Dietary potassium and the kidney:lifesaving physiology

Potassium often has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia include a low potassium diet or potassium binders. Yet, emerging data indicate that dietary potassium may be beneficial for patients with CKD. Epidemiological studies have shown that a higher urinary potassium excretion (as proxy for higher dietary potassium intake) is associated with lower blood pressure (BP) and lower cardiovascular risk, as well as better kidney outcomes. Considering that the composition of our current diet is characterized by a high sodium and low potassium content, increasing dietary potassium may be equally important as reducing sodium. Recent studies have revealed that dietary potassium modulates the activity of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule (DCT). The DCT acts as a potassium sensor to control the delivery of sodium to the collecting duct, the potassium-secreting portion of the kidney. Physiologically, this allows immediate kaliuresis after a potassium load, and conservation of potassium during potassium deficiency. Clinically, it provides a novel explanation for the inverse relationship between dietary potassium and BP. Moreover, increasing dietary potassium intake can exert BP-independent effects on the kidney by relieving the deleterious effects of a low potassium diet (inflammation, oxidative stress and fibrosis). The aim of this comprehensive review is to link physiology with clinical medicine by proposing that the same mechanisms that allow us to excrete an acute potassium load also protect us from hypertension, cardiovascular disease and CKD

The role of Doppler ultrasonography in vascular access surveillance—controversies continue

: Chronic hemodialysis therapy required regular entry into the patient's blood stream with adequate flow. The use of arteriovenous fistulas and grafts is linked with lower morbidity and mortality than the use of catheters. However, these types of accesses are frequently affected by stenoses, which decrease the flow and lead to both inadequate dialysis and access thrombosis. The idea of duplex Doppler ultrasound surveillance is based on the presumption that in-time diagnosis of an asymptomatic significant stenosis and its treatment prolongs access patency. Details of performed trials are conflicting, and current guidelines do not support ultrasound surveillance. This review article summarizes the trials performed and focuses on the reasons of conflicting results. We stress the need of precise standardized criteria of significant access stenosis and the weakness of the metaanalyses performed

Vicarious calibration of the Tropospheric Monitoring Instrument (TROPOMI) short-wave infrared (SWIR) module over the Railroad Valley Playa

The short-wave infrared (SWIR) module of the Tropospheric Monitoring Instrument (TROPOMI) on board the ESA's Sentinel-5 precursor (S5p) satellite has been very stable during its 5 years in orbit. Calibration was performed on the ground, complemented by measurements during in-flight instrument commissioning. The radiometric response and general performance of the SWIR module are monitored by on-board calibration sources. We show that after 5 years in orbit, TROPOMI-SWIR has continued to show excellent performance with degradation of at most 0.1 % in transmission and having lost less than 0.3 % of the detector pixels. Independent validation of the instrument calibration, via vicarious calibration, can be done through comparisons with ground-based reflectance data. In this work, ground measurements at the Railroad Valley Playa, a valley in central Nevada that is often used as a reference for satellite measurements, are used to perform vicarious calibration of the TROPOMI-SWIR measurements. This is done using dedicated measurement campaigns as well as automated reflectance measurements within the RADCALNET programme. As such, TROPOMI-SWIR is an excellent test case to explore the methodology of vicarious calibration applied to infrared spectroscopy. Using methodology developed for the vicarious calibration of the OCO-2 and GOSAT missions, the absolute radiometry of TROPOMI-SWIR performance is independently verified to be stable down to ∼ 6 %–10 % using the Railroad Valley when both the absolute and relative radiometric calibrations are applied. Differences with the on-board calibration originate from the bidirectional reflection distribution function (BRDF) effects of the desert surface, the large variety in viewing angles, and the different sizes of footprints of the TROPOMI pixels. Vicarious calibration is shown to be an additional valuable tool in validating radiance-level performances of infrared instruments such as TROPOMI-SWIR in the field of atmospheric composition. It remains clear that for instruments of similar design and resolution to TROPOMI-SWIR, on-board calibration sources will continue to provide superior results due to the limitations of the vicarious calibration method.</p

Urinary Potassium Excretion, Fibroblast Growth Factor 23, and Incident Hypertension in the General Population-Based PREVEND Cohort

High plasma fibroblast growth factor 23 (FGF23) and low potassium intake have each been associated with incident hypertension. We recently demonstrated that potassium supplementation reduces FGF23 levels in pre-hypertensive individuals. The aim of the current study was to address whether 24-h urinary potassium excretion, reflecting dietary potassium intake, is associated with FGF23, and whether FGF23 mediates the association between urinary potassium excretion and incident hypertension in the general population. At baseline, 4194 community-dwelling individuals without hypertension were included. Mean urinary potassium excretion was 76 (23) mmol/24 h in men, and 64 (20) mmol/24 h in women. Plasma C-terminal FGF23 was 64.5 (54.2–77.8) RU/mL in men, and 70.3 (56.5–89.5) RU/mL in women. Urinary potassium excretion was inversely associated with FGF23, independent of age, sex, urinary sodium excretion, bone and mineral parameters, inflammation, and iron status (St. β −0.02, p < 0.05). The lowest sex-specific urinary potassium excretion tertile (HR 1.18 (95% CI 1.01–1.37)), and the highest sex-specific tertile of FGF23 (HR 1.17 (95% CI 1.01–1.37)) were each associated with incident hypertension, compared with the reference tertile. FGF23 did not mediate the association between urinary potassium excretion and incident hypertension. Increasing potassium intake, and reducing plasma FGF23 could be independent targets to reduce the risk of hypertension in the general population

Effect of sodium bicarbonate supplementation on the renin-angiotensin system in patients with chronic kidney disease and acidosis:a randomized clinical trial

Background Acidosis-induced kidney injury is mediated by the intrarenal renin-angiotensin system, for which urinary renin is a potential marker. Therefore, we hypothesized that sodium bicarbonate supplementation reduces urinary renin excretion in patients with chronic kidney disease (CKD) and metabolic acidosis. Methods Patients with CKD stage G4 and plasma bicarbonate 15-24 mmol/l were randomized to receive sodium bicarbonate (3 x 1000 mg/day, similar to 0.5 mEq/kg), sodium chloride (2 x 1,00 mg/day), or no treatment for 4 weeks (n = 15/arm). The effects on urinary renin excretion (primary outcome), other plasma and urine parameters of the renin-angiotensin system, endothelin-1, and proteinuria were analyzed. Results Forty-five patients were included (62 +/- 15 years, eGFR 21 +/- 5 ml/min/1.73m(2), plasma bicarbonate 21.7 +/- 3.3 mmol/l). Sodium bicarbonate supplementation increased plasma bicarbonate (20.8 to 23.8 mmol/l) and reduced urinary ammonium excretion (15 to 8 mmol/day, both P <0.05). Furthermore, a trend towards lower plasma aldosterone (291 to 204 ng/L, P = 0.07) and potassium (5.1 to 4.8 mmol/l, P = 0.06) was observed in patients receiving sodium bicarbonate. Sodium bicarbonate did not significantly change the urinary excretion of renin, angiotensinogen, aldosterone, endothelin-1, albumin, or alpha 1-microglobulin. Sodium chloride supplementation reduced plasma renin (166 to 122 ng/L), and increased the urinary excretions of angiotensinogen, albumin, and alpha 1-microglobulin (all P <0.05). Conclusions Despite correction of acidosis and reduction in urinary ammonium excretion, sodium bicarbonate supplementation did not improve urinary markers of the renin-angiotensin system, endothelin-1, or proteinuria. Possible explanations include bicarbonate dose, short treatment time, or the inability of urinary renin to reflect intrarenal renin-angiotensin system activity

Vascular remodeling and intimal hyperplasia in a novel murine model of arteriovenous fistula failure

