The pathomechanisms of glomerulosclerosis in diabetic nephropathy (DN) are considered to be related with glycometabolism disorder, podocyte injury, intra-renal hemodynamics abnormality, fibrogenic cytokines over-expression, oxidative stress and inflammatory reaction. Chinese herbal medicine could delay the progression of glomerulosclerosis in DN by ameliorating the harmful factors of these pathological changes. Therefore, it is possible to postpone the progress of DN to end-stage renal disease through the treatment with Chinese herbal medicine.
Animals ; Diabetic Nephropathies ; drug therapy ; immunology ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Glomerulonephritis ; drug therapy ; immunology ; metabolism ; prevention & control ; Humans ; Oxidative Stress ; drug effects

PURPOSE: This study aimed to evaluate the preventive effects of Camellia sinensis var. assamica (CSVA) on diabetic nephropathy in in vitro and in vivo models. MATERIALS AND METHODS: MDCK cells were incubated with 1 mM of oxalate with or without different concentrations of CSVA, then MTT and malondialdehyde (MDA) assays were performed to investigate the preventive effects of CSVA on oxalate-induced cytotoxicity and oxidative stress. Thirty male db/db mice were divided into three groups. Group 1 were fed AIN-93G ad libitum; group 2 were fed AIN-93G mixed with 10% fermented CSVA ad libitum; group 3 were fed AIN-93G mixed with 10% non-fermented CSVA ad libitum. The mice were sacrificed 14 weeks later, and the serum glucose level, 24-hour urine chemistry, and morphological changes in the kidneys were examined. RESULTS: As CSVA concentrations increased, viable MDCK cells increased in concentration. MDA production decreased over time in the CSVA treated group. The creatinine clearance of group 3 was lower than those of groups 1 and 2. The amount of urine microalbumin and protein in group 1 were higher than those in groups 2 and 3. Also, more glomerulus basement membrane foot processes were preserved in groups 2 and 3. CONCLUSION: In conclusion, CSVA has beneficial preventive tendencies towards diabetic nephropathy in both in vitro and in vivo models.
Animals ; *Camellia sinensis/chemistry ; Cell Line ; Cell Survival/drug effects ; Diabetes Mellitus, Type 2/complications ; Diabetic Nephropathies/*drug therapy/*prevention & control ; Disease Models, Animal ; Dogs ; Kidney/cytology/*drug effects ; Male ; Mice ; Mice, Mutant Strains ; Plant Extracts/*pharmacology ; *Tea/chemistry

OBJECTIVETo investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats.

METHODSThirty Sprague-dawley female rats were randomly divided into three groups (n = 10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy.

RESULTSBefore diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group.

CONCLUSIONOur results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP-1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; pathology ; Diabetic Nephropathies ; metabolism ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Kidney ; drug effects ; metabolism ; pathology ; ultrastructure ; Lamiaceae ; chemistry ; Rats ; Rats, Sprague-Dawley ; Thrombospondin 1 ; metabolism

OBJECTIVETo observe the preventive effects of multi-glycoside of Tripterygium wilfordii (GTW) on glomerular lesions in experimental diabetic nephropathy (DN).

METHODThe DN model of rats was established with streptozotocin (STZ) and intervened with GTW. In the same time, normal, benazepril, and vehicle control groups were set up. After 8 weeks of oral treatment with GTW (50 mg x kg(-1) BW), benazepril (6 mg x kg(-1) BW), and vehicle (physiological saline), the changes of body weight, urine albumin (UA1b), blood glucose (BG), serum creatinine (Scr), blood urea nitrogen (BUN) and glomerular morphology were examined. In addition, the level of protein expression of alpha-smooth muscle actin (alpha-SMA) and collagen type I in glomeruli was determined by immunofluorescence.

