The gut–kidney–heart axis in chronic kidney disease

The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in health and disease. Emerging evidence has revealed that the gut microbiota is significantly altered in patients with chronic kidney disease (CKD), along with impaired intestinal barrier function. These alterations allow translocation of various gut-derived products into the systemic circulation, contributing to the development and progression of CKD and cardiovascular disease (CVD), partly mediated by chronic inflammation. Among potentially toxic gut-derived products identifiable in the systemic circulation, bacterial endotoxin and gut metabolites (e.g., p-cresyl sulfate and trimethylamine-N-oxide) have been extensively studied for their immunostimulatory and atherogenic properties. Recent studies have also suggested similar biological properties of bacterial DNA fragments circulating in the blood of patients with CKD, even in the absence of overt infections. Despite the accumulating evidence of the gut microbiota in CKD and its therapeutic potential for CVD, the precise mechanisms for multidirectional interactions between the gut, kidney, and heart remain poorly understood. This review aims to provide recent evidence on the associations between the gut microbiota, CKD, and CVD, and summarize current understanding of the potential pathophysiological mechanisms underlying the “gut–kidney–heart” axis in CKD

Provision of meals on wheels to the elderly : case studies in the era of local government reform

Australia’s ageing population is on the increase. It is predicted that by 2021 one quarter of Victoria’s elderly population will be aged 60 and over. Not only are people living longer, but they also wish to remain living in the community. The Home and Community Care (HACC) Program was established in 1985 to facilitate and assist the elderly and disabled to remain in their home. In Victoria around 51% of HACC funds are managed by local governments, a level of government that has recently undergone major reforms, which ultimately impacted on the manner in which services were provided. The HACC program funds Meals on Wheels, a service that provides meals for those elderly who no longer can prepare their own meals. The aim of this study was to assess the Meals on Wheels service provided by two Melbourne councils with different service philosophies. The study has four main components: (1) Menu analysis by food and variety; (2) Analysis of actual meals; (3) Clients assessment of Food Services; and (4) Client assessment of the organoleptic qualities of Meals on Wheels. Two Melbourne councils were chosen for their different approaches to service delivery. The City of South tendered out both meal production and delivery, while the City of North maintained its MOW service in-house. The case study method of research allowed for each council’s service to be assessed objectively and without comparison. Several methodologies were used for collecting data in this study. Menu analysis was carried out by comparing the MOW menus with the HACC menu planning guidelines together with general menu planning principles. Analysis of actual meals was in two stages. The weights of the meals were recorded and compared with the HACC recommended food serving portions and meal combinations over a five-day period were analysed for their nutrient contents. Face to face interviews were conducted with clients for their assessment of MOW and the assessment of the organoleptic qualities of the meals was carried out over a five-day period. The results concluded that both councils menus were based on sound menu planning principles, but did not conform with Home and Community Care menu planning guidelines fully and did not include a serve of bread, fruit and milk. The weight analysis of the meal combinations revealed some discrepancies between actual meals and Home and Community Care guidelines by not meeting the recommended serving sizes. Meal combinations generally met Home and Community Care standard for kilojoule and protein, but other nutrients, such as thiamin, riboflavin, magnesium, calcium and zinc were generally below the recommended levels for Meals On Wheels. The majority of study group lived alone and received four to five meals per week. Delivery times of meals, selective menus and food quality were issues raised by clients. Whilst the quality and variety of vegetables was raised by clients they generally rated the organoleptic qualities of the meals as satisfactory. This study examined the four components of the service. A simple method of evaluation the service was developed, which highlight discrepancies with HACC standards and encouraged the councils to set a customer satisfaction standard. A number of recommendations are made to ensure that meals are aesthetically pleasing, including a list of different methods for preparing vegetables. The provision of additional foods, such as a “snack pack” is recommended to improve the supply of essential nutrients that were below the Home and Community Care standards. Meals on Wheels is a vital support service for the elderly living in the community and as such should aim to provide a high quality service that meets the needs of its clients

An Evaluation of the Pharmacodynamics, Safety, and Tolerability of the Potassium Binder RDX7675

Hyperkalemia is common in patients with heart failure or chronic kidney disease, particularly those taking renin‐angiotensin‐aldosterone system inhibitors, and can cause arrhythmias and sudden cardiac death. The most widely used treatment, sodium polystyrene sulfonate (SPS), limits gastrointestinal potassium absorption, but has poor palatability. RDX7675 (RDX227675) is the calcium salt of a reengineered polystyrene sulfonate‐based resin with improved palatability over SPS. The pharmacodynamic effects and safety of RDX7675 were assessed in a phase 1, single‐center, randomized, active‐controlled study. Healthy volunteers received nominal active doses of RDX7675 4.6 g twice a day (BID), 4.6 g 3 times a day (TID), 6.9 g BID, 13.7 g daily (QD), 9.2 g TID, or 13.7 g BID (n = 12 each), or equivalent doses of SPS (n = 3 each), for 4 days. RDX7675 dosing increased stool potassium excretion and decreased urinary potassium excretion from baseline. Stool potassium excretion increased by up to 1481 mg/day with RDX7675 (6.9 g BID), and urinary potassium excretion decreased by up to 939 mg/day (13.7 g BID). Similar levels of potassium excretion were observed using QD, BID, or TID dosing of a 13.7 g total daily RDX7675 dose. Few adverse events were reported. In conclusion, repeated oral dosing with RDX7675 over 4 days reduced potassium absorption in healthy volunteers; the results support QD dosing of RDX7675 in future clinical studies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145273/1/jcph1102.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145273/2/jcph1102_am.pd

Infrequent dialysis: a new paradigm for hemodialysis initiation.

