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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 evaluate the quality of clinical practice guidelines for kidney diseases in China and provide reference for selecting suitable high-quality guidelines for primary care and developing standardized guidelines.@*Methods@#The China Guideline Clearinghouse, China Biology Medicine disc, VIP Database, Wanfang Database and CNKI, and other resources were searched from January 2013 to July 2018. In accordance with the criteria for inclusion and exclusion, the published guidelines for kidney diseases were screened. The Appraisal of Guidelines Research and Evaluation-China (AGREE-China) was used to systematically assess the current status of domestic guidelines for kidney diseases.@*Results@#A total of 18 guidelines for kidney diseases were included, covering different types of kidney disease such as glomerulonephritis, nephrotic syndrome, end-stage renal disease and other diseases. The overall score ranged from 30 to 68, with an average score of 47.3. The average scores of these guidelines were 20.1, 12.8, 0.5, 9.9 and 3.9 in five review fields including scientificity/rigorism, effectiveness/safety, economy, availability/feasibility, and conflicts of interest, respectively. Of these 18 guidelines, 8(44.4%) guidelines were strongly recommended, and 10(55.6%) guidelines were weakly recommended.@*Conclusions@#There are still deficiencies in scientificity/rigorism and economy in current guidelines for kidney diseases in China. The AGREE-China can be used as an evaluation tool for guidelines for kidney diseases in accordance with China's situation, while its practicability and feasibility still need further verification and improvement.
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Objective To study the effect of blood pressure (BP) control on the progression of renal function in elderly patients with chronic kidney disease (CKD) stages 3 and 4.Methods Patients aged 65 years or older in our CKD clinic with baseline CKD stages 3 and 4 and with more than one-year followup until February 2014 were included in this study.Those who had an annual loss of epidermal growth factor receptor(eGFR) for more than 5 ml · min-1 · 1.73 m-2,or reached CKD stage 5,and/or initiated renal replacement therapy were regarded as progression of CKD.Cox regression was used to analyze the effect of BP control on the progression of CKD.Results A total of 118 patients [57 men,mean age (73.8 ± 5.1) years] were enrolled in the final analysis with median baseline eGFR of 37.9 (29.3,46.7) ml ·min-1· 1.73m-2.The baseline BP was (137.0±18.0)/(72.5±10.3)mmHg(1 mmHg=0.133 kPa).During the median 26 months (12-94 m) follow-up period,the average treated BP was (136.2 ± 12.1)/ (70.5 ±6.9)mmHg.Among all the subjects,64.4％ of them reached the BP target (＜ 140/90 mmHg) and 23.7％ had progression of CKD.Treated systolic BP (HR =1.504,95％ CI 1.023-2.212) and baseline eGFR (HR =0.923,95％ CI 0.872-0.977) were independent risk factors for renal function progression in multivariate Cox analysis.Patients with treated systolic BP over 140 mmHg had higher risk to develop progression of CKD compared with those with systolic BP ≤ 140 mmHg (HR =2.505,95％ CI 1.090-5.756).Conclusions Tight blood pressure control is important in the routine care of elderly patients with CKD stage 3 and stage 4.
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Objective To clarify whether the NADPH oxidases (NOXs) family contributed to the reactive oxygen species (ROS) production and subsequent interstitial fibrosis in unilateral ureter obstruction (UUO) rats.Methods Male Wistar rats were randomly divided into sham operation group (n =8),sham operation + apocynin treatment group (n =8),UUO operation group (n =8) and UUO operation+apocynin treatment group (n =8).Either vehicle or apocynin (100 mg/kg per day) were given by gavage for 7 days after surgery.Rats were sacrificed at 7th day.ELISA was used to detect the activity of superoxide dismutase (SOD) and catalase (CAT),and the level of 8-iso-prostaglandin F2alpha (8-isoPGF2α) in renal tissue.Western blotting was used to detect the protein expressions of NADPH oxidase subunit NOX2 and NOX4,α-smooth muscle actin(α-SMA),collagen Ⅰ (COL-Ⅰ) and the level of ERK1/ 2 phosphorylation (p-ERK1/2).Results UUO rats with vehicle displayed increased oxidative stress,as measured by renal tissue 8-iso-PGF2α,accompanied with increased renal expression of NADPH oxidases (NOX2,1.5-fold and NOX4,1.7-fold,respectively),compared with sham-operated rats (P ＜0.05).Furthermore,vehicle treated UUO rats showed increased renal COL-Ⅰ and α-SMA levels,compared with sham-operated rats (P ＜ 0.05).ERK1/2 was also activated as detected by p-ERK1/2 expression in UUO rats with vehicle (P ＜ 0.05).Apocynin treatment significantly decreased renal tissue 8-iso-PGF2α level and expressions of NOX2 (-28.7％) and NOX4 (-31.0％) in UUO rats,respectively,compared with vehicle treated rats (P ＜ 0.05).And significant decrease of COL-Ⅰ (-26.4％) and α-SMA expression (-80.0％) were also observed (P ＜ 0.05).The activation of ERK1/2 in UUO rats was greatly inhibited by apocynin treatment (P ＜ 0.01).Despite the pronounced dysregulation of pro-oxidative NOXs family,no compensatory increase of antioxidative enzyme activities occurred.Conclusion The NOXs family contributes largely to the production of ROS and subsequent interstitial fibrosis after ureter ligation,and inhibition of the NOXs family may be a choice for preventing interstitial fibrosis.
