Nutritional Treatment as a Synergic Intervention to Pharmacological Therapy in CKD Patients.

Nutritional and pharmacological therapies represent the basis for non-dialysis management of CKD patients. Both kinds of treatments have specific and unchangeable features and, in certain cases, they also have a synergic action. For instance, dietary sodium restriction enhances the anti-proteinuric and anti-hypertensive effects of RAAS inhibitors, low protein intake reduces insulin resistance and enhances responsiveness to epoetin therapy, and phosphate restriction cooperates with phosphate binders to reduce the net phosphate intake and its consequences on mineral metabolism. It can also be speculated that a reduction in either protein or salt intake can potentially amplify the anti-proteinuric and reno-protective effects of SGLT2 inhibitors. Therefore, the synergic use of nutritional therapy and medications optimizes CKD treatment. Quality of care management is improved and becomes more effective when compared to either treatment alone, with lower costs and fewer risks of unwanted side effects. This narrative review summarizes the established evidence of the synergistic action carried out by the combination of nutritional and pharmacological treatments, underlying how they are not alternative but complementary in CKD patient care.

Effects of a low-sodium diet in patients with idiopathic hyperaldosteronism: a randomized controlled trial.

Background: Idiopathic hyperaldosteronism (IHA) is one of the most common types of primary aldosteronism (PA), an important cause of hypertension. Although high dietary sodium is a major risk factor for hypertension, there is no consensus on the recommended dietary sodium intake for IHA. Objective: This study investigated the effect of a low-sodium diet on hemodynamic variables and relevant disease biomarkers in IHA patients, with the aim of providing a useful reference for clinical treatment. Methods: Fifty IHA patients were evenly randomized into two groups and provided, after a 7-day run-in period (100 mmol/d sodium), either a low-sodium diet (50 mmol/d sodium) or a normal sodium diet (100 mmol/d sodium) for an additional 7 days. After the 14-day intervention (conducted without potassium supplementation), changes in blood pressure (BP) and serum potassium were evaluated in both groups. Results: After the dietary intervention, the low sodium group exhibited, compared to the normal sodium group, decreased BP (SBP: 121.8 ± 12.8 vs. 129.9 ± 12.1 mmHg, p < 0.05; DBP: 82.6 ± 7.6 vs. 86.4 ± 8.2 mmHg, p < 0.05; MAP: 95.7 ± 8.8 vs. 100.9 ± 8.4 mmHg, p < 0.05) and increased serum potassium levels (3.38 ± 0.33 vs. 3.07 ± 0.27 mmol/L, p < 0.001). The low sodium group showed also better control of both BP and serum potassium: BP <140/90 mmHg in 70.0% of total patients (76.0% vs. 64.0%, in the low and normal sodium groups, respectively; p > 0.05), BP <130/85 mmHg in 38.0% of total patients (56.0% vs. 20.0%, p < 0.05), BP <120/80 mmHg in 28.0% of total patients (44.0% vs. 12.0%, p < 0.05); serum potassium ≥3.5 mmol/L in 22.0% of total patients (32.0% vs. 12.0% in the low and normal sodium groups, respectively; p = 0.088). There were differences between the controlled BP group (<120/80 mmHg) and the non-controlled BP group (≥120/80 mmHg) in gender, BP at baseline, and type of diet (low vs. normal sodium). Female gender and low-sodium diet were protective factors for BP control. Conclusions: A low-sodium diet is effective in lowering BP and elevating serum potassium in IHA patients. Female patients on a low-sodium diet are more likely to achieve BP control (<120/80 mmHg). We advocate a dietary sodium intake of 50 mmol/d for IHA patients. Clinical trial registration: https://clinicaltrials.gov, Identifier NCT05649631.

[Can salt substitution or reduction replace pharmaceuticals for arterial hypertension?] / Kann eine Salzsubstitution oder -reduktion bei arterieller Hypertonie Arzneimittel ersetzen?

