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Renal anemia is a frequently encountered complication in patients suffering from advanced chronic kidney disease. This is mainly due to the decreased secretion of erythropoietin by the diseased kidneys. The current treatment of renal anemia is based on iron substitution and administration of recombinant erythropoietin. The discovery of HIF (Hypoxia-Inducible Factor) has led to the development of a new class of molecules that block the activity of prolyl-4-hydroxylases and stabilize HIF (Hypoxia-Inducible Factor), a transcription factor that plays an essential role in numerous cellular pathways, including those linked to erythropoiesis and iron metabolism. In this article, we discuss the current understanding of the pathophysiological mechanisms underlying renal anemia and the potential role of the new HIF-stabilizers in its treatment.

Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90 th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value-16 ). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

BackgroundChronic dialysis patients are classified as patients with increased risk for COVID-19. Knowledge about the incidence and survival of chronic dialysis patients infected with SARS-CoV-2 in Switzerland - a high-income country with high density of relatively small dialysis centers - is scarce. We present the findings regarding incidence, survival and regional differences, compared to those of the general population in Switzerland.MethodsInformation on chronic dialysis patients who tested positive for SARS-CoV-2 between February 24, 2020 and February 28, 2022 were reported to the Swiss dialysis registry by all 94 Swiss dialysis centers. Hereafter, these results were linked with clinical characteristics from the Swiss dialysis registry.ResultsThroughout the study period 1,120 out of ~4,700 dialysis patients tested positive for SARS-CoV-2 in Switzerland: 96 cases occurred in the first wave, 472 in the second wave and 5 in between. During the first wave, Italian-speaking Ticino was most severely affected, with a 7-fold higher incidence of dialysis patients compared to the general Swiss population. In the second wave, the majority of cases were found in the French-speaking part of Switzerland, with a 2.5 times higher incidence vs. non-dialysis patients. A total of 123 deaths were recorded in the first two waves, of which COVID-19 was the main cause of death in 100 patients. This corresponds to a highly increased overall mortality rate of 17.5% compared to 1.7% in the general population. Age was identified as the only risk factor for mortality in dialysis patients. During the third, fourth and fifth wave, 61, 43 and 443 cases, respectively, were recorded, resulting in 6 (mortality rate 9.8%), 1 (mortality rate 2.3%) and 13 deaths (mortality rate 2.9%).ConclusionChronic dialysis patients in Switzerland were more likely to be infected by SARS-CoV-2 during the first and second wave than the rest of the population, but an inverse trend was observed during the third, fourth and fifth wave, probably thanks to vaccination. In addition, mortality is significantly increased compared to non-dialysis patients. In Swiss dialysis patients, age is the strongest risk factor for death.

The kidneys play a central role in the regulation of blood pressure and are also one of the main culprits of arterial hypertension (HT). Renal ultrasound is a valuable diagnostic tool that can provide instant information at the bedside on possible underlying causes and consequences of HT. Its role in the screening for renal artery stenosis is well-known. However, renal ultrasound can also detect abnormalities in renal parenchyma, morphology, or the vascularization of the kidneys, and as such directly influence further diagnostic work-up and treatment. The significance of the renal resistive index and the place of renal ultrasound in the latest international guidelines on HT are reviewed in this article.

During the actual pandemic of COVID-19, it has become clear that the virus causing this devastating disease, SARS-CoV2, targets not only the lungs but also other organs. In this article, we discuss the known or suspected interactions between the virus and the kidneys, as well as their clinical presentations. We also discuss how the pandemic has altered the activities of nephrologists and the logistics of a Swiss dialysis center.

Peritoneal dialysis (PD) has often been considered as a renal replacement method that is not feasible for the elderly population. Numerous recent studies have shown that this method is in fact very well, if not better tolerated by elderly patients. In Switzerland and abroad, its economic advantages have also been underlined during the past ten years. As a consequence, the use of PD is increasing, and primary care physicians are more often confronted to PD patients. Therefore, they have to be aware of some basic treatment principles, which are reviewed in this article.

Over the last decades, an increasing number of cases of chronic and end-stage kidney disease has been observed in Central America and Asia. This kidney disease mainly affects young farmers without classic renal risk factors. The clinical presentation includes a progressive decrease of the glomerular filtration rate, minimal proteinuria and the presence of tubulo-interstitial nephritis at renal biopsy. A close link with global warming is suspected for this disease, called (according to its location) meso-american nephropathy, Sri Lanka nephropathy or chronic kidney disease of unknown etiology. Others have suggested that intake of water contaminated with pesticides may be responsible. This article provides an overview of this new kidney disease. Measures to prevent acute kidney injury during heat waves in Switzerland are also discussed.

Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action 'Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease' (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally we investigate the extent to which AL is genetically determined. We included 803 participants (52 women mean age 48±16years) from a population and family based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular metabolic lipidic oxidative hypothalamus pituitary adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status stress alcohol intake smoking dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99 95CI [1.22;13.05]) while the opposite was observed for men (middle vs. high OR=0.48 95CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54 95CI [1.69;7.4]/OR=1.59 95CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5 ±7.9. Our results suggest that generalized physiological dysregulation as measured by AL is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component which explains approximately 70 of the phenotypic variance.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD the gene coding for uromodulin are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown and were therefore explored in this study. DESIGN SETTING PARTICIPANTS MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD 45±17 years) who underwent renal ultrasonography and performed a 24 hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD Epidemiology Collaboration formula and by 24 hour creatinine clearance. RESULTS: In both studies positive associations were found between uromodulin and urinary sodium chloride and potassium excretion and osmolality. In SKIPOGH 24 hour uromodulin excretion (median 41 [interquartile range 29 57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24 hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR

European Society of Hypertension/European Society of Cardiology guidelines recommend calculation of estimated glomerular filtration rate and evaluation of urinary albumin excretion rate as routine tests in the initial evaluation and during the follow-up of all hypertensive patients. However, from a clinical point of view, renal ultrasound-a noninvasive, readily available and cheap imaging modality-could contribute to the better evaluation of a hypertensive patient by identifying common causes of secondary hypertension (HTN) originating from the kidney and more recently by detecting renal injury in severe or long-standing essential HTN by measuring renal resistive indexes. The purpose of this review is to summarize the actual evidence which could support a larger use of renal ultrasound in the work-up of patients with newly diagnosed HTN. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin an established surrogate for AVP with parameters of renal function and morphology in a multicentric population based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L respectively (P

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP known as desphospho uncarboxylated MGP (dp ucMGP) can be measured in plasma and has been associated with various cardiovascular markers cardiovascular outcomes and mortality. In this study we hypothesized that high levels of dp ucMGP are associated with increased PWV. We recruited participants via a multicenter family based cross sectional study in Switzerland. Dp ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp ucMGP adjusting for age renal function and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp ucMGP. PWV was positively associated with dp ucMGP both before and after adjustment for sex age body mass index height systolic and diastolic blood pressure (BP) heart rate renal function low and high density lipoprotein glucose smoking status diabetes mellitus BP and cholesterol lowering drugs and history of cardiovascular disease (P=0.01). In conclusion high levels of dp ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors renal function and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

The goal of this study was to investigate the effect of sodium intake on renal tissue oxygenation in humans. To this purpose we measured renal hemodynamics renal sodium handling and renal oxygenation in normotensive (NT) and hypertensive (HT) subjects after 1 week of a high sodium and 1 week of a low sodium diet. Renal oxygenation was measured using blood oxygen level dependent magnetic resonance. Tissue oxygenation was determined by the measurement of R2 maps on 4 coronal slices covering both kidneys. The mean R2 values in the medulla and cortex were calculated with a low R2 indicating a high tissue oxygenation. Ten male NT (mean age: 26.5+/ 7.4 years) and 8 matched HT subjects (mean age: 28.8+/ 5.7 years) were studied. Cortical R2 was not different under the 2 conditions of salt intake. Medullary R2 was significantly lower under low sodium than high sodium in both NT and HT subjects (28.1+/ 0.8 versus 31.3+/ 0.6 s( 1); P

BOLD-MRI (blood oxygenation-level dependent magnetic resonance imaging) allows non-invasive measurement of renal tissue oxygenation in humans, without the need for contrast products. BOLD-MRI uses the fact that magnetic properties of hemoglobin depend of its oxygenated state:: the higher local deoxyhemoglobin, the higher the so called apparent relaxation rate R2(*) (sec(-1)), and the lower local tissue oxygen content. Several factors other than deoxyhemoglobin (such as hydration status, dietary sodium intake, and susceptibility effects) influence the BOLD signal, and need to be taken into account when interpreting results. The last 5 years have witnessed important improvements in the standardization of these factors, and the appearance of new, highly reproducible analysis techniques of BOLD-images, that are reviewed in this article. Using these new BOLD-MRI analysis techniques, it has recently been shown that persons suffering from chronic kidney diseases (CKD) have lower cortical oxygenation than normotensive controls, thus confirming the chronic hypoxia hypothesis. The acute alterations in R2(*) after the administration of furosemide are smaller in CKD, and represent an estimate of the oxygen-dependent tubular transport of sodium. BOLD-MRI-alone or in combination with other functional MRI methods- can be used to monitor the renal effects of drugs, and is increasingly used in the preclinical setting. The near future will tell whether or not BOLD-MRI represents a new tool to predict renal function decline an adverse renal outcome.

Hypertension and chronic kidney disease (CKD) are complex traits representing major global health problems. Multiple genome-wide association studies have identified common variants in the promoter of the UMOD gene, which encodes uromodulin, the major protein secreted in normal urine, that cause independent susceptibility to CKD and hypertension. Despite compelling genetic evidence for the association between UMOD risk variants and disease susceptibility in the general population, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants increased UMOD expression in vitro and in vivo. Uromodulin overexpression in transgenic mice led to salt-sensitive hypertension and to the presence of age-dependent renal lesions similar to those observed in elderly individuals homozygous for UMOD promoter risk variants. The link between uromodulin and hypertension is due to activation of the renal sodium cotransporter NKCC2. We demonstrated the relevance of this mechanism in humans by showing that pharmacological inhibition of NKCC2 was more effective in lowering blood pressure in hypertensive patients who are homozygous for UMOD promoter risk variants than in other hypertensive patients. Our findings link genetic susceptibility to hypertension and CKD to the level of uromodulin expression and uromodulin's effect on salt reabsorption in the kidney. These findings point to uromodulin as a therapeutic target for lowering blood pressure and preserving renal function.

Poor long-term adherence and persistence to drug therapy is universally recognized as one of the major clinical issues in the management of chronic diseases, and patients with renal diseases are also concerned by this important phenomenon. Chronic kidney disease (CKD) patients belong to the group of subjects with one of the highest burdens of daily pill intake with up to >20 pills per day depending on the severity of their disease. The purpose of the present review is to discuss the difficulties encountered by nephrologists in diagnosing and managing poor adherence and persistence in CKD patients including in patients receiving maintenance dialysis. Our review will also attempt to provide some clues and new perspectives on how drug adherence could actually be addressed and possibly improved. Working on drug adherence may look like a long and tedious path, but physicians and healthcare providers should always be aware that drug adherence is in general much lower than what they may think and that there are many ways to improve and support drug adherence and persistence so that renal patients obtain the full benefits of their treatments.