Contributions to nephrology
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The pathogenesis of sepsis-induced acute kidney injury (AKI) is not fully understood, and may involve altered systemic hemodynamics and renal circulation, renal hypoxia and perhaps direct tubular toxicity. Oxidative stress, induced by systemic and intrarenal generation of reactive oxygen species (ROS) can directly exert renal parenchymal damage and may intensify renal microvascular and functional dysregulation, with a feedforward loop of hypoxia and ROS generation. Herein we review compelling evidence that sepsis is associated with systemic and intrarenal intense oxidative and nitrosative stress with a depletion of antioxidant capacity. ⋯ Though oxidative and nitrosative stress are likely to participate in the pathogenesis of sepsis-induced AKI, it is impossible to clearly identify their isolated independent role and renal-specific effect since there are complex interactions involved linking various affected organs, ROS generation with altered systemic hemodynamics, compromised microcirculation, hypoxia and distorted cellular function. Facing this complex disease entity, alleviation of oxidative stress single-handedly is unlikely to be effective in the prevention of sepsis-associated renal dysfunction. However, the addition of antioxidants to a comprehensive treatment strategy seems a reasonable approach.
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Acute kidney injury (AKI) can no longer be considered a surrogate marker for severity of illness. Recent epidemiologic data demonstrate the association of AKI and mortality. Even small decreases of kidney function are associated with increased mortality. ⋯ Infection and antimicrobial therapy can be the cause of AKI, but infection can also be a consequence of AKI. Finally, inadequate antimicrobial dosing probably plays an important role in the morbidity and mortality of AKI. These findings have led to a paradigm shift: patients die because of AKI rather than with AKI.
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In the US and Europe, approximately 90% of heart failure (HF) hospitalizations are due to symptoms and signs of sodium and fluid excess. Congestion is associated with HF progression. According to data from large national registries, approximately 40% of hospitalized HF patients are discharged with unresolved congestion, which may contribute to unacceptably high rehospitalization rates. ⋯ Clinical studies of ultrafiltration have shown that removal of isotonic fluid relieves symptoms of congestion, improves cardiac filling pressures and exercise capacity, and restores diuretic responsiveness in patients with diuretic resistance, concomitantly with favorable effects on pulmonary function, ventilatory efficiency, and neurohormonal activation. Ultrafiltration has been shown to reduce rehospitalizations in a randomized controlled trial of patients with decompensated HF. Future larger controlled clinical trials should evaluate the effect of ultrafiltration on survival.
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Since 1984 reports of renal involvement in AIDS patients have been presented in the literature. Different forms of renal disease were noted in the AIDS population including those related to systemic and local renal infections, tubulointerstitial disease, renal involvement by neoplasm and glomerular disease including collapsing glomerulopathy (CG). HIV-associated nephropathy (HIVAN) has been demonstrated to be more severe in the black population. ⋯ In a rat model of CG developed by our group, the injection of serum from CG patients resulted in proteinuria, glomerular tuft retraction and podocyte damage at the ultrastructural level (visceral epithelial cell foot-process effacement). No ultrastructural or light microscopy abnormalities were seen in rats injected with serum from non-collapsing FSGS or healthy subjects. Based on the experience of our group, circulating factors play a dominant role in the pathogenesis of idiopathic CG.
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In order to prevent a disease, its temporal nature (or at least when it starts) needs to be clearly defined. In acute kidney injury (AKI), this is usually not possible because the current diagnostic criteria are retrospective. Contrast-induced nephropathy (CIN) and cardiac surgery-associated acute kidney injury (CSA-AKI) are both thought of as potentially preventable acute renal lesions because the timing of the insult is known precisely. ⋯ Despite this, progress in prevention has been slow, and to date there are no therapies indicated for preventing either CIN or CSA-AKI. The best we can currently do is to recommend aggressive parenteral hydration, avoid compounds we know are nephrotoxic, and avoid unnecessary hypoxia and hypotension. While there is still clearly a long way to go before either of these acute kidney conditions can be described as preventable, the use of major adverse kidney events - death, dialysis and incident or progressive chronic kidney disease at 90 days - as a composite endpoint in clinical trials of putative prevention agents would represent a significant step forwards.