Showing papers in "Current Opinion in Nephrology and Hypertension in 2007"
TL;DR: The previously unsuspected complexity of the renin–angiotensin system, unmasked by novel findings, has revealed new possibilities for exploring its physiological and pathophysiological roles.
Abstract: Purpose of reviewIn this review we will focus on the recent findings related to angiotensin-(1–7) as an angiotensin II counter-regulatory peptide within the renin–angiotensin system.Recent findingsThe identification of the angiotensin-converting enzyme homologue ACE2 as an angiotensin peptide proces
158 citations
TL;DR: The role of immunohistochemistry – the current standard of care in amyloid typing – is evolving with emergence of alternative biochemical methods, and presents an attractive venue for the application of proteomics methodologies, despite their inherent complexities.
Abstract: Purpose of review This review aims to summarize recent developments in the area of systemic amyloidoses with emphasis on pathologic diagnosis. Recent findings In recent years, management of amyloidosis has shifted from a purely supportive approach to quite diverse, radical and aggressive treatments. The central issue is the understanding that treatment of systemic amyloidoses depends on the molecular type of the amyloid protein. In the United States and the Western world, AL-amyloidosis is the most prevalent type of systemic amyloidosis, but hereditary amyloidoses are being diagnosed with increasing frequency; genetics also plays a role in a subset of familial AA amyloidoses. The biggest challenge is in the diagnosis of AL-type with confidence and in differentiation of AL and hereditary amyloidoses. While careful clinico-pathologic correlation is recommended for all patients with amyloidosis, it is, in itself, not a substitute for amyloid typing. Summary The diagnosis of the amyloid type ultimately depends on the examination of the amyloid protein within the deposits. The role of immunohistochemistry ‐ the current standard of care in amyloid typing ‐ is evolving with emergence of alternative biochemical methods. Amyloid, being essentially a protein disorder, presents an attractive venue for the application of proteomics methodologies, despite their inherent complexities.
114 citations
TL;DR: The field of TLR research elucidates the molecular mechanisms of infection-associated kidney diseases but may also further support the concept that innate immunity significantly contributes to the so-called types of nonimmune kidney diseases.
Abstract: Purpose of reviewTo summarize the recent advances in the role of Toll-like receptors (TLRs) in innate immunity, with a special focus on recent studies addressing the expression and function of TLRs in kidney disease.Recent findingsPathogen-recognition receptors including TLRs mediate immune activati
113 citations
TL;DR: FGF23 discovery has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling and pharmacological regulation of FGF23 levels may provide novel treatments.
Abstract: Purpose of review To describe emerging understanding of fibroblast growth factor 23 (FGF23) - a bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by kidney and participates as the principle phosphaturic factor in a bone-kidney axis coordinating systemic phosphate homeostasis and bone mineralization. Recent findings FGF23 (a circulating factor made by osteocytes in bone) inhibits phosphate reabsorption and 1,25(OH)2D production by kidney. Physiologically, FGF23 is a counter-regulatory phosphaturic hormone for vitamin D and coordinates systemic phosphate homeostasis with skeletal mineralization. Pathologically, high circulating FGF23 levels cause hypophosphatemia, decreased 1,25(OH)2D production, elevated parathyroid hormone and rickets/osteomalacia. FGF23 mutations impairing its degradation cause autosomal dominant hypophosphatemic rickets. Respective loss-of-function mutations of osteocyte gene products DMP1 and Phex cause autosomal recessive hypophosphatemic rickets and X-linked hypophosphatemic rickets, initiating increased FGF23 production. Low FGF23 levels lead to hyperphosphatemia, elevated 1,25(OH)2D, and soft-tissue calcifications. FGF23 is markedly increased in chronic renal disease, but its role remains undefined. Summary FGF23 discovery has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling. FGF23 assessment will become important in diagnosing hypophosphatemic and hyperphosphatemic disorders, for which pharmacological regulation of FGF23 levels may provide novel treatments.
113 citations
TL;DR: Clinical studies of newer biomarkers of kidney injury and glomerular filtration rate hold the promise of substantially improving the diagnostic approach to acute kidney injury.
