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Background and aim of the study In hemodialysis patients, sedentarism is a potentially modifiable mortality risk factor. We explored whether healthcare staff’s attitude towards exercise interacts with patient-perceived barriers in modifying the level of physical activity in this population. Methods In this prospective, cross-sectional, multicenter study we recruited 608 adult patients and 330 members of the healthcare staff in 16 hemodialysis units in Italy. We assessed patient-perceived barriers to, and healthcare staff’s attitude towards, exercise by specific questionnaires. We fitted multilevel linear models to analyze the relationships of either barriers or staff’s attitude, and their interaction, with a measure of patient self-reported physical activity (the Human Activity Profile–Adjusted Activity Score [HAP-AAS]), adjusting for multiple confounders. We also employed latent class analysis to dichotomize patients into those endorsing or not endorsing barriers. Results Most barriers were negatively associated with the HAP-AAS (adjusted change attributable to a given barrier ranging between -5.1 [“Feeling too old”, 95% Confidence Interval: -9.4 to -0.8] and -15.6 [“Ulcers on legs and feet”, 95%CI: -24.8 to -6.5]. We found a significant interaction between staff’s attitude and barriers (adjusted P values ranging between 0.03 [“I do not believe that it is physician’s or nurse’s role providing advice on exercise to patients on dialysis”] and 0.001 [“I do not often ask patients about exercise”]). A beneficial effect of a proactive staff’s attitude was evident only in patients not endorsing barriers. Conclusions Barriers and non-proactive staff’s attitude reduce physical activity in hemodialysis patients. Patients not endorsing barriers benefit the most from a proactive staff’s attitude.

Whereas the adequate intake of potassium is relatively high in healthy adults, i.e., 4.7 g per day, a dietary potassium restriction of usually less than 3 g per day is recommended in the management of patients with reduced kidney function, especially those who tend to develop hyperkalaemia including patients who are treated with angiotensin pathway modulators. Most potassium-rich foods are considered heart-healthy nutrients with high fibre, high anti-oxidant vitamins and high alkali content such as fresh fruits and vegetables; hence, the main challenge of dietary potassium management is to maintain high fibre intake and a low net fixed-acid load, because constipation and metabolic acidosis are per se major risk factors for hyperkalaemia. To achieve a careful reduction of dietary potassium load without a decrease in alkali or fibre intake, we recommend the implementation of certain pragmatic dietary interventions as follows: Improving knowledge and education about the type of foods with excess potassium (per serving or per unit of weight); identifying foods that are needed for healthy nutrition in renal patients; classification of foods based on their potassium content normalized per unit of dietary fibre; education about the use of cooking procedures (such as boiling) in order to achieve effective potassium reduction before eating; and attention to hidden sources of potassium, in particular additives in preserved foods and low-sodium salt substitutes. The present paper aims to review dietary potassium handling and gives information about practical approaches to limit potassium load in chronic kidney disease patients at risk of hyperkalaemia.

Background Arterial hypertension is very common in chronic kidney disease (CKD) patients and its prevalence increases with lowering estimated glomerular filtration rate (eGFR). Blood pressure (BP) control is a cornerstone in the treatment of CKD patients but still most treatment decisions are based on office BP measurement (OBPM). The aim of this cross-sectional, retrospective study is to investigate the prevalence of hypertension phenotypes in CKD patients and whether different home (HBPM) or OBPM are associated with a different CKD stage and cardiovascular comorbidities. Methods We analyzed 560 consecutive patients (359 men, age 70±13 years), affected by stage 3-5 CKD, who performed HBPM recording; OBPM during a single visit was also assessed. Uncontrolled hypertension was defined as OBPM values ≥140/90 mmHg and HBPM values ≥135/85 mmHg, respectively. Results Systolic and diastolic HBPM values were lower than OBPM values. A white coat effect (systolic BP +18±12 mmHg) was detected in 62.5%, while a masked effect (systolic BP -14±10 mmHg) was detected in 22.7%. No relationship was found between BP differences and body weight, CKD stage, eGFR or presence of diabetes. Based on OBPM, 18.6% of patients showed controlled systolic and diastolic BP, whereas 37.8% had sustained hypertension. White-coat hypertension was detected in 23.4% and Masked hypertension in 12.1%. The multiple logistic regression model showed that masked uncontrolled hypertensive patients showed a higher probability of having ischemic heart disease (OR=2.54 [1.02-6.36]), while sustained hypertension was associated with an increased prevalence of stroke in comparison to normotensive or true control BP group (OR=4.72 [1.30-17.07]). Age, gender, diabetes or CKD stage, were not different among the four hypertension phenotypes. Conclusions We observed a quite high rate of masked uncontrolled hypertension and of white coat hypertension in stage 3-5ND CKD patients. Office BP measurement, as a single tool, is an inadequate diagnostic procedure in the clinical management of CKD patients. HBPM should be routinely implemented for identifying hypertensive phenotypes and then for avoiding misdiagnosis and mistreatment of pre-dialysis CKD patients in a tertiary care setting.

