Year : 2008 | Volume
: 19 | Issue : 5 | Page : 802--805
Plasma Cell Dyscrasia; LCDD vs Immunotactoid glomerulopathy
Wael L Jabur, Hareth M Saeed, Khalid Abdulla
Nephrology Department, Al-Karamah Teaching Hospital, Baghdad, Iraq
Wael L Jabur
Department of Nephrology, NMC Specialty Hospital, P.O. Box 7832, Dubai, UAE
Light chain deposit disease is a plasma cell disorder characterized by production of a large amount of monoclonal immunoglobulin light chain or part of it, which is usually deposited as an amorphous substance in the kidneys. Immunotactoid glomerulopathy is an uncommon disease, which might be related to plasma cell dyscrasia, and characteristically manifest as organized glomerular ultra structural fibrils or microtubules. In this article, we report a case of a combined presentation of light chain disease and immunotactoid glomerulopathy in a patient with multiple myeloma and reversible advanced renal failure.
|How to cite this article:|
Jabur WL, Saeed HM, Abdulla K. Plasma Cell Dyscrasia; LCDD vs Immunotactoid glomerulopathy.Saudi J Kidney Dis Transpl 2008;19:802-805
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Jabur WL, Saeed HM, Abdulla K. Plasma Cell Dyscrasia; LCDD vs Immunotactoid glomerulopathy. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Dec 8 ];19:802-805
Available from: https://www.sjkdt.org/text.asp?2008/19/5/802/42465
Light chain deposition disease (LCDD)  is part of the monoclonal immunoglobulin deposit disease (MIDD), which implies deposition of light chain (LCDD), heavy chain (Randall's disease) or both in many tissues especially the kidneys.  It is detected in serum protein electrophoresis as M-band. Either of Kappa or Lambda types is found in serum immunofixation study, and by the presence of Bence Jones protein in urine.
Light chains, especially Kappa type, are deposited in the glomeruli, tubular walls and the interstitium, reacting with mesangial cells in the kidneys and provoking the accumulation of the extra cellular matrix detected by Periodic Acid Schiff (PAS). This results in glomerular and tubular basement membrane thickening, nodular glomerulosclerosis, and interstitial fibrosis.  LCDD is usually diagnosed by immunoflourescence study and electron microscopy.  Light chains may cause damage and atrophy of the proximal tubular epithelial cells that manifests as Fanconi syndrome and in advanced cases as renal failure.  Depending on its type and affinity to Tamm-Horsfall protein, light chains may also cause cast nephropathy, which is the commonest cause of oliguric renal failure in multiple myeloma (myeloma kidney). ,
On the other hand, immunotactoid glomerulopathy is a disease that reveals as a variety of histopathological lesions, which include mesangial proliferation, membranous, and membranoproliferative glomerulonephritisis. The disease is diagnosed by electron microscopy, and it manifests as organized fibrils or microtubules in mesangium or glomerular capillaries. Deposits are composed of a monoclonal immunoglobulin of IgG type, and the disease is frequently associated with paraproteinemia. 
In this article, we report a case of a combined presentation of light chain disease and immunotactoid glomerulopathy in a patient with multiple myeloma and reversible advanced renal failure.
A 50-year-old man was discovered on routine work-up for anemia to have renal function impairment. The past medical history was remarkable for normochromic normocytic anemia of unknown etiology, hyperuricemia and glucosuria for the last two years. Drug history was unremarkable.
On examination he was anemic, hypertensive with blood pressure of 164/94. Otherwise the physical exam was unremarkable.
Investigations revealed serum calcium: 10.9 mg/dL, serum uric acid: 10.5 mg/dL, 24–hour urine volume: 2400 ml and protein: 1 gram, serum creatinine: 5.7 mg/dL, and glomerular filtration rate (GFR): 14.8 ml/min.
Connective tissue screening, compliment system, ANCA, and virology screening were unremarkable. Plasma protein electrophoresis revealed M-band of 5.3 gm/dL. Serum immunofixation was positive for monoclonal Kappa light chains with suppression of all other immunoglobulins. Bence Jones protein was positive of monoclonal Kappa light chain.
Ultrasound examination illustrated normal sized kidneys with normal echogenecity and corticomedullary differentiation.
