Incidence,Clinicopathological Features And Prognosis Of Crescentic Glomerulonephritis

Crescentic glomerulonephritis is one of the most severe forms of glomerulonephritis,clinically presenting with rapidly progressive glomerulonephritis,rapidly progressing to oliguria and renal failure.Current epidemiological data from large national renal biopsy registries including Saudi,USA,India,Japan and Spain show that crescentic glomerulonephritis accounts for approximately 4-10%of total renal biopsies.The distribution of etiology varies in different countries.In 2003,we described our experience on the clinical features and renal histology in 172 consecutive patients with CrGN during 1989-2001.We demonstrated that immune-complex CrGN,especially lupus nephritis and IgA nephropathy,was the most common type of CrGN in China and have noticed an increasing incidence of CrGN associated with increasing cases of renal biopsy.The distinction between subtypes based on immunofluorescence and serological findings has important implications for therapy and outcome.However,detailed epidemiological and clinicopathological data from China are missing during the last decade.The aim of this study is to investigate the incidence,clinicopathological features and prognosis of crescentic glomerulonephritis in a large representative centre from China,based on histological diagnosis,seen over a 10-year period.Part 1.Incidence,clinicopathological features and prognosis of crescentic glomerulonephritisObjective:To clarify the incidence,clinicopathological features and prognosis of crescentic glomerulonephritis in China.Methods:A total of 528 patients with biopsy-proven CrGN diagnosed from January 2003 to January 2013 were retrospectively reviewed.CrGN was classified into 3 types according to immunofluorescence findings;type Ⅰ was defined as a linear deposition of immunoglobulins along the glomerular basement membrane(GBM),type Ⅱ as a glomerular deposition of immune-complex and type Ⅲ as a pauci-immune deposition.Results:A total of 528/33747(1.56%)patients were diagnosed as CrGN,208(39.4%)were male and 320(60.6%)were female,with an average age of 37.6±16.4 years at renal biopsy.Initial clinical features included:RPGN(52.5%),nephrotic syndrome(18.2%),chronic renal failure(12.1%),acute nephritic syndrome(9.7%)and asymptomatic urinary abnormalities(7.6%).A total of 61/528(11.6%)patients were type Ⅰ CrGN,331/528(62.7%)were type Ⅱ and 136/528(25.8%)were type Ⅲ.ANCA was positive in 11(18.0%)patients in type Ⅰ,15(4.5%)patients in type Ⅱ and 117(86.0%)patients in type Ⅲ.Anti-GBM was positive in 60(98.4%)patients in type I and 5(3.7%)patients in type Ⅲ.The 5-year cumulative renal survival rates of type I,type Ⅱ,and type ⅢI were 17.6%,70.1%and 44.3%,respectively.Conclusions:Lupus nephritis might be the most common type of CrGN in China,followed by pauci-immune CrGN and IgA nephropathy.Almost half of the patients presented with rapidly progressive glomerulonephritis,while 12.1%of cases showed chronic renal failure and 7.6%presented with asymptomatic urinary abnormalities.The clinical manifestations and outcomes varied with different types of CrGN.The 5-year cumulative renal survival rates of type Ⅰ,type Ⅱ,and type Ⅲ were 17.6%,70.1%and 44.3%,respectively.Part 2.Significance of histological crescent formation ratio in patients with diffuse proliferative lupus nephritisObjective:To investigate the clinicopathological features and outcome of diffuse proliferative lupus nephritis patients with different degree of crescents.Methods:520 DPLN patients with more than 10%histological crescents(cDPLN)diagnosed from January 2000 to Decmber 2010 were enrolled in this retrospective study.They were divided into three groups:group 1(10%≤Crescent%<25,n=240),group 2(25%<Crescent%<50,n=160),and group 3(Crescent%≥50,n=120).Another 100 patients without histological crescents were enrolled as a control group.Their clinicopathological features,treatment response and outcome were compared among four groups.Results:They were 450(86.6%)females and 70(13.4%)males with an average age of 31.7±11.4ys.Compared with controls,cDPLN patients had shorter LN duration(20.7±34.1)vs(30.4±48.9)mo,higher prevalence of RPGN(21.8%),and gross hematuria(26.7%).Laboratory findings indicated more severe hypo-proteinemia,hyperlipoidemia,and renal insufficiency,heavier proteinuria and microscopic hematuria,higher levels of tubular injury parameters and lower serological activity in crescentic groups.Histologically,cDPLN patients had severe glomerular and tubulointerstitial lesions,extensive leukocyte infiltration,together with a lesser degree of immune complex deposition.Crescent ratio correlated positively with the ratio of serositis,hypertension,anemia,gross hematuria,positive ANCA,cappilary necrosis,the levels of urea nitrogen,creatinine,complement C3,C4,urine NAG enzyme,RBP enzyme and AI,Cl scores,while correlated negatively age,LN duration,SLE duration and the proportion of histological platinum ear phenomenon.Conclusions:cDPLN patients with acute onset and short disease duration mostly show severe renal manifestations,less extra-renal organ involvement,lower serological activity,serious capillary necrosis,severe tubulointerstitial inflammation,atrophy and fibrosis,prominent leukocyte infiltration,less glomerular immune complex deposition.Part 3.Prediction of renal outcomes in patients with crescentic lupus nephritisObjective:To identify the renal survival and risk factors in patients with crescentic lupus nephritis(cLN).Methods:One hundred and twenty-four cases of biopsy-proven LN with>50%crescents(cLN)followed for more than one year were included in this study.Another 100 LN patients without crescents were randomely enrolled as a control group.Their clinicopathological data and long-term outcome were compared.Results:There were 101 females and 23 males with an average age of 32.0±13.5 years followed for a median period of 4 years.At biopsy,the mean SCr level was 2.4±2.0mg/dl and the mean percentage of crescents was 64.4±13.3%.The renal survival rates at years 15 3 and 5 after biopsy of cLN group and the control group were 82.3%vs 97.8%,78.4%vs 92.6%and 70.2%vs 84.9%,respectively.Multivariate Cox regression revealed initial SCr concentration as the only independent risk factor for ESRD(HR 1.433,P<0.001).Logistic regression showed that the risk of ESRD at 5 years after biopsy increased rapidly at SCr>1.4mg/dl and reached 90%at SCr>5.5mg/dl.Conclusions:Crescentic LN had worse treatment response and lower probability of renal survival than those without crescents.The renal survival rates at 5-year after biopsy of cLN was 70.2%,MMF combined with FK506 was an effective induction therapy for crescentic LN.Initial SCr concentration may predict kidney failure in patients with cresentic disease.