Human phosphate (P) homeostasis includes regulation of intestinal absorption from diet, bone turnover, and urinary excretion, and it is regulated by the combined actions of parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D (calcitriol), and fibroblast growth factor 23; the kidney threshold

In chronic kidney disease (CKD), cardiovascular (CV) damage is present in parallel which leads to an increased risk of CV disease. Both traditional and non-traditional risk factors contribute to CV damage in CKD. The systemic role of the microbiota as a central player in the pathophysiology of many organs is progressively emerging in the literature: the microbiota is indeed involved in a complex, bi-directional network between many organs, including the kidney and heart connection, although many of these relationships still need to be elucidated through in-depth mechanistic studies. The aim of this review is to provide evidence that microbiota metabolites influence non-traditional risk factors, such as inflammation and endothelial dysfunction in CKD-associated CV damage. Here, we report our current understanding and hypotheses on the gut-kidney and gut-heart axes and provide details on the potential mechanisms mediated by microbial metabolites. More specifically, we summarize some novel hypotheses linking the microbiota to blood pressure regulation and hypertension. We also emphasise the idea that the nutritional management of CKD should be redesigned and include the new findings from research on the intrinsic plasticity of the microbiota and its metabolites in response to food intake. The need is felt to integrate the classical salt and protein restriction approach for CKD patients with foods that enhance intestinal wellness. Finally, we discuss the new perspectives, especially the importance of taking care of the microbiota in order to prevent the risk of developing CKD and hypertension, as well as the still not tested but very promising CKD innovative treatments, such as postbiotic supplementation and bacteriotherapy. This interesting area of research offers potential complementary approaches to the management of CKD and CV damage assuming that the causal mechanisms underlying the gut-kidney and gut-heart axes are clarified. This will pave the way to the design of new personalized therapies targeting gut microbiota.

CKD-related nutritional therapy (NT) is a crucial cornerstone of CKD patients' treatment, but the role of NT has not been clearly investigated in autosomal dominant polycystic kidney disease (ADPKD). Several clinical studies have focused on new pharmacological approaches to delay cystic disease progression, but there are no data on dietary interventions in ADPKD patients. The aim of this paper is to analyze the evidence from the literature on the impact of five nutritional aspects (water, sodium, phosphorus, protein intake, and net acid load) in CKD-related ADPKD extrapolating-where information is unavailable-from what occurs in CKD non-ADPKD patients Sodium intake restriction could be useful in decreasing the growth rate of cysts. Although further evidence is needed, restriction of phosphorus and protein intake restriction represent cornerstones of the dietary support of renal non-ADPKD patients and common sense can guide their use. It could be also helpful to limit animal protein, increasing fruit and vegetables intake together with a full correction of metabolic acidosis. Finally, fluid intake may be recommended in the early stages of the disease, although it is not to be prescribed in the presence of moderate to severe reduction of renal function.

Adamasco Cupisti, Valentina Vigo, Maria Enrica Baronti, Claudia D'Alessandro, Lorenzo Ghiadoni, Maria Francesca Egidi Nephrology, Transplant and Dialysis Division, AOUP, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Abstract: This study investigated the factors associated with hypovitaminosis D, in a cohort of 405 prevalent patients with chronic kidney disease (CKD) stages 2–4, living in Italy and followed-up in tertiary care. The effect of cholecalciferol 10,000 IU once-a-week for 12 months was evaluated in a subgroup of 100 consecutive patients with hypovitaminosis D. Vitamin D deficiency was observed in 269 patients (66.4%) whereas vitamin D insufficiency was found in 67 patients (16.5%). In diabetic patients, 25-hydroxyvitamin D deficiency was detected in 80% of cases. In patients older than 65 years, the prevalence of hypovitaminosis D was 89%. In the univariate analysis, 25-hydroxyvitamin D was negatively related to age, parathyroid hormone (PTH), proteinuria, and Charlson index, while a positive relationship has emerged with hemoglobin level. On multiple regression analysis, only age and PTH levels were independently associated with 25-hydroxyvitamin D levels. No relationship emerged between vitamin D deficiency and renal function. Serum levels of 25-hydroxyvitamin D or prevalence of hypovitaminosis D did not differ between patients on a free-choice diet and on a renal diet, including low-protein, low-phosphorus regimens. Twelve-month oral cholecalciferol administration increased 25-hydroxyvitamin D and reduced PTH serum levels. In summary, hypovitaminosis D is very prevalent in CKD patients (83%) in Italy, and it is similar to other locations. PTH serum levels and age, but not renal function, are the major correlates of hypovitaminosis D. Implementation of renal diets is not associated with higher risk of vitamin D depletion. Oral cholecalciferol administration increased 25-hydroxyvitamin D and mildly reduced PTH serum levels. Oral cholecalciferol supplementation should be recommended as a regular practice in CKD patients, also when serum 25-hydroxyvitamin D determination is not available or feasible. Keywords: CKD, vitamin D, cholecalciferol, calcifediol, hypovitaminosis, PTH, renal disease, CKD-MBD

