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The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3–4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = −0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.

Background and objectives For older patients with kidney failure, lowering symptom burden may be more important than prolonging life. Dialysis initiation may affect individual kidney failure-related symptoms differently, but the change in symptoms before and after start of dialysis has not been studied. Therefore, we investigated the course of total and individual symptom number and burden before and after starting dialysis in older patients.Design, setting, participants, & measurements The European Quality (EQUAL) study is an ongoing, prospective, multicenter study in patients >= 65 years with an incident eGFR

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Background Dry weight assessment in hemodialysis (HD) remains a challenge. The aim of the study was to investigate the prevalence of subclinical pulmonary congestion using lung ultrasound (LUS) in maintenance HD patients with no clinical or bioimpedance signs of hyperhydration. The correlation between B-lines Score (BLS) and brain natriuretic peptide (BNP) was also evaluated. Methods Twenty-four HD patients underwent LUS and BNP dosage at the end of the mid-week HD session, monthly for 6 months . LUS was considered as positive when BLS was >15. Hospitalizations and cardiovascular events were also evaluated in relation to the BLS. Results LUS+ patients at baseline were 16 (67%), whereas 11 (46%) showed LUS + in at least 50% of the measurements (rLUS+ patients). Only the rLUS+ patients had a higher number of cardiovascular events [p=0.019, OR: 7.4 (CI 95%. 1.32-39.8)] and hospitalizations [p=0.034, OR 5.5 (CI 95% 1.22- 24.89)]. A BNP level of 165 pg/ml was identified as cut-off value for predicting pulmonary congestion, defined by BLS >15. Conclusion Prevalence of pulmonary congestion as assessed by LUS and persistent or recurrent BLS >15 were quite prevalent findings in euvolemic HD patients. In the patients defined as rLUS+, a higher rate of cardiovascular events and hospital admissions was registered. BNP serum levels > 165 pg/ml resulted predictive of pulmonary congestion at LUS. In the dialysis care, regular LUS examination should be reasonably included among the methods useful to detect subclinical lung congestion and to adjust patients’ dry weight.

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

The correct management of energy intake is crucial in CKD (chronic kidney disease) patients to limit the risk of protein energy wasting especially during low-protein regimes, but also to prevent overweight/obesity. The aim of this study was to assess the energy requirement of older CKD patients using objective measurements. This cross-sectional study enrolled 67 patients (aged 60–86 years) with CKD stages 3–5 not on dialysis, all of whom were metabolically and nutritionally stable. All patients underwent indirect calorimetry and measurement of daily physical activity level expressed by the average daily Metabolic Equivalent Task, using an accelerometer, in order to measure total energy expenditure (mTEE). Estimated TEE (eTEE) was derived from predictive equations for resting energy expenditure and physical activity levels coefficients. The mTEE were lower than eTEE-based on Harris–Benedict or Schofield or Mifflin equations (1689 ± 523 vs. 2320 ± 434 or 2357 ± 410 or 2237 ± 375 Kcal, p &lt, 0.001, respectively). On average mTEE was 36.5% lower than eTEE. When eTEE was recalculated using ideal body weight the gap between mTEE and eTEE was reduced to 26.3%. A high prevalence of a sedentary lifestyle and reduced physical capabilities were also detected. In conclusion, our data support the energy intake of 25–35 Kcal/Kg/d recently proposed by the NKF-KDOQI (National Kidney Foundation-Kidney Disease Improving Quality Initiative) guidelines on nutritional treatment of CKD, which seem to be more adequate and applicable than that of previous guidelines (30–35 Kcal/Kg/d) in elderly stable CKD patients with a sedentary lifestyle. According to our findings we believe that an energy intake even lower than 25 Kcal/Kg/d may be adequate in metabolically stable, elderly CKD patients with a sedentary lifestyle.

