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Objective: To investigate perspectives and changes in treatment selection by Chinese surgeons since introduction of the watch-and-wait approach after neoadjuvant therapy for rectal cancer. Methods: A cross-sectional survey was conducted using a questionnaire distributed through the "Wenjuanxing" online survey platform. The survey focused on the recognition and practices of Chinese surgeons regarding the strategy of watch-and-wait after neoadjuvant therapy for rectal cancer and was disseminated within the China Watch-and-Wait Database (CWWD) WeChat group. This group targets surgeons of deputy chief physician level and above in surgical, radiotherapy, or internal medicine departments of nationally accredited tumor-specialist or comprehensive hospitals (at provincial or municipal levels) who are involved in colorectal cancer diagnosis and treatment. From 13 to 16 December 2023, 321 questionnaires were sent with questionnaire links in the CWWD WeChat group. The questionnaires comprised 32 questions encompassing: (1) basic physician characteristics (including surgical volume); (2) assessment methods and criteria for clinical complete response (cCR); (3) patients eligible for watch-and-wait; (4) neoadjuvant therapies and other measures for achieving cCR; (5) willingness to implement watch-and-wait and factors influencing that willingness; (6) risks and monitoring of watch-and-wait; (7) subsequent treatment and follow-up post watch-and-wait; (8) suggestions for development of the CWWD. Descriptive statistics were employed for data analysis, with intergroup comparisons conducted using the χ2 or Fisher's exact probability tests. Results: The response rate was 31.5%, comprising 101 responses from the 321 individuals in the WeChat group. Respondents comprised 101 physicians from 70 centers across 23 provinces, municipalities, and autonomous regions nationwide, 85.1% (86/101) of whom represented provincial tertiary hospitals. Among the respondents, 87.1% (88/101) had implemented the watch-and-wait strategy. The approval rate (65.6%, 21/32) and proportion of patients often informed (68.8%, 22/32) were both significantly higher for doctors in oncology hospitals than for those in general hospitals (27.7%, 18/65; 32.4%, 22/68) (χ2=12.83, P<0.001; χ2=11.70, P=0.001, respectively). The most used methods for diagnosing cCR were digital rectal examination (90.1%, 91/101), colonoscopy (91.1%, 92/101), and rectal T2-weighted magnetic resonance imaging (86.1%, 87/101). Criteria used to identify cCR comprised absence of a palpable mass on digital rectal examination (87.1%, 88/101), flat white scars or new capillaries on colonoscopy (77.2%, 78/101), absence of evident tumor signals on rectal T2-weighted sequences or T2WI low signals or signals equivalent to the intestinal wall (83.2%, 84/101), and absence of tumor hyperintensity on diffusion-weighted imaging with no corresponding hypointensity on apparent diffusion coefficient maps (66.3%, 67/101). As for selection of neoadjuvant regimen and assessment of cCR, 57.4% (58/101) of physicians preferred a long course of radiotherapy with or without induction and/or consolidation capecitabine + oxaliplatin, whereas 25.7% (26/101) preferred immunotherapy in combination with chemotherapy and concurrent radiotherapy. Most (96.0%, 97/101) physicians believed that the primary lesion should be assessed ≤12 weeks after completion of radiotherapy. Patients were frequently informed about the possibility of achieving cCR after neoadjuvant therapy and the strategy of watch-and-wait by 43.6% (44/101) of the responding physicians and 38.6% (39/101) preferred watch-and-wait for patients who achieved cCR or near cCR after neoadjuvant therapy for rectal cancer. Capability for multiple follow-up evaluations (70.3%, 71/101) was a crucial factor influencing physicians' choice of watch-and-wait after cCR. The proportion who patients who did not achieve cCR and underwent surgical treatment was lower in provincial tertiary hospitals (74.2%, 23/31) than in provincial general hospitals (94.5%, 52/55) and municipal hospitals (12/15); these differences are statistically significant (χ2=7.43, P=0.020). The difference between local recurrence and local regrowth was understood by 88.1% (89/101) of respondents and 87.2% (88/101) agreed with monitoring every 3 months for 5 years. An increase in local excision or puncture rates to reduce organ resections in patients with pCR was proposed by 64.4% (65/101) of respondents. Conclusion: Compared with the results of a previous survey, Chinese surgeons' awareness of the watch-and-wait concept has improved significantly. Oncologists in oncology hospitals are more aware of the concept of watch-and-wait.
