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 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.
Nephron Clin Pract 2003 Jan
PMID:Prevention of acute renal failure in the critically ill. 1241 54

Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development.
Nephron Clin Pract 2006
PMID:Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents. 1654 55

Various definitions of acute kidney injury (AKI) exist, making comparisons among studies difficult. Despite this, significant changes have occurred in the epidemiology of AKI during the last decade. Recent studies, including PICARD and BEST, have examined the epidemiology of ICU-related AKI in the USA and worldwide, respectively, and found that AKI remains a major cause of morbidity and mortality. The incidence of AKI has increased, most likely due to a trend toward older, more severely and chronically ill patients admitted to the hospital. Sepsis and multi-organ system failure continue to be strongly associated with AKI, as well as pre-morbid chronic kidney disease. The proportion of patients with AKI requiring dialysis is high. The mortality of ICU-related AKI, although still very elevated, may be decreasing. Understanding these changes, in the context of standardized definitions, will be essential for the design of successful interventional studies.
Nephron Clin Pract 2008
PMID:The epidemiology of severe acute kidney injury: from BEST to PICARD, in acute kidney injury: new concepts. 1880 66

Over the past several years, advances in our understanding of the pathogenesis of acute kidney injury (AKI) have demonstrated the role of oxidant stress and reactive oxygen metabolites (ROM) in the development of AKI in a variety of clinical settings. This review serves to define the pathways that lead to the generation of ROM following a variety of insults, as well as to review the current literature concerning the role of antioxidant therapy in the prevention and treatment of AKI in several clinical settings. Investigators have explored the potential therapeutic role of anti-oxidants in both experimental animal models and human studies of AKI in several clinical settings, including cardiac and aortic occlusive surgeries, sepsis, drug nephrotoxicity (cisplatin and gentamicin), as well as rhabdomyolysis. While the experimental animal studies have generally been more successful, taken together this literature supports the hypothesis that oxidant stress-induced production of ROM plays a major role in the pathogenesis of many forms of AKI, and continues to suggest the potential utility of antioxidant therapy in human AKI. Ongoing trials in concert with improved diagnostic techniques will hopefully lead to improved outcomes in the setting of AKI through the prophylactic or early therapeutic use of antioxidant therapy.
Nephron Exp Nephrol 2008
PMID:Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury? 1880 73

The treatment of severe acute kidney injury (AKI) with dialysis or hemofiltration remains suboptimal with high levels of morbidity and mortality. Current renal replacement therapies substitute for the small solute clearance function of the kidney but do not replace the lost reclamation, metabolic and endocrine functions of this organ. Cell therapy and tissue engineering offer hope of fuller replacement of kidney function in renal failure patients. A renal tubule assist device (RAD) that includes a conventional hemodialysis filter and a bioreactor containing living renal proximal tubule cells has been successfully engineered. Differentiated activity of these cells and survival advantages have been demonstrated in large-animal models of sepsis and AKI. Data from phase I/II and phase II clinical studies have shown that the addition of renal tubule cell therapy to conventional continuous renal replacement therapy (CRRT) treatment resulted in a significant clinical impact on survival, and that RAD treatment demonstrated an acceptable safety profile. Another substantive advance for the treatment of AKI will be the development of nanofabrication technology to further improve the clearance function of the kidney to replicate glomerular permselectivity while retaining high rates of hydraulic permeability. New developments in this translational research area will improve the unmet medical needs of patients with renal failure.
Nephron Exp Nephrol 2008
PMID:The bioartificial kidney and bioengineered membranes in acute kidney injury. 1880 74

Acute kidney injury (AKI) is a serious condition that affects many ICU patients. The most common causes of AKI in ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite of our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to kidney ischemia. However, recent models of experimental sepsis have challenged this notion by demonstrating that, in experimental states, which simulate the hemodynamic picture most typically seen in man (e.g. hyperdynamic sepsis) renal blood flow, actually increases as renal vascular resistance decreases. These experimental observations provide proof of concept that septic AKI can occur in the setting of renal hyperemia and that ischemia is not necessary for loss of glomerular filtration rate (GFR) to occur. They also suggest that similar hemodynamic event may occur in man. In addition, preliminary studies in septic sheep show that, when ATP is measured using an implanted phosphorus coil and magnetic resonance technology, renal bioenergetics are preserved in the setting of advanced septic shock. While these findings need to be confirmed, they challenge established paradigms and offer a new conceptual framework of reference for further investigation and intervention in man.
Nephron Exp Nephrol 2008
PMID:Septic acute kidney injury: new concepts. 1880 75