Muscle wasting is a frequent finding in patients with chronic kidney disease (CKD), especially in those with end-stage kidney disease (ESKD) on chronic dialysis. Muscle wasting in CKD is a main feature of malnutrition, and results principally from a vast array of metabolic derangements typical of the syndrome, that converge in determining reduced protein synthesis and accelerated protein catabolism. In this clinical setting, muscle wasting is also frequently associated with disability, frailty, infections, depression, worsened quality of life and increased mortality. On these grounds, the evaluation of nutritional status is crucial for an adequate management of renal patients, and consists of a comprehensive assessment allowing for the identification of malnourished patients and patients at nutritional risk. It is based essentially on the assessment of the extent and trend of body weight loss, as well as of spontaneous dietary intake. Another key component of this evaluation is the determination of body composition, which, depending on the selected method among several ones available, can identify accurately patients with decreased muscle mass. The choice will depend on the availability and ease of application of a specific technique in clinical practice based on local experience, staff resources and good repeatability over time. Surrogate methods, such as anthropometry and bioimpedance analysis (BIA), represent the most readily available techniques. Other methods based on imaging modalities [dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and whole body computed tomography (CT)] are considered to be the "gold standard" reference methods for muscle mass evaluation, but their use is mainly confined to research purposes. New imaging modalities, such as segmental CT scan and muscle ultrasound have been proposed in recent years. Particularly, ultrasound is a promising technique in this field, as it is commonly available for bedside evaluation of renal patients in nephrology wards. However, more data are needed before a routine use of ultrasound for muscle mass evaluation can be recommended in clinical practice.

Dialysis and nutrition are two sides of the same coin—dialysis depurates metabolic waste that is typically produced by food intake. Hence, dietetic restrictions are commonly imposed in order to limit potassium and phosphate and avoid fluid overload. Conversely, malnutrition is a major challenge and, albeit to differing degrees, all nutritional markers are associated with survival. Dialysis-related malnutrition has a multifactorial origin related to uremic syndrome and comorbidities but also to dialysis treatment. Both an insufficient dialysis dose and excessive removal are contributing factors. It is thus not surprising that dialysis alone, without proper nutritional management, often fails to be effective in combatting malnutrition. While composite indexes can be used to identify patients with poor prognosis, none is fully satisfactory, and the definitions of malnutrition and protein energy wasting are still controversial. Furthermore, most nutritional markers and interventions were assessed in hemodialysis patients, while hemodiafiltration and peritoneal dialysis have been less extensively studied. The significant loss of albumin in these two dialysis modalities makes it extremely difficult to interpret common markers and scores. Despite these problems, hemodialysis sessions represent a valuable opportunity to monitor nutritional status and prescribe nutritional interventions, and several approaches have been tried. In this concept paper, we review the current evidence on intradialytic nutrition and propose an algorithm for adapting nutritional interventions to individual patients.

In the almost 30 years that have passed since the postulation of the “Developmental Origins of Health and Disease” theory, it has been clearly demonstrated that a mother’s dietary habits during pregnancy have potential consequences for her offspring that go far beyond in utero development. Protein malnutrition during pregnancy, for instance, can cause severe alterations ranging from intrauterine growth retardation to organ damage and increased susceptibility to hypertension, diabetes mellitus, cardiovascular diseases and chronic kidney disease (CKD) later in life both in experimental animals and humans. Conversely, a balanced mild protein restriction in patients affected by CKD has been shown to mitigate the biochemical derangements associated with kidney disease and even slow its progression. The first reports on the management of pregnant CKD women with a moderately protein-restricted plant-based diet appeared in the literature a few years ago. Today, this approach is still being debated, as is the optimal source of protein during gestation in CKD. The aim of this report is to critically review the available literature on the topic, focusing on the similarities and differences between animal and clinical studies.

BackgroundConcerns about adherence and quality of life (QoL) limit the diffusion of low-protein diets (LPDs) as a way to slow chronic kidney disease (CKD) progression and postpone dialysis. The aim of this multicentre study is to assess dietary satisfaction in stable CKD patients.MethodsThis was a multicentre cross-sectional study with long-term follow-up data. Prevalent patients on LPD for at least 6 months were selected in four Italian centres. QoL was assessed using the World Health Organization Quality of Life questionnaire, and diet satisfaction with the Modification of Diet in Renal Disease satisfaction questionnaire. Comorbidity was assessed by Charlson Comorbidity Index, estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation and protein intake by Maroni–Mitch formula. Survival was analysed with Kaplan–Meier curves and Cox Proportional Hazard Model.ResultsFour hundred and twenty-two CKD Stages 3–5 patients were enrolled. Over 95% were on moderately restricted diets (0.6 g/kg/day). Compliance was good (protein intake: 0.59 g/kg/day at baseline, 0.72 at the end of follow-up). Median dietary satisfaction was 4 on a 1–5 scale. QoL was not affected by the type of diet, but was influenced by age, comorbidity and setting of care. Two years later, at the end of follow-up, 66.6% of the patients were still on a diet; the main causes of discontinuation were dialysis and death. The dropout rate was low (5.5%); in Cox analysis, patient and renal survival were influenced by age and eGFR, but not by QoL, setting of care or type of diet.ConclusionsLPDs are compatible with high dietary satisfaction and minimal dropout, at least in patients who are able to follow such a diet for at least 6 months.

Hyperkalemia (HK) is a frequent complication of chronic kidney disease (CKD). Vegetable-based renal diets are considered at risk due to the high potassium (K) content. The aim of this study was to describe the prevalence and correlates of chronic hyperkalemia (HK) in CKD patients on nutritional care, and in particular, the risk of HK in patients on plant-based versus animal-based low-protein diets. We recruited adult patients affected by CKD not on dialysis, afferent to our renal nutrition clinic from November 2014 to May 2019. We evaluated a total of 870 accesses in 219 patients (172 m, 47 f, age 67 ± 13 years). HK was defined as mild when K serum level was 5.1–5.9 mEq/l, moderate when K serum level was 6.0–6.9 mEq/l, and severe HK when K serum level was ≥ 7 mEq/l. Biochemical, anthropometric data and medications were recorded. The prevalence of HK in all the renal nutrition visits was 26.1%; all but six cases were mild HK, whereas no severe HK was observed. The prevalence of HK was associated with decreased eGFR, up to 36.5% for eGFR

Kidney stone disease should be viewed as a systemic disorder, associated with or predictive of hypertension, insulin resistance, chronic kidney disease and cardiovascular damage. Dietary and lifestyle changes represent an important strategy for the prevention of kidney stone recurrences and cardiovascular damage. A full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, yet it is rarely performed outside of stone specialist clinics. Many patients have a history of kidney stone disease while lacking a satisfactory metabolic profile. Nonetheless, in a real-world clinical practice a rational management of kidney stone patients is still possible. Different scenarios, with different types of dietary approaches based on diagnosis accuracy level can be envisaged. The aim of this review is to give patient-tailored dietary suggestions whatever the level of clinical and biochemistry evaluation. This can help to deliver a useful recommendation, while avoiding excessive dietary restrictions especially when they are not based on a specific diagnosis, and therefore potentially useless or even harmful. We focused our attention on calcium stones and the different scenarios we may find in the daily clinical practice, including the case of patients who reported renal colic episodes and/or passed stones with no information on stone composition, urinary risk factors or metabolic cardiovascular risk factors; or the case of patients with partial and incomplete information; or the case of patients with full information on stone composition, urinary risk factors and metabolic cardiovascular profile.

Background: Sarcopenia is a widespread concern in chronic kidney disease (CKD) as well in elderly patients and is one of the main reasons why low-protein diets for this population are controversial. The aim of this study was to assess the prevalence and correlates of sarcopenia among elderly male patients affected by CKD followed up in an outpatient nephrology clinic, where moderate protein restriction (0.6&ndash, 0.8 g/Kg/day) is routinely recommended to patients in CKD stage 3b-5 not on dialysis. Methods: This observational study included 80 clinically-stable male out-patients aged &gt, 60, affected by stage 3b-4 CKD. Forty patients aged &ge, 75 (older seniors) were compared to the other forty patients aged 60&ndash, 74 (younger seniors). All patients underwent a comprehensive nutritional and functional assessment. Results: Older seniors showed lower serum albumin, hand-grip strength, body mass index (BMI), skeletal muscle mass, and resting energy expenditure. Protein intake was significantly lower in older seniors whereas energy intake was similar. Average daily physical activity was lower in the older seniors than in the younger ones. Sarcopenia was more prevalent in older than in younger seniors. Among older seniors, sarcopenic and non-sarcopenic ones differed in age and performance on the Six-Minute Walk test, whereas the estimated glomerular filtration rate (eGFR), biochemistry, dietary protein, and energy intakes were similar. Conclusions: Older senior CKD male patients have lower muscle mass, muscle strength, and physical capacity and activity levels, with a higher prevalence of sarcopenia than younger patients. This occurs at the same residual renal function and metabolic profile and protein intake. Energy intake was at the target in both subgroups. In this CKD cohort, sarcopenia was associated with age and physical capacity, but not with eGFR or dietary intakes.

The Italian nephrology has a long tradition and experience in the field of dietetic-nutritional therapy (DNT), which is an important component in the conservative management of the patient suffering from a chronic kidney disease, which precedes and integrates the pharmacological therapies. The objectives of DNT include the maintenance of an optimal nutritional status, the prevention and/or correction of signs, symptoms and complications of chronic renal failure and, possibly, the delay in starting of dialysis. The DNT includes modulation of protein intake, adequacy of caloric intake, control of sodium and potassium intake, and reduction of phosphorus intake. For all dietary-nutritional therapies, and in particular those aimed at the patient with chronic renal failure, the problem of patient adherence to the dietetic-nutritional scheme is a key element for the success and safety of the DNT and it can be favored by an interdisciplinary and multi-professional approach of information, education, dietary prescription and follow-up. This consensus document, which defines twenty essential points of the nutritional approach to patients with advanced chronic renal failure, has been written, discussed and shared by the Italian nephrologists together with representatives of dietitians (ANDID) and patients (ANED).

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.

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.

Background & aims Vitamin K acts as a coenzyme in the γ-carboxylation of vitamin K-dependent proteins, including coagulation factors, osteocalcin, matrix Gla protein (MGP), and the growth arrest-specific 6 (GAS6) protein. Osteocalcin is a key factor for bone matrix formation. MGP is a local inhibitor of soft tissue calcification. GAS6 activity prevents the apoptosis of vascular smooth muscle cells. Few data on vitamin K intake in chronic kidney disease patients and no data in patients on a Mediterranean diet are available. In the present study, we evaluate the dietary intake of vitamin K1 in a cohort of patients undergoing haemodialysis. Methods In this multi-centre controlled observational study, data were collected from 91 patients aged >18 years on dialysis treatment for at least 12 months and from 85 age-matched control subjects with normal renal function. Participants completed a food journal of seven consecutive days for the estimation of dietary intakes of macro- and micro-nutrients (minerals and vitamins). Results Compared to controls, dialysis patients had a significant lower total energy intake, along with a lower dietary intake of proteins, fats, carbohydrates, fibres, and of all the examined minerals (Ca, P, Fe, Na, K, Zn, Cu, and Mg). With the exception of vitamin B12, vitamins intake followed a similar pattern, with a lower intake in vitamin A, B1, B2, C, D, E, folates, K1 and PP. These finding were confirmed also when normalized for total energy intake or for body weight. In respect to the adequate intakes recommended in the literature, the prevalence of a deficient vitamin K intake was very high (70–90%) and roughly double than in controls. Multivariate logistic model identified vitamin A and iron intake as predictors of vitamin K deficiency. Conclusions Haemodialysis patients had a significantly low intake in vitamin K1, which could contribute to increase the risk of bone fractures and vascular calcifications. Since the deficiency of vitamin K intake seems to be remarkable, dietary counselling to HD patients should also address the adequacy of vitamin K dietary intake and bioavailability. Whether diets with higher amounts of vitamin K1 or vitamin K supplementation can improve clinical outcomes in dialysis patients remains to be demonstrated. © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

This is a case report on a patient with non-dialysis chronic kidney disease (CKD) in whom several nutritional issues are briefly discussed from a practical point of view. The article is accompanied by an editorial published in this Journal in relation to the 2nd International Conference of the European Renal Nutrition working group at ERA-EDTA—“Retarding CKD progression: readily available through comprehensive nutritional management?”— and focuses on several practical topics associated with the nutritional approach for the conservative treatment of non-dialysis CKD. The article is divided into 3 sections—basic nutritional assessment, nutritional targets, and nutritional follow-up in non-dialysis CKD—linked to 3 consecutive steps of the clinical follow-up of the patient and the related nutritional concerns and intervention. First visit: Baseline nutritional assessment and basic nutritional considerations in non-dialysis chronic kidney disease (CKD) • What nutritional assessment/monitoring for protein-energy wasting (PEW) should be employed? • Is a body mass index (BMI) of 21 kg/m2 adequate? • What phosphate target should be pursued? • What are the nutritional habits in patients with incident CKD? • What protein needs and amount of dietary protein should be pursued? • Does the quality of protein matter? • What amount of dietary salt should be employed? How should this be obtained? • How should normal serum phosphate be achieved? • What diet should be recommended? Is a vegetarian diet an option? Second visit: Major nutritional targets in non-dialysis CKD • Consequences of unintentional weight loss • What is the role of the renal dietitian in helping the patient adhere to a renal diet? Intermediate visits: Nutritional follow-up in non-dialysis CKD • What treatment for calcium/parathyroid hormone (PTH) will affect CKD progression? Final visits: • Would a dietary recall/intensive dietary education improve adherence with the diet? • Would a very-low-protein diet (VLPD)/ketodiet be indicated for this patient?

Phosphorus retention plays a pivotal role in the onset of mineral and bone disorders (MBD) in chronic kidney disease (CKD). Phosphorus retention commonly occurs as a result of net intestinal absorption exceeding renal excretion or dialysis removal. The dietary phosphorus load is crucial since the early stages of CKD, throughout the whole course of the disease, up to dialysis-dependent end-stage renal disease. Agreement exits regarding the need for dietary phosphate control, but it is quite challenging in the real-life setting. Effective strategies to control dietary phosphorus intake include restricting phosphorus-rich foods, preferring phosphorus sourced from plant origin, boiling as the preferred cooking procedure and avoiding foods with phosphorus-containing additives. Nutritional education is crucial in this regard. Based on the existing literature, we developed the “phosphorus pyramid”, namely a novel, visual, user-friendly tool for the nutritional education of patients and health-care professionals. The pyramid consists of six levels in which foods are arranged on the basis of their phosphorus content, phosphorus to protein ratio and phosphorus bioavailability. Each has a colored edge (from green to red) that corresponds to recommended intake frequency, ranging from “unrestricted” to “avoid as much as possible”. The aim of the phosphorus pyramid is to support dietary counseling in order to reduce the phosphorus load, a crucial aspect of integrated CKD-MBD management.

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

BACKGROUND AND AIM Assessment of physical activity level and of energy expenditure is important in the clinical and nutritional care of dialysis patients, but it is not so easy to accomplish. The SenseWear™ Armband (SWA) is a novel multisensory device that is worn on the upper arm and collects a variety of physiologic data related to physical activity. Thus, duration and intensity of physical activity is recorded and expressed as METs (Metabolic Equivalent Task), and energy expenditure is estimated. The aim of our study was to assess interdialytic spontaneous physical activity in stable chronic hemodialysis (HD) patients and the relation to nutritional status and dietary nutrient intake. PATIENTS AND METHODS In 50 stable patients on maintenance hemodialysis treatment and 33 normal subjects (control group), level of spontaneous physical activity and estimated daily energy expenditure was assessed by SWA and related to biochemistry and anthropometry data, bioelectric impedance vector analysis, and energy and nutrient intake information coming from a 3-day food recall. RESULTS In respect to controls, HD patients showed lower mean daily METs value (1.3 ± 0.3 vs. 1.5 ± 0.2, p 3 METs (89 ± 85 vs. 143 ± 104 min/day, p < 0.05), lower number of steps per day (5,584 ± 3,734 vs. 11,735 ± 5,130, p < 0.001), resulting in a lower estimated energy expenditure (2,190 ± 629 vs. 2,462 ± 443 Kcal/day, p < 0.05). 31 out of the 50 HD patients (62%) had a mean daily value < 1.4 METs and hence were defined as sedentary. They differed from the active patients for higher age (63 ± 12 vs. 54 ± 12 y, p < 0.01), lower energy intake (26.1 ± 6.4 vs. 32.4 ± 11.3 Kcal/day, p < 0.05) and lower phase angle (5.5 ± 1.0 vs. 6.3 ± 0.9, p < 0.05). SWA-based estimation of daily energy expenditure was negatively related to age (r = -0.31, p < 0.05), whereas positive relations were observed with BMI (r = 0.51, p < 0.001), phase angle (r = 0.40, p < 0.01), serum phosphate (r = 0.49, p < 0.001) and albumin (r = 0.41, p < 0.01). The mean daily METs values were strongly related to normalized energy intake (r = 0.47, p < 0.001) and also to protein intake (r = 0.33, p < 0.05) and to phase angle (r = 0.38, p < 0.01). Multiple regression analysis showed that energy intake and dietary protein intake were independently related to the intensity of physical activity. CONCLUSION Our findings indicate that poor physical activity is highly prevalent in stable dialysis patients even when free from physical or neurological disabilities or severe comorbid conditions. The level and intensity of physical activity is positively related to body composition and to dietary nutrient intake. This confirms the strong interrelationship between exercise and nutrition, which in turn are associated with survival, rehabilitation and quality of life in dialysis patients.

The pathogenesis of CKD-MBD is multifactorial but the tendency towards phosphorus retention due to an excessive dietary intake for the residual renal function plays a central role. The dietary phosphorus is absorbed in the intestine as inorganic free phosphorus. The share of intestinal absorption (about 60% on average) is negligible for plant phosphorus (in the form of phytate), while it is maximal for phosphate or polyphosphates contained in food additives. The latter represent a dangerous extra load of phosphorus because they are poorly recognized by patients and widely used in modern nutrition, in particular in low-cost food. In a free mixed diet, the phosphorus content is directly related to that of proteins. It follows that protein-rich foods are the main source of phosphorus. This is a favorable condition for CKD patients in conservative therapy when a low-protein diet is implemented, while it represents a huge problem for dialysis patients, who need a high-protein diet. A simple and effective approach to reduce the load of dietary phosphorus without reducing protein intake is to educate patients to avoid foods high in phosphorus (cheese, egg yolk, nuts, etc.), and particularly those containing phosphorus additives. In addition, they should prefer boiling (resulting also in a decrease in sodium and potassium) to other methods of cooking. Counseling by a dietician is important for successful patient care. The dietician provides nutritional education, can help the patient with the choice of food, and may favor the adherence to dietary prescriptions, which is a crucial aspect in an integrated approach to CKD-MBD.

Restriction of dietary phosphorus is a major aspect of patient care in those with renal disease. Restriction of dietary phosphorus is necessary to control for phosphate balance during both conservative therapy and dialysis treatment. The extra amount of phosphorus which is consumed as a result of phosphate-containing food additives is a real challenge for patients with renal disease and for dieticians because it represents a "hidden" phosphate load. The objective of this study was to measure phosphorus content in foods, common protein sources in particular, and comprised both those which included a listing of phosphate additives and those which did not.Determinations of dry matter, nitrogen, total and soluble phosphate ions were carried out in 60 samples of foods, namely cooked ham, roast breast turkey, and roast breast chicken, of which, 30 were with declared phosphate additives and the other 30 similar items were without additives.Total phosphorus (290 ± 40 mg/100 g vs. 185 ± 23 mg/100 g, P.001) and soluble phosphorus (164 ± 25 mg/100 g vs. 100 ± 19 mg/100 g, P.001) content were higher in products containing additives than in foods without additives. No difference was detected between the 2 groups regarding dry matter (27.2 ± 2.0 g/100 g vs. 26.7 ± 1.9 g/100 g) or total nitrogen (3.15 ± 0.40 g/100 g vs. 3.19 ± 0.40 g/100 g). Consequently, phosphorus intake per gram of protein was much greater in the foods containing phosphorus additives (15.0 ± 3.1 mg/g vs. 9.3 ± 0.7 mg/g, P.001).Our results show that those foods which contain phosphate additives have a phosphorus content nearly 70% higher than the samples which did not contain additives. This creates a special concern because this extra amount of phosphorus is almost completely absorbed by the intestinal tract. These hidden phosphates worsen phosphate balance control and increase the need for phosphate binders and related costs. Information and educational programs are essential to make patients with renal disease aware of the existence of foods with phosphate additives. Moreover, these facts highlight the need for national and international authorities to devote more attention to food labels which should clearly report the amount of natural or added phosphorus.

Asymmetric dimethylarginine (ADMA)and symmetric dimethylarginine (SDMA) originate from hydrolysis of methylated proteins, including dietary proteins, and are retained in end-stage renal disease(ESRD). This study aimed to detect the correlation of ADMA and SDMA to nutritional parameters in dialysis patients.Before and after a single dialysis session, larginine, ADMA and SDMA plasma levels were measured in 38 hemodialysis patients by HPLC-tandem mass spectrometry. Biochemistry, protein intake, anthropometry and bioelectric impedance analysis were evaluated.Predialysis plasma levels of ADMA were higher than in normal controls (n=20) (1.14 +/- 0.27 mumol/Lvs. 0.56 +/- 0.09 mumol/L, p0.001), as were SDMA levels(3.49 +/- 1.00 mumol/L vs. 0.44 +/- 0.13 mumol/L, p0.001).On univariate analysis, predialysis ADMA levels were inversely related to BMI and albumin levels, whereas SDMA was directly related to nPNA, phase angle, prealbumin and creatinine serum levels. ADMA/SDMA ratio was inversely related to prealbumin and albumin, creatinine, urea and phosphorus serum levels, as wellas nPNA, but positively to C-reactive protein. On multiple regression analysis, serum albumin and BMI were the stronger predictors of ADMA, whereas prealbumin serum levels followed by dietary protein intake were the stronger predictors of SDMA. Prealbumin followed by C-reactive protein was predictive of the ADMA/SDMA molar ratio.Our results confirm that ADMA and SDMA levels are increased in ESRD patients and suggest that a link may exist with inflammation and nutritional status. High ADMA levels associated with reduced SDMA may be a predictive marker of malnutrition-inflammation-atherosclerosis syndrome.

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p

The aim of the present study was to evaluate the effect of a soy-protein diet on plasma lipid levels of renal transplant recipients with moderate hypercholesterolemia.Dietary intervention case-control observational study.Renal transplantation outpatient clinic.Fifteen stable patients who had renal transplantation (serum creatinine2 mg/dL) with moderate hypercholesterolemia (low-density lipoprotein [LDL] cholesterol140 mg/dL).After a baseline dietary interview, dietary counseling was given individually with the goal of substituting 25 g of animal protein with 25 g of soy protein for a 5-week period, using commercially available soy foods, according to each patient's own preference. Main outcome measures Before and after the soy-diet period, plasma lipid profiles including total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1 and B were determined. Protein catabolic rate was assumed as a measure of dietary protein intake.Two patients dropped out. After the soy diet, total cholesterol (254 +/- 22 to 231 +/- 31 mg/dL, P.05) and LDL cholesterol (165 +/- 20 versus 143 +/- 20 mg/dL, P.01) decreased significantly. No significant changes were observed regarding HDL cholesterol and triglycerides. Dietary protein intake did not differ at baseline (73.2 +/- 22.9 g/day) and during the soy diet (72.6 +/- 15.6 g/day), when the reported actual soy protein intake resulted 26 +/- 8 g/day.This study shows that soy proteins given as part of the daily protein intake have beneficial effects on serum LDL cholesterol levels of renal transplant recipients with moderate hypercholesterolemia. Soy proteins could be of use in the nutritional management of renal transplant recipients.

Telmisartan is a type 1 angiotensin II (AT(1)) receptor blocker, effective and safe in the treatment of arterial hypertension. However, data with respect to circadian blood pressure (BP) monitoring and urinary protein (uP) excretion are lacking in normotensive or mild hypertensive patients with chronic renal diseases. This study has evaluated the effects of 80 mg telmisartan, given as monotherapy, on 24 h BP levels and uP loss in 16 non-diabetic patients affected by proteinuric renal disease. These patients did not meet the recommended values of mean BP, i.e.98 mmHg, when proteinuria was 0.5-1.0 g/d and mean BP92 mmHg, when proteinuria was 1-3 g/d. Patients with diastolic BP114 mmHg, nephrotic syndrome or severe renal failure (creatinine clearance20 ml/min) were excluded. After 4.2 +/- 2.7 month therapy, ambulatory BP monitoring showed a significant decrease (P0.001) of 24 h BP levels: systolic 135 +/- 11 vs. 122 +/- 13 mmHg, diastolic 84.4 +/- 8.1 vs. 75.9 +/- 8.5 mmHg, mean 101 +/- 8 vs. 91 +/- 9 mmHg. The effect was quite evident during either day-time or night-time. Clinic BP levels also significantly decreased (P0.001), and five patients reached the target values. uP excretion lowered by 37% (median) from 1.60 +/- 0.90 to 1.06 +/- 0.63 g/24 h (P0.01). No change in creatinine clearance (53.3 +/- 31.1 vs. 51.7 +/- 30.9 ml/min) or serum potassium level (4.3 +/- 0.3 vs. 4.4 +/- 0.4 mEq/l) was observed. Our results show that 80 mg of telmisartan, taken once daily, is effective in reducing uP excretion and BP throughout the 24 h, in normotensive or mild hypertensive renal patients. Since evidence exists that adequate control of BP, including during night-time, and reduction of proteinuria play a crucial role in the protection of renal function, telmisartan can be usefully considered in the conservative treatment of renal patients.

Insulator elements can be functionally identified by their ability to shield promoters from regulators in a position-dependent manner or their ability to protect adjacent transgenes from position effects. We have previously reported the identification of a 265 bp sns DNA fragment at the 3' end of the sea urchin H2A early histone gene that blocked expression of a reporter gene in transgenic embryos when placed between the enhancer and the promoter. Here we show that sns interferes with enhancer-promoter interaction in a directional manner. When sns is placed between the H2A modulator and the inducible tet operator, the modulator is barred from interaction with the basal promoter. However, the tet activator (tTA) can still activate the promoter, even in the presence of sns, demonstrating that sns does not interfere with activity of a downstream enhancer. In addition, the H2A modulator can still drive expression of a divergently oriented transcription unit, suggesting that sns does not inhibit binding of transcription factor(s) to the enhancer. To identify cis-acting sequence elements within sns which are responsible for insulator activity, we have performed in vitro DNase I footprinting and EMSA analysis, and in vivo functional assays by microinjection into sea urchin embryos. We have identified three binding sites for protein complexes: a palindrome, a direct repeat, and a C+T sequence that corresponds to seven GAGA motifs on the transcribed strand. Insulator function requires all three cis-acting elements. Based on these results, we conclude that sns displays properties similar to the best characterized insulators and suggest that directional blocking of enhancer-activated transcription by sns depends on the assembly of distinct DNA-protein complexes. (C) 2000 Academic Press.

Dietary therapy represents an important tool in the management of chronic kidney disease (CKD), mainly through a balanced reduction of protein intake aimed at giving the remnant nephrons in damaged kidneys a “functional rest”. While dialysis, transplantation, and pharmacological therapies are usually seen as “high tech” medicine, non pharmacological interventions, including diets, are frequently considered lifestyle-complementary treatments. Diet is one of the oldest CKD treatments, and it is usually considered a part of “mainstream” management. In this narrative review we discuss how the lessons of complementary alternative medicines (CAMs) can be useful for the implementation and study of low-protein diets in CKD. While high tech medicine is mainly prescriptive, prescribing a “good” life-style change is usually not enough and comprehensive counselling is required; the empathic educational approach, on which CAMs are mainly, though not exclusively based, may support a successful personalized nutritional intervention. There is no gold-standard, low-protein diet for all CKD patients: from among a relatively vast choice, the best compliance is probably obtained by personalization. This approach interferes with the traditional RCT-based analyses which are grounded upon an assumption of equal preference of treatments (ideally blinded). Whole system approaches and narrative medicine, that are widely used in the study of CAMs, may offer ways to integrate EBM and personalised medicine in the search for innovative solutions respecting individualization, but gaining sound data, such as with partially-randomised patient preference trials.