IgA nephropathy to proliferative glomerulonephritis with monoclonal IgAκ deposits: a pattern switch.

We report the case of a 31-year-old male who presented with repeated episodes of nephritic-nephrotic syndrome in concomitance with infection. IgA was diagnosed and was initially responsive to treatment with immunosuppressors but further disease flare did not respond to treatment. Based on three consecutive renal biopsies over 8 years, a pattern switch from endocapillary proliferative IgA nephropathy to membranous proliferative glomerulonephritis with monoclonal IgAκ deposits was observed. Bortezomib-dexamethasone combination therapy finally led to a favorable renal response. This case provides new insights into the pathophysiological mechanisms of proliferative glomerulonephritis with monoclonal immunoglobin deposits (PGNMID), highlighting the importance of repeat renal biopsies and routine evaluation of monoclonal immunoglobin deposits in proliferative glomerulonephritis with refractory nephrotic syndrome.

IgA Nephropathy: Current Understanding and Perspectives on Pathogenesis and Targeted Treatment.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with varied clinical and histopathological features between individuals, particularly across races. As an autoimmune disease, IgAN arises from consequences of increased circulating levels of galactose-deficient IgA1 and mesangial deposition of IgA-containing immune complexes, which are recognized as key events in the widely accepted "multi-hit" pathogenesis of IgAN. The emerging evidence further provides insights into the role of genes, environment, mucosal immunity and complement system. These developments are paralleled by the increasing availability of diagnostic tools, potential biomarkers and therapeutic agents. In this review, we summarize current evidence and outline novel findings in the prognosis, clinical trials and translational research from the updated perspectives of IgAN pathogenesis.

Deep Learning Based Tongue Prickles Detection in Traditional Chinese Medicine.

Tongue diagnosis is a convenient and noninvasive clinical practice of traditional Chinese medicine (TCM), having existed for thousands of years. Prickle, as an essential indicator in TCM, appears as a large number of red thorns protruding from the tongue. The term "prickly tongue" has been used to describe the flow of qi and blood in TCM and assess the conditions of disease as well as the health status of subhealthy people. Different location and density of prickles indicate different symptoms. As proved by modern medical research, the prickles originate in the fungiform papillae, which are enlarged and protrude to form spikes like awn. Prickle recognition, however, is subjective, burdensome, and susceptible to external factors. To solve this issue, an end-to-end prickle detection workflow based on deep learning is proposed. First, raw tongue images are fed into the Swin Transformer to remove interference information. Then, segmented tongues are partitioned into four areas: root, center, tip, and margin. We manually labeled the prickles on 224 tongue images with the assistance of an OpenCV spot detector. After training on the labeled dataset, the super-resolutionfaster-RCNN extracts advanced tongue features and predicts the bounding box of each single prickle. We show the synergy of deep learning and TCM by achieving a 92.42% recall, which is 2.52% higher than the previous work. This work provides a quantitative perspective for symptoms and disease diagnosis according to tongue characteristics. Furthermore, it is convenient to transfer this portable model to detect petechiae or tooth-marks on tongue images.

Anti-glomerular basement membrane disease with IgA nephropathy: A case report.

BACKGROUND: Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disease manifesting as acute progressive nephritis syndrome with or without varying degrees of pulmonary hemorrhage. Anti-GBM disease coexisting with Immunoglobulin A (IgA) nephropathy is rarer and has different clinical manifestations and prognoses than simple anti-GBM disease. We describe a case of coexistence of these two diseases. CASE SUMMARY: A 49-year-old man with hematuria and proteinuria accompanied by a slight elevation of serum creatinine was admitted to our hospital. The pathological results of renal biopsy and the elevated serum anti-GBM antibody titer supported a diagnosis of anti-GBM disease combined with IgA nephropathy. After treatment with corticosteroids and cyclophosphamide, the patient's serum creatinine was relatively stable, and the hematuria and proteinuria moderately improved in the subsequent six months. CONCLUSION: Anti-GBM disease coexisting with IgA nephropathy is rare. The clinical manifestations and prognosis are better than those of simple anti-GBM disease. In this case, the patient's condition was improved and his renal function remained relatively stable with corticosteroid and cyclophosphamide treatment. New detection methods to identify whether the crescents in this case were derived from anti-GBM disease or IgA nephropathy are worthy of further exploration.

