The Interpretation of Standard Cardiopulmonary Exercise Test Indices of Cardiac Function in Chronic Kidney Disease.

BACKGROUND AND AIMS: As there is growing interest in the application of cardiopulmonary exercise test (CPX) in chronic kidney disease (CKD), it is important to understand the utility of conventional exercise test parameters in quantifying the cardiopulmonary fitness of patients with CKD. Merely extrapolating information from heart failure (HF) patients would not suffice. In the present study, we evaluated the utility of CPX parameters such as the peak O2-pulse and the estimated stroke volume (SV) in assessing the peak SV by comparing with the actual measured values. Furthermore, we compared the anaerobic threshold (AT), peak circulatory power, and ventilatory power with that of the measured values of the peak cardiac power (CPOpeak) in representing the cardiac functional reserve in CKD. We also performed such analyses in patients with HF for comparison. METHOD: A cross sectional study of 70 asymptomatic male CKD patients [CKD stages 2-5 (pre-dialysis)] without primary cardiac disease or diabetes mellitus and 25 HF patients. A specialized CPX with a CO2 rebreathing technique was utilized to measure the peak cardiac output and peak cardiac power output. The peak O2 consumption (VO2peak) and AT were also measured during the test. Parameters such as the O2-pulse, stroke volume, arteriovenous difference in O2 concentration [C(a-v)O2], peak circulatory power, and peak ventilatory power were all calculated. Pearson's correlation, univariate, and multivariate analyses were applied. RESULTS: Whereas there was a strong correlation between the peak O2-pulse and measured peak SV in HF, the correlation was less robust in CKD. Similarly, the correlation between the estimated SV and the measured SV was less robust in CKD compared to HF. The AT only showed a modest correlation with the CPOpeak in HF and only a weak correlation in CKD. A stronger correlation was demonstrated between the peak circulatory power and CPOpeak, and the ventilatory power and CPOpeak. In HF, the central cardiac factor was the predominant determinant of the standard CPX-derived surrogate indices of cardiac performance. By contrast, in CKD both central and peripheral factors played an equally important role, making such indices less reliable markers of cardiac performance per se in CKD. CONCLUSION: The results highlight that the standard CPX-derived surrogate markers of cardiac performance may be less reliable in CKD, and that further prospective studies comparing such surrogate markers with directly measured cardiac hemodynamics are required before adopting such markers into clinical practice or research in CKD.

Decision aids to assist patients and professionals in choosing the right treatment for kidney failure.

Background: Kidney services vary in the way they involve people with kidney failure (PwKF) in treatment decisions as management needs change. We discuss how decision-science applications support proactively PwKF to make informed decisions between treatment options with kidney professionals. Methods: A conceptual review of findings about decision making and use of decision aids in kidney services, synthesized with reference to: the Making Informed Decisions-Individually and Together (MIND-IT) multiple stakeholder decision makers framework; and the Medical Research Council-Complex Intervention Development and Evaluation research framework. Results: This schema represents the different types of decision aids that support PwKF and professional reasoning as they manage kidney disease individually and together; adjustments at micro, meso and macro levels supports integration in practice. Conclusion: Innovating services to meet clinical guidelines on enhancing shared decision making processes means enabling all stakeholders to use decision aids to meet their goals within kidney pathways at individual, service and organizational levels.

Changes in Environment and Management Practices Improve Foot Health in Zoo-Housed Flamingos.

Foot lesions are a highly prevalent phenomenon among zoo-housed flamingos, with up to 99.8% of birds affected. These lesions are a recognized welfare concern, increasing the likelihood of bacterial infections, and even septicemia. Although several risk factors have been linked to foot lesions in flamingos (including age, climate, and substrate), there have been few studies looking at changes in foot lesions over time. This study tracked changes in foot lesions for an individual flock of Chilean Flamingos (97 birds) at Dublin Zoo, Ireland, over an 18-month period in response to a mandatory indoor housing order imposed by the Irish Government as a seasonal precautionary measure to prevent the spread of avian influenza. Using a pre-defined scoring system for four common types of foot lesions (hyperkeratosis, fissures, nodular lesions, and papillomatous growths), we show that providing unrestricted access to outdoor habitats and natural substrates (both terrestrial and aquatic) can improve the health and wellbeing of zoo-housed flamingos. This longitudinal study highlights the importance of regular foot health monitoring in flamingos, and the importance of natural aquatic substrates when managing flamingos. As many zoo-housed birds have been spending more time indoors on artificial substrates over recent years due to avian influenza housing orders, it is critical that we assess the impact of such changes in management and habitat access on bird health and welfare.