Introduction: Delayed childbearing is increasing, and advanced maternal age has been associated with an increased risk of obstetrical complications. The purpose of this study was to evaluate pregnancy outcomes in women with advanced maternal age (≥ 40 years). Methods: Maternal and obstetrical data were collected from the Department of Obstetrics and Gynecology of the University of Wuerzburg for the period from 2006 to 2011. In this retrospective analysis we compared the outcomes for women aged ≥ 40 years (n = 405) with those of three younger subgroups (I

In the general population, moderate exercise is associated with several health benefits including a decreased risk of obesity, coronary heart disease, stroke, certain types of cancer and all-cause mortality. In chronic kidney disease (CKD), physical inability is an independent risk of death. Health benefits of regular exercise in CKD patients include improvements in functional and psychological measures such as aerobic and walking capacity and health-related quality of life. Nonetheless, in CKD patients exercise rehabilitation is not routinely prescribed. Renal patients are heterogeneous across the different stages of CKD so that the assessment of physical capability is mandatory for a correct exercise program prescription. To plan appropriate exercise programs in the CKD setting, targeted professional figures should be actively involved as many psychological or logistic barriers may hamper exercise implementation in these subjects. Different approaches, such as home exercise rehabilitation programs, supervised exercise training or in-hospital gym may theoretically be proposed. However, physical exercise should always be tailored to the individual capacity and comorbidities and each patient should ideally be involved in the decision-making process.

Background Nutritional treatment has always represented a major feature of CKD management. Over the decades, the use of nutritional treatment in CKD patients has been marked by several goals. The first of these include the attainment of metabolic and fluid control together with the prevention and correction of signs, symptoms and complications of advanced CKD. The aim of this first stage is the prevention of malnutrition and a delay in the commencement of dialysis. Subsequently, nutritional manipulations have also been applied in association with other therapeutic interventions in an attempt to control several cardiovascular risk factors associated with CKD and to improve the patient's overall outcome. Over time and in reference to multiple aims, the modalities of nutritional treatment have been focused not only on protein intake but also on other nutrients. Discussion This paper describes the pathophysiological basis and rationale of nutritional treatment in CKD and also provides a report on extensive experience in the field of renal diets in Italy, with special attention given to approaches in clinical practice and management. Summary Italian nephrologists have a longstanding tradition in implementing low protein diets in the treatment of CKD patients, with the principle objective of alleviating uremic symptoms, improving nutritional status and also a possibility of slowing down the progression of CKD or delaying the start of dialysis. A renewed interest in this field is based on the aim of implementing a wider nutritional therapy other than only reducing the protein intake, paying careful attention to factors such as energy intake, the quality of proteins and phosphate and sodium intakes, making today’s low-protein diet program much more ambitious than previous. The motivation was the reduction in progression of renal insufficiency through reduction of proteinuria, a better control of blood pressure values and also through correction of metabolic acidosis. One major goal of the flexible and innovative Italian approach to the low-protein diet in CKD patients is the improvement of patient adherence, a crucial factor in the successful implementation of a low-protein diet program.

In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians.

