Progress in Pathogenesis of Proteinuria

Aims. Proteinuria not only is a sign of kidney damage, but also is involved in the progression of renal diseases as an independent pathologic factor. Clinically, glomerular proteinuria is most commonly observed, which relates to structural and functional anomalies in the glomerular filtration barrier. The aim of this paper was to describe the pathogenesis of glomerular proteinuria. Data Sources. Articles on glomerular proteinuria retrieved from Pubmed and MEDLINE in the recent 5 years were reviewed. Results. The new understanding of the roles of glomerular endothelial cells and the glomerular basement membrane (GBM) in the pathogenesis of glomerular proteinuria was gained. The close relationships of slit diaphragm (SD) molecules such as nephrin, podocin, CD2-associated protein (CD2AP), a-actinin-4, transient receptor potential cation channel 6 (TRPC6), Densin and membrane-associated guanylate kinase inverted 1 (MAGI-1), α3β1 integrin, WT1, phospholipase C epsilon-1 (PLCE1), Lmx1b, and MYH9, and mitochondrial disorders and circulating factors in the pathogenesis of glomerular proteinuria were also gradually discovered. Conclusion. Renal proteinuria is a manifestation of glomerular filtration barrier dysfunction. Not only glomerular endothelial cells and GBM, but also the glomerular podocytes and their SDs play an important role in the pathogenesis of glomerular proteinuria

New Insights into the PPAR γ

Diabetic nephropathy (DN) is a severe complication of diabetes and serves as the leading cause of chronic renal failure. In the past decades, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) based first-line therapy can slow but cannot stop the progression of DN, which urgently requests the innovation of therapeutic strategies. Thiazolidinediones (TZDs), the synthetic exogenous ligands of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ), had been thought to be a promising candidate for strengthening the therapy of DN. However, the severe adverse effects including fluid retention, cardiovascular complications, and bone loss greatly limited their use in clinic. Recently, numerous novel PPARγ agonists involving the endogenous PPARγ ligands and selective PPARγ modulators (SPPARMs) are emerging as the promising candidates of the next generation of antidiabetic drugs instead of TZDs. Due to the higher selectivity of these novel PPARγ agonists on the regulation of the antidiabetes-associated genes than that of the side effect-associated genes, they present fewer adverse effects than TZDs. The present review was undertaken to address the advancements and the therapeutic potential of these newly developed PPARγ agonists in dealing with diabetic kidney disease. At the same time, the new insights into the therapeutic strategies of DN based on the PPARγ agonists were fully addressed

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases

Three members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα, PPARγ, and PPARβ/δ, have been investigated widely over the past few decades. Although the roles of these PPARs and their agonists/antagonists were defined in clinical and basic studies, the conflicting results from these studies indicate that more analysis is needed to understand the roles of PPARs. PPARα is a ligand-activated transcription factor that contributes to the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. In this review, we focus on the function and mechanisms of PPARα in the cardiovascular system under various pathological conditions, including vascular and heart injury, blood pressure regulation, and lipid disorder-related cardiovascular injury, as well as its polymorphisms and pharmacogenetic associations with cardiovascular diseases. The anti-inflammatory effect of PPARα in cardiovascular injury is mainly through inhibition of pro-inflammatory signaling pathways and improvement of the lipid profile. Moreover, PPARα also modulates the activity of endothelial nitric oxide synthase and resets the renin-angiotensin system to regulate vascular tone. PPARα gene variants appear to be associated with some cardiovascular risk factors, such as higher plasma lipid levels, cardiac growth, and increased risk of coronary artery disease. Nowadays, novel PPARα drugs with broad safety margins and therapeutic potential for metabolic syndrome and cardiovascular diseases are being developed and applied in the clinical setting. The insights from the current review shed new light on areas of further study and provide a better understanding of the role of PPARα in cardiovascular diseases

Clinical Evaluation of Fused/Ankylosed Hip with Severe Flexion Deformity after Conversion to Total Hip Arthroplasty

Introduction: Fused or Ankylosed hip is late complication of chronic inflammatory disorder with progressive changes in and around articular as well as periarticular structures with alteration in bio-force line of body which later lead to severe flexion deformity of joint. This not only results decreased movements of hip, it’s also increase pain around the hip, back and contralateral hip. Methods: Retrospectively, all patients aged 18 years or older undergoing THA between June 2006 to June 2012 were reviewed with selection criteria. The five ankylosed hips (three left and two right) with severe flexion deformities which ankylosed spontaneously were successfully converted to THA at time period of 2006 to June 2012. Range of Motion (ROM), Harris Hip Score and Flexion Deformity Angle at preoperative, postoperative and follow-up periods were used as evaluation. Results: Mean follow up is 42 months. Mean HHS increased from 21.6±4.97 to 81.8±4.02 points with one excellent, two good and two fair cases. The FDA is corrected to mean 8°±10.95 postoperatively and 4°±5.47 at final follow up from 81.6°±4.39 with two hips of 10° residual deformity. Hip ROM is improved as flexion 70° to 100°, adduction 10° to 20°, abduction 10° to 30°, internal rotation 5° to 10° and external rotation 2° to 50° from 0° activity. As complications, one hip had loose prosthesis, two had early postoperative dislocations, one had Deep Vein Thrombosis and one had femoral nerve palsy with quadriceps weakness. Conclusions: THA is an effective treatment for ankylosed hip with severe flexion deformity although complications are noted more than routine hip arthroplasties.  Keywords: ankylosed hip; fused hip; severe flexion deformity; total hip arthroplasty. | PubMe

Clinical Evaluation of Fused/Ankylosed Hip with Severe Flexion Deformity after Conversion to Total Hip Arthroplasty

Introduction: Fused or Ankylosed hip is late complication of chronic inflammatory disorder with progressive changes in and around articular as well as periarticular structures with alteration in bio-force line of body which later lead to severe flexion deformity of joint. This not only results decreased movements of hip, it’s also increase pain around the hip, back and contralateral hip. Methods: Retrospectively, all patients aged 18 years or older undergoing THA between June 2006 to June 2012 were reviewed with selection criteria. The five ankylosed hips (three left and two right) with severe flexion deformities which ankylosed spontaneously were successfully converted to THA at time period of 2006 to June 2012. Range of Motion (ROM), Harris Hip Score and Flexion Deformity Angle at preoperative, postoperative and follow-up periods were used as evaluation. Results: Mean follow up is 42 months. Mean HHS increased from 21.6±4.97 to 81.8±4.02 points with one excellent, two good and two fair cases. The FDA is corrected to mean 8°±10.95 postoperatively and 4°±5.47 at final follow up from 81.6°±4.39 with two hips of 10° residual deformity. Hip ROM is improved as flexion 70° to 100°, adduction 10° to 20°, abduction 10° to 30°, internal rotation 5° to 10° and external rotation 2° to 50° from 0° activity. As complications, one hip had loose prosthesis, two had early postoperative dislocations, one had Deep Vein Thrombosis and one had femoral nerve palsy with quadriceps weakness. Conclusions: THA is an effective treatment for ankylosed hip with severe flexion deformity although complications are noted more than routine hip arthroplasties. Keywords: ankylosed hip; fused hip; severe flexion deformity; total hip arthroplasty. | PubMe