RESULTBoth GTW and benazepril reduced UA1b. GTW ameliorated glomerular injury, such as mesangial cell proliferation, alpha-SMA and collagen type I over-expression, in DN model. Compared with benazepril, beneficial effects of GTW on glomerulusclerosis were more significant (total cell number: GTW group 54.44 +/- 2.41, benazepril group microg/67.83 +/- 4.41, P < 0.05; alpha-SMA score: GTW group 1.98 +/- 0.52, benazepril group 2.27 +/- 0.46, P < 0.05; collagen type I score: GTW group 2.11 +/- 0.37, benazepril group 2.88 +/- 0.58, P < 0.05).

CONCLUSIONPreventive effects of GTW on glomerular lesion in DN model are related to decreasing UA1b and ameliorating glomerulusclerosis.

Animals ; Diabetic Nephropathies ; drug therapy ; metabolism ; prevention & control ; Disease Models, Animal ; Glycosides ; administration & dosage ; Humans ; Kidney Glomerulus ; drug effects ; injuries ; metabolism ; Male ; Plant Extracts ; administration & dosage ; Random Allocation ; Rats ; Tripterygium ; chemistry

BACKGROUND/AIMS: Thiazolidinediones reduce urinary albumin excretion and may prevent the development of renal injury. We evaluated the long-term effects of rosiglitazone on the progression of renal dysfunction in patients with type 2 diabetes mellitus. METHODS: We enrolled patients with type 2 diabetes mellitus who initially had normal or mildly impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of 60-120 mL/min per 1.73 m2, and normoalbuminuria. Patients were divided into two groups according to their use of rosiglitazone during 3 years of follow-up: those treated with rosiglitazone (rosiglitazone group, n=52) and those treated without rosiglitazone (control group, n=85). Progression of renal dysfunction was defined as a decrease in eGFR of > or =9 mL/min per 1.73 m2 after 3 years. RESULTS: A greater difference was observed in the decrease in eGFR between the rosiglitazone and control groups after 3 years (3.8+/-9.9 vs. 12.6+/-10.5 mL/min per 1.73 m2, p<0.001). Seventeen of 52 (32.7%) patients in the rosiglitazone group and 53 of 85 (62.3%) patients in the control group showed progression of renal dysfunction (p=0.001). The progressors had a longer duration of diabetes (6.7+/-5.9 vs. 3.9+/-4.1 years, p=0.002), higher HbA1c levels (7.4+/-1.8 vs. 6.8+/-1.3%, p=0.023), and less frequent use of rosiglitazone (24.2 vs. 52.2%, p<0.001) compared to non-progressors. Multiple logistic regression analysis revealed that the use of rosiglitazone was a significant and independent predictor of the progression of renal dysfunction. CONCLUSIONS: This study suggests that rosiglitazone theatment slows the progressive deterioration of renal function in patients with type 2 diabetes.
Adult ; Aged ; Diabetes Mellitus, Type 2/*drug therapy/physiopathology ; Diabetic Nephropathies/*prevention & control ; Female ; Glomerular Filtration Rate ; Humans ; Hypoglycemic Agents/*therapeutic use ; Kidney/*physiopathology ; Male ; Middle Aged ; Retrospective Studies ; Thiazolidinediones/*therapeutic use

OBJECTIVE: To investigate the effect of mycophenolate mofetil(MMF) on early inflammatory reaction of renal lesion in streptozotocin(STZ)-induced diabetic rats. METHODS: Thirty-six male Sprague-Dawley rats were randomly divided into 3 groups after uninephrectomy: normal control group, diabetic model group, and MMF-treated group. Six rats in each group were sacrificed at the 4th week and 14th week after STZ injection. Twenty-four hour urinary protein (24 h Upro) count was measured before death. The expressions of regulated on activation of normal T expressed and secreted (RANTES),ectodermal dysplasia (ED-1)and Col-IV protein in the renal tissue were detected by immunohistochemistry. The expression of RANTES mRNA in the renal tissue was detected by RT-PCR. RESULTS: MMF prevented the increasing of 24h Upro in diabetic rats,and the expressions of RANTES,ED-1,Col-IV protein and RANTES mRNA in the kidney of MMF-treated rats were significantly decreased. CONCLUSION MMF plays an early renal protective role in diabetic nephropathy, possibly through inhibition of early inflammatory reaction.
Animals ; Chemokine CCL5 ; biosynthesis ; genetics ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Nephropathies ; metabolism ; prevention & control ; Ectodysplasins ; biosynthesis ; genetics ; Inflammation ; metabolism ; Kidney ; metabolism ; Male ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUNDDiabetic nephropathy is a major cause of renal failure in diabetes mellitus (DM). It has been known that renin-angiotensin system (RAS) blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin II receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin (STZ)-induced DM rats.