A Survey Study on Soy Food Consumption in Patients with Chronic Kidney Diseases.

Chronic kidney disease (CKD) is one of the major and exacerbating global health burdens, which is characterized by no curative treatments and high morbidity and mortality. Since malnutrition has become an important factor determining the final clinical outcomes of CKD, soy products, high-quality plant-based sources of proteins and other nutrients, are recommended by many physicians for CKD patients. However, it has been reported that adherence to this dietary advice among those patients is low. In order to dissect the potential reasons behind this phenomenon and to subsequently develop target intervention to improve the current situation, we designed and conducted a self-administered questionnaire survey in 3 medical centers in China. Total 570 patients responded to our survey and data analysis reveals that 85.6% of the respondents were aware of the necessaries of high-quality protein diets for CKD patients, but only 41.9% of patients knew that soy foods provide high-quality proteins needed. In contrast, up to 90.4% of patients were affected by the notion that patients with CKD should avoid soy products. Besides, comparing with other groups, higher percentage of patients undergoing peritoneal dialysis recognized soy products as foods with high-quality proteins, however, as many as 68.8% of them did not consume any soy foods due to the concerns of adverse effects on the progress of CKD. Our data suggest that a significant portion of patients with CKD do not consume soy foods, which could be mainly resulted from their misconception towards soy products delivered by medical workers or social media. Evidence-based updated education of patients and medical workers on soy foods would be a necessary strategy for improving nutrition status of CKD patients and their clinical outcomes.

Monoclonal Gammopathy of Renal Significance (MGRS): Prospects for Treatment in Integrated Chinese and Western Medicine.

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.

Chrysophanol Inhibits the Progression of Diabetic Nephropathy via Inactivation of TGF-ß Pathway.

BACKGROUND: Diabetic nephropathy (DN) is a common form of diabetic complication which threatens the health of patients with diabetes. It has been reported that chrysophanol (CHR) can alleviate the progression of diabetes; however, the role of CHR in DN remains unclear. METHODS: To mimic DN in vitro, human podocytes (AB8/13 cells) were treated with high glucose (HG). Meanwhile, Western blot was performed to detect protein expressions. CCK-8 assay was used to test cell viability and cell proliferation was detected by Ki-67 staining. In addition, flow cytometry was performed to investigate cell apoptosis and cycle and cell migration was tested by transwell assay. Moreover, in vivo model of DN was established to detect the effect of CHR on DN in vivo. RESULTS: HG-induced AB8/13 cell growth inhibition was significantly rescued by CHR. In addition, HG notably promoted the migration of AB8/13 cells, while this phenomenon was obviously reversed by CHR. Moreover, CHR inhibited the progression of DN via inactivation of TGF-ß/EMT axis. Furthermore, CHR alleviated the symptom of DN in vivo. CONCLUSION: CHR significantly alleviated the progression of DN via inactivation of TGF-ß/EMT signaling in vitro and in vivo. Our findings were helpful to uncover the mechanism by which CHR regulates DN, as well as inspire the development of novel therapy against DN.

New Goals and Strategies of Chinese Medicine in Prevention and Treatment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is a clinical syndrome with a series of clinical manifestations and metabolic disorders caused by many diseases, which are characterized by progressive deterioration or irreversible damage of renal structures and functions. With the progress of epidemiological research, CKD has brought about huge economic and psychological burdens. There is a considerable risk of cardiovascular events or death than progression to end-stage renal disease for patients. Particular attentions should be paid to the new goals of reducing cardiovascular events and all-cause mortality. It is important to analyze the etiology and pathogenesis according to patients' ages, regions, primary disease as well as different stages of disease, and choose the appropriate therapeutic strategies accordingly. In clinical practice, due to the uncertainty of therapeutic effects of modern medicine based on the risk factors, it is necessary to use Chinese medicine (CM) to delay the disease progression and reduce comorbidities. Turbid toxin and blood stasis are two critical pathological factors worthy of concerns in the theory of CM. In addition, appropriate use of CM may help improve the quality of life of patients with CKD.

Understanding and Therapeutic Strategies of Chinese Medicine on Gut-Derived Uremic Toxins in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins (UTs). Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modern medicine. There is a certain relevance between toxins and "turbid toxin" in the theory of Chinese medicine (CM). CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.

