since its first description in 1971 , the spectrum of glomerular diseases associated with deposition and precipitation of monoclonal immunoglobulin components has expanded . the first category includes diseases with organized fibrillar ( amyloidosis ) and microtubular ( cryoglobulinemia , immunotactoid glomerulonephritis [ gn ] ) deposits . the second category is characterized by nonorganized electron - dense deposits , usually granular , located along the basement membranes in most tissues , mainly in the kidney and defines the monoclonal immunoglobulin deposition disease ( midd ) . furthermore , in some cases , nonorganized electron - dense deposits correspond to dense deposit disease ( ddd ) and c3 gn ( c3gn ) , now classified under the heading of c3 glomerulopathies and differ from classic midd by the presence of isolated deposits of c3 on immunofluorescence . we report the case of a patient with monoclonal gammopathy and glomerular disease , characterized by isolated c3 deposits without monoclonal immunoglobulin deposits . unlike other rare reported cases , the evolution in this case was favorable . to our knowledge , this is the second observation of a case where a complete renal remission was obtained after controlling hematologic disease by autologous stem cell ( asc ) transplant . the serum creatinine was 4.5 mg / dl and 24- urine protein 10 g / day . the rest of biological data showed hypoalbuminemia at 3.0 g / dl and hypercalcemia at 13.3 mg / dl . tests for serum rheumatoid factor , hepatitis ( b and c ) , and hiv infection were negative . antinuclear , anti - double - stranded deoxyribonucleic acid and m2 antimitochondrial antibodies were not detected . the serum protein electrophoresis test identified a thin monoclonal band in the beta 2 globulin position . l ( kappa at 331 mg / l and kappa / lambda ratio at 19 ) . the bone marrow aspiration showed atypical plasma cells > 90% of marrow cells with some normal hematopoietic elements . the patient was diagnosed with a lambda light chain multiple myeloma associated with renal impairment . common causes of renal failure were excluded and a renal biopsy was performed and showed the aspect of a membranoproliferative gn with isolated c3 deposits , which confirmed the diagnosis of c3 glomerulopathy . the light microscopic appearance of glomerular lesions was characterized by a mesangial proliferation with neutrophilic leukocyte afflux in glomerular tufts and deposited in the mesangium and glomerular capillary walls [ figure 1 ] . moderate chronic lesions , including global glomerular sclerosis , tubular atrophy , interstitial fibrosis , and arteriosclerosis , were also present . immunofluorescence showed diffuse and intense staining for c3 along the glomerular , tubular , and bowman 's capsule basement membranes , as well as mesangial rings [ figure 2 ] . no significant staining was observed with anti - kappa , lambda , c4 , c1q , and immunoglobulins ( a , g , and m ) conjugates . unfortunately , electronic microscopy was not performed to establish the distinction between ddd and c3gn . glomerular lesions with mesangial proliferation and neutrophilic leukocyte afflux in glomerular tufts ( light microscopy , masson trichrome stain , 100 ) intense staining for c3 along the glomerular basement membranes and mesangial rings ( immunofluorescence , 100 ) the patient received hydration with alkalinization which allowed his renal function to improve ( creatinine 30 mg / l at the time of his discharge ) and his serum calcium to normalize . chemotherapy consisted of cyclophosphamide ( 500 mg on days 1 , 8 , and 15 per month ) , dexamethasone ( 40 mg from day 1 to day 4 each week during the first 2 months , then from day 1 to day 4 each month ) , and thalidomide ( 100 mg daily for 1 month followed by 200 mg / day ) . this treatment was extended through 9 months after which the patient was referred for an asc transplant . the clinical course was favorable with an improved renal function , remission of the nephrotic syndrome , and complete hematologic remission over 1 year follow - up after asc transplant . serum c3 complement levels returned to normal at 6 months after the initiation of treatment . prevalence of monoclonal gammopathy appears to be higher in patients with c3 glomerulopathy compared to the general population , which does not favor a simple coincidence . sethi et al . found that among 14 patients with ddd , ten ( 71.4% ) had a serum monoclonal immunoglobulin g. several hypotheses have been advanced to