Dietary Potassium Restriction Research Articles

A multicentral prospective cohort trial of a pharmacist-led nutritional intervention on serum potassium levels in outpatients with chronic kidney disease: The MieYaku-Chronic Kidney Disease project.

Although dietary potassium restriction is an acceptable approach to hyperkalemia prevention, it may be insufficient for outpatients with chronic kidney disease (CKD). Most outpatients with CKD use community pharmacies owing to the free access scheme in Japan. The MieYaku-CKD project included a community pharmacist-led nutritional intervention for dietary potassium restriction, with the goal of determining its efficacy for patients' awareness of potassium restriction and serum potassium levels in outpatients with CKD. This was a five-community pharmacy multicenter prospective cohort study with an open-label, before-and-after comparison design. Eligible patients (n = 25) with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 received nutritional guidance from community pharmacists. The primary outcome was a change in serum potassium levels at 12 weeks post-intervention. The eligible patients' knowledge, awareness, and implementation of potassium restriction were evaluated using a questionnaire. The median value of serum potassium was significantly reduced from 4.7 mEq/L before to 4.4 mEq/L after the intervention [p < 0.001, 95% confidence interval (CI): 0.156-0.500], with no changes in eGFR (p = 0.563, 95% CI: -2.427-2.555) and blood urine nitrogen/serum creatinine ratio (p = 0.904, 95% CI: -1.793-1.214). The value of serum potassium had a tendency of attenuation from 5.3 to 4.6 mEq/L (p = 0.046, 95% CI: 0.272-1.114) in the eGFR < 30 mL/min/1.73 m2 group. A questionnaire revealed that after the intervention, knowledge and attitudes regarding dietary potassium restriction were much greater than before, suggesting that the decrease in serum potassium levels may be related to this nutritional guidance. Our findings indicate that implementing a dietary potassium restriction guidance program in community pharmacies is feasible and may result in lower serum potassium levels in outpatients with CKD.

Overview of research progress on the association of dietary potassium intake with serum potassium and survival in hemodialysis patients, does dietary potassium restriction really benefit hemodialysis patients?

For the general population, increasing potassium intake can reduce the incidence of cardiovascular and cerebrovascular diseases. However, since hyperkalemia is a common and life-threatening complication in maintenance hemodialysis patients, which can increase the risk of malignant arrhythmia and sudden death, the current mainstream of management for hemodialysis patients is dietary potassium restriction in order to prevent hyperkalemia. Hemodialysis patients are usually advised to reduce dietary potassium intake and limit potassium-rich fruits and vegetables, but there is limited evidence to support this approach can reduce mortality and improve quality of life. There is still no consistent conclusion on the association between dietary potassium intake and serum potassium and survival in hemodialysis patients. According to the current small observational studies, there was little or even no association between dietary potassium intake and serum potassium in hemodialysis patients when assurance of adequate dialysis and specific dietary patterns (such as the plant-based diet mentioned in the article) are being followed, and excessive dietary potassium restriction may not benefit the survival of hemodialysis patients. Additionally, when assessing the effect of diet on serum potassium, researchers should not only focus on the potassium content of foods, but also consider the type of food and the content of other nutrients. However, more large-scale, multi-center clinical trials are required to provide high-quality evidence support. Besides, further research is also needed to determine the optimal daily potassium intake and beneficial dietary patterns for hemodialysis patients.

Safety and efficacy of sodium zirconium cyclosilicate for the management of acute and chronic hyperkalemia in children with chronic kidney disease 4-5 and on dialysis.

Sodium zirconium cyclosilicate (SZC), an ion-exchange resin, is effective in the control of hyperkalemia in adults with chronic kidney disease (CKD); reports of use in children are limited. Prolonged therapy with SZC to relax dietary potassium restriction in CKD has not been examined. We conducted a retrospective chart review of patients 6months to 18years of age with CKD stage 4-5 or on dialysis (5D) administered SZC for sustained hyperkalemia (potassium ≥ 5.5mEq/L, three consecutive values). Patients received SZC (0.5-10g per dose; age-based) either short-term (< 30days) or long-term (> 30days). Twenty patients with median age 10.8 (inter-quartile range 3.9, 13.4) years were treated with SZC. Short-term SZC, for 5 (3, 19) days, was associated with safe management of dialysis catheter insertions (n = 5) and access dysfunction (n = 4), and was useful during palliative care (n = 1). Serum potassium levels decreased from 6.7 (6.1, 6.9) to 4.4 (3.7, 5.2) mEq/L (P < 0.001). Long-term SZC for 5.3 (4.2, 10.1) months achieved decline in serum potassium from 6.1 (5.8, 6.4) to 4.8 (4.2, 5.4) mEq/L (P < 0.001). SZC use was associated with liberalization of diet (n = 6) and was useful in patients with poor adherence to dietary restriction (n = 3). Adverse events or edema were not observed; serum sodium and blood pressure remained stable. SZC was safe and effective for the management of acute and chronic hyperkalemia in children with CKD4-5/5D. Its use was associated with relaxation of dietary potassium restriction. Studies to examine its routine use to improve diet and nutritional status in children with CKD are required.

