The Clinico-pathological Characteristics And Prognosis In Patients With Thrombotic Microangiopathy

Thrombotic microangiopathy(TMA)is associated with a cluster of diseases.It may show a wide variety of clinical manifestations,including microangiopathic hemolytic anemia(MAHA),thrombocytopenia,and renal insufficiency.And renal biopsy can reveal various histological changes,including thrombi,endothelial swelling,widening of the subendothelial space,mesangial interposition,variable mesangiolysis in the glomeruli;luminal thrombi,mucoid intimal hyperplasia"onion-skinning" changes and intimal fibroplasia in the arterioles and/or arteries.Different TMA related diseases have their specific characteristics of morphologic changes.The therapeutic strategies and prognoses are different according to the etiologies.To date,limited cohorts of patients with biopsy-proven TMA in China were reported,and such studies were almost in small samples.Thus,the present study sought to explore the clinico-pathological characteristics of the most common forms TMA of atypical HUS(aHUS),lupus nephritis-associated TMA(LN-TMA),pregnancy-associated TMA(P-TMA),and malignant hypertension-associated TMA,and the rare but disastrous condition with pregnancy-associated acute renal cortical necrosis(RCN),to increase the knowledge in patients with TMA.Part one:A comparison of clinico-pathological characteristics and prognosis in patients with thrombotic microangiopathyof different etiologiesObjective:Thrombotic microangiopathy(TMA)is associated with a cluster of diseases.This study sought to compare the clinico-pathological characteristics and prognosis in biopsy-proven TMA patients.Methods:Patients with atypical hemolytic uremic syndrome(aHUS)(n=38),lupus nephritis-associated TMA(LN-TMA)(n=37),and pregnancy-associated TMA(P-TMA)(n=22)were enrolled.This study compared the clinico-pathological characteristics and the prognoses of these patients.Results:aHUS cases presented with a highest median serum creatinine level(aHUS 791.2(396.9-1148.3)?mol/L vs.LN-TMA 388.1(189.2-581.7)?mol/L vs.P-TMA 69.8(53.9-556.9)?mol/L)and a highest incidence of anemia(aHUS 100%vs.LN-TMA 97.3%vs.P-TMA 63.6%),with a wide variety of TMA lesions.P-TMA cases presented the lowest level of systemic involvement,with the lowest incidences of renal insufficiency(aHUS 100%vs.LN-TMA 89.2%vs.P-TMA 50.0%),thrombocytopenia(aHUS 76.3%vs.LN-TMA 75.7%vs.P-TMA 27.3%)and anemia,and the highest incidence glomerular basement membrane(GBM)reduplication(aHUS 55.3%vs.LN-TMA 45.9%vs.P-TMA 95.5%).LN-TMA cases presented the highest level of proteinuria(aHUS 1.38(0.74-2.58)g/24h vs.LN-TMA 2.65(1.87-5.33)g/24h vs.P-TMA 1.18(0.68-1.64)g/24h)and the highest incidence of microscopic hematuria(aHUS 65.8%vs.LN-TMA 89.2%vs.P-TMA 50.0%),with arterial and glomerular thrombi dominantly(aHUS 57.9%vs.LN-TMA 83.8%vs.P-TMA 22.7%;aHUS 26.3%vs.LN-TMA 59.5%vs.P-TMA 4.5%,respectively).At the end of follow-up,aHUS patients exhibited the poorest renal outcomes of progression to end-stage renal disease(ESRD)(aHUS 63.2%vs.LN-TMA 24.3%vs.P-TMA 18.2%),whereas LN-TMA patients had the highest incidence of recovery of renal insufficiency(aHUS 15.8%vs.LN-TMA 27.0%vs.P-TMA 18.2%).The percentage of tubular atrophy/interstitial fibrosis(TAIF)independently influenced the renal survival.The presence of arteriolar/arterial intimal fibroplasia,the increased percentages of glomerulosclerosis and TAIF were risk factors for non-recovering from renal insufficiency.Conclusions:TMA of different associated diseases presented a wide variety of clinico-pathological characteristics and prognoses.In these three groups,patients with aHUS had the worst prognoses,whereas patients with LN-TMA and P-TMA had better prognoses.Part two:Clinico-pathological characteristics and outcomes of patients with biopsy-proven hypertensive nephrosclerosisBackground:This study aimed to investigate renal outcomes