Beneficial effects of Fu-Zheng-Qu-Zhuo oral liquid combined with standard integrated therapy in patients with chronic kidney disease (stage 3-4): A randomized placebo-controlled clinical trial.

BACKGROUND: The high worldwide prevalence of chronic kidney disease (CKD) is a critical health problem and the development of more effective therapies is urgently needed. We conducted a randomized, double-blinded, placebo-controlled clinical trial from October 2010 to December 2012 to assess whether Fu-Zheng-Qu-Zhuo oral liquid (FZQZ) has a beneficial effect in preventing CKD progression when added to standard integrated therapies. METHODS: Patients with CKD stage 3 to 4 from 3 hospitals in Beijing, China were enrolled. Patients were randomly assigned to the FZQZ or placebo groups and were treated with standard integrated therapy plus FZQZ or placebo (20 mL each time, 3 times/d) for 12 months. Patients received post-trial follow-up until October 2014. The primary outcome was the estimated glomerular filtration rate (eGFR)-Slope (mL/min per 1.73 m2 per month) during the in-trial time, which was calculated by the eGFR regression curve estimated from each serum creatinine measurement during the in-trial period. Secondary outcomes were changes in 24-h urine protein excretion (24-h UP) and albumin and hemoglobin levels from baseline during the in-trial period. Time to composite endpoint events (initiation of long-term dialysis, doubling of serum creatinine, or CKD-related death during the in-trial and post-trial phases) was assessed as a secondary outcome. RESULTS: A total of 68 patients (43 in the FZQZ group and 25 in the placebo group) completed the in-trial and post-trial phases, with an average follow-up time of 31.6 ±â€Š9.6months. The FZQZ group had amean eGFR-Slope of 0.25 ±â€Š1.44 as compared with -0.72 ±â€Š1.46 (mL/min per 1.73m2 per month) in the placebo group during the in-trial period (P = .003). The FZQZ group showed decreased 24-h UP, with a change from baseline of -0.08 (interquartile range [IQR], -0.33 to 0.01) versus 0.01 (IQR, -0.19 to 0.33) g/24h in the placebo group (P = .049). Decreased risk of composite endpoint events was observed only in the post-trial phase (hazard ratio = 0.42, 95% confidence interval: 0.16-1.11, P = .038). No significant differences in albumin and hemoglobin level changes were observed. CONCLUSION: Adding FZQZ oral liquid to standard integrated therapies may aid in attenuating CKD progression.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

OBJECTIVE: To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). METHODS: A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. RESULTS: After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). CONCLUSION: HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

[Therapeutic effect of Astragalus and Angelica mixture on the renal function and TCM syndrome factors in treating stage 3 and 4 chronic kidney disease patients].

OBJECTIVE: To compare the therapeutic effect of Astragalus and Angelica Mixture (AAM) on treating CKD patients according to different CKD primary diseases, staging and TCM syndromes. METHODS: A multicentre, open-label, and self control clinical design was used, and thirty-two patients in line with inclusive criteria were recruited. Based on maintaining their previous basic CKD treatment, patients additionally took AAM (Astragalus and Angelica each 30 g), once a day, three months consisted of one therapeutic course. Serum creatinine (SCr), estimated glomerular filtration rate (eG- FR), 24 h urinary total protein (UTP), plasma albumin (ALB), hemoglobin (Hb), and changes of TCM syndrome factor integrals were compared before treatment, at the end of month 1, 2, and 3. The differences in the aforesaid indices were compared between CKD patients with different CKD primary diseases (chronic glomerulonephritis, chronic renal tubulointerstitial disease, hypertensive renal damage), different CKD stages (CKD 3 and CKD 4), and patients of qi-blood deficiency syndrome (QBDS) and non-QBDS. RESULTS: AAM could improve 78.12% (25/32) patients' renal function. Compared with before treatment, SCr decreased (12.08% +/- 10.11%), eGFR increased (21.14% +/- 18.55%), and ALB increased (2.76% +/- 1.97%) at the end of 3-month treatment (all P < 0.05). As for TCM syndrome factor integrals, compared with before treatment, the integrals for qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome decreased, while the integrals for dampness heat syndrome and turbid-toxin syndrome increased (all P < 0.05). There was no obvious difference in all indices except the integral for hypertensive renal damage patients of yin deficiency syndrome (P > 0.05). The SCr decreasing percent was 19.82% +/- 8.30% for patients of non-QBDS and 5.24% +/- 10.75% for patients of QBDS. The latter was higher with statistical difference (P < 0.05). As for TCM syndrome factor integrals, the integral differences of qi deficiency and blood deficiency were obviously higher in patients of QBDS, when compared with patients of non-QBDS (P < 0.05). CONCLUSION: AAM could improve the renal function of CKD patients, elevate their ALB levels, and ameliorate associated qi deficiency syndrome, blood deficiency syndrome, and yin deficiency syndrome, especially for CKD patients of QBDS.

