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Welcome to the first issue of Kidney and Blood Pressure Research Digest (KBPR Digest) in 2010. Since we established this successful format last year, we have been continuously drawing your attention to articles of outstanding importance in the field of nephrology and hypertension. We would like to continue to present short summaries of noteworthy articles to the scientific community in the form of KBPR Digest.
KBPR Digest provides readers from all over the world with a free and concise overview on interesting topics which are part of the current issue of Kidney and Blood Pressure Research. We hope that you will be inspired to get to know more about the details of the articles which are discussed below.
Professor Thomas Quaschning, MD, PHD
On behalf of the Editorial Board of Kidney and Blood Pressure Research
mail@thomas-quaschning.de
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Digest of issue 2/2010
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Issue 1/2010 of Kidney and Blood Pressure Research covers a wide spectrum of clinical and preclinical topics. It contains a study which explores the impact of mycophenolate mofetil on wound complications and lymphoceles after kidney transplantation as well as an analysis of the impact of genetic predisposition to advanced glycation end products toxicity on the prognosis of chronic hemodialysis patients. A third study examines the bio-mechanical properties in musculocutaneous resistance arteries during angiotensin-II hypertension and its recovery.
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Modern immunosuppressive combinations allow 1-year graft survival coming close to 100 percent with extraordinarily low rejection rates after kidney transplantation. However, also the newer immunosuppressive agents like sirolimus, everolimus and mycophenol acid derivates are not free from significant side effects. Wound healing disorders as well as lymphoceles have been reported as potentially serious postoperative problems in up to 20 percent of all kidney transplant recipients. In their present study, Lopau and coworkers from the University of Würzburg (Kidney Blood Press Res 2010;33:52-59) investigated the possible interactions of mycophenolate mofetil (MMF) with wound healing and lymphocele formation after kidney transplantation. The authors conducted a retrospective single-center analysis in 144 patients receiving a cyclosporine A-based immunosuppression with prednisolone and either MMF (n=77) or azathioprine (AZA, n=77). Endpoints were incidence of lymphocele formation and non-primary wound healing during 6 months' follow-up. The authors demonstrated that AZA-treated patients had more rejection episodes and consecutively more steroid pulses, both being potential risk factors for endpoints. No graft was lost in any group, and graft function was comparable. AZA patients showed a trend for more frequent wound infections. Fluid accumulation around the graft, however, was more frequent in the MMF group.
The authors show for the first time that MMF administration after kidney transplantation appears to result in more lymphoceles without impairment of graft function or graft survival. They therefore recommend to avoid potential risk factors for lymphocele formation in case of early MMF administration post-transplantation and highlight the impact of meticulous preparation of lymphatic vessels in the hilus of the donor organ as well as around the recipient vessels.
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Cardiovascular complications are the major cause of death in patients with chronic kidney disease. Apart from traditional risk factors, non-traditional mechanisms and uremia-specific ones have to be taken into consideration when evaluating the risk. Similar to other molecules formed via oxidative and carbonyl stress, advanced glycation end products (AGEs) accumulate in patients with impaired renal function and belong to uremic toxins. Some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients, and some RAGE gene polymorphisms are implicated in various pathological states. Therefore, Kalousova and coworkers (Kidney Blood Press Res 2010;33:30-36) studied the relationship of A419C GLO I and four RAGE polymorphisms (-429T/C, -374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. 214 chronic HD patients were prospectively followed up for 43 months. During the observation period 100 patients died; 48 of them due to cardiovascular causes. The Kaplan-Meier analysis showed a higher mortality in patients mutated homozygote for RAGE -429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model in comparison to wild-type homozygote patients: RAGE -429CC 2.28 (95 percent CI 1.04-4.99), RAGE 2184GG 3.16 (95 percent CI 1.44-6.93), and GLO I 419CC 1.75 (95 percent CI 1.08-2.86). Both RAGE polymorphisms were also significantly associated with cardiovascular mortality. In summary, the Czech scientists demonstrate for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients. Future studies will have to confirm the role of genetic analysis in the assessment of prognosis in HD patients.
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Sustained hypertension is accompanied by remodeling of the wall of resistance arteries. At the segmental level, this remodeling is characterized by a narrowed lumen, increased wall thickness and rigidity alterations in myogenic and drug-induced contractility, and reduced endothelial dilation.
The aim of the present study of Nadasy and coworkers (Kidney Blood Press Res 2010;33:37-47) was to identify the relationship between systemic and local hemodynamics, as well as segmental bio-mechanical properties in a musculocutaneous resistance artery during angiotensin-II hypertension and its recovery. Rats were therefore infused with angiotensin-II using implanted osmotic minipumps for 4 weeks. Measurements were made either immediately following infusion or after an additional 4-week recovery period. Parallel controls were created. Segmental geometry and blood flow were determined in vivo on microsurgically exposed segments of the saphenous arterial branch. Pressure-radius plots of excised cylindrical segments were recorded by pressure arteriography. Eutrophic hypertensive wall remodeling developed, with reduced passive radius, increased wall thickness, elevated low-stress elastic modulus, reduced norepinephrine contraction, and reduced endothelium-mediated dilation. Relaxed wall geometry fully healed during the 4 weeks of recovery, but an increased contractility and a reduced in vivo lumen persisted. Regional hemodynamic resistance correlated positively with systemic arterial pressure and wall thickness in vivo, and negatively with in vivo lumen size throughout these studies, suggesting a partial recovery of the biomechanical parameters. The authors conclude that healing of eutrophic hypertensive remodeling of the resistance artery wall is a complex biomechanical process and cannot be considered a simple reversal of the original pathological development.
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