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Objective:To investigate the urinary sediment findings and the clinicopathologic features of IgA nephropathy (IgAN) patients with acute kidney injury (AKI).Methods:It was a retrospective study. The patients with renal biopsy-proven primary IgAN in Peking University First Hospital from January 31, 2013 to July 31, 2015 were selected. According to whether AKI occurred at renal biopsy or not, the patients were divided into AKI group and non-AKI group. Morning urine samples were obtained on the day of renal biopsy. Urine sediments, including various cells and casts, were examined. The clinical data, urinary sediments, and renal pathological changes were compared between the two groups. Logistic regression analysis was performed to identify the association between clinical pathological changes, urinary sediment indicators and AKI, or clinical pathological changes and urinary sediment indicators.Results:There were 502 IgAN patients enrolled in this study, with age of (36.1±12.1) years old and 261 males (52.0%). The incidence of AKI was 11.4% (57/502) among the enrolled patients at the time of renal biopsy. Common causes of AKI included gross hematuria-induced AKI (10 cases), acute tubulointerstitial nephritis (10 cases), crescentic IgAN (9 cases), malignant hypertensive renal damage (6 cases), and multiple etioloqy or unknown etiology (22 cases). Compared with non-AKI group, AKI group had higher proportions of males and malignant hypertension, higher levels of proteinuria and urinary erythrocyte counts, and higher frequencies of gross hematuria, leukocyturia, renal tubular epithelial cells, and granular casts (all P<0.05). AKI group also had higher proportions of severe tubular atrophy/interstitial fibrosis (T2) and cellular/cellular fibrous crescent formation (C2) than non-AKI group (both P<0.05). Logistic regression analysis results showed that, there were statistically significant differences in the correlation between AKI and gender, 24 h urinary protein, urinary erythrocyte counts, granular casts and renal tubular atrophy/interstitial fibrosis (T) scores (all P<0.05). Hematuria, leukocyturia, red blood cell casts, white blood cell casts, granular casts, and fatty casts were correlated with endothelial hypercellularity (E) and cellular/cellular fibrous crescent formation (C) scores, respectively (all P<0.05). Hematuria was correlated with mesangial hypercellularity (M) scores ( OR=2.613, 95% CI 1.520-4.493, P=0.001). Hematuria ( OR=1.723, 95% CI 1.017-2.919, P=0.043) and fatty casts ( OR=2.646, 95% CI 1.122-6.238, P=0.026) were correlated with segmental sclerosis or adhesion (S) scores. Leukocyturia ( OR=1.645, 95% CI 1.154-2.347, P=0.006) and fatty casts ( OR=2.344, 95% CI 1.202-4.572, P=0.012) were correlated with T scores. Epithelial cell cast was correlated with C scores ( OR=1.857, 95% CI 1.174-2.939, P=0.008). Conclusions:AKI is a common complication among IgAN patients with diverse etiology and more severe clinicopathological features. Urinary sediment findings can reflect renal pathological changes to some extent, and therefore assist in the clinical diagnosis and treatment of IgAN patients with AKI.
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The paper reports a case of coenzyme Q10 deficiency nephrotic syndrome associated with coenzyme Q2 gene mutation and reviews the literature on this topic. The patient presented with hematuria, proteinuria, and a diminution of vision as clinical manifestations. But the proteinuria was not relieved after sufficient doses of glucocorticoids for over 2 months. The patient′s birth history was unremarkable, and his parents were both healthy and not consanguineous. Whole exome sequencing revealed that the patient had a mutation of coenzyme Q2 gene at c.973A>G(p.T325A) and c.517C>T(p.R173C). Combined with renal biopsy pathology, the patient was diagnosed with hereditary nephropathy and started the supplements of coenzyme Q10 after stopping glucocorticoid treatments immediately. After 5 weeks of therapy, the patient′s 24-h urine protein quantification decreased from 6.01 g to 1.53 g.
