Fluid balance-adjusted creatinine in diagnosing acute kidney injury in the critically ill

Background Acute kidney injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjustments lead to a different incidence of AKI when used in conjunction with urine output (UO) criteria is unknown. Methods This was a post hoc analysis of the Finnish Acute Kidney Injury study. Hourly UO and daily plasma Cr were measured during the first 5 days of intensive care unit admission. Cr values were adjusted following the previously used formula and combined with the UO criteria. Resulting incidences and mortality rates were compared with the results based on unadjusted values. Results In total, 2044 critically ill patients were analyzed. The mean difference between the adjusted and unadjusted Cr of all 7279 observations was 5 (+/- 15) mu mol/L. Using adjusted Cr in combination with UO and renal replacement therapy criteria resulted in the diagnosis of 19 (1%) additional AKI patients. The absolute difference in the incidence was 0.9% (95% confidence interval [CI]: 0.3%-1.6%). Mortality rates were not significantly different between the reclassified AKI patients using the full set of Kidney Disease: Improving Global Outcomes criteria. Conclusion Fluid balance-adjusted Cr resulted in little change in AKI incidence, and only minor differences in mortality between patients who changed category after adjustment and those who did not. Using adjusted Cr values to diagnose AKI does not seem worthwhile in critically ill patients.Peer reviewe

Fluid management in patients with acute kidney injury-A post-hoc analysis of the FINNAKI study

Purpose: Whether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized. Materials and methods: This was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-AKI critically ill patients. Results: We matched 616 AKI (diagnosed during the three first intensive care unit (ICU) days) and non-AKI patients using propensity score. During the three first ICU days, AKI patients received median [IQR] of 11.4 L [8.0-15.2]L fluids and non-AKI patients 10.2 L [7.5-13.7]L, p < 0.001 while the fluid output among AKI patients was 4.7 L [3.0-7.2]L and among non-AKI patients 5.8 L [4.1-8.0]L, p < 0.001. In AKI patients, the median [IQR] cumulative fluid balance was 2.5 L [-0.2-6.0]L compared to 0.9 L [-1.4-3.6]L among non-AKI patients, p < 0.001. Among the 824 AKI patients, smaller volumes of fluid input with a multivariable OR of 0.90 (0.88-0.93) and better fluid output (multivariable OR 1.12 (1.07-1.18)) associated with enhanced change of resolution of AKI. Conclusions: AKI patients received more fluids albeit having lower fluid output compared to matched critically ill non-AKI patients. Smaller volumes of fluid input and higher fluid output were associated with better AKI recovery. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEXTM Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89–1.28, p = 0.51) and 0.92 (95% CI 0.80–1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients

Neutrophil activation in septic acute kidney injury : A post hoc analysis of the FINNAKI study

Background Inflammation, reflected by high plasma interleukin-6 concentration, is associated with acute kidney injury (AKI) in septic patients. Neutrophil activation has pathophysiological significance in experimental septic AKI. We hypothesized that neutrophil activation is associated with AKI in critically ill sepsis patients. Methods We measured plasma (n = 182) and urine (n = 118) activin A (a rapidly released cytosolic neutrophil protein), interleukin-8 (a chemotactic factor for neutrophils), myeloperoxidase (a neutrophil biomarker released in tissues), and interleukin-6 on intensive care unit admission (plasma and urine) and 24 hours later (plasma) in sepsis patients manifesting their first organ dysfunction between 24 hours preceding admission and the second calendar day in intensive care unit. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria. Results Plasma admission interleukin-8 (240 [60-971] vs 50 [19-164] pg/mL, P <.001) and activin A (845 [554-1895] vs 469 [285-862] pg/mL, P <.001) were but myeloperoxidase (169 [111-300] vs 144 [88-215] ng/mL, P = .059) was not higher among patients with AKI compared with those without. Urine admission interleukin-8 (50.4 [19.8-145.3] vs 9.5 [2.7-28.7] ng/mL, P <.001) and myeloperoxidase (7.7 [1.5-12.6] vs 1.9 [0.4-6.9] ng/mL, P <.001) were but activin A (9.7 [1.4-42.6] vs 4.0 [0.0-33.0] ng/mL, P = .064) was not higher in AKI than non-AKI patients. Urine myeloperoxidase correlated with urine interleukin-8 (R = .627, P <.001) but not with plasma myeloperoxidase (R = .131, P = .158). Conclusion Interleukin-8 in plasma and urine was associated with septic AKI. Elevated plasma activin A indicates intravascular neutrophil activation in septic AKI. Concomitant plasma and urine myeloperoxidase measurements suggest neutrophil accumulation into injured kidneys.Peer reviewe