[Understanding of diabetic kidney disease and reflecting of the current clinical research situation of Chinese medicine].

Along with the development of clinical and pathological studies, and the wide spreading of the concepts or ideas of chronic kidney disease (CKD) and diabetic kidney disease (DKD), the clinical research of DKD has entered a new stage, which has brought new requirements for Chinese medicine treatment of DKD. It is necessary to carry out good design, have reasonable inclusion and exclusion criteria, select appropriate biomarkers capable of reflecting the pathophysiology of DKD, choose convincible hard endpoints capable of reflecting the prognosis of DKD, and conduct observations of enough long therapeutic course. This is the main trend of conducting clinical trials of DKD and scientifically assessing the efficacy of Chinese medicine treatment of DKD.

Effects of Huanshuai Recipe Oral Liquid on restructuring glomerular microvasculature and expression of vascular endothelial growth factor in subtotal nephrectomized rats.

OBJECTIVES: To explore the effects and significance of Huanshuai Recipe Oral Liquid (, HSR), a formula with supplementing qi, nourishing blood and activating blood on restructuring glomerular microvasculature and expression of vascular endothelial growth factor (VEGF) in subtotal nephrectomized (SNX) rats. METHODS: A total of 76 male Wistar rats were randomly divided into four groups: 16 in the sham-operated group and fed with tap water 10 mL/kg per day; 20 in the model group were operated with 5/6 SNX and fed with tap water 10 mL/ kg per day; 20 SNX rats in the HSR group were treated with HSR 10 mL/kg per day; 20 SNX rats in the losartan group were treated with losartan 40 mg/kg per day. Serum creatinine (SCr) and urinary protein excretion (Upro) were examined at the 2nd, 4th, 8th, and 12th weeks of the treatment, and the remnant kidneys were harvested. Changes in histological microstructure were evaluated using light microscopy, and the expression of VEGF was detected by using ELISA. RESULTS: Upro, microvasculature injury and glomerulosclerosis were found to be alleviated in HSR and Losartan groups, respectively. The change of VEGF expression showed positive correlation with glomerular capillary area and peritubular capillary number (r=0.448, r=0.422, P<0.01), but negative correlation with that of SCr and Upro (r=-0.592, r=-0.481, P<0.01). CONCLUSIONS: HSR could regulate the VEGF expression, reduce the loss of microvasculature, which demonstrated similar renal protective effects to losartan in SNX rats. Examination of Chinese herbal medicine influence on VEGF signaling and restructuring renal microvasculature may elucidate the molecular mechanism of renal protection to a certain degree.

Study on the relationship between blood stasis syndrome and clinical pathology in 227 patients with primary glomerular disease.

OBJECTIVE: To investigate the relationship between the severity of Chinese medicine (CM) blood stasis syndrome (BSS) with clinical features and renal lesion indexes of the primary glomerular disease. METHODS: An epidemiological survey was conducted to collect the data of 227 patients diagnosed as chronic primary glomerular diseases, and their severity of BSS were scored three days before renal biopsies were performed. The following clinical indexes were analyzed: age, course of glomerular diseases, 24-h urine protein ration (Upro), hypertension and blood pressure (BP) progress, serum creatinine levels (Scr), estimation of glomerular filtration rate based on the predigesting equation of MDRD (eGFR), blood urea nitrogen (BUN), uric acid (UA), triglyceride (TG), cholesterol (CHO), haematoglobin (HGB), albumin (ALB), and the correlation among renal pathological types, pathology lesion indexes, and BSS scores. RESULTS: (1) Among the 227 patients, 207 (91.19%) were diagnosed as BSS, in which 95 cases were considered as moderate and the rest 112 cases as severe. (2) There was a negative correlation between age, gender, grades of the hypertension, and the BSS score. Multiple stepwise regression analysis showed that Upro, CHO, TG, and eGFR were positively related to the BSS score (P<0.05). (3) The BSS score has a positive correlation with indexes of chronic renal pathology, especially the tubular atrophy and interstitial fibrosis. The severity of proliferation and glomerular sclerosis was accompanied with higher BSS scores with a significant difference (P<0.05). CONCLUSIONS: BSS is one of the most common CM syndromes among patients with the primary glomerular diseases; the BSS score has a positive correlation with Upro, CHO, TG, eGFR, as well as the index of chronic renal pathology. Based on these observations, the BSS may be used as an indicator of the development of renal diseases. Being positively diagnosed as BSS could indicate the beginning of the chronic phase of the primary glomerular diseases.