Dietary potassium restriction reprograms the distal tubule causing adverse metabolic consequences

Low potassium (K) intake has adverse health effects, including hypertension, osteoporosis, and nephrolithiasis. Dietary K restriction rapidly activates a K switch in the distal nephron to maintain homeostasis by reducing K excretion and activating the sodium chloride cotransporter (NCC). The distal convoluted tubule (DCT) is morphologically and functionally divided into DCT1 and DCT2, with each segment specialized for a different function. Here, we define the differences between DCT1 and DCT2 transcriptionally, examine their unique responses to potassium restriction, and detrimental physiological responses in mice.The K restriction effects were examined at 3 time points, overnight (acute), 4 days (short-term), and 4 weeks (chronic). Electrophysiology was used to assess effects of acute K deprivation on basolateral K channel (Kir4.1/5.1) activity. To determine effects of K restriction for 4 days, the DCT-targeted single-nucleus RNA-sequencing (snRNAseq) approach was applied. Female NCC-Cre-INTACT (PMID: 26087164) mice were provided either normal (NK) or K deficient (KD) diet for 4 days (short-term) and kidneys were snap-frozen for targeted snRNAseq (10X Chromium, NovaSeq) (3 mice per diet, 10,000 nuclei per mouse). Effects of chronic K-restriction were assessed by serum electrolytes, tissue clearing, and western blot.Acute K restriction stimulated basolateral K channel activity in DCT1, but not in DCT2, indicating that DCT1 and DCT2 respond differently. Although both DCT1 and DCT2 express NCC, snRNAseq data showed that DCT1 and DCT2 have distinct transcriptional signatures, with DCT1 expressing genes involved in magnesium reabsorption, and DCT2 expressing genes involved in calcium reabsorption and electrogenic sodium channel (ENaC). Four days of K restriction switched the DCT from a K-wasting state to K-sparing state, shown by reduction of gENaC ( Scnn1g) and Kallikrein ( Klk1) expression. Furthermore, K restriction decreased the expression of the calcium-handling genes Slc8a1, Calb and Vdr. When prolonged, K restriction led to increases in NCC, reduction in ENaC cleavage, and elongation of the DCT. It also led to calcium wasting (plasma iCa in NK, 1.38 ± 0.03, n=7; KD, 1.24 ± 0.01 mM, n=6) and reduction in calbindin D-28k protein.Our results suggest that DCT1 and DCT2 both express NCC, but have distinct transcriptomic signatures with unique roles in magnesium and calcium transport, respectively. Dietary K restriction reprograms DCT2 cells to be more like DCT1 cells, thereby maintaining K balance but contributing to calcium wasting as a complication. NIH DK51496, NIH DK054983, VA 1I01BX002228, LeDucq Fondation This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dietary Potassium Restriction Activates a Proliferative Cell Population to Remodel the Distal Convoluted Tubule

Dietary Potassium Restriction Activates a Proliferative Cell Population to Remodel the Distal Convoluted Tubule

Dietary potassium intake, kidney function, and survival in a nationally representative cohort

In healthy adults, higher dietary potassium intake is recommended given that potassium-rich foods are major sources of micronutrients, antioxidants, and fiber. Yet among patients with advanced kidney dysfunction, guidelines recommend dietary potassium restriction given concerns about hyperkalemia leading to malignant arrhythmias and mortality. Given sparse data informing these recommendations, we examined associations of dietary potassium intake with mortality in a nationally representative cohort of adults from the NHANES. We examined associations between daily dietary potassium intake scaled to energy intake (mg/1000kcal), ascertained by 24-h dietary recall, and all-cause mortality among 37,893 continuous NHANES (1999-2014) participants stratified according to impaired and normal kidney function (estimated glomerular filtration rates <60 and ≥60mL · min-1 · 1.73m-2, respectively) using multivariable Cox models. We also examined the impact of the interplay between dietary potassium, source of potassium intake (animal- compared with plant-based sources), and coexisting macronutrient and mineral consumption upon mortality. Among participants with impaired and normal kidney function, the lowest tertile of dietary potassium scaled to energy intake was associated with higher mortality (ref: highest tertile) [adjusted HR (aHR): 1.18; 95% CI: 1.02, 1.38 and aHR: 1.17; 95% CI: 1.06, 1.28, respectively]. Compared with high potassium intake from plant-dominant sources, participants with low potassium intake from animal-dominant sources had higher mortality irrespective of kidney function. Among participants with impaired kidney function, pairings of low potassium intake with high protein, low fiber, or high phosphorus consumption were each associated with higher death risk. Lower dietary potassium scaled to energy intake was associated with higher mortality, irrespective of kidney function. There was also a synergistic relation of higher potassium intake, plant-based sources, and macronutrient/mineral consumption with survival. Further studies are needed to elucidate pathways linking potassium intake and coexisting dietary factors with survival in populations with and without chronic kidney disease.

Potassium Intake-(Un)Expected Non-Predictor of Higher Serum Potassium Levels in Hemodialysis DASH Diet Consumers.

As high serum potassium levels can lead to adverse outcomes in hemodialysis (HD) patients, dietary potassium is frequently restricted in these patients. However, recent studies have questioned whether dietary potassium really affects serum potassium levels. The dietary approaches to stop hypertension (DASH) diet is considered a healthy dietary pattern that has been related to lower risk of developing end-stage kidney disease. The aim of this study was to analyze the association between a dietary pattern with high content of potassium-rich foods and serum potassium levels in HD patients. This was an observational, cross-sectional, multicenter study with 582 HD patients from 37 dialysis centers. Clinical and biochemical data were registered. Dietary intake was obtained using the Food Frequency Questionnaire. Adherence to the DASH dietary pattern was obtained from Fung’s DASH index. All statistical tests were performed using SPSS 26.0 software. A p-value lower than 0.05 was considered statistically significant. Patients’ mean age was 67.8 ± 17.7 years and median HD vintage was 65 (43–104) months. Mean serum potassium was 5.3 ± 0.67 mEq/L, dietary potassium intake was 2465 ± 1005 mg/day and mean Fung´s Dash Index was 23.9 ± 3.9. Compared to the lower adherence to the DASH dietary pattern, patients with a higher adherence to the DASH dietary pattern were older (p < 0.001); presented lower serum potassium (p = 0.021), serum sodium (p = 0.028), total fat intake (p = 0.001) and sodium intake (p < 0.001); and had higher carbohydrate intake (p < 0.001), fiber intake (p < 0.001), potassium intake (p < 0.001), phosphorus intake (p < 0.001) and body mass index (p = 0.002). A higher adherence to this dietary pattern was a predictor of lower serum potassium levels (p = 0.004), even in the adjusted model (p = 0.016). Following the DASH dietary pattern, which is rich in potassium, is not associated with increased serum potassium levels in HD patients. Furthermore, a higher adherence to the DASH dietary pattern predicts lower serum potassium levels. Therefore, generalized dietary potassium restrictions may not be adequate, at least for those with a DASH diet plan.

MO487: Rates of Hyperkal a EMIA and Management Patterns in a Tertiary Outpatient Renal Clinic

Abstract BACKGROUND AND AIMS The optimal ambulatory management of hyperkalaemia (HK) in patients with chronic kidney disease (CKD) is still an important unmet challenge. Common strategies include dose reduction or discontinuation of nephroprotective medications (e.g. renin-angiotensin-aldosterone system inhibitors [RAASi]), dietary restriction of potassium (K), loop diuretics, bicarbonate and sodium polystyrene sulfonate; all the above interventions are characterized by specific pitfalls and limitations. However, new potassium binders are available that might improve the management of chronic hyperkalaemia. In the light of their widespread use, it will be important to increase our knowledge of the incidence, characteristics and current real-life management patterns of hyperkalaemia in CKD patients. METHOD We performed a retrospective analysis of patients followed at our tertiary outpatient renal clinic from 1 April 2016 to 31 December 2021. HK was defined as serum K &amp;gt; 5.0 mmol/L and stratified according to severity. eGFR was estimated with the CKD-EPI equation and stratified according to the KDIGO criteria. The time span between each episode of HK was assessed with Poisson regression models. A sample of 100 HK events was selected at random for manual chart review of the management strategies performed: Information was abstracted using a standardized form. RESULTS The final analysis included 1844 patients, contributing 4480 occasions. Baseline characteristics by hyperkalaemia status are reported in Table 1. Patients with HK were older, with lower eGFR and a higher prevalence of diabetes. At least one episode of HK was documented in 525 patients (28.5%) and among them, 166 patients (31.6%) had at least two HK episodes (on average, 1.55 episodes/patient). HK events were more frequent among patients with more advanced stages of CKD. The time span between episodes decreased significantly (Fig. 1): on average, each episode was 17% [95% confidence interval (95% CI), 3%–29%) closer to the subsequent (P = .016). Of the 100 HK episodes randomly reviewed, 79% received no intervention, whereas 21% triggered at least one intervention. The probability of intervention increased with increasing severity of HK: 8.6%, 35.9%, 50.0% and 100% for K-values 5.0–5.4, 5.5–5.9, 6.0–6.4 and ≥6.5 mmol/L, respectively. Most interventions included dose reduction or discontinuation of RAASi. One patient was sent to the emergency department for urgent examination and treatment (K 7.0 mmol/L). CONCLUSION Hyperkalaemia is a common and recurring problem for patients with renal impairment: It occurs in almost one-third of the overall population of this study, and many hyperkalaemic patients experience recurring events. As expected, the prevalence rates of hyperkalaemia increase with worsening CKD severity. Furthermore, the decreased time span between consecutive episodes highlights an accelerated recurrence pattern of hyperkalaemia despite interventions.