Abstract: Purpose of reviewThe identification of acute kidney injury relies on tests like blood urea nitrogen and serum creatinine that were identified and incorporated into clinical practice several decades ago. This review summarizes clinical studies of newer biomarkers that may permit earlier and more accu
108 citations
TL;DR: This review summarizes the major epidemiologic studies that have informed the understanding of the incidence and prognostic significance of acute kidney injury and provides further details into this heterogeneous syndrome.
Abstract: Purpose of reviewAcute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. This review summarizes the major epidemiologic studies that have informed our understanding of the incidence and prognostic significance of acute kidney injury.Recent fi
105 citations
TL;DR: The experimental data confirmed the pivotal role of the (pro)renin receptor in cell surface generation of angiotensin and suggested its potential role in tissue fibrosis via receptor activation and intracellular signaling.
Abstract: Purpose of reviewThe pathophysiological role of the (pro)renin receptor is yet to be established. The present review summarizes the findings, suggesting that it may play pathological role in cardiac and renal fibrosis, and in hypertensive and diabetic nephropathy.Recent findingsIn-vitro and animal s
85 citations
TL;DR: The roles of a few cl Claudins in the renal tubule, including claudins 2, 8, 10, 16 and 19, have now been elucidated and reveal tantalizing clues to claudin biology and function.
Abstract: Purpose of review Claudins are tight junction proteins that form paracellular barriers and pores. The purpose of this timely review is to provide an update on the exciting new advances in our understanding of claudin biology and their relevance to renal physiology and pathophysiology. Recent findings Accumulating evidence from numerous studies indicates that the primary role of claudins is to determine the permeability and charge selectivity of the paracellular pathway to small ions. Studies in which claudins are overexpressed in cell lines have potential limitations and need to be interpreted cautiously. Ribonucleic acid interference is a novel approach to functional characterization. Claudins are believed to assemble into multimers by homophilic and heterophilic side-by-side and head-to-head interaction; however, there is still limited evidence for this. The roles of a few claudins in the renal tubule, including claudins 2, 8, 10, 16 and 19, have now been elucidated. Summary These findings reveal tantalizing clues to claudin biology and function. Much remains unknown, however, and these findings will hopefully encourage further research in this important area.
82 citations
TL;DR: Nontransporting features of NHE1 are analogous to recently observed nonconducting actions of ion channels in regulating cell behaviors and represent an emerging paradigm of ion transporters as multifunctional proteins.
Abstract: Purpose of reviewThe sodium–hydrogen exchanger isoform-1 (NHE1) functions in intracellular pH and cell volume homeostasis by catalyzing an electroneutral exchange of extracellular sodium and intracellular hydrogen. Recent studies have revealed the structural functions of NHE1 as an anchor for actin
82 citations
TL;DR: Members of this multifunctional anion transporter family play evolving roles in the etiology of nephrolithiasis and hypertension and their roles in renal physiology and pathophysiology are not yet known.
Abstract: Purpose of review The multifunctional anion exchanger family (Slc26) encompasses 11 identified genes, but only 10 encode real proteins (Slc26a10 is a pseudogene). Most of the Slc26 proteins function primarily as anion exchangers, exchanging sulfate, iodide, formate, oxalate, hydroxyl ion, and bicarbonate anions, whereas other Slc26 proteins function as chloride ion channels or anion-gated molecular motors. The aim of this review is to present recent studies on the molecular function of the Slc26 family and its role in renal physiology and pathophysiology. Recent findings In proximal tubules, Slc26a1 (Sat-1) mediates sulfate and oxalate transport across the basolateral membrane, while Slc26a6 (CFEX, Pat-1) mediates a variety of anion exchange at the apical membrane to facilitate transcellular sodium chloride absorption. Targeted deletion of murine Slc26a6 leads to intestinal hyperabsorption of oxalate, hyperoxaluria, and kidney stones. Slc26a4 (pendrin) and Slc26a7 are expressed in intercalated cells, and are involved in acid–base homeostasis and blood pressure regulation. Messenger RNA for Slc26a2, Slc26a9, and Slc26a11 is also present in the kidney, yet the roles of these family members in renal physiology or pathophysiology are not clear. Summary Members of this multifunctional anion transporter family play evolving roles in the etiology of nephrolithiasis (Slc26a6) and hypertension (Slc26a4 and Slc26a6). Other Slc26 family members (Slc26a2, Slc26a9, Slc26a11) express mRNA in the kidney but their roles in renal physiology are not yet known.