[Surrogate end points for clinical trials on chronic kidney disease and research of Chinese medicine].

Chronic kidney disease is a kind of disease with the condition always worsening over time passing through a sequence of stages, and the evaluation on its clinical treatment is mainly by observing the speed of renal function deteriorating and the time of terminal renal failure occurrence. In order to conduct the trial go on wheels, the authors proposed that the "surrogate end points (SEP)" should be introduced. It is the biologic mark for substitute the clinical terminal point (event), formed depending upon the scientific evidences of epidemiology, pathophysiology, drug-therapy and other scientific evidence, which could be used for predicting the efficacy or damage of a certain measure, present or absent. This article aimed to explain the definition of SEP and to discuss the usable SEP for clinical trial on chronic kidney disease, such as proteinuria, declination of glomerular filtration rate and its slope coefficient as well as the time of terminal occurrence. Moreover, through analyzing the existent problems in clinical researches concerning TCM treatment of chronic kidney disease, the authors suggested that some improvements, chiefly the utilization of SEP for efficacy evaluation, are necessary in the clinical observation methodologies for chronic kidney disease.

[Correlation analysis on blood stasis syndrome, clinical features and renal pathology in 174 patients with primary glomerular diseases].

OBJECTIVE: To investigate the relationship between degree of TCM blood-stasis syndrome (BSS) with clinic features and renal pathological type of primary glomerular disease (PGD). METHODS: On-site investigation was adopted, 174 patients with PGD conforming to the inclusive/exclusive criteria were enrolled, and their degree of BSS and deficiency syndrome were scored in 3 days before renal biopsies. The relation of clinical indexes, including age, course of disease, symptoms of deficiency syndrome, 24-h urinary protein excretion (Upro), condition of hypertension and its controlling, glomerular filtrating rate (GFR) based on the predigesting equation of MDRD, and blood levels of uric acid (UA), triglyceride (TG), cholesterol (CHO), hemoglobin (Hb), and albumin (ALB), with the renal pathological type and the BSS score were analyzed. RESULTS: (1) Among the 174 patients, 159 cases (91.38%) were differentiated as BSS, with the degree of moderate in 111 cases and severe in 48 cases; (2) The BSS score was significantly correlated with the level of Upro, CHO, TG, ALB and deficiency syndrome (P < 0.01), but showed insignificant correlation with age, course of disease, grade of the hypertension, and GFR, UA and Hb levels. Multivariate stepwise regression analysis showed that the level of Upro and TG and score of deficiency syndrome had significance for regression equation establishment (P<0.01). (3) Further analysis on renal pathological type in 119 patients of non-nephrotic syndrome showed that the BSS score was insignificantly different among patients with different renal pathological types as the minor/minimal type (3 cases), the focal/segmental glomerular type (72 cases), and the diffuse glomerulonephritis (44 cases, P > 0.05). Further stratified analysis on the 72 cases with focal/segmental lesion showed that BSS score in patients of focal proliferative sclerosing glomerulonephritis were significantly higher than that in those of focal proliferative glomerulonephritis (P < 0.01). CONCLUSION: BSS is a TCM syndrome most commonly seen in patients with primary glomerular disease, BSS score is significantly correlated with the level of Upro, TG and deficiency syndrome score, and exhibits a higher level in patients with focal proliferative glomerulonephritis accompanying glomerulus sclerosis, indicating that the BSS could give certain clues of the renal chronic changes of primary glomerular disease, being one of risk factors in TCM syndrome in the development of renal diseases.