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Terapia Neoadyuvante , Neoplasias del Recto , Cirujanos , Humanos , Neoplasias del Recto/terapia , Encuestas y Cuestionarios , Estudios Transversales , China , Espera Vigilante , Femenino , Masculino , Pautas de la Práctica en Medicina , Pueblos del Este de AsiaRESUMEN
Objective: To investigate the perceptions, attitudes, and surgical strategies of Chinese surgeons, toward stoma management. Methods: We conducted a nationwide, cross-sectional, questionnaire-based survey among individuals working at relevant departments in any tier of hospitals, including general surgery, gastrointestinal surgery, surgical oncology, emergency, and others, that was involved in managing enterostomies. We required that participants be senior surgeons who had participated in performing enterostomy surgery. The questionnaire consisted of five dimensions: personnel qualification and training, attitude toward ostomy complications, preoperative siting, the process of acquiring ostomy-related surgical skills, and awareness and adoption of relevant techniques. Descriptive statistical analysis was performed. Results: From July 2021 to July 2022, we sent 488 questionnaires through a WeChat link or two-dimensional barcode. We received 467 (95.7%) responses from 196 hospitals in 26 provinces. Among the respondents, 426 (91.2%) were from tertiary hospitals, the departments of which comprised general surgery (130, 27.8%), gastrointestinal surgery (210, 45.0%), surgical oncology (116, 24.8%), and other departments (11, 2.4%). Senior surgeons accounted for 311(66.6%) of the participants. We found that: (1) mentorship by senior surgeons was the primary source of knowledge about ostomies (83.3%, 389/467), followed by mentorship by others and surgical atlases (44.8%, 209/467), and self-education (42.0%, 196/467). (2) Concerns about correlations between complications and surgical procedures that were believed to be "closely" or "probably" related to complications (79.0%, 369/467) were expressed by 99.4% (464/467) of the surgeons. Stenosis and intestinal obstruction requiring unplanned surgery were not uncommon (61.0%, 285/467). Of the listed complications, 46.7% (218/467) were believed to be related to surgical procedures and 79.0% (369/467) avoidable. Only 58.7% (274/467) of surgeons had participated in training and discussion of stoma complications whereas 99.1% (463/467) believed that joint training and discussions between surgeons and enterostomal therapists were necessary. (3) The main reasons for creation of stomas that were not consistent with prior siting included: stoma site marked preoperatively not a suitable trocar site (56.1%, 262/467), defunctioning stoma marking according to standards for permanent stomas (50.7%, 237/467), and inappropriate marking (43.3%, 202/467). (4) The rate of awareness of relevant procedures was generally high; however, it was less than 75% for stoma creation by circular stapler (64.1%, 257/401) and parastomal drainage (44.1%, 177/401). Eversion suture of mucosa and supporting rods were utilized in 65.6% (263/401) and 56.4% (226/401), respectively. Peritoneum (or posterior rectus abdominis sheath) (68.3%, 274/401), anterior rectus abdominis sheath (54.4%, 218/401), and skin (80.6%, 323/401) were the most commonly used tissues for fixation and suture layers of defunctioning and permanent stomas. However, closure of subcutaneous tissue was controversial, suturing being advocated by 26.7% (107/401) and 32.7% (131/401) of surgeons, respectively. Complications were considered to depend mainly on technical skills rather than the amount of suturing by 81.5% (327/401) of the participating surgeons. Conclusions: The complications of stoma surgery are related to the awareness and technical skills of surgeons, indicating there are insufficient training, education, management, and research. Standardization of enterostomy technical strategies and stoma management are therefore imperative.
