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 ## Contents ### Page 1 Impact of hemoglobin increase in patients with acute kidney injuryand severe anemia on major adverse kidney events Guillermo navarro-Blackallera,bca,bdbbaa,baaa,ba,baaba,babcd[](http://orcid.org/0000-0003-2786-6667) https://doi.org/10.1080/0886022X.2026.2681245 CONTACT Jonathan S. Chávez-Íñiguez jonarchi_10@hotmail.com nephrology Service, Hospital Civil de Guadalajara Fray antonioalcalde, Hospital 278, Colonia Centro. C.P. 44150. Guadalajara, Jalisco, Mexico. ARTICLE HISTORY Received 17 april 2026 Revised 24 May 2026 accepted 25 May 2026 This is an Open access article distributed under the terms of the Creative Commons attribution license (), whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has beenpublished allow the posting of the accepted Manuscript in a repository by the author(s) or with their consent. KEYWORDS acute kidney injury;anemia; hemoglobincorrection; major adversekidney events (MaKE);kidney replacementtherapy [](http://www.tandfonline.com/) [](http://crossmark.crossref.org/dialog/?doi=10.1080/0886022X.2026.2681245&domain=pdf&date_stamp=2026-6-1) CliniCal Study © 2026 The author(s). Published by informa uK limited, trading as Taylor & Francis Group. ### Page 2 ]. instead, clinical management focuses on treating metabolic complications and,in the most severe cases, providing kidney replacement therapy (KRt) []. among these complications,clinical efforts are primarily directed toward correcting severe hyperkalemia, volume overload, metabolicacidosis, and uremia []. However, aKi is a syndrome of multiorgan dysfunction that promotes severalmetabolic abnormalities often overlooked in the acute setting, including hematologic alterations mani-fested as a reduction in hemoglobin (Hb) []. this complication may plausibly have a major impact onphysiological processes and, consequently, on the clinical course of aKi []. a decline in Hb may com-promise adequate tissue oxygenation and nutrient delivery, thereby hindering recovery during an epi-sode of aKi, promoting maladaptive cellular responses, and favoring a pathogenic transition towardchronic kidney disease (CKd) [,]. Because an association has been documented between abrupt reduc-tions in hemoglobin (Hb) and the risk of developing aKi [], it is reasonable to consider that this rela-tionship may also operate bidirectionally. in other words, increasing Hb levels during hospitalization foraKi could potentially be associated with improved clinical trajectories and lower rates of major adversekidney events (MaKE). although this association has been explored in other critical care contexts [], itsspecific impact on kidney recovery in the setting of aKi remains largely unaddressed and subject toongoing debate. Clarifying these relationships is clinically important because hemoglobin (Hb) is rou-tinely measured, is potentially modifiable, and may serve as a pragmatic tool for risk stratification.Furthermore, given the distinct risks and mechanisms of action of available interventions, it is clinicallyrelevant to examine whether the strategy used to increase Hb, either through blood transfusions and/orerythropoiesis-stimulating agents (ESas), yields differential effects on kidney outcomes during aKi.therefore, to address this critical knowledge gap and inform clinical practice, we investigated the asso-ciation between early Hb correction in hospitalized patients with severe anemia and aKi and the occur-rence of MaKE across short and medium term follow-up periods. Methods this retrospective cohort study was conducted at Hospital Civil de Guadalajara Fray antonio alcalde,Mexico, a tertiary academic referral center. all hospitalized patients with aKi who received a nephrol-ogy consultation were screened for eligibility. We focused on a specific clinical phenotype consistingof patients with aKi and severe anemia at baseline, defined as a Hb concentration <8.0 g/dl. Eligibilityfurther required at least three Hb measurements during follow-up to adequately characterize Hb tra-jectories, with the baseline value (<8.0 g/dl) compared with subsequent measurements. Hb levelswere measured in the hospital’s certified central laboratory using the Cell-dyn Ruby® hematologyanalyzer. Patients who achieved at least one Hb measurement >10 g/dl during follow-up were classified as thecorrection group, whereas those who did not were classified as the non-correction group. the Hb thresh-old of <8 g/dl was selected to identify severe anemia, whereas Hb correction >10 g/dl was considereda clinically meaningful increase beyond the severe anemia range. at least three Hb measurements wererequired to characterize Hb trajectories during follow-up, while correction was defined as the achieve-ment of at least one Hb value >10 g/dl within the first 10 days of hospitalization. Hb target goals anddecisions regarding intervention were highly individualized and based exclusively on the clinical judg-ment of the attending physicians and nephrology specialists. anemia management strategies reflectedreal-world physician-directed practice and included red blood cell transfusion and, in selected patients,the use of erythropoiesis-stimulating agents (ESas), specifically human recombinant erythropoietin (epo-etin alfa) and erythropoietin analogs (darbepoetin). the diagnosis of aKi was established using serumcreatinine (sCr) criteria as defined by the Kidney disease: improving Global Outcomes (KdiGO) guidelines[]. For this study, patients were required to have a known baseline sCr level, defined as the mostrecent stable measurement obtained within six months prior to hospitalization. availability of follow-upsCr measurements during subsequent hospital days was mandatory to evaluate the primary and second-ary outcomes (MaKE10 and MaKE90). MaKE were defined as a composite of death, initiation of KRt, or ### Page 3 a ≥ 25% decline in estimated glomerular filtration rate (eGFR) from baseline []. the MaKE10 and MaKE90composite outcomes were selected to improve consistency and comparability of aKi-related endpointsacross studies. in accordance with recommendations from the 31st acute disease Quality initiative (adQi)consensus, we identified the subphenotype of patients with aKi and severe anemia as a potential markerof response to transfusion and erythropoiesis-stimulating agent (ESa) therapy []. Patients were excluded if they had experienced aKi within the preceding three months, were youngerthan 18 years, had CKd stage 5, were receiving chronic dialysis, had undergone kidney transplantation,had a hospital stay shorter than 48 h, or had missing data that precluded complete analysis. Clinicalcharacteristics, demographic information, and laboratory data were obtained through automatedextraction from the institutional electronic medical record system. indications for initiation of KRtincluded diuretic resistant fluid overload, severe hyperkalemia, severe metabolic acidosis, and uremiccomplications such as encephalopathy, pericarditis, or seizures []. Study objectives the primary objective was to evaluate the association between Hb correction (>10 g/dl within 10 daysof hospitalization) and the occurrence of MaKE10 in hospitalized patients with aKi and severe anemia(Hb <8.0 g/dl). Secondary objectives were to assess the association between early Hb correction and theindividual components of MaKE death, initiation of KRt, or a ≥ 25% decline in eGFR from baseline, as wellas the association between Hb correction and the occurrence of MaKE90. an exploratory objective wasto evaluate whether the strategy used to increase Hb, through blood transfusion alone or transfusioncombined with ESas, resulted in differential effects on kidney outcomes. this study was funded by a grant from the Secretaría de Salud Jalisco and the Consejo nacional deCiencia, Humanidades y tecnología (COnaHCyt) number Sni1. the requirement for written informedconsent was waived by the institutional Review Board (iRB) due to the retrospective nature of the study.the study was approved by