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Objective To analyze the baseline clinical characteristics of the chronic kidney disease (CKD) in aged people in the clinic.Methods Patients aged 18 years or older in our CKD clinic from October 2003 to December 2012 were included in this study.According to their age patients were divided into 2 groups:aged CKD group:aged 65 or older and non-aged CKD group:younger than 65.A group of the elderly without CKD from health screening program were selected as aged non-CKD control group.Causes,distributions of stages and complications of CKD in three groups were analyzed.Results The major cause of the elderly CKD was hypertension,different from that of younger CKD.The distribution of CKD stage in the elderly was mainly in the G3b stage,different from that in the younger.Anemia and mineral bone disease presented in earlier CKD stage in the aged CKD patients and the prevalence was higher than in the aged non-CKD group.The prevalence of hypertension had no statistical difference between the two CKD groups,but hypertension control rate was lower in aged CKD patients.Conclusions The clinical characteristics including causes and renal stage are different between the young and aged CKD patients.Complications such as anemia and mineral bone disease presents in earlier renal stage in aged CKD patients which means we should monitor and interfere earlier.
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<p><b>OBJECTIVE</b>The imbalance between extracellular matrix (ECM) synthesis and degradation induces the excessive ECM deposition and thus renal fibrosis. The decoction (A&A) which is a combination of two Chinese herbs, Astragalus membranaceus var. mongholicus and Angelica sinensis, has been shown to alleviate ECM production in animal models of chronic kidney diseases. In this paper, the effect of A&A on ECM degradation was investigated with interstitial fibrosis in rats.</p><p><b>METHOD</b>Male Wistar rats were randomly divided into sham, unilateral ureteral obstruction (UUO) and UAA (UUO plus A&A administration) groups. After administration of A&A (14 g x kg(-1) x d(-1)) by gavage for 3, 7 and 10 days, morphological changes were evaluated by HE, PAS and Sirius red staining technique. The expression of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), the activity of PAI-1 and t-PA were determined by ELISA. The activity of matrix metalloproteinases (MMP-9, MMP-2), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were evaluated by gelatin zymography or reverse gelatin zymography, respectively.</p><p><b>RESULT</b>Morphological analysis showed severe interstitial mononuclear cells infiltration, tubular atrophy, renal fibrosis and collagen expression in kidneys of UUO group, which was reduced by A&A administration (P < 0.05, UAA vs UUO group). Compared with the sham group, the expression of PAI-1 was significantly increased in UUO group by 63%, 91% and 112% at day 3, 7 and 10 respectively; and there were a remarkable decrease in UAA group by 44%, 43% and 52% at day 3, 7 and 10. The expression of active PAI-1 was strikingly increased in UUO group at day 3 [(30.5 +/- 23.8) ng x g(-1) vs. (0.0 +/- 0.0) ng x g(-1), P < 0.05)], day 7 [(36.5 +/- 11.2) ng x g(-1) vs. (0.0 +/- 0.0) ng x g(-1), P < 0.05)], and day 10 [(54.5 +/- 14.2) ng x g(-1) vs. (0.5 +/- 0.5) ng x g(-1), P < 0.05)]. The active PAI-1 was decreased in UAA group at day 7 [(14.9 +/- 0.5) ng x g(-1) vs. (36.5 +/- 11.2) ng x g(-1), P < 0.05] and day 10 [(15.4 +/- 4.8) ng x g(-1) vs. (54.5 +/- 14.2) ng x g(-1), P < 0.05]. The expression of t-PA was increased in UUO group only at day 3 [(58.1 +/- 16.5) microg x g(-1) vs. (30.1 +/- 17.3) microg x g(-1)], P < 0.05), meanwhile decreased in UAA group [(26.3 +/- 8.7) microg x g(-1) vs. (58.1 +/- 16.5) microg x g(-1), P < 0.05)]. But the expression of active t-PA was shown no significantly difference among the three groups. For MMP-2 and MMP-9 activity, they were significantly higher compared with the sham group in UUO group, but no significantly change after A&A treatment. The TIMP-1 activity was significantly increased in UUO group by 28% and 63% at day 7 and 10 respectively, significantly decreased in UAA group by 40% and 39% at the same time point.</p><p><b>CONCLUSION</b>The anti-fibrosis effects of A&A might be associated with modulating the imbalance of PAs/PAIs system as well as MMPs/TIMPs system, thereby alleviate ECM accumulation and interstitial fibrosis.</p>
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Animals , Humans , Male , Rats , Angelica sinensis , Chemistry , Astragalus Plant , Chemistry , Drugs, Chinese Herbal , Extracellular Matrix , Metabolism , Fibrosis , Kidney , Metabolism , Pathology , Kidney Diseases , Drug Therapy , Metabolism , Pathology , Matrix Metalloproteinase 1 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Plasminogen Activator Inhibitor 1 , Metabolism , Rats, Wistar , Tissue Plasminogen Activator , MetabolismABSTRACT
Objective To identify the risk factors for progression of advanced chronic kidney disease(CKD) patients who were cared by nephrologists in a specific CKD outpatient management clinic.Methods A prospective monocentric cohort study was performed.CKD patients of stage 3, 4 and 5 without renal replacement treatment were followed up regularly by nephrologists in this specific CKD management clinic.Patients with established atherosclerotic renal artery stenosis(ARAS) and chronic tubulointerstitial nephritis, and those who had not been followed-up for at least 12 months before Jun.30, 2010 were excluded.Clinical and laboratory data including blood pressure (BP), proteinuria, hemoglobulin (Hb), calcium phosphate product (Ca×P) and serum creatinine were consecutively collected.The treatment regimen was also recorded.Estimated glomerular filtration rate(eGFR) was calculated with the formula modified for Chinese to evaluate the change of renal function.The progression of kidney disease was defined as initiation of renal replacement therapy, the annual decrease of eGFR＞4 ml·min-1·(1.73 m2)-1, and/or death associated with renal disease.Results A total of 138 patients were enrolled in the final analysis with 84 patients of CKD stage 3, 36 of CKD stage 4 and 18 of CKD stage 5, respectively.At the time of enrollment, patients had an average age of (56.5:±:16.7) years old with an average eGFR of (32.3±13.4) ml·min-1·(1.73 m2)-1.During a mean follow-up interval of (27.1±12.1) months, the patients were well-controlled with an average blood pressure of (126.5±12.4)/(76.4±7.9) mm Hg in 50.7％(70/138), less than or equal to 130/80 mm Hg, an average Hb of(123.8±17.1) g/L in 73.9％(102/138), above or equal to 110 g/L and an average Ca×P of (45.2±7.7) mg2/dl2 in 89.1％(123/138), less than or equal to 55 mg2/dl2.Sixty-two patients (44.9％) had progression of kidney disease. On univariate analysis, factors predicting progression were low eGFR at referral, high systolic pressure, low Hb level, high Ca×P and proteinuria during follow-up, and renin-angiotensin system inhibitors treatment did not affect the progression.After the adjustment, multivariate analysis revealed proteinuria and low Hb level were independent factors for the progression of kidney disease.Conclusions The co-morbidities of advanced CKD patients can be managed efficiently in specific CKD outpatient management clinic.Control of proteinuria and correction of anemia may be beneficial to prevent the progression of advanced CKD.
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<p><b>OBJECTIVE</b>The decoction of Astragali Radix and Angelicae Sinensis Radix (A&A) has shown antifibrotic effects in rats with unilateral ureteral obstruction (UUO). The aim of this study was to track the effective parts of A&A for its renoprotective effects, according to the improvement of renal function and renal tubulointerstitial damage.</p><p><b>METHOD</b>A&A was sequentially extracted by using different solvents for three times and eleven different parts were gained. Wistar rats were randomly divided into Sham, UUO and the treatment groups with A&A or each part of A&A. After administration of A&A or its parts for 10 days, the levels of serum creatinin (Scr) and urea were measured. The morphological changes of kidneys were also semi-quantitatively analyzed by HE, Masson stained tissue sections, which including interstitial cell infiltration, tubular atrophy and interstitial fibrosis.</p><p><b>RESULT</b>The levels of Scr, urea were significantly increased, accompanied with severe renal damage in rats with UUO. As same as A&A, the part I in the first extraction and part IC in the second extraction were all shown to decrease the levels of Scr and urea and the index of renal interstitial damage. However, the following 4 parts extracted from IC in the third extraction were shown no effect on the above indexes.</p><p><b>CONCLUSION</b>The extract part I and part IC could be considered as the predominant parts of A&A for its renoprotective effects, due to their improvement of renal damage in interstitial nephropathy.</p>
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Animals , Humans , Male , Rats , Angelica sinensis , Chemistry , Astragalus Plant , Chemistry , Chronic Disease , Therapeutics , Disease Models, Animal , Drugs, Chinese Herbal , Kidney Diseases , Drug Therapy , Protective Agents , Random Allocation , Rats, WistarABSTRACT
