scholarly journals Evidences of histologic thrombotic microangiopathy and the impact in renal outcomes of patients with IgA nephropathy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0233199 ◽  
Author(s):  
Precil Diego Miranda de Menezes Neves ◽  
Rafael A. Souza ◽  
Fábio M. Torres ◽  
Fábio A. Reis ◽  
Rafaela B. Pinheiro ◽  
...  
2020 ◽  
Author(s):  
Precil D Neves ◽  
Rafael A Souza ◽  
Fábio M Torres ◽  
Fábio A Reis ◽  
Rafaela B Pinheiro ◽  
...  

ABSTRACTIntroductionIgA nephropathy (IgAN) is the most common primary glomerulopathy worldwide. According to the Oxford Classification, changes in the kidney vascular compartment are not related with worse outcomes. This paper aims to assess the impact of thrombotic microangiopathy (TMA) in the outcomes of Brazilian patients with IgAN.Materials and MethodsAnalysis of clinical data and kidney biopsy findings from patients with IgAN to assess the impact of TMA on renal outcomes.ResultsThe majority of the 118 patients included were females (54.3%); mean age of 33 years (25;43); hypertension and hematuria were observed in 67.8% and 89.8%, respectively. Median creatinine: 1.45mg/dL; eGFR: 48.8ml/min/1.73m2; 24-hour proteinuria: 2.01g; low serum C3: 12.5%. Regarding to Oxford Classification: M1: 76.3%; E1: 35.6%; S1: 70.3%; T1/T2: 38.3%; C1/C2: 28.8%. Average follow-up: 65 months. Histologic evidence of TMA were detected in 21 (17.8%) patients and those ones presented more frequently hypertension (100% vs. 61%, p <0.0001), hematuria (100% vs 87.6%, p=0.0001), worse creatinine levels (3.8 vs. 1.38 mg/dL, p=0.0001), eGFR (18 vs. 60 ml/min/1.73m2), p =0.0001), low serum C3 (28.5% vs. 10.4%, p =0.003), lower hemoglobin levels (10.6 vs. 12.7g/dL, p<0.001) and platelet counts (207,000 vs. 267,000, p=0.001). Biopsy findings of individuals with TMA revealed only greater proportions of E1 (68% vs. 32%, p = 0.002). Individuals with TMA were followed for less time (7 vs. 65 months, p<0.0001) since they progressed more frequently to chronic kidney disease (CKD) requiring renal replacement therapy (RRT) (71.4% vs. 21,6%, p<0.0001). Male sex, T1/T2, and TMA were independently associated with progression to CKD-RRT.ConclusionsIn this study patients with TMA had worse clinical manifestations and outcomes. In terms of histologic evidence, E1 distinguished patients with TMA from other patients. These findings indicate that vascular compartment may also be a prognostic marker in IgAN patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Tan ◽  
Yi Tang ◽  
Gaiqin Pei ◽  
Zhengxia Zhong ◽  
Jiaxing Tan ◽  
...  

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.


2021 ◽  
Vol 73 (10) ◽  
pp. 687-694
Author(s):  
Thanaporn Chaiyapak ◽  
Anirut Pattaragarn ◽  
Suroj Supavekin ◽  
Nuntawan Piyaphanee ◽  
Kraisoon Lomjansook ◽  
...  

Background: Henoch-Schönlein purpura nephritis (HSPN) is considered the systemic form of IgA nephropathy (IgAN). However, differing clinicopathological features and renal outcomes of children with IgAN and HSPN have been reported in some studies. Methods: This study retrospectively reviewed children with IgAN and HSPN younger than 18 years, between January 2004 and December 2015. The clinicopathological characteristics at diagnosis and the renal outcomes after at least 1 year of follow-up were compared between the two groups. Results: A total of 54 children, comprising 21 with IgAN and 33 with HSPN, were recruited. The children with HSPN were younger than the children with IgAN. Gross hematuria and nephritic syndrome at the initial presentation were more common in children with IgAN. Regarding the pathological findings, IgAN had greater chronicity than HSPN. After a median follow-up period from first presentation to renal outcomes measurement of 4.0 years (1.3-12.2) in children with IgAN and 4.2 years (1.1-11.4) in children with HSPN, the renal outcomes were better in the latter group. The incidence of chronic kidney disease (CKD) was 28.6% in children with IgAN and 6.1% in children with HSPN (p = 0.02). Complete recovery was observed more frequently in children with HSPN than in children with IgAN (57.1% in IgAN vs. 87.9% in HSPN, p = 0.01). Conclusions: Childhood IgAN has greater chronicity and worse renal outcomes than childhood HSPN, with a lower rate of complete recovery and a higher frequency of CKD. We recommend long-term follow-up for CKD in children with IgAN.


2019 ◽  
Vol 70 (4) ◽  
pp. 1380
Author(s):  
E.R. Charles ◽  
D. Lui ◽  
J. Delf ◽  
R.D. Sayers ◽  
M.J. Bown ◽  
...  