Maximizing the potential for living cell banks to contribute to global conservation priorities.

Although cryobanking represents a powerful conservation tool, a lack of standardized information on the species represented in global cryobanks, and inconsistent prioritization of species for future sampling, hinder the conservation potential of cryobanking, resulting in missed conservation opportunities. We analyze the representation of amphibian, bird, mammal, and reptile species within the San Diego Zoo Wildlife Alliance Frozen Zoo® living cell collection (as of April 2019) and implement a qualitative framework for the prioritization of species for future sampling. We use global conservation assessment schemes (including the International Union for Conservation of Nature (IUCN) Red List of Threatened Species™, the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), the Alliance for Zero Extinction, the EDGE of Existence, and Climate Change Vulnerability), and opportunities for sample acquisition from the global zoo and aquarium community, to identify priority species for cryobanking. We show that 965 species, including 5% of all IUCN Red List "Threatened" amphibians, birds, mammals, and reptiles, were represented in the collection and that sampling from within existing zoo and aquarium collections could increase representation to 16.6% (by sampling an additional 707 "Threatened" species). High-priority species for future cryobanking efforts include the whooping crane (Grus americana), crested ibis (Nipponia nippon), and Siberian crane (Leucogeranus leucogeranus). Each of these species are listed under every conservation assessment scheme and have ex situ populations available for sampling. We also provide species prioritizations based on subsets of these assessment schemes together with sampling opportunities from the global zoo and aquarium community. We highlight the difficulties in obtaining in situ samples, and encourage the formation of a global cryobanking database together with the establishment of new cryobanks in biodiversity-rich regions.

Flock size and structure influence reproductive success in four species of flamingo in 540 captive populations worldwide.

As global wildlife populations continue to decline, the health and sustainability of ex situ populations in zoos and aquariums have become increasingly important. However, the majority of managed ex situ populations are not meeting sustainability criteria and are not viable in the long term. Historically, ex situ flamingo (Phoenicopteriformes) populations have shown low rates of reproductive success and improvements are needed for long-term viability. Both flock size and environmental suitability have previously been shown to be important determinants of ex situ flamingo reproductive success in a limited number of sites in some species. Here we combined current and historic globally shared zoological records for four of the six extant species of flamingo (Phoeniconaias minor, Phoenicopterus chilensis, Phoenicopterus roseus, and Phoenicopterus ruber) to analyze how flock size, structure, and climatic variables have influenced reproductive success in ex situ flamingo populations at 540 zoological institutions from 1990 to 2019. Flock size had a strong nonlinear relationship with reproductive success for all species, with flock sizes of 41-100 birds necessary to achieve ca. 50% probability of reproduction. Additionally, an even sex ratio and the introduction of new individuals to a flock both increased ex situ reproductive success in some cases, while climatic variables played a limited role. We demonstrate the conservation management potential from globally shared zoological data and provide species-specific management recommendations to increase the reproductive success of global ex situ flamingo populations: minimum flock sizes should be increased, and we encourage greater collaboration between individual institutions and regional associations in exchanging birds between flocks.

Beta Blockade Prevents Cardiac Morphological and Molecular Remodelling in Experimental Uremia.

Heart failure and chronic kidney disease (CKD) share several mediators of cardiac pathological remodelling. Akin to heart failure, this remodelling sets in motion a vicious cycle of progressive pathological hypertrophy and myocardial dysfunction in CKD. Several decades of heart failure research have shown that beta blockade is a powerful tool in preventing cardiac remodelling and breaking this vicious cycle. This phenomenon remains hitherto untested in CKD. Therefore, we set out to test the hypothesis that beta blockade prevents cardiac pathological remodelling in experimental uremia. Wistar rats had subtotal nephrectomy or sham surgery and were followed up for 10 weeks. The animals were randomly allocated to the beta blocker metoprolol (10 mg/kg/day) or vehicle. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted, and protein expression was quantified using immunoblotting. Histological analyses were performed to quantify myocardial fibrosis. Beta blockade attenuated cardiac pathological remodelling in nephrectomised animals. The echocardiographic left ventricular mass and the heart weight to tibial length ratio were significantly lower in nephrectomised animals treated with metoprolol. Furthermore, beta blockade attenuated myocardial fibrosis associated with subtotal nephrectomy. In addition, the Ca++- calmodulin-dependent kinase II (CAMKII) pathway was shown to be activated in uremia and attenuated by beta blockade, offering a potential mechanism of action. In conclusion, beta blockade attenuated hypertrophic signalling pathways and ameliorated cardiac pathological remodelling in experimental uremia. The study provides a strong scientific rationale for repurposing beta blockers, a tried and tested treatment in heart failure, for the benefit of patients with CKD.