METHODSDM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment (OLM + DM) group. The normal group (non-DM) were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated: slope of flow-pressure (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature), slope of pressure-GFR (glomerular filtration capacity against pressure) and threshold pressure for beginning filtration at pressure-GFR (preglomerular to postglomerular vascular resistance ratio). Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.

RESULTSThe body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight, urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM + DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats (P < 0.05). But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats (P < 0.05) with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan (P < 0.05). Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats (P < 0.05). The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.

CONCLUSIONSTreatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Animals ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Diabetic Nephropathies ; drug therapy ; prevention & control ; Hemodynamics ; drug effects ; Imidazoles ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Organ Size ; drug effects ; Rats ; Rats, Wistar ; Tetrazoles

OBJECTIVETo investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes.

METHODSDiabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old),and divided into an untreated and three treated groups: 1) cilazapril treated group; 2) bosentan+amlodipine treated group; and 3) amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin II levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-beta1 were determined at the end of the 4th week.

RESULTSMean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotens in II levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-beta1 by Western blot analysis and reduced the accumulation of collagen type IV, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters.

CONCLUSIONBosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-beta1 in diabetes with a hypertensive state.

Amlodipine ; administration & dosage ; Angiotensin II ; analysis ; Animals ; Calcium Channel Blockers ; administration & dosage ; Collagen Type IV ; analysis ; Diabetic Nephropathies ; prevention & control ; Drug Therapy, Combination ; Endothelin Receptor Antagonists ; Hypertension ; complications ; drug therapy ; Kidney ; drug effects ; Male ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Sulfonamides ; administration & dosage ; Transforming Growth Factor beta ; analysis ; Transforming Growth Factor beta1

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.
Aldehyde Reductase/*antagonists & inhibitors ; Animals ; Antihypertensive Agents/therapeutic use ; Diabetes Mellitus, Experimental/*drug therapy/*metabolism ; Diabetic Nephropathies/prevention & control ; Imidazolidines/*therapeutic use ; Kidney/*drug effects/*metabolism/pathology ; Losartan/therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Angiotensin/*antagonists & inhibitors ; Vascular Endothelial Growth Factor A

OBJECTIVETo explore methods of preventing and reversing rejection after simultaneous pancreas-kidney transplantation (SPK).

METHODSSeventeen patients performed SPK operation from Sep, 1999 to Sep, 2003 were reviewed retrospectively. Immunosuppression was achieved by triple regimen consisting of cyclosporine, mycophenolate mofetil (MMF)/azathioprine and steroid. 2 patients were treated with Dalizumab, the other three patients used OKT3 as immune induction.

RESULTS1 patient experienced the accelerated rejection, the pancreas and kidney grafts were resected because of failure of conservative therapy. 8 patients experienced renal acute rejection, 2 cases suffered from pancreas acute rejection at the same time. All these patients received daily high dose pulse steroid for 3 days. OKT3 was administered in 2 patients with steroid resistance rejection. All the grafts were successfully rescued.

CONCLUSIONSReasonable application of immunosuppression after SPK operation and adoption of systemic measures which can reduce sensitivity of high risk receptor before SPK operation are the effective methods of preventing and treating rejection.

Administration, Oral ; Adult ; Azathioprine ; administration & dosage ; Cyclosporine ; administration & dosage ; Diabetic Nephropathies ; surgery ; Drug Therapy, Combination ; Female ; Glucocorticoids ; administration & dosage ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; administration & dosage ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Pancreas Transplantation ; immunology ; Prednisolone ; administration & dosage ; Retrospective Studies ; Transplantation, Homologous