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Purpose@#The role of vacuolar protein sorting 34 (Vps34), an indispensable protein required for cell vesicular trafficking, in the biological behavior of hepatocellular carcinoma (HCC) has yet to be studied. @*Materials and Methods@#In the present study, the expression of Vps34 in HCC and the effect of Vps34 on HCC cell invasion was detected both in vivo and in vitro. Furthermore, by modulating the RILP and Rab11, which regulate juxtanuclear lysosome aggregation and recycling endosome respectively, the underlying mechanism was investigated. @*Results@#Vps34 was significantly decreased in HCC and negatively correlated with the HCC invasiveness both in vivo and in vitro. Moreover, Vps34 could promote lysosomal juxtanuclear accumulation, reduce the invasive ability of HCC cells via the Rab7-RILP pathway. In addition, the deficiency of Vps34 in HCC cells affected the endosome-lysosome system, resulting in enhanced Rab11 mediated endocytic recycling of cell surface receptor and increased invasion of HCC cells. @*Conclusion@#Our study reveals that Vps34 acts as an invasion suppressor in HCC cells, and more importantly, the endosome-lysosome trafficking regulated by Vps34 has the potential to become a target pathway in HCC treatment.
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Objective:To analyze the clinicopathological characteristics, treatment responses and kidney outcomes of patients with atypical membranous nephropathy (MN), and to provide information for the clinical practice.Methods:The clinical data of patients with atypical MN and synchronous primary MN who were diagnosed, treated and followed up in Peking University First Hospital from January 2008 to June 2020 were retrospectively collected and analyzed. Clinicopathological features, treatment responses and kidney prognosis were compared between the two groups. The expression of phospholipase A2 receptor (PLA2R) in kidney tissues was detected by immunofluorescence. Serum anti-PLA2R antibody was detected by enzyme-linked immunosorbent assay. Clinicopathological indexes were compared between PLA2R-related MN group and non-PLA2R-related MN group. Kaplan-Meier (Log-rank test) survival curve and multivariate Cox regression analysis methods were used to analyze the influencing factors of kidney prognosis in patients with atypical MN. The primary endpoint of renal adverse outcome was renal insufficiency, defined as end-stage renal disease or estimated glomerular filtration rate (eGFR) decline>30% baseline and<60 ml·min -1·(1.73 m 2) -1. Results:A total of 65 atypical MN patients were enrolled in this study. Compared with primary MN ( n=324), patients with atypical MN had younger age ( Z=-4.229, P<0.001), higher proportion of hematuria ( χ2=5.555, P=0.018), higher level of urinary protein ( Z=2.228, P=0.026) and lower level of eGFR ( t=-5.108, P<0.001); the proportion of IgG4 deposition in kidneys was lower ( χ2=8.081, P=0.004), and the proportions of IgA ( χ2=16.969, P<0.001) and IgM ( χ2=9.281, P=0.002) deposition were higher. There was no significant difference on gender, serum albumin, positive proportion of anti-PLA2R antibody, anti-PLA2R antibody level and kidney C3/C1q deposition between the two groups (all P>0.05). The proportions of atypical MN patients receiving renin-angiotensin aldosterone system inhibitors (49.3% vs 57.1%), calcineurin inhibitors (27.7% vs 19.1%) and cyclophosphamide (21.5% vs 23.8%) were comparable to those of primary MN patients (all P>0.05). The rates of clinical remission (80.0% vs 77.2%), partial remission (44.6% vs 44.1%), complete remission (35.4% vs 33.1%), spontaneous remission (36.9% vs 42.6%), response to cyclophosphamide (85.7% vs 81.8%), response to calcineurin inhibitor (88.9% vs 79.0%), and relapse (30.8% vs 26.8%) in atypical MN patients were comparable to those in primary MN patients (all P>0.05). During the follow-up 30.0(21.5, 61.5) months, 15 atypical MN patients (23.1%) had eGFR reduction>30%, among whom 7 patients (10.8%) had eGFR reduction>50% and 3 patients (4.6%) had end-stage kidney disease. There was no significant difference on poor kidney prognosis between the two groups (all P>0.05). Kaplan-Meier survival curve showed that patients with age>39 years old ( χ2=10.092, P=0.001), eGFR≤100 ml·min -1·(1.73 m 2) -1( χ2=5.491, P=0.019), tubular interstitial lesion ( χ2=6.999, P=0.008) and no nephropathy remission ( χ2=22.952, P<0.001) had earlier poor renal prognosis. Multivariate Cox regression analysis showed that no nephropathy remission ( HR=12.604, 95% CI 2.691-59.037, P=0.001) was an independent influencing factor for poor renal prognosis in atypical MN patients. Conclusion:No significant difference is found between atypical MN and primary MN on treatment responses and kidney prognosis, which implies that clinical practice of atypical MN can be performed by referring to the guidelines and experience of primary MN.