ObjectiveThe arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient outward remodeling and intimal hyperplasia (IH) formation from which the exact mechanism is largely unknown. A suitable animal model is of vital importance in the unraveling of the underlying pathophysiology. However, current murine models of AVF failure do not incorporate the surgical configuration that is commonly used in humans. Because the hemodynamic profile is one of the key determinants that play a role in vascular remodeling in the AVF, it is preferable to use this same configuration in an animal model. Here we describe a novel murine model of AVF failure in which the configuration (end-to-side) is similar to what is most frequently performed in humans.MethodsAn AVF was created in 45 C57BL/6 mice by anastomosing the end of a branch of the external jugular vein to the side of the common carotid artery with interrupted sutures. The AVFs were harvested and analyzed histologically at days 7, 14, and 28. Identical veins of unoperated-on mice served as controls. Intravenous near-infrared fluorescent fluorophores were used to assess the patency of the fistula.ResultsThe patency rates at days 7, 14, and 28 days were 88%, 90%, and 50%, respectively. The mean circumference increased up to day 14, with a maximum 1.4-fold increase at day 7 compared with the control group (1.82 ± 0.7 vs 1.33 ± 0.3 mm; P = .443). Between days 14 and 28, the circumference remained constant (2.36 ± 0.2 vs 2.45 ± 0.2 mm; P = .996). At 7 days after surgery, the intimal area consisted mainly of an acellular layer that was structurally analogous to a focal adherent thrombus. Starting at 14 days after surgery, venous IH increased significantly compared with the unoperated-on group (14 days: 115,090 ± 22,594 μm2, 28 days: 234,619 ± 47,828 μm2, unoperated group: 2368 ± 1056 μm2; P = .001 and P < .001, respectively) and was mainly composed of cells positive for α-smooth muscle actin. We observed leukocytes in the adventitial side of the vein at all time points.ConclusionsOur novel murine AVF model, which incorporates a clinically relevant configuration of the anastomosis, displays similar features that are characteristic of failing human AVFs. Moreover, our findings suggest that coagulation and inflammation could both potentially play an important role in the formation of IH and subsequent AVF failure. Near-infrared fluoroscopy was a suitable alternative for conventional imaging techniques. This murine AVF-model is a valuable addition to the AVF animal model arsenal.Clinical RelevanceThe autologous arteriovenous fistula is considered the preferred choice for vascular access in hemodialysis. However, this type of vascular access suffers from a high failure rate, of which the exact pathophysiology is poorly understood. The use of a clinically relevant murine model provides us with a tool to unravel the pathophysiology and also to develop new therapeutic strategies that can improve the patency of the arteriovenous fistula in hemodialysis patients