Nonpharmacological treatment is still an important supplement to the pharmacological treatment of hypertension. Thereby, either an elevated blood pressure can be lowered further or, alternatively, the use of antihypertensive drugs can be reduced. In the context of nonpharmacological treatment of hypertension, sodium restriction plays an important role. Sodium intake can either be reduced by lowering excessive dietary salt consumption or by the use of table salts with reduced sodium content. Lower dietary sodium consumption lowers blood pressure. This was controversial for a long time; however, now more and more observational and interventional studies have confirmed this fact. Nevertheless, some studies have shown an association of low salt consumption with increased mortality. This observation is explained by the so-called reverse epidemiology. This means that diseases with increased mortality, such as consuming diseases or severe heart diseases are associated with lowered food intake and as a consequence, with lower sodium intake. In addition to sodium restriction, the use of so-called salt substitutes with lower sodium content is also effective in lowering blood pressure. In most of the salt substitutes examined so far sodium chloride is partly replaced by potassium chloride. Numerous investigations show that these salt substitutes lower blood pressure. From a statistical point of view side effects such as hyperkalemia are very rare; however, hyperkalemia is potentially life-threatening. Therefore, the broader use of these salt substitutes is principally helpful but these salts should only be used after medical consultation. Especially renal insufficiency and the use of certain drugs, such as potassium-sparing diuretics and blockers of the renin-angiotensin system increase the risk of hyperkalemia.

New wrinkles in hypertension management 2022.

PURPOSE OF REVIEW: High blood pressure (BP) is the world's leading risk factor for cardiovascular disease (CVD) and death. This review highlights findings during the past 18 months that apply to the management of high BP in adults in the context of the 2017 American College of Cardiology/American Heart Association (AHA) BP guideline. RECENT FINDINGS: A comprehensive meta-analysis of clinical trials that employed a novel statistical method identified a substantially linear relationship between dietary sodium intake and BP, strongly supporting the AHA daily dietary sodium intake recommendation of less than 1500 mg/day but suggesting that any reduction in sodium intake is likely to be beneficial. Among adults with hypertension, use of a salt substitute (containing reduced sodium and enhanced potassium) led to striking reductions in CVD outcomes. Young adults with stage 1 hypertension and a low 10-year atherosclerotic CVD risk score should be started on a 6-month course of vigorous lifestyle modification; if their BP treatment goal is not achieved, a first-line antihypertensive agent should be added to the lifestyle modification intervention. In patients with stage 4 renal disease, the thiazide-like diuretic chlorthalidone (as add-on therapy) lowered BP markedly compared with placebo. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) represent a new class of MRA that has been shown to lower BP and provide significant CVD protection. In Chinese adults aged 60-80 years at baseline, intensive BP control with a SBP target of 110-129 compared with 130-149 mmHg reduced CVD events with minimal side effects. SUMMARY: Recent findings have advanced our knowledge of hypertension management, clarifying, amplifying and supporting the 2017 ACC/AHA BP guideline recommendations.

Sodium-glucose co-transporter 2 inhibitor therapy: use in chronic kidney disease and adjunctive sodium restriction.

The global burden of chronic kidney disease (CKD) has increased significantly over the past few decades. This reflects the rising prevalence of type 2 diabetes mellitus (T2DM) and hypertension, two leading causes of CKD. Hypertension, which can also be a complication of CKD, accelerates renal disease progression and augments cardiovascular risk, especially in individuals with diabetic kidney disease. Hence, blood pressure (BP) reduction is a vital component of CKD management. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a relatively novel class of medications developed to treat T2DM by inducing glycosuria and hence, lowering glycaemia. Additionally, SGLT2 inhibitors are antihypertensive, renoprotective and cardioprotective, even in individuals without T2DM, making them effective therapeutic agents for CKD. Another therapy that has proven to be antihypertensive, renoprotective and cardioprotective is dietary sodium restriction. This review evaluates the potential combined benefits of SGLT2 inhibition and dietary sodium restriction on the BP and renal parameters of individuals with CKD.

The Dietary Approach to the Treatment of the Rare Genetic Tubulopathies Gitelman's and Bartter's Syndromes.

