Multiple Myeloma With Treatment Kappa Lambada Ratio Normal Now High Again
Indian J Nephrol. 2010 April; 20(2): 94–96.
Consummate remission of lambda light chain myeloma presenting with acute renal failure following treatment with bortezomib and steroids
M. Pavan
Department of Nephrology, Lilavati Infirmary and Enquiry Centre, Mumbai, Bharat
Yard. A. Ashwini
Department of Nephrology, Lilavati Hospital and Research Heart, Bombay, India
R. Ravi
Department of Nephrology, Lilavati Hospital and Research Centre, Bombay, India
50. H. Suratkal
Department of Nephrology, Lilavati Hospital and Research Centre, Bombay, Republic of india
Abstract
About one in five people with multiple myeloma produce only calorie-free chains. Patients with lambda light chain affliction have a three times worse prognosis than kappa low-cal chain illness. We report a case of lambda light chain deposition disease in a 35-twelvemonth-old female who presented with acute renal failure requiring hemodialysis. She had complete recovery and is now in complete remission following handling with bortezomib and steroids.
Keywords: Acute renal failure, bortezomib, lambda and kappa light chains, multiple myeloma, steroids
Introduction
Light chain deposition disease is an uncommon monoclonal gammopathy, which should be considered carefully in patients who have both renal illness and a lymphoplasmacytic disorder capable of producing monoclonal light chains- myeloma, macroglobulinaemia, lymphoma, chronic lymphatic leukemia. Patients ordinarily present with the nephrotic syndrome (NS) or asymptomatic proteinuria with renal impairment which may exist progressive and quickly so in some cases. The diagnostic histological finding is the deposition of a single light concatenation isotype (kappa in lxxx% of cases) in the glomerular capillaries and nodules along Bowmen's capsule and the tubular basement membrane.[i] We nowadays a case with rare lambda lite concatenation myeloma with calorie-free concatenation deposition in renal tubules. She underwent into complete remission post-obit treatment with Bortezomib and steroids.
Example Report
A 35-year-erstwhile woman was admitted to our hospital with complaints of anorexia, nausea, episodic airsickness and loss of appetite for the last seven days and decreased urine output for two days, complete urine close downwards since one day. She denied whatever history of fever, pain abdomen, dysuria, hemeturia and pedal edema. She did not accept diabetes or hypertension.
Physical exam revealed a heart age woman in no acute distress. Blood pressure was 110/70 mm of Hg. The pulse was 82 beats/min and regular. She had mild pallor. Rest of the systemic examination was unremarkable. Initial laboratory work up revealed: hemoglobin 9.6gm/dl, packed cell volume- 28.3%, total leukocyte count-12900/mmthree. Routine urine test showed specific gravity of urine one.005, pH>6, urinary albumin- 1, WBC- 12-15/loftier power field and RBC's – negative. Renal contour was done and values were: blood urea nitrogen 45mg/dl, creatinine 12.03 mg/dl, uric acid nine.xxx mg/dl, calcium seven.83 mg/dl, phosphorus 4.96 mg/dl, serum total proteins 6.0 one thousand/dl, albumin 3.0 g/dl, globulin; three.0 grand/dl, spot urine for poly peptide creatinine ratio 6.0. Patient was negative for HIV 1and 2, hepatitis B surface antigen, HCV antibodies. Complement factor C3 and C4 were inside normal limits. Patient was worked up for vasculitis and connective tissue disorder with ANA, Anti dsDNA, c-ANCA, p-ANCA and anti glomerular basement membrane antibodies and all the parameters were negative. Ultrasonography of the abdomen revealed bilateral bulky kidneys with mild increase in cortical reflectivity and cortico medullary differentiation was normal.
In view of worsening azotemia she was initiated on hemodialysis. Kidney biopsy was performed in view of acute onset of unexplained renal failure, afterward iv sessions of hemodialysis. The histopathological finding showed that the glomeruli were normocellular, in that location was mild increase in mesangial matrix, tubules showed multiple fractured casts and crystals within the casts. There was polymorpho nuclear and histiocytic reaction effectually the crystals with denudation of tubular epithelium. A few casts showed behemothic prison cell reaction around them. At that place was focal interstitial infiltrate of lymphocytes and plasma cells [Effigy one]. Immuno histochemical staining was washed to demonstrate the presence of light chains and which showed the positive lambda and negative kappa chains [Effigy 2]. Electron microscopy showed sclerosed and totally obliterated glomerulus. The tubules contained casts of condensed osmophilic material and large vacuoles in the surrounding epithelial cells.
