glomeruli are involved in 75 - 90% of cases , clinical correlate of which is nephrotic - range proteinuria and slow progression to chronic kidney disease .
it is seldom appreciated that extracapillary glomerulonephritis may be superimposed on amyloidosis in such cases .
a 50-year - old man presented with the complaint of swelling of feet and facial puffiness of 1 month duration accompanied by oliguria .
he was not a diabetic or hypertensive and had no significant illness in the past . on examination
respiratory system examination revealed bilateral basal crepitations . abdominal examination showed the presence of ascites without any evidence of organomegaly .
laboratory examination showed hemoglobin of 10 mg/ dl , total leukocyte count of 14.4  10/l with 76% of polymorphs in differential count .
biochemical parameters were as follows : random blood sugar 127 mg / dl , serum creatinine 1.4 mg / dl , blood urea 34 mg / dl , and serum albumin 0.9 g / dl .
urine analysis showed 3 + protein , 23 pus cells / hpf , and inactive sediments .
abdominal sonogram showed moderate ascites with bilateral pleural effusion and bilateral normal - sized kidneys .
light microscopy showed 24 glomeruli , all of which showed pale , eosinophilic , acellular , weakly periodic acid - schiff ( pas)-positive material in the mesangium and basement membrane , focally forming nodules [ figure 1 ] .
immunofluorescence showed ten viable glomeruli that were negative for igg , iga , igm , c3c , c1q , and fibrin .
immunohistochemical studies were positive for amyloid a protein in the deposits [ figure 2 ] .
a diagnosis of renal amyloid a ( aa ) amyloidosis causing secondary nephrotic syndrome was reached and the patient was put on enalapril , atorvastatin , and diuretics .
three glomeruli displaying global deposition of pale eosinophilic acellular weakly pas - positive material deposited in the mesangial region and along capillaries , obliteration of capillary lumen and patent bowmans space .
scanty amyloid material is seen in the vessel wall ( 20 , pas ) amyloid deposits are strongly positive for amyloid a protein ( a ) , and lack of light chain restriction with kappa ( b ) and lambda ( c ) light chains ( 40 , immunoperoxidase ) he returned for follow - up after 1 month with complaints of anorexia , nausea , and oliguria .
on evaluation , he had anasarca and had blood pressure of 130/80 mmhg . clinically , the patient had persisting bilateral pleural effusion and ascites .
laboratory tests were as follows : hemoglobin 6.5 g / dl , blood urea 157 mg / dl , serum albumin 1.8 g/ dl , and serum creatinine 6.5 mg / dl .
antineutrophil cytoplasmic antibody ( by immunoblot assay ) was negative and serum c3 was 93.8 mg / dl ( normal , 90180 mg / dl ) . considering the rapid deterioration of renal function and sudden drop in hemoglobin ,
fourteen viable glomeruli were seen on light microscopy , of which 30% of them showed active cellular crescents occupying circumferentially in addition to amyloid deposits [ figure 3 ] .
immunofluorescence showed eight viable glomeruli that were negative for igg , iga , igm , c3c , c1q , and fibrin .
repeat biopsy : glomerulus shows global deposition of amyloid material that is silver - negative and an active cellular crescent seen circumferentially along with fibrinous material in the crescentic area ( 40 , pasm stain ) the patient was treated with large doses of diuretics .
the patient gradually had increasing urine output and was symptomatically better at discharge , with serum creatinine improving to 3.5 mg / dl .
amyloidosis of the kidney is characterized by deposition of amyloid protein in the renal parenchyma .
patients present with heavy proteinuria and a progressive course , leading to slow decline in renal functions and end - stage renal disease .
this may be in the form of ablation of plasma cells in myeloma - associated amyloidosis , or suppression of acute phase response and treatment of underlying chronic inflammatory / infective condition in aa amyloidosis .
eprodisate is a new drug being tried in secondary amyloidosis . with all these different therapies ,
the course of the decline in renal functions can be further slowed down or even arrested .
rapid decline of renal functions is unusual and is attributed to the severe nephrotic state causing prerenal type of renal insufficiency . progressive deposition of amyloid itself has been found to be the cause in a few cases .