Resurrecting biodiversity: advanced assisted reproductive technologies and biobanking.

Biodiversity is defined as the presence of a variety of living organisms on the Earth that is essential for human survival. However, anthropogenic activities are causing the sixth mass extinction, threatening even our own species. For many animals, dwindling numbers are becoming fragmented populations with low genetic diversity, threatening long-term species viability. With extinction rates 1000-10,000 times greater than natural, ex situ and in situ conservation programmes need additional support to save species. The indefinite storage of cryopreserved (-196°C) viable cells and tissues (cryobanking), followed by assisted or advanced assisted reproductive technology (ART: utilisation of oocytes and spermatozoa to generate offspring; aART: utilisation of somatic cell genetic material to generate offspring), may be the only hope for species' long-term survival. As such, cryobanking should be considered a necessity for all future conservation strategies. Following cryopreservation, ART/aART can be used to reinstate lost genetics back into a population, resurrecting biodiversity. However, for this to be successful, species-specific protocol optimisation and increased knowledge of basic biology for many taxa are required. Current ART/aART is primarily focused on mammalian taxa; however, this needs to be extended to all, including to some of the most endangered species: amphibians. Gamete, reproductive tissue and somatic cell cryobanking can fill the gap between losing genetic diversity today and future technological developments. This review explores species prioritisation for cryobanking and the successes and challenges of cryopreservation and multiple ARTs/aARTs. We here discuss the value of cryobanking before more species are lost and the potential of advanced reproductive technologies not only to halt but also to reverse biodiversity loss. Lay summary: The world is undergoing its sixth mass extinction; however, unlike previous events, the latest is caused by human activities and is resulting in the largest loss of biodiversity (all living things on Earth) for 65 million years. With an extinction rate 1000-10,000-fold greater than natural, this catastrophic decline in biodiversity is threatening our own survival. As the number of individuals within a species declines, genetic diversity reduces, threatening their long-term existence. In this review, the authors summarise approaches to indefinitely preserve living cells and tissues at low temperatures (cryobanking) and the technologies required to resurrect biodiversity. In the future when appropriate techniques become available, these living samples can be thawed and used to reinstate genetic diversity and produce live young ones of endangered species, enabling their long-term survival. The successes and challenges of genome resource cryopreservation are discussed to enable a move towards a future of stable biodiversity.

The myriad of complex demographic responses of terrestrial mammals to climate change and gaps of knowledge: A global analysis.

Approximately 25% of mammals are currently threatened with extinction, a risk that is amplified under climate change. Species persistence under climate change is determined by the combined effects of climatic factors on multiple demographic rates (survival, development and reproduction), and hence, population dynamics. Thus, to quantify which species and regions on Earth are most vulnerable to climate-driven extinction, a global understanding of how different demographic rates respond to climate is urgently needed. Here, we perform a systematic review of literature on demographic responses to climate, focusing on terrestrial mammals, for which extensive demographic data are available. To assess the full spectrum of responses, we synthesize information from studies that quantitatively link climate to multiple demographic rates. We find only 106 such studies, corresponding to 87 mammal species. These 87 species constitute <1% of all terrestrial mammals. Our synthesis reveals a strong mismatch between the locations of demographic studies and the regions and taxa currently recognized as most vulnerable to climate change. Surprisingly, for most mammals and regions sensitive to climate change, holistic demographic responses to climate remain unknown. At the same time, we reveal that filling this knowledge gap is critical as the effects of climate change will operate via complex demographic mechanisms: a vast majority of mammal populations display projected increases in some demographic rates but declines in others, often depending on the specific environmental context, complicating simple projections of population fates. Assessments of population viability under climate change are in critical need to gather data that account for multiple demographic responses, and coordinated actions to assess demography holistically should be prioritized for mammals and other taxa.

Outcomes and care priorities for older people living with frailty and advanced chronic kidney disease: a multiprofessional scoping review protocol.

