Adult ; Cyclosporine ; Glomerulosclerosis, Focal Segmental/drug therapy* ; Humans ; Leflunomide/therapeutic use* ; Nephrosis, Lipoid/drug therapy* ; Nephrotic Syndrome ; Steroids

Type IV collagen is a component of the extracellular matrix in the basement membrane. Abnormal secretion or assembly of type IV collagen may lead to kidney lesions resulting in numerous nephropathy symptoms, e.g., Alport syndrome, thin basement membrane nephropathy, and focal segmental glomerulosclerosis. Treatment for type IV collagen-related nephropathy includes drugs, kidney transplantation, gene and cell therapy. However, drugs are not always effective, and kidney transplantation is hindered by the shortage of donors. Moreover, basement membrane nephritis often occurs after kidney transplantation. Therefore, gene and cell therapy probably is the most promising treatment for type IV collagen related nephropathies.
Cell- and Tissue-Based Therapy ; Collagen Type IV ; Glomerulosclerosis, Focal Segmental ; Hematuria ; Humans ; Nephritis, Hereditary

Drugs, Chinese Herbal ; therapeutic use ; Glomerulosclerosis, Focal Segmental ; drug therapy ; Humans ; Sclerosis

OBJECTIVE: To explore the eff ect of Qiluxiaobai (QLXB) decoction on rats with adriamycin (ADR)- induced focal segmental glomerular sclerosis (FSGS) nephropathy (ADN). METHODS: Adriamycin was injected into tail vein at total dose of 7.5 mg/kg for twice per week. According to random number table, rats were divided into 4 groups: the control group, the ADN group, the Losartan group [intragastric, 5.19 mg/(kg.d)], and the QLXB group [intragastric,134.40 mg/(kg.d)]. Eight weeks later, serum creatinine (SCr), blood urea nitrogen (BUN), serum cholesterol (CHO), serum triglycerides (TG) and albuminuria (ALB) were measured by routine biochemical methods. Pathological changes in the rat kidneys were observed under light microscopes. Connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA) and fibronectin (FN) mRNA and protein expression levels were measured by real-time PCR and Western blot, respectively. RESULTS: In the ADN group, SCr, BUN, CHO, TG was increased (P<0.05) while ALB was decreased (P<0.05), ALB was decreased (P<0.05) compared to the control group. In the QLXB and Losartan group, SCr, BUN, CHO, TG and ALB was improved compared to the ADN group (P<0.05). CTGF, FN, α-SMA mRNA and protein expression was decreased in QLXB group compared to ADN group (P<0.05). CONCLUSION QLXB could partly improve glomerular sclerosis in adriamycin-induced nephropathy, which was related to inhibition of CTGF, FN and α-SMA expression.
Actins ; metabolism ; Animals ; Connective Tissue Growth Factor ; metabolism ; Doxorubicin ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Fibronectins ; metabolism ; Glomerulosclerosis, Focal Segmental ; chemically induced ; drug therapy ; Kidney ; pathology ; Rats ; Real-Time Polymerase Chain Reaction ; Sclerosis

OBJECTIVE: To determine the factors associated with the eff ect of steroid on adult primary nephrotic syndrome. METHODS: The general information, laboratory examination and renal pathological type of 425 patients with primary nephrotic syndrome were retrospectively analyzed. RESULTS: Th ere were significant differences in the response to steroid among the pathological types of minimal change disease, focal segmental glomerulosclerosis and IgA nephropathy. Th e patients in the age of 14-24 years old showed the strongest response to steroid (P<0.05). Th e IgA level in the steroid resistance group was lower than that in the non-steroid resistance group (P<0.05). There was no significant difference in urine protein in 24 hour quantitation in the steroid resistance group between pre- and post-treatment (P>0.05), while there was significant difference in urine protein in 24 hour quantitation in the non-steroid resistance group between pre- and post-treatment (P<0.05). CONCLUSION Pathological types and ages of the patients are related to the steroid curative effect. The decrease in IgA probably affects the effect of steroid on primary nephrotic syndrome.
Adolescent ; Adult ; Glomerulonephritis, IGA ; drug therapy ; Glomerulosclerosis, Focal Segmental ; drug therapy ; Humans ; Kidney ; physiopathology ; Nephrosis, Lipoid ; drug therapy ; Nephrotic Syndrome ; drug therapy ; Proteinuria ; Retrospective Studies ; Steroids ; therapeutic use ; Urinalysis ; Young Adult

OBJECTIVETo investigate the mechanism of "Jianpi Qinghua Decoction" (JQD) on renal fibrosis by observing the impact of JQD on serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and kidney tumor necrosis factor-Α (TNF-Α) expressions in focal segmental glomerulosclerosis rats induced by nephrectomy combined with adriamycin.

