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Introduction This case highlights the importance of getting a thorough workup for acute kidney injury before assigning a diagnosis. Case presentation A 68-year-old male was referred to our clinic after a recent outside hospitalization for septic knee arthritis and acute kidney injury requiring hemodialysis. He had chronic kidney disease presumed secondary to diabetes with baseline GFR 50 mL/min. He complained of fatigue and weight loss. Vital signs were within normal limits. Exam was notable for trace ankle edema, healed right knee scar, and right internal jugular hemodialysis catheter. Medications included amlodipine, aspirin, atorvastatin, furosemide, sevelamer, and cephalexin. Calculated creatinine clearance was 6 mL/min with urine output 2 L/day. Urinalysis showed 1+ protein, 2+ glucose, and fine granular casts. Clinical impression was ischemic acute tubular necrosis in recovery phase. However, when he did not improve and continued requiring dialysis, further workup showed elevated serum κ free light chains and urine Bence-Jones protein. Renal biopsy showed κ light chain crystalline tubulopathy, interstitial inflammation, and extensive fibrosis. Subsequent bone marrow biopsy showed 15% κ-restricted plasma cells. Multiple myeloma was diagnosed, and chemotherapy initiated. With decrease in κ light chain burden, kidney function improved, and patient was able to come off dialysis. Conclusion This case describes a rare presentation of κ light chain crystalline tubulopathy and illustrates the value of a comprehensive evaluation for acute kidney injury to enable prompt diagnosis and therapy. .

Background The International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy. Objective This study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population. Methods Sixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 - March 2018. Measured 24-h urine BJP was compared to two estimated 24-h BJP excretions calculated as follows: Estimation 1 (E1): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 10. Estimation 2 (E2): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 15 mg/kg for women or × 20 mg/kg for men. Results Correlation of estimation equations E1 and E2 to the measured 24-h urine BJP was 0.893. Patients showed no difference in classification of treatment response using either the E1 or E2 estimation equations when compared to the measured 24-h urine BJP results. Conclusion This study demonstrates that the estimated 24-h BJP shows a high degree of correlation with the measured 24-h BJP and can likely be used to monitor treatment response in South African patients with MM.

A 64-year-old African American male presented to the emergency department with subacute low back pain for two weeks and decreased urine output. He was found to have a potassium level of 9.2 mmol/L and was uremic with a creatinine level of 28.5 mg/dL and blood urea nitrogen (BUN) level of 201 mg/dL. He also tested positive for COVID-19. He was then started on continuous renal replacement therapy (CRRT). His urinalysis showed more than 500 mg/dL of protein. A workup for multiple myeloma was also conducted, and urine protein electrophoresis test was positive for free lambda light chains with a level of 17,700 mg/L and free kappa light chains with a level of 88.30 mg/L with a kappa:lambda free light chain ratio of 0.005. Additionally, serum Bence Jones protein level was elevated at 240 mg/dL, and serum beta-2 microglobulin level was elevated at 31.41 mg/L. An immunoglobulin (Ig) panel also showed low levels of IgG, IgA, and IgM. Kidney biopsy for this patient showed definite cast nephropathy and minimal chronic changes, with only one of over 20 glomeruli sclerosed and minimal interstitial deposits. The patient was started on chemotherapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD).

We herein report a case of a combined crystalline light chain tubulopathy, podocytopathy, histiocytosis, and cast nephropathy in a patient with monoclonal gammopathy of renal significance (MGRS). A 66-year-old female with impaired renal function was referred to our department. Despite intravenous fluid resuscitation, the kidney function worsened progressively; thus, a kidney biopsy was performed. The kidney biopsy revealed light chain proximal tubulopathy (LCPT) with crystals, light chain crystal podocytopathy (LCCP), crystal-storing histiocytosis (CSH), and light chain cast nephropathy (LCCN). Of note, LCCP and CSH were diagnosed via electron microscopy. Serum and urine immunoelectrophoresis (IEP) revealed the presence of monoclonal Bence–Jones protein and free κ light chains. Bone marrow aspiration showed

Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (0.26 & 1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR > or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.

The detection and quantification of immunoglobulin free light chains in serum and urine is recommended for the diagnosis and monitoring of monoclonal gammopathies according to the guidelines of the International Myeloma Working Group (IMWG). Several tests are currently available in the clinical laboratory to detect and quantify free light chains but although quality, efficiency, and effectiveness have been improved, the results are still variable and poorly harmonized and standardized. The present review article wants to analyze these aspects, with a keen eye on techniques, such as mass spectrometry, that could replace in the practical clinical laboratory the current methods including Bence-Jones protein assay and free light chain immunoassays.

