The role of salt intake and salt sensitivity in the management of hypertension in South Asian people with chronic kidney disease: A randomized controlled trial

Background The effectiveness of salt restriction to lower blood pressure (BP) in Bangladeshi patients with chronic kidney disease (CKD) is uncertain. Objective To test the hypothesis that a tailored intervention intended to reduce salt intake in addition to standard care will achieve a greater reduction in BP in UK Bangladeshi patients with CKD than standard care alone. Design A randomised parallel-group controlled trial conducted over a 6 month period. Setting A tertiary renal unit based in acute care hospital in East London. Participants 56 adult participants of Bangladeshi origin with CKD and BP >130/80 mm Hg or on antihypertensive medication. Intervention Participants were randomly allocated to receive a tailored low-salt diet or the standard low-salt advice. BP medication, physical activity and weight were monitored. Main outcome measures The primary outcome was change in ambulatory BP. Adherence to dietary advice was assessed by measurement of 24 h urinary salt excretion. Results Of 56 participants randomised, six withdrew at the start of the study. During the study, one intervention group participant died, one control group participant moved to Bangladesh. Data were available for the primary endpoint on 48 participants. Compared with control group the intervention urinary sodium excretion fell from 260 mmol/d to 103 mmol/d (131 to 76, p<0.001) at 6 months and resulted in mean (95% CI) falls in 24 h systolic/diastolic BP of 8 mm Hg (11 to 5)/2 (?4 to 2) both p<0.001. Conclusions A tailored intervention can achieve moderate salt restriction in patients with CKD, resulting in clinically meaningful falls in BP independent of hypertensive medication

Oncology-led early identification of nutritional risk: a pragmatic, evidence-based protocol (PRONTO)

Simple Summary Early identification of patients on antineoplastic therapy who are at risk for or already malnourished is critical for optimizing treatment success. Malnourished patients are at increased risk for being unable to tolerate the most effective 'level' and 'duration' of treatment, with grave implications for both the short- (during treatment) and long-term outcomes. Herein, we provide a practical PROtocol for NuTritional risk in Oncology (PRONTO) to enable oncologists to identify patients with or at risk of malnutrition for further evaluation and follow-up with members of the multidisciplinary care team (MDT). Additional guidance is included on the oncologist-led provision of nutritional support if referral to a dietary service is not available. Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available

Predicting the safety and efficacy of butter therapy to raise tumour pHe: an integrative modelling study

Background: Clinical positron emission tomography imaging has demonstrated the vast majority of human cancers exhibit significantly increased glucose metabolism when compared with adjacent normal tissue, resulting in an acidic tumour microenvironment. Recent studies demonstrated reducing this acidity through systemic buffers significantly inhibits development and growth of metastases in mouse xenografts.\ud \ud Methods: We apply and extend a previously developed mathematical model of blood and tumour buffering to examine the impact of oral administration of bicarbonate buffer in mice, and the potential impact in humans. We recapitulate the experimentally observed tumour pHe effect of buffer therapy, testing a model prediction in vivo in mice. We parameterise the model to humans to determine the translational safety and efficacy, and predict patient subgroups who could have enhanced treatment response, and the most promising combination or alternative buffer therapies.\ud \ud Results: The model predicts a previously unseen potentially dangerous elevation in blood pHe resulting from bicarbonate therapy in mice, which is confirmed by our in vivo experiments. Simulations predict limited efficacy of bicarbonate, especially in humans with more aggressive cancers. We predict buffer therapy would be most effectual: in elderly patients or individuals with renal impairments; in combination with proton production inhibitors (such as dichloroacetate), renal glomular filtration rate inhibitors (such as non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors), or with an alternative buffer reagent possessing an optimal pK of 7.1–7.2.\ud \ud Conclusion: Our mathematical model confirms bicarbonate acts as an effective agent to raise tumour pHe, but potentially induces metabolic alkalosis at the high doses necessary for tumour pHe normalisation. We predict use in elderly patients or in combination with proton production inhibitors or buffers with a pK of 7.1–7.2 is most promising

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

The rhesus protein RhCG: a new perspective in ammonium transport and distal urinary acidification

Urinary acidification is a complex process requiring the coordinated action of enzymes and transport proteins and resulting in the removal of acid and the regeneration of bicarbonate. Proton secretion is mediated by luminal H(+)-ATPases and requires the parallel movement of NH(3), and its protonation to NH(4)(+), to provide sufficient buffering. It has been long assumed that ammonia secretion is a passive process occurring by means of simple diffusion driven by the urinary trapping of ammonium. However, new data indicate that mammalian cells possess specific membrane proteins from the family of rhesus proteins involved in ammonia/μm permeability. Rhesus proteins were first identified in yeast and later also in plants, algae, and mammals. In rodents, RhBG and RhCG are expressed in the collecting duct, whereas in humans only RhCG was detected. Their expression increases with maturation of the kidney and accelerates after birth in parallel with other acid-base transport proteins. Deletion of RhBG in mice had no effect on renal ammonium excretion, whereas RhCG deficiency reduces renal ammonium secretion strongly, causes metabolic acidosis in acid-challenged mice, and impairs restoration of normal acid-base status. Microperfusion experiments or functional reconstitution in liposomes demonstrates that ammonia is the most likely substrate of RhCG. Similarly, crystal structures of human RhCG and the homologous bacterial AmtB protein suggest that these proteins may form gas channels.Kidney International advance online publication, 6 October 2010; doi:10.1038/ki.2010.386