METHODSTotally 56 male SD rats were divided into normal group, sham operation group, model group, JQD group, Yiqi Jianpi group, Qingre Huashi group, and Niaoduqing group (all n=8). The model of focal segmental glomerulosclerosis was established by the unilateral nephrectomy and the injection of adriamycin in caudal vein of rat at a dose of 3 mg/kg in the latter 5 groups. JQD, the disassembled prescription of Jianpi Qinghua Decoction (Yiqi Jianpi Decoction and Qingre Huashi Decoction), and Niaoduqing Capsule were administered separately for 8 weeks. The serum TC, TG, LDL, and VLDL levels and the expression of Kidney TNF-Α were determined.

RESULTSCompared with normal group and sham operation group, the serum TC, TG, LDL, and VLDL levels and the kidney TNF-Α expression in the model group were significantly higher (all P<0.01). Compared with the model group, the JQD group, Qingre Huashi group, and Niaoduqing group had significantly lower serum TC, TG, LDL, and VLDL levels and kidney TNF-Α expression (all P<0.01). Compared with the model group, the Yiqi Jianpi group had significantly lower serum TC ,TG, and VLDL levels (all P<0.01), while the serum LDL level and kidney TNF-Α expression remained unchanged (all P>0.05).

CONCLUSIONSJQD can regulate serum lipids and lower the TNF-Α expression in kidney tissue and thus improve the renal inflammation and relieve renal fibrosis. The heat-clearing and dampness-removing herbs in the prescription play a central role in fighting against renal fibrosis.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fibrosis ; Glomerulosclerosis, Focal Segmental ; blood ; drug therapy ; Kidney ; metabolism ; pathology ; Lipids ; blood ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Alkyl and Aryl Transferases ; genetics ; Child ; DNA, Mitochondrial ; genetics ; Fibroblasts ; metabolism ; Glomerulosclerosis, Focal Segmental ; diagnosis ; drug therapy ; genetics ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; genetics ; Mitochondrial Diseases ; diagnosis ; drug therapy ; genetics ; Mutation ; Nephrotic Syndrome ; diagnosis ; drug therapy ; genetics ; Protein Kinases ; genetics ; Ubiquinone ; analogs & derivatives ; biosynthesis ; deficiency ; therapeutic use

Metabolic acidosis is a cause of renal disease progression, and alkali therapy ameliorates its progression. However, there are few reports on the role of renal acid-base transporters during alkali therapy. We evaluated the effect of sodium bicarbonate therapy and the role of acid-base transporters on renal disease progression in rats with a remnant kidney. Sprague-Dawley rats consumed dietary sodium bicarbonate (NaHCO3) or sodium chloride (NaCl) with 20% casein after a 5/6 nephrectomy. After being provided with a casein diet, the NaHCO3-treated group had higher levels of serum bicarbonate than the control group. At week 4, the glomerular filtration rate in the NaHCO3 group was higher than that in the NaCl group, and the difference became prominent at week 10. The glomerulosclerosis and tubulointerstitial damage indices in the NaHCO3 group were less severe compared with controls at week 4 and 10. The expression of the Na/H exchanger (NHE) was decreased, and apical reactivity was decreased in the NaHCO3 group, compared with the NaCl group. Endothelin-1 levels in the kidney were also decreased in the NaHCO3 group. Dietary sodium bicarbonate has the effects of ameliorating renal disease progression, which may be related to the altered expression of NHE in the remaining kidney.
Acidosis/*drug therapy ; Alkalies/*therapeutic use ; Animals ; Caseins/administration & dosage ; Disease Progression ; Glomerular Filtration Rate/drug effects ; Glomerulosclerosis, Focal Segmental/drug therapy ; Kidney/injuries ; Male ; Nephrectomy ; Nephritis, Interstitial/drug therapy ; Rats ; Rats, Sprague-Dawley ; Renal Insufficiency/*drug therapy ; Sodium Bicarbonate/*therapeutic use ; Sodium Chloride/administration & dosage ; Sodium-Hydrogen Antiporter/*antagonists & inhibitors