Multiple myeloma (MM) is the most common malignancy associated with end-stage renal disease; the presence of renal involvement reduces the median survival of patients with MM. Recently the term “monoclonal gammopathy of renal significance” (MGRS) has been defined that describes all B cell or plasma cell proliferative disorders that produce a monoclonal immunoglobulin associated with progressive kidney injury. The excessive amount of clonal light chains is completely filtered and adsorbed till the maximum capacity of proximal tubule that could be saturated, so the excess of FLC presents in the urine as Bence Jones proteinuria. The different biochemical characteristics of FLC determine a different histological involvement, which imply the variable clinical presentation ranging from severe acute kidney injury to chronic renal failure with different grade of proteinuria. Actual therapies are directed to prompt FLC removal from circulation by apheresis and control of their production by proteasome inhibitors and the immunomodulatory drugs used in MM. They are needed to prevent progression of the renal involvement and improve renal prognosis.

Leptomeningeal myelomatosis (LMM) is a fatal complication that occurs in < 1% of patients with multiple myeloma. Many patients with LMM present with neurologic symptoms referable to cranial neuropathies, while the manifestation of communicating hydrocephalus has been underrecognized. A Japanese man with Bence Jones protein-κ multiple myeloma developed fever and headache at age 54 years. He then became somnolent and went into a coma. Neuroimaging analyses identified rapidly progressive communicating hydrocephalus due to meningitis. He died 83 days after the onset of headache without any response to treatment at age 55 years. No symptoms or signs associated with cranial nerves were found during the course of illness. Postmortem examination revealed hydrocephalus and diffuse infiltration of myeloma cells into the subarachnoid space of the cerebrum, cerebellum, and brainstem. In addition, the interstitial tissue of the choroid plexuses was filled with myeloma cells. These myeloma cells were positive for CD156 and light chain κ. The Ki-67 labeling index in myeloma cells of the central nervous system (CNS) was 30-40%. Histopathological examination further revealed many myeloma cells on the surface of the lateral, third and fourth ventricles and at the area postrema of the medulla oblongata. Patients with LMM can develop an aggressive form of communicating hydrocephalus. Given that cerebrospinal fluid, produced by epithelial cells in the choroid plexuses of the ventricles, passes into the subarachnoid space through the third and fourth ventricles, myeloma cells may invade the CNS through the choroid plexuses.

AL amyloidosis (AL) is a systemic disorder due to extracellular tissue deposition of amyloid fibrils, composed of immunoglobulin light chains. Since the description of AL involving temporal arteries in 1986, this disorder has been known as one of the differential diagnoses of giant cell arteritis (GCA). We encountered a case of an elderly female presenting with headache and tender and enlarged temporal arteries, that was pathologically diagnosed with temporal artery involvement of AL due to Bence-Jones-type MM. To our knowledge, this was the first case of AL with temporal artery involvement in Japan, that presented with GCA-like features. Literature review of AL cases with temporal artery involvement showed close similarity between these disorders, but suggested that vasculature involvement (extremity claudication, kidney or heart), macroglossia, carpal tunnel syndrome and normal or low (0.5 mg/dL) CRP levels may predict AL rather than GCA. Physicians should keep in mind that AL involving temporal arteries can be a pitfall in the diagnosis of GCA, as seen in our and previous cases.

Testing urine for Bence Jones Protein (BJP) had been a time old procedure used for screening and monitoring of monoclonal disorders since its description. However, has poor sensitivity and despite advances in diagnostic methods of monoclonal disorders it is being continued to be requested in individuals for evaluation of myeloma or plasma cell disorders. Effective utilization and minimizing untimely or unnecessary investigations is important in the evaluation and management of any medical condition. Though, we are hard-wired during our education with some “trigger” or “peculiar” words that make us jump to actions too quickly, without comprehending the actual problem. Supporting evidence is presented to avoid reflexive use of multiple tests and utilize tests that improve utilization, reduce waste, and uphold the Choosing Wisely principles in providing optimal care to the patients.

