Kidney Dial., Volume 2, Issue 2 (June 2022) – 18 articles

SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes mellitus and slow the progression towards end-stage kidney disease. Blocking tubular SGLT2 and spilling glucose into the urine, which triggers a metabolic counter-regulation similar to fasting, provides unique benefits, not only as an anti-hyperglycemic strategy. These include a low hypoglycemia risk and a shift from carbohydrate to lipid utilization and mild ketogenesis, thereby reducing body weight and providing an additional energy source. SGLT2 inhibitors counteract hyperreabsorption in the early proximal tubule, which acutely lowers glomerular pressure and filtration and thereby reduces the physical stress on the filtration barrier, the filtration of tubule-toxic compounds, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity and improved mitochondrial function and autophagy, can reduce pro-inflammatory, pro-senescence, and pro-fibrotic signaling and preserve tubular function and GFR in the long-term. By shifting transport downstream, SGLT2 inhibitors more equally distribute the transport burden along the nephron and may mimic systemic hypoxia to stimulate erythropoiesis, which improves oxygen delivery to the kidney and other organs. SGLT1 inhibition improves glucose homeostasis by delaying intestinal glucose absorption and by increasing the release of gastrointestinal incretins. Combined SGLT1 and SGLT2 inhibition has additive effects on renal glucose excretion and blood glucose control. SGLT1 in the macula densa senses luminal glucose, which affects glomerular hemodynamics and has implications for blood pressure control. More studies are needed to better define the therapeutic potential of SGLT1 inhibition to protect the kidney, alone or in combination with SGLT2 inhibition. Full article

One of the key goals of hemodialysis is to control sodium balance and volume status. The traditional view is that inter-dialytic sodium gains can be adequately controlled by ultrafiltration with the convective removal of sodium. However, dialyzing all patients using the same dialysate sodium concentration may potentially lead to excessive losses on the one hand and sodium gains on the other depending on dietary sodium intake, resulting in increased intra-dialytic hypotension and cramps, or greater inter-dialytic weight gains and hypertension. Full article

Metabolic derangements such as obesity, dyslipidemia, chronic inflammation, and oxidative stress are commonly seen in patients with chronic kidney disease (CKD) and are implicated in the exaggerated cardiovascular disease (CVD) risk observed in this patient population. Lifestyle interventions including healthy dietary patterns and exercise training have been proven effective in modifying these CVD risk factors in the general population. The efficacy and safety of these interventions in CKD patients remain elusive. This review article aims to provide a summary of the current evidence on the effects of different types of dietary and exercise interventions on metabolic biomarkers associated with cardiovascular disease in patients with moderate to advanced CKD. Full article

Physical inactivity is highly prevalent after solid organ transplantation and leads to unfavourable outcomes. This review aimed to understand posttransplant physical activity behaviour and propose physical activity interventions. Michie’s Behavioural Change Wheel was applied, in which the Context and Implementation of Complex Interventions framework, the Capability-Opportunity-Motivation and Behaviour model, and the Theoretical Domains Framework were embedded. Various contextual factors were found to modulate physical activity behaviour. Promising strategies to promote long-term physical activity included (i) tailoring of physical activity programs to patients’ abilities and preferences; (ii) incitement of intrinsic and autonomous motivation to change; (iii) SMART goals setting (e.g., Specific, Measurable, Achievable, Realistic, Timebound), (iv) autonomy-supportive co-design of action plans; (v) foster new habit formation; (vi) self-monitoring of physical activity; (vii) follow-up opportunities for evaluation and adjustment; (viii) education of transplant recipients, healthcare providers, and the patients’ social network; (iv) improvement of self-efficacy through incremental successes, verbal persuasion, peer modelling, and awareness of exercise-related bodily signals; (x) providing physical activity opportunity within patients’ social and environmental setting; (xi) encouragement and support from patients’ social network and healthcare providers; and (xii) governmental action that alleviates financial barriers and restructures the physical environment to promote physical activity. These new insights may contribute to physical activity program development for transplantation recipients. Full article

