OBJECTIVE: To identify the main active components in Ⅲ and their targets and explore the mechanism by which Ⅲ alleviates proteinuria in chronic kidney disease (CKD) based on network pharmacology. METHODS: The active components of Ⅲ and their potential targets, along with the oral bioavailability and drug-like properties of each component were searched in the TCMSP database. The proteinuria-related targets were searched in the GeneCards database. The active component-target network was constructed using Cytoscape software, and the acquired information of the targets from ClueGO was used for enrichment analysis of the gene pathways. RESULTS: A total of 102 active components were identified from Ⅲ. These active components acted on 126 targets, among which 69 were related to proteinuria. Enrichment analysis revealed fluid shear stress- and atherosclerosisrelated pathways as the highly significant pathways in proteinuria associated with CKD. CONCLUSIONS We preliminarily validated the prescription of Ⅲ and obtained scientific evidence that supported its use for treatment of proteinuria in CKD. The findings in this study provide a theoretical basis for further study of the mechanism of Ⅲ in the treatment of proteinuria in CKD.
Biological Availability ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; therapeutic use ; Humans ; Proteinuria ; drug therapy ; etiology ; metabolism ; Renal Insufficiency, Chronic ; complications ; metabolism

OBJECTIVETo investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.

METHODSRats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.

RESULTSHQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.

CONCLUSIONHQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Animals ; Apoptosis ; drug effects ; Body Weight ; drug effects ; Caspase 3 ; metabolism ; Chromatography, High Pressure Liquid ; Cytochromes c ; metabolism ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Kidney ; drug effects ; pathology ; Kidney Diseases ; blood ; chemically induced ; complications ; drug therapy ; Kidney Glomerulus ; drug effects ; pathology ; ultrastructure ; Kidney Tubules ; drug effects ; pathology ; ultrastructure ; Male ; Membrane Proteins ; metabolism ; NF-KappaB Inhibitor alpha ; metabolism ; NF-kappa B ; metabolism ; Organ Size ; drug effects ; Proteinuria ; blood ; complications ; drug therapy ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN.

METHODS102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed.

RESULTSSeveral findings were demonstrated with the increase of serum HBV DNA: 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly (P%lt;0.05), while the plasma level of albumin decreased significantly (P%lt;0.05); The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group (P%lt;0.01).

CONCLUSIONWith the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; DNA Replication ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Glomerulonephritis ; etiology ; Hepatitis B ; complications ; drug therapy ; Hepatitis B virus ; genetics ; Humans ; Lamivudine ; therapeutic use ; Male ; Middle Aged ; Organophosphonates ; therapeutic use ; Prognosis ; Proteinuria ; etiology ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of Flos Abelmoschus manihot (Malvaceae) on type 2 diabetic nephropathy (DN).

METHODSThe Cochrane Library, PubMed/MEDLINE, Excerpta Medical Database, Chinese electronic literature databases, and the references of relevant articles were searched in March 2012 for randomized controlled trials (RCTs) that reported the effects of Flos A. manihot on type 2 DN patients with overt but subnephrotic-range proteinuria (500-3,500 mg/24 h). The quality of trials was evaluated using the Cochrane-recommended method. The results were summarized as risk ratios (RRs) for dichotomous outcomes or mean differences (MDs) for continuous outcomes.

RESULTSSeven trials (531 patients) were included. Flos A. manihot significantly decreased proteinuria [MD -317.32 mg/24 h, 95% confidence interval (CI) [-470.48, -164.17],P<0.01]. After excluding a trial that only included patients with well-preserved renal function, Flos A. manihot was associated with a significant decrease in serum creatinine (MD -11.99 μmol/L, 95% CI [-16.95, -7.04],P<0.01). Serious adverse events were not observed. The most common adverse event was mild to moderate gastrointestinal discomfort; however, patients receiving this herb did not have an increased risk for tolerated gastrointestinal discomfort (RR 1.48, 95% CI [0.39, 5.68],P=0.57).

CONCLUSIONSFlos A. manihot may be considered as an important adjunctive therapy with the first-line and indispensable therapeutic strategies for type 2 DN. High-quality RCTs are urgently needed to confirm the effect of Flos A. manihot on definite endpoints such as end-stage renal disease.

Abelmoschus ; chemistry ; Clinical Trials as Topic ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Diabetic Nephropathies ; complications ; drug therapy ; Flowers ; chemistry ; Humans ; Plant Extracts ; adverse effects ; therapeutic use ; Proteinuria ; complications ; Publication Bias ; Treatment Outcome

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.
Aged ; Antineoplastic Agents/*adverse effects ; Carcinoma, Renal Cell/complications/drug therapy/mortality ; Female ; Humans ; Incidence ; Indoles/*adverse effects ; Kidney Neoplasms/complications/drug therapy/mortality ; Male ; Middle Aged ; Proteinuria/*chemically induced/epidemiology ; Pyrroles/*adverse effects ; Renal Insufficiency/*chemically induced/epidemiology ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Treatment Outcome

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.
Biomarkers ; urine ; Diabetic Nephropathies ; complications ; drug therapy ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Proteinuria ; complications

OBJECTIVETo evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease.

