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      Do Tubular Changes in the Diabetic Kidney Affect the Susceptibility to Acute Kidney Injury?


      Nephron Clinical Practice

      S. Karger AG

      Diabetic nephropathy, Tubular hypothesis, Tubular injury, Regeneration, Clinical studies, Risk factor

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          Diabetes is the single largest contributor to the growing prevalence of chronic kidney disease (CKD), and episodes of acute kidney injury (AKI) increase the risk of advanced CKD in diabetic patients. Here we discuss whether the pathophysiological changes that occur in the tubular system of the diabetic kidney affect the intrinsic susceptibility to AKI. There is abundant data showing that drug-induced nephrotoxicity is attenuated in rodents with experimental diabetes mellitus, and some mechanistic explanations have been provided, in particular in response to aminoglycosides. Besides downregulation in proximal tubular megalin, which mediates the aminoglycoside uptake in proximal tubules, a role for hyperglycemia-induced activation of regenerative mechanisms has been proposed. The available clinical data, however, indicates that diabetes is a risk factor for AKI, including aminoglycoside nephrotoxicity. While much needs to be learned about this disconnect, the isolated induction of diabetes in otherwise healthy young adult rodents may simply not fully mimic the influence that diabetes exerts in the setting of a critically ill and often elderly patient. We speculate that diabetic tubular growth and the associated molecular signature (including upregulation of TGF-β, senescence, and inflammation) set up the development of diabetic nephropathy and renal failure in part by increasing the susceptibility to AKI, which further promotes hypoxia and apoptosis. Considering the strong association between AKI episodes and the cumulative risk of developing advanced CKD in diabetes, strategies that reduce AKI in these patients are expected to help reduce the growing burden of end-stage renal disease.

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          Most cited references 29

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          A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.

          We sought to develop a simple risk score of contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI). Although several risk factors for CIN have been identified, the cumulative risk rendered by their combination is unknown. A total of 8,357 patients were randomly assigned to a development and a validation dataset. The baseline clinical and procedural characteristics of the 5,571 patients in the development dataset were considered as candidate univariate predictors of CIN (increase >or=25% and/or >or=0.5 mg/dl in serum creatinine at 48 h after PCI vs. baseline). Multivariate logistic regression was then used to identify independent predictors of CIN with a p value 75 years, anemia, and volume of contrast) were assigned a weighted integer; the sum of the integers was a total risk score for each patient. The overall occurrence of CIN in the development set was 13.1% (range 7.5% to 57.3% for a low [ or=16] risk score, respectively); the rate of CIN increased exponentially with increasing risk score (Cochran Armitage chi-square, p < 0.0001). In the 2,786 patients of the validation dataset, the model demonstrated good discriminative power (c statistic = 0.67); the increasing risk score was again strongly associated with CIN (range 8.4% to 55.9% for a low and high risk score, respectively). The risk of CIN after PCI can be simply assessed using readily available information. This risk score can be used for both clinical and investigational purposes.
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            Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention.

            In patients undergoing percutaneous coronary intervention (PCI) in the modern era, the incidence and prognostic implications of acute renal failure (ARF) are unknown. With a retrospective analysis of the Mayo Clinic PCI registry, we determined the incidence of, risk factors for, and prognostic implications of ARF (defined as an increase in serum creatinine [Cr] >0.5 mg/dL from baseline) after PCI. Of 7586 patients, 254 (3.3%) experienced ARF. Among patients with baseline Cr 2.0, all had a significant risk of ARF. In multivariate analysis, ARF was associated with baseline serum Cr, acute myocardial infarction, shock, and volume of contrast medium administered. Twenty-two percent of patients with ARF died during the index hospitalization compared with only 1.4% of patients without ARF (P 2.0 are at high risk for ARF. ARF was highly correlated with death during the index hospitalization and after dismissal.
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              Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.

                Author and article information

                Nephron Clin Pract
                Nephron Clinical Practice
                S. Karger AG
                September 2014
                24 September 2014
                : 127
                : 1-4
                : 133-138
                Division of Nephrology-Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, and VA San Diego Healthcare System, San Diego, Calif., USA
                Author notes
                *Volker Vallon, MD, Division of Nephrology-Hypertension, Departments of Medicine and Pharmacology, University of California San Diego, and VA San Diego Healthcare System, 3350 La Jolla Village Drive (9151), San Diego, CA 92161 (USA), E-Mail
                363554 Nephron Clin Pract 2014;127:133-138
                © 2014 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 1, Pages: 6
                Original Paper


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