Hemodialysis patients typically have extremely low physical activity levels, which contributes to poor physical function and quality of life (QOL). Numerous studies show that exercise, intradialytic cycling in particular, may improve physical and cardiovascular function and QOL. But there are also significant inconsistencies in the literature, and the benefits in many studies are modest. This may be due in part to methodological limitations in intradialytic cycling trials, including small sample sizes, short interventions, low volume, and intensity of exercise prescriptions, and/or low retention and protocol adherence rates. The goal of this review is twofold. First, we summarize the current literature on intradialytic cycling in HD patients, highlighting benefits and concerns noted in several recently published trials that were among the most robust and clinically relevant trials conducted to date. Second, we will consider strategies for moving forward with exercise and physical activity interventions in HD, including promoting intradialytic cycling as a core component of a more patient-centric and comprehensive strategy that helps progress patients towards standard physical activity guidelines. We urge researchers and exercise professionals to consider intradialytic cycling as a valuable component of a comprehensive patient-centered, lifestyle intervention, as opposed to a stand-alone exercise prescription. Full article

Chronic Kidney Disease (CKD) is a progressive condition characterised by declining eGFR and associated, particularly in advanced stages, with increased morbidity and cardiovascular mortality. Current treatment options for delaying disease progression are limited to a small number of pharmacological agents. Considering that rates of kidney function decline are greater in patients with lower levels of habitual physical activity, there is interest in the potential benefits of structured exercise training in delaying CKD progression. This discursive review summarises the current state-of-play in this field of research by critically analysing the published systematic reviews of randomised controlled trials of structured exercise training in the non-dialysis CKD population. Several issues are highlighted that hamper definite conclusions as to the therapeutic effectiveness of exercise training for this purpose. However, following an overview of the pathophysiology and risk factors for kidney function decline, several potential mechanisms explaining how exercise training may benefit CKD progression are offered. Finally, suggestions for future research in this area are made. The review concludes that there is a need for further research on the effectiveness of exercise before it can be recommended as part of routine care for the purpose of delaying CKD progression. Exercise can be recommended, however, to individual patients because of a potential benefit to kidney function, and definite benefits to other outcomes such as quality of life, with no apparent evidence of harm. Full article

Frailty is highly prevalent within people living with chronic kidney disease (CKD) and is associated with the increased risk of falls, hospitalisation, and mortality. Alongside this, individuals with CKD report a high incidence of depression and reduced quality of life. The identification of frailty within nephrology clinics is needed to establish comprehensive management plans to improve clinical outcomes and quality of life for people with CKD. Current research exploring the role of non-pharmacological management has primarily focussed on exercise and physical activity interventions in the frail CKD population. However, there is a growing evidence base and interest in this area. This review provides an up-to-date overview of the literature into frailty assessment in CKD and subsequent non-pharmacological treatment approaches. Full article

Chronic Kidney Disease (CKD) is a global health problem and a significant contributor to mortality, morbidity and disability from non-communicable diseases (NCD). The current consensus amongst researchers in the field of renal rehabilitation and healthcare practitioners involved in the management of people with CKD, is that physical dysfunction and inactivity are severe and prevalent in all ages and CKD stages compared to normative data. The negative impact of CKD on independence is cumulative, and health interventions and policies should target prevention of deterioration of kidney function and its consequences for physical frailty, disability and ultimately, quality of life. Accurate and feasible assessment of physical function is key for supporting the clinical implementation of current clinical care management guidelines. This overview, therefore, presents the rationale and some key scientific evidence to support the recommendation of physical function measurement tools that reflect function limitations for immediate implementation in clinical practice. Measurement property characteristics of the proposed measurement tools are also summarised in order to support health and exercise professionals in selecting the right tool and in interpreting and evaluating the measured outcomes. Full article

In this narrative review, we briefly describe the general features of constipation, our understanding of its physiopathology, and its diagnosis and treatment, focusing on chronic kidney disease (CKD). Considering that constipation is poorly characterized in CKD, we referred to studies that used the Rome criteria to diagnose constipation in patients to describe a more realistic prevalence based on a standardized tool. A highly variable prevalence of the condition was reported, ranging from 4.5% to 71.7%. The main risk factors associated with constipation reported in these studies were advanced age, low fruit intake, presence of diabetes, and medication use, and the main consequence of constipation in CKD was a worse quality of life. We found a paucity of interventional studies for constipation treatment in CKD; however, in the general population, meta-analyses published in the last decade have reported the beneficial effects of non-pharmacological strategies, which may guide the management of constipated patients with CKD. These strategies include the consumption of fiber, prebiotics, and probiotics, as well as physical exercise and acupuncture. In conclusion, although constipation is a frequent complaint among patients with CKD, there remains a considerable knowledge gap regarding its epidemiology, prognosis, and treatment. Full article