The formation in β-structured protein aggregates in tissues and fluids of the body is one of the most dangerouse complications of various diseases. The most famous of them are amyloidoses, but they such deposits are observed at other, much more widespread, diseases. The generally accepted approach to amyloids’detectionis based on high-specific coloring by Congo Red dye. However, the Abbe's diffraction limit excludes the seeing of the objects smaller than 0.61 wavelengths (about 240 nm). Such nanoscale formations are capable to disrup the functioning of surrounding tissues, to causethe complications and recurrences of the disease, and to pass through biological barriers with the following accumulation in body’s fluids. It’s likely that these conditions are the cause of the urinary congophilia, that is associated with preeclampsia at pregnancy and chronic kidney disease. Nor the less suspicious object is the Bens-Jones protein that appears in the urine at multiple myeloma and some other diseases, which are in more or less extent,are related to the disturbance of protein metabolism. The purpose of this study was to clarify the aggregate state of the Bens-Jones protein as a possible β-structured supramolecular associate. Methods.The subject of the study was the freshly received urine from a patient with multiple myeloma. The presence of the Bens-Jones protein was checked by thermopacification of the acidified sample. For control, the urine was used by a healthy person with the addition of certain amounts of human serum albumin ("Reanal", Hungary) with a concentration of 0, 0.01, 0.1 and 1%. Result. The obtained data testify to the appropriateness of such a point of view and create preresquites for the expanding of diagnostic possibilities. Conclusions.The results obtained during the study testify to the peculiarity of the structure of the Bens-Jones protein, which is nano-sized beta-structured supramolecular

We herein report a 65-year-old man with elevated serum IgG4 levels, enlarged thyroid, and renal dysfunction, mimicking IgG4-related disease (IgG4-RD). The definitive diagnosis of IgG4-RD was not established because a tissue biopsy revealed no IgG4-positive cell infiltration or fibrosis. The presence of an M peak in the β fraction, Bence Jones protein in urine, and progressive anemia suggested multiple myeloma (MM). The κ/λ ratio was >100, tumor plasma cells were present at >20% in bone marrow, and immunostaining revealed IgG4-positive plasma cells; therefore, he was diagnosed with IgG4-type MM. Patients with elevated IgG4 levels with no significant mass lesions should undergo systemic examinations to exclude malignancy.

Multiple myeloma nephropathy occurs due to the aggregate formation by monoclonal immunoglobulin light chains (Bence-Jones proteins) in kidneys of patients with multiple myeloma. The mechanism of amyloid deposit formation is still unclear. Earlier, the key role in the fibril formation has been assigned to the variable domains that acquired amyloidogenic properties as a result of somatic mutations. However, fibril formation by the Bence-Jones protein BIF was found to be the function of its constant domain. The substitution of Ser177 by Asn in the constant domain of the BIF protein is most likely an inherited than a somatic mutation. To study the role of this mutation in amyloidogenesis, the recombinant Bence-Jones protein BIF and its mutant with the N177S substitution typical for the known immunoglobulin Cκ allotypes Km1, Km1,2, and Km3 were isolated. The morphology of aggregates formed by the recombinant proteins under conditions similar to those occurring during the protein transport in bloodstream and its filtration into the renal glomerulus, in the distal tubules, and in the proximal renal tubules was analyzed by atomic force microscopy. The nature of the aggregates formed by BIF and its N177S mutant during incubation for 14 days at 37°C strongly differed and depended on both pH and the presence of a reducing agent. BIF formed fibrils at pH 7.2, 6.5, and 10.1, while the N177S mutant formed fibrils only at alkaline pH 10.1. The refolding of both proteins in the presence of 5 mM dithiothreitol resulted in the formation of branched structures.

The first well-documented case of multiple myeloma was reported in 1844 by Samuel Solly. In this article, the author presents a historical review of the disease. In particular, the review is focused on the main steps, including the definition of Bence Jones proteinuria, the characterization of tumoral plasma cells and serum globulins, and the fundamental contribution of Jan Waldenstrom. Finally, treatment of multiple myeloma, as well as the development of new agents, is discussed.

It is now accepted that the ability of a protein to form amyloid fibrils could be associated both kinetic and thermodynamic protein folding parameters. A recent study from our laboratory using recombinant full-length (encompassing the variable and constant domain) immunoglobulin light chains found a strong kinetic control of the protein unfolding for these proteins. In this study, we are extending our analysis by using urine-derived Bence Jones proteins (BJPs) from five patients with light chain (AL) amyloidosis and four patients with multiple myeloma (MM). We observed lower stability in κ proteins compared to λ proteins (for both MM and AL proteins) in agreement with previous studies. The kinetic component of protein stability is not a universal feature of BJPs and the hysteresis observed during refolding reactions could be attributed to the inability of the protein to refold all domains. The most stable proteins exhibited 3-state unfolding transitions. While these proteins do not refold reversibly, partial refolding shows 2-state partial refolding transitions, suggesting that one of the domains (possibly the variable domain) does not refold completely. Sequences were aligned with their respective germlines and the location and nature of the mutations were analyzed. The location of the mutations were analyzed and compared with the stability and amyloidogenic properties for the proteins in this study, increasing our understanding of light chain unfolding and amyloidogenic potential.

