The indications for delaying the start of dialysis have revived interest in low-protein diets (LPDs). In this observational prospective study, we enrolled all patients with chronic kidney disease (CKD) who followed a moderately restricted LPD in 2007–2015 in a nephrology unit in Italy: 449 patients, 847 years of observation. At the start of the diet, the median glomerular filtration rate (GFR) was 20 mL/min, the median age was 70, the median Charlson Index was 7. Standardized mortality rates for the “on-diet” population were significantly lower than for patients on dialysis (United States Renal Data System (USRDS): 0.44 (0.36–0.54); Italian Dialysis Registry: 0.73 (0.59–0.88); French Dialysis Registry 0.70 (0.57–0.85)). Considering only the follow-up at low GFR (≤15 mL/min), survival remained significantly higher than in the USRDS, and was equivalent to the Italian and French registries, with an advantage in younger patients. Below the e-GFR of 15 mL/min, 50% of the patients reached a dialysis-free follow-up of ≥2 years; 25% have been dialysis-free for five years. Considering an average yearly cost of about 50,000 Euros for dialysis and 1200 Euros for the diet, and different hypotheses of “spared” dialysis years, treating 100 patients on a moderately restricted LPD would allow saving one to four million Euros. Therefore, our study suggests that in patients with advanced CKD, moderately restricted LPDs may allow prolonging dialysis-free follow-up with comparable survival to dialysis at a lower cost.

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.

Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited.

There is no single, gold-standard, low-protein diet (LPD) for CKD patients; the best compliance is probably obtained by personalization. This study tests the hypothesis that a multiple choice diet network allows patients to attain a good compliance level, and that, in an open-choice system, overall results are not dependent upon the specific diet, but upon the clinical characteristics of the patients.

Low-protein diets (LPDs) are often considered as contraindicated in diabetic patients, and are seldom studied. The aim of this observational study was to provide new data on this issue. It involved 149 diabetic and 300 non-diabetic patients who followed a LPD, with a personalized approach aimed at moderate protein restriction (0.6 g/day). Survival analysis was performed according to Kaplan–Meier, and multivariate analysis with Cox model. Diabetic versus non-diabetic patients were of similar age (median 70 years) and creatinine levels at the start of the diet (2.78 mg/dL vs. 2.80 mg/dL). There was higher prevalence of nephrotic proteinuria in diabetic patients (27.52% vs. 13.67%, p = 0.002) as well as comorbidity (median Charlson index 8 vs. 6 p = 0.002). Patient survival was lower in diabetic patients, but differences levelled off considering only cases with Charlson index > 7, the only relevant covariate in Cox analysis. Dialysis-free survival was superimposable in the setting of good compliance (Mitch formula: 0.47 g/kg/day in both groups): about 50% of the cases remained dialysis-free 2 years after the first finding of e-GFR (estimated glomerular filtration rate) < 15 mL/min, and 1 year after reaching e-GFR < 10 mL/min. In patients with type 2 diabetes, higher proteinuria was associated with mortality and initiation of dialysis. In conclusion, moderately restricted LPDs allow similar results in diabetic and non non-diabetic patients with similar comorbidity.

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low‐flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start‐to‐end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca‐phosphate (P)‐parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. “Severe” secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8–2.1 m2), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca‐P‐PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start‐to‐end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in “severe” secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on “low‐flow” daily home dialysis, in “severe” secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.

Literature provides reports only of a limited follow-up single injection of botulinum toxin-A (BoNT-A) in patients with sialorrhea. The aim of our study is to evaluate the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for severe sialorrhea secondary to neurological dysphagia. We enrolled 38 severe adult sialorrhea patients referred consecutively to the neurology unit and performed bilateral parotid and submandibular gland BoNT-A injections under ultrasound guidance. The outcomes of the study were reduction of sialorrhea, duration of therapeutic effect, and subjective patient- and caregiver-reported satisfaction. A total of 113 BoNT-A administrations were given during the study period with a mean duration of follow-up of 20.2 ± 4.4 months. We observed a significant decrease from baseline in mean number of daily aspirations and a significant improvement in patient- and caregiver-reported outcomes following ultrasound-guided BoNT-A injections (p < 0.001 vs baseline for all comparisons) and the mean duration of the efficacy was 5.6 ± 1 months. No major treatment-related adverse events occurred and a low incidence of minor adverse events was reported. This study confirms the long-lasting efficacy and safety of ultrasound-guided BoNT-A injections for sialorrhea, regardless of the causative neurological disorder. These results should encourage the use of BoNT-A in the treatment of severe sialorrhea and highlight the role of ultrasound guidance to obtain optimal results in terms of safety and reproducible outcomes.

BackgroundAlthough vegan-vegetarian diets are increasingly popular, no recent systematic reviews on vegan-vegetarian diets in pregnancy exist.ObjectivesTo review the literature on vegan-vegetarian diets and pregnancy outcomes.Search strategyPubMed, Embase, and the Cochrane library were searched from inception to September2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms.Selection criteriaVegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan-vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate.Data collection and analysisThe high heterogeneity of the studies led to a narrative review.Main resultsWe obtained 262 full texts from 2329 references; 22 selected papers reporting maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan-vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitaminB12 and iron deficiencies.Author's conclusionsThe evidence on vegan-vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.

Low-protein diets (LPDs) have encountered various fortunes, and several questions remain open. No single study, including the famous Modification of Diet in Renal Disease, was conclusive and even if systematic reviews are in favour of protein restriction, at least in non-diabetic adults, implementation is lagging. LPDs are considered difficult, malnutrition is a threat and compliance is poor. LPDs have been reappraised in this era of reconsideration of dialysis indications and timing. The definition of a normal-adequate protein diet has shifted in the overall population from 1 to 1.2 to 0.8 g/kg/day. Vegan-vegetarian diets are increasingly widespread, thus setting the groundwork for easier integration of moderate protein restriction in Chronic Kidney Disease. There are four main moderately restricted LPDs (0.6 g/kg/day). Two of them require careful planning of quantity and quality of food: a 'traditional' one, with mixed proteins that works on the quantity and quality of food and a vegan one, which integrates grains and legumes. Two further options may be seen as a way to simplify LPDs while being on the safe side for malnutrition: adding supplements of essential amino and keto acids (various doses) allows an easier shift from omnivorous to vegan diets, while protein-free food intake allows for an increase in calories. Very-low-protein diets (vLPDs: 0.3 g/kg/day) combine both approaches and usually require higher doses of supplements. Moderately restricted LPDs may be adapted to virtually any cuisine and should be tailored to the patients' preferences, while vLPDs usually require trained, compliant patients; a broader offer of diet options may lead to more widespread use of LPDs, without competition among the various schemas.

UNLABELLED:Obesity is increasingly encountered in dialysis patients, who have difficulty to lose weight. Several Transplant Centres require BMI <30-35 Kg/m2 at waiting-list. Thus, losing weight becomes a must for young obese patients, however the best policy to obtain it (if any) is not defined. The aim of the present case report is to suggest that tailored dialysis and intensive diets could be a successful combination, that should be tested on a larger scale. A 56-year-old obese male patient (BMI 37.7 kg/m²) on daily home hemodialysis since 10 months (ESRD due to focal segmental glomerulosclerosis) started a coach-assisted qualitative ad libitum diet. The diet, alternating 8 weeks of rapid weight loss and maintenance phases, was based on a combinations of different foods, chosen on the account of glycaemic index and biochemical properties. It was salt free and olive oil was permitted in liberal quantities. Dialysis duration was increased to allow weight loss, and dialysate Na was incremented to permit a strict low sodium diet. Over a period of 21 months, the patient attained a -18.5 Kg weight loss (50% overweight loss; BMI -6.3 Kg/m²), reaching the goal to be included in a kidney transplant waiting list. Main metabolic data remained stable (pre diet and end of the diet period: albumin 3.5-3.8 g/dL; HCO3 26.1-24.8 mmol/L discontinuing citrate) or improved (haemoglobin 11.4-12.1 g/dL, halving EPO dose; calcium 2.3-2.5 mmol/L; phosphate 1.5-1.5 mmol/L; PTHi 1718-251 pg/mL, reducing chelation).CONCLUSION:Daily dialysis may allow enrolling obese hemodialysis patients in intensive weight loss programs, under strict clinical control.

Obesity is a growing problem on dialysis. The best approach to weight loss has not been established. The risks of malnutrition may offset the advantages of weight loss. Personalized hemodialysis schedules, with an incremental approach, are gaining interest; to date, no studies have explored its potential in allowing weight loss. This case series reports on combining flexible, incremental hemodialysis, and intensive weight loss. Setting: a small Dialysis Unit, following incremental personalized schedules (2–6 sessions/week, depending on residual function), tailored to an equivalent renal clearance >12 mL/min. Four obese and two overweigh patients (5 male, 1 female; age: 40–63 years; body mass index [BMI] 31.1 kg/m2) were enrolled in a coach‐assisted weight loss program, with an “ad libitum” approach (3–6 foods/day chosen on the basis of their glycemic index and glycemic load). The diet consists of 8 weeks of rapid weight loss followed by 8–12 weeks of maintenance; both phases can be repeated. This study measures weight loss, side effects, and patients' opinions. Over 12–30 months, all patients lost weight (median −10.3 kg [5.7–20], median ΔBMI–3.2). Serum albumin (pre‐diet 3.78; post‐diet 3.83 g/dL), hemoglobin (pre‐diet 11; post‐diet 11.2 g/dL), and acid–base balance (HCO3 pre‐diet: 23.3; post‐diet: 23.4 mmol/L) remained stable, with decreasing needs for erythropoietin and citrate or bicarbonate supplements. Calcium‐phosphate‐parathyroid hormone (PTH) balance improved (PTH‐pre 576; post 286 pg/mL). Three out of 4 hypertensive patients discontinued, 1 decreased antihypertensives. None experienced severe side effects. Patient satisfaction was high (9 on a 0–10 analog scale). Personalized, incremental hemodialysis schedules allow patient enrollment in intensive personalized weight loss programs, with promising results.

Renal function recovery (RFR), defined as the discontinuation of dialysis after 3 months of replacement therapy, is reported in about 1% of chronic dialysis patients. The role of personalized, intensive dialysis schedules and of resuming low-protein diets has not been studied to date. This report describes three patients with RFR who were recently treated at a new dialysis unit set up to offer intensive hemodialysis. All three patients were females, aged 73, 75, and 78 years. Kidney disease included vascular-cholesterol emboli, diabetic nephropathy and vascular and dysmetabolic disease. At time of RFR, the patients had been dialysis-dependent from 3 months to 1 year. Dialysis was started with different schedules and was progressively discontinued with a "decremental" policy, progressively decreasing number and duration of the sessions. A moderately restricted low-protein diet (proteins 0.6 g/kg/day) was started immediately after dialysis discontinuation. The most recent update showed that two patients are well off dialysis for 5 and 6 months; the diabetic patient died (sudden death) 3 months after dialysis discontinuation. Within the limits of small numbers, our case series may suggest a role for personalized dialysis treatments and for including low-protein diets in the therapy, in enhancing long-term RFR in elderly dialysis patients.

BACKGROUND: Natural killer (NK) cells are a key component of innate immunity; their activity is modulated by cytokines and hormones and is influenced by diet. In obesity, a higher risk of cancer and infections has been demonstrated. Studies on NK cell activity have yielded inconsistent results; NK cell sensitivity to modulators has not been assessed before. OBJECTIVE: In this case–control study, we assessed both spontaneous NK cell activity and responsiveness to positive (interleukin (IL)-2) and negative (cortisol) modulators in uncomplicated obesity; we searched for correlations between NK cell activity and anthropometric, dietary and metabolic variables. METHODS: In all, 21 obese (six males/15 females) and 21 age- and sex-matched healthy nonobese subjects underwent clinical examination and dietary and laboratory analyses. Spontaneous and modulated NK activities of peripheral blood mononuclear cells were measured by enzyme-release cytotoxicity assay. RESULTS: Spontaneous NK cell activity was not different in obese subjects vs controls. IL-2 stimulated and cortisol inhibited NK cell activity in both populations. Cortisol-dependent inhibition was lower in the obese than in the control group (−24.4±2.9 vs −38.6±3.3%, P =0.002), but decreased sensitivity was restricted to women ( P =0.0007). In obese subjects, cortisol-dependent inhibition negatively correlated with serum leptin levels ( r =−0.54, P =0.02) and, in women, with body mass index ( r =−0.63, P =0.01); IL-2-dependent stimulation positively correlated with dietary carbohydrates ( r =0.61, P =0.005) and serum LDL levels ( r =0.55, P =0.009) and negatively correlated with dietary lipids ( r =−0.71, P =0.0006). CONCLUSION: Spontaneous and IL-2-inducible NK cell activity is normal in uncomplicated obesity. Sensitivity to IL-2 correlates with fat and carbohydrate intake. Sensitivity to glucocorticoids negatively correlates with serum leptin levels and is significantly diminished in obese women, in whom it correlates with body mass index.

BACKGROUND The aim of the study was to evaluate the validity and reliability of a risk of malnutrition screening tool (MST) proposed by Ferguson et al. for adult hospital patients. METHODS The study included 207 consecutive patients admitted to a Hospital (118 males, 89 females, aged 61+/-16 years) including internal medicine (89), lung (60) and surgical (58) patients. The MST, consisting of three questions regarding appetite and recent unintentional weight loss, was applied to each patients. Peripheral lymphocytes and serum albumin considered as predictor of nutritional status were also evaluated. RESULTS Forty-two patients (20% of overall population) resulted malnourished at admission and nutrition support was rapidly established. Of the remaining, 141 (85%), according to the score of MST were not at risk of malnutrition, while 24 (15%) were classified at risk. Peripheral lymphocytes and serum albumin were unable to discriminate the risk in well-nourished patients. CONCLUSIONS The proposed MST is confirmed as strongly predictor of nutritional status. It is a simple, quick, reliable, valid tool and can be carried out nursing staff. Its routine application will consistently identify patients at risk of malnutrition so that nutrition care can be promptly started.

Fractional systemic bioavailability of orally administered drugs was found to be unexpectedly low in liver cirrhosis, even after surgical portal–systemic shunting. Fecal loss or intestinal first-pass elimination were assumed to explain the finding. In this paper we evaluated alternative pathophysiological interpretations relating low bioavailability to adaptive circulatory modifications. d-Sorbitol was used because its hepatic extraction is very high and hepatic removal follows a flow-dependent clearance regimen. d-Sorbitol bioavailability was measured at steady state in pigs submitted to end-to-side portacaval anastomosis, immediately after surgery and four weeks later. Intestinal first-pass elimination dependent on fecal loss and intraluminal degradation was excluded by administering D-sorbitol into the superior mesenteric artery. Almost complete bioavailability was observed immediately after surgery (N = 6, 0.96 ± 0.08); four weeks later the bioavailability dropped (−36.8 ± 18.7%; P < 0.001) while hepatic clearance significantly increased (+83.6 ± 47.9%; P < 0.01). Experimental data support the hypothesis that adaptive circulatory changes spontaneously occur after some time, leading to a lower than expected portal bioavailability.

D-Sorbitol (SOR) is safe, is easy to measure, and has an exceptionally high extraction ratio in the normal liver of 0.93+/-0.05 (mean+/-SD). Together with the general interest in hepatic hemodynamics, these facts motivated us to review the usefulness of this compound for the assessment of liver plasma flow in humans. We concluded that in subjects without liver disease the nonrenal clearance of SOR-measured noninvasively-very closely approximates hepatic plasma flow. Because of its lower and more variable extraction ratio, indocyanine green should no longer be used without hepatic vein catheterization. Even in patients with cirrhosis, SOR exhibits higher hepatic extraction ratios than indocyanine green. To fully explore the potential of SOR in the evaluation of such patients attention needs to be paid to the complex changes in architecture and function occurring in this disease. In cirrhotics the noninvasively measured nonrenal clearance of SOR presumably approximates the flow through intact and capillarized sinusoids (functional flow) and reflects the amount of blood having functional contact with hepatocytes. The theoretic background of the method, its accuracy, further research needs, and potentials of various approaches are discussed in detail.

Angiographic visualization of the hepatic vascular bed by selective angiography can be profitably complemented with the evaluation of functional portal-systemic shunting by D-sorbitol bioavailability. Seventeen patients requiring diagnostic arterial catheterization were studied: most of them had biopsy-proven liver cirrhosis. Patients were studied at rest and after overnight fasting on two subsequent days, in which a sterile pyrogen-free solution (1.5%) of D-sorbitol was administered by direct infusion (15 mg/min for 20 min) into the superior mesenteric artery and an antecubital vein, respectively. The fractional bioavailability (Fma) of D-sorbitol was calculated as the ratio between the net cumulative urinary outputs obtained after infusion through the catheter into the superior mesenteric artery and the systemic vein, respectively. A good correlation was found between the estimated fractional portal-systemic shunting, which in the present study ranged between 1.4% and 96.7%, and a suitable index scoring the clinical evidence of collateral circulation. Since the hepatic removal of D-sorbitol is not affected by sinusoidal capillarization and its hepatic extraction ratio is quite high and only slightly modified by reduction in the number or functional activity of hepatocytes, the measured Fma can be assumed as a parameter reflecting the entity of portal-systemic shunting. The test is safe and inexpensive, and appears potentially useful in several situations in which portal-systemic shunting is pathophysiologically relevant.

Aims/Methods: The present study aimed to examine whether the galactose elimination capacity can be used to predict the survival of patients with advanced liver disease. We studied 194 patients with cirrhosis. belonging to Child class B and C, for 2 years each.Results: The overall probability of survival was 79% at 6 months, 72% at 1 year and 62% at 2 years. Variables significantly associated with the duration of survival, as assessed by univariate analysis, were the Child-Pugh score, presence of ascites, size of esophageal varices, prothrombin time, albumin, bilirubin, urea, creatinine, glucose and galactose elimination capacity. By a multivariable analysis, only Pugh score (p=0.005), creatinine (p<0.001), varices (p=0.001) and galactose elimination capacity (p<0.001) were independent predictors of mortality. The galactose elimination capacity was even more sensitive when the endpoint was limited to deaths due to liver failure and hepatorenal syndrome. A new score obtained by summing the Pugh score with a score derived from galactose elimination capacity was quite simple and accurate for predicting survival.Conclusions: The quantitative measurement of liver function as the galactose elimination capacity could be of use to identify patients with cirrhosis and probable short survival who might benefit most from urgent transplantation.