explain how kidney damages in c3 glomerulopathy can be linked to monoclonal gammopathy . the role of monoclonal immunoglobulin in the systemic activation of cap , leading to glomerular proliferative lesions and subsequent c3 deposits , is questionable . no genetic abnormality was found in all tested patients , so a genetic predisposition in favor of activation of the cap does not seem necessary to provoke kidney lesions . in one of the six patients , however , a control biopsy performed 4 years later showed a colocalization of c3 deposits and lambda light chain , suggesting that the isolated c3 deposition might be the initial step , which precedes the secondary deposit of immunoglobulin . in the previous reported cases , isolated glomerular c3 deposits were associated with monoclonal gammopathy of unknown significance , rather than a high - mass myeloma . this finding can suggest that prolonged cap activation by the monoclonal immunoglobulin is required for the development of glomerular lesions . the role of monoclonal immunoglobulin in the activation of cap has been demonstrated in recent observations . meri et al . in a similar case showed that purified monoclonal light chains can interact with factor h and activated the cap . also isolated monoclonal light chains from a patient with ddd and demonstrated the ability of these autoantibodies to activate the cap . recently , zand et al . suggested that elevated cytokines in multiple myeloma such as interleukin 6 could explain an excessive activation of cap by an elevated activity of complement factor i. indeed , transcriptional activity of factor i is enhanced in the presence of these cytokines . decreased serum c3 and the main differential diagnosis is postinfectious gn which can produce a similar clinical syndrome . as poststreptococcal gn , c3 glomerulopathies may also be preceded by upper respiratory tract infection . in our case , depression of c3 persisted for several months and became normal only after hematologic remission , whereas low c3 is usually transient in postinfectious gn . on the other hand , in immunofluorescence microscopy , immunoglobulins were absent which indicate that it was not an immune complex - mediated disease . in addition to serum c3 and c4 , special diagnostic tests should be obtained in patients with c3 glomerulopathy ( if possible ) since the results can help to determine a specific therapeutic approach ( c3 nephritic factor ( c3nef ) , serum factor h , complement factor h - related protein gene mutations , serum factor b , serum factor i , membrane cofactor protein ( cd46 ) , and soluble c5b-9 ) . c3nef , an autoantibody that stabilizes the c3 convertase , is found frequently in patients with c3 glomerulopathy . in this case , c3nef was undetectable ; however , unfortunately , its determination was not performed until several months after treatment beginning when the patient was already in remission of his hematological disease . plasma exchange , fresh frozen plasma infusions , or immunosuppressive therapy has not been required to maintain normal levels of c3 . these arguments are not in favor of a genetic anomaly as a possible pathogenic cause . an acquired disorder ( for example , the suggested role of the monoclonal immunoglobulin in cap excessive activation ) rather than genetic seems more likely , but genetic testing for an inherited disorder was not performed . indeed , the outcome of the most reported cases was poor with frequent progression to end - stage renal disease . improvement in renal function , reduction of proteinuria , and normalization of c3 level in parallel with the control of the hematologic disease are a strong argument for a probable role of monoclonal gammopathy in the pathogenesis of this case . however , it is possible that the improvement in proteinuria following treatment is attributable to switching off the production of lambda light chains , thus preventing their overflow into the urine , rather than the regression of glomerular lesions . overall , we considered that the renal damage in our case was reversible , and a posttreatment biopsy was not performed .
a 32-year - old male presented with advanced renal failure and nephrotic proteinuria due to lambda light chain multiple myeloma . 
 renal biopsy showed a proliferative glomerulonephritis with isolated c3 deposits . 
 renal recovery was obtained after chemotherapy and autologous stem cell transplant . 
 we review previously described cases of c3 glomerulopathy associated with monoclonal gammopathy .