A 55-year-old man was admitted to our institute to undergo evaluation for proteinuria (5.4 g/day) with lambda-type Bence-Jones protein (BJP). Primary amyloid light chain (AL) amyloidosis and acquired factor X deficiency were diagnosed. High-dose melphalan combined with autologous stem cell transplantation was performed. After three years, the patient's proteinuria normalized, he was negative for urinary BJP, and his factor X activity improved to 105%. Serial renal biopsy showed no progression of amyloid deposition at a biopsy after 5 years, but showed a slight increase in the amyloid deposition after 11 years. This therapy can improve the prognosis of AL amyloidosis; however, there are limitations to the strategy.

Primary amyloidosis is a rare condition characterised by the deposition of free light chains in different tissues and organs (e.g. kidney, heart, liver, gastrointestinal system). The aim of the therapy in patients with primary amyloidosis is to suppress the monoclonal plasma cells that produce the amyloidogenic free light chains and to preserve the organ function. Thus, the new criteria for the haematological disease response include the measurement of serum free light chains concentrations. The case is presented on a patient diagnosed with primary amyloidosis, where the difference between bound and free serum free light chains (dFLC) was used to evaluate the haematological response to the treatment, as well as any biological progression. In contrast to dFLC, Bence Jones Protein in urine was positive but ineffective to evaluate the response to the treatment.

Multiple myeloma (MM) is about 1 % of all malignancies and 10–15 % in the structure of hemoblastoses. In most patients, MM develops as a result of monoclonal gammopathy of undetermined significance, which is usually diagnosed accidentally in 3–5 % of people over 50 years of age. The average risk of MM progression is about 1 % per year. Thanks to modern diagnostic methods, the diagnosis of MM is now being established faster, which allows the treatment to be started as soon as possible. Polychemotherapy plays a leading role in the comprehensive treatment of MM. At the present stage, novel, particularly targeted, drugs are being developed, the use of which is more effective. An important place in the treatment of MM belongs to high-dose chemotherapy followed by transplantation of stem cells. Some problems in the diagnosis and treatment of patients with MM remain unresolved, so they need more detailed revision, further development of pharmacological drugs and treatment regimens, additional clinical studies. The literature review is based on clinical research data, guidelines of the European Society for Medical Oncology, National Comprehensive Cancer Network, obtained using the PubMed search resource., Множественная миелома (ММ) составляет около 1 % всех злокачественных новообразований и 10–15 % в структуре гемобластозов. У большинства пациентов ММ развивается на основе моноклональной гаммапатии не­ясного генеза, которая диагностируется, как правило, случайно у 3–5 % людей в возрасте старше 50 лет. Средний риск прогрессирования ММ составляет около 1 % в год. Благодаря современным методам диагностики диагноз ММ на текущий момент устанавливается быстрее, что позволяет начать лечение в кратчайшие сроки. Ведущую роль в комплексном лечении ММ играет полихимиотерапия. На современном этапе разработаны новые, в том числе таргетные препараты, применение которых позволяет повысить эффективность лечения. Важное место в лечении ММ занимает высокодозная химиотерапия с последующей трансплантацией стволовых клеток. Отдельные проблемы диагностики и лечения больных с ММ остаются не до конца решенными, поэтому нуждаются в более детальном изу­чении, дальнейшей разработке фармакологических препаратов и схем лечения, проведении дополнительных клинических исследований. Настоящий обзор основан на данных клинических исследований, рекомендаций European Society for Medical Oncology, National Comprehensive Cancer Network, полученных с использованием поискового ресурса PubMed., Множинна мієлома (ММ) становить близько 1 % від усіх злоякісних новоутворень та 10–15 % у структурі гемобластозів. У більшості пацієнтів ММ розвивається на основі моноклональної гаммапатії неясного генезу, що діагностується, зазвичай, випадково у 3–5 % людей віком понад 50 років. Середній ризик прогресування ММ дорівнює близько 1 % у рік. Завдяки сучасним методам діагностики діагноз ММ наразі встановлюють швидше, що дозволяє розпочати лікування в найкоротші терміни. Провідну роль в комплексному лікуванні ММ відіграє поліхіміотерапія. На сучасному етапі розроблені нові, зокрема таргетні, препарати, застосування яких є більш ефективним. Важливе місце в лікуванні ММ посідає високодозова хіміотерапія з подальшою трансплантацією стовбурових клітин. Окремі проблеми діагностики та лікування хворих із ММ залишаються не до кінця вирішеними, тому потребують детальнішого доопрацювання, подальшої розробки фармакологічних препаратів та схем лікування, проведення додаткових клінічних досліджень. Огляд літератури базується на даних клінічних досліджень, рекомендацій European Society for Medical Oncology, National Comprehensive Cancer Network, отриманих з використанням пошукового ресурсу PubMed.