75 citations
TL;DR: Findings indicate that epithelial sodium channels are activated by the proteolytic release of inhibitory peptides from the α and γ subunits, which plays a key role in modulating epithelial Sodium channel activity through changes in channel open probability.
Abstract: PURPOSE OF REVIEW Epithelial sodium channels mediate Na+ transport across high resistance, Na+-transporting epithelia This review describes recent findings that indicate that epithelial sodium channels are activated by the proteolytic release of inhibitory peptides from the alpha and gamma subunits RECENT FINDINGS Non-cleaved channels have a low intrinsic open probability that may reflect enhanced channel inhibition by external Na+--a process referred to as Na+ self-inhibition Cleavage at a minimum of two sites within the alpha or gamma subunits is required to activate the channel, presumably by releasing inhibitory fragments The extent of epithelial sodium channel proteolysis is dependent on channel residency time at the plasma membrane, as well as on the balance between levels of expression of proteases that activate epithelial sodium channels and inhibitors of these proteases Regulated epithelial sodium channel proteolysis has been observed in rat kidney and in human airway epithelia SUMMARY Proteolysis of epithelial sodium channel subunits plays a key role in modulating epithelial sodium channel activity through changes in channel open probability
TL;DR: The currently defined mechanisms underpinning the tubular reabsorption of albumin, how these are modified by pathology and pharmacology, and the clinical implications are the subject of this review.
Abstract: Purpose of review Significant epidemiological and clinical trial evidence supports the association between increased urinary albumin excretion, cardiovascular events and renal failure. An increase in albumin excretion has traditionally been considered to reflect a 'glomerular' leak of protein; however, it is now recognized that significant tubular reabsorption of albumin occurs under physiological conditions that may be modified by genetic determinants, systemic disease and drug therapies. Recent findings The endocytosis of albumin by the proximal tubule is a highly regulated process depending on protein-protein interactions between several membrane proteins and scaffolding and regulatory molecules. The elucidation of these interactions is an ongoing research focus. There is also mounting evidence for a transcytotic pathway for retrieval of albumin from the tubular filtrate. The molecular basis for the role of albuminuria in both interstitial renal disease. and cardiovascular pathology continues to be defined. The clinical implications of albuminuria due to a glomerular leak vs: reduced tubular reabsorption of albumin area however;, now under consideration. In particular, the prognostic implication of microalbuminuria induced; by the more potent 3-hydroiy-3-methylglutaryl coenzyme A reductase inhibitors is under study: Summary The currently defined mechanisms underpinning the tubular reabsorption of albumin, how these are modified by pathology and pharmacology, and the clinical implications are the subject of this review.
TL;DR: Although ABO incompatible kidney transplantation entails increased expense, when compared with maintenance dialysis and taking into account the health related quality of life benefits of a successful transplant, it is clearly cost effective.
Abstract: Purpose of review Although ABO incompatible kidney transplantation is increasingly recognized as effective, the procedure is still evolving. The purpose of this review is to summarize recent advances in this area. Recent findings Short to intermediate-term outcome appears good, although long-term results are still preliminary. Pretransplant risk stratification based on antidonor antibody titer may be of limited value. Splenectomy, previously reported to be an important component of ABO incompatible transplantation, appears to be avoidable under many circumstances. The wider implementation of A2 blood group incompatible transplantation shortens waiting time for deceased donor transplantation of blood group B recipients without significantly disadvantaging others. The diagnosis of acute humoral rejection has become clearer following the recognition that C4d deposition commonly occurs in well functioning ABO incompatible allografts. The long-term implications of acute humoral rejection appear substantial even following successful acute therapy, with a significant percentage of patients developing chronic humoral rejection manifested as transplant glomerulopathy. Finally, although ABO incompatible transplantation entails increased expense, when compared with maintenance dialysis and taking into account the health related quality of life benefits of a successful transplant, it is clearly cost effective. Summary ABO incompatible kidney transplantation is an effective therapy, and will become more widely implemented in the future.