Societal Innovation: between dream and reality lies complexity

Jan Rotmans (1961) is one of the founders of Integrated Assessment (IA), and has outstanding experience in IA modeling, scenario-building, uncertainty management and transition management. During the past twenty years he has led a diversity of innovative projects in the field of climate change, global change, sustainable development and transitions and system innovations. He is founder and director of the International Centre for Integrative Studies (ICIS) (1998) at Maastricht University. Since 2004 he is a full professor in Transitions and Transition Management at Erasmus University Rotterdam in the Netherlands, where he founded the DRIFT-institute: Dutch Research Institute For Transitions. He is vice-president of The Integrated Assessment Society (TIAS), and founder and director of the Dutch Knowledge Network on System Innovations and Transitions (KSI). Jan Rotmans is founder of two scientific journals, Environmental Modeling and Assessment and Integrated Assessment, and has published ten books and more than 150 peer-reviewed scientific articles in journals and books in the fields of environment, sustainability, governance, transitions and system innovations.There are no easy, off-the-shelf solutions for persistent societal problems, because these are caused by fundamental flaws in our societal systems. Such systemic errors demand radical changes in our thinking and actions, i.e. transitions and system innovations. Transitions require a long period (one to two generations), and take time, patience, money, confidence, but also courage, daring and perseverance to gain the upper hand over various types of resistance. Research into transitions is by definition multidisciplinary and interdisciplinary. For this we need knowledge and experience from systems analysis, social administration, history, innovation science, economics, business administration and technology. The nature of research into transitions is fundamental, explorative, creative and practical. A conceptual framework for research into transitions is presented that consists of four interlinked conceptual building blocks, which in turn provide an outline of a transition theory in its embryonic stages. These concepts are rooted in common notions from complexity theory, new forms of governance and social theory. Central here is the concept of transition management, for which a new management framework is developed. Transition management is an attempt to tackle persistent stubborn problems by steering them in a more sustainable direction, through a visionary, cyclical process of putting issues on the agenda, learning, orchestrating and experimenting. Not based on management and control but through clever, subtle changes and adjustments at several levels concurrently. Transition management is a very promising management concept that can initially be applied to a wide range of complex societal problems: from health care to energy provision, and from social security to mobility. Transition management can also be applied to complex processes of change in a business context.Voor hardnekkige maatschappelijke problemen bestaan geen pasklare oplossingen. Deze zijn het gevolg van weeffouten in onze maatschappelijke stelsels. Deze systeemfouten vergen radicale veranderingen in ons denken en handelen: transities en systeeminnovaties. Transities vergen een lange periode (1 à 2 generaties), en kosten tijd, geduld, geld, vertrouwen, maar ook moed, durf en doorzettingsvermogen om verschillende soorten weerstand te overwinnen. Onderzoek naar transities is per definitie multi-en interdisciplinair, waarbij kennis nodig is vanuit de systeemkunde, bestuurskunde, geschiedenis, innovatiewetenschappen, economie, bedrijfskunde en techniek. Transitieonderzoek is zowel fundamenteel, exploratief, ontwerpend en praktisch van aard. Een conceptueel kader voor transitieonderzoek wordt gepresenteerd, dat bestaat uit een viertal samenhangende conceptuele bouwstenen, die de contouren vormen van een transitietheorie in wording. Deze concepten zijn geworteld in gemeenschappelijke noties uit de complexiteitstheorie, nieuwe vormen van governance en de sociale theorie. Centraal hierin staat het concept van transitiemanagement, waarvoor een nieuw sturingsraamwerk is ontwikkeld. Transitiemanagement beoogt hardnekkige problemen bij te sturen in een meer duurzame richting, via een visionair, cyclisch proces van agenderen, leren, instrumenteren en experimenteren. Niet op basis van controle en beheersing, maar via slim, subtiel schakelen en bijsturen op meerdere niveaus. Transitiemanagement is een veelbelovend sturingsconcept wat in beginsel toepasbaar is op tal van complexe maatschappelijke problemen: van gezondheidszorg tot energievoorziening, en van sociale zekerheid tot mobiliteit. Ook in de bedrijfscontext kan transitiemanagement worden toegepast op complexe veranderingsprocessen

Contribution of bone marrow-derived cells to in situ engineered tissue capsules in a rat model of chronic kidney disease

Nephrolog

A novel method for engineering autologous non-thrombogenic in situ tissue-engineered blood vessels for arteriovenous grafting

The durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue engineered blood vessels (TEBVs) might offer a tailor-made autologous alternative for prosthetic grafts. We have designed a method in which TEBVs are grown in vivo, by utilizing the foreign body response to subcutaneously implanted polymeric rods in goats, resulting in the formation of an autologous fibrocellular tissue capsule (TC). One month after implantation, the polymeric rod is extracted, whereupon TCs (length 6 cm, diameter 6.8 mm) were grafted as arteriovenous conduit between the carotid artery and jugular vein of the same goats. At time of grafting, the TCs were shown to have sufficient mechanical strength in terms of bursting pressure (2382 +/- 129 mmHg), and suture retention strength (SRS: 1.97 +/- 0.49 N). The AV grafts were harvested at 1 or 2 months after grafting. In an ex vivo whole blood perfusion system, the lumen of the vascular grafts was shown to be less thrombogenic compared to the initial TCs and ePTFE grafts. At 8 weeks after grafting, the entire graft was covered with an endothelial layer and abundant elastin expression was present throughout the graft. Patency at 1 and 2 months was comparable with ePTFE AV-grafts. In conclusion, we demonstrate the remodeling capacity of cellularized in vivo engineered TEBVs, and their potential as autologous alternative for prosthetic vascular grafts.Vascular Surger