METHODSThis multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects.

RESULTSThe patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05).

CONCLUSIONSyndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.

Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Losartan ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; Prospective Studies ; Proteinuria ; drug therapy ; etiology ; Renal Insufficiency, Chronic ; complications ; drug therapy

OBJECTIVETo study the characteristics of clinicopathology and prognosis of 3 pediatric cases diagnosed as C3 glomerulopathy, and to improve the understanding of C3 glomerulopathy in children.

METHODThe medical record, plasma complement C3, Factor H (FH) and its autoantibody, and therapeutic response of the 3 cases were analyzed, and their prognosis were followed up.

RESULTOf the 3 cases, 2 were male and 1 was female, the age of onset was 9 years, 12 years, 5 years 4 months, the duration from onset to renal biopsy was 3 months, 7 months and 20 days, and the follow-up period were 2.6 years, 8 months and 1.5 years respectively.

CLINICAL MANIFESTATIONSAll the 3 cases showed microscopic hematuria, with or without gross hematuria and proteinuria. Two showed persistently decreased plasma complement C3, in the other one C3 was in normal lower limit, all presented with decreased FH concertration, in 1 case anti-FH antibody was positive. Their clinical diagnosis was post-streptococcal glomerulonephritis, nephrotic syndrome (NS) nephritis type, and mesangial proliferative glomerulonephritis respectively.

PATHOLOGICAL FINDINGSAll showed evident deposition of C3 on glomerular basement membrance (GBM) and mesangial region by immunofluorescence (IF) and electron dense deposit in GBM, mesangial region or para-mesangial region by Electron microscopic (EM) examination Treatment and prognosis: The case with NS showed no response to steroid, so steroid was gradually stopped after renal biopsy and replaced by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonist (ARB). The other two cases were treated with ACEI and renal protective treatment. Of the 3 cases, one gradually showed elevated serum creatinine (Scr) and decreased creatinine clearance rate (Ccr), the other two were normal, but slightly increased indications for early kidney injury.

CONCLUSIONC3 glomerulopathy is characterized by evident C3 deposition under IF. Its clinical and pathological manifestations vary a lot. The decreased plasma C3 and FH suggest that the abnormal regulation of complement system play an importment role in its pathogenesis.

Angiotensin Receptor Antagonists ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Child ; Child, Preschool ; Complement C3 ; metabolism ; Complement Factor H ; deficiency ; metabolism ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis ; complications ; drug therapy ; metabolism ; pathology ; Hematuria ; etiology ; pathology ; Humans ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Nephrotic Syndrome ; etiology ; pathology ; Proteinuria ; etiology ; pathology

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.
Acute Kidney Injury/etiology/pathology ; Antimalarials/therapeutic use ; Creatinine/blood ; Glomerulonephritis, IGA/*diagnosis/*etiology ; Hematuria/etiology ; Humans ; Immunoglobulin A/*metabolism ; Malaria/*complications/drug therapy/*pathology ; Male ; Middle Aged ; Plasmodium falciparum/*isolation & purification ; Proteinuria/etiology ; Quinine/therapeutic use

Various forms of hypogammaglobulinemia can occur in patients with autoimmune diseases and vice versa. We report a 13-yr-old boy with membranous nephropathy and common variable immunodeficiency. He presented with the nephrotic syndrome, pneumonia with bronchiectasis, and profound hypogammaglobulinemia. Renal biopsy showed diffusely thickened glomerular capillary walls with 'spikes' suggesting a membranous nephropathy. Secondary causes were ruled out by laboratory studies; however, heavy proteinuria persisted with steroid therapy. Cyclosporine and intravenous immunoglobulin were added, and the patient was discharged with decreased proteinuria. Hypogammaglobulinemia may have a deleterious impact on the immune dysregulation in some patients with membranous nephropathy.
Adolescent ; Bronchiectasis/etiology ; Common Variable Immunodeficiency/complications/*diagnosis/drug therapy ; Cyclosporine/therapeutic use ; Drug Therapy, Combination ; Glomerulonephritis, Membranous/complications/*diagnosis/drug therapy ; Humans ; Immunoglobulins/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Injections, Intravenous ; Kidney/pathology ; Male ; Pneumonia/etiology ; Proteinuria/etiology ; Steroids/therapeutic use