Background: The aim was to compare the effects of high-flux hemodialysis (HF-HD) versus high-volume post-dilution hemodiafiltration (HV-HDF) on mortality risk. Methods: Retrospective observational study of prevalent patients on hemodialysis who were followed for two years and treated in 28 kidney centers in Colombia. In this study, we included all adult patients who had been on dialysis for at least 90 days treated with an arteriovenous fistula. They were classified as HF-HD if they underwent this treatment exclusively (100% of time). For HV-HDF, if they received this treatment in more than 90% of the observation period. The primary outcome variable was mortality, and the type of hemodialysis therapy was considered as the exposure variable. Propensity score matching (PSM) and Cox regression models were used to evaluate the effect of dialysis modality on the mortality risk. Results: A total of 2933 patients were analyzed, 2361 patients with HF-HD and 572 with HV-HDF. After PSM, 1010 prevalent patients remained; mortality rate was 14.2% (95% Confidence Interval—CI: 11.3–17.6%) and 5.9% (95%CI: 4.0–8.4%) in HF-HD and HV-HDF group, respectively. HV-HDF therapy was associated with a 55% reduction in mortality compared with the HF-HD group (Hazards ratio-HR: 0.45 [95%CI 0.32–0.64] p < 0.001). Cardiovascular mortality rate was not statistically different between groups (HF-HD: 7.1% (36), HV-HDF: 3.4% (17), HR: 0.51 (95%CI: 0.21–1.28), p: 0.152). However, in patients younger than 60 years, a beneficial effect was observed in favor to HV-HDF therapy with a 79% reduction in cardiovascular mortality risk (HR: 0.21, (95%CI: 0.05–0.79), p: 0.021). Conclusion: After adjustment for different confounders, this study suggests that HV-HDF could reduce all-cause mortality compared to HF-HD therapy in prevalent patients on hemodialysis. Full article

Lifestyle interventions can play an important role in improving patients’ health outcomes and helping them to live well with chronic kidney disease (CKD). The key to living well is ‘life participation’, defined as ‘the ability to do meaningful activities of life including, but not limited to, work, study, family responsibilities, travel, sport, social, and recreational activities’. Pharmaceutical, clinical, and surgical interventions such as dialysis and transplantation can deliver beneficial health outcomes for patients. Yet CKD patients say that the focus of renal appointments is ‘bloods, urine, blood pressure and kidney function’ and their treatment. Little time is provided to discuss non-clinical symptoms or concerns and recommend other treatments, such as lifestyle interventions. There are no highly ranked evidence-based guidelines for lifestyle interventions in CKD due to a historic lack of evidence. Diet advice, for example, is widely requested by patients on the internet and online forums but access to reliable information is highly variable. The lack of patient reported outcome measures (PROMs) is a barrier to monitoring and gathering evidence, but regulatory changes and the efforts of international organisations should soon deliver validated tools for research and guidelines which can be implemented in holistic care pathways. A global call to action to focus on lifestyle interventions is proposed. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of renal failure and has limited pharmacological treatment options. Disease progression is relentless, and regression is not a known feature of ADPKD even with pharmacological intervention. Recent research has uncovered underlying pathogenic mechanisms that may be amenable to dietary interventions. Cyst cells in ADPKD are thought to depend on glucose for energy and are unable to metabolize fatty acids and ketones. High-carbohydrate diets and lifestyles leading to hyperglycemia appear to worsen progression of ADPKD. Additionally, renal stressors such as oxalate, phosphate and uric acid, that lead to renal tubular micro-crystal burden appear to accelerate disease progression. Based on these research findings, we have created a remote, dietitian-supervised training program to teach individuals with ADPKD the implementation of dietary and lifestyle changes to avoid factors that may worsen disease progression. Using web-based platforms, digital tools, one-on-one remote meetings, and video group meetings, participants learn to implement a plant-focused ketogenic diet that avoids renal stressors, the science behind these changes, how to self-measure health parameters, and track nutrient intake. Dietary changes are supplemented with a medical food containing the ketone beta-hydroxybutyrate and alkaline citrate, and mindfulness exercises. Here, we report the first experience with this program from a beta test with approximately 24 participants. Most participants completed the program and reported improvements in their health and well-being including pain levels, weight loss, hypertension, and eGFR. Adherence to the program was very high and the feasibility of the dietary and lifestyle changes was rated highly. The Ren.Nu program is now publicly available to individuals with ADPKD. Full article