MO904: Potassium Intake Does Not Predict High Serum Potassium Levels in Haemodialysis Dash Diet Consumers

Abstract BACKGROUND AND AIMS As high serum potassium levels can lead to adverse outcomes in haemodialysis (HD) patients, dietary potassium is frequently restricted in these patients. However, recent studies have questioned whether dietary potassium really affects serum potassium levels. Dietary approaches to stop hypertension (DASH) emphasizes the consumption of potassium rich foods, specially from plant sources, such as: fruits, vegetables, whole grains, nuts and seeds. The aim of this study was to analyze the association between the DASH dietary pattern and serum potassium levels. METHOD This was an observational cross-sectional multicentre study with 582 HD patients from 37 dialysis centers. Clinical and biochemical data were registered. Dietary intake was obtained using the Food Frequency Questionnaire. Adherence to DASH dietary pattern was obtained from Fung´s DASH index (8–40 points). For the statistical analysis, Fung´s DASH index was categorized into terciles and mean differences were analyzed with one-way ANOVA. Linear regression was used to analyze the relationship between serum potassium and adherence to the Dash dietary pattern. The multivariate model was adjusted to age, gender, presence of diabetes mellitus, energy intake, dietary potassium intake, residual diuresis, dialysis adequacy (Kt/V), dialysis vintage and intake of potassium binders. All statistical tests were performed using SPSS 26.0 software. A P-value lower than 0.05, was considered statistically significant. RESULTS Patients’ mean age was 67.8 ± 17.7 years and median HD vintage was 65 (43–104) months. Mean serum potassium was 5.3 ± 0.67 mEq/L, dietary potassium intake was 2465 ± 1005 mg/day and mean Fung´s Dash Index was 23.9 ± 3.9. Of the whole sample, 36.4% of the patients presented low adherence to the DASH dietary pattern (0–22 points), 39.0% presented a moderate adherence (23–26 points) whereas 24.6% a high adherence (≥27 points). Comparing to the lower adherence, patients with a higher adherence to the DASH dietary pattern were older (P &amp;lt; 0.005), presented lower serum potassium (P = 0.021), serum sodium (P = 0.028), albumin (P = 0.030), creatinine (P &amp;lt; 0.005), energy intake (P = 0.006), protein intake (P = 0.010), total fat intake (P = 0.001), sodium intake (P &amp;lt; 0.005), lean tissue index (P = 0.006) and higher carbohydrates intake (P = 0.007), fiber intake (P &amp;lt; 0.005), potassium intake (P &amp;lt; 0.005), body mass index (P = 0.002) and fat tissue index (P &amp;lt; 0.005). No differences were observed in potassium binders, Kt/V, C-reactive protein nor haemoglobin. A higher adherence to this dietary pattern was a predictor of lower serum potassium levels (P = 0.004), even in the adjusted model (P = 0.016). CONCLUSION Most of the patients presented a moderate adherence to the DASH dietary pattern. Following this dietary pattern, which is rich in potassium, is not associated with increased serum potassium levels in HD patients. What is more, a higher adherence to the DASH dietary pattern predicts lower serum potassium levels. Therefore, tight dietary potassium restrictions may not be adequate, at least for those with a DASH diet plan as a more flexible diet, especially regarding plant-based foods rich in potassium, may promote other health benefits and reduce patient´s dietary plan limitations.

Phosphorylation‐Dependent Endocytosis of ROMK Limits Urinary Potassium Loss

ROMK channels in the aldosterone‐sensitive distal nephron are tightly regulated to maintain potassium balance. In response to potassium restriction, ROMK channels are internalized from the apical membrane, safeguarding against extensive potassium loss. Previously, we found the clathrin adaptor protein, ARH, directly binds to ROMK to stimulate endocytosis (Fang et al, JCI ‘09). WNK signaling pathway has been implicated in activating ROMK endocytosis, but the mechanism is not clear, and physiological significance of ARH‐mediated ROMK regulation remains uncertain. To tackle these questions, we explored how WNK kinases activate ARH and compared the homeostatic response to dietary potassium restriction in wild type and ARH KO mice.In vitro phosphorylation studies revealed ARH is phosphorylated by ERK, which in turn is activated by L‐WNK1 or WNK4. Examination of the phosphorylation cascade revealed that dietary potassium restriction increases phosphorylation of ERK and ARH‐S14 in the kidney, coincident with phospho‐activation of the WNKs, and reduction of ROMK apical surface expression. We found phosphorylation of ARH at S14 prevents its degradation, stimulates its membrane association, and this enhances ROMK endocytosis. ARH KO mice exhibit an increase in glycosylated ROMK in the renal cortex without changes in the abundance of the core‐glycosylated or unglycosylated forms, consistent with inhibition of post‐endocytic degradation. In dietary potassium deficiency, ARH KO mice are unable to reduce ROMK protein to the same extent as WT mice, and thus exhibit excessive urinary potassium loss compared to WT mice.These studies identify ARH as a downstream effector of the WNK/ERK pathway that stimulates ROMK endocytosis in potassium deficiency.

Uncovering Distal Convoluted Tubule (DCT) Heterogeneity with Enriched DCT Single‐Nucleus RNA‐Sequencing

The mammalian kidneys play a critical role in regulation of electrolyte balance and blood pressure. At least 14 kidney tubule segments are described, of which the distal convoluted tubule (DCT) is the shortest; yet this short segment plays a crucial role in a variety of homeostatic processes, including sodium, potassium, calcium and magnesium handling. The DCT is morphologically and functionally heterogeneous and comprises DCT1 and DCT2. A “shotgun” single‐cell RNA sequencing (scRNAseq) approach transcriptionally profiles all cells from a piece of kidney tissue, which may allow abundant cell types to overwhelm minority cell types, such as DCT, thereby masking their complex heterogeneity. Recently, Chen et al. used the targeted scRNAseq analysis and identified 6 populations of DCT1 cells; yet the DCT2 was not well represented and therefore poorly resolved.To understand the heterogeneity within the DCT2 population, we used “Isolation of Nuclei TAgged in specific Cell Types” (INTACT), which fluorescently labels nuclei from genetically targetable cells. Combined with the NCC (sodium chloride cotransporter)‐driven inducible Cre recombinase, DCT nuclei can be enriched using Fluorescence‐Activated Nuclei Sorting (FANS). Female NCC‐Cre‐INTACT mice were treated with Tamoxifen to induce expression of the GFP‐tagged SUN1, a nuclear membrane protein. Mice were provided either normal (NK) or potassium deficient diet (KD) for 4 days and kidneys were harvested. Nuclei from one kidney cortex were isolated and 10,000 GFP‐positive nuclei from each mouse were input into 10X Genomics Chromium Controller and the libraries were sequenced using NovaSeq. The resulting dataset was analyzed using Seurat to determine the number of populations and their identities using the UMAP algorithm for analysis and visualization.After data quality control, we detected 24,054 genes across 70,233 cells. Unbiased clustering and UMAP visualization revealed 12 clusters, with most cells from the DCT (78%) indicating the success of the enrichment process. Among those, 70% of the cells were from DCT1 and 30% from DCT2. There was clear separation of DCT1 from DCT2, with DCT1 enriched in Trpm7, Egf, Umod and Erbb4, and DCT2 in Slc8a1, Calb1, S100g, Trpv5, and Scnn1g. After further analysis of the DCT2 population, we identified two specialized populations, DCT2‐α and DCT2‐β. The DCT2‐α is enriched in NCC, magnesium and calcium‐related genes (Slc12a3, Wnk1, Slc8a1, Calb1, Trpm6, etc.) whereas DCT2‐β is enriched in mineralocorticoid receptors and epithelial sodium channel‐related genes (Nr3c2, Klk1, Scnn1b, Scnn1g, etc.), indicating that DCT2‐α is more similar to DCT1 and DCT2‐β to collecting duct. Four‐day KD treatment decreased the Klk1, Scnn1b and Scnn1g expression levels in DCT2‐β, indicating that some DCT2 cells may reprogram to retain potassium in response to the short‐term potassium deficiency.Our results suggest that DCT2 cells fall into specialized populations that likely serve different functions in electrolyte handling. The DCT2 is plastic and can transform from potassium excretion to potassium sparing in response to dietary potassium restriction to maintain electrolyte balance.

Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis.

Dietary potassium restriction in people receiving maintenance hemodialysis is standard practice and is recommended in guidelines, despite a lack of evidence. We aimed to assess the association between dietary potassium intake and mortality and whether hyperkalemia mediates this association. A total of 8043 adults undergoing maintenance hemodialysis in Europe and South America were included in the DIETary intake, death and hospitalization in adults with end-stage kidney disease treated with HemoDialysis (DIET-HD) study. We measured baseline potassium intake from the Global Allergy and Asthma European Network food frequency questionnaire and performed time-to-event and mediation analyses. The median potassium intake at baseline was 3.5 (interquartile range, 2.5-5.0) g/d. During a median follow-up of 4.0 years (25,890 person-years), we observed 2921 (36%) deaths. After adjusting for baseline characteristics, including cardiac disease and food groups, dietary potassium intake was not associated with all-cause mortality (per 1 g/d higher dietary potassium intake: hazard ratio, 1.00; 95% confidence interval [95% CI], 0.95 to 1.05). A mediation analysis showed no association of potassium intake with mortality, either through or independent of serum potassium (hazard ratio, 1.00; 95% CI, 1.00 to 1.00 and hazard ratio, 1.01; 95% CI, 0.96 to 1.06, respectively). Potassium intake was not significantly associated with serum levels (0.03; 95% CI, -0.01 to 0.07 mEq/L per 1 g/d higher dietary potassium intake) or the prevalence of hyperkalemia (≥6.0 mEq/L) at baseline (odds ratio, 1.11; 95% CI, 0.89 to 1.37 per 1 g/d higher dietary potassium intake). Hyperkalemia was associated with cardiovascular death (hazard ratio, 1.23; 95% CI, 1.03 to 1.48). Higher dietary intake of potassium is not associated with hyperkalemia or death in patients treated with hemodialysis.

Management of Hyperkalemia in Heart Failure.

Hyperkalemia is a common electrolyte abnormality in heart failure (HF) that can cause potentially life-threatening cardiac arrhythmias and sudden cardiac death. HF patients with diabetes, chronic kidney disease and older age are at higher risk of hyperkalemia. Moreover, hyperkalemia is also often associated with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and sacubitril-valsartan. In clinical practice, the occurrence of hyperkalemia is a major concern among the clinicians and often limits RAASi use and/or lead to dose reduction or discontinuation, thereby reducing their potential benefits for HF. Furthermore, recurrent hyperkalemia is frequent in the long-term and is associated with an increase in hyperkalemia-related hospitalizations. Therefore, management of hyperkalemia has a special importance in HF patients. However, treatment options in chronic management are currently limited. Dietary restriction of potassium is usually ineffective with variable adherence. Sodium polystyrene sulfonate is commonly used, but its effectiveness is uncertain and reported to be associated with intestinal toxicity. New therapeutic options such as potassium binders have been suggested as potentially beneficial agents in the management of hyperkalemia. This document discusses prevalence, predictors and management of hyperkalemia in HF, emphasizing the importance of careful patient selection for medical treatment, uptitration of the doses of RAASi, regular surveillance of potassium and treatment options of hyperkalemia.

Dietary Modelling to Explore the Impact of Potassium Chloride Replacement for Sodium in Bread for Adults with Chronic Kidney Disease.

Food manufacturers are increasingly substituting potassium chloride (KCl) in food products so as to reduce the sodium chloride content. Bread and bread products are common staple foods in many Western households and are a target for recipe reformulation using KCl. Given that chronic kidney disease (CKD) is a medical condition of global importance that requires dietary potassium restriction in the later stages, we sought to evaluate the impact and safety of varying levels of KCl substitution in bread products. We undertook a secondary analysis of dietary data from the National Nutrition and Physical Activity Survey 2011–2012 for 12,152 participants (154 participants with CKD). The sodium chloride content in bread and bread-based products was substituted with 20%, 30%, and 40% of KCl. The contribution of these alterations in the dietary potassium intake to the total daily potassium intake were then examined. The replacement of sodium in bread with varying amounts of KCl (20%, 30%, and 40%) resulted in one third of people with CKD exceeding the safe limits for dietary potassium consumption (31.8%, 32.6%, and 33%, respectively). KCl substitution in staple foods such as bread and bread products have serious and potentially fatal consequences for people who need to restrict dietary potassium. Improved food labelling is required for consumers to avoid excessive consumption.

Behavioural strategies to self-manage low-potassium diets in chronic kidney disease.

Dietary potassium restrictions may be challenging to follow, due in part to the restrictive nature of recommendations on foods people enjoy. Little is known how people incorporate low-potassium diets into their lifestyles. To examine the self-directed behavioural strategies people employ to follow low-potassium advice. Qualitative methodology. Thirty-four adults with chronic kidney disease. Semistructured interviews were undertaken in an outpatient department. Thematic analysis was undertaken on transcribed interviews. Analysis identified three themes: 'Differing opinions of food'; 'Food generates positive emotions'; and 'Doing what works'. Participants described foods providing different levels of enjoyment. Favourite foods in their habitual diet held either a physiological or a psychological value to them. Five subthemes underpinned the 'Doing what works' theme that described the self-management behaviours used by participants to follow low-potassium dietary advice. These were positive reframing; reflection; self-talk; social support; decisional balance; paradoxical instruction; and knowledge shaping. These techniques helped overcome the conflict between favourite food preferences and dietary restrictions. Dietary restrictions proved more challenging where an emotional connection to a favourite food existed. Restrictions on less preferred foods did not present participants with the same self-management challenges. Promoting behavioural change techniques such as decisional balance, and social support may be a useful strategy to empower people following dietary restrictions. Practitioners should understand whether suggested dietary restrictions include an individual's favourite food; the value attached to it, and explore specific ways to include favourite foods in some way when discussing a low-potassium diet.

Dietary Potassium Intake and Mortality in a Prospective Hemodialysis Cohort

Among hemodialysis patients, clinical practice guidelines recommend dietary potassium restriction given concerns about potential hyperkalemia leading to malignant arrhythmias and mortality. However, there are sparse data informing recommendations for dietary potassium intake in this population. We thus sought to examine the relationship between dietary potassium intake and death risk in a prospective cohort of hemodialysis patients. Among 415 hemodialysis patients from the prospective "Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease" cohort recruited across 16 outpatient dialysis clinics, information regarding dietary potassium intake was obtained using Food Frequency Questionnaires administered over October 2011 to March 2015. We first examined associations of baseline dietary potassium intake categorized as tertiles with mortality risk using Cox regression. We then examined clinical characteristics associated with low dietary potassium intake (defined as the lowest tertile) using logistic regression. In expanded case-mix Cox analyses, patients whose dietary potassium intake was in the lowest tertile had higher mortality (ref: highest tertile) (adjusted hazard ratio 1.74, 95% confidence interval 1.14-2.66). These associations had even greater magnitude of risk following adjustment for laboratory and nutritional covariates (adjusted hazard ratio 2.65, 95% confidence interval 1.40-5.04). In expanded case-mix restricted cubic spline analyses, there was a monotonic increase in mortality risk with incrementally lower dietary potassium intake. In expanded case-mix logistic regression models, female sex; higher serum bicarbonate; and lower dietary energy, protein, and fiber intake were associated with low dietary potassium intake. In a prospective cohort of hemodialysis patients, lower dietary potassium intake was associated with higher mortality risk. These findings suggest that excessive dietary potassium restriction may be deleterious in hemodialysis patients, and further studies are needed to determine the optimal dietary potassium intake in this population.

Handouts for Low-Potassium Diets Disproportionately Restrict Fruits and Vegetables

Several recent publications, including an expert summary on hyperkalemia management, have encouraged plant-based foods for patients with chronic kidney disease (CKD) and highlighted the impact of potassium additives on total potassium intake. The aim of this research brief was to investigate if and/or how current recommendations for low-potassium diet may incorporate these new recommendations. Using a geographical approach, each province's and territory's government health and renal program (where applicable) website was reviewed for resources on dietary potassium restriction. All handouts/booklets/printable webpages were obtained and reviewed. Eighteen resources from 6 provincial health agencies in Canada were included. Six additional resources from national agencies were also included, 4 from Canada and 2 from the United States. The 5 most commonly restricted foods were bananas, potatoes, oranges, cantaloupe, and avocados. All resources recommended restriction of fruits and vegetables, 67% recommended restriction of dairy products, 57% recommended restriction of whole grain products, 62% recommended restrictions of plant-based proteins, and 67% mentioned restriction of other foods (such as coffee, tea, and chocolate), 28% mentioned restriction of potassium additives in ultraprocessed foods. Low-potassium diets primarily restrict fruits and vegetables while the least common restriction is ultraprocessed food. Several recent publics have recommended a greater focus on ultraprocessed versus unprocessed food for hyperkalemia management. These new recommendations differ from current teaching materials that predominately restrict plant-based foods to manage hyperkalemia in CKD. Updates will likely be needed to current resources to reflect new recommendations.