Gitelman's (GS) and Bartter's (BS) syndromes are rare, inherited autosomal recessive tubulopathies characterized by hypokalemia, metabolic alkalosis, renal sodium, chloride, and potassium and magnesium-wasting. While the treatment based on potassium, sodium, chloride, and magnesium supplementation in addition to other pharmacologic options are widely established, recommendations about the dietary approach to GS and BS still remain generic. In this review we focus on the dietary strategies to increase sodium, potassium, and magnesium intake in GS and BS patients. Potassium and magnesium-rich foods and supplements are considered together with those that may reduce through different mechanisms the potassium and magnesium plasma level. Magnesium supplementation is often poorly tolerated, causing abdominal pain and diarrhea in most patients. New formulations using liposome and, in particular, sucrosomial technology have been recently proposed for magnesium supplementation in order to increase magnesium supplement tolerability and intestinal absorption. The dietary approach to GS and BS may be very important in the therapeutic approach to these syndromes. Due to the relevance of the dietary approach to these syndromes, a nutritional counseling should always be recommended and the nutritionist should join nephrologists in the follow-up of GS and BS patient care.

Positive and Negative Aspects of Sodium Intake in Dialysis and Non-Dialysis CKD Patients.

Sodium intake theoretically has dual effects on both non-dialysis chronic kidney disease (CKD) patients and dialysis patients. One negatively affects mortality by increasing proteinuria and blood pressure. The other positively affects mortality by ameliorating nutritional status through appetite induced by salt intake and the amount of food itself, which is proportional to the amount of salt under the same salty taste. Sodium restriction with enough water intake easily causes hyponatremia in CKD and dialysis patients. Moreover, the balance of these dual effects in dialysis patients is likely different from their balance in non-dialysis CKD patients because dialysis patients lose kidney function. Sodium intake is strongly related to water intake via the thirst center. Therefore, sodium intake is strongly related to extracellular fluid volume, blood pressure, appetite, nutritional status, and mortality. To decrease mortality in both non-dialysis and dialysis CKD patients, sodium restriction is an essential and important factor that can be changed by the patients themselves. However, under sodium restriction, it is important to maintain the balance of negative and positive effects from sodium intake not only in dialysis and non-dialysis CKD patients but also in the general population.

Validez y limitaciones de los métodos para medir la ingesta y la eliminación de sal / Validity and limitations of methods to measure the intake and elimination of salt

La hipertensión arterial (HTA) es el principal factor de riesgo cardiovascular modificable. La HTA se puede relacionar con el consumo elevado de sal. Para medir la ingesta no todas las encuestas de alimentación son comparables y válidas. El procedimiento de referencia para valorar la ingesta de sal consiste en medir la excreción urinaria de sodio en orina recolectada durante 24 h, aunque se han propuesto métodos alternativos, como las recolecciones de muestras de orina puntuales y cronometradas. En esta revisión analizamos qué instrumentos permiten valorar la ingesta de sal y cuáles de ellos han aportado una mayor validez y fiabilidad a través de los estudios de concordancia con la eliminación de sodio en orina. Las encuestas actuales de consumo de alimentos son inadecuados debido a su amplia variabilidad y relativamente baja correlación con la eliminación de sodio en orina de 24 h. Su principal limitación es la necesidad de validación en diferentes grupos poblacionales. En Atención Primaria se debería valorar la ingesta de sal mediante la utilización de cuestionarios de frecuencia de consumo que recojan alimentos con elevado contenido en sal, el consumo de platos preelaborados y preguntas que cuantifiquen la adición de sal en la preparación de alimentos o en la mesa. Para la validación de estos cuestionarios debe emplearse como gold standard la eliminación de sodio en orina de 24 h ajustada según el aclaramiento de creatinina

High blood pressure (HBP) is the main modifiable cardiovascular risk factor. HBP can be related to high salt intake. To measure intake, not all feeding surveys are comparable and valid. The reference procedure for assessing salt intake consists of measuring the urinary excretion of sodium in urine collected during 24 hours, although alternative methods have been proposed, such as the collection of punctual and timed urine samples. In this review, we analyze which instruments allow the assessment of salt intake and which of them have provided greater validity and reliability through studies of concordance with the elimination of sodium in urine. Current food consumption surveys are inadequate because of their wide variability and relatively low correlation with the elimination of sodium in 24-hour urine. Its main limitation is the need for validation in different population groups. In primary care, salt intake should be assessed by using frequency-of-consumption questionnaires that collect foods with a high salt content, the consumption of preprepared dishes and questions that quantify the addition of salt in the preparation of food or at the table. For the validation of these questionnaires, the standard gold elimination of 24-hour urine sodium adjusted according to creatinine clearance should be used

Maximising benefits and minimising adverse effects of micronutrient interventions in low- and middle-income countries.