TL;DR: Appropriate selection of transplant candidates, pretranspant and posttransplant cancer surveillance and judicious evidence-based use of newer immunosuppressants may help reduce the incidence and improve the outcome of posttrans transplant cancer.
Abstract: Purpose of review Prolonged waiting times for renal transplantation, an increase in the average age of recipients, decreased acute rejection rates due to use of newer potent immunosuppressives and improving long-term transplant survival have raised concerns in the transplant community regarding posttransplant cancer. In view of the fact that transplant recipients are living longer, it is of paramount importance that we continue to translate discoveries at the bench to the bedside and document cancers in the posttransplant recipient registries. Analysis of data will help in optimizing patient management. Recent findings Recent evidence indicates that sirolimus is associated with a decreased incidence of posttransplant de-novo cancer and remission of Kaposi's sarcoma and nonmelanoma skin cancer. Mycophenolate mofetil has been shown to have an antiproliferative activity against leukemia and lymphoma and an anti-tumor effect against colon and prostate cancer. Clinically it has been shown to be associated with a reduced incidence of cancers like posttransplant lymphoproliferative disorder. Summary Appropriate selection of transplant candidates, pretransplant and posttransplant cancer surveillance and judicious evidence-based use of newer immunosuppressants may help reduce the incidence and improve the outcome of posttransplant cancer.
TL;DR: Vascular maladaptation, with increased vasomotor tone, endothelial dysfunction, increased sensitivity to angiotensin II and norepinephrine, and multiorgan dysfunction seen in preeclampsia, may be explained by angiotENSin II-mediated mechanisms.
Abstract: PURPOSE OF REVIEW Preeclampsia is a disorder of gestation characterized by hypertension and proteinuria and can be complicated by eclamptic seizures. This review describes recent advances in the role of the renin-angiotensin system and angiogenic and anti-angiogenic factors of placental origin in its pathogenesis. RECENT FINDINGS Deficient uteroplacental perfusion has been recognized to be a feature in all preeclampsia syndromes. Increased renin expression observed in humans and animal models supports the concept that activation of the decidual renin-angiotensin system may mediate the pathogenesis of preeclampsia. Novel angiotensin II-related biomolecular mechanisms, angiotensin II type 1-B2 receptor heterodimerization and autoantibody against angiotensin II type 1 have recently been described in preeclampsia. New evidence suggests that vascular endothelial growth factor and its receptors, antagonists, and reduced placental growth factor may play a role in the development of proteinuria and other renal injury-mediated manifestations in preeclampsia. SUMMARY Vascular maladaptation, with increased vasomotor tone, endothelial dysfunction, increased sensitivity to angiotensin II and norepinephrine, and multiorgan dysfunction seen in preeclampsia, may be explained by angiotensin II-mediated mechanisms. Future investigations need to define the mechanism of activation of the decidual renin-angiotensin system and the release of placental factors in the pathogenesis of preeclampsia.
TL;DR: Modulation of Pit-1 expression or its transport activity may provide a novel therapeutic target for intervention of vascular calcification, which is associated with cardiovascular events in patients with end-stage renal disease and diabetes.
Abstract: Purpose of reviewVascular calcification is associated with cardiovascular events in patients with end-stage renal disease and diabetes. Hyperphosphatemia is a risk factor for vascular calcification in these patients. Sodium-dependent phosphate cotransporters are required for cellular phosphate uptak
TL;DR: The experimental data suggesting that renalase replacement may be an important therapeutic modality suggest that the renalase pathway is a previously unrecognized mechanism for regulating circulating catecholamines, and, therefore, cardiac function, and blood pressure.
