the term  progressive glomuerulonephritis with monoclonal igg deposits ( pgnmids) was coined by nasr to reflect a disorder that typically presented with nephrotic or nephritic syndrome [ 1 , 2 ] . while membranoproliferative and endocapillary proliferative patterns are the most commonly observed in pgnmid , a few cases of crescent formation have also been noted . igg3 is the major subtype of monoclonal deposition , but pgnmid is generally not associated with hematological malignancies such as multiple myeloma or lymphoma , and is differentiated from light- and heavy - chain deposition disease and type 1 cryoglobulinemic glomerulopathy by the absence of any characteristic organized deposition as detected by electron microscopy . in our current report , we describe a case of recurrent pgnmid as diffuse cellular crescentic glomerulonephritis 8 years after the initial development of membranoproliferative glomerulonephritis ( mpgn ) in this patient . we performed immunofluorescence studies using initial biopsied specimens to confirm the same monoclonal igg depositions on the glomeruli . a 41-year - old man presented at our hospital with gross hematuria and pretibial edema 3 weeks after developing upper airway inflammation . eight years prior to this episode , he had undergone a renal biopsy at another hospital due to acute nephritic syndrome and was diagnosed with mpgn at that time . he had then been administered prednisolone for around 3 years , but discontinued this medication on his own volition . a physical examination of this patient at our hospital revealed a blood pressure of 154/84 mmhg , and a weight of 92.4 kg , representing a 3.4 kg gain in his ordinal weight . urinalysis revealed 3 + proteinuria and 1 + hematuria , and a 24-h protein excretion of 1.2 g / day . further laboratory tests revealed chronic renal failure associated with hypogammaglobulinemia and slight hypocomplementemia ( table  1 ) . we detected no anti - dna , anti - glomerular basement membrane or anti - neutrophil cytoplasmic antibodies , and no hepatitis b , hepatitis c nor hiv . cryoglobulins were not detected , and protein electrophoresis of serum and urine did not show a paraprotein . the results of a chest x - ray were unremarkable and abdominal computed tomography showed bilateral kidney enlargement but no tumor lesion was detected . given the rapid increase in his serum creatinine level , we performed a second renal biopsy for this patient at our hospital . table  1.laboratory data for the pgnmid subjectat presentationafter plasmapheresisreference rangetotal protein ( g / l)48376580serum urea nitrogen ( mmol / l)21.515.62.97.1serum creatinine ( mol / l)86445035.488.4egfr ( ml / min/1.73 m)5.9n / a90urinary protein/24 h ( g/24 h)1.28.7<0.2igg ( g / l)4.28n / a8.717.0complement c3 ( mg / dl)78n / a86160complement c4 ( mg / dl)31n / a1745 laboratory data for the pgnmid subject the kidney biopsy sample obtained from this patient at our hospital showed 26 glomeruli under light microscopy , none of which were sclerosed . all of these glomeruli showed cellular crescents , and circumferential global crescents , so - called full - moon changes , were also obvious . capillary tufts were found to be compressed by the crescents , and focal endocapillary proliferative changes were noted . immunofluorescence studies revealed igg3 monoclonal deposits in the glomeruli , as well as a mild positivity of c1q and c3 , but iga and igm were both negative . electron microscopy analysis revealed mesangial dense deposits , and subendothelial deposits with mesangial interposition were also noted , but no subepithelial deposit was evident . no organized structure was observed in the deposits at higher magnification under electron microscopy ( figure  1 ) . circumferential cellular crescents with endocapillary proliferation were clearly detectable ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . an immunofluorescence photomicrograph showing monoclonal igg deposition of the mesangium and glomerular basement membrane is shown ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . ( i ) electron microscopy showing marked subendothelial dense deposits ( arrows ) with a mesangial interposition ( asterisks ) . circumferential cellular crescents with endocapillary proliferation were clearly detectable ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . an immunofluorescence photomicrograph showing monoclonal igg deposition of the mesangium and glomerular basement membrane is shown ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . ( i ) electron microscopy showing marked subendothelial dense deposits ( arrows ) with a mesangial interposition ( asterisks ) . the clinicians who previously treated our patient kindly provided us with glass slides of his first renal biopsy specimens . this first biopsy was an open wedge procedure and the sample submitted for light microscopy contained over 100 glomeruli , none of which were sclerosed . light microscopy revealed glomerular lobulation with marked mesangial proliferation of the glomeruli , consistent with mpgn . to determine the monoclonality of the deposits , cryosections were freshly prepared for staining of igg subclasses and immunofluorescence analyses of these samples subsequently confirmed monoclonal deposition of igg3 of the glomeruli ( figure  2 ) . 