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Objective:To investigate the clinicopathological characteristics of renal leukocyte chemotactic factor 2 amyloidosis (ALECT2).Methods:The patients with renal ALECT2 diagnosed by renal biopsy in Peking University First Hospital, Shanxi Medical University Second Hospital and Shanxi Bethune Hospital from January 2001 to October 2021 were retrospectively enrolled. According to whether the patients had concurrent glomerular diseases, they were classified into two groups: isolated ALECT2 group and ALECT2 with concurrent renal diseases group. Clinicopathological data of the two groups were compared. Light microscopy, immunofluorescence and immunoelectron microscopy were applied to investigate pathological characteristics of renal tissues. Mass spectrometry was used to analyze the composition of renal amyloid deposits. Gene sequencing was employed to detect the leukocyte chemotactic factor 2 ( LECT2) gene sequence in peripheral blood of the patients. Results:Sixteen patients with ALECT2 were enrolled in this study and nine of them had concurrent renal diseases. The age of 16 patients was (65.00±8.45) years old. The sex ratio of males to females was 7 to 9. Most of patients were Han ethnicity (15/16). Eight patients came from Shanxi province. Fifteen patients presented with varying degree of proteinuria [2.16(1.07, 4.72) g/24 h]; 5 patients had nephrotic syndrome; 11 patients had renal insufficiency; 12 patients had microscopic hematuria. Part of patients also had hypertension (12/16) and diabetics (6/16). Compared with isolated ALECT2, the ALECT2 group with concurrent renal diseases had a higher proportion of nephrotic syndrome (5/9 vs 0/7, P=0.034). Renal biopsy results showed that all patients (16/16) had amyloid deposits in the interstitium of renal cortex with varying degree of inflammatory cell infiltration and fibrosis, and glomeruli (12/16) and arterioles (14/16) were involved by amyloid deposits. The amyloid deposits were strongly congophilic and immunohistochemistry for LECT2 was positive. By semi-quantitative analysis, the proportions of glomerular and overall amyloid loads in ALECT2 with concurrent renal diseases group were lower than those in isolated ALECT2 group (both P<0.05). Electron microscopy revealed randomly oriented and non-branching fibrils with a diameter of 8-12 nm. The LECT2 peptides were detected by mass spectrometry in renal amyloid deposits of 8 patients, and homozygous G allele of LECT2 was found in 7 patients by gene sequencing. Complete follow-up data of 13 patients showed that 2 patients died, 1 patient developed end-stage renal disease at the time of renal biopsy, and most of the rest patients had stable renal function (8/10). Conclusions:Patients with renal ALECT2 mainly present with proteinuria, along with a high incidence of renal insufficiency, microscopic hematuria, and concurrent renal diseases. The pathologic feature is the preferential deposition of amyloid in renal cortical interstitium.
