ABSTRACT
Background: Accumulating evidences during the past decade suggest that erythropoietin (EPO) may have many beneficial actions other than on erythropoiesis because many non-hematopoietic cells, including kidney cells, also express EPO receptors. Objective: To summarize evidences of the renoprotective effects of EPO and review the possible mechanisms of renoprotection provided by EPO. Results: Experimental studies have demonstrated the renoprotective effects of EPO in acute as well as chronic renal injury models. These renoprotective actions are likely to be mediated by several mechanisms, either directly or indirectly. However, EPO therapy is also associated with adverse effects. Conclusion: EPO is potentially a novel renoprotective drug. Clinical use of EPO for renoprotection could not be beneficial if adverse side effects of EPO have been overcome.
ABSTRACT
OBJECTIVE: Increased urinary excretion of protein and transforming growth factor-beta (TGF-beta) are associated with progression of diabetic nephropathy (DN). Thiazolidinediones (TZD) could reduce urinary protein excretion in patients with microalbuminuric DN. There is little data of patients with macroalbuminuric DN. Also, there are no available clinical data regarding the effect of TZD on TGF-beta and type IV collagen in clinical DN. The present study was carried out to evaluate the effect of pioglitazone (PGZ), a member of TZD, on urinary protein, urinary TGF-beta, and urinary type IV collagen excretion in type 2 diabetic patients with macroalbuminuric DN. MATERIAL AND METHOD: Forty patients with type 2 diabetes and overt nephropathy, proteinuria more than 500 mg/day, were randomly assigned to receive PGZ (30 mg/day, n = 24) or placebo (control group, n = 16), for 12 weeks. Blood pressure, plasma glucose, glycated hemoglobin, lipid profile, 24-hour proteinuria, urinary TGF-beta and urinary type IV collagen were determined and compared. RESULTS: Glycemic control and blood pressure in both groups were not significant different. At baseline, the levels of proteinuria, urinary TGF-beta, and type IV collagen were not significant different between both groups. The geometric mean of urinary protein excretion in the PGZ group was progressively reduced from 1.64 to 0.98 gram/day (g/d), or 40.1% decrease which was significantly different (p < 0.05) from the 4.3% increase (from 1.72 to 1.80 g/d) in the control group. Urinary TGF-beta excretion in the PGZ group was decreased by 47.8% which significantly differed from the 59.7% increase in the control group (p < 0.05). Urinary type IV collagen levels in the PGZ group were decreased by 35% which was slightly, but not significantly, different from the 51.6% elevation in the control group (p = 0.06). CONCLUSION: Besides the effectiveness in blood sugar control, pioglitazone could salutarily reduce proteinuria and synthesis of TGF-beta as well as type IV collagen. These beneficial effects of pioglitazone on diabetic nephropathy are comparable to angiotensin converting enzyme inhibitors and angiotensin receptor blockers
Subject(s)
Administration, Oral , Aged , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/diagnosis , Diabetic Nephropathies/diagnosis , Dose-Response Relationship, Drug , Female , Humans , Hypoglycemic Agents/therapeutic use , Kidney Function Tests , Male , Middle Aged , Probability , Proteinuria/physiopathology , Reference Values , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Single-Blind Method , Thiazolidinediones/therapeutic use , Transforming Growth Factor beta/analysis , Treatment OutcomeABSTRACT
BACKGROUND: Many children with brain tumors have abnormalities in water and sodium homeostasis, such as diabetes insipidus (DI), the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSW), either pre-operatively or post-operatively. But little data have been published on the incidence, time of onset and clinical course of water and sodium disorders in children with brain tumors. OBJECTIVES: To characterize the water and sodium disorders in children undergoing surgical treatment for brain tumors. PATIENTS AND METHOD: The medical records of children with brain tumors admitted for surgery at King Chulalongkorn Memorial Hospital from January 1997 to December 2002 were retrospectively reviewed. RESULTS: There were 79 patients, 46 males and 33 females included in this study. Water and sodium disorders occurred in 36 patients (45.57%), 23 patients had DI, 12 patients had SIADH and 1 patient had cerebral salt wasting syndrome (CSW). Nine of the 36 patients had pre-operative onset of water and sodium disorders (8 DI and 1 SIADH). The development of DI and SIADH was associated with the location of the brain tumors. Patients with sellar and suprasellar tumors had the highest incidence of DI (75.86%). Patients with tumors of the cerebral hemispheres had the highest incidence of SIADH (44.44%). Onset of post-operative DI ranged from 2 to 19 hours (mean 9.68 hours) and most patients developed SIADH within 24 hours post-operatively. CONCLUSIONS: DI and SIADH are common problems in children with brain tumors, especially after surgical treatment and the onset usually occurs within 24 hours after surgery. Patients with sellar and suprasellar tumors are more likely to have DI, patients with tumors of cerebral hemispheres and posterior fossa tumors are more likely to have SIADH.