Iohexol plasma clearance measurement protocol standardization for adults: a consensus paper of the European Kidney Function Consortium.

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation.

[SGLT2 inhibitors for heart and kidney]. / SGLT2-Inhibitoren für Herz und Niere.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors can block glucose reabsorption in the proximal tubule and thus play an important role in glycemic control in diabetes mellitus. In addition to glucosuric effects, surprisingly very extensive other positive effects were observed in chronic renal dysfunction and strong cardioprotective effects in heart failure. In the meantime, numerous mechanisms have been identified apart from the pure sugar-influencing effect of the SGLT2 inhibitors, which can have a direct positive influence heart and kidneys.In recent years there has been an extensive clinical study program, which has dealt with the effects of SGLT2 inhibitors on the progression of diabetic and non-diabetic chronic renal failure. It could be shown that patients with albuminuria have a significant benefit from the use of SGLT2 inhibitors. Therefore, the progression of renal dysfunction is slowed down significantly, while at the same time, positive cardiovascular endpoints could be influenced. Numerous studies have also been conducted in patients with and without diabetes or with heart failure, with and without, preserved ejection fraction. Impressive protection was also shown here, with the benefit of using SGLT2 inhibitors to reduce heart failure worsening.In a short period of 10 years, the use of SGLT2 inhibitors was established as an essential therapy for cardio-renal indications to inhibit the progression of renal failure as well as to protect against heart failure apart from pure diabetes therapy. In numerous guidelines (ESC heart failure, KDGIO diabetes, ESH hypertension), the early use of SGLT2 inhibitors is now recommended for protection against cardio-renal events and is an important first-line addition to the previously established therapies. Apart from diabetes therapy, it offers patients completely new options in cardio-renal protection.

Incidence of hospital-acquired acute kidney injury and trajectories of glomerular filtration rate in older adults.

BACKGROUND: In older adults, epidemiological data on incidence rates (IR) of hospital-acquired acute kidney injury (AKI) are scarce. Also, little is known about trajectories of kidney function before hospitalization with AKI. METHODS: We used data from biennial face-to-face study visits from the prospective Berlin Initiative Study (BIS) including community-dwelling participants aged 70+ with repeat estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. Primary outcome was first incident of hospital-acquired AKI assessed through linked insurance claims data. In a nested case-control study, kidney function decline prior to hospitalization with and without AKI was investigated using eGFR trajectories estimated with mixed-effects models adjusted for traditional cardiovascular comorbidities. RESULTS: Out of 2020 study participants (52.9% women; mean age 80.4 years) without prior AKI, 383 developed a first incident AKI, 1518 were hospitalized without AKI, and 119 were never hospitalized during a median follow-up of 8.8 years. IR per 1000 person years for hospital-acquired AKI was 26.8 (95% confidence interval (CI): 24.1-29.6); higher for men than women (33.9 (29.5-38.7) vs. 21.2 (18.1-24.6)). IR (CI) were lowest for persons aged 70-75 (13.1; 10.0-16.8) and highest for ≥ 90 years (54.6; 40.0-72.9). eGFR trajectories declined more steeply in men and women with AKI compared to men and women without AKI years before hospitalization. These differences in eGFR trajectories remained after adjustment for traditional comorbidities. CONCLUSION: AKI is a frequent in-hospital complication in individuals aged 70 + showing a striking increase of IR with age. eGFR decline was steeper in elderly patients with AKI compared to elderly patients without AKI years prior to hospitalization emphasising the need for long-term kidney function monitoring pre-admission to improve risk stratification.

[The new recommendations for hypertension therapy]. / Die neuen Empfehlungen zur Hypertonietherapie.

The new guidelines of the European Society of Hypertension (ESH) are a milestone for the improved care of patients with hypertension. The aim was to provide a comprehensive guide and a detailed description of uncomplicated but also complicated hypertension with its comorbidities for everyday practice. Numerous new aspects were added, and clinical situations were also described and recommendations for action were given. The most important general aspects of practical high-pressure diagnostics, prognosis assessment, and basic treatment with the blood pressure goals, as well as follow-up care are presented in the overview.

Association of kidney function and albuminuria with frailty worsening and death in very old adults.

BACKGROUND AND OBJECTIVES: Studies analysing the association of albuminuria and prevalent frailty in community-dwelling very old adults are scarce and lack information on incident frailty. We investigated the association of kidney function decline and increase of albuminuria with frailty worsening or death in very old adults. DESIGN: Longitudinal analyses with biennial visits of the Berlin Initiative (cohort) Study and a frailty follow-up of 2.1 years. SETTING/SUBJECTS: 1,076 participants with a mean age of 84.3 (5.6) years of whom 54% were female. METHODS: Partial proportional odds models were used to assess the association of estimated glomerular filtration rate (eGFR) decline and/or albuminuria (albumin creatinine ratio, ACR) with frailty worsening or death. RESULTS: At frailty baseline, 1,076 participants with an eGFR of 50 (13) ml/min/1.73 m2, 48% being prefrail and 31% frail were included. After median 2.1 years, 960 (90%) participants had valid information on frailty transition: 187 (17.5%) worsened and 111 (10.3%) died. In the multivariable model, the odds of frailty worsening for participants with albuminuria in combination with eGFR <60 ml/min/1.73 m2 were elevated [OR (95% CI): 2.47 (1.41-4.31)] compared to participants without albuminuria and eGFR ≥60 ml/min/1.73 m2 as there was a rapid eGFR decline of ≥3 ml/min/1.73 m2 per year [1.55 (1.04-2.33)] and albuminuria trajectories six years prior [1.53 (1.11-2.10)] to frailty baseline. The odds of death for each exposure were even higher. CONCLUSIONS: In older adults, advanced stages of CKD and albuminuria alone were associated with 2-fold odds of frailty worsening independent of death.