Collapsing glomerulopathy (CG) has become an important cause of end-stage renal disease (ESRD). First delineated from other proteinuric glomerular lesions in the 1980s, CG is now recognized as a common, distinct pattern of proliferative parenchymal injury that portends a rapid loss of renal function and poor responses to empirical therapy. The first cases in the literature trace back to human-immunodeficiency-virus (HIV)-negative patients who underwent biopsy in 1979. A 45-year-old male patient complained of hematuria and proteinuria eight years ago. He showed an abrupt serum creatinine increase from 1.75 to 2.65mg/dL in the last preceding months. Afterwards, his serum creatinine progressively increased up to 6.82mg/dL. Moreover, his 24 h urine protein level was determined to have reached 6,171 mg/day, as opposed to 670 mg/day a year earlier. Consequently, renal biopsy was performed, and its result showed collapsing glomerulopathy, compatible with the diagnosis. He has undergone continuous ambulatory peritoneal dialysis as renal replacement therapy. Thus, it is reported herein that a patient clinically diagnosed with chronic kidney disease eight years ago showed a sudden renal-function decrease and was clinicopathologically diagnosed with collapsing glomerulopathy based on the results of his renal biopsy.
Biopsy ; Creatinine ; Glomerulosclerosis, Focal Segmental ; Hematuria ; Humans ; Kidney Failure, Chronic ; Male ; Peritoneal Dialysis, Continuous Ambulatory ; Proteinuria ; Renal Insufficiency, Chronic ; Renal Replacement Therapy

OBJECTIVETo observe the effects of Shensu II Recipe on the renal function, mesangial extracellular matrix (ECM) accumulation, the expressions of transforming growth factor-beta1, (TGF-beta1), and plasminogen activator inhibitor-1 (PAI-1) in the focal segmental glomerulosclerosis (FSGS) rats.

METHODSFSGS SD rat model was induced by injecting adriamycin. They were randomly divided into the model group, the Western medicine group, and the Chinese medicine group according to body weight. Besides, another 12 rats was taken as the blank control group. Of them, benazepril (0.33 mg/100 g) was given to rats in the Western medicine group by gastrogavage, while Shensu II Recipe (3.5 g/100 g) was given to rats in the Chinese medicine group by gastrogavage. Normal saline was given to rats in the control group and the model group by gastrogavage. Six rats died during the experiment process, among which, one in the control group, two in the model group, one in the Western medicine group, and two in the Chinese medicine group. The changes of 24 h urinary protein (24 hU, pyrogallol red method), blood urea nitrogen (BUN, urease method), serum creatinine (SCr, enzymatic assay of creatinine), serum total protein (TP, biuret colorimetry), serum albumin (ALB, bromocresol green colormetry) were detected. The pathomorphological changes of the glomerulus were observed. Fibronection (FN), collagen IV (Col IV), glomerulus sclerosis index (GSI), ECM/glomerulus area (GA), expressions of TGF-beta1, and PAI-1 were determined by semi-quantitative analysis.

RESULTSAt the end of the 12th week, improvement was shown in the Chinese medicine group (24 hU: 38.55 +/- 2.49 mg; BUN:10.87 +/- 1.78 mmol/L; SCr: 51.70 +/- 1.50 micromol/L; TP: 68.28 +/- 2.31 g/L; and ALB: 42.43 +/- 1.95 g/L). The pathomorphological observation showed that the development of glomerulosclerosis (GS) was significantly slowed down. Semi-quantitative analysis showed significant difference when compared with the model group (GSI: 1.68 +/- 0.33 grade; ECM/GA: 7.11% +/- 2.46%; FN: 4.15% +/- 1.55%; Col IV:1.47% +/- 0.48%; TGF-beta1:19.70% +/- 5.05%; PAI-1: 22.57% +/- 10.65%) ( P < 0.05, P < 0.01).

CONCLUSIONShensu II Recipe could postpone the development of GS in FSGS rats possibly through inhibiting the expressions of TGF-beta1 and PAI-1, hindering the over-accumulation of mesangial matrix.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Extracellular Matrix ; drug effects ; Glomerular Mesangium ; drug effects ; Glomerulosclerosis, Focal Segmental ; drug therapy ; metabolism ; Male ; Plasminogen Activator Inhibitor 1 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism