The current and future landscape of dialysis Himmelfarb, Jonathan; Vanholder, Raymond; Mehrotra, Rajnish ...
Nature reviews. Nephrology,
10/2020, Letnik:
16, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The development of dialysis by early pioneers such as Willem Kolff and Belding Scribner set in motion several dramatic changes in the epidemiology, economics and ethical frameworks for the treatment ...of kidney failure. However, despite a rapid expansion in the provision of dialysis - particularly haemodialysis and most notably in high-income countries (HICs) - the rate of true patient-centred innovation has slowed. Current trends are particularly concerning from a global perspective: current costs are not sustainable, even for HICs, and globally, most people who develop kidney failure forego treatment, resulting in millions of deaths every year. Thus, there is an urgent need to develop new approaches and dialysis modalities that are cost-effective, accessible and offer improved patient outcomes. Nephrology researchers are increasingly engaging with patients to determine their priorities for meaningful outcomes that should be used to measure progress. The overarching message from this engagement is that while patients value longevity, reducing symptom burden and achieving maximal functional and social rehabilitation are prioritized more highly. In response, patients, payors, regulators and health-care systems are increasingly demanding improved value, which can only come about through true patient-centred innovation that supports high-quality, high-value care. Substantial efforts are now underway to support requisite transformative changes. These efforts need to be catalysed, promoted and fostered through international collaboration and harmonization.
Chronic kidney disease (CKD) induces modifications in lipid and lipoprotein metabolism and homeostasis. These modifications can promote, modulate and/or accelerate CKD and secondary cardiovascular ...disease (CVD). Lipid and lipoprotein abnormalities - involving triglyceride-rich lipoproteins, LDL and/or HDL - not only involve changes in concentration but also changes in molecular structure, including protein composition, incorporation of small molecules and post-translational modifications. These alterations modify the function of lipoproteins and can trigger pro-inflammatory and pro-atherogenic processes, as well as oxidative stress. Serum fatty acid levels are also often altered in patients with CKD and lead to changes in fatty acid metabolism - a key process in intracellular energy production - that induce mitochondrial dysfunction and cellular damage. These fatty acid changes might not only have a negative impact on the heart, but also contribute to the progression of kidney damage. The presence of these lipoprotein alterations within a biological environment characterized by increased inflammation and oxidative stress, as well as the competing risk of non-atherosclerotic cardiovascular death as kidney function declines, has important therapeutic implications. Additional research is needed to clarify the pathophysiological link between lipid and lipoprotein modifications, and kidney dysfunction, as well as the genesis and/or progression of CVD in patients with kidney disease.
Green Nephrology Vanholder, Raymond
Kidney and dialysis,
09/2022, Letnik:
2, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The greenhouse effect of carbon dioxide, nitrous oxide, and methane release resulted in an exponential rise of land temperatures over the last decades ...
p-Cresyl Sulfate Gryp, Tessa; Vanholder, Raymond; Vaneechoutte, Mario ...
Toxins,
01/2017, Letnik:
9, Številka:
2
Journal Article, Book Review
Recenzirano
Odprti dostop
If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins.
-Cresyl ...sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to
studies, the intestinal bacteria generating phenolic compounds mainly belong to the families
, and
. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden.
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds ...along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered. The inflammatory, cardio-vascular and fibrogenic systems were those most frequently affected and they are one by one major actors in the high morbidity and mortality of CKD but also the mechanisms that have most frequently been studied. A scoring system was built with the intention to classify the reviewed compounds according to the experimental evidence of their toxicity (number of systems affected) and overall experimental and clinical evidence. Among the highest globally scoring solutes were 3 small water-soluble compounds asymmetric dimethylarginine (ADMA); trimethylamine-N-oxide (TMAO); uric acid, 6 protein bound compounds or groups of protein bound compounds advanced glycation end products (AGEs); p-cresyl sulfate; indoxyl sulfate; indole acetic acid; the kynurenines; phenyl acetic acid; and 3 middle molecules β₂-microglobulin; ghrelin; parathyroid hormone). In general, more experimental data were provided for the protein bound molecules but for almost half of them clinical evidence was missing in spite of robust experimental data. The picture emanating is one of a complex disorder, where multiple factors contribute to a multisystem complication profile, so that it seems of not much use to pursue a decrease of concentration of a single compound.
Acute kidney injury: an increasing global concern Lameire, Norbert H, Prof; Bagga, Arvind, Prof; Cruz, Dinna, MD ...
The Lancet (British edition),
07/2013, Letnik:
382, Številka:
9887
Journal Article
Recenzirano
Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic ...options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.
Also known as the “second human genome,” the gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. The symbiotic relationship between host and ...microbiome is disturbed due to the proliferation of dysbiotic bacteria in patients with chronic kidney disease (CKD). Fermentation of protein and amino acids by gut bacteria generates excess amounts of potentially toxic compounds such as ammonia, amines, thiols, phenols, and indoles, but the generation of short-chain fatty acids is reduced. Impaired intestinal barrier function in patients with CKD permits translocation of gut-derived uremic toxins into the systemic circulation, contributing to the progression of CKD, cardiovascular disease, insulin resistance, and protein-energy wasting. The field of microbiome research is still nascent, but is evolving rapidly. Establishing symbiosis to treat uremic syndrome is a novel concept, but if proved effective, it will have a significant impact on the management of patients with CKD.
Recognition is increasing for the effect of AKI on patients, and the resulting societal burden from its long-term effects, including development of chronic kidney disease and end-stage renal disease ...needing dialysis or transplantation.2 Few systematic efforts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease.
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