Objective To investigate the influence of a combination of Chinese herbs,Astragalus membranaceus var.mongholicus and A ngelica sinensis (A&A)on the production and elimination of reactive oxygen species (ROS)and the underlying mechanism during the process of renal interstitial fibrosis in the obstructive kidneys of rats with unilateral ureteral obstruction(uuo).Method Male Wistar rats were randomly divided into control,sham,UUO and UAA (UUO+A&A)groups.The rats in UAA group were administered with A&A(14 g/kg)by oral gavage once daily:the ones in sham and UUO group were given with equal volumes of water.Three days after setting up models,pathological injury of renal tissue was evaluated.Level of total antioxidant capacity(T-AOC)and activity of CuZn superoxide dismutase(CuZn-SOD)in renal homogenates were measured bv spectrophotometry.Expression of NADPH oxidase subunits p47-phox,p22-phox and nintrotyrosine was analyzed by Western blot. Results Severe interstitial inflammatory cells infiltration, mild tubular atrophy and interstitial fibrosis were found in UUO group, which were alleviated by A&A administration. Compared to sham group, T-AOC of UUO group was not significantly changed, but the expression of the nitrotyrosine, NADPH oxidase subunits p47-phox and p22-phox was increased significantly (P<0.05). After A&A administration, T-AOC level was increased (2.5±1.1 vs 1.5±0.5, P<0.05) and the expression of nitrotyrosine was decreased (P< 0.05) in UAA group compared with UUO group. Additionally, the expression of p47-phox was reduced at day 3 (P<0.05), accompanied with a reduced expression of p22-phox (P< 0.05). CuZn-SOD activity was not significantly changed among the groups. Conclusion The inhibition of A&A in NADPH oxidase subunits p47-phox and p22-phox, which is responsible for reduction of oxidative stress, is associated with the alleviation of renal fibrosis in obstructive rat kidney.
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Objective:To explore whether Chinese herbs Astragalus and Angelica mixture(A&A) have renoprotective effects on chronic renal failure in rats.Methods:5/6 nephrectomized kidney in rats was used as chronic renal failure model.Rats were randomly divided into four groups which included sham,Model,A&A and enalapril(Ena) groups.The remnant kidney was harvested after 2,4,8,12 weeks,and levels of serum creatinine(scr),urea and urinary protein excretion were measured using routine biochemical methods.The pathological lesions were observed by light microscope.The expressions of fibronectin(FN) and collagen Ⅳ(Col-Ⅳ) in glomeruli and interstitium were detected by immnuohistochemistry.Results:5/6 nephrectomized rats were presented with the characteristics of increasing scr and urea,persistent proteinuria at the end of the 2nd,4th,8th,12th weeks,respectively.They had increasing size of glomeruli with progressive proliferation of mesangial cells and mesangial matrix followed by glomerulosclerosis and progressive elevated expressions of FN and Col-Ⅳ.Compared with Model group,the administration of A&A could decrease urinary protein excretion for 34%,44%,25%,45% at the end of the 2nd,4th,8th and 12th weeks,respectively(P
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Objective To investigate the therapeutic effects of Astragalus & Angelica (A&A) , the mixture of Chinese herbs, on different vasoconstrictors and vasodilators in the process of renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO). Methods Wistar rats were randomly divided into Sham,UUO and UAA (UUO+A&A) groups. After administration of A&A (14 g?kg-1?d-1) for 0, 3, 7 and 10 days, the levels of Ang-II , ET-1, nitric oxide(NO) and the activities of different NOS in renal homogenate were measured by RIA or enzyme method. The expression levels of eNOS, nNOS, iNOS were detected in the kidney by immunohistochemistry and semi-quantitively assessed by Western blot. Results After A&A administration, the levels of Ang- II and ET-1 were increased in UUO at all time points (P
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Aim The mixture of Chinese herbs,Astragalus & Angelica(A&A) has been found that has antifibrotic effect in rats.Methods To elucidate themechanisms underlying the renoprotective effects of A&A in the process of renal interstitial fibrosis,we investigated the pathology changes of kidneys in unilateral ureteral obstruction(UUO) rats.In the study,Wistar rats were randomly divided into CON,Sham,UUO and UUA(UUO+A&A) groups.After administration of A&A(12 g?kg?d~(-1)) for 0,3,7 and 10 d,renal damage including interstitial cell infiltration,tubular atrophy and interstitial fibrosis were quantified on HE and Masson stained tissue sections.The expression of ?-smooth muscle actin(?-SMA),transforming growth factor-?_1(TGF-?_1) and fibronectin(FN) was measured using computer image analysis of immunohistochemistry staining sections,ELISA and Western Blot.Results Renal damage and the expression of ?-SMA,TGF-?_1 and FN were all significantly exacerbated in UUO group compared with those of Sham group(P