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Procedimientos Quirúrgicos del Sistema Digestivo , Enterostomía , Estomas Quirúrgicos , Humanos , Estudios Transversales , Encuestas y CuestionariosRESUMEN
Objective: To estimate the prevalence of hyperkalemia and hypokalemia in patients with chronic kidney disease (CKD), analyze the influencing factors and explore the impact on disease prognosis. Methods: A total of 3 190 patients with CKD stage 1-4 from 39 tertiary clinical centers in China between November 2011 and December 2016 were recruited. The baseline characteristics of the patients were collected through face-to-face questionnaire investigation, physical examination and laboratory test. Meanwhile, the data of patient's end-stage renal disease, cardiovascular disease events and deaths were obtained up to December 2017 through active monitoring. The patients were categorized into three groups based on their baseline level of serum potassium (hypokalemia:<3.5 mmol/L, normal range: 3.5-<5.0 mmol/L, hyperkalemia: ≥5 mmol/L). Multi-nominal logistic regression was employed to evaluate the association between clinical characteristics and the presence of hyperkalemia or hypokalemia. The competing risk-based subdistribution Cox proportional hazards regression was used to assess the association between baseline level of serum potassium and various outcomes. Results: The mean age of the patients was (50±14) years, with a male rate of 57.6% (1 839/3 190) and a majority of glomerulonephritis (59.7%, 1 668/2 792). Patients with CKD stage 3-4 accounted for 70.8% (2 260/3 190), and the mean level of serum potassium was (4.4±0.7) mmol/L. The prevalence of hypokalemia and hyperkalemia was 3.7% (n=118) and 17.6% (n=561), respectively. In the multivariable adjusted analysis, presence of history of cardiovascular disease (OR=0.33, 95%CI: 0.13-0.83, P=0.019) and estimated glomerular filtration rate (OR=0.95, 95%CI: 0.91-0.98, P=0.001) were inversely associated with hypokalemia, while use of thiazide or loop diuretic (OR=2.06, 95%CI: 1.51-2.81, P<0.001) and estimated glomerular filtration rate (OR=1.13, 95%CI: 1.12-1.16, P<0.001) were positively associated with hyperkalemia. After adjusting for relevant cardiovascular and renal risk factors, the result only showed a significant association between hypokalemia and risk of all-cause mortality (HR=2.12, 95%CI: 1.06-4.24, P=0.034). Conclusions: Hypokalemia and hyperkalemia were not rare in patients with CKD in China, with the latter more prevalent. Hypokalemia was independently associated with the risk of death.
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Hiperpotasemia , Insuficiencia Renal Crónica , Adulto , Humanos , Hiperpotasemia/epidemiología , Masculino , Persona de Mediana Edad , Potasio , Prevalencia , Pronóstico , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Objective: To summarize the clinical characteristics of cardiomyopathy complicated with ventricular thrombosis. Methods: The clinical data of inpatients suffered from cardiomyopathy complicated with ventricular thrombosis in Fuwai Hospital between January 2015 and May 2019 were analyzed retrospectively. Results: A total of 125 cases were reviewed, and 24.8% were female. Dilated cardiomyopathy was the most common disease (62.4%), followed by arrhythmogenic right ventricular cardiomyopathy (ARVC) (13.6%) and hypertrophic cardiomyopathy (11.2%). There were 74.4% thrombosis in left ventricle, 12.8% in right ventricle and 12.8% in biventricle. The proportions of right ventricle thrombosis were higher in ARVC than in other cardiomyopathies (52.9% vs 6.5%, P<0.01). The majority suffered from cardiac function New York Heart Association (NYHA) Class â ¢ (45.6%) and class â £ (39.2%). The ratio of NYHA Class â £ was higher in female patients than in male ones (25.8% vs 10.6%, P<0.05). In lab detection, positive results of D-Dimer and N terminal-pro B type natriuretic peptide (NT-proBNP) accounted for 72.8% and 97.6%, respectively. There were 2.5% patients died in the hospital or discharged because of the worsening of illness, the chances were higher in female than male patients (9.7% vs 0, P<0.01). Among these patients, one succumbed to massive ischemic stroke caused by ventricular thrombus detachment under standard anticoagulation therapy. Conclusions: Dilated cardiomyopathy is the most common cardiomyopathy complicated with ventricular thrombosis. The most common location of thrombosis is left ventricle. Right ventricle thrombosis is more common in ARVC. The majority suffer from moderate or severe cardiac dysfunction. Higer proportion of female patients suffer from anemia, severe condition and poor prognosis.