Effect of stage-based education provided by dedicated dietitians on hyperphosphataemic haemodialysis patients: results from the Nutrition Education for Management of Osteodystrophy randomised controlled trial

© 2017 The British Dietetic Association Ltd. Background: The Nutrition Education for Management of Osteodystrophy trial showed that stage-based nutrition education by dedicated dietitians surpasses existing practices in Lebanon with respect to lowering serum phosphorus among general haemodialysis patients. The present study explores the effect of nutrition education specifically on hyperphosphataemic patients from this trial. Methods: Hyperphosphataemic haemodialysis patients were allocated to a dedicated dietitian (DD), a trained hospital dietitian (THD) and existing practice (EP) protocols. From time-point (t)-0 until t-1 (6 months), the DD group (n = 47) received 15 min of biweekly nutrition education by dedicated dietitians trained on renal nutrition; the THD group (n = 89) received the usual care from trained hospital dietitians; and the EP group (n = 42) received the usual care from untrained hospital dietitians. Patients were followed-up from t-1 until t-2 (6 months). Analyses used two-way repeated measures analysis of variance and Cohen\u27s effect sizes (d). Results: At t-1, phosphataemia significantly decreased in all groups (DD:−0.27 mmol L−1; EP:−0.15 mmol L−1; THD:−0.12 mmol L−1; P \u3c 0.05); the DD protocol had the greatest effect relative to EP (d = −0.35) and THD (d = −0.50). Only the DD group showed more readiness to adhere to a low phosphorus diet at t-1; although, at t-2, this regressed to baseline levels. The malnutrition inflammation score remained stable only in the DD group, whereas the EP and THD groups exhibited a significant increase (DD: 6.74, 6.97 and 7.91; EP: 5.82, 8.69 and 8.13; THD: 5.33, 7.92 and 9.42, at t-0, t-1 and t-2, respectively). Conclusions: The results of the present study suggest that the DD protocol decreases serum phosphorus compared to EP and THD, at the same time as maintaining the nutritional status of hyperphosphataemic haemodialysis patients. Assessing the cost-effectiveness of the DD protocol is recommended

Wasting in chronic kidney disease

Wasting/cachexia is prevalent among patients with chronic kidney disease (CKD). It is to be distinguished from malnutrition, which is defined as the consequence of insufficient food intake or an improper diet. Malnutrition is characterized by hunger, which is an adaptive response, whereas anorexia is prevalent in patients with wasting/cachexia. Energy expenditure decreases as a protective mechanism in malnutrition whereas it remains inappropriately high in cachexia/wasting. In malnutrition, fat mass is preferentially lost and lean body mass and muscle mass is preserved. In cachexia/wasting, muscle is wasted and fat is relatively underutilized. Restoring adequate food intake or altering the composition of the diet reverses malnutrition. Nutrition supplementation does not totally reverse cachexia/wasting. The diagnostic criteria of cachexia/protein–energy wasting in CKD are considered. The association of wasting surrogates, such as serum albumin and prealbumin, with mortality is strong making them robust outcome predictors. At the patient level, longevity has consistently been observed in patients with CKD who have more muscle and/or fat, who report better appetite and who eat more. Although inadequate nutritional intake may contribute to wasting or cachexia, recent evidence indicates that other factors, including systemic inflammation, perturbations of appetite-controlling hormones from reduced renal clearance, aberrant neuropeptide signaling, insulin and insulin-like growth factor resistance, and metabolic acidosis, may be important in the pathogenesis of CKD-associated wasting. A number of novel therapeutic approaches, such as ghrelin agonists and melanocortin receptor antagonists are currently at the experimental level and await confirmation by randomized controlled clinical trials in patients with CKD-associated cachexia/wasting syndrome

Epidemiology of chronic kidney disease in children

In the past 30 years there have been major improvements in the care of children with chronic kidney disease (CKD). However, most of the available epidemiological data stem from end-stage renal disease (ESRD) registries and information on the earlier stages of pediatric CKD is still limited. The median reported incidence of renal replacement therapy (RRT) in children aged 0–19 years across the world in 2008 was 9 per million of the age-related population (4–18 years). The prevalence of RRT in 2008 ranged from 18 to 100 per million of the age-related population. Congenital disorders, including congenital anomalies of the kidney and urinary tract (CAKUT) and hereditary nephropathies, are responsible for about two thirds of all cases of CKD in developed countries, while acquired causes predominate in developing countries. Children with congenital disorders experience a slower progression of CKD than those with glomerulonephritis, resulting in a lower proportion of CAKUT in the ESRD population compared with less advanced stages of CKD. Most children with ESRD start on dialysis and then receive a transplant. While the survival rate of children with ERSD has improved, it remains about 30 times lower than that of healthy peers. Children now mainly die of cardiovascular causes and infection rather than from renal failure