The immunoglobulin (Ig) D type is a rare variant of multiple myeloma (MM), that accounts for 1-2% of all cases. Compared to the more common types of MM, IgD MM is known to have more severe symptoms at presentation, and a poorer prognosis. A woman was admitted to our hospital for severe acute kidney disease and disorder (AKD) and back pain, and was started on hemodialysis. The renal biopsy revealed light chain cast nephropathy. She was diagnosed with IgD-λ MM based on Bence-Jones protein expression and high IgD serum levels, and started bortezomib therapy with plasma exchange (PE). After three sessions of PE, the serum free light chain levels decreased by 92%, and she was withdrawn from dialysis. The patient underwent autologous transplantation and is still in remission, demonstrating the benefits of a bortezomib-based regimen in combination with PE for IgD MM with AKD.

Background:Immunofixation electrophoresis of urinary proteins, coupled with densitometric analysis, is the gold standard method for determining urinary monoclonal free light chains (FLCs), i.e. Bence Jones protein. Recently, immunochemical methods have been developed for Bence Jones protein quantification, but no such method has been widely adopted. This study evaluated a new antibody-based immunoturbidimetry method for urinary FLC quantification, using immunofixation electrophoresis as reference.Methods:κ and λ FLCs were measured in urine specimens from 95 (training cohort) and 103 (testing cohort) patients by both immunofixation electrophoresis and immunoturbidimetry.Results:There was almost perfect concordance in the training cohort between the new immunoturbidimetry assay and immunofixation electrophoresis and substantial agreement, with Cohen kappa of 0.85 and 0.75, for κ and λ FLC determination, respectively. Results were confirmed in the testing cohort, where Cohen kappa was 0.86 for κ and 0.94 for λ FLCs. The κ FLC assay had 88% sensitivity and 98%–100% specificity; the λ FLC assay had 94% and 96% sensitivity and 91% and 99% specificity in the training and testing cohorts, respectively.Conclusions:The new immunochemical method has a satisfactory performance and almost perfect agreement with immunofixation electrophoresis and gives the advantage of FLC quantification.

Background We experienced a patient with multiple myeloma whose urine contained a considerable amount of Bence Jones protein (BJP), which demonstrated poor thermal reactivity in heat coagulation test. The mechanism for this phenomenon was assessed. Methods Immunoelectrophoretic analyses reveal that a band corresponding to BJP in the urine had 2,600 Dalton by reduction after glycosidase treatment, but not after sialidase treatment. In addition, the glycosidase-treated urine tested positive in heat coagulation test. Conclusions Glycosylation of the immunoglobulin light chain, which has rarely been seen, is the cause of the unexpected behavior of this patent's BJP in heat coagulation tests.

Aim: DKK1 is reported to be produced at high levels by myeloma cells. Therefore, the applicability of DKK1 as a tumor marker for multiple myeloma (MM) diagnosis was examined. Methods: Serum samples were collected and analyzed by DKK1 concentration kit and capillary zone electrophoresis. Then, the obtained results were statically analyzed. Results: It has been determined that the 10 ng/ml of DKK1 is the optimal level for MM diagnosis. Moreover, there was an ascending linear correlation between the DKK1 concentration and γ peak. Discussion: The observed correlation could be rooted in the positive feedback loop between MM cells and the mesenchymal stem cells. In view of these results, DKK1 could be deemed as diagnostic marker for MM.

OBJECTIVE: To determine demographic and clinico-pathological characteristics of patients suffering from multiple myeloma (MM) in Peshawar, Pakistan. METHODS: This descriptive, retrospective study was conducted at Pathology Department, Rehman Medical Institute, Peshawar, Pakistan from January 2006 to September 2018. Detailed information of forty patients diagnosed with MM was collected. World Health Organization (WHO) set criterion was utilized to diagnose MM. SPSS version 22 was used for Statistical analysis. RESULTS: Out of 40 patients, 72.5% were males with M:F ratio of 2.63:1 and mean age of patients was 59.26±13.1 years. The common presenting complaints were body/bony pain (87.5%), fatigue (72.5%), body tenderness (45%) and backache (42.5%). Pallor was present in 33 (82.5%) patients. Laboratory studies showed mean hemoglobin level of 8.6±2.1 g/dl, anemia (92.5%), thrombocytopenia (27.5%) and hypercalcemia (17.5%). Elevated ESR (>100) was noted in 29 (72.5%) cases. Renal impairment was established in 35% of patients. Urinary Bence Jones protein was present in 13 (32.5%). Serum protein electrophoresis showed M band in 39 (97.5%) cases. Lytic lesions were detected in X-rays of 31 (77.5%) patients. Based on international staging system, nine (22.5%) cases were in stage I, 16 (40%) in stage II and 15 (37.5%) in stage III. CONCLUSION: Majority of multiple myeloma patients in our study were in the 6th decade of life. Bone pain and fatigue were the most common presenting symptoms. Anemia and elevated ESR were the most common laboratory parameter. Most of the patients were diagnosed in later stages (stage II and III).