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Displasia Ventricular Derecha Arritmogénica , Cardiomiopatías , Cardiomiopatía Dilatada , Trombosis , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Our study aims to evaluate the endothelial cell-podocyte crosstalk in proliferative lupus nephritis (LN). The semi-quantification scores of glomerular endothelial cell injury and the foot process width (FPW) were processed in 110 proliferative LN patients. Podocytes were stimulated with LN-derived IgG. Glomerular endothelial cells were treated with podocyte-conditioned medium (PCM), and then podocytes were incubated with endothelial cell-conditioned medium (ECM). The levels of vascular endothelial growth factor-A (VEGF-A) in PCM and endothelin-1 in ECM were analyzed, and the injury of podocyte and glomerular endothelial cells were further evaluated. The pathological score of glomerular endothelial cell injury was correlated with FPW in LN complicated with thrombotic microangiopathy. In vitro study showed the following: 1. Stimulation of podocytes by IgG from LN led to decline in the expression of nephrin with cytoskeleton rearrangement, and reduction of VEGF-A levels. 2. Exposure of glomerular endothelial cells to PCM incubated with LN-derived IgG (PCM-LN) induced more endothelin-1 secretion and disruption of intercellular tight junction. 3. Exposure of podocytes to ECM stimulated with PCM-LN could induce cytoskeleton redistribution with decrease of nephrin. In conclusion, the pathological glomerular endothelial cell lesions were associated with FPW and the VEGF-endothelin-1 system might play a critical role in the endothelial cell-podocyte crosstalk in LN.
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Células Endoteliales/metabolismo , Glomérulos Renales/metabolismo , Nefritis Lúpica/metabolismo , Nefritis Lúpica/patología , Podocitos/metabolismo , Receptor Cross-Talk/fisiología , Adulto , Biopsia , Estudios de Casos y Controles , Células Cultivadas , Células Endoteliales/patología , Endotelina-1/metabolismo , Femenino , Humanos , Inmunohistoquímica , Riñón/metabolismo , Riñón/patología , Glomérulos Renales/lesiones , Glomérulos Renales/patología , Nefritis Lúpica/sangre , Masculino , Podocitos/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters. METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available. Seven complement components (C1q, MBL, Bb, C4d, C3a, C5a, soluble C5b-9) were measured by enzyme-linked immunosorbent assay (Elisa), and any associations between their levels and clinicopathological parameters were then investigated. RESULTS: In DN patients, plasma levels of C1q, MBL, Bb, C4d, C3a, C5a and sC5b-9 were significantly higher than in diabetes patients without renal involvement, as were also urinary levels except for C1q, which showed no significant differences between the two groups. Also, urinary levels of C3a and C5a were significantly correlated with serum creatinine, urinary protein and estimated glomerular filtration rate, whereas urinary sC5b-9 was significantly correlated with the latter two (and not serum creatinine). In addition, urinary levels of MBL, Bb and C4d were significantly correlated with urinary protein, while C3a, C4d and Bb significantly correlated with the classification of glomerular lesions in DN. CONCLUSION: In DN patients, the complement system is activated and, of the three possible complement pathways, activation of the lectin and alternative pathways is associated with renal damage.
