Expert Consensus on Clinical Diseases Responding Specifically to Traditional Chinese Medicine：Membranous Nephropathy / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） is a great treasure house， exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years， and has become the first cause of primary glomerular diseases. However， its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy， but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine （CACM） invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy， which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine， this paper also detailed TCM cognition， syndrome differentiation， and therapeutic schemes of membranous nephropathy， aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

Objective@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*Data sources@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*Study selection@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*Results@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*Conclusions@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Cryoglobulinemic vasculitis and glomerulonephritis: concerns in clinical practice / 中华医学杂志(英文版)

OBJECTIVE@#Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice.@*DATA SOURCES@#All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019.@*STUDY SELECTION@#This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia.@*RESULTS@#Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances.@*CONCLUSIONS@#Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.

Establishment of a new rat model of chronic cyclosporine A nephrotoxicity / 中国医学科学院学报

<p><b>OBJECTIVE</b>To establish a new rat model of chronic cyclosporine A nephrotoxicity and explore its features.</p><p><b>METHODS</b>Totally 24 male SD rats were equally randomized divided into 3 groups: sham-adrenalectomized (sham-ADX) group, ADX group and ADX plus cyclosporine A (CsA) group. Rats in ADX and CsA group first underwent adrenalectomy, followed by the administration of placebo or dexamethasone, respectively. Rats in sham-ADX group received sham adrenalectomy and distilled water as control. Six weeks later, all rats were sacrificed and the following indicators were evaluated: urine protein excretion, creatinine clearance, aldosterone level in serum and urine, aldosterone level and its synthase CYP11B2 gene expression in kidney, serum natrium and potassium, urine natrium and potassium excretion, and tubulointerstitial fibrosis by masson trichrome stain.</p><p><b>RESULTS</b>In ADX and CsA group, serum and urine aldosterone were undetectable on the second post-operative day, with other observations including natriuresis, hyponatremia, decreased urine potassium excretion, and hyperpotassemia, suggesting that adrenals were removed intact and the adrenalectomy was successful. Rats in CsA group showed increased urine protein, decreased creatinine clearance and tubulointerstitial fibrosis, suggesting that a model of chronic CsA nephrotoxicity was successfully established. At the endpoint, serum potassium, serum aldosterone, urine potassium and urine aldosterone excretion partially retrieved. Natrium in serum and urine was not significant different between ADX group/CsA group and sham-ADX group. Local renal aldosterone and its gene expression were remarkably upregulated.</p><p><b>CONCLUSIONS</b>We successfully established a new rat model of chronic CsA nephrotoxicity by adrenalectomy without low sodium diet. After adrenalectomy, local renal aldosterone in kidney may compensate for circulatory aldosterone deficit to maintain electrolyte balance.</p>

Effects of Hirsutella sinensis on TGF-beta1 and Snail expressions and transdifferentiation of tubular epithelial-myofibroblast in renal tissue of rats with chronic aristolochic acid nephropathy / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the antagonizing effect of Hirsutella sinensis (HS) on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) and its possible pathogenic mechanism in rats with chronic aristolochic acid nephropathy (CAAN).</p><p><b>METHODS</b>Eighteen male Sprague-Dawley rats were equally divided into 3 groups, the model (M) group, the intervention (I) group and the control (C) group. The 24 h urinary protein (UP) in rats was measured before intervention and at the end of the 1st, 4th, 8th, and 12th week, and creatinine clearance rate (CCr) was measured before intervention and at the end of the 12th week respectively. All rats were sacrificed at the end of the 12th week, their kidney was taken for examining the degree of fibrosis in renal interstitial with Masson's stain and determining mRNA and protein expressions of transforming growth factor-beta1 (TGF-beta1), Snail, alpha-smooth muscle actin (alpha-SMA) and cytokeratin in renal tissue by Real-time RT-PCR and immunohistochemistry staining, respectively.</p><p><b>RESULTS</b>Compared with the C group, CCr was significantly lower, while 24 h UP was higher; the relative area of interstitial fibrosis was significantly larger in the M group; besides, the mRNA and protein expressions of TGF-beta1, Snail and alpha-SMA were significantly up-regulated (P < 0.01 or P < 0.05), and those of cytokeratin were significantly down-regulated (P < 0.01) in renal tissue of the M group. While in the I group, all the above-mentioned abnormalities were restored to some extent (P < 0.05) and showed significant difference (all P < 0.05) as compared with those in the M group.</p><p><b>CONCLUSION</b>HS can downregulate TGF-beta1 and Snail expressions in renal tissue, antagonize TEMT and renal interstitial fibrosis, and improve renal function in CAAN rats.</p>

Organic anion transporter system mediates the transport of aristolochic acid in tubular epithelial cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate whether aristolochic acid can be transported into human kidney proximal tubular cell (HKC) and its potential mechanism.</p><p><b>METHODS</b>Intracellular aristolochic acid was measured by liquid chromatography-tandem mass spectrometry. The release of lactate dehydrogenase (LDH) induced by aristolochic acid in the presence of organic anion transporter inhibitor (probenecid) or organic cation transporter inhibitor (tetraethylammonium) was evaluated. The effects of probenecid on aristolochic acid induced connective tissue growth factor (CTGF) mRNA and protein expression were also examined by real time polymerase chain reaction and Western blot, respectively.</p><p><b>RESULTS</b>Aristolochic acid was detected in the suspension of the denatured HKC after incubation with aristolochic acid sodium salt. The release of LDH from HKC, which was induced by 60 mg/L aristolochic acid sodium salt, was significantly inhibited by 1 mmol/L probenecid (P < 0.01), but not by 1 mmol/L tetraethylammonium. The increased CTGF mRNA and protein expression in HKC stimulated by 40 mg/L aristolochic acid sodium salt was significantly down-regulated by 1 mmol/L probenecid (P < 0.05), with an inhibition rate of 16% and 21%, respectively.</p><p><b>CONCLUSION</b>Aristolochic acid can be transported into HKC by organic anion transport system, and then exerts its biological effects.</p>