Nearly a half-century ago, the thrice-weekly hemodialysis schedule was empirically established as a means to provide an adequate dialysis dose while also treating the greatest number of end-stage renal disease (ESRD) patients using limited resources. Landmark trials of hemodialysis adequacy have historically been anchored to thrice-weekly regimens, but a recent randomized controlled trial demonstrated that frequent hemodialysis (six times per week) confers cardiovascular and survival benefits. Based on these collective data and experience, clinical practice guidelines advise against a less than thrice-weekly treatment schedule in patients without residual renal function, yet provide limited guidance on the optimal treatment frequency when substantial native kidney function is present. Thus, during the transition from Stage 5 chronic kidney disease to ESRD, the current paradigm is to initiate hemodialysis on a "full-dose" thrice-weekly regimen even among patients with substantial residual renal function. However, emerging data suggest that frequent hemodialysis accelerates residual renal function decline, and infrequent regimens may provide better preservation of native kidney function. Given the high mortality rates during the first 6 months of hemodialysis and the survival benefits of preserved native kidney function, initiation with twice-weekly treatment schedules ("infrequent hemodialysis") with an incremental increase in frequency over time may provide an opportunity to optimize patient survival. This review outlines the clinical benefits of post-hemodialysis residual renal function, studies of twice-weekly treatment regimens, and the potential risks and benefits of infrequent hemodialysis

Association of long-term aspirin use with kidney disease progression

BackgroundChronic microinflammation contributes to the progression of chronic kidney disease (CKD). Aspirin (ASA) has been used to treat inflammation for centuries. The effects of long-term low-dose ASA on CKD progression are unclear.MethodsWe examined the association of long-term use of newly initiated low-dose ASA (50–200 mg/day) with all-cause mortality using Cox proportional hazard models; with cardiovascular/cerebrovascular (CV) mortality and with end stage kidney disease (ESKD) using Fine and Gray competing risk regression models; with progression of CKD defined as patients’ eGFR slopes steeper than −5 mL/min/1.73m2/year using logistic regression models in a nationwide cohort of US Veterans with incident CKD. Among 831,963 patients, we identified 385,457 who either initiated ASA (N = 21,228) within 1 year of CKD diagnosis or never received ASA (N = 364,229). We used propensity score matching to account for differences in key characteristics, yielding 29,480 patients (14,740 in each group).ResultsIn the matched cohort, over a 4.9-year median follow-up period, 11,846 (40.2%) patients (6,017 vs. 5,829 ASA users vs. non-users) died with 25.8% CV deaths, and 934 (3.2%) patients (476 vs. 458) reached ESKD. ASA users had a higher risk of faster decline of kidney functions, i.e., steeper slopes (OR 1.30 [95%CI: 1.18, 1.44], p < 0.01), but did not have apparent benefits on mortality (HR 0.97 [95%CI: 0.94, 1.01], p = 0.17), CV mortality (Sub-Hazard Ratio [SHR]1.06 [95%CI: 0.99–1.14], p = 0.11), or ESKD (SHR1.00 [95%CI: 0.88, 1.13], p = 0.95).ConclusionChronic low-dose ASA use was associated with faster kidney function deterioration, and no association was observed with mortality or risk of ESKD

Recipient‐related predictors of kidney transplantation outcomes in the elderly

Background It is not clear whether in old people with end‐stage renal disease kidney transplantation is superior to dialysis therapy. Methods We compared mortality rates between kidney transplant recipients ( KTR s) and the general population across different age categories. We also examined patient and allograft survival in 15 667 elderly KTR s (65–30 kg/m 2 ) was associated with 19% higher risk of graft failure ( HR : 1.19 [1.07–1.33], p = 0.002). Diabetes was a predictor of worse patient survival in all age groups but poorer allograft outcome in the youngest age group (65–<70 yr old) only. None of the examined risk factors affected allograft outcome in the oldest group (≥75 yr old) although there was a 49% lower trend of graft failure in very old Hispanic recipients ( HR : 0.51 [0.26–1.01], p = 0.05). Conclusions Kidney transplantation may attenuate the age‐associated increase in mortality, and its superior survival gain is most prominent in the oldest recipients (≥75 yr old). The potential protective effect of kidney transplantation on longevity in the elderly deserves further investigation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98362/1/ctr12106.pd

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in Incident Peritoneal Dialysis Patients.