rapidly progressive glomerulonephritis ( rpgn ) in the background of amyloidosis is distinctly rare and has been described in anecdotal reports .
panner reported the first two cases of possible renal amyloidosis that presented as rpgn , one of whom had ra .
there are some other reports of rapidly progressive renal failure in patients with longstanding ra that demonstrated amyloidosis on renal biopsy , associated with crescentic glomerulonephritis .
crescents have been described in al amyloidosis as well . in a recent report , crosthwaite et al .
have reported one case of crescentic glomerulonephritis in a case of al amyloidosis , which is probably the first report of an association of al amyloidosis with crescents .
nagata et al . have proposed that damage to the glomerular basement membrane ( gbm ) ultrastructure by the amyloid fibrils led to crescent formation . in their series of 105 cases of renal amyloidosis studied on autopsy or biopsy , glomerular crescents were seen in 14 cases ( 13% ) .
immunohistochemical studies among these cases documented amyloid protein of aa type in 12 cases ( 85% ) .
they recorded that crescent formation was more closely associated with the site of amyloid deposition and not with the level of proteinuria , with mesangial deposition being more commonly associated with crescents .
electron microscopic studies showed areas of the gbm disruption in areas of amyloid deposition supporting their hypothesis .
leakage of fibrin - fibrinogen caused by gaps in the gbm incites inflammatory reaction and plays a crucial role in extracapillary proliferation .
it is also likely , however , that crescents may be of a different pathophysiology and the association with renal amyloid may be incidental . in another case report
, a patient with chronic inflammatory bowel disease treated with infliximab developed rapidly progressive renal failure 3 months later .
on renal biopsy , crescents and vasculitis , presumably due to infliximab , were seen in addition to aa amyloidosis . in our patient ,
we considered the crescentic transformation was either due to vasculitis in view of the sudden drop in hemoglobin and renal insufficiency or drug ( colchicine ) induced .
however , the anca profile was negative and the literature is silent with regard to colchicine associated with crescent formation . on the contrary , there are reports that suggest that colchicine is an immunomodulatory drug and downregulates inflammatory response .
the patient was treated with fresh frozen plasma in addition to ace inhibitors in an effort to alleviate the nephritic edema and third - space collections . in addition , as the renal function declines and urine output drops , the quantity of urinary protein loss comes down , which could possibly explain the improvement in serum albumin levels .
it is possible that association of crescents in a proven case of amyloidosis may be more common than previously considered .
the association may be missed as such patients may not be subjected to a repeat biopsy even when they present with rapid deterioration in renal function .
the benefits of aggressive immunosuppression with a combination of steroids and cytotoxic drugs in patients who are already protein depleted and malnourished are not well documented and may cause more harm than good .
it appears that that these patients do worse than patients with rpgn without underlying amyloidosis . however , there are isolated case reports that indicate that aggressive treatment may salvage the kidney function , at least partially .
there is one case report of rpgn associated with amyloidosis in a 53-year - old lady with ra who was successfully treated with intensive plasma exchange and immunosuppression . in this patient ,
moroni et al . , in their report of three cases of crescentic glomerulonephritis superimposed on amyloidosis , have documented partial recovery of renal functions in two patients after treatment with intravenous pulse methylprednisolone , immunosuppressive agents , and oral corticosteroids . to the best of our knowledge ,
our patient had aa amyloidosis as proven by immunohistochemical studies , but no underlying disease could be identified .
he was treated with pulse methylprednisolone along with iv cyclophosphamide , but had nephrotic - range proteinuria and moderate renal dysfunction till last follow - up . in summary ,
crescentic glomerulonephritis associated with renal amyloidosis is a rare occurrence and it is important that clinicians suspect this possibility when confronted with a case of renal amyloidosis and rapid worsening of renal functions .
 renal amyloidosis is characterized by progressive deposition of extracellular material , most commonly in the glomeruli . 
 most often , patients present with nephrotic range proteinuria and the disease progresses gradually to renal failure . rapid worsening of renal functions is rare . 
 we report a case of crescentic glomerulonephritis superimposed on amyloidosis , clinically presenting as rapidly progressive renal failure , and present a review of the literature . 
Introduction
Case Report
Discussion