igg4-related disease is a relatively new term coined to encompass a little known condition of unknown aetiology , characterized by multi - organ tissue infiltration by igg4 + plasma cells . the first affected organ identified was the pancreas , but it is now increasingly apparent that a variety of organs may be affected , including the salivary glands , retroperitoneum , aorta , thyroid , lungs , kidneys , lymph nodes , periorbital tissue , skin , pericardium , breast , prostate and thyroid glands . the case below demonstrates the importance of recognizing the biochemical , radiological and histological features representative of renal igg4 disease , when there is no obvious extra - renal involvement . a 29-year - old man of indian extraction , born and raised in london , initially presented to physicians in beijing where he had been teaching art for the past 18 months . whilst his complaints of sinusitis , lethargy and wheeze were being investigated , he was found to be hypertensive with a creatinine level of 262 mol / l , an active urinary sediment and a protein creatinine ratio of 237 mg / mmol . his hepatitis b , c and hiv status were all negative and his chest radiograph was normal . immunology revealed a positive pr3 with normal anf , complements and a negative anti - gbm titre . his renal ultrasound scan ( uss ) demonstrated a 9.1 cm right kidney and an 11.7 cm left kidney with multiple hyper - reflective foci in the renal cortices . he proceeded to have a renal biopsy in china which was reported to contain 20 glomeruli , of which 11 were sclerosed . there was focal segmental increase in the mesangial matrix and cellularity , with diffuse tubular atrophy , interstitial fibrosis and inflammatory cell infiltration . a diagnosis of chronic tubulointerstital nephritis ( tin ) with glomerular sclerosis was made and the patient was prescribed losartan 50 mg od and amlodipine 5 mg od . after 3 months , the patient returned to the uk and presented himself to a nephrologist . mol / l with a normal full blood count , lipid profile , coagulation screen , fasting glucose and electrolytes . his urinary protein excretion at this time was 0.35 g/24 h. his total immunoglobulin levels showed an igg of 22.18 g / l ( 8.018.0 g / l ) but normal iga and igm levels . another uss again revealed irregular renal outlines with focal hyper - reflective areas ( figure  1 ) . 1.a 9.7 cm right kidney with focal hyper - reflective areas scattered patchily throughout the cortex , possibly demonstrating some mass effect . this has resulted in an irregular renal outline with a solid rather than a cystic appearance . a 9.7 cm right kidney with focal hyper - reflective areas scattered patchily throughout the cortex , possibly demonstrating some mass effect . this has resulted in an irregular renal outline with a solid rather than a cystic appearance . the lobulated renal outlines raised the suspicion of a possible infiltrative or infective process and a magnetic resonance imaging ( mri ) scan was arranged . this showed areas of high t2 signal change throughout the parenchyma , conforming to lobular boundaries with some sparing of the lobules and with no other abdominal abnormalities . a micro - bubble contrast uss demonstrated uniform enhancement throughout the cortical medullary areas without evidence of abnormal washout and with symmetrical cortical perfusion . the irregular outline was , therefore , thought secondary to long standing fibrosis or scarring and the patient returned to china . the patient presented again 4 months later , asymptomatic but with an increased creatinine level of 310 mol / l , which prompted a repeat biopsy . , there was extensive storiform fibrosis with a mixed chronic inflammatory infiltrate containing prominent plasma cells and scattered eosinophils . the patient 's immunoglobulin subclasses were measured at this point and showed a markedly elevated total igg4 subclass only , at 19.8 g / l ( 0.81.4 he was , therefore , diagnosed with igg4-related tin and treatment with 40 mg of oral prednisolone was initiated ( figure  2 ) . there is extensive tubular atrophy with storiform interstitial fibrosis and a chronic inflammatory infiltrate ( h&e ) . ( b ) at higher power , the interstitial infiltrate is seen to contain many plasma cells and scattered eosinophils ( h&e ) . ( c ) immunohistochemistry demonstrates that most of the plasma cells contain igg4 ( immunoperoxidase stain for igg4 ) . ( d ) em shows electron dense deposits within a tubular basement membrane ( arrows ) consistent with immune complex deposition ( 8000 ) there is extensive tubular atrophy with storiform interstitial fibrosis and a chronic inflammatory infiltrate ( h&e ) . ( b ) at higher power , the interstitial infiltrate is seen to contain many plasma cells and scattered eosinophils ( h&e ) . ( c ) immunohistochemistry demonstrates that most of the plasma cells contain igg4 ( immunoperoxidase stain for igg4 ) . ( d ) em shows electron dense deposits within a tubular basement membrane ( arrows ) consistent with immune complex deposition ( 8000 ) . the initial suspicion of igg4-related renal disease may arise following the finding of an active urinary sediment , radiological abnormalities or reduced renal function and this may then prompt a renal biopsy . an accurate diagnosis is very important as this disease is often acutely sensitive to steroids ; however , there is not always a sustained response and there have been reports of rituximab being used for refractory disease . most case reports of renal involvement in igg4-related disease are from asia and in 2011 , the all japan igg4 team proposed a set of organ - specific diagnostic criteria to aid recognition of this syndrome . although igg4 levels are deemed neither necessary nor sufficient to secure a diagnosis , elevated levels are useful as a serological disease marker [ 1 , 6 ] . the radiological findings on uss and mri , described in our case report , are typical of renal involvement . have coined the term  renal rim sign to describe the peri - renal soft tissue rim found on computed tomography contrast studies which they say reflects the plasma cells , lymphocytes and fibrosis found on histopathological examination of the interstitium . the characteristic renal biopsy appearances were well illustrated by this case with an interstitial infiltrate containing igg4 + plasma cells and the presence of immune complexes on tubular basement membranes . in some cases , our patient requires long - term follow - up , not only to monitor for extra - renal involvement but also to ensure a sustained response to steroid treatment , largely guided by changes in creatinine . whether or not changing igg4 levels can aid prognosis or determine treatment strength or duration remains unknown . after 2 months of a reducing steroid regimen , the patient now has a creatinine level of 233 mol / l .
igg4-related tubulointerstitial nephritis is an uncommon cause of renal impairment . 
 it has been associated with dysfunction in a number of other organs giving rise to the term igg4-related systemic disease ; organ involvement can occur metachronously , hence , making it more difficult to identify patients . 
 the exact cause of this condition remains unknown . 
 here , we present a case of isolated renal involvement which demonstrates how particular biochemical , radiological and histopathological changes should raise the suspicion of igg4-related nephropathy , especially when there is an absence of clues from any other organ .