Diabetic kidney disease (DKD) represents a major public health issue, currently posing an important burden on healthcare systems. Renin–angiotensin system (RAS) blockers are considered the cornerstone of treatment of albuminuric DKD. However, a high residual risk of progression to more advanced CKD stages under RAS blockade still remains, while relevant studies did not show significant declines in cardiovascular events with these agents in patients with DKD. Among several other pharmacological classes, mineralocorticoid receptor antagonists (MRAs) have received increasing interest, due to a growing body of high-quality evidence showing that spironolactone and eplerenone can significantly lower blood pressure and albuminuria in patients with CKD. Furthermore, finerenone, a novel nonsteroidal MRA with unique physicochemical properties, was shown to effectively reduce cardiovascular events and death, as well as the incidence of end-stage kidney disease in patients with type 2 diabetes. This review discusses previous and recent clinical evidence on the issue of nephroprotection and cardioprotection in DKD offered by mineralocorticoid receptor antagonism, aiming to aid clinicians in their treatment decisions for diabetic patients. Full article

Dialysis is life-saving for an exponentially growing number of kidney failure patients. Yet, the current concept also has several drawbacks, such as high societal cost, incomplete kidney function replacement, dismal outcomes, low quality of life and a considerable ecologic footprint. In spite of many changes over the last fifty years, the original concept remained largely unmodified and the drawbacks did not disappear. In this article, we present a number of alternative solutions that are currently considered or tested which might have a potential impact on uremic toxin concentration, quality of life or environmental footprint that goes beyond what is currently achieved with traditional dialysis. These comprise applications of regenerative medicine; bioartificial kidney; conceptual changes in extracorporeal removal; energy-neutral, water-limiting dialysis; material recycling; keto-analogues; xenobiotics; and preservation of residual kidney function. As metabolism generating uremic toxins also generates beneficial compounds, some of these options may also maintain or restore this balance in contrast to dialysis that likely removes without distinction. All proposed options are also exemplary of how out-of-the-box thinking is needed to disrupt the status quo in treatment of kidney diseases that has now persisted for too long. Full article

Point-of-care ultrasound (POCUS) refers to the use of portable ultrasound systems by clinicians at a patient’s bedside for diagnostic and therapeutic purposes. It is not a substitute but rather a complement to clinical examination, and contrary to the classic ultrasound examination performed by radiologists, POCUS is not a detailed morphologic examination but focuses on answering specific clinical questions in an effort to reduce time to diagnosis and treatment, improve patient safety and decrease complication rates. In this article, we present the POCUS in hemodialysis units for and beyond vascular-access purposes, arguing that its implementation will help the practicing nephrologist who is treating hemodialysis patients on a daily basis to rapidly and efficiently answer several clinical questions that are common to dialysis patients, such as vascular-access assessment and cannulation, and assessment of volume status. POCUS aims to answer specific clinical questions, so a question-answer format is used. This review is divided in two parts. In the first part we will answer specific clinical questions exclusively concerning vascular access. The second part is dedicated to the use of POCUS for the assessment of volume status and dry-weight determination. Full article

The current interpretation of the controversial and dynamic nature of the literature reports in this area leads me to lean towards the preference of a standard DNa+ in the upper range (138 mEq/L) of the current international utilization and preference of clinical directors in Brazil. My opinion to individualize (plus and minus 2 mmol/L of DNa+ prescription) would be based on clinically relevant signals of excessive interdialytic weight gain and uncontrolled hypertension (to decrease DNa+ concentration), or intradialytic hypotension episodes (to increase DNa+ concentration). In my experience, the individualization, based on this approach, would be applicable to a minority (less than 15%) of patients. As new data from randomized clinical trials emerge (particularly the robust RESOLVE trial), I would certainly need (and would be happy) to revise my point of view on this issue. Full article

Human beings evolved on a diet that was balanced in omega-6/omega-3 fatty acids, and was rich in fruits and vegetables with a ratio of animal to vegetable intake of 35:65. Such a diet is a base-producing anti-inflammatory diet and one in which our genes have been programmed to respond. Current Western diets are acid-producing diets and are also high in omega-6 fatty acids, leading to a proinflammatory state. From an evolutionary perspective a mild systemic metabolic alkalosis, resulting from chronic net-base loading, is the natural and optimal systemic acid–base homeostasis of humans. Western diets that lead to a metabolic acidosis increase susceptibility to kidney disease as has been shown from the proinflammatory biomarkers that produce a cytokine storm. Healthy dietary patterns, including the Dietary Approach to Stop Hypertension (DASH) Study, and Mediterranean diets, such as the diet of Crete, both of which have a healthy dietary pattern, are associated with a lower incidence of chronic kidney disease and may prevent or decrease albuminuria and improve the estimated glomerular filtration rate (eGFR). Full article