focal segmental glomerulosclerosis ( fsgs ) is a pathological term to indicate glomerular lesion associated with various etiological factors . in native kidneys ,
, fsgs can be classified as recurrent disease or fsgs associated with chronic transplant glomerulopathy , calcineurin inhibitor ( cni ) toxicity and in long - standing grafts with hyperfiltration injury .
the incidence of recurrent fsgs is approximately 30% and secondary disease occurs in 10 - 20% of the cases .
the distinction between these various types is difficult because of lack of pretransplant diagnosis and overlapping morphological features .
we analyzed 24 graft biopsies with fsgs and tried to etiologically classify them basing on the accompanying morphological features on the graft biopsies and clinical features .
it is important to diagnose the condition adequately and promptly to protect the graft and inhibit the progression of the disease .
out of 363 allograft biopsies received between january 2012 and december 2013 , 24 diagnosed as fsgs were included in the study .
three routine stains were done in all biopsies , which included hematoxylin and eosin , periodic acid - schiff 's , and masson 's trichrome .
immunofluorescence with immunoglobulin ( ig ) g , igm , iga , c3c and c1q was done .
criteria to diagnose fsgs included segmental sclerosis , hyalinosis and or lipid deposition , focal or segmental collapse of the tuft with prominence of podocytes of variable degree depending on the histological type of lesion diagnosed .
mean serum creatinine level was 2.7 mg / dl and mean 24 h urinary protein was 3.2 g. secondary fsgs was reported in 18 cases ( 75% ) .
causes included chronic humoral rejection in seven cases ( 38% ) , cni ( cyclosporine and tacrolimus ) toxicity in six cases ( 33% ) , and in long - standing grafts with hypertensive nephron loss and hyperfiltration injury in five cases ( 29% ) .
the type of donor , biochemical parameters and pretransplant diagnosis for various categories are given in table 1 .
recurrent and new - onset primary diseases seven cases with chronic glomerular and tubulointerstitial changes with positive c4d were classified as chronic humoral rejection .
glomerular changes included thickening and duplication of basement membrane , increase in mesangial matrix and cellularity , and focal segmental sclerosis [ figure 1 ] .
c4d was given as positive when 10 - 50% of capillaries ( c4d2 ) or more than 50% of capillaries ( c4d3 ) showed linear circumferential staining .
positive c4d and segmental lesion in chronic humoral rejection ( 200 ) chronic humoral rejection mean serum creatinine level was 2.7 mg / dl and 24 h urinary protein was 2.8 g. six lesions were classified as cni toxicity .
histological features included striped fibrosis in interstitium and nodular hyaline arteriolar sclerosis ( ah2 and ah3 ) in vessels [ figure 2 ] .
nodular hyaline arteriolar sclerosis ( periodic acid - schiff , 200 ) calcineurin inhibitor toxicity mean serum creatinine level was 2.1 mg / dl and mean 24 h urinary protein was 800 mg .
hyperfiltration injury was diagnosed in five cases where hypertensive glomerular changes such as thickening and wrinkling of basement membrane , ischemic collapse of the tuft , and widening of bowman 's space and fsgs was seen .
vessels showed marked subintimal fibrosis with > 50% narrowing of lumen and associated with chronic tubulointerstitial changes .
mean serum creatinine level was 2.1 mg / dl and mean 24 h urinary protein was 300 mg . clinical and morphological details are given in table 4 .
focal segmental glomerulosclerosis is a pathological term to indicate glomerular lesion associated with various clinical situations in renal allografts .
fsgs is a common cause of end - stage disease and recurrence in grafts is approximately 30% .
we classified fsgs in renal grafts as recurrent disease , new - onset primary fsgs in cases where the native diagnosis was not fsgs , and secondary fsgs when associated with drug toxicity , chronic rejection or hypertension , depending on the clinical features and in correlation with various morphological features that are associated with fsgs .
this number does not indicate the exact incidence , as native biopsy diagnosis is not available in many cases .
risk of recurrence includes young age of the patient , presence of mesangial proliferation , and rapid progression to end - stage disease and pretransplant bilateral nephrectomy .
recurrence occurs in renal grafts in early post - transplant period . these patients present with heavy proteinuria usually of nephrotic range .
this criterion and an available diagnosis of native disease are helpful in diagnosing recurrent disease . in our series , all the four cases had a biopsy diagnosis of fsgs .
the type of fsgs in native kidney was available in three cases , and recurrence disease had a similar pattern to native disease .
recurrence can be classified as recurrence of same variant ( 51% ) , recurrence of same variant preceded by minimal change disease ( 19% ) and recurrence with a different variant of fsgs ( 19% ) .
graft survival is poor and progression to end - stage renal disease is rapid and is as high as 50% . it is therefore important to diagnose and differentiate this entity from other causes of fsgs . ( a ) collapsing glomerulopathy ( jones , 200 ) .
( b ) focal segmental glomerulosclerosis - not otherwise specified ( h and e , 200 ) chronic transplant glomerulopathy and chronic humoral rejection are other conditions in which fsgs can occur .
the mechanism for this is chronic immunological glomerular endothelial and podocyte injury , which is resulting in fsgs .
this particular lesion is relatively easy to diagnose as associated features of chronic graft damage are seen , and c4d is positive .
these patients presented in late post - transplant period mostly after 3 years and presentation is due to the rise in creatinine and mild proteinuria .
these lesions are purely based on pathology diagnosis as serum levels do not correlate with the extent of renal damage and clinical features are not specific .
glomerular changes include glomerular hypertrophy , capillary collapse , focal segmental or focal global sclerosis .
fsgs results from hyperfiltration injury due to loss of functioning nephrons rather than direct toxic effects on podocytes .
presence of hyaline arteriopathy , stripped fibrosis , [ figure 4 ] tubular atrophy with or without isometric vacuolation , and absence of heavy proteinuria help to diagnose this particular entity .
striped fibrosis ( masson 's trichrome , 100 ) the true incidence of glomerulonephritis in grafts is not exactly known and ranges from 4% to 20% .
membranous nephropathy and fsgs are most common of the glomerulonephropathies that can be seen in grafts with an incidence of 1 - 9% .
we diagnosed two cases of new - onset fsgs in patients presenting with nephrotic range proteinuria .
histologically , there were no features of hypertension or cni toxicity and c4d was negative .
new - onset fsgs has favorable clinical course when compared with recurrent disease and hence it is important to identify this lesion . in long - standing grafts with nephron loss and chronic tubulointerstitial changes
we described this entity separately when arterial changes are predominant and tell - tale signs of cni toxicity are absent .
an attempt was made to etiologically classify these lesions as there is a difference in treatment and prognosis .
it is important to make a diagnosis carefully using clinical information and pathology when a decision about second transplant has to be made .
 recurrence of fsgs in renal allo grafts is a major cause of graft loss . in this context 
 , we tried to diagnose and classify fsgs in renal allografts . 
 indications for biopsy included graft dysfunction and/or proteinuria . 
 three hundred and sixty - three graft biopsies were studied over a period of 2 years . 
 we classified fsgs into recurrent fsgs , new - onset primary fsgs and fsgs secondary to chronic humoral rejection , calcineurin inhibitor toxicity , and nephron loss and hyperfiltration injury . 
 twenty - four cases were diagnosed as fsgs , constituting 6.6% . 
 secondary fsgs was the most common fsgs in grafts in our study . 
 incidence of recurrent fsgs may not be accurate as pretransplant biopsy is available in very few cases . 