Abstract: Purpose of review Renalase is a secreted amine oxidase that metabolizes catecholamines. The approach used to identify this novel renal hormone will be discussed, as will the experimental data suggesting it regulates cardiovascular function, and its deficiency contributes to heightened cardiovascular risks in patients with chronic kidney disease. Recent findings The sympathetic nervous system is activated in chronic kidney disease and end-stage renal disease, and patients have a significant increase in cardiovascular disease. Parenteral administration of either native or recombinant renalase lowers blood pressure and heart rate by metabolizing circulating catecholamines. Plasma levels are markedly reduced in patients with chronic kidney disease and end-stage renal disease. Renalase deficiency occurs in salt-sensitive Dahl rats as they develop hypertension. Renalase inhibition by antisense RNA increases baseline blood pressure, and leads to an exaggerated blood pressure response to adrenergic stress. Most recently, two single nucleotide polymorphisms in the renalase gene were found to be associated with essential hypertension in humans. Summary The renalase pathway is a previously unrecognized mechanism for regulating circulating catecholamines, and, therefore, cardiac function, and blood pressure. Abnormalities in the renalase pathway are evident in animal models of chronic kidney disease and hypertension. Collectively, these data suggest that renalase replacement may be an important therapeutic modality.
TL;DR: As a screening test, SCr should be interpreted as a marker of CKD probability in the context of the patient's clinical presentation and GFR estimating equations should be reserved for patients with identified CKD.
Abstract: Purpose of reviewGlomerular filtration rate (GFR) can be estimated using serum markers such as serum creatinine (SCr) or cystatin C. This review presents new insights into estimated GFR based on theory, validation studies, SCr assay standardization, cystatin C, and longitudinal comparison with measu
TL;DR: Characterization of the function of small GTP-binding proteins, mitogen-activated protein kinases and their effectors in cardiovascular pathophysiology can be readily identified by using select inhibitors, dominant-negative gene transfer and the generation of select gene-targeted animals.
Abstract: Purpose of reviewTo summarize the most recent findings concerning the targeting of mitogen-activated protein kinases and small GTP-binding proteins toward vascular remodeling together with molecular mechanisms of their activations in vascular pathophisiology.Recent findingsIn addition to targeting t
TL;DR: Vascular access dysfunction remains a significant cause of morbidity and mortality for hemodialysis patients and a better understanding of the biological mechanisms will help guide the development of novel therapies to prevent and treat dialysis access stenosis.
Abstract: Purpose of reviewThe aim of this review will be to summarize recent concepts pertaining to the pathophysiology of dialysis access stenosis and to then use this information to highlight novel interventions (both diagnostic and therapeutic) for dialysis access dysfunction. The studies covered in this
TL;DR: Evidence that excess weight contributes to chronic kidney disease and end-stage renal disease over and above its role in hypertension and diabetes is reviewed and weight loss may represent a novel intervention to reduce risk of Chronic kidney disease development and progression.
Abstract: Purpose of reviewThe increasing incidence of end-stage renal disease and the epidemic of obesity are major public health problems. We review recent epidemiological evidence that excess weight is an important risk factor for chronic kidney disease and end-stage renal disease.Recent findingsA cohort s
TL;DR: The balance of angiotensin II and nitric oxide determines the sensitivity of the tubuloglomerular feedback mechanism, renal vascular resistance and filtration rate, and their modulation by reactive oxygen species in the control of renal blood flow.
Abstract: PURPOSE OF REVIEW: The balance of angiotensin II and nitric oxide determines the sensitivity of the tubuloglomerular feedback mechanism, renal vascular resistance and filtration rate. Angiotensin II induces nitric oxide release, but the role of angiotensin II receptors here is not fully understood. Further, the angiotensin II-nitric oxide interaction can be modulated by reactive oxygen species. This review focuses on the angiotensin II-nitric oxide interaction and their modulation by reactive oxygen species in the control of renal blood flow. RECENT FINDINGS: Ideas about the role of angiotensin II type 1 and angiotensin II type 2 receptors are extended by the observation of angiotensin II type 1-mediated nitric oxide release with direct effects on vascular tone, tubuloglomerular feedback and sympathetic neurotransmission. Angiotensin receptors elicit disparate effects on intrarenal circulation. Angiotensin II-nitric oxide interactions are modulated by reactive oxygen species, as shown by angiotensin II type 1-mediated activation of superoxide and depression of antioxidant enzymes leading to reduced nitric oxide concentration - mechanisms that may be also important in angiotensin II-dependent hypertension. SUMMARY: Recent studies show that angiotensin II stimulates the nitric oxide system via angiotensin II type 1 and angiotensin II type 2 receptors, whereas receptors exert different effects on renal and medullary flow. The interaction via angiotensin II type 1 is modulated by reactive oxygen species.
