Prognostic robustness of serum creatinine based AKI definitions in patients with sepsis: a prospective cohort study

Background: It is unclear how modifications in the way to calculate serum creatinine (sCr) increase and in the cut-off value applied, influences the prognostic value of Acute Kidney Injury (AKI). We wanted to evaluate whether these modifications alter the prognostic value of AKI for prediction of mortality at 3 months, 1 and 2 years. Methods: We prospectively included 195 septic patients and evaluated the prognostic value of AKI by using three different algorithms to calculate sCr increase: either as the difference between the highest value in the first 24 h after ICU admission and a pre-admission historical (Delta HIS) or an estimated (Delta EST) baseline value, or by subtracting the ICU admission value from the sCr value 24 h after ICU admission (Delta ADM). Different cut-off levels of sCr increase (0.1, 0.2, 0.3, 0.4 and 0.5 mg/dl) were evaluated. Results: Mortality at 3 months, 1 and 2 years in AKI defined as Delta ADM > 0.3 mg/dl was 48.1 %, 63.0 % and 63.0 % vs 27.7 %, 39.8 % and 47.6 % in no AKI respectively (OR(95%CI): 2.42(1.06-5.54), 2.58(1.11-5.97) and 1.87(0.81-4.33); 0.3 mg/dl was the lowest cut-off value that was discriminatory. When AKI was defined as Delta HIS > 0.3 mg/dl or Delta EST > 0.3 mg/dl, there was no significant difference in mortality between AKI and no AKI. Conclusions: The prognostic value of a 0.3 mg/dl increase in sCr, on mortality in sepsis, depends on how this sCr increase is calculated. Only if the evolution of serum creatinine over the first 24 h after ICU admission is taken into account, an association with mortality is found

The cell cycle biomarkers : promising research, but do not oversell them

This review focuses on the most recent scientific and clinical information on the development and clinical applicability of the cell cycle biomarkers TIMP-2 and IGFBP-7 in the diagnosis and prognosis of patients at risk for and suffering from acute kidney injury (AKI). A number of evaluation studies have demonstrated that compared with existing biomarkers, urinary excretion of the product of both biomarkers, [TIMP-2]•[IGFBP-7], improved diagnostic performance in assessing the risk for AKI, predicting the need for renal replacement therapy, AKI-related complications and short- and long-term prognoses. The reference intervals for these biomarkers, measured by the recently approved NephroCheck test, have been determined in apparently healthy adults and those with stable chronic morbid conditions without AKI. This review recognizes that the combination of these two cell cycle arrest markers for the early detection of AKI is promising but concludes that its clinical impact is still unproved. Clinicians should understand the utility and limitations of this test before deciding whether to make it available at their institution

Haste makes waste : should current guideline recommendations for initiation of renal replacement therapy for acute kidney injury be changed?

There is broad consensus among guideline organizations that renal replacement therapy (RRT) should not be delayed in case of life-threatening conditions. However, in case of severe acute kidney injury (AKI) without these conditions, it is unclear whether immediate RRT has an advantage over delayed RRT. Two recently published randomized controlled trials (AKIKI and ELAIN) with seemingly opposite results have reignited the discussion whether guideline recommendations on initiation strategies in severe AKI should be adapted. This editorial discusses RRT initiation strategies in severe AKI, based on recent literature and highlights the potential advantages and disadvantages of immediate vs delayed start. Overall, evidence in favor of immediate compared to delayed strategies is sparse and there is wide heterogeneity across studies making it difficult to draw firm conclusions. RRT should not be delayed in case of refractory hyperkalemia, severe metabolic acidosis or pulmonary edema resistant to diuretics. In all other cases, a delayed strategy seems justified and might enhance renal recovery. RRT is not a it doesn't hurt to try technique and can expose the patient to a higher risk of bleeding, hemodynamic problems, under-dosing of antibiotics, loss of nutrients, catheter-related complications and the uncertain effects of blood-membrane interactions. There is no compelling reason to change current guideline recommendations and research focus should shift toward the development of algorithms as a decision aid tool for RRT initiation in severe AKI