the Hospital Civil de Guadalajara Fray antonio alcalde iRB (HCG/CEi-0550/15).all procedures were conducted in accordance with the Strengthening the Reporting of ObservationalStudies in Epidemiology (StROBE) guidelines [] and the REporting of Studies Conducted usingObservational Routinely Collected Health data (RECORd) statement []. Statistical analysis Continuous variables were assessed for normality using the Shapiro–Wilk test and visual inspection ofhistograms. Given the non-normal distribution typical of critically ill populations, continuous variables arereported as medians with interquartile ranges (iQR). Categorical variables are expressed as absolute fre-quencies and percentages. Baseline characteristics between the exposure group (patients achieving Hbcorrection >10 g/dl within 10 days) and the non-correction group were compared using the Mann–Whitney u test for continuous variables and the chi-square test or Fisher’s exact test for categoricalvariables, as appropriate. to assess the impact of Hb correction on the primary outcome, unadjusted risk ratios (RR) and abso-lute risk differences were calculated. For multivariable analysis, logistic regression models were con-structed to estimate odds ratios (OR) with 95% confidence intervals (Ci). the primary model for MaKE10was adjusted a priori for clinically relevant confounders, including age, sex, and baseline estimated glo-merular filtration rate (eGFR), calculated using the CKd-EPi 2021 equation. to minimize selection bias andpreserve statistical power, variables with substantial missingness (e.g., admission lactate) were excludedfrom the final multivariable model, allowing inclusion of the entire cohort (N = 232) in the regressionanalysis. Secondary analyses included: (1) separate logistic regression models for each individual component ofMaKE10 and (2) assessment of long-term outcomes using MaKE90. as an exploratory analysis, we eval-uated the differential impact of the hemoglobin correction strategy (blood transfusion alone versus ESas.Hb trajectories over the first nine days of hospitalization were visualized using mean values with stan-dard errors (SEM). a forest plot was generated to graphically summarize adjusted odds ratios across allprimary and secondary outcomes. ### Page 4 all statistical analyses were performed using Stata software, version 16.1 (StataCorp, College Station,tX, uSa). a two-tailed p value <0.05 was considered statistically significant. Results Between august 2020 and december 2024, a total of 232 hospitalized patients with aKi and baseline Hb<8.0 g/dl were included in the final analysis. the cohort was stratified into two groups according to Hbcorrection (Hb >10 g/dl) status during the first 10 days of hospitalization. as shown in, 47patients (20.3%) achieved Hb correction, whereas 185 patients (79.7%) did not reach this target. Demographic and clinical characteristics Baseline characteristics were well balanced between the two groups, indicating a homogeneous popula-tion at study entry, as shown in. the median age of the cohort was 49.0 years (iQR, 38.0–64.0), and53.9% of patients were male. there were no significant differences in baseline sCr (0.90 [0.70–1.22] vs. 0.80[0.70–1.00] mg/dl, p = 0.21) or median eGFR (100.6 [82.3–110.0] vs. 99.6 [91.9–105.3] ml/min/1.73 m2,p = 0.48) between groups. sCr at study inclusion was also similar between groups (4.68 vs. 4.09 mg/dl,p = 0.20), as was the distribution of KdiGO aKi stages (p = 0.49). notably, KdiGO stage 3 predominated,accounting for 84.8% of the study population. Sepsis was the leading cause of aKi in both groups (45.0%vs. 36.2%; p = 0.32). Hypovolemia was significantly more frequent among patients who achieved hemoglo-bin correction (25.5% vs. 13.0%; p = 0.04), whereas cardiorenal, nephrotoxic, and post-surgical etiologiesshowed no significant differences between groups. Markers of critical illness severity at admission, including serum lactate (1.3 vs. 1.5 mmol/l, p = 0.22),were comparable between groups. Key metabolic