2.re-evaluation of previous renal biopsy specimens from our pgnmid case which were prepared 8 years before at a different hospital . light microscopy revealed membranoproliferative changes of the glomeruli with occasional double contours ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . immunofluorescence analyses revealed monoclonal igg deposits of the glomerulus ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . re - evaluation of previous renal biopsy specimens from our pgnmid case which were prepared 8 years before at a different hospital . light microscopy revealed membranoproliferative changes of the glomeruli with occasional double contours ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . immunofluorescence analyses revealed monoclonal igg deposits of the glomerulus ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . the patient was diagnosed with recurrent pgnmid in accordance with the monoclonal pattern of igg3 deposition found in both the first and second renal biopsy specimens . the patient underwent hemodialysis the day after his first presentation at our hospital due to a severely worsening kidney function . although steroid half - pulse therapy ( prednisolone 500 mg daily for 3 days ) and subsequent oral administration of 40 mg / day of prednisolone were performed , no improvement in his renal function was observed after 2 weeks . intravenous cyclophosphamide and 6 days of plasmapheresis treatment were additionally performed , but severe proteinuria persisted and his serum creatinine level remained high . a 41-year - old man presented at our hospital with gross hematuria and pretibial edema 3 weeks after developing upper airway inflammation . eight years prior to this episode , he had undergone a renal biopsy at another hospital due to acute nephritic syndrome and was diagnosed with mpgn at that time . he had then been administered prednisolone for around 3 years , but discontinued this medication on his own volition . a physical examination of this patient at our hospital revealed a blood pressure of 154/84 mmhg , and a weight of 92.4 kg , representing a 3.4 kg gain in his ordinal weight . urinalysis revealed 3 + proteinuria and 1 + hematuria , and a 24-h protein excretion of 1.2 g / day . further laboratory tests revealed chronic renal failure associated with hypogammaglobulinemia and slight hypocomplementemia ( table  1 ) . we detected no anti - dna , anti - glomerular basement membrane or anti - neutrophil cytoplasmic antibodies , and no hepatitis b , hepatitis c nor hiv . cryoglobulins were not detected , and protein electrophoresis of serum and urine did not show a paraprotein . the results of a chest x - ray were unremarkable and abdominal computed tomography showed bilateral kidney enlargement but no tumor lesion was detected . given the rapid increase in his serum creatinine level , we performed a second renal biopsy for this patient at our hospital . table  1.laboratory data for the pgnmid subjectat presentationafter plasmapheresisreference rangetotal protein ( g / l)48376580serum urea nitrogen ( mmol / l)21.515.62.97.1serum creatinine ( mol / l)86445035.488.4egfr ( ml / min/1.73 m)5.9n / a90urinary protein/24 h ( g/24 h)1.28.7<0.2igg ( g / l)4.28n / a8.717.0complement c3 ( mg / dl)78n / a86160complement c4 ( mg / dl)31n / a1745 laboratory data for the pgnmid subject the kidney biopsy sample obtained from this patient at our hospital showed 26 glomeruli under light microscopy , none of which were sclerosed . all of these glomeruli showed cellular crescents , and circumferential global crescents , so - called full - moon changes , were also obvious . capillary tufts were found to be compressed by the crescents , and focal endocapillary proliferative changes were noted . immunofluorescence studies revealed igg3 monoclonal deposits in the glomeruli , as well as a mild positivity of c1q and c3 , but iga and igm were both negative . electron microscopy analysis revealed mesangial dense deposits , and subendothelial deposits with mesangial interposition were also noted , but no subepithelial deposit was evident . no organized structure was observed in the deposits at higher magnification under electron microscopy ( figure  1 ) . circumferential cellular crescents with endocapillary proliferation were clearly detectable ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . an immunofluorescence photomicrograph showing monoclonal igg deposition of the mesangium and glomerular basement membrane is shown ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . ( i ) electron microscopy showing marked subendothelial dense deposits ( arrows ) with a mesangial interposition ( asterisks ) . circumferential cellular crescents with endocapillary proliferation were clearly detectable ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . an immunofluorescence photomicrograph showing monoclonal igg deposition of the mesangium and glomerular basement membrane is shown ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . ( i ) electron microscopy showing marked subendothelial dense deposits ( arrows ) with a mesangial interposition ( asterisks ) . the clinicians who previously treated our patient kindly provided us with glass slides of his first renal biopsy specimens . this first biopsy was an open wedge procedure and the sample submitted for light microscopy contained over 100 glomeruli , none of which were sclerosed . light microscopy revealed glomerular lobulation with marked mesangial proliferation of the glomeruli , consistent with mpgn . to determine the monoclonality of the deposits , cryosections were freshly prepared for staining of igg subclasses and immunofluorescence analyses of these samples subsequently confirmed monoclonal deposition of igg3 of the glomeruli ( figure  2 ) . 