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      Low-protein diets for chronic kidney disease patients: the Italian experience


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          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.


          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.


          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.

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          Evidence on the Chronic Care Model in the new millennium.

          Developed more than a decade ago, the Chronic Care Model (CCM) is a widely adopted approach to improving ambulatory care that has guided clinical quality initiatives in the United States and around the world. We examine the evidence of the CCM's effectiveness by reviewing articles published since 2000 that used one of five key CCM papers as a reference. Accumulated evidence appears to support the CCM as an integrated framework to guide practice redesign. Although work remains to be done in areas such as cost-effectiveness, these studies suggest that redesigning care using the CCM leads to improved patient care and better health outcomes.
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            Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients.

            As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients. One-hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled. Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 +/- 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification. The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
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              Timing of onset of CKD-related metabolic complications.

              Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.

                Author and article information

                +39 089 672881-83 , vincenzo.bellizzi@tin.it
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                11 July 2016
                11 July 2016
                : 17
                : 77
                [ ]Nephrology Unit, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Via San Leonardo, 84131 Salerno, Italy
                [ ]Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
                [ ]Nephrology Department, Alessandro Manzoni Hospital, Lecco, Italy
                [ ]Territorial Department of Nephrology and Dialysis, ASL Cagliari, Italy
                [ ]Nephrology Unit, Santa Chiara Hospital, Trento, Italy
                [ ]O.U. Nephrology, A.O. Spedali Civili Brescia and University of Brescia, Brescia, Italy
                [ ]Nephrology Division, Second University of Naples, Naples, Italy
                [ ]Nephrology Unit, Landolfi Hospital, Solofra (AV), Italy
                [ ]Pathophysiology of Renal Failure Unit, University of Parma, Parma, Italy
                [ ]Nephrology Unit, University of Genoa and IRCCS A.O.U. San Martino IST, Genoa, Italy
                [ ]Nephrology and Dialysis Unit, Ospedale S. Maria della Scaletta, Imola (BO), Italy
                [ ]O.U. Nephrology and Dialysis, Fracastoro Hospital, San Bonifacio (VR), Italy
                [ ]Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
                [ ]Nephrologie, CH Le Mans, Le Mans France, Italy
                [ ]O.U. Nephrology, Dialysis and Transplantation, Santa Maria della Misericordia Hospital, Udine, Italy
                [ ]Perugia Department of Internal Medicine, University of Messina, Messina, Italy
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                : 23 January 2016
                : 14 June 2016
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