parameters, including serum potassium, sodium, bicar-bonate, pH, lactate, and urea, were also similar between groups (all p > 0.05). as expected given thestratification strategy, patients who achieved Hb correction had a higher frequency of blood transfusioncompared with the non-correction group (97.9% vs. 85.4%, p = 0.019); however, the total number of ![Flowchart shows AKI patient selection: 1,056 assessed, 824 excluded, 232 included; hemoglobin groups: <10 g/dL \(185\) and >10 g/dL \(47\). Flowchart detailing patient selection for an AKI study. A total of 1,056 patients were initially assessed, with 824 excluded for various reasons, including age, existing conditions, and hemoglobin levels. This left 232 patients included in the study based on hemoglobin levels: 185 patients had hemoglobin <10 g/dL \(highlighted in pink\), while 47 patients had hemoglobin <10 g/dL \(highlighted in blue\).]() Figure 1. Study flow chart of the cohort. Flowchart illustrating the screening, exclusion, and final inclusion of patientswith aKi and severe anemia. Abbreviations: aKi, acute Kidney injury; Hb, Hemoglobin. ### Page 5 transfused units did not differ between groups (median, 5 units; p = 0.52). the use of ESas, includinghuman recombinant erythropoietin, epoetin alfa (21.1%) and darbepoetin (3.0%), was similar betweengroups, with no statistically significant differences (all p > 0.05). the difference in Hb levels between groups became evident from day 2 and was sustained through-out the follow-up period, as shown in, confirming the effectiveness of the correction strate-gies employed. A ≥ 25% decline in eGFR from baseline occurred in 178 patients (76.7%), with nosignificant difference between groups (75.7% vs. 80.9%, p = 0.58). the proportion of patients requiringKRt was 90 (38.8%) and was nearly identical between groups (38.4% vs. 40.4%, p = 0.80). Overall, 54patients (23.3%) died during follow-up, with similar mortality rates between groups (24.9% vs. 17.0%,p = 0.35). Primary outcome in unadjusted bivariate analyses, achieving Hb levels >10 g/dl appeared to be strongly protective. theincidence of MaKE10 was significantly lower in the correction group (14.9%) compared with thenon-correction group (93.5%), yielding a crude risk ratio of 0.16 (95% Ci, 0.07–0.32; p < 0.001). However,this association was substantially attenuated after adjustment for confounders in the multivariable logis-tic regression model (). after controlling for age, sex, and baseline eGFR in the full cohort (N = 232),Hb correction was no longer independently associated with a reduction in MaKE10 (adjusted OR, 1.04;95% Ci, 0.41–2.62; p = 0.93). this discrepancy between crude and adjusted estimates suggests that theapparent unadjusted benefit may have been driven by underlying clinical characteristics or physiologicalreserve that favored patients more likely to respond to hematologic interventions, rather than Hb correc-tion itself being the primary determinant of kidney recovery. Table 1. Baseline demographic and clinical characteristics of the study population stratified by Hb correction. | Variable | no correction n = 185 | Correction n = 47 | Total n = 232 | p | | - | - | - | - | - | | age (y) | 47.0 (38.0–64.0) | 56.0 (40.0–64.0) | 49.0 (38.0–64.0) | 0.17 | | Male sex | 101 (54.6%) | 24 (51.1%) | 125 (53.9%) | 0.66 | | Baseline creatinine (mg/dl) | 0.90 (0.70–1.22) | 0.80 (0.70–1.00) | 0.90 (0.70–1.20) | 0.21 | | Baseline eGFR (ml/min/1.73 m2) | 100.6 (82.3–110.0) | 99.6 (91.9–105.3) | 100.4 (85.5–109.5) | 0.48 | | Creatinine at inclusion (mg/dl) | 4.68 (2.80–6.81) | 4.09 (2.33–5.70) | 4.50 (2.71–6.70) | 0.20 | | Stages of aKi | 0.49 | | Stage 1 | 8 (4.3%) | 3 (6.4%) | 11 (4.7%) | | Stage 2 | 7 (3.8%) | 3 (6.4%) | 10 (4.3%) | | Stage 3 | 157 (84.9%) | 40 (85.1%) | 197 (84.9%) | | Hb (g/dl) | 7.2 (6.5–7.6) | 7.1 (6.3–7.7) | 7.2 (6.5–7.6) | 0.98 | | aKi etiologies | | Sepsis | 83 (45%) | 17 (36.2%) | 100 (43.1%) | 0.32 | | Hypovolemia | 24 (13.0%) | 12 (25.5%) | 36 (15.5%) | 0.04 | | Cardiorenal | 19 (10.3%) | 