INTRODUCTION: Reported outcomes for older people with advanced chronic kidney disease (CKD) often focus on survival and mortality and little attention is paid to symptom burden and health-related quality of life. Recognising frailty and providing interventions that may improve outcomes have been studied in the general population with a growing research interest within CKD. METHODS AND ANALYSIS: A scoping review will be undertaken following a recommended process to understand relevant research and priorities for older people living with frailty and advanced CKD. Databases will be searched and following a systematic process by a core team, a final list of included studies will be analysed. Focus groups will then be conducted with older people with advanced CKD to incorporate stakeholder views. ETHICS AND DISSEMINATION: Our scoping review will use robust methodology to identify relevant literature focused on outcomes and care priorities for older people with advanced CKD. Ethical approval will be sought to conduct the focus groups. The result of this review will be disseminated through patient networks and national conferences. The interdisciplinary team collaborating plan to continue work in this area to improve the care and management of older people with advanced CKD.

Cardiac and Noncardiac Determinants of Exercise Capacity in CKD.

BACKGROUND: Impaired exercise capacity is a significant symptom of CKD and is associated with poor survival. Furthermore, there is a growing interest in applying exercise as a diagnostic tool or as therapy in CKD. However, an in-depth understanding of exercise physiology in CKD is still lacking. METHODS: To evaluate the role of cardiac (central) and noncardiac (peripheral) determinants of exercise capacity in CKD, we conducted a cross-sectional study of 70 male patients with CKD (stages 2-5) without diabetes or cardiac disease, 35 healthy controls, and 25 patients with heart failure. An integrated cardiopulmonary exercise test using a CO2 rebreathing technique was used to measure peak O2 consumption (VO2peak) and peak cardiac output simultaneously, and to calculate peak peripheral O2 extraction (C[a-v]O2), the peripheral determinant (the ability of exercising skeletal muscles to extract oxygen). We performed multiple regression analysis and used Bayesian information criteria (BIC) changes to quantitatively assess the individual contribution of central and peripheral factors. RESULTS: Compared with healthy controls, in patients with CKD, the VO2peak was impaired proportionate to its severity. Peak cardiac output was the predominant determinant of VO2peak in healthy controls and patients with heart failure, whereas C(a-v)O2 played a more significant role in determining VO2peak in CKD (ß=0.68, P<0.001) compared with cardiac output (ß=0.63, P<0.001). In addition, the magnitude of BIC reduction was greater for C(a-v)O2 compared with cardiac output (BIC, 298.72 versus 287.68) in CKD. CONCLUSIONS: In CKD, both peak cardiac output and peak C(a-v)O2 are independent predictors of VO2peak, and the more significant roleplayed by peak C(a-v)O2 highlights the importance of noncardiac factors in determining exercise capacity in CKD.

Kidney disease pathways, options and decisions: an environmental scan of international patient decision aids.

BACKGROUND: Conservative management is recognized as an acceptable treatment for people with worsening chronic kidney disease; however, patients consistently report they lack understanding about their changing disease state and feel unsupported in making shared decisions about future treatment. The purpose of this review was to critically evaluate patient decision aids (PtDAs) developed to support patient-professional shared decision-making between dialysis and conservative management treatment pathways. METHODS: We performed a systematic review of resources accessible in English using environmental scan methods. Data sources included online databases of research publications, repositories for clinical guidelines, research projects and PtDAs, international PtDA expert lists and reference lists from relevant publications. The resource selection was from 56 screened records; 17 PtDAs were included. A data extraction sheet was applied to all eligible resources, eliciting resource characteristics, decision architecture to boost/bias thinking, indicators of quality such as International Standards for Patient Decision Aids Standards checklist and engagement with health services. RESULTS: PtDAs were developed in five countries; eleven were publically available via the Internet. Treatment options described were dialysis (n = 17), conservative management (n = 9) and transplant (n = 5). Eight resources signposted conservative management as an option rather than an active choice. Ten different labels across 14 resources were used to name 'conservative management'. The readability of the resources was good. Six publications detail decision aid development and/or evaluation research. Using PtDAs improved treatment decision-making by patients. Only resources identified as PtDAs and available in English were included. CONCLUSIONS: PtDAs are used by some services to support patients choosing between dialysis options or end-of-life options. PtDAs developed to proactively support people making informed decisions between conservative management and dialysis treatments are likely to enable services to meet current best practice.

Critical review of leaflets about conservative management used in uk renal services.