Hintergrund und Ziele In Deutschland soll die tatsachliche Anzahl der Schwangerschaftsabbruche einschlieslich der Dunkelziffer jahrlich uber 200.000 liegen. Bei den legalen Schwangerschaftsabbruchen kommen medikamentose und operative Verfahren zum Einsatz. Es ist anzunehmen, dass diese Verfahren auch bei den illegal durchgefuhrten Schwangerschaftsabbruchen eingesetzt werden. Historisch kamen diverse andere, nicht-medikamentose Substanzen zum Einsatz. Bisher liegen keine neuzeitlichen Berichte vor uber Schwangerschaftsabbruche durch den gezielten illegalen Einsatz von Medikamenten mit anderem Indikationsspektrum. Methode In zwei Kasuistiken wird eine schwere Marcumarintoxikation in der Schwangerschaft geschildert. Es werden die aktuellen legalen und die historischen Moglichkeiten der Abtreibung sowie ihre Komplikationen bis zur Entwicklung des heutigen §218 des Strafgesetzbuches skizziert. Ergebnisse Nach Ausschlus anderer Ursachen ergab sich in beiden Fallen der Verdacht auf eine vorsatzliche Einnahme von Marcumar durch die Schwangere selbst mit der mutmaslichen Absicht der Abtreibung. Vor dem historischen Hintergrund erscheint der in den Kasuistiken geschilderte Versuch der Abtreibung durch Marcumar als eine neuzeitliche auserlegale Selbstabtreibung durch die Schwangere mit einem nicht zu diesem Zweck bestimmten Wirkstoff mit betrachtlicher Komplikationsgefahr. Schlusfolgerung Arztlicherseits sollte man in gegebener klinischer Konstellation an diese Differentialdiagnose denken.

Renal diets for advanced chronic kidney disease (CKD) are structured to achieve a lower protein, phosphate and sodium intake, while supplying adequate energy. The aim of this nutritional intervention is to prevent or correct signs, symptoms and complications of renal insufficiency, delaying the start of dialysis and preserving nutritional status. This paper focuses on three additional aspects of renal diets that can play an important role in the management of CKD patients: the vitamin K1 and fiber content, and the alkalizing potential. We examined the energy and nutrients composition of four types of renal diets according to their protein content: normal diet (ND, 0.8 g protein/kg body weight (bw)), low protein diet (LPD, 0.6 g protein/kg bw), vegan diet (VD, 0.7 g protein/kg bw), very low protein diet (VLPD, 0.3 g protein/kg bw). Fiber content is much higher in the VD and in the VLPD than in the ND or LPD. Vitamin K1 content seems to follow the same trend, but vitamin K2 content, which could not be investigated, might have a different pattern. The net endogenous acid production (NEAP) value decreases from the ND and LPD to the vegetarian diets, namely VD and VLPD; the same finding occurred for the potential renal acid load (PRAL). In conclusion, renal diets may provide additional benefits, and this is the case of vegetarian diets. Namely, VD and VLPD also provide high amounts of fibers and Vitamin K1, with a very low acid load. These features may have favorable effects on Vitamin K1 status, intestinal microbiota and acid-base balance. Hence, we can speculate as to the potential beneficial effects on vascular calcification and bone disease, on protein metabolism, on colonic environment and circulating levels of microbial-derived uremic toxins. In the case of vegetarian diets, attention must be paid to serum potassium levels.

Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.

Background This study aimed to evaluate the prevalence of sedentarism, and to assess physical capacity and nutritional status in a cohort of older patients on peritoneal dialysis (PD), with respect to age-matched non-dialysis CKD population, using highly accessible, simple methods, namely the Rapid Assessment of Physical activity (RAPA) test and the 30″ Sit-to-stand (STS) test. Methods This cross-sectional multicenter study included 151 renal patients older than 60 years; 71 pts. (44 m, age 72 ± 7 yrs) were on PD and 80 pts. (63 m, age 74 ± 7 yrs) were affected by 3–4 stage CKD. Results The prevalence of sedentary/underactive patients was double of that of the active patients as assessed by RAPA test, both in the PD (65.3%) and in the CKD (67.5%) cohort. The 30"STS test showed a reduced physical performance in both groups: 84.5% of PD patients and 87.5% of CKD patients did not reach the expected number of stands by age and gender. A malnutrition-inflammation score (MIS) ≥ 6 occurred in 37 % of PD patients and in 2.5 % of CKD patients. In PD patients, an independent significant association was observed between 30”STS test and MIS (beta -0.510, p = 0.013), as well as between RAPA and MIS (beta -0.544, p = 003) and phase angle (beta -0.506, p = 0.028). Conclusions A high prevalence of low- performance capacity and sedentarism has been detected among elderly patients on PD or with CKD stage 3–4. Apart from age, a condition of malnutrition-inflammation was the major determinant of poor physical activity and capacity in PD patients. Better body composition seems to be positively associated with physical activity in PD and with physical capacity in CKD patients. Routine clinical management should include a close evaluation of nutritional status and evaluation of physical activity and capacity which can be easily assessed by RAPA and 30″STS tests.