Renal involvement may be the presenting feature in a vast majority of patients with multiple myeloma and is one of the key for clinical manifestations of symptomatic multiple myeloma. The purpose of the study was to find out the pattern of renal involvement at the time of presentation of multiple myeloma and to explore its association with clinical, laboratory and pathologic features of these cases. This cross sectional study was conducted in the Department of Nephrology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from February 2016 to September 2017. Forty seven (47) patients of newly diagnosed multiple myeloma having renal involvement were included in the study. Multiple myeloma was diagnosed as per criteria proposed by the International Myeloma Working Group, 2003. Renal involvement was considered to be present when any one of proteinuria, microscopic haematuria, renal impairment or urinary tract infection (UTI) was found in the patient. Renal biopsy was done in suitable patients under ultrasound guidance after taking informed written consent. The pattern of renal involvement was detected and status of renal function was assessed and its clinical, laboratory and pathologic associations were analyzed. Data were managed by using computer based software, the Statistical Package for Social Sciences (SPSS) version 23 (IBM Corp.). Median age at presentation was 59 years with the range of 37-76 years. Female (53.2%) was slightly predominant than male (46.8%) and male to female ratio was 1:1.14. Renal impairment, microscopic haematuria, proteinuria, nephrotic range proteinuria, urinary Bence Jones protein and UTI were found in 70%, 19%, 79%, 25%, 19% and 17% of patients respectively. Median serum creatinine and proteinuria were 256μmol/l and 1.24gm/day. Hypercalcaemia and Bence Jones proteinuria were detected in 36% and 27% of patients respectively with renal impairment which were statistically significant. The precipitating factors for renal impairment were NSAIDs use (67%), hyperuricaemia (49%), hypercalcaemia (36%), dehydration (27%), UTI (18%) and no identifiable factor (3%). Dialysis was required in 15% new myeloma patient. Renal biopsy and histopathological examination revealed myeloma cast nephropathy (30%), amyloidosis (30%), glomerulosclerosis (chronic kidney disease) (20%), monoclonal immunoglobulin deposition disease (MIDD) (10%) and interstitial nephritis with fibrosis (10%). Renal involvement was a common and severe complication of multiple myeloma. Renal impairment was strongly associated with hypercalcaemia, NSAIDs use, hyperuricaemia, Bence Jones proteinuria etc.

Objectives Multiple myeloma (MM) is a malignant disorder characterized by proliferation of a single clone of plasma cells derived from β-cells in the bone marrow. It is the second most common adult hematological malignancy, and it is the most common cancer with skeletal components as its primary site. The purpose of the retrospective study was to assess the hematological profile, different biochemical parameters, and the serum electrophoresis patterns of patients consistent with clinical symptoms of multiple myeloma. Materials and methods A retrospective study of 99 patients diagnosed with multiple myeloma (MM) was carried out at the Hematology Department of Benghazi Medical Center (BMC) in Benghazi, Libya from January 2010 to March 2017. Information on the laboratory features was obtained at presentation (before treatment) and analyzed. Results Of the 99 study detected cases of multiple myeloma at diagnosis, 14% were younger than 45 years and 35% were 70 years or older. The mean age was 61 years, of which 42 (42.4%) were males and 57 (57.6%) were females. Anemia was seen in roughly half of the diagnosed cases, most of which was normocytic normochromic anemia. High erythrocyte sedimentation rate (ESR) was seen in 65.3% of cases and increased neutrophil-to-lymphocyte ratio (NLR) was seen in 29.7%. Other abnormal serum levels with regard to the cases are as follows: hyperproteinemia in 30%, low albumin/globulin (A/G) ratio in 54.2%, hypercalcemia in 11.3%, serum creatinine level of >2.0 mg/dL in 27.2% cases, and increased β2-microglobulin in 67%. Serum protein electrophoresis revealed a localized band in 70.8% of patients. Monoclonal bands were seen in 44 cases (95.7%) and a bi-clonal pattern in two cases (4.3%), 78% of M-band showed migration to γ-region of electrophoretogram and 18% to β-region. Hypogammaglobulinemia was detected in 32.8% and hypergammaglobulinemia was detected in 49.2%. Of the hypergammaglobulinemia, 18.1% showed polyclonal gammaglobulinemia. Bence Jones protein was positive in 50% cases. IgG was the commonest type, followed by IgA then light chain. In 26.5% of cases, the only diagnosis was multiple myeloma. Light chain multiple myeloma patients had high α2 globulin concentration and normal A/G ratio. Apart from the diagnosis of multiple myeloma, a number of cases had varying diagnoses including the following: 4% non-secretory myeloma, 2% amyloidosis with nephrotic syndrome, 2% liver cirrhosis, and 18.2% renal failure. Most patients presented in stage III. Conclusions The presence of anemia, high ESR, and low A/G ratio in elderly patients should alert the clinician to investigate along the lines of multiple myeloma. In this study, unfortunately, the laboratory investigations were insufficient for diagnosing this disease in most patients. Most patients were diagnosed at stage III. Absence of paraprotein in the blood does not exclude multiple myeloma. It was further observed that most of the patients presented with significant renal damage, which attributed to hyperuricemia, hypercalcemia, or high NLR. Multiple causes of renal failure occur in myeloma and are often present at the time of diagnosis.