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Activación de Complemento/fisiología , Proteínas del Sistema Complemento/metabolismo , Nefropatías Diabéticas/inmunología , Riñón/inmunología , Adulto , Anciano , Creatinina/sangre , Nefropatías Diabéticas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
AIMS: As the potential role of the complement system in diabetic nephropathy (DN) is increasingly reported, this study aimed to investigate C1q and C3c deposition as seen on renal histopathology, as well as its association with clinical and pathological parameters, in DN patients. METHODS: Renal biopsy specimens from 161 DN patients were investigated using direct immunofluorescence, light, and electron microscopy. For direct immunofluorescence, staining for C1q and C3c on fresh-frozen renal tissue was performed immediately after biopsy. Complement deposition was defined as the presence of C1q or C3c of at least 1 + on a 0-4 + Scale. The association between complement deposition and clinicopathological data was also analyzed. RESULTS: On direct immunofluorescence microscopy, C1q and C3c were detected in specimens from 44/161 (27.3%) and 89/161 (55.3%) patients, respectively. Regarding clinical data, patients with C1q deposition had a significantly higher level of urinary protein (7.25 ± 4.20 g/24 h vs. 4.97 ± 3.76 g/24 h; P < 0.01) and significantly lower estimated glomerular filtration rate (eGFR; 34.16 ± 25.21 mL/min/1.73 m2 vs. 51.17 ± 31.56 mL/min/1.73 m2, respectively; P < 0.01), whereas patients with vs. without C3c deposition had a significantly lower eGFR (40.09 ± 27.97 mL/min/1.73 m2 vs. 54.48 ± 32.49 mL/min/1.73 m2, respectively; P < 0.01). On renal histopathology, patients with C1q deposition had significantly higher Scores for interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation and vascular lesions (P < 0.01, P < 0.05 and P < 0.05, respectively), whereas patients with C3c deposition had significantly higher IFTA Scores and proportions of global sclerosis (P < 0.01 and P < 0.01, respectively). CONCLUSION: Complement deposition of C1q and C3c on renal histopathology is associated with more severe kidney damage in patients with DN.
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Proteínas del Sistema Complemento/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Riñón/metabolismo , Riñón/patología , Adulto , Biopsia , Estudios de Casos y Controles , Nefropatías Diabéticas/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Masculino , Persona de Mediana EdadRESUMEN
Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed. Receiver operating characteristic curves were performed and the Cox regression model was applied to identify prognostic factors associated with renal outcomes. Results Active lupus nephritis patients exhibited elevated urinary levels of KIM-1, NGAL, and MCP-1 compared with lupus nephritis patients in remission ( P < 0.001) and normal controls ( P < 0.001). The urinary KIM-1 level was correlated with pathological tubular atrophy ( r = 0.208, P < 0.05) and increased significantly in the presence of interstitial inflammatory lesions ( P = 0.031). Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions than in those with only chronic lesions ( P = 0.015, P = 0.230, and P = 0.086, respectively). A combination of KIM-1, NGAL, and MCP-1 was a good indicator for diagnosing active tubulointerstitial lesions (area under the curve: 0.796). The combination of KIM-1 and NGAL was identified as an independent risk factor for renal outcomes (hazard ratio = 7.491, P < 0.05). Conclusion Urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis. The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes.
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Biomarcadores/orina , Túbulos Renales/patología , Nefritis Lúpica/orina , Adulto , Beijing , Estudios de Casos y Controles , Quimiocina CCL2/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A/análisis , Humanos , Lipocalina 2/orina , Nefritis Lúpica/patología , Masculino , Modelos de Riesgos Proporcionales , Curva ROC , Adulto JovenRESUMEN