BackgroundAbnormalities in serum potassium are risk factors for sudden cardiac death and arrhythmias among dialysis patients. Although a previous study in hemodialysis patients has shown that race/ethnicity may impact the relationship between serum potassium and mortality, the relationship remains unclear among peritoneal dialysis (PD) patients where the dynamics of serum potassium is more stable.MethodsAmong 17,664 patients who started PD between January 1, 2007 and December 31, 2011 in a large US dialysis organization, we evaluated the association of serum potassium levels with all-cause and arrhythmia-related deaths across race/ethnicity using time-dependent Cox models with adjustments for demographics. We also used restricted cubic spline functions for serum potassium levels to explore non-linear associations.ResultsBaseline serum potassium levels were the highest among Hispanics (4.2 ± 0.7 mEq/L) and lowest among non-Hispanic blacks (4.0 ± 0.7 mEq/L). Among 2,949 deaths during the follow-up of median 2.2 (interquartile ranges 1.3-3.2) years, 683 (23%) were arrhythmia-related deaths. Overall, both hyperkalemia and hypokalemia (i.e., serum potassium levels &gt;5.0 and &lt;3.5 mEq/L, respectively) were associated with higher all-cause and arrhythmia-related mortality. In a stratified analysis according to race/ethnicity, the association of hypokalemia with all-cause and arrhythmia-related mortality was consistent with an attenuation for arrhythmia-related mortality in non-Hispanic blacks. Hyperkalemia was associated with all-cause and arrhythmia-related mortality in non-Hispanic whites and non-Hispanic blacks, but no association was observed in Hispanics.ConclusionAmong incident PD patients, hypokalemia was consistently associated with all-cause and arrhythmia-related deaths irrespective of race/ethnicity. However, while hyperkalemia was associated with both death outcomes in non-Hispanic blacks and whites, it was not associated with either death outcome in Hispanic patients. Further studies are needed to demonstrate whether different strategies should be followed for the management of serum potassium levels according to race/ethnicity

Dietary Restrictions in Dialysis Patients: Is There Anything Left to Eat?

A significant number of dietary restrictions are imposed traditionally and uniformly on maintenance dialysis patients, whereas there is very little data to support their benefits. Recent studies indicate that dietary restrictions of phosphorus may lead to worse survival and poorer nutritional status. Restricting dietary potassium may deprive dialysis patients of heart-healthy diets and lead to intake of more atherogenic diets. There is little data about the survival benefits of dietary sodium restriction, and limiting fluid intake may inherently lead to lower protein and calorie consumption, when in fact dialysis patients often need higher protein intake to prevent and correct protein-energy wasting. Restricting dietary carbohydrates in diabetic dialysis patients may not be beneficial in those with burnt-out diabetes. Dietary fat including omega-3 fatty acids may be important caloric sources and should not be restricted. Data to justify other dietary restrictions related to calcium, vitamins, and trace elements are scarce and often contradictory. The restriction of eating during hemodialysis treatment is likely another incorrect practice that may worsen hemodialysis induced hypoglycemia and nutritional derangements. We suggest careful relaxation of most dietary restrictions and adoption of a more balanced and individualized approach, thereby easing some of these overzealous restrictions that have not been proven to offer major advantages to patients and their outcomes and which may in fact worsen patients' quality of life and satisfaction. This manuscript critically reviews the current paradigms and practices of recommended dietary regimens in dialysis patients including those related to dietary protein, carbohydrate, fat, phosphorus, potassium, sodium, and calcium, and discusses the feasibility and implications of adherence to ardent dietary restrictions and future research

Glycemic Control and Cardiovascular Mortality in Hemodialysis Patients With Diabetes

Previous observational studies using differing methodologies have yielded inconsistent results regarding the association between glycemic control and outcomes in diabetic patients receiving maintenance hemodialysis (MHD). We examined mortality predictability of A1C and random serum glucose over time in a contemporary cohort of 54,757 diabetic MHD patients (age 63 ± 13 years, 51% men, 30% African Americans, 19% Hispanics). Adjusted all-cause death hazard ratio (HR) for baseline A1C increments of 8.0–8.9, 9.0–9.9, and ≥10%, compared with 7.0–7.9% (reference), was 1.06 (95% CI 1.01–1.12), 1.05 (0.99–1.12), and 1.19 (1.12–1.28), respectively, and for time-averaged A1C was 1.11 (1.05–1.16), 1.36 (1.27–1.45), and 1.59 (1.46–1.72). A symmetric increase in mortality also occurred with time-averaged A1C levels in the low range (6.0–6.9%, HR 1.05 [95% CI 1.01–1.08]; 5.0–5.9%, 1.08 [1.04–1.11], and ≤5%, 1.35 [1.29–1.42]) compared with 7.0–7.9% in fully adjusted models. Adjusted all-cause death HR for time-averaged blood glucose 175–199, 200–249, 250–299, and ≥300 mg/dL, compared with 150–175 mg/dL (reference), was 1.03 (95% CI 0.99–1.07), 1.14 (1.10–1.19), 1.30 (1.23–1.37), and 1.66 (1.56–1.76), respectively. Hence, poor glycemic control (A1C ≥8% or serum glucose ≥200 mg/dL) appears to be associated with high all-cause and cardiovascular death in MHD patients. Very low glycemic levels are also associated with high mortality risk