Micronutrient deficiencies are widespread and disproportionately affect women and children in low- and middle-income countries (LMIC). Among various interventions, food fortification and supplementation with micronutrients have been proven to be cost-effective. The aim of the present paper is to review existing literature to assess risks of excessive intake in LMIC to then highlight programmatic changes required to maximise benefits of micronutrient interventions while minimising risks of adverse effects. While very few LMIC have national food consumption surveys that can inform fortification programmes, many more are implementing mandatory fortification programmes. The risks of inadequate micronutrient intakes were common, but risks of excessive intakes were also present for iodine, vitamin A, folic acid and iron. Excessive salt consumption, high concentrations of iodine in ground-water and excessive levels of iodisation were linked with excessive iodine intake. For vitamin A, overlapping interventions were the main risk for excessive intake; whereas for iron, contamination with iron from soil and screw-wares of millers and high iron concentration in drinking-water increased the risk of excessive intake, which could be further exacerbated with fortification. Before implementing micronutrient interventions, adherence to the basic principles of documenting evidence confirming that the deficiency in question exists and that fortification will correct this deficiency is needed. This can be supported with dietary intake assessments and biochemical screening that help diagnose nutrient deficiencies. Targeting micronutrient interventions, although programmatically challenging, should be considered whenever possible. Moreover, closer monitoring of appropriate fortification of foods and overlapping interventions is needed.

Considerations for ultra-endurance activities: part 2 - hydration.

It is not unusual for those participating in ultra-endurance (> 4 hr) events to develop varying degrees of either hypohydration or hyperhydration. Yet, it is important for ultra-endurance athletes to avoid the performance limiting and potentially fatal consequences of these conditions. During short periods of exercise (< 1 hr), trivial effects on the relationship between body mass change and hydration status result from body mass loss due to oxidation of endogenous fuel stores, and water supporting the intravascular volume being generated from endogenous fuel oxidation and released with glycogen oxidation. However, these effects have meaningful implications during prolonged exercise. In fact, body mass loses well over 2% may be required during some ultra-endurance activities to avoid hyperhydration. Therefore, the typical hydration guidelines to avoid more than 2% body mass loss do not apply in ultra-endurance activities and can potentially result in hyperhydration. Fortunately, achieving the balance of proper hydration during ultra-endurance activities need not be complicated and has been well demonstrated to generally be achieved by simply drinking to thirst and avoiding excessive sodium supplementation with intention of replacing all sodium losses during the exercise.

High-Salt Intake Ameliorates Hyperglycemia and Insulin Resistance in WBN/Kob-Leprfa/fa Rats: A New Model of Type 2 Diabetes Mellitus.

High-salt intake is a major risk factor for developing hypertension in type 2 diabetes mellitus, but its effects on glucose homeostasis are controversial. We previously found that high-salt intake induces severe hypertension in WBN/Kob diabetic fatty (WBKDF) rats. In the present study, we examined the effects of a high-salt intake on glucose homeostasis in WBKDF rats. Male WBKDF rats and age-matched Wistar rats at 6 weeks of age were each divided into two groups and fed either a normal-sodium (NS, 0.26%) diet or high-sodium (HS, 8%) diet for 7 weeks. Systolic blood pressure and urine volume were increased in WBKDF-HS and Wistar-HS. Body weight gain and food consumption were comparable between NS and HS in both strains. Plasma and urine glucose levels were significantly increased in WBKDF-NS but not in WBKDF-HS. HOMA-IR in WBKDF-HS was significantly lower compared with that in WBKDF-NS. The high plasma adiponectin level in WBKDF-NS compared with that in Wistar-NS was further enhanced in WBKDF-HS. Glycogen deposits and fat droplets in the livers of WBKDF-HS were reduced compared with those of WBKDF-NS. The present study demonstrated that HS intake ameliorated hyperglycemia and insulin resistance in WBKDF rats, which may be due to increased plasma levels of adiponectin.

Acute Symptomatic Hyponatremia After Computed Tomography Renal Protocol.

Computed tomography (CT) is a widely used imaging modality. Although hyponatremia after CT imaging is rare, its effects can be devastating. Hyperosmolar radiocontrast acts as effective osmoles and causes fluid migration from intracellular into extracellular compartment. Dilutional hyponatremia will ensue if translocation of fluid is in excess of diuresis. This case report detailed an unusual case of acute symptomatic hyponatremia after CT renal protocol and the treatments given after its recognition.