Dialytic therapies have undergone major technological developments in the last decade and emerging techniques are promoted not only for acute kidney injury, but also for sepsis, acute decompensated heart failure, and acute and acute-on-chronic liver failure. New devices specifically target the pathophysiological mechanisms involved in these conditions. In septic shock and sepsis, high-volume hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and high permeability hemofiltration enhance removal of pro-inflammatory mediators, while in liver failure, Molecular Adsorbents recycling System (MARS) and Prometheus favor the elimination of albumin-bound toxins such as bilirubin. In acute decompensated heart failure, simplified ultrafiltration machines are used to reach negative fluid balance in a minimalist setting. In the context of limited resources and growing expansion in the availability of technologies, a critical assessment is required and the use of these devices needs to be put in perspective. This article reviews the mechanisms, advantages and limitations of these techniques along with the current evidence available regarding their influence on major clinical outcomes.
Nephron Physiol 2008
PMID:Emerging therapies for extracorporeal support. 1880 80

Sepsis is a common cause of acute renal failure in intensive care units (ICU) with mortality rates as high as 60%. In this study, the clinical and laboratory predictors of acute kidney injury (AKI) in critically ill Turkish patients with sepsis/systemic inflammatory response syndrome were identified. We studied 139 (67 females/72 males) patients admitted to our ICUs with sepsis/systemic inflammatory response syndrome without renal failure. The clinical and laboratory parameters and treatments were recorded. Patients were classified as those without AKI (n = 60; 43.20%) and those with AKI (n = 79; 56.80%) based on the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria. Those with AKI were further classified as: risk in 27 (19%), injury in 25 (17.9%), failure in 25 (17.9%), and loss in 2 (1.4%). We found that the mortality rate increased with the severity of renal involvement: 56% in risk, 68% in injury, 72% in failure, and 100% in loss categories. Patients with AKI had a more positive fluid balance, higher central venous pressure, more vasopressor use, and lower systolic blood pressure. In multivariate analysis, the sequential organ failure assessment score, blood pressure, serum creatinine, and fluid balance were risk factors for the development of AKI. In this population, the incidence of AKI was higher and contrary to previous knowledge. A positive fluid balance also carries a risk for AKI and mortality in septic ICU patients. The RIFLE criteria were found to be applicable to our ICU population.
Nephron Clin Pract 2010
PMID:Evaluation of sepsis/systemic inflammatory response syndrome, acute kidney injury, and RIFLE criteria in two tertiary hospital intensive care units in Turkey. 2042 78

Metformin is the first-line oral agent in the treatment of type 2 diabetes and has many established benefits, including the reduction of macrovascular complications of diabetes. Its prescription in patients with renal impairment is limited by concerns relating to the theoretical risk of lactic acidosis, a fear which is perpetuated by numerous case reports in which it is implicated. Critical review of this literature calls into question the validity of these claims, with metformin usually acting as an 'innocent bystander' in acutely unwell patients with conditions well recognised to precipitate lactic acidosis such as sepsis or hypovolaemia. In fact, the evidence supports the safe use of appropriate doses of metformin in patients with chronic stable renal impairment, and highlights the important possible greater risks of the alternatives, most notably severe hypoglycaemia in patients taking sulphonylureas and/or insulin and fluid retention in patients taking a thiazolidinedione. Other traditional contraindications to metformin use such as heart failure are also being re-evaluated, as the benefits of metformin in these patients are increasingly recognised. Physicians should weigh this evidence carefully before deciding to withdraw metformin therapy in their patients with stable chronic kidney disease.
Nephron Clin Pract 2011
PMID:Metformin: the safest hypoglycaemic agent in chronic kidney disease? 2132 70

Diabetes is commonly complicated by the development of chronic kidney disease (CKD). Equally prevalent is the development of diabetic foot disease and it is now recognised that there is a higher risk of the development of foot disease and major amputation in those patients with CKD. This is particularly marked in those patients with end-stage kidney disease receiving renal replacement therapy for which there are many possible mechanisms, including the effect of dialysis on tissue hypoxia. What has been recognised recently is that the risk of the development of foot disease appears to start prior to the onset of renal replacement therapy. Whilst this may be due to the fact that the emphasis of care shifts towards the requirements of the patients' renal disease, here we discuss the possibility that the presence of a foot ulcer itself may contribute to the development or progression of CKD through repeated episodes of sepsis or chronic inflammation, or both.
Nephron Clin Pract 2013
PMID:Chronic kidney disease and the foot in diabetes--is inflammation the missing link? 2375 38


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