Photomicrograph showing cast nephropathy (H and Due east, ×440)
Immunihistochemistry showing positivity for lambda chain (×440)
Based on the history, clinical features and laboratory investigations, patient was diagnosed as cast nephropathy suggestive of plasma jail cell myeloma. This was farther confirmed with the help of serum protein electrophoresis which showed Thousand band in gamma region. Urine Bence-Jones protein was absent-minded and serum allowed fixation (qualitative) was positive for monoclonal gammopathy in lambda region, which was quantitated and values were equally follows: free kappa low-cal concatenation 37.twenty (normal three.3-19.4) mg/l, free lambda low-cal chain 8220.00 (five.71-26.3) mg/l, free kappa/lambda ratio; below 0.01 (0.26-one.65). Increased plasma cells (22%) were seen in bone marrow aspiration and bone marrow biopsy was consistent with plasma prison cell myeloma.
She was treated with five cycles of plasma exchange therapy along with regular hemodialysis. Her plasma exchange prescription included 2 liters of commutation/bike (35 ml/kg) with blood period of 100 ml/min, simultaneously replaced albumin and fresh frozen plasma in 50:50 mixtures using heparin as anticoagulant. Along with plasmapheresis she was started on bortezomib (2 mg Iv bolus on 1, 4, 8, 11thursday day) and dexamethasone xl mg/day for starting time three days under the guidance of a haematologist in each cycle. At the end of the first cycle, her urine output improved significantly and she went off hemodialysis. Her renal function too improved and her serum creatinine levels stabilized at iii mg/dl without requiring haemodialysis. Her tumor brunt too came down in a pregnant fashion. At the end of first cycle of chemotherapy her serum free lambda low-cal chain levels dropped from 8220 mg/l to 136 mg/50. Her serum-free kappa/lambda ratio came back to normal (0.30). She was treated with two more cycles of chemotherapy with 10 days of rest in between each cycle. Similarly, her serum-free lite chain, serum creatinine and protein electrophoresis was performed at the end of each cycle. At the end of the threerd wheel her renal function returned to normal (serum creatinine 1.0 mg/dl). Her tumor burden also returned to normalcy (serum free lambda calorie-free chain-25 mg/l) without having M band in protein electrophoresis and now she is under complete remission.
Discussion
The presence of simply a low-cal concatenation monoclonal poly peptide is seen in ~20% of multiple myeloma cases and the status is known equally light chain myeloma.[2] Light concatenation myeloma patients secrete either low molecular weight kappa or lambda chains which get filtered at glomerulus, reabsorbed and catabolized in renal tubules. Patients with light concatenation myeloma have low-cal-chain deposition in many organs, including the kidneys, liver, and heart, every bit well as in the skin and nervous system. Proteinuria or renal insufficiencies are the most common presenting complaints. Two-thirds of patients with light-chain degradation have myeloma or other lymphoplasmocytic proliferative diseases. The remaining one-third of patients has no demonstrable systemic illnesses.[3]
In patients with established renal failure, peritoneal dialysis or hemodialysis can exist used. Unfortunately, the prognosis for myeloma patients with acute renal failure is poor despite aggressive intervention. In several series, renal role recovered in only a small fraction of the patients, and a large fraction of the patients died inside a few months.[iii]
Plasmapheresis has occasionally been effective in the treatment of ARF. Zucchelli and colleagues reported that handling with plasmapheresis, chemotherapy, and haemodialysis, when needed, was superior to handling with chemotherapy and pre-emptive intermittent peritoneal dialysis.[4] Recently Pillon et al. supports the use of plasmapheresis in treating biopsy proven myeloma cast nephropathy.[5] A study past Leung et al. suggests plasma exchange may be beneficial in the treatment of bandage nephropathy. They constitute that the relationship between renal recovery and complimentary light chain reduction using plasmapheresis was present merely in patients with biopsy proven cast nephropathy showing the importance of extracorporeal light chain removal in this disease.[6] Not all patients treated with plasmapheresis have renal recovery, withal, Cserti et al. reported plasmapheresis failed to effectively lower serum free light chain levels and concluded that plasmapheresis is an ineffective adjunct to chemotherapy for myeloma associated acute renal failure.[7]
Bortezomib, a reversible proteasome inhibitor, has shown significant action in myeloma patients and is safely administered to patients with renal failure, fifty-fifty those under dialysis. In one study, the combination of Bortezomib with high dose Dexamethasone resulted in rapid reduction of toxic light chains and improvement of renal function. It concludes that this is an active combination that results in rapid hematologic responses, rapid decrease of proteinuria, and improvement of renal function in patients with light chain deposition disease.[8]
In our patient, nosotros followed the aforementioned regimen along with plasmapheresis which resulted in rapid reduction of free light bondage along with complete recovery of renal office.
Acknowledgments
I would similar to acknowledge Dr. Jeevan K Shetty, Assistant Professor, Biochemistry, KMC Manipal, Dr Abhay Bhave and Dr. Anup Chaudhari, Lilavati hospital, Bombay, for their contribution in preparation of manuscript.
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931142/
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