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Objective:To summarize and analyze the clinicopathological characteristics of patients with DNAJ heat shock protein family member B9 (DNAJB9)-positive fibrillary glomerulonephritis (FGN).Methods:The clinical and pathological data of 5 patients with DNAJB9-positive FGN diagnosed in Peking University First Hospital from January 2011 to January 2021 were retrospectively collected and analyzed.Results:Among the 5 patients, the female to male ratio was 4∶1, and the median age was 29 years old (24-71 years old). The clinical manifestations included 2 cases with nephrotic syndrome and 3 cases with proteinuria. One patient had gross hematuria, and 4 cases had mild microscopic hematuria. None of the 5 patients had evidence of monoclonal gammopathy. The renal pathological pattern of FGN showed mesangial-proliferative glomerulonephritis, mesangial nodular sclerosis, membranoproliferative glomerulonephritis, and atypical membranous nephropathy. Crescents formation could be accompanied. Immunofluorescence staining showed smudgy and granular IgG and C3 deposition in the mesangial region and capillary wall, and the subtypes of IgG were mainly IgG1 and IgG4. Under electron microscopy, fibrillary deposits with a diameter of 8-30 nm were observed in the mesangial and subendothelial area, accompanied by deposition in basement membrane and occasionally subepithelial area. The renal prognosis of FGN patients was poor. One patient entered end-stage renal disease within one week, and another patient entered end-stage renal disease within one year despite immunosuppressant therapy in 2 cases with nephrotic syndrome at onset. One patient had worsening proteinuria despite renin-angiotensin system (RAS) blocker treatment. Two patients achieved complete renal remission and stable renal function after RAS blocker treatment.Conclusions:Most FGN patients in China are young people. The main clinical manifestations are proteinuria or mild microscopic hematuria. The diagnosis depends on the discovery of fibrillary deposits in the mesangial area and subendothelial area with a diameter of about 10-30 nm under the electron microscope. DNAJB9 protein immunohistochemical staining can be used as an important marker for the diagnosis of FGN. The prognosis of FGN kidney is poor, and there is no effective targeted treatment option now.
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Objective:To analyze clinical data of 3 children with LMX1B-associated disease characterized by asymptomatic glomerular proteinuria, thus improving the recognition of asymptomatic proteinuria with genetic causes. Methods:Three patients with LMX1B-associated disease presented with prominent asymptomatic proteinuria diagnosed by the next-generation sequencing in Department of Pediatrics, Peking University First Hospital from April 2014 to October 2017 were included in this study.Clinical data, including renal and extrarenal manifestations, renal biopsy, and family history, were collected and retrospectively analyzed. Results:All 3 children were girls, the age of onset were 2 years, 1 year, and 4 years, respectively, and the diagnosis age were 11 years, 5 years and 6 years, respectively.All of them had glomerular proteinuria, and nephrotic-level proteinuria occurred in one patient.Microscopic hematuria was found in 2 patients.All of them had normal renal function.Only one patient underwent renal biopsy.Electron microscopy of the first time of biopsy revealed segmental thinning of the glomerular basement membrane.Re-biopsy 4 years later showed irregular thickening of the glomerular basement membrane, moth-eaten appearance and collagen fibrillar material deposition.No abnormalities of nails, limbs and joints were observed by physical examination.Two patients had a family history of renal disease.Conclusions:Genetic factors should be considered in children with obscure onset asymptomatic proteinuria without definite clinical causes.Genetic testing can help diagnose and guide treatment as early as possible.
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OBJECTIVE@#To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis.@*METHODS@#Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family.@*RESULTS@#A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic.@*CONCLUSION@#The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.
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Child , Humans , Genomics , Mutation, Missense , Nephrotic Syndrome/genetics , Sclerosis , TRPC6 Cation Channel/geneticsABSTRACT
Objective:To investigate the clinicopathological characteristics of renal light and heavy chain amyloidosis (AHL).Methods:Ten patients with renal AHL diagnosed by renal biopsy in Peking University First Hospital and Institute of Nephrology of Peking University from January 2015 to June 2020 were enrolled. Clinicopathological data of these patients was collected and reviewed.Results:AHL typically affected older patients, with a male/female ratio of 7:3. The clinical manifestations were mainly edema and heavy proteinuria. At the same time, 7/10 of patients presented with nephrotic syndrome, 7/10 presented with microscopic hematuria, and 3/10 presented with renal insufficiency. Laboratory examinations showed monoclonal immunoglobulin in blood and urine in all patients, and IgGλ was the most common one (5/10). Decreased serum complement could be seen in some patients. The ratio of serum free κ light chain and free λ light chain was abnormal in all patients who underwent serum free light chain test. None of the 10 patients met the diagnostic criteria of multiple myeloma. Except for one of the 10 patients who was diagnosed as Waldenstrom's macroglobulinemia, the rest were diagnosed as monoclonal gammopathy of renal significance (MGRS). Bone marrow of 2/6 of patients were positive for amyloid. Cardiac involvement was confirmed in only one patient. Renal biopsy demonstrated amorphous eosinophilic material, which was Congo red positive, was deposited in glomerular mesangial area (10/10), capillary vessels (8/10), renal interstitium (9/10), peritubular capillary walls (9/10) and arterioles (8/10). This material showed apple green birefringence under polarized light. Immunofluorescence showed that single heavy chain and single light chain were positive at the same time, which was consistent with the results of mass spectrometry analysis. Ultrastructural evaluation revealed randomly oriented, non-branching fibrils with a diameter of 8-12 nm.Conclusions:Main clinical manifestations of AHL amyloidosis are edema and massive proteinuria, along with a high incidence of hematuria, a low portion of heart involvement and high frequency of whole molecule of monoclonal immunoglobulin (IgGλ dominant) by serum immunofixation electrophoresis. Renal pathology shows the commonly involved kidney compartments of amyloid deposits are glomerular capillary walls and peritubular capillary walls in patients with AHL amyloidosis.
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Objective@#To investigate the clinical and pathological features of ischemia renal injury.@*Methods@#Patients with biopsy-proven ischemia renal injury in the Department of Nephrology, Peking University First Hospital from 2010 to 2018 were retrospectively enrolled in the present study. The demographic information and laboratory data were collected. And the severity of pathologic changes including glomeruli, arteriole and tubulo-interstitial fibrosis (IFTA) were semi-quantitatively scored. Arterioles with a ratio of inner/outer luminal diameter greater than 0.5 without hyalinosis were diagnosed as normal ones. The relationships between estimated glomerular filtration rate (eGFR), urine protein excretion and pathological changes were analyzed.@*Results@#A total of 52 patients were enrolled in the study, including 39 males (75.0%). The age of the patients was (45.0±12.7) years at biopsy. Among them, 50 patients (96.2%) had a history of hypertension with a median duration of 66 (24, 138) months. Forty-one patients (78.9%) were overweight or obese. The median urinary protein excretion was 0.75 (0.27, 1.32) g/d with 3 cases over 3 g/d. Fifteen patients (28.8%) presented with microhematuria and twenty-seven patients (51.9%) with eGFR lower than 60 ml·min-1·(1.73 m2)-1, respectively. The ratio of arteriolar inner/outer luminal diameter was 0.43±0.05 and the percentage of normal arterioles was 29.0%±17.0%. There were 21 patients (40.4%) found with arteriole hyalinosis. The ratio of arteriolar inner/outer luminal diameter correlated with the percentage of glomerular lesions (rs=-0.312, P=0.024), the semiquantitative scale of IFTA (rs=-0.291, P=0.037) and eGFR (r=0.339, P=0.014), respectively. Hypertension duration and body mass index (BMI) showed a negative correlation with the ratio of arteriolar inner/outer luminal diameter (rs=-0.303, P=0.029 and rs=-0.274, P=0.050, respectively) and a positive correlation with serum complement 3 level (rs=0.358, P=0.020 and rs=0.432, P=0.004, respectively).@*Conclusions@#Renal ischemia injury may be found in young and middle-aged patients. The characteristic of clinical features is mild to moderate proteinuria accompanied with a certain degree of eGFR decline, while a small number of patients may have microhematuria and marked proteinuria. The ratio of arteriolar inner/outer luminal diameter has a negative correlation with the percentage of glomerular lesions and the semiquantitative scale of IFTA and a positive correlation with eGFR, respectively. Hypertension and obesity are closely related to vascular lesions.
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Objective:To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension.Methods:Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes.Results:A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein ( P=0.002), worse renal function ( P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points ( χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients ( HR=1.872, 95% CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion:It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.
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Objective To investigate the clinical and pathological features of ischemia renal injury.Methods Patients with biopsy-proven ischemia renal injury in the Department of Nephrology,Peking University First Hospital from 2010 to 2018 were retrospectively enrolled in the present study.The demographic information and laboratory data were collected.And the severity of pathologic changes including glomeruli,arteriole and tubulo-interstitial fibrosis (IFTA) were semiquantitatively scored.Arterioles with a ratio of inner/outer luminal diameter greater than 0.5 without hyalinosis were diagnosed as normal ones.The relationships between estimated glomerular filtration rate (eGFR),urine protein excretion and pathological changes were analyzed.Results A total of 52 patients were enrolled in the study,including 39 males (75.0％).The age of the patients was (45.0±12.7) years at biopsy.Among them,50 patients (96.2％) had a history of hypertension with a median duration of 66 (24,138) months.Forty-one patients (78.9％) were overweight or obese.The median urinary protein excretion was 0.75 (0.27,1.32) g/d with 3 cases over 3 g/d.Fifteen patients (28.8％)presented with microhematuria and twenty-seven patients (51.9％) with eGFR lower than 60 ml· min-1·(1.73 m2)-1,respectively.The ratio of arteriolar inner/outer luminal diameter was 0.43+0.05 and the percentage of normal arterioles was 29.0％+17.0％.There were 21 patients (40.4％) found with arteriole hyalinosis.The ratio of arteriolar inner/outer luminal diameter correlated with the percentage of glomerular lesions (rs=-0.312,P=0.024),the semiquantitative scale of IFTA (rs=-0.291,P=0.037) and eGFR (r=0.339,P=0.014),respectively.Hypertension duration and body mass index (BMI) showed a negative correlation with the ratio of arteriolar inner/outer luminal diameter (rs=-0.303,P=0.029 and rs=-0.274,P=0.050,respectively) and a positive correlation with serum complement 3 level (rs=0.358,P=0.020 and rs=0.432,P=0.004,respectively).Conclusions Renal ischemia injury may be found in young and middle-aged patients.The characteristic of clinical features is mild to moderate proteinuria accompanied with a certain degree of eGFR decline,while a small number of patients may have microhematuria and marked proteinuria.The ratio of arteriolar inner/outer luminal diameter has a negative correlation with the percentage of glomerular lesions and the semiquantitative scale of IFTA and a positive correlation with eGFR,respectively.Hypertension and obesity are closely related to vascular lesions.
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In this retrospective cohort study, we aim to evaluate the effect of endocapillary hypercellularity (E) lesions on the renal prognosis and response to immunosuppressive therapy, especially diffuse endocapillary hypercellularity lesion in IgA nephropathy (IgAN). A total of 365 patients with IgAN and E lesions and 31 patients with diffuse E lesions and over 12-month follow-up period were included in this study. We performed an 1∶1 propensity score to identify controls with matched clinical and pathological features from 769 IgAN patients without E lesions. The end-point was defined as a 30% decrease in estimated glomerular filtration rate (eGFR) or end-stage kidney disease. The kidney survival of the two groups was compared by Kaplan-Meier analysis. During median follow-up period of 41 months, kidney survival rates in patients with E lesions were 96.0% at 1 year, 83.6% at 3 years, 67.7% at 5 years; while they were 96.9% at 1 year, 83.6% at 3 years, and 68.7% at 5 years in patients without E lesions ( P=0.265).The HRof immunosuppressive therapy was 1.038 (95% CI 0.749-1.440) and 1.113 (95% CI 0.770-1.609) in patients not receiving immunosuppressive therapy ( P=0.781). (2) During median follow-up period of 52.5 months, the kidney survival rates in patients with diffuse E-lesion were 100.0% at 1 year, 96.2% at 3 years, 74.5% at 5 years; while they were 96.2% at 1 year, 82.3% at 3 years, and 63.7% at 5 years in patients without E-lesion ( P=0.158). The HR of immunosuppressive therapy was 0.625 (95% CI 0.213-1.839) and 0.447 (95% CI 0.028-7.191) in patients not receiving immunosuppressive therapy ( P=0.825). E lesion or diffuse E lesion may not be associated with prognosis or response to immunosuppressive therapy.
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Objective@#To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN).@*Methods@#Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells.@*Results@#A total of 24 patients were enrolled in the study, including 21 males (87.5%), 3 females (12.5%). The age was (58.0±10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7%) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2%) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028).@*Conclusions@#Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.
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Objective To investigate the clinicopathological characteristics of renal light chain deposition disease coexisted with cast nephropathy (LCDD&LCN).Methods Patients with LCDD&LCN (n=10),isolated LCDD (I-LCDD,n=21) and isolated LCN(I-LCN,n=17) diagnosed byrenal biopsy in Peking University First Hospital from January 1,2000 to March 31,2018 were enrolled,and all cases were examined by light microscopy,immunofluorescence (IF) (including light chain) and electron microscopy (EM).The semi-quantitative evaluation of the main features of renal pathology was performed.The clinical manifestations and pathological features were reviewed and compared.Results LCDD&LCN was more prevalent in middle-aged males.Nine patients showed acute renal insufficiency with small molecular proteinuria (97.1％) and microscopic hematuria.The hematologic diseases included 9 patients of multiple myeloma.The type of monoclonal light chain in serum and urine by immunofixation electrophoresis showed λ dominant (5/8).By light microscopy,glomerular lesions presented with mild mesangial proliferation in most patients,and only one of them displayed mesangial nodular sclerosis.At the same time,acute tubular injury with light chain casts was the prominent feature,and the clinical manifestations and histological features of LCDD&LCN were similar to that of I-LCN.IF revealed linear staining of monoclonal light chain along the glomerular basement membrane (GBM),tubular basement membrane (TBM) and Bowman's capsule,and also positive in tubular casts.By electron microscopy,diffuse powder-like or granular electron-dense deposits located in the inner side of the GBM,the outer layer of the TBM,renal interstitium and arteriolar walls were observed.Conclusions Patients with LCDD&LCN manifest as acute renal insufficiency,and the majority have multiple myeloma.The pathology of LCDD&LCN possesses the features of both I-LCDD and I-LCN.The IF stain of light chains(κ,λ) and ultrastructural examination by electron microscopy are the inevitable methods for the diagnosis of LCDD&LCN.
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Objective To evaluate the clinicopathological characteristics and outcomes of IgA nephropathy (IgAN) with acute tubulointerstitial nephropathy (ATIN).Methods Patients who were diagnosed as IgAN with ATIN and IgAN without ATIN by renal biopsy in Peking University First Hospital were enrolled.There were 74 cases of IgAN with ATIN,and seventy-four cases of IgAN without ATIN were enrolled based on stratified sampling (chosen by 1∶ 1).The two groups were well matched with age,gender,follow-up time,mesangial hypercellularity(M),endocapillaryhypercellularity (E),segmental glomerulosclerosis(S),tubular atrophy/interstitial fibrosis(T) and cellular/fibrocellular crescent(C).The clinicopathological characteristics and outcomes of two groups were retrospectively analyzed.A composite end point,defined as 30％ or 50％ estimated glomerular filtration rate (eGFR)decline and end stage renal disease (ESRD) was used.Renal function and proteinuria during follow-up were observed.Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multivariate Cox regression models.Results Seventy-four cases of IgAN with ATIN and seventy-four cases of IgAN without ATIN were enrolled.Serum creatinine [(185.6±83.2) μmol/L vs (146.3 ±69.2) μmol/L,P=0.010] and incidence of acute kidney disease (AKD) (31.1％ vs 5.4％,P ＜ 0.001) were higher in IgAN with ATIN group than those in IgAN without ATIN group.Patients in ATIN group received more immunosuppressive treatment (86.5％vs 58.1％,P＜ 0.001).During 1 year after biopsy,mean eGFR increased significantly in IgAN with ATIN group [(39.7+ 14.6) ml· min-1· (1.73 m2)-1 vs (47.2+ 19.9) ml· min-1· (1.73 m2)-1,P=0.017],but mean eGFR was not statistic different in IgAN without ATIN group [(60.0±30.5) ml· min-1· (1.73 m2)-1 vs (59.0±31.7) ml· min-1· (1.73 m2)-1,P=0.567].Median follow-up was 23.0 months in IgAN with ATIN group,and Median follow-up was 30.0 months in IgAN without ATIN group.Incidence of composite end point had no significant differences between two groups.IgAN with ATIN was not the independent risk factor for end point.IgAN patients with ATIN were divided into two groups (with AKD and without AKD),then renal survival rate was higher (Log-rank test,x2=5.293,P=0.021) and the risk for composite end point decreased by 79.2％ (HR=0.208,95％CI 0.046-0.939,P=0.041) in the group with AKD.Conclusions In IgAN,there is a subgroup of patients with the specific pathological phenotype combined with ATIN.Compared with those without AKD,the risk for composite end point of IgAN patients with ATIN and AKD showed a 79.2％ decrease.
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Objective To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN). Methods Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells. Results A total of 24 patients were enrolled in the study, including 21 males (87.5％), 3 females (12.5％). The age was (58.0 ± 10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7％) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2％) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028). Conclusions Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.
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Objective To elucidate the clinical and pathological characteristics of the patients with thymoma-associated glomerulonephropathy.Methods In this retrospective study,the clinicopathologic characteristics of patients diagnosed as thymoma-associated glomerulonephropathy inPeking University First Hospital during the period between Oct 2008 and Jun 2017 were analyzed,including the histological classfication of thymoma,the clinicopathological features and the short-term prognosis.Results Altogether twelve patients were included with an average age of (55+ 16) years;male/female ratio was 3∶ 1.The B2 type thymoma was the most common type.Nine cases also suffered from myasthenia gravis,and eight cases of glomerulopathy accompanied by thymoma activity.The clinical presentation of glomerulopathy included nephrotic syndrome (11/12),acute kidney injury (10/12).Eleven patients received renal biopsy,among which five cases were minimal change nephropathy,three cases were membranous nephropathy,and the other three cases were focal segmental glomerulosclerosis,thrombotic microangiopathy and endocapillary proliferative glomerulonephritis,respectively.Eleven patients received immunosuppression therapy.After a median 12 months follow up,the proteinuria decreased in 7 cases,and renal function completely or partially recovered in 6 cases.Conclusions Minimal change disease is the most frequent pathological type of thymoma-associated glomerulonephropathy.Immunotherapy with glucocorticoid as first-line drug may be considered for thymoma-associated glomerulonephropathy with surgery,chemoradiation contraindications or non-remission of kidney disease after anti-tumor therapy.
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Lorenz plot (LP) method which gives a global view of long-time electrocardiogram signals, is an efficient simple visualization tool to analyze cardiac arrhythmias, and the morphologies and positions of the extracted attractors may reveal the underlying mechanisms of the onset and termination of arrhythmias. But automatic diagnosis is still impossible because it is lack of the method of extracting attractors by now. We presented here a methodology of attractor extraction and recognition based upon homogeneously statistical properties of the location parameters of scatter points in three dimensional LP (3DLP), which was constructed by three successive RR intervals as , and axis in Cartesian coordinate system. Validation experiments were tested in a group of RR-interval time series and tags data with frequent unifocal premature complexes exported from a 24-hour Holter system. The results showed that this method had excellent effective not only on extraction of attractors, but also on automatic recognition of attractors by the location parameters such as the azimuth of the points peak frequency ( ) of eccentric attractors once stereographic projection of 3DLP along the space diagonal. Besides, was still a powerful index of differential diagnosis of atrial and ventricular extrasystole. Additional experiments proved that this method was also available on several other arrhythmias. Moreover, there were extremely relevant relationships between 3DLP and two dimensional LPs which indicate any conventional achievement of LPs could be implanted into 3DLP. It would have a broad application prospect to integrate this method into conventional long-time electrocardiogram monitoring and analysis system.
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Objective To investigate interactions of vaginal epithelial cells (VEC) with Candida albicans and the protective effect of Lactobacillus crispatus on VEC. Methods VK2/E6E7 VEC cell line was cultured. Candida albicans and Lactobacillus crispatus suspension were prepared respectively. Ultrastructural morphological changes of VEC infected with Candida albicans and treated with Lactobacillus crispatus were observed by scanning electron microscope (SEM). Results Candida albicans invaded into VEC mainly through endocytosis after an early infection of 6 hours. Pseudopods of VEC increased, contacted and covered the surface of pseudohyphae. After 12 hours infection, active penetration developed into the predominant invasion mechanism. Candida albicans directly penetrated through VEC, destroyed the surface structures, and even led to cell death. A reduction of pseudopods on VEC was observed. After co-incubation with Lactobacillus crispatus, SEM revealed a morphological recovery of VEC and destruction of pseudohyphae. Conclusions Candida albicans invade VEC mainly through endocytosis and active penetration. Lactobacillus crispatus could utilize occupying effect to exert protective effect on VEC during the infection with Candida albicans.