TL;DR: Weight loss appears to be beneficial in obese patients both with and without chronic kidney disease, and the safety of intentional weight loss in obese ESRD patients, however, remains questionable.
Abstract: Purpose of reviewObesity is the number one preventable risk factor for chronic kidney disease. Obesity is, however, associated with improved survival in patients with end-stage renal disease (ESRD).Recent findingsMultiple observational studies have documented an association between obesity and risk
TL;DR: The hypothesis that molecules released by injured cells elicit inflammation, which may be so useful that nature has evolved mechanisms for programming necrotic death via poly(ADP-ribose) polymerase and cyclophilin D, is examined.
Abstract: Purpose of review Ischemic acute kidney injury may be exacerbated by an inflammatory response. How injury elicits inflammation remains a major question in understanding acute kidney injury. The present review examines the hypothesis that molecules released by injured cells elicit inflammation. Recent findings After necrotic death, intracellular molecules find their way into the extracellular space. These molecules include heat shock proteins and HMGB1. Receptors for these proteins include TLR4, TLR2, CD91 and RAGE. These proinflammatory mechanisms may be so useful that nature has evolved mechanisms for programming necrotic death via poly(ADP-ribose) polymerase and cyclophilin D. In addition, apoptosis may also elicit inflammation. Summary The concepts discussed in this review are important for clinical medicine. Drugs and genetic manipulation may ameliorate ischemic kidney injury by regulating the inflammatory response to cell injury.
TL;DR: How acute renal failure (ARF) Epidemiology relates to end-stage renal disease (ESRD) epidemiology and chronic kidney disease (CKD) epidemiological studies is addressed.
Abstract: []IntroductionBefore addressing how acute renal failure (ARF) epidemiology relates to end-stage renal disease (ESRD) epidemiology and chronic kidney disease (CKD) epidemiology, it is worthwhile reviewing some recent literature regarding the latter two.End-stage renal disease population epidemiologyH
TL;DR: Recent mouse genetic studies have broadened the understanding of biochemical/molecular pathways involved in phosphate homeostasis, and linked FGF-23 to such regulation, and understanding the molecular interactions of essential calcium and phosphate regulators will enhance knowledge of the coordinated regulation of mineral ion metabolism.
Abstract: Purpose of review—Our understanding of the regulation of mineral ion homeostasis is rather stagnant, and until recently the regulation of phosphate homeostasis was thought to be a passive process mediated largely by the well known calciotrophic hormones PTH and 1,25(OH)2D3. This article summarizes the emerging trends that i) show an active regulation of phosphate homeostasis by FGF-23, a process that appears to be fairly independent of calcium homeostasis, and ii) how altered mineral ion metabolism might affect the aging process. Recent findings—A major breakthrough in FGF-23 biology has been achieved by the demonstration of strikingly similar physical and biochemical phenotypes of Fgf-23 knockout and klotho hypomorph mice, which eventually led to the identification of klotho as a cofactor in FGF-23 and its receptor interactions. A new regulatory pathway has been defined, where FGF23, in presence of klotho has shown to activate downstream signaling events, by phosphorylation of FGF receptor substrate-2α, ERK, and Egr-1. Furthermore, FGF-23 has emerged as a counter regulatory hormone that influences 1α(OH)ase and NaPi2a activities in the kidney to regulate phosphate homeostasis. Finally, studies also point towards a role of DMP1 in influencing the regulation of phosphate homeostasis, in coordination with FGF-23. Summary—Recent in vivo mouse genetic studies have expanded our understanding of the biochemical and molecular pathways involved in phosphate homeostasis, and linked FGF-23 to the genesis of such regulation. A clear understanding of the molecular interactions of essential calcium and phosphate regulating factors will enhance our understanding of the coordinated regulation of mineral ion metabolism, and will help us to redefine the molecular pathology of age-associated lesions accompanied by abnormal mineral ion metabolism, that include but are not limited to vascular calcifications, and osteoporosis.
