Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease

Recent Therapeutic Advances

Although the efficacy of a low-sodium diet for relieving volume overload and hypertension in CKD is clear, educating patients with CKD to reduce dietary sodium is difficult. This was seen in an open label, randomized, controlled trial in 138 patients with stage G3–4 CKD (7). Patients were randomly assigned to self-managed sodium restriction, including self-measurement of 24-hour urinary sodium excretion by an innovative point-of-care chip device, or usual care for 3 months. As a part of the education program, patients were coached by three psychologists and one dietician who were all trained in motivational interviewing techniques. The self-management intervention was well accepted by patients, but at 3 months, it produced just a mild decrease in 24-hour sodium excretion (−30 mmol/d) as well as a small decrease in 24-hour ambulatory BP monitoring (systolic −2.2 mm Hg/diastolic −2.4 mm Hg) and fluid overload (body weight −1.5 kg). Proteinuria, a secondary outcome measure, decreased significantly (−0.4 g; −57%). However, the effects of this self-managed intervention were not seen at 6 months, and at this time, the difference in sodium excretion between the study arms was minimal (<10 mmol/d) and not significant.

An exploratory study in patients with predialysis CKD suggests that the application of BIS may improve treatment-resistant hypertension in this population (8). Similarly, a pilot trial in patients on hemodialysis showed that the application of BIS may be useful to guide dry weight prescription and reduce the risk of death in these patients (9).

Clinical Implications of Recent Advances

As discussed, a resource-intensive educational intervention to lower sodium intake produces small and transient benefits for patients with CKD. Adherence to a low-sodium diet remains an unmet clinical need in this population.

The use of diuretics is fundamental to achieve adequate volume control. Furosemide and thiazides, like hydrochlorothiazide or metazolone, have a synergistic action on natriuresis in patients with CKD. In those unresponsive to a single diuretic agent, an increase in sodium excretion can be achieved by combining these drugs. However, intensification of the use of diuretics in CKD should be done with all caution given the risk for hypokalemia, excessive volume depletion, and AKI.

High-Priority Areas for Research

Future studies in patients with CKD should investigate whether the effects of educational interventions to reduce sodium intake can be improved by educational reinforcement techniques that continuously reinforce critical points. The use of devices for self-measurement of urine sodium, a strategy similar to that adopted in patients with diabetes for the self-measurement of glucose, is an attractive possibility. Potentially cost-effective technologic options (electronic coaching) for the nutritional management of patients with CKD already exist, and ones profiled to the individual needs can be designed. Involving families and patients’ social environments, although difficult, has shown potential for improving nutrition management in other chronic diseases. Accurate evaluation of the feasibility, efficacy, and cost-effectiveness of these interventions in appropriate trials is fundamental to assess their usefulness in clinical practice. In the United States, >70% of the sodium consumed derives from processed or prepared food. Tackling the problem of industrially added sodium and poverty, which limits access to healthy foods, is a public health issue of paramount importance for the general population, and it is even more critical for the CKD population.

The low frequency of appropriate diuretic use is a notorious problem in patients with CKD. This may depend on the fact that intensive use of these drugs causes hemodynamic and metabolic side effects that demand closer clinical surveillance; these side effects are difficult to monitor in most countries with a resource-limited health scenario. Objective measurements of volume status in CKD may help to guide dietary sodium prescription and the use of diuretics. In this regard, the use of brain natriuretic peptide and probrain natriuretic peptide is of modest, if any, help for the identification of patients who are volume expanded, because these peptides mainly reflect left ventricular hypertrophy and left ventricular dysfunction in patients with CKD and in patients on dialysis. As alluded to before, BIS allows the identification of not only patients with CKD who are fluid overloaded (prevalence: 40% or higher) but also, patients with CKD who are actually volume depleted (prevalence: 20%) and may, therefore, experience side effects when exposed to these treatments. On the other hand, lung US may be useful to detect lung congestion at a preclinical stage in patients with CKD with left ventricular dysfunction. Studying these techniques is a priority research area in patients with CKD.

Although the detection of fluid overload by BIS is a useful surrogate of “hemodynamic congestion” (i.e., blood volume expansion), this technique does not provide information on “lung congestion” (that is, fluid accumulation in the most critical area of the central circulation). Because of the high prevalence of left ventricular dysfunction, patients treated by hemodialysis (6) or peritoneal dialysis (10) are almost uniquely prone to develop lung congestion, which remains asymptomatic in most patients. Lung congestion, a sequela of hemodynamic congestion, is the earliest sign of cardiopulmonary volume overload. Therefore, the application of lung US may be useful to prevent the most severe stage of lung congestion (i.e., clinical congestion), the stage characterized by dyspnea and pulmonary edema.

Although promising, these techniques still deserve proper assessment. BIS and lung US should be tested in clinical trials comparing treatment strategies guided by these techniques with standard care. In this respect, the Crit-Line Intradialytic Monitoring Benefit Study, which tested the effect of hematocrit-based intradialytic monitoring using Crit-Line on morbidity associated with ultrafiltration in comparison with standard management, represents a strong cautionary note against the superficial adoption of clinical policies guided by biomarkers before rigorous evaluation of the same policies in clinical trials. A trial testing the effect of a treatment policy guided by lung US in high-risk patients on hemodialysis, the Lung Water by Ultrasound-Guided Treatment to Prevent Death and Cardiovascular Complications in High-Risk ESKD Patients with Cardiomyopathy, is ongoing (ClinicalTrials.gov Identifier: NCT02310061). Parallel efforts are being made for testing the usefulness of BIS in patients on peritoneal dialysis in the Bioimpedance-Guided Fluid Management in Chronic Peritoneal Dialysis Patients Trial (ClinicalTrials.gov Identifier: NCT03004963).

Testing well integrated, multilevel interventions aimed at improving patient adherence to low-sodium diets and treatment policies guided by objective measures of fluid volume represent a true priority for clinical research in nephrology.

Disclosures

None.