8 (17.0%) | 27 (11.6%) | 0.20 | | nephrotoxic | 34 (18.4%) | 6 (12.8%) | 40 (17.2%) | 0.51 | | Post-surgical | 25 (13.5%) | 4 (8.5%) | 29 (12.5%) | 0.46 | | leukocytes (/μl) | 12.9 (8.4–18.1) | 13.8 (8.3–19.4) | 13.0 (8.3–18.2) | 0.70 | | Platelets (/μl) | 174 (88–304) | 242 (122–322) | 189 (93–314) | 0.083 | | Potassium (meq/l) | 4.7 (4.1–5.5) | 4.9 (4.2–5.9) | 4.8 (4.1–5.6) | 0.50 | | Sodium (meq/l) | 135 (130–140) | 136 (131–140) | 135 (130–140) | 0.44 | | Bicarbonate (meq/l) | 17.9 (13.0–22.0) | 19.1 (17.2–23.2) | 18.3 (13.2–22.0) | 0.31 | | pH | 7.35 (7.28–7.41) | 7.39 (7.33–7.41) | 7.36 (7.30–7.41) | 0.53 | | lactate (μmol/l)) | 1.3 (0.8–2.9) | 2.1 (0.8–3.5) | 1.5 (0.8–3.0) | 0.22 | | urea (mg/dl) | 163 (109–218) | 137 (89–203) | 158 (106–218) | 0.11 | | Transfused | 158 (85.4%) | 46 (97.9%) | 204 (87.9%) | 0.019 | | Transfusions | 5 (2–9) | 5 (2–7) | 5 (2–8) | 0.52 | | erythropoietin alfa | 40 (21.6%) | 9 (19.1%) | 49 (21.1%) | 0.71 | | Darbepoetin | 7 (3.8%) | 0 (0.0%) | 7 (3.0%) | 0.18 | | ≥25% decline in eGFR from baseline) | 140 (75.7%) | 38 (80.9%) | 178 (76.7%) | 0.58 | | KRT | 71 (38.4%) | 19 (40.4%) | 90 (38.8%) | 0.80 | | Death | 46 (24.9%) | 8 (17.0%) | 54 (23.3%) | 0.35 | | Data are presented as median (interquartile range [iQR]) for continuous variables and frequency (percentage) for categorical variables. P-valueswere calculated using the Mann-Whitney u test for continuous data and the Chi-square test for categorical data. Hb Correction: Defined asachieving a hemoglobin level >10 g/dl within the first 10 days. | | eGFR: estimated Glomerular Filtration Rate calculated using the CKD-ePi 2021 creatinine equation. KRT: Kidney Replacement Therapy. Significantdifferences (p < 0.05). | ### Page 6 Secondary outcomes We further analyzed the individual components of the composite MaKE10 outcome to identify potentialsignals of benefit or harm (). Hb correction was not independently associated withreduced mortality (adjusted OR, 0.59; 95% Ci, 0.25–1.40; p = 0.23). Similarly, the risk of requiring new KRt(adjusted OR, 1.17; 95% Ci, 0.60–2.31) and the likelihood of an eGFR decline >25% from baseline (adjustedOR, 1.22; 95% Ci, 0.52–2.86) did not differ significantly between groups. Medium-term outcomes wereconsistent with these short-term findings, as no significant association was observed between early Hbcorrection and the composite MaKE90 outcome (adjusted OR, 0.86; 95% Ci, 0.41–1.80; p = 0.68). in exploratory multivariable analyses stratified by anemia correction strategy (blood transfusion aloneversus transfusion plus ESas), neither approach was independently associated with improved MaKE out-comes. this consistency across treatment modalities reinforces the interpretation that attainment of anHb target >10 g/dl, irrespective of the method used, likely reflects the underlying clinical trajectoryrather than a direct independent therapeutic effect on kidney outcomes. Discussion in patients with aKi and severe anemia, achieving an increase in Hb to >10 g/dl within the first 10 daysof hospitalization was not associated with improved short- or medium-term MaKE, nor with any of theindividual components of this composite outcome. Furthermore, no differential effect was observed ![Line graph showing hemoglobin levels over nine days, with corrected levels in dark blue and uncorrected in gray. A line graph displays hemoglobin levels \(g/dL\) over nine follow-up days. Two lines represent "Uncorrected Hb" \(dashed gray, <10 g/dL\) and "Corrected Hb" \(solid dark blue, >=10 g/dL\). Corrected Hb rises from ∼7 g/dL to about 10 g/dL by day 3, fluctuating thereafter. Uncorrected Hb remains stable below 8 g/dL. Error bars indicate variability at each data point, with the highest recorded corrected hemoglobin at approximately 10.5 g/dL.]() Figure 2. Temporal trajectory of mean hemoglobin levels during the first 10 days of follow-up. Comparison of dailyhemoglobin concentrations (g/dl) between patients who achieved the correction target (>10 g/dl, blue line) and thosewho did