TL;DR: A better understanding of how signaling molecules compartmentalize in lipid rafts/caveolae will provide further insights into molecular mechanisms underlying vascular damage in cardiovascular disease.
Abstract: Purpose of review: Lipid rafts are emerging as key players in the integration of cellular responses. Alterations in these highly regulated signaling cascades are important in structural, mechanical and functional abnormalities that underlie vascular pathological processes. The present review focuses on recent advances in signal transduction through caveolae/lipid rafts, implicated in hypertensive processes. Recent findings: Caveolae/lipid rafts function as sites of dynamic regulatory events in receptor-induced signal transduction. Mediators of vascular function, including G-protein coupled receptors, Src family tyrosine kinases, receptor tyrosine kinases, protein phosphatases and nitric oxide synthase, are concentrated within these microdomains. The assembly of functionally active nicotinamide adenine dinucleotide phosphate oxidase and subsequent reactive oxygen species production are also dependent on interactions within the caveolae/lipid rafts. Recent findings have also demonstrated the importance of actin-cytoskeleton and focal adhesion sites for protein interactions with caveolae/lipid raft. Summary: Many vascular signaling processes are altered in hypertension. Whether these events involve lipid rafts/caveolae remains unclear. A better understanding of how signaling molecules compartmentalize in lipid rafts/caveolae will provide further insights into molecular mechanisms underlying vascular damage in cardiovascular disease.
TL;DR: A review of the potential role of the kallikrein-kinin system in the development of diabetic nephropathy, and its clinical relevance is presented in this paper.
Abstract: Purpose of review
Diabetic nephropathy is one of the most common complications in diabetes mellitus Multiple pathogenic mechanisms are now believed to contribute to this disease, including inflammatory cytokines, autacoids and oxidative stress Numerous studies have shown that the kallikrein–kinin system may be involved in these mechanisms This review focuses on recent research advance on the potential role of the kallikrein–kinin system in the development of diabetic nephropathy, and its clinical relevance
TL;DR: Electrical baroreflex stimulation appears safe and effective, and may represent a useful adjunct to medical therapy in patients with resistant hypertension.
Abstract: Purpose of review It is not uncommon for hypertension to be resistant to the effects of medical therapy, and this poses a significant risk of adverse cardiovascular events. Electrical stimulation of the carotid sinus is a novel treatment for hypertension, and has been shown to reduce blood pressure by activating the baroreflex and reducing sympathetic tone. Recent findings Evidence suggests that the baroreceptors play a more important role in long-term blood pressure regulation than was once believed. It appears that the baroreflex attenuates chronic hypertension in large part by inhibiting renal sympathetic tone. Animal and human studies have demonstrated a safe and effective lowering of blood pressure with chronic electrical stimulation of the carotid sinus, and have generated enthusiasm for implantable carotid sinus stimulators in the treatment of hypertension. Summary Electrical baroreflex stimulation appears safe and effective, and may represent a useful adjunct to medical therapy in patients with resistant hypertension.
TL;DR: The importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia is highlighted and the potential of peripheral administration of melanOCortin-4 receptor antagonists as a novel therapeutic approach is highlighted.
Abstract: Purpose of review This review will update clinicians and basic scientists who are interested in the clinical relevance and molecular mechanism of uremic cachexia. Recent studies that examine the role of cytokines and hypothalamic neuropeptides are emphasized. Recent findings A current hypothesis of the cause of cachexia in chronic illness is that proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and leptin, act on the central nervous system to alter the release and function of several key neurotransmitters, thereby altering both appetite and metabolic rate. Proinflammatory cytokines also activate the transcription factor nuclear factor-kappaB, resulting in decreased protein synthesis, and activate the ubiquitin-mediated proteolytic system, which is the major system involved in increased protein degradation. Summary This review highlights the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and the potential of peripheral administration of melanocortin-4 receptor antagonists as a novel therapeutic approach.