RESUMO
Monoclonal gammopathy of renal significance (MGRS) is a pathological state which presents with a spectrum of renal lesions. MGRS is characterized by pathogenic monoclonal immunoglobulins or light chains produced by a premalignant plasma cell or B cell clone. In view of inadequate understanding in the past, the low detection rate of MGRS often results in poor outcomes and reduces quality of life of patients. Thus, MGRS stands for a group of clinical refractory renal diseases. To date, no standard treatment strategy for MGRS is available. Current consensus suggests a clone-directed approach that aims to eradicate the offending clone, but its long-term prognosis is not clear. In this article, we discuss the diagnostic methods, highlight treatment advances, and introduce integrated Chinese and Western medicine in the management of MGRS.
Assuntos
Nefropatias , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , China , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/terapia , Qualidade de VidaRESUMO
BACKGROUND: IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. METHODS/DESIGN: The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. DISCUSSION: The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Falência Renal Crônica/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/patologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/imunologia , Falência Renal Crônica/patologia , Falência Renal Crônica/terapia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Terapia de Substituição Renal/estatística & dados numéricos , Resultado do Tratamento , Adulto JovemRESUMO
To clarify the effects of cotton straw returning on the composition and contents of nu-trients in different particle sizes of aggregates, two treatments with or without cotton straw returning were tested in continuous three years. After three years straw treatments, we collected undisturbed soil within 0-5, 5-10, 10-20 and 20-30 cm soil layers, and to measure the composition, soil organic carbon, nitrogen, phosphorus and potassium contents in different particle sizes of aggregates classified using dry sieving. Returning cotton straw into the field significantly increased particle contents of 2-5 mm and >5 mm aggregates in 0-5 cm soil layer, while the content of <0.25 mm micro-aggregates was decreased. Cotton straw returning significantly improved soil organic carbon, nitrogen, and potassium contents by 19.2%, 14.2% and 17.3%, respectively, compared to no returning control. In 5-10 cm soil layer, cotton straw returning increased the contents of 2-5 mm and >5 mm aggregates, reduced the content of <0.25 mm micro-aggregate, but significantly increased contents of soil organic carbon, available nitrogen and potassium by 19.6%, 12.6% and 23.4%, compared to no straw returning control. In 10-20 cm soil layer, cotton straw returning significantly reduced the content of <0.25 mm micro-aggregates, and significantly enhanced soil organic carbon, nitrogen, and potassium contents by 8.4%, 10.9% and 11.5%, compared to the control. However, in 20-30 cm soil layer, cotton straw returning only increased soil available potassium content by 12.0%, while there were no significant changes in particle size, organic carbon, nitrogen and phosphorus contents. We concluded that cotton straw returning could significantly improve the structure of surface soil by increasing the number of macro-aggregates, contents of organic carbon, available nitrogen and potassium in aggregates, while decreasing micro-aggregate content. The enhancement of the contribution of macro-aggregates to soil fertility by returning cotton straw could improve soil physical structure, fertility and then increase cotton yield.
Assuntos
Gossypium , Solo/química , Agricultura , Carbono/análise , Nitrogênio/análise , Fósforo/análise , Potássio/análiseRESUMO
OBJECTIVE: To observe the effects of different doses of Wenxiao Decoction on the expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in experimental atherosclerotic rabbits and to explore the mechanism by which it alleviates atherosclerosis. METHODS: Sixty New Zealand rabbits were randomly divided into six groups: a blank group, a model group, a Simvastatin group, and high-, medium-, and low-dosage Wenxiao Decoction groups. Except for those in the blank group, all rabbits were fed with a high-cholesterol diet. Carotid atherosclerosis was established by balloon-induced carotid artery endothelium injury in conjunction with the high-cholesterol diet. After 8 weeks, all animals were euthanized to evaluate levels of IL-6 and ICAM-1 expressions (by enzyme linked immunosorbent assay) and of MCP-1 (by immunohistochemistry staining). RESULTS: The expressions of IL-6, ICAM-1, and MCP-1 were significantly increased in all groups except the blank group (P<0.05). However, the rabbits in the Wenxiao Decoction groups and the Simvastatin group showed significantly lower levels of IL-6, ICAM-1, and MCP-1 expression than those in the model group (P<0.05). The expressions of IL-6, ICAM-1, and MCP-1 in the highdosage Wenxiao Decoction group and the Simvastatin group were lower than those in the low-dosage Wenxiao Decoction group (P<0.05). The expression of MCP-1 in medium-dosage Wenxiao Decoction group was lower than that in the low-dosage group (P<0.05). CONCLUSIONS: High, medium, and low doses of Wenxiao Decoction can inhibit the expressions of IL-6, ICAM-1, and MCP-1, which may prevent and stabilize atherosclerotic plaques. There may be a direct relationship between dosage and therapeutic efficacy of Wenxiao Decoction.