Kidney biopsy with PAS staining disclosed mild mesangial cell hyperplasia and expansion of mesangial matrix. With Mason trichrome staining, the interstitium revealed moderate fibrosis with thickening of tubular basement membrane, tubular atrophy, and diffuse mononuclear cells infiltration. There was no evidence of obstructing casts in the tubules.Immunohistochemistry revealed mild positive reaction against IgG and C3 in the capillary walls, and it was negative for light chains. Electron microscopy examination revealed organized fibrillary and coarse granular dense deposits on the outer surface of the basement membrane.
Bone marrow biopsy was diagnostic of multiple myeloma.
The patient was treated conservatively with angiotensin converting enzyme inhibitors (ACEI), Erythropoetin alpha, one-alpha cholecalciferol, calcium supplement, folic acid, Vit. B complex and iron supplement. He was prepared for creation of vascular access, and he was initiated on thalidomide and dexamethasone. Unexpectedly the patient's renal function improved on conservative measures even before the start of antimyeloma therapy. One month after presentation his serum creatinine returned to 1.5 mg/dL (GFR: 59 ml/min).
The presence of light chain spikes in the plasma and urine in the context of advanced renal failure and histopathological picture of tubulointerstitial disease and ultrastructural granular dense deposits in our patient were more consistent with LCDD, even though the immunohistochemistry for light chains was negative. Some authors have reported glomerular immunoflourescent negative LCDD.  Others found that dense deposits were absent in one third of the LCDD patients.  On the other hand, the immunohistochemistry finding of capillary IgG deposits and most importantly the ultrastructural glomerular finding of organized fibrillary deposits were more consistent with immunotactoid glomerulopathy.
The tubulointerstitial changes were more prominent than the glomerular lesions in light microscopy. Some researchers even suggested that LCDD could be labeled as tubulointerstitial syndrome.  The immune-electron microscopy might be helpful to prove the deposition of light chains in the glomerular and tubular lesions.  On the contrary, tubulointerstitial disease is very rare in immunotactoid glomerulopathy. 
The classical glomerular lesion in LCDD is nodular glomerulosclerosis (60% to 100%),  Otherwise variable expansion of extra-cellular matrix is the rule. In our patient, the glomerular lesion manifested as mild mesangial expansion and hyperplasia. This is either, as Ronco et al suggested, due to an early stage of the disease or to a weaker sclerotic effect of the light chain. 
The typical electron microscopy feature in LCDD is granular dense deposit, where it is usually subendothelial and adherent to the lamina rara interna. Sometimes it invades the lamina densa.  In our patient the dense deposits were constructed from fibrillary [Figure 1] and granular [Figure 2] deposits. Some authors have suggested that the coarse granular deposit might be an early stage of fibrillosis,  however, we believe that they represent different pathologic processes. Although the association of LCDD with amyloidosis is well established, the Congo-red stain was negative in our patient. This highlights the debate of non-amyloidotic fibrillary deposits not related to light chains. ,
The other unusual feature of our case is the sub-epithelial location of the granular dense deposits in addition to the fibrillary deposits. Since he manifested no evidence of cryoglobulinemia or Lupus syndrome, these finding supports the association of plasma cell dyscrasia and immunotactoid glomerulopathy, an association reported by some authors  and denied by others.  However, the clinical and histopathological presentations are different,  and the association of LCDD and immunotactoid glomerulopathy has, to our knowledge, not been reported.
The reversibility of renal failure in our patient cannot be explained by dehydration, hyperuricemia, hypercalcemia, pyelonephritis, NSAID or ACEI.  A mild renal failure is common in multiple myeloma, which could be corrected conservatively. , Moreover, although cast nephropathy is the commonest cause of renal failure in multiple myeloma,  the rapid improvement of our patient on conservative measures is not consistent with this diagnosis.  The acuteness and reversibility of renal failure might be explained by acute interstitial nephritis, which is rarely reported in LCDD. , Repeating the renal biopsy was not contemplated because of the rapid and marked improvement of the patient.
Usually the advanced renal failure in multiple myeloma needs early and intensive hemodialysis with initiation of chemotherapy to suppress light chain production with plasmapharesis in case of excessive light chain load. This aggressive approach might improve the outcome since multiple myeloma is one of the reversible causes of dialysis dependent renal failure. 
Finally, the presence of glucosuria early in the course of the illness probably points to a prominent tubulopathic rather than glomerulopathic light chain effect and it may be part of a Fanconi syndrome. ,,, This is consistent with the findings in our patient.
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