2.re-evaluation of previous renal biopsy specimens from our pgnmid case which were prepared 8 years before at a different hospital . light microscopy revealed membranoproliferative changes of the glomeruli with occasional double contours ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . immunofluorescence analyses revealed monoclonal igg deposits of the glomerulus ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . re - evaluation of previous renal biopsy specimens from our pgnmid case which were prepared 8 years before at a different hospital . light microscopy revealed membranoproliferative changes of the glomeruli with occasional double contours ( a , periodic acid - schiff ; b , periodic acid - schiff - methenamine silver ) . immunofluorescence analyses revealed monoclonal igg deposits of the glomerulus ( c ,  ; d ,  ; e , igg1 ; f , igg2 ; g , igg3 ; h , igg4 ) . the patient was diagnosed with recurrent pgnmid in accordance with the monoclonal pattern of igg3 deposition found in both the first and second renal biopsy specimens . the patient underwent hemodialysis the day after his first presentation at our hospital due to a severely worsening kidney function . although steroid half - pulse therapy ( prednisolone 500 mg daily for 3 days ) and subsequent oral administration of 40 mg / day of prednisolone were performed , no improvement in his renal function was observed after 2 weeks . intravenous cyclophosphamide and 6 days of plasmapheresis treatment were additionally performed , but severe proteinuria persisted and his serum creatinine level remained high . immunofluorescence analysis of our current patient led us to conclude that it was a pgnmid case with igg3 deposition since this patient initially developed renal dysfunction 8 years prior to his presentation at our hospital . our current case first developed mpgn as revealed by light microscopy , and a second biopsy performed at our hospital revealed diffuse global crescent formation , indicating histological transformation of his pgnmid . nasr et al .   have reported four previous cases of recurrent pgnmid in renal allografts , two of which recurred in the native kidney before transplantation . of note in this regard , both of these cases developed crescent formation in biopsy specimens taken 4 or 8 months prior to hemodialysis . crescents would thus seem to indicate a severely poor prognosis for the patient 's kidney function . indeed , a higher percentage of crescents has been found to correlate with the rate of progression to end - stage renal disease ( esrd ) in a univariate analysis by cox regression . although the pathogenesis of pgnmid remains elusive , our current case study suggests that some infection causing upper airway inflammation exacerbates this condition to result in crescentic glomerulonephritis . have reported the development of pgnmid with crescent formation 1 month after upper airway infection , and nasr et al . have also described a case of pgnmid with an upper respiratory tract infection 5 days prior to a presentation of renal failure , although the underlying histological pattern was not detailed . hence , pgnmid should be differentiated from bacterial infection - related glomerulonephritis since both pgnmid and irgn share several unique clinicopathological features such as hypocomplementemia and endocapillary proliferative change . nasr et al .   have reported that 7 out of a cohort of 32 ( 21.9% ) patients with pgnmid progressed to esrd , indicating an aggressive course in at least a sub - population of pgnmid . although raghino et al .   have reported a case of pgnmid that was successfully treated with plasmapheresis , an intervention with intravenous cyclophosphamide and plasmapheresis in our current case did not enable a withdrawal from dialysis . moreover , in previous allograft cases , aggressive immunosuppressive administration including rituximab has been found to successfully ameliorate impaired renal function . prompt administration of such therapeutic options at an early stage thus appears to be necessary to induce a complete remission of pgnmid . although infection is a risk factor for a poor prognosis in this disease , long - term and careful follow - up examinations of additional pgnmid patients will be required to develop more optimal treatment options . with this aim in mind , immunofluorescence studies , especially for  ,  , and igg subclasses , will be invaluable for specimens with dominant or co - dominant igg deposition to collect definitively established cases of pgnmids .
several types of glomerulonephritis associated with dysproteinemia , such as al - amyloidosis , light- and heavy - chain deposition disease , and type 1 cryoglobulinemic glomerulopathy , demonstrate monoclonal immunoglobulin deposition . 
 progressive glomerulonephritis with monoclonal igg deposits ( pgnmid ) is also known to feature monoclonal glomerular deposits , but most of these cases occur without underlying disease . 
 we here report a case of recurrent pgnmid that developed as diffuse cellular crescentic glomerulonephritis 8 years after an initial diagnosis of membranoproliferative glomerulonephritis ( mpgn ) . 
 determination of the monoclonality of the deposited immunoglobulin is vital to make the correct diagnosis and enable an early administration of aggressive immunosuppressive therapy .