We describe a chromatographic approach for the purification of urinary free light chains (FLCs) viz., lambda free light chains (λ-FLCs) and kappa free light chains (κ-FLCs). Isolated urinary FLCs were analyzed by SDS-PAGE, immunoblotting and mass spectrometry (MS). The relative molecular masses of λ-FLC and κ-FLC are 22,933.397 and 23,544.336Da respectively. Moreover, dimer forms of each FLC were also detected in mass spectrum which corresponds to 45,737.747 and 47,348.028Da respectively for λ-FLCs and κ-FLCs. Peptide mass fingerprint analysis of the purified λ-FLCs and κ-FLCs has yielded peptides that partially match with known light chain sequences viz., gi|218783338 and gi|48475432 respectively. The tryptic digestion profile of isolated FLCs infers the exclusive nature of them and they may be additive molecules in the dictionary of urinary proteins. This is the first report of characterization and validation of FLCs from large volume samples by peptide sequencing. This simple and cost-effective approach to purification of FLCs, together with the easy availability of urine samples make the large-scale production of FLCs possible, allowing exploration of various bioclinical as well as biodiagnostic applications.

Introduction. Bence-Jones myeloma multiplex is a progressive disease characterized by excessive numbers of abnormal plasma cells in the bone marrow and overproduction of incomplete immunoglobulins, containing only the light chain portion of the immunoglobulins. This type of myeloma occurs 15-20%. The median overall survival is approximately 4 years. Aim of this study was to define prognostic factors affecting overall survival in Bence-Jones multiple myeloma patients. Material and Methods. From 1995 to 2015, we treated 75 patients (49 men and 26 female), average age 55.9 years (range 31-85). Results. Conventional chemotherapy introductory clinical response was achieved in 54 patients (72%), while in 21 patients (28%) the established disease was resistant. Transplantation was done in 45 patients (60%), while 30 patients (40%) were treated with conventional chemotherapy. In the group of patients with transplantation done, tandem was carried out in 11 patients and secondary stem cell transplantation was done in 5 relapsed patients. With 1 patient with tandem stem cell transplantation allogenic (singen) stem cell transplantation was done. Transplant related mortality is 1.5%. The transplanted patients had significantly longer PFS (mediana 13 months vs 7 months, p

We report a 70-year-old woman with Sjogren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjogren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins. Given the involvement in other organs, systemic AL amyloidosis was diagnosed. The patient underwent chemotherapy, but hemodialysis was ultimately instituted. It should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis.

