Diet as a system: an observational study investigating a multi-choice system of moderately restricted low-protein diets.

BACKGROUND: 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. METHODS: Observational study: Three LPD options were offered to all patients with severe or rapidly progressive CKD: vegan diets supplemented with alpha-ketoacids and essential aminoacids; protein-free food in substitution of normal bread and pasta; other (traditional, vegan non supplemented and tailored). Dialysis-free follow-up and survival were analyzed by Kaplan Meier curves according to diet, comorbidity and age. Compliance and metabolic control were estimated in 147 subjects on diet at March 2015, with recent complete data, prescribed protein intake 0.6 g/Kg/day. Protein intake was assessed by Maroni Mitch formula. RESULTS: Four hundreds and forty nine patients followed a LPD in December, 2007- March, 2015 (90% moderately restricted LPDs, 0.6 g/Kg/day of protein, 10% at lower targets); age (median 70 (19-97)) and comorbidity (Charlson index: 7) characterized our population as being in line with the usual CKD European population. Median e-GFR at start of the diet was 20 mL/min, 33.2% of the patients were diabetics. Baseline data differ significantly across diets: protein-free schemas are preferred by older, high-comorbidity patients (median age 76 years, Charlson index 8, GFR 20.5 mL/min, Proteinuria: 0.3 g/day), supplemented vegan diets by younger patients with lower GFR and higher proteinuria (median age 65 years, Charlson index 6, GFR 18.9 mL/min; Proteinuria: 1.2 g/day); other diets are chosen by an intermediate population (median age 71 years, Charlson index 6; GFR 22.5 mL/min; Proteinuria: 0.9 g/day); (p <0.001 for age, Charlson index, proteinuria, GFR). Adherence was good, only 1.1% of the patients were lost to follow-up and protein intake was at target in most of the cases with no differences among LPDs (protein intake: 0.47 (0.26-0.86) g/Kg/day). After adjustment for confounders, and/or selection of similar populations, no difference in mortality or dialysis start was observed on the different LPDs. Below the threshold of e-GFR 15 mL/min, 50% of the patients remain dialysis free for at least two years. CONCLUSION: A multiple choice LPD system may allow reaching good adherence, without competition among diets, and with promising results in terms of dialysis-free follow-up. The advantages with respect to a non-customized approach deserve confirmation in further comparative studies or RCTs.

Patient Survival and Costs on Moderately Restricted Low-Protein Diets in Advanced CKD: Equivalent Survival at Lower Costs?

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.

Low-Protein Diets in Diabetic Chronic Kidney Disease (CKD) Patients: Are They Feasible and Worth the Effort?

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.

Vegan-vegetarian low-protein supplemented diets in pregnant CKD patients: fifteen years of experience.

BACKGROUND: Pregnancy in women with advanced CKD becoming increasingly common. However, experience with low-protein diets in CKD patients in pregnancy is still limited. Aim of this study is to review the results obtained over the last 15 years with moderately restricted low-protein diets in pregnant CKD women (combining: CKD stages 3-5, proteinuria: nephrotic at any time, or > =1 g/24 at start or referral; nephrotic in previous pregnancy). CKD patients on unrestricted diets were employed for comparison. STUDY PERIOD: January, 2000 to September, 2015: 36 on-diet pregnancies (31 singleton deliveries, 3 twin deliveries, 1 pregnancy termination, 1 miscarriage); 47 controls (42 singleton deliveries, 5 miscarriages). The diet is basically vegan; since occasional milk and yoghurt are allowed, we defined it vegan-vegetarian; protein intake (0.6-0.8 g/Kg/day), keto-acid supplementation, protein-unrestricted meals (1-3/week) are prescribed according to CKD stage and nutritional status. Statistical analysis was performed as implemented on SPSS. RESULTS: Patients and controls were similar (p: ns) at baseline with regard to age (33 vs 33.5), referral week (7 vs 9), kidney function (CKD 3-5: 48.4 % vs 64.3 %); prevalence of hypertension (51.6 % vs 40.5 %) and proteinuria >3 g/24 h (16.1 % vs 12.2 %). There were more diabetic nephropathies in on-diet patients (on diet: 31.0 % vs controls 5.3 %; p 0.007 (Fisher)) while lupus nephropathies were non-significantly higher in controls (on diet: 10.3 % vs controls 23.7 %; p 0.28 (Fisher)). The incidence of preterm delivery was similar (<37 weeks: on-diet singletons 77.4 %; controls: 71.4 %). The incidence of other adverse pregnancy related outcomes was non-significantly lower in on-diet patients (early preterm delivery: on diet: 32.3 % vs controls 35.7 %; birth-weight = <1.500 g: on diet: 9.7 % vs controls 23.8 %). None of the singletons in the on-diet series died, while two perinatal deaths occurred among the controls (p = 0.505). The incidence of small for gestational age (SGA <10th centile) and/or extremely preterm babies (<28th week) was significantly lower in singletons from on-diet mothers than in controls (on diet: 12.9 % vs controls: 33.3 %; p: 0.04 (Fisher)). CONCLUSION: Moderate protein restriction in the context of a vegan-vegetarian supplemented diet is confirmed as a safe option in the management of pregnant CKD patients.

Low protein diets in patients with chronic kidney disease: a bridge between mainstream and complementary-alternative medicines?

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.

Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia.

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.

Calcium-phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules.

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 m(2) ), 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.

Low-protein diets in CKD: how can we achieve them? A narrative, pragmatic review.

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.

Intensive weight loss combining flexible dialysis with a personalized, ad libitum, coach-assisted diet program. A "pilot" case series.

UNLABELLED: 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/m(2)) 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 (HCO(3) 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.

Tailoring dialysis and resuming low-protein diets may favor chronic dialysis discontinuation: report on three cases.

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.

[Intensive weight-loss in dialysis: a personalized approach]. / La sfida del dimagrimento nell'obeso in trattamento dialitico. Case report.

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.