POTASSIUM-RICH SALT SUBSTITUTES IN KIDNEY TRANSPLANT RECIPIENTS

Overview

Excessive sodium intake and inadequate potassium intake in the diet are known risk factors for the development of arterial hypertension and an increased risk of cardiovascular events. Data from randomized controlled trials show that the use of salt substitutes with reduced sodium and increased potassium content represent an effective way to reduce dietary sodium intake, blood pressure and the occurrence of cardiovascular events. Patients adhere well to the use of salt substitutes as they do not have to change their daily cooking and seasoning habits and the taste is comparable to that of regular salt. The World Health Organization (WHO) also suggests the use of salt substitutes as an acceptable strategy for reducing dietary salt intake and thus lowering blood pressure and the burden of cardiovascular disease. Recommendations for the use of salt substitutes are not uniform, primarily because of the potential risk of adverse events with increased potassium intake in some individuals, such as patients with advanced chronic kidney disease (CKD), patients receiving potassium-sparing diuretics, and patients receiving potassium supplements. Nephrology guidelines rarely comment on the use of potassium-rich salt substitutes or discourage their use in patients with advanced stage 4 and 5 CKD, with the exception of Chinese guidelines, which mention the use of potassium-rich salt substitutes in CKD patients not on dialysis depending on serum potassium levels. CKD patients have largely been excluded from clinical trials of potassium-rich salt substitutes, so there is insufficient data on their safety and efficacy in CKD patients. In this randomized controlled trial, we will investigate the effects of using potassium-enriched salt substitutes on blood pressure control and serum potassium levels in kidney transplant recipients. In the intervention group, patients will use potassium-enriched salt substitutes at home in a ratio of 75% sodium chloride and 25% potassium chloride instead of regular table salt (100% sodium chloride) for cooking and seasoning food. In the control group, patients will use regular salt at home for cooking and seasoning food. The intervention and control groups will each include 40 to 50 patients who will be monitored for 12 weeks. The study's main focus will be the change in serum potassium and blood pressure before and after the intervention. We expect to confirm the positive effects of potassium-enriched salt substitutes on blood pressure in kidney transplant recipients without causing undesirable hyperkalemia.

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, especially in patients with chronic kidney disease and kidney transplantation. Arterial hypertension is one of the most important risk factors for the occurrence of cardiovascular diseases. Despite advances in modern medicine, the treatment of arterial hypertension is often a major challenge, partly due to patients' poor adherence to medication and lifestyle changes, including adherence to dietary recommendations. In addition to a reduced sodium intake, an increased potassium intake also plays an important role in lowering blood pressure. The mechanism of increased sodium intake in the development of high blood pressure is probably related to the inability of the kidneys to excrete excess sodium. Potassium deficiency leads to additional sodium retention as it stimulates the activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Conversely, an increased potassium intake has the effect of reducing salt sensitivity. Increased potassium intake inhibits the phosphorylation of the NaCl cotransporter and simultaneously reduces sodium reabsorption in the proximal tubule and/or in the ascending limb of the loop of Henle. Numerous epidemiological studies have shown an inverse relationship between potassium intake and blood pressure. The large international INTERSALT study showed that systolic blood pressure falls by an average of 2 to 3 mmHg when potassium intake is increased by 30 to 45 mmol/day. Reducing sodium intake and increasing potassium intake is likely to be an effective measure for treating arterial hypertension and cardiovascular disease in the population. Recommendations for the use of salt substitutes to lower blood pressure and prevent cardiovascular disease are not uniform, primarily because of the potential risk of adverse events (especially hyperkalemia) with increased potassium intake in certain individuals such as patients with advanced chronic kidney disease (CKD), patients receiving potassium-sparing diuretics and patients receiving potassium supplements. Nephrology guidelines rarely mention the use of potassium-rich salt substitutes or advise against it in patients with advanced CKD stages 4 and 5, with the exception of Chinese guidelines, which mention the use of potassium-enriched salt substitutes in non-dialysis CKD patients, depending on the serum potassium level. CKD patients have been mostly excluded from clinical studies of the use of potassium-enriched salt substitutes, so there is not enough data available for CKD patients on the safety and efficacy of potassium-enriched salt substitutes. A review of the literature suggests that different sources of potassium (diet or potassium supplements) have different effects on serum potassium levels in patients with CKD. The effect of potassium-enriched salt substitutes on serum potassium levels in renal patients is unknown. A study is currently underway in the United States to study the effect of salt substitutes on serum potassium and blood pressure in hemodialysis patients. Since this is a population of patients at increased risk for hyperkalemia, the primary goal is safety, namely the detection of hyperkalemia. In this randomized single-blind controlled trial, we want to examine the effect of using potassium-enriched salt substitutes on serum potassium and blood pressure in kidney transplant patients with hypertension. In the intervention group, patients will use potassium-enriched salt substitutes at home in a ratio of 75% sodium chloride and 25% potassium chloride instead of regular table salt for cooking and seasoning food. In the control group, patients will use table salt (100% sodium chloride) at home for cooking and seasoning food. Potassium-enriched salt substitutes and 100% sodium chloride will be prepared for patients in the hospital pharmacy. During the study, we will not introduce new antihypertensive medications or medications that affect serum potassium. If the patient is receiving potassium supplements before inclusion in the study, they will be discontinued at least a week before the start of the study. Before the start of the intervention, we will measure the patients' body composition and check the patients' dietary habits using a questionnaire. After the intervention, the patients will report any changes in the taste of home-cooked food. The main purpose of the study is: * to show that the use of salt substitutes in kidney transplant patients does not lead to a significantly increased risk of hyperkalemia. * to show that the use of salt substitutes in kidney transplant recipients has an effect on lowering blood pressure and is thus a safe and effective measure in the management of arterial hypertension in this population. We expect a mild effect on blood pressure reduction in kidney transplant recipients with no significant increased risk of hyperkalemia.