Exertional Hyponatremia and Serum Sodium Change During Ultraendurance Cycling.

INTRODUCTION: Exertional hyponatremia (EH) during prolonged exercise involves all avenues of fluid-electrolyte gain and loss. Although previous research implicates retention of excess fluid, EH may involve either loss, gain, or no change of body mass. Thus, the etiology, predisposing factors, and recommendations for prevention are vague-except for advice to avoid excessive drinking. PURPOSE: This retrospective field study presents case reports of two unacquainted recreational cyclists (LC, 31y and AM, 39 years) who began exercise with normal serum electrolytes but finished a summer 164-km ride (ambient, 34±5°C) with a serum [Na+] of 130 mmol/L. METHODS: To clarify the etiology of EH, their pre- and post-exercise measurements were compared to a control group (CON) of 31 normonatremic cyclists (mean ± SD; 37±6 years; 141±3 mmol Na+/L). RESULTS: Anthropomorphic characteristics, exercise time, and post-exercise ratings of thermal sensation, perceived exertion and muscle cramp were similar for LC, AM and CON. These two hyponatremic cyclists consumed a large and similar volume of fluid (191 and 189 ml/kg), experienced an 11 mmol/L decrease of serum [Na+], reported low thirst sensations; however, LC gained 3.1 kg (+4.3% of body mass) during 8.9 hr of exercise and AM maintained body mass (+0.1kg, +0.1%, 10.6h). In the entire cohort (n = 33), post-event serum [Na+] was strongly correlated with total fluid intake (R2 = 0.45, p < .0001), and correlated moderately with dietary sodium intake (R2=0.28, p = .004) and body mass change (R2 = 0.22, p = .02). Linear regression analyses predicted the threshold of EH onset (<135 mmol Na+/L) as 168 ml fluid/kg. CONCLUSIONS: The wide range of serum [Na+] changes (+6 to -11 mmol/L) led us to recommend an individualized rehydration plan to athletes because the interactions of factors were complex and idiosyncratic.

Neonates with Bartter syndrome have enormous fluid and sodium requirements.

AIM: Managing neonatal Bartter syndrome by achieving adequate weight gain is challenging. We assessed the correlation between weight gain in neonatal Bartter syndrome and the introduction of fluid and sodium supplementations and indomethacin during the first 4 weeks of life. METHODS: Daily fluid and electrolytes requirements were analysed using linear regression and Spearman correlation coefficients. The weight gain coefficient was calculated as daily weight gain after physiological neonatal weight loss. RESULTS: We studied seven infants. The highest weight gain coefficients occurred between weeks two and four in the five neonates who either received prompt amounts of fluid (maximum 810 mL/kg/day) and sodium (maximum 70 mmol/kg/day) or were treated with indomethacin. For the two patients with the highest weight gain coefficient, water and sodium supplementations were decreased in weeks two to four leading to a significant negative Spearman correlation between weight gain and fluid supplements (r = -0.55 and -0.68) and weight gain and sodium supplementations (r = -0.96 and -0.72). The two patients with the lowest weight gain coefficient had positive Spearman correlation coefficients between weight gain and fluid and sodium supplementations. CONCLUSION: Infants with neonatal Bartter syndrome required rapid and enormous fluid and sodium supplementations or the early introduction of indomethacin treatment to achieve adequate weight gain during the early postnatal period.

Interventions for the symptoms and signs resulting from jellyfish stings.