and their predictors in biopsy-proven hypertensive nephrosclerosis(HN)patients and to compare clinico-pathological characteristics and prognoses between HN with TMA and HN without TMA patients.Methods:Data for biopsy-proven HN patients were retrospectively analyzed.Renal survival rates and relationships between clinico-pathological characteristics and outcomes were assessed.Results:A total of 194 patients were enrolled;the mean age at biopsy was 43.8 ±4.1 years,and male gender predominated(82.5%).The median duration of hypertension was 5.0 years,and the mean systolic and diastolic blood pressures were 195±37 and 126±26 mmHg,respectively.The median serum creatinine(Scr)level,estimated glomerular filtration rate(eGFR),and proteinuria level were 142.3?mol/L,49.6 ml/min/1.73 m2,and 0.80 g/24 h,respectively.HN with TMA and HN without TMA found by renal biopsy were 87 cases and 107 cases,respectively.At biopsy,HN with TMA patients were younger,had a higher male:female ratio,had a shorter duration of hypertension,and had higher median Scr and proteinuria levels,higher incidences of anemia,hypertensive heart disease and hypertensive retinopathy,and worse renal outcomes than HN without TMA patients.During a median follow-up period of 3.0 years,36 patients(18.6%)reached end-stage renal disease(ESRD),and the 5-and 10-year cumulative renal survival rates for HN patients were 84.5%and 48.9%,respectively.A decreased baseline eGFR,an increased baseline proteinuria level,anemia,increased percentage of global glomerulosclerosis and tubular atrophy and interstitial fibrosis(TAIF)were independent predictors of future ESRD.Conclusions:The renal outcomes of HN patients were independently associated with the baseline eGFR and proteinuria level,anemia,percentage of global glomerulosclerosis and TAIF.The clinico-pathological characteristics and prognoses were significantly different between the HN with TMA and HN without TMA patients.Part three:Clinico-pathological characteristics and outcomes of patients with pregnancy-associated acute renal cortical necrosisObjective:This study aimed to investigate clinico-pathological characteristics and prognoses in patients with pregnancy-associated acute renal cortical necrosis(RCN).Methods:Data for RCN patients from 2003 January to 2015 June in Jinling Hospital were retrospectively analyzed.Five patients with pregnancy-associated acute RCN were enrolled in this study.Results:The mean age at biopsy was 28.6±4.7 years.Three patients presented with severe preeclampsia and 1 with pregnancy-induced hypertension during the pregnancy.Twin pregnancy occurred in 3 patients,and placental abruption occurred in 2.All of the patients were presented with acute kidney injury(AKI).Out of them,4 were anuric and 1 was oliguric.All of them had anemia with an average hemoglobin of 81.6±13.6g/L and an elevated lactate dehydrogenase(LDH)of 280?4783U/L,and 3 out of 4 patients had reticulocytosis.Thrombocytopenia was found in 3 patients.One patient presented with disseminated intravascular coagulation(DIC).All of the patients exhibited multiple organ dysfunction of liver involved(3 cases),heart involved(2 cases),lung involved(2 cases),pancreas involved(1 case),alimentary tract hemorrhage(1 case)and serositis(4 cases).All five patients underwent renal biopsies which revealed acute RCN accompanied with TMA lesions.All of the patients received the dialysis and supportive measures,2 out of 5 received plasma therapy,and 3 out of 5 treated with glucocorticoid.At the end of follow-up,2 patients progressed to ESRD and the other 3 completely or partially recovered from renal dysfunction.Conclusions:pregnancy-associated acute RCN presented with acute onset anuric or oliguric AKI,accompanied with multiple organ dysfunction and microangiopathic hemolytic anemia,with or without thrombocytopenia,and more than half patients completely or partial recovered of renal dysfunction.