Urine NGAL as a biomarker for septic AKI : a critical appraisal of clinical utility-data from the observational FINNAKI study

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is released from kidney tubular cells under stress as well as from neutrophils during inflammation. It has been suggested as a biomarker for acute kidney injury (AKI) in critically ill patients with sepsis. To evaluate clinical usefulness of urine NGAL (uNGAL), we post-hoc applied recently introduced statistical methods to a sub-cohort of septic patients from the prospective observational Finnish Acute Kidney Injury (FINNAKI) study. Accordingly, in 484 adult intensive care unit patients with sepsis by Sepsis-3 criteria, we calculated areas under the receiver operating characteristic curves (AUCs) for the first available uNGAL to assess discrimination for four outcomes: AKI defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, severe (KDIGO 2-3) AKI, and renal replacement therapy (RRT) during the first 3 days of intensive care, and mortality at day 90. We constructed clinical prediction models for the outcomes and used risk assessment plots and decision curve analysis with predefined threshold probabilities to test whether adding uNGAL to the models improved reclassification or decision making in clinical practice. Results: Incidences of AKI, severe AKI, RRT, and mortality were 44.8% (217/484), 27.7% (134/484), 9.5% (46/484), and 28.1% (136/484). Corresponding AUCs for uNGAL were 0.690, 0.728, 0.769, and 0.600. Adding uNGAL to the clinical prediction models improved discrimination of AKI, severe AKI, and RRT. However, the net benefits for the new models were only 1.4% (severe AKI and RRT) to 2.5% (AKI), and the number of patients needed to be tested per one extra true-positive varied from 40 (AKI) to 74 (RRT) at the predefined threshold probabilities. Conclusions: The results of the recommended new statistical methods do not support the use of uNGAL in critically ill septic patients to predict AKI or clinical outcomes.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (pPeer reviewe

Subphenotypes in acute kidney injury : a narrative review

Acute kidney injury (AKI) is a frequently encountered syndrome especially among the critically ill. Current diagnosis of AKI is based on acute deterioration of kidney function, indicated by an increase in creatinine and/or reduced urine output. However, this syndromic definition encompasses a wide variety of distinct clinical features, varying pathophysiology, etiology and risk factors, and finally very different short- and long-term outcomes. Lumping all AKI together may conceal unique pathophysiologic processes specific to certain AKI populations, and discovering these AKI subphenotypes might help to develop targeted therapies tackling unique pathophysiological processes. In this review, we discuss the concept of AKI subphenotypes, current knowledge regarding both clinical and biomarker-driven subphenotypes, interplay with AKI subphenotypes and other ICU syndromes, and potential future and clinical implications.Peer reviewe

Subphenotypes in acute kidney injury : a narrative review

Acute kidney injury (AKI) is a frequently encountered syndrome especially among the critically ill. Current diagnosis of AKI is based on acute deterioration of kidney function, indicated by an increase in creatinine and/or reduced urine output. However, this syndromic definition encompasses a wide variety of distinct clinical features, varying pathophysiology, etiology and risk factors, and finally very different short- and long-term outcomes. Lumping all AKI together may conceal unique pathophysiologic processes specific to certain AKI populations, and discovering these AKI subphenotypes might help to develop targeted therapies tackling unique pathophysiological processes. In this review, we discuss the concept of AKI subphenotypes, current knowledge regarding both clinical and biomarker-driven subphenotypes, interplay with AKI subphenotypes and other ICU syndromes, and potential future and clinical implications.Peer reviewe

Cystatin C and derived measures of renal function as risk factors for mortality and acute kidney injury in sepsis - A post-hoc analysis of the FINNAKI cohort

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