BACKGROUND: Jellyfish envenomations are common amongst temperate coastal regions and vary in severity depending on the species. Stings result in a variety of symptoms and signs, including pain, dermatological reactions and, in some species, Irukandji syndrome (including abdominal/back/chest pain, tachycardia, hypertension, sweating, piloerection, agitation and sometimes cardiac complications). Many treatments have been suggested for the symptoms and signs of jellyfish stings. However, it is unclear which interventions are most effective. OBJECTIVES: To determine the benefits and harms associated with the use of any intervention, in both adults and children, for the treatment of jellyfish stings, as assessed from randomised trials. SEARCH METHODS: We searched the following electronic databases in October 2012 and again in October 2013: the Cochrane Central Register of Controlled Trials (CENTRAL;The Cochrane Library, Issue 9, 2013); MEDLINE via Ovid SP (1948 to 22 October 2013); EMBASE via Ovid SP (1980 to 21 October 2013); and Web of Science (all databases; 1899 to 21 October 2013). We also searched reference lists from eligible studies and guidelines, conference proceedings and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and contacted content experts to identify trials. SELECTION CRITERIA: We included randomised controlled trials that compared any intervention(s) to active and/or non-active controls for the treatment of symptoms and signs of jellyfish sting envenomation. No language, publication date or publication status restrictions were applied. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted study selection and data extraction and assessed risk of bias using a standardised form. Disagreements were resolved by consensus with a third review author when necessary. MAIN RESULTS: We included seven trials with a total of 435 participants. Three trials focused on Physalia (Bluebottle) jellyfish, one trial on Carukia jellyfish and three on Carybdea alata (Hawaiian box) jellyfish. Two ongoing trials were identified.Six of the seven trials were judged as having high risk of bias. Blinding was not feasible in four of the included trials because of the nature of the interventions. A wide range of interventions were assessed across trials, and a wide range of outcomes were measured. We reported results from the two trials for which data were available and reported the effects of interventions according to our definition of primary or secondary outcomes.Hot water immersion was superior to ice packs in achieving clinically significant (at least 50%) pain relief at 10 minutes (one trial, 96 participants, risk ratio (RR) 1.66, 95% confidence interval (CI) 1.01 to 2.72; low-quality evidence) and 20 minutes (one trial, 88 participants, RR 2.66, 95% CI 1.71 to 4.15; low-quality evidence). No statistically significant differences between hot water immersion and ice packs were demonstrated for dermatological outcomes.Treatment with vinegar or Adolph's meat tenderizer compared with hot water made skin appear worse (one trial, 25 participants, RR 0.31, 95% CI 0.14 to 0.72; low-quality evidence).Adverse events due to treatment were not reported in any trial. AUTHORS' CONCLUSIONS: This review located a small number of trials that assessed a variety of different interventions applied in different ways and in different settings. Although heat appears to be an effective treatment for Physalia (Bluebottle) stings, this evidence is based on a single trial of low-quality evidence. It is still unclear what type of application, temperature, duration of treatment and type of water (salt or fresh) constitute the most effective treatment. In addition, these results may not apply to other species of jellyfish with different envenomation characteristics. Future research should further assess the most effective interventions using standardised research methodology.

Resistant hypertension and the neglected antihypertensive: sodium restriction.

Resistant hypertension is defined as blood pressure (BP) that remains above goal (such as 140/90 mmHg or more) in spite of the concurrent use of three antihypertensive agents of different classes. Ideally, one of the three agents should be a diuretic and all agents should be prescribed at optimal dose amounts. Prevalent among 15% of the treated hypertensives, the risk factors for resistant hypertension include older age, chronic kidney disease (CKD), obesity and diabetes mellitus. Causes of resistant hypertension can be classified into four groups: poor adherence, biological-behavioral factors, CKD and secondary causes, and drugs or exogenous substances. However, before labeling the diagnosis of resistant hypertension, it is important to exclude pseudo-resistant hypertension using home BP monitoring in most patients and ambulatory BP monitoring in a few. Before thinking about the next antihypertensive drug, it is important to restrict dietary sodium. Educating the patient on how to interpret the food label and providing feedback by assessing sodium intake with 24 h urine collection are effective sodium restriction strategies. Sodium restriction can lower BP and among patients with proteinuria can even enhance the anti-proteinuric effects of drugs that block the renin-angiotensin system. Sodium restriction is therefore a valuable but a neglected antihypertensive.

Long-term effects of dietary sodium intake on cytokines and neurohormonal activation in patients with recently compensated congestive heart failure.