OBJECTIVE: To explore the association between anemia and cardiovascular disease and all-cause mortality among diabetic patients, and whether the association is modified by the presence of chronic kidney disease (CKD). METHODS: Physical examination data of 8 563 patients with diabetes who met the inclusion and exclusion criteria between 2010 and 2011 were collected, based on the prospective cohort data of Kailuan study. The deadline of the follow-up was December 31, 2015, and the endpoints comprised all-cause mortality and cardiovascular disease. Survival analysis was performed by Kaplan-Meier method. Cox proportional hazards regression model was used to assess the association between anemia with or without CKD, and cardiovascular events and all-cause mortality after adjustment for confounding factors. RESULTS: The average age of the subjects was (57.3±10.3) years, of whom the patients with anemia accounted for 5.2%. The proportion of the patients with anemia combined with CKD was higher than that of the patients without anemia (27.2% vs. 20.8%, P=0.001). The median follow-up time was 4.9 years (interquartile range: 4.6-5.2 years). During the follow-up period, 559 patients died, and 434 patients had cardiovascular disease. Compared with the patients without anemia, the all-cause mortality rate of the patients with anemia was higher (3 220.3/100 000 person-years vs. 1 257.9/100 000 person-years, P<0.001). There was no statistically significant difference in the incidence of cardiovascular disease between the above two groups (999.8/100 000 person-years vs. 1 081.2/100 000 person-years, P>0.05). The mortality and incidence of cardiovascular disease among the patients with CKD were higher than those of the patients without CKD (2 558.3/100 000 person-years vs. 1 044.0/100 000 person-years, P<0.001; 1 605.9/100 000 person-years vs. 941.6/100 000 person-years, P<0.001). Results of Cox regression model showed that, after adjustment for confounding factors, the all-cause mortality risk increased by 95% in the diabetic patients with anemia (HR=1.95, 95% CI: 1.50-2.54). Anemia and CKD significantly increased the mortality risk among diabetic patients (HR=3.61, 95% CI: 2.48-5.26). The CKD patients without anemia had an increased risk of cardiovascular disease (HR=1.41, 95% CI: 1.13-1.74). CONCLUSION: Anemia is associated with an increased mortality risk in Chinese diabetic patients. Patients with CKD have an increased risk of cardiovascular disease and mortality. The all-cause mortality risk increases significantly in anemia patients with the presence of CKD, which indicates that we should focus on the prevention and treatment of diabetic patients with anemia and CKD.
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Anemia/epidemiología , Enfermedades Cardiovasculares/epidemiología , Insuficiencia Renal Crónica/epidemiología , Diabetes Mellitus Tipo 2 , Humanos , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Objectives The aim of this study was to investigate plasma ADAMTS-13 activity in patients with proliferative lupus nephritis and to evaluate the role of clinical, laboratory and pathological features, especially the vascular lesions in lupus nephritis. Methods Plasma samples from 163 class III and IV lupus nephritis patients confirmed by biopsy examinations and 98 normal controls were collected. ADAMTS-13 activity was evaluated by a residual collagen binding assay. IgG autoantibodies against ADAMTS-13 were detected by ELISA using recombinant ADAMTS-13 as a solid-phase ligand. Levels of vWF were measured by ELISA. Their associations with clinical, laboratory and pathological features were further assessed. Results Plasma ADAMTS-13 activity in lupus nephritis patients was significantly lower than that in normal controls (84 ± 21% vs. 90 ± 13%, p = 0.005). IgG ADAMTS-13 autoantibodies were detected in only three patients. The plasma level of vWF was significantly higher in the lupus nephritis group than in normal controls (1.00 ± 0.79 vs. 0.70 ± 0.30, p = 0.025). Plasma ADAMTS-13 activity was negatively correlated with the level of serum creatinine and proteinuria ( r = -0.354, p < 0.001; r = -0.200, p = 0.011, respectively). Patients with a higher level of ADAMTS-13 activity had significantly higher levels of factor H (401.51 ± 183.01 µg/ml vs. 239.02 ± 155.45 µg/ml, p = 0.005). Plasma ADAMTS-13 activity was negatively associated with total pathological AI scores ( r = -0.326, p < 0.001), endocapillary hypercellularity ( r = -0.419, p < 0.001), cellular crescents ( r = -0.274, p < 0.001), subendothelial hyaline deposits ( r = -0.266, p = 0.001), interstitial inflammatory cell infiltration ( r = -0.304, P < 0.001), tubular atrophy ( r = -0.199, p = 0.011), acute glomerular vascular lesions ( r = -0.344, p < 0.001) and acute renal vascular lesions ( r = -0.338, p < 0.001). No association was found between level of vWF and plasma ADAMTS-13 activity ( r = 0.033, p = 0.671). Low level of ADAMTS-13 activity was a risk factor for renal outcomes ( p = 0.039, HR = 0.047, 95% CI: 0.120-1.005). Conclusions Decreased ADAMTS-13 activity was found in patients with proliferative lupus nephritis, and plasma ADAMTS-13 activity was closely associated with renal injury indices, especially pathological vascular scores. The role of ADAMTS-13 in the disease remains to be further investigated.