BACKGROUND: Written information supplements nurse-led education about treatment options. It is unclear if this information enhances patients' reasoning about conservative management (CM) and renal replacement therapy decisions. AIM: This study describes a critical review of resources U.K. renal staff use when providing CM options to people with Established Kidney Disease (EKD) during usual pre-dialysis education. DESIGN: A survey using mixed methods identified and critically analysed leaflets about CM. PARTICIPANTS & MEASUREMENTS: All 72 renal units in the United Kingdom received an 11-item questionnaire to elicit how CM education is delivered, satisfaction and/or needs with patient resources and staff training. Copies of leaflets were requested. A coding frame was utilised to produce a quality score for each leaflet. RESULTS: Fifty-four (75%) units participated. Patients discuss CM with a nephrologist (98%) or nurse (100%). Eighteen leaflets were reviewed, mean scores were 8.44 out of 12 (range 5-12, SD = 2.49) for information presentation; 3.50 out of 6 (range 0-6, SD = 1.58) for inclusion of information known to support shared decision-making and 2.28 out of 6 (range 1-4, SD = 0.96) for presenting non-biased information. CONCLUSIONS: Nurses preferred communicating via face-to-face contact with patients and/or families because of the emotional consequences and complexity of planning treatment for the next stage of a person's worsening kidney disease. Conversations were supplemented with written information; 66% of which were produced locally. Staff perceived a need for using leaflets, and spend time and resources developing them to support their services. However, no leaflets included the components needed to help people reason about conservative care and renal replacement therapy options during EKD education consultations.

A system wide approach to managing zoo collections for visitor attendance and in situ conservation.

Zoos contribute substantial resources to in situ conservation projects in natural habitats using revenue from visitor attendance, as well as other sources. We use a global dataset of over 450 zoos to develop a model of how zoo composition and socio-economic factors directly and indirectly influence visitor attendance and in situ project activity. We find that zoos with many animals, large animals, high species richness (particularly of mammals), and which are dissimilar to other zoos achieve higher numbers of visitors and contribute to more in situ conservation projects. However, the model strongly supports a trade-off between number of animals and body mass indicating that alternative composition strategies, such as having many small animals, may also be effective. The evidence-base presented here can be used to help guide collection planning processes and increase the in situ contributions from zoos, helping to reduce global biodiversity loss.

Renal Association Clinical Practice Guideline on Haemodialysis.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease.

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2⁻5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.

A comparison of helminth infections as assessed through coprological analysis and adult worm burdens in a wild host.

Coprological analysis is the most widely used diagnostic tool for helminth infection in both domestic and wild mammals. Evaluation of the efficacy of this technique is rare, due to the lack of availability of adult worm burden. Where information is available the majority of studies are in small ruminants and seldom in a wild host. This study of 289 wild badgers is the first to report the relationship between faecal egg/larval counts and adult worm burden in badgers whilst also evaluating the reliability of coprological analysis as a diagnostic tool for hookworm (Uncinaria criniformis) and lungworm (Aelurostrongylus falciformis) infection. The prevalence of hookworm and lungworm infection, as assessed through adult worm burden was 59.2% and 20.8% respectively. For both species of helminth, infection was consistently under-reported by coprological analysis compared to adult worm burden with a reported 41% sensitivity for hookworm and 10% for lungworm. A significant positive relationship was found between faecal counts and adult worm burden for both species of helminths. Additionally the density -dependent relationship often reported in helminth infection appears to be weak or non-existent in this study, up to the observed worm intensity of 500.

Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Background: Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance. Methods: In a cross-sectional study (n = 130) we investigated 70 male non-diabetic CKD patients (21 CKD stage 2-3a, 27 CKD stage 3b-4 and 22 CKD stage 5) employing specialized cardiopulmonary exercise testing to measure peak cardiac output and cardiac power output non-invasively. Data from 35 age-matched healthy male volunteers were obtained for comparison. In addition, as a positive control, data from 25 age-matched male HF patients in New York Heart Association class II and III were also obtained. Results: The study subjects showed a graded reduction in peak cardiac power, with 6.13 ± 1.11 W in controls, 5.02 ± 0.78 W in CKD 2-3a, 4.59 ± 0.53 W in CKD 3b-4 and 4.02 ± 0.73 W in CKD 5, although not as impaired as in HF, with 2.34 ± 0.63 W (all P < 0.005 versus control). The central haemodynamic characteristics of the cardiac impairment in CKD mirrored that of HF, with reduced flow and pressure-generating capacities, reduced chronotropic reserve and impaired contractility. Conclusions: The study demonstrates for the first time impaired peak cardiac performance and cardiac functional reserve in asymptomatic CKD patients. The evidence of myocardial dysfunction in the absence of comorbid cardiac disease and diabetes warrants further evaluation of current pathophysiological concepts of cardiovascular disease in CKD.