2017 ◽  
Vol 45 (4) ◽  
pp. 293-300 ◽  
Author(s):  
Di Liu ◽  
Yexin Liu ◽  
Guochun Chen ◽  
Liyu He ◽  
Chengyuan Tang ◽  
...  

Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.


2011 ◽  
Vol 23 (1) ◽  
pp. 137-148 ◽  
Author(s):  
Khalil El Karoui ◽  
Gary S. Hill ◽  
Alexandre Karras ◽  
Christian Jacquot ◽  
Luc Moulonguet ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dilukshi Pilapitiya ◽  
Nayomi Wadduwage ◽  
Chanaka Aberathna ◽  
Chinthana Galahitiyawa ◽  
Chula Herath ◽  
...  

Abstract Background and Aims Histopathological analysis of renal biopsy is the cornerstone of diagnosis in renal disease and guides treatment and prognosis. The prevalence of various renal diseases varies according to the geographical area, socioeconomic condition, race, age, demography and indication of renal biopsy. Method A retrospective study of all native and transplant kidney biopsies performed at the renal unit of Sri Jayewardenepura General Hospital, Sri Lanka, between 1st October 2012 and 30th September 2019. Samples were processed for light microscopy in all cases, with immunofluorescence in most cases. Results 771 biopsies were analyzed. Majority of biopsies 514 (67%) were male patients. Most biopsies (n= 345, 45%) were in 40 – 59yr age group, followed by 267 (35%) 20–39yr, 117 (15%) 60–69yr, 12 (1%) &gt;70yrs, 30 (4%) 12–19yr age groups. Maximum age was 84 years. In 35 cases, tissue were inadequate. 547 (71%) were native biopsies and 224 (29%) were graft biopsies. Among transplants, majority was for an indication (n=146, 66%) followed by time-zeroes (n=59, 26%) and protocols (n=19, 9%). Rising creatinine (81%) was the strongest reason for transplant biopsies, next proteinuria (10%) and delayed graft function (7%). Time zeroes: majority were normal, few ATN, 1 chronic tubulointerstitial nephritis, and 1 hypertensive glomerulosclerosis. Grafts revealed, acute antibody-mediated rejection 41 (18%) with acute cell-mediated rejection 27 (12%), (total rejections n=68, 30%) followed by normal histology 48 (21%), acute tubular necrosis 43 (19%), chronic allograft nephropathy 23 (10%), BKV nephropathy 5 (2%), and 18% other etiologies: CNI-toxicity (n=4), hypertensive glomerulosclerosis (n=3), diabetic nephropathy (n=2), thrombotic microangiopathy (n=2), FSGS (n=2), MPGN (n=1), vasculitis (n=2), PTLD (n=1), cast nephropathy (n=1), and granulomatous interstitial nephritis (n=1). The most common indication for native biopsy was nephrotic syndrome 209 (38%), followed by non-proteinuric CKD 105 (19%), unexplained renal failure 77 (14%), sub-nephrotic proteinuria 102 (18%), nephritic syndrome 54 (9%). Primary glomerulonephritis (GN) was the commonest 291 (53%). Commonest lesion amidst primary GN was IgA nephropathy 90 (16%), followed by FSGS 63 (12%), CGN 27 (4%), minimal change 36 (6%), MPGN 32 (5%), membranous 6 (1%), DPGN 22 (4%), mesangiocapillary GN 3 (0.5%) and post-streptococcal GN 11 (2%). In the secondary forms of GN, SLE was the commonest 39 (7%), next diabetic nephropathy 29 (5%), amyloidosis 2 (0.3%). Chronic tubulointerstitial nephritis 92 (16%) was the second common, with 42 (7%) CINAC – chronic interstitial nephritis in agricultural communities. Other etiologies: acute tubulointerstitial nephritis 14 (2.5%), hypertensive glomerulosclerosis 12 (2%), thrombotic microangiopathy 6 (1%), ischemic nephropathy 9 (1%), end stage disease 6 (1%), inconclusive 13 (2%). 5 cast nephropathy due to multiple myeloma, 1 monoclonal deposition disease due to lambda chain deposition, 1 sarcoidosis, 1 cholesterol embolism. Conclusion Female: male ratio 1:2 with commonest age group being 40 – 59yrs. Strongest indication for transplant biopsy was rising creatinine. Acute rejection was the most frequent finding in grafts, with normal histology being the next, probably due to high number of time zeroes and protocols performed in our centre. Biopsy proven BKV nephropathy was 2% (n=5). Nephrotic range proteinuria was the commonest native biopsy indication, with non-proteinuric CKD being the second. Primary GN was the commonest finding with IgA nephropathy scoring the highest. This does not coincide with global data, which shows FSGS to be the leading cause. The second common histology was FSGS, and primary CTIN was third. The prevalence of biopsy-proven GN varies due to a wide array of factors and different studies have shown different leading patterns.


2006 ◽  
Vol 66 (12) ◽  
pp. 397-404 ◽  
Author(s):  
A. Chang ◽  
J. Kowalewska ◽  
K.D. Smith ◽  
R.F. Nicosia ◽  
C.E. Alpers

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