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Proteína ADAMTS13/sangre , Autoanticuerpos/sangre , Riñón/patología , Nefritis Lúpica/sangre , Nefritis Lúpica/patología , Adolescente , Adulto , Anciano , China , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Nefritis Lúpica/complicaciones , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Microangiopatías Trombóticas/epidemiología , Adulto Joven , Factor de von Willebrand/metabolismoRESUMEN
Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort. A total of 102 lupus nephritis patients were enrolled from another four centers as the validation cohort. The status of TBM deposits was retrospectively assessed using electron microscopy, and the associations of the deposits with clinical data, pathological characteristics and renal outcomes were further analyzed. The percentage of positive TBM deposits was nearly 30% in the lupus nephritis patients. Using immuno-gold labeling, we found that 10/10 patients were positive for IgG, 7/10 were C3d positive, 6/10 were C1q positive, and 1/10 were C4d positive. Patients with TBM deposits presented with more active features, including a higher SLEDAI score (SLE Disease Activity Index) ( p < 0.001), higher serum creatinine level ( p = 0.001) and lower serum C3 level ( p < 0.001). These patients also presented with higher scores for most renal pathological indices, including the total activity indices score ( p < 0.001) and total chronicity indices score ( p = 0.001). TBM deposits affected renal outcomes in the univariate Cox hazards regression analysis (HR = 4.2, 95% CI = 1.3-14.3, p = 0.02). In conclusion, TBM deposits were common in lupus nephritis patients and correlated closely with the clinical disease activity and renal outcome.
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Complejo Antígeno-Anticuerpo/inmunología , Membrana Basal Glomerular/inmunología , Túbulos Renales/inmunología , Nefritis Lúpica/inmunología , Adulto , Complejo Antígeno-Anticuerpo/ultraestructura , Biopsia , Distribución de Chi-Cuadrado , China , Complemento C1q/análisis , Complemento C3d/análisis , Complemento C4b/análisis , Femenino , Membrana Basal Glomerular/efectos de los fármacos , Membrana Basal Glomerular/ultraestructura , Humanos , Inmunoglobulina G/análisis , Inmunosupresores/uso terapéutico , Estimación de Kaplan-Meier , Túbulos Renales/efectos de los fármacos , Túbulos Renales/ultraestructura , Nefritis Lúpica/tratamiento farmacológico , Nefritis Lúpica/patología , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Análisis Multivariante , Fragmentos de Péptidos/análisis , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Objective Genetic variants in FH (complement factor H) were reported to associate with susceptibility to systemic lupus erythematosus (SLE). This study proposed that the genetic defects of FH in the susceptibility and in the development of lupus nephritis might be different. Methods This study enrolled 334 lupus nephritis patients, 269 SLE patients without clinical renal involvement and 350 controls. Two-step genotyping was performed. First, all the exons of the FH gene were fully sequenced in 100 lupus nephritis patients and 100 healthy controls. Second, genotyping of three common variants reported to be functional, rs1061170, rs800292 and rs6677604, was conducted in all the recruited individuals. Further, analysis of their associations with SLE/lupus nephritis susceptibility and the clinico-pathological parameters in the lupus nephritis group was performed. Results No significant differences were observed in allele and genotype frequencies of the three single nucleotide polymorphisms between lupus patients and controls. There was a significantly higher ratio of CC/CT genotypes of rs1061170 in lupus nephritis patients with class III than in the other two classes (class III vs. class IV vs. class V: 21.0% vs. 9.7% vs. 9.4%; P = .044). The rs6677604-GG genotype was observed to be associated with the absence of anti-ds DNA antibody ( P = .021), and the rs800292-TT genotype was associated with a higher level of circulating C3 ( P = 0.20) in lupus nephritis. Conclusion In an independent cohort, this is the first genetic association analysis focusing on FH genetic variants in Chinese lupus nephritis patients. It was found that the variants in the FH gene might affect the histopathologic subtypes and some clinical features of the disease.