Nutritional Management of the Pediatric CKD Patient

Children with chronic kidney disease (CKD) have unique nutritional needs related to decreased kidney function. This review discusses outcomes related to nutritional status in children with CKD. It reviews recommendations specific to children with CKD including nutritional assessment, energy needs, and macro- and micronutrient requirements. In addition, other considerations including supplemental feeding and potential barriers are briefly summarized. While malnutrition has been long associated with CKD, obesity is increasingly being recognized in CKD and may contribute to progression of disease. The practice of dietary potassium restriction is being questioned. Education regarding phosphorus management should include inorganic sources from food additives and preservatives in addition to the usual organic sources of phosphorus. There are emerging options for formula alternatives including blenderized diets that meet the dietary restrictions of this population. Recognizing and addressing food insecurity and providing guidance on cooking techniques may enhance adherence. The nutritional management of children with CKD is complex. An individualized approach by a multi-disciplinary team can help educate and promote success in these lifelong dietary modifications.

Experiences of the Dietary Management of Serum Potassium in Chronic Kidney Disease: Interviews With UK Adults on Maintenance Hemodialysis

Dietary potassium restrictions in kidney disease are complex to follow and may reduce quality of life. However, details on this impact are sparse. We therefore sought to explore patients' perspectives on the experienced impact of following low-potassium diets, to inform clinical practice and research. Qualitative semistructured interviews were undertaken in a UK teaching hospital with adults undergoing maintenance hemodialysis. Audio-recorded, transcribed interviews underwent thematic analysis. 34 adults (19 women, 15 men, and mean age 66.7±10.9years) with chronic kidney disease (CKD) participated. Our analysis identified three themes with subthemes: "What is left for me to eat now?"; "I'm obviously different"; "Food can be socially awkward", and one outlying theme: "Money doesn't grow on trees." Practical difficulties experienced when coming to terms with dietary restrictions meant testing out advice and experimenting with low- and high-potassium foods, to find a reasonable compromise, despite worries they could die from eating too much potassium. Interactions with food providers were dependent on pre-existing relationships, and maintaining these, at the expense of their dietary needs. Obtaining dietary requirements in restaurants often resulted in conflict with less concern for maintaining a relationship with those in the restaurant. Some individuals experienced financial difficulties, and decisions were made to prioritize family needs over their own dietary requirements. Low-potassium diets bring practical and psychosocial consequences which significantly impacts people living with CKD. Renal health professionals should offer more support to people on a low-potassium diet. Public education on dietary potassium requirements in CKD, particularly in the food service industry to increase awareness, may be a worthwhile intervention.

Four weeks of dietary potassium restriction causes distal convoluted tubule remodeling

Previous studies have described a ‘renal potassium switch’ within the distal nephron that turns on the thiazide‐sensitive Na‐Cl cotransporter (NCC) in the distal convoluted tubule (DCT) in response to low potassium intake and off in response to high potassium intake. Studies using genetically modified mice indicate that decreased NCC activity is associated with decreased DCT length and mass; increased NCC activity is associated with increased, DCT length and mass. The aim of our study was to test whether dietary potassium intake causes the DCT remodeling physiologically.Male C57Bl/6 mice were provided either control potassium diet or low potassium diet for four weeks and blood and kidneys were harvested. To determine the length of the DCT in three dimensions, we used Ethyl‐cinnamate‐based optical clearing, combined with whole‐mount immunolabeling, confocal microscopy and three‐dimensional morphometric analysis.Mice on low potassium diet for four weeks were severely hypokalemic (plasma potassium &lt;2 mM) compared with mice on control diet (4.1 mM). Western‐blot analysis of the whole kidney confirmed that total and phosphorylated NCC were higher in mice on low potassium diet, compared to mice on control diet. By immunolabeling with pThr53‐NCC antibody, we visualized the DCTs in optically cleared kidney slices. Three‐dimensional morphometric analysis suggested that four‐weeks of low potassium diet (487±16 μm, n=5) increased DCT length by 13% compared to NK diet (431±3 μm, n=3).Our results indicate that the DCT remodels physiologically to maintain potassium homeostasis. Additional animals are currently being studied.Support or Funding InformationLeDucq Fondation, KidneyCure