Clinical practice guidelines for anemia in chronic kidney disease: problems and solutions. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

The development of clinical practice guidelines for the treatment of anemia in chronic kidney disease has been instrumental in identifying and reducing variations in the use of erythropoiesis-stimulating agents and iron replacement. Challenges to the effectiveness and safety of recommendations made in these guidelines were magnified when recent clinical trials showed no benefit or harm with respect to cardiovascular outcomes in subjects randomized to higher target hemoglobin levels. To address these concerns, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international conference to examine the problems and shortcomings of existing anemia guidelines, which are a prime example of duplication of efforts to derive recommendations from a limited evidence base. The meeting was attended by representatives of the major guideline developing organizations, who agreed to avoid future duplicative efforts and to save resources in generating a common evidence report, whose recommendations could then be prioritized and implemented locally. This is a report to the international nephrology community of the recommendations for and timeline of the next anemia guidelines. It has been reviewed by the conference participants and approved as a position statement by the KDIGO Board of Directors.

A framework and key research questions in AKI diagnosis and staging in different environments.

BACKGROUND AND OBJECTIVES: Acute Kidney Injury (AKI) is common worldwide, and associated with significant morbidity, mortality, and resource utilization. The RIFLE system of staging AKI correlates with survival in AKI in several settings. A similar AKI definition and staging system that also incorporates lesser degrees of serum creatinine elevation was proposed at the inaugural Acute Kidney Injury Network (AKIN) meeting in 2005. At the Second AKIN meeting in Vancouver, Canada in September 2006, our group developed a research agenda that would test the utility of these diagnostic and staging criteria to predict patient outcomes in a variety of clinical settings and patient groups. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Three-day, international, consensus conference. A multidisciplinary stakeholder committee was divided into work groups. Recommendations for clinical practice and for future research were developed by the committee as an iterative process. This procedure consisted of a literature review phase and focus group interactions with presentations to the entire committee. RESULTS: We first proposed a conceptual framework of disease that describes a series of AKI stages, antecedents and outcomes, and allows a description of research recommendations based on transition between AKI stages. We further proposed methods for testing of the definition and development of research questions to establish the utility of new biomarkers for the diagnosis and staging of AKI and associated illnesses. CONCLUSIONS: Retrospective studies should be conducted to initiate the process of validating the AKIN definition of AKI, followed by comprehensive prospective studies that incorporate sampling for emerging AKI biomarkers.

Acute-on-chronic renal failure in the rat: functional compensation and hypoxia tolerance.

BACKGROUND: We hypothesized that chronic renal parenchymal disease may predispose to acute renal failure (ARF), facilitating the induction of hypoxic medullary tubular injury. METHODS: To induce chronic renal parenchymal injury, rats underwent sham operation (control) or bilateral 50-min clamping of the renal artery [ischemia-reperfusion (IR)]. One or 3 months later, both groups were subjected to an ARF protocol, consisting of radiocontrast and the inhibition of prostaglandin and nitric oxide synthesis. Renal function and morphology were determined 24 h later. RESULTS: Chronic tubulointerstitial changes (fibrosis, atrophy and hypertrophy) in the IR group correlated with baseline tubular function, but glomerular function was preserved. Functional deterioration after the ARF protocol was only marginally more pronounced in the IR group, and the degree of medullary acute tubular necrosis (ATN) was unaffected by prior IR. The extent of both tubular necrosis and chronic tubulointerstitial changes independently predicted the acute decline in renal function. Immunostaining of IR kidneys disclosed critically low medullary pO2 (determined by pimonidazole adducts), regional hypoxic cell response (hypoxia-inducible factors) and upregulation of endothelin-B receptors. CONCLUSIONS: Compensatory changes result in normal plasma creatinine 1 and 3 months after IR, despite diminished tubular function. Preexisting renal disease only marginally predisposes to ARF, and the extent of ATN is not significantly enhanced. These findings illustrate the complex interaction between chronic and acute renal injury and dysfunction and parallel the difficulty of their assessment in the clinical practice. Adaptive cellular responses to chronic hypoxia in conjunction with parenchymal loss and decreased oxygen demand might alleviate acute hypoxic injury.