Influence of severity of illness on neutrophil gelatinase-associated lipocalin performance as a marker of acute kidney injury : a prospective cohort study of patients with sepsis

Background: The role of neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic marker for acute kidney injury (AKI) in sepsis is still debated. We hypothesized that in sepsis, the performance of serum(s) and urinary(u) NGAL can be negatively impacted by severity of illness and inflammation, and that both uNGAL and sNGAL levels can be increased regardless of presence of AKI. Methods: One hundred and seven patients with sepsis were included. uNGAL and sNGAL were measured at admission (T0) and 4 hours (T4) and 24 hours later (T24). Transient and intrinsic AKI were respectively defined as AKI according to RIFLE during the first 72 hours that did or did not recover to "no AKI" in the following 72 hours. Patients were classified according to tertiles of CRP and APACHE II score increase. The relationship between sNGAL and uNGAL was assessed by linear regression. Results: Fifty-seven patients developed transient and 22 intrinsic AKI. Prevalence of transient and intrinsic AKI were higher in patients with versus without septic shock (OR (95% CI): 3.3(1.4-8.2)). uNGAL was associated with sNGAL, and this with parallel slopes but different intercepts for AKI (Y = 0.87*X + 314.3, R-2 = 0.31) and no AKI (Y = 0.87*X + 20.1, R-2 = 0.38). At T4, median uNGAL and sNGAL levels were higher in septic patients with versus without shock but this is independent of AKI ((545 ng/mL vs 196 ng/ml for uNGAL and 474 ng/ml vs 287 ng/ml for sNGAL (both P = 0.003)). Both uNGAL and sNGAL levels increased with tertiles of CRP and APACHE II score increase. Conclusions: Serum and uNGAL levels are influenced by severity of illness and inflammation, and this was found to be independent of the presence of AKI. There is a strong correlation between sNGAL and uNGAL levels in patients with sepsis, indicating that increased levels of uNGAL can also be due to overspill from the systemic circulation, blurring the discriminative value of NGAL as a biomarker for AKI in patients with sepsis

Diagnosis and treatment of hyponatremia : a systematic review of clinical practice guidelines and consensus statements

Background: Hyponatremia is a common electrolyte disorder. Multiple organizations have published guidance documents to assist clinicians in managing hyponatremia. We aimed to explore the scope, content, and consistency of these documents. Methods: We searched MEDLINE, EMBASE, and websites of guideline organizations and professional societies to September 2014 without language restriction for Clinical Practice Guidelines (defined as any document providing guidance informed by systematic literature review) and Consensus Statements (any other guidance document) developed specifically to guide differential diagnosis or treatment of hyponatremia. Four reviewers appraised guideline quality using the 23-item AGREE II instrument, which rates reporting of the guidance development process across six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Total scores were calculated as standardized averages by domain. Results: We found ten guidance documents; five clinical practice guidelines and five consensus statements. Overall, quality was mixed: two clinical practice guidelines attained an average score of > 50% for all of the domains, three rated the evidence in a systematic way and two graded strength of the recommendations. All five consensus statements received AGREE scores below 60% for each of the specific domains. The guidance documents varied widely in scope. All dealt with therapy and seven included recommendations on diagnosis, using serum osmolality to confirm hypotonic hyponatremia, and volume status, urinary sodium concentration, and urinary osmolality for further classification of the hyponatremia. They differed, however, in classification thresholds, what additional tests to consider, and when to initiate diagnostic work-up. Eight guidance documents advocated hypertonic NaCl in severely symptomatic, acute onset ( 48 h) or asymptomatic cases, recommended treatments were NaCl 0.9%, fluid restriction, and cause-specific therapy for hypovolemic, euvolemic, and hypervolemic hyponatremia, respectively. Eight guidance documents recommended limits for speed of increase of sodium concentration, but these varied between 8 and 12 mmol/L per 24 h. Inconsistencies also existed in the recommended dose of NaCl, its initial infusion speed, and which second line interventions to consider. Conclusions: Current guidance documents on the assessment and treatment of hyponatremia vary in methodological rigor and recommendations are not always consistent