Detection of total free light chains (FLC) of immunoglobulins and their ratio (kappa/lambda quotient) are used in diagnostics and monitoring of multiple myeloma and other gammapathies, primary amyloidosis and multiple sclerosis. Previously described immunoassays with monoclonal antibodies (Mabs) against cryptic and constantly exposed epitopes of FLC failed to recognize rare variants of lambda Bence-Jones proteins and a significant proportion of lambda chains excreted with urine. Aiming to improve this approach, a novel murine Mab (IgG2b coded as 1C8) was employed, which specifically binds free lambda chains but doesn’t interact with native IgA, IgG, and IgM. The novel Mab recognized an epitope exposed at free lambda chains in peripheral blood of healthy donors and patients with multiple myeloma. It is not destroyed or masked upon renal filtration. The aim of this study was to determine basic features of improved assay system, and to estimate its potential in diagnostics of monoclonal gammapathies. The mixtures of three Bence-Jones proteins of either kappa- or lambda- types purified from the urine of multiple myeloma patients were used as calibrator samples. Improved immunometric assay is able to detect free kappa and lambda chains in serum and urine at a scale of 1 to 100 ng/ml, thus being three orders more sensitive than, e.g., detection levels of Freelite method based on polyclonal antibodies. A novel assay allows to detect free kappa and lambda chains at comparable levels in serum or urine, and to deduce kappa/lambda ratio. The proposed assay is able to detect FLC in 10,000-fold excess of whole IgG molecules. The calibrating plots for both antigens are linear on log-log scales, with very similar slopes. Detection thresholds for kappa or lambda chains proved to be 5 and 3 ng/ml, respectively. Mean concentrations of free kappa chains in sera of healthy donors were 6.7±2.1, in urine, 4.2±3.8 mcg/ml. Mean concentrations of free lambda chains were 4.7±1.96, and 1.6±1.0 mcg/ml, respectively. This method, if applied to serum and urine samples from multiple myeloma patients, revealed free light chains were similar to the paraproteins detected by means of electrophoresis/immunofixation. The values of kappa/lambda ratios corresponded to the types of gammapathies revealed.

The paper describes a clinical case of a female woman with nephropathy due to light chain deposition disease caused by secretion of κ Bence-Jones protein. Complete immunochemical remission was achieved after induction therapy using a bortezomib + cyclophosphamide + dexamethasone regimen. Renal function remained unchanged (glomerular filtration rate 16 ml/min), there was a reduction in proteinuria from 5.8 to 2.6 g/day. High-dose melphalan (200 mg/m2) chemotherapy with peripheral blood stem cell autotransplantation was performed as consolidation of remission. A year posttransplantation, there was no secretion of κ light chains; however, monoclonal IgG lambda emerged in a quantity of 3.2 g/l. At the same period, nephrotic syndrome became progressive (daily proteinuria 12 g) and dialysis-dependent renal failure developed. A repeat renal biopsy specimen revealed changes, suggesting that there was a decrease in renal deposits of κ light chains. Simultaneously with this, the obvious negative trend as progressive nephrosclerosis and fixation of IgG and λ light chains in the glomeruli (in the sclerotic areas) cause IgGλ monoclonal protein to be involved in the genesis of further kidney injury. Attention is also paid to different characteristics of capillary wall deposits by density (according to the electron microscopic findings), which may point to their different qualitative composition and possibly different formation duration. Papaprotein Gλ disappeared after a year without therapy, suggesting its reactivity. The findings confirm that worse renal function is caused by the action of paraprotein Gλ due to secondary (after autologous hematopoietic stem cells transplantation) monoclonal gammopathy.Представлено клиническое наблюдение пациентки с нефропатией вследствие болезни депозитов легких цепей, обусловленной секрецией белка Бенс-Джонса κ. После индукционной терапии по схеме бортезомиб + циклофосфамид + дексаметазон достигнута полная иммунохимическая ремиссия. Функция почек оставалась без изменений (скорость клубочковой фильтрации 16 мл/мин), отмечалось уменьшение протеинурии с 5,8 до 2,6 г/сут. Для консолидации ремиссии выполнена высокодозная химиотерапия мелфаланом (200 мг/м2) с аутотрансплантацией периферических стволовых клеток крови. Через год после трансплантации секреция легких цепей κ отсутствовала, однако появился моноклональный IgGλ в количестве 3,2 г/л. В этот же период стал прогрессировать нефротический синдром (суточная протеинурия 12 г), развилась зависимая от диализа почечная недостаточность. В повторном биоптате почки выявленные изменения свидетельствовали об уменьшении количества депозитов в почках, состоящих из легких цепей κ. Вместе с тем явная отрицательная динамика в виде прогрессирования нефросклероза, а также фиксация IgG и легких цепей λ в клубочках (в зонах склероза) заставляют предполагать участие моноклонального белка IgGλ в генезе дальнейшего повреждения почки. Обращено также внимание на разные характеристики депозитов в стенке капилляров по плотности (по данным электронной микроскопии), что может указывать на их различный качественный состав и, возможно, различную давность формирования. Парапротеин Gλ исчез через год без терапии, что свидетельствует о его реактивном характере. Полученные данные подтверждают, что ухудшение функции почек обусловлено воздействием парапротена Gλ вследствие вторичной (после трансплантации аутологичных гемопоэтических стволовых клеток) моноклональной гаммапатии.