BACKGROUND: A growing body of evidence suggests that the fluid accumulation plays a key role in the pathophysiology of heart failure (HF) and that the inflammatory and neurohormonal activation contribute strongly to the progression of this disorder. METHODS AND RESULTS: The study evaluated the long-term effects of 2 different sodium diets on cytokines neurohormones, body hydration and clinical outcome in compensated HF outpatients (New York Heart Association Class II). A total of 173 patients (105 males, mean age 72.5+/-7) recently hospitalized for worsening advanced HF and discharged in normal hydration and in clinical compensation were randomized in 2 groups (double blind). In Group 1, 86 patients received a moderate restriction in sodium (120mmol to 2.8g/day) plus oral furosemide (125 to 250mg bid); in Group 2, 87 patients: received a low-sodium diet (80mmol to 1.8g/day) plus oral furosemide (125 to 250mg bid). Both groups were followed for 12 months and the treatment was associated with a drink intake of 1000mL daily. Neurohormonal (brain natriuretic peptide, aldosterone, plasma rennin activity) and cytokines values (tumor necrosis factor-alpha, interleukin-6) were significantly reduced with a significant increase of the anti-inflammatory cytokine interleukin-10 at 12 months in normal, P < .0001) than low-sodium group. The low-sodium diet showed a significant activation of neurohormones and cytokines and worsening the body hydration, whereas moderate sodium restriction maintained dry weigh and improved outcome in the long term. CONCLUSIONS: Our results appear to suggest a surprising efficacy of a new strategy to improve the chronic diuretic response by increasing Na intake and limiting fluid intake. This counterintuitive approach underlines the need for a better understanding of factors that regulate sodium and water handling in chronic congestive HF. A larger sample of patients and further studies are required to evaluate whether this is due to the high dose of diuretic used or the low-sodium diet.

Treatment strategies for pediatric idiopathic hypercalciuria.

Idiopathic hypercalciuria (IH) is a common metabolic disorder in children and is associated with the development of renal calculi, nephrocalcinosis, hematuria and osteopenia. The effect of various dietary modifications and available pharmacologic therapies on reducing urinary calcium excretion and/or urinary supersaturation is discussed in this article. The importance of a multidisciplinary approach involving the patient, their families, and health-care professionals is also addressed.

Effect of renin-angiotensin-aldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial.

BACKGROUND: Tubulointerstitial damage plays an important role in chronic kidney disease (CKD) with proteinuria. Urinary kidney injury molecule 1 (KIM-1) reflects tubular KIM-1 and is considered a sensitive biomarker for early tubular damage. We hypothesized that a decrease in proteinuria by using therapeutic interventions is associated with decreased urinary KIM-1 levels. STUDY DESIGN: Post hoc analysis of a randomized, double-blind, placebo-controlled, crossover trial. SETTING & PARTICIPANTS: 34 proteinuric patients without diabetes from our outpatient renal clinic. INTERVENTION: Stepwise 6-week interventions of losartan, sodium restriction (low-sodium [LS] diet), their combination, losartan plus hydrochlorothiazide (HCT), and the latter plus an LS diet. OUTCOMES & MEASUREMENTS: Urinary excretion of KIM-1, total protein, and N-acetyl-beta-d-glucosaminidase (NAG) as a positive control for tubular injury. RESULTS: Mean baseline urine protein level was 3.8 +/- 0.4 (SE) g/d, and KIM-1 level was 1,706 +/- 498 ng/d (increased compared with healthy controls; 74 ng/d). KIM-1 level was decreased by using placebo/LS (1,201 +/- 388 ng/d; P = 0.04), losartan/high sodium (1,184 +/- 296 ng/d; P = 0.09), losartan/LS (921 +/- 176 ng/d; P = 0.008), losartan/high sodium plus HCT (862 +/- 151 ng/d; P = 0.008) and losartan/LS plus HCT (743 +/- 170 ng/d; P = 0.001). The decrease in urinary KIM-1 levels paralleled the decrease in proteinuria (R = 0.523; P < 0.001), but not blood pressure or creatinine clearance. 16 patients reached target proteinuria with protein less than 1 g/d, whereas KIM-1 levels normalized in only 2 patients. Urinary NAG level was increased at baseline and significantly decreased during the treatment periods of combined losartan plus HCT only. The decrease in urinary NAG levels was not closely related to proteinuria. LIMITATIONS: Post hoc analysis. CONCLUSIONS: Urinary KIM-1 level was increased in patients with nondiabetic CKD with proteinuria and decreased in parallel with proteinuria by using losartan, sodium restriction, their combination, losartan plus HCT, and the latter plus sodium restriction. These results are consistent with the hypothesis of amelioration of proteinuria-induced tubular damage. Long-term studies are warranted to evaluate whether targeting treatment on KIM-1 can improve outcomes in patients with CKD with proteinuria.