Biomechanical Properties of the Aortic Wall: Changes during Vascular Calcification.

Medial vascular calcification (MAC) is characterized by the deposition of hydroxyapatite (HAP) in the medial layer of the vessel wall, leading to disruption of vessel integrity and vascular stiffness. Because currently no direct therapeutic interventions for MAC are available, studying the MAC pathogenesis is of high research interest. Several methods exist to measure and describe the pathophysiological processes in the vessel wall, such as histological staining and gene expression. However, no method describing the physiological properties of the arterial wall is currently available. This study aims to close that gap and validate a method to measure the biomechanical properties of the arterial wall during vascular calcification. Therefore, a stress-stretch curve is monitored using small-vessel-myography upon ex vivo calcification of rat aortic tissue. The measurement of biomechanical properties could help to gain further insights into vessel integrity during calcification progression.

[Blood pressure goals in chronic kidney disease : What is the optimal blood pressure for inhibition of progression and risk reduction?] / Blutdruckzielwerte bei eingeschränkter Nierenfunktion : Was ist der optimale Blutdruck zur Progressionshemmung und Risikoreduktion?

Well-controlled blood pressure is an essential factor in inhibiting the progression of renal failure and also in controlling cardiovascular mortality and morbidity. For decades there has been an intensive search for the optimal blood pressure target values in order to reduce the progression of renal insufficiency to a physiological level as far as possible. In the last few decades, very different target blood pressure values have been defined, which time and again contribute more to confusion than clarity in everyday clinical practice. The present work considers the relevant guidelines; it analyzes the basis on which the sometimes widely varying guidelines were created. All guidelines agree that blood pressure control with a target of less than 140 mm Hg systolic should be achieved in patients with impaired renal function. The European guidelines recommend aiming for a target of 130-140 mm Hg systolic. The American guidelines go one step further and specify a systolic blood pressure target of less than 130 mm Hg. The Kidney Disease: Improving Global Outcomes (KDIGO) organization is even more ambitious. It recommends a blood pressure target of less than 120 mm Hg, whereby in contrast to the European and American guidelines, the level of evidence required in the guidelines is considered to be very weak and the goals should also be achieved if automated, standardized blood pressure measurement is carried out, which is rarely available in everyday practice and may not be feasible. The present overview discusses the arguments for lowering blood pressure with different goals and presents the evidence. Of course, the blood pressure goals in the presence or absence of albuminuria should also be considered.

Molecular Imaging and Quantification of Smooth Muscle Cell and Aortic Tissue Calcification In Vitro and Ex Vivo with a Fluorescent Hydroxyapatite-Specific Probe.

Vessel calcification is characterized by the precipitation of hydroxyapatite (HAP) in the vasculature. Currently, no causal therapy exists to reduce or prevent vessel calcification. Studying the underlying pathways within vascular smooth muscle cells and testing pharmacological intervention is a major challenge in the vascular research field. This study aims to establish a rapid and efficient working protocol for specific HAP detection in cells and tissue using the synthetic bisphosphonate fluorescence dye OsteoSense™. This protocol facilitates especially early quantification of the fluorescence signal and permits co-staining with other markers of interest, enabling smaller experimental set-ups with lesser primary cells consumption and fast workflows. The fluorescence-based detection of vascular calcification with OsteoSense™ combines a high specificity with improved sensitivity. Therefore, this methodology can improve research of the pathogenesis of vascular calcification, especially for testing the therapeutic benefit of inhibitors in the case of in vitro and ex vivo settings.

Uremic mouse model to study vascular calcification and "inflamm-aging".

Calcification and chronic inflammation of the vascular wall is a high-risk factor for cardiovascular mortality, especially in patients with chronic uremia. For the reduction or prevention of rapid disease progression, no specific treatment options are currently available. This study aimed to evaluate an adenine-based uremic mouse model for studying medial vessel calcification and senescence-associated secretory phenotype (SASP) changes of aortic tissue to unravel molecular pathogenesis and provide a model for therapy testing. The dietary adenine administration induced a stable and similar degree of chronic uremia in DBA2/N mice with an increase of uremia blood markers such as blood urea nitrogen, calcium, creatinine, alkaline phosphatase, and parathyroid hormone. Also, renal fibrosis and crystal deposits were detected upon adenine feeding. The uremic condition is related to a moderate to severe medial vessel calcification and subsequent elastin disorganization. In addition, expression of osteogenic markers as Bmp-2 and its transcription factor Sox-9 as well as p21 as senescence marker were increased in uremic mice compared to controls. Pro-inflammatory uremic proteins such as serum amyloid A, interleukin (Il)-1ß, and Il-6 increased. This novel model of chronic uremia provides a simple method for investigation of signaling pathways in vascular inflammation and calcification and therefore offers an experimental basis for the development of potential therapeutic intervention studies.