the most common form of renal involvement , accounting for 33 to > 60% of cases , is cast nephropathy characterized by an overabundance of toxic light chains in the tubular system . light - chain deposition disease , primary amyloidosis , often complicated by nephrotic syndrome , proximal and distal tubular dysfunction , renal vein thrombosis due to hyperviscosity or type 1 cryoglobulinaemia are less commonly seen . rapidly progressive glomerulonephritis is an unusual complication of multiple myeloma that has rarely been reported in the literature [ 15 ] . it is characterized by severe glomerular damage often involving > 50% of the glomeruli in a renal biopsy . due to the associated rapid decline of renal function , often within weeks , prompt initiation of therapy is crucial to prevent additional damage . in general , the most common cause is pauci - immune glomerulonephritis with a mean age at presentation of 60 years [ 68 ] . this form of extracapillary - proliferative glomerulonephritis is closely correlated with circulating pathogenic anti - neutrophil cytoplasmic antibodies ( ancas ) in 8090% of patients . immune complex - mediated glomerulonephritis and anti - glomerular basement membrane nephritis are less frequently diagnosed in this setting . standard treatment of extracapillary - proliferative glomerulonephritis includes induction therapy with cyclophosphamide and steroids . in severe kidney and pulmonary disease , plasmapheresis to remove circulating antibodies may be beneficial . rituximab as a b - cell - depleting therapy has also been successfully used [ 9 , 10 ] . in multiple myeloma , bortezomib therapy in combination with dexamethasone recently became a first - line therapy for patients with myeloma - induced renal insufficiency . several studies documented a significant improvement in kidney function , usually within the initial two to three cycles of treatment . we report a case of monoclonal gammopathy - associated pauci - immune extracapillary - proliferative glomerulonephritis successfully treated with the proteasome inhibitor bortezomib . a 60-year - old male was referred to our department in april 2011 by his nephrologist due to an increase in his serum creatinine to 140.8 mol / l ( 1.6 mg / dl ) , haematuria of 290 erythrocytes/l and spot urine protein  creatinine ratio ( upcr ) of 1.9 g / g . he subsequently underwent renal biopsy showing pauci - immune extracapillary - proliferative glomerulonephritis ( 4 of 14 crescents ) with mild tubular atrophy and interstitial fibrosis ( 20% ) , as well as lymphohistiocytic infiltration ( figure 1a ) . immunofluorescence revealed minimal mesangial deposits of c3 and complement complex c5b-9 as well as igm . informed consent was obtained from the patient prior to submission of this manuscript . during therapy , serum creatinine stabilized to 132.0 mol / l ( 1.5 mg / dl ) , proteinuria ( upcr ) decreased to 0.5 g / g and haematuria improved to 32 erythrocytes/l , respectively . maintenance treatment with azathioprine was started and the patient returned to the care of his nephrologist . 1.renal biopsy findings in a 60-year - old patient with pauci - immune extracapillary - proliferative glomerulonephritis due to igg kappa multiple myeloma . ( a ) biopsy before bortezomib treatment ( 200 , pas ) showing a proliferating glomerular crescent . ( b ) biopsy after bortezomib treatment ( 200 , pas ) showing sclerosing glomeruli and sclerosing crescents , interstitial fibrosis and tubular atrophy with only scarce inflammatory infiltrates . renal biopsy findings in a 60-year - old patient with pauci - immune extracapillary - proliferative glomerulonephritis due to igg kappa multiple myeloma . ( a ) biopsy before bortezomib treatment ( 200 , pas ) showing a proliferating glomerular crescent . ( b ) biopsy after bortezomib treatment ( 200 , pas ) showing sclerosing glomeruli and sclerosing crescents , interstitial fibrosis and tubular atrophy with only scarce inflammatory infiltrates . after 10 months , the patient was referred to our service again with newly diagnosed macrohaematuria , increased ucpr of 5 g / g and elevated serum creatinine of 169.8 mol / l ( 1.93 mg / dl ) . a thorough investigation revealed an increased serum 2-microglobulin of 3.5 mg / l and a pathological serum igg kappa / lambda free light - chain ratio of 5.2 ( normal value : 0.261.65 ) due to elevated serum igg kappa light chains of 74.0 mg / l ( normal range : 3.319.4 mg / l ) . a bone marrow biopsy showed an increase of monoclonal kappa - positive plasma cells to 10% . re - evaluating the initial renal biopsy , no evidence of light - chain deposition disease , fibrillary glomerulonephritis or amyloidosis was present . a new renal biopsy was performed , again showing pauci - immune extracapillary - proliferating glomerulonephritis ( 4 of 10 crescents ) with mild interstitial fibrosis . in this biopsy , there was also no evidence of classical myeloma - associated kidney disease . due to the relapse of rapidly progressive glomerulonephritis after cyclophosphamide therapy and leucopenia during azathioprine treatment , we decided to administer two doses of 1 g of rituximab i.v . within 4 weeks and maintained the patient on a reduced dose of azathioprine in combination with cyclosporine a [ 1 , 10 ] . unfortunately , the patient showed rapid deterioration of his renal function within the following 8 weeks to a serum creatinine level of 303.6 mol / l ( 3.45 mg / dl ) , an increase of proteinuria to 9 g / g and an increase of haematuria . the serum kappa / lambda free light - chain ratio also increased to 9.1 . because of the underlying plasma cell dyscrasia and rapidly worsening kidney function , we decided to start the patient on the proteasome inhibitor bortezomib ( 1.3 mg / m body surface i.v . on days 1 , 8 , 15 , 22 ) in combination with dexamethasone based on the treatment recommendations for multiple myeloma . after the first cycle of bortezomib / dexamethasone , serum creatinine decreased to 140.8 mol / l ( 1.6 mg / dl ) , and urinalysis showed reduced proteinuria of 2 g / g . a control biopsy was performed revealing residual sclerosed crescents , completely sclerosed glomeruli , mild interstitial fibrosis and tubular atrophy ( figure 1b ) . after the second cycle of bortezomib / dexamethasone , the patient showed clinical remission with serum creatinine levels of 103.8 mol / l ( 1.18 mg / dl ) , minimal proteinuria of 0.48 g / g , no haematuria and well - controlled hypertension . maintenance therapy of monthly bortezomib was initiated , and the patient showed stable serum creatinine values as well as stable proteinuria with 8 months of follow - up . glomerulonephritis with crescents , although rare , is a well - documented complication of multiple myeloma . this association was first described by kaplan and kaplan in 1970 , presenting a 49-year - old patient with renal failure due to extracapillary - proliferative glomerulonephritis , nephrotic syndrome and an igg paraprotein . described three cases of extracapillary - proliferative glomerulonephritis in which plasma cell dyscrasia was identified in two patients and waldenstrom 's macroglobulinaemia in one patient as the underlying cause of renal disease . renal function was stabilized by melphalan and steroids in the first patient and by steroids in combination with plasmapheresis in the third patient . rapidly progressive glomerulonephritis has also been reported in patients with primary and secondary amyloidosis [ 1 , 4 , 14 , 15 ] . the presence of paraproteins without characteristics of multiple myeloma ( hypercalcaemia , anaemia , bone disease ) is referred to as  monoclonal gammopathy of undetermined significance ( mgus ) . recently , leung et al .   suggested to introduce the term  monoclonal gammopathy of renal significance ( mgrs ) if renal damage is present in these patients . in this report , we describe a patient with pauci - immune extracapillary - proliferative glomerulonephritis due to igg kappa monoclonal gammopathy , in which bortezomib and dexamethasone treatment significantly improved his renal function . histologically , after bortezomib therapy , crescents were sclerosed , a mild interstitial fibrosis and tubular atrophy developed and proliferative glomerulonephritis was stopped . the improvement of renal function after treatment with bortezomib was very rapid , suggesting a direct effect of bortezomib on the proliferative and inflammatory glomerular lesions . this drug is known to inhibit protein degradation especially in high - turnover tumour cells , interfering with cell - cycle regulation and cell proliferation . due to the rapid improvement of the patient 's kidney function , we hypothesize that bortezomib exerted its beneficial effects not only through a control of plasma cell proliferation and paraprotein secretion , but also through direct inhibition of cell proliferation in the kidney . in a mouse model of anca - associated necrotizing crescentic glomerulonephritis interestingly , no additional hallmarks of myeloma - associated kidney involvement were present in this patient 's renal biopsy . recently described a patient with primary al amyloidosis and igg kappa multiple myeloma that developed rapidly progressive glomerulonephritis in the setting of renal amyloidosis . in this patient , bortezomib and dexamethasone treatment led to a decrease of paraproteinaemia , but one month after initiation of therapy his serum creatinine started to rise and he became dialysis - dependent , suggesting that bortezomib treatment might be less effective if renal amyloidosis is present . in our patient , the diagnosis of his underlying disease was not made until the second episode of rapid deterioration of kidney function when a thorough workup revealed elevated serum igg kappa light chains . the fact that monoclonal gammopathy was not discovered earlier indicates that this disease was not primarily taken into account as a cause for his progressive glomerulonephritis . therefore , we suggest that monoclonal gammopathy and multiple myeloma should be ruled out , especially in patients with anca - negative rapidly progressive glomerulonephritis . in summary , this case demonstrates that in pauci - immune extracapillary - proliferative glomerulonephritis , the presence of monoclonal gammopathy and multiple myeloma , although a rare differential diagnosis , should be considered . bortezomib therapy is a promising therapeutic approach to reverse severe kidney damage in myeloma - associated pauci - immune extracapillary - proliferative glomerulonephritis .
extracapillary - proliferative glomerulonephritis is a rare complication of multiple myeloma . 
 partial remission of kidney involvement with cyclophosphamide therapy has previously been described . 
 we report the case of a 60-year - old male patient diagnosed with rapidly progressive glomerulonephritis associated with igg kappa monoclonal gammopathy . 
 his kidney biopsy revealed pauci - immune extracapillary - proliferative glomerulonephritis without cryoglobulinaemia . 
 treatment with the proteasome inhibitor bortezomib induced rapid clinical and histological remission of his kidney disease . 
 the patient 's renal function remained stable on bortezomib maintenance therapy . 
 our findings suggest that bortezomib is a promising therapeutic approach to ameliorate severe kidney damage in monoclonal gammopathy- and myeloma - associated pauci - immune extracapillary - proliferative glomerulonephritis .