic renal injury in multiple myeloma, diagnosed after EM analysis of the patient's renal biopsy, we discuss the pathogenetic pathways of this condition along with the clinical implications. Due to intrinsic structural properties of the crystals, they frequently escape detection by routine LM, necessitating EM analysis for their diagnosis. Given the prognostic implications of tubulopathies complicating myeloma, LCPT is a critically important diagnosis, highlighting the need for a comprehensive renal biopsy evaluation inclusive of EM for the practice of precision medicine in such scenarios.

Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.

PURPOSE OF REVIEW: To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephropathy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event. RECENT FINDINGS: The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein.

Unusual Presentation of Light Chain Deposition Disease: A Case Report.

Light Chain Deposition Disease (LCDD) is a rare disease characterized by deposition of monoclonal non-amyloid light chains in multiple organs. We report an unusual histologic manifestation of LCDD in a 55-year-old female patient, who presented with nephrotic syndrome and an increased serum creatinine. This case of LCDD had features of cast nephropathy on biopsy which is diagnostic of myeloma kidney, when the patient was clinically asymptomatic. Serum electrophoresis showed no abnormal band. There was no other evidence of a B-cell clonal disorder or amyloidosis. Following chemotherapy, improvement in renal function correlated with a reduction in circulating light-chain levels.

Mieloma múltiple de cadenas ligeras con compromiso renal / Light cain multiiple myeloma with renal invovvement

El mieloma múltiple es una enfermedad caracterizada por una proliferación de: células B en la cual la afección renal es una complicación frecuente tanto al momento del diagnóstico como durante su evolución. La nefropatía es multifactorial siendo el riñón del mieloma la más frecuente. Además existen factores precipitantes que agravan la afección. Se presenta el caso de un paciente con el diagnóstico de mieloma múltiple de cadenas ligeras kappa que debutó con afección renal Recibió manejo de sostén combinado con quimioterapia presentando una evolución favorable y reversibilidad de la afección renal que mejora la supervivencia.

Multiple myeloma is a disease characterized by a proliferation of B cells in which renal disease is a common complication at diagnosis and during its evolution Nephropathy is multifactorial and myeloma kidney is the most common cause. There are also precipitating factors that aggravate the condition. This is a case of a male adult patient diagnosed with multiple myeloma kappa light chain who debuted with kidney disease. He received support management combined with chemotherapy and he had a favorable evolution and reversibility of renal disease.

A Case of Multiple Myeloma of Kappa Light Chain Type Associated with Gastric Amyloidosis and Acute Renal Failure and Pathologic Fracture Due to Femur Plasmacytoma / 대한신장학회잡지

Primary amyloidosis has been reported to develop in 6 to 15% of patients with multiple myeloma and especially in 20 to 24% of patients with light chain myeloma. Although deposition of amyloid in the gastric mucosa is common in primary systemic amyloidosis(AL), gastric amyloidosis in AL type is rarely symptomatic. Also, pathologic fracture of the femur secondary to plasmacytoma is quite rare for the first manifestation of multiple myeloma. A case of gastric amyloidosis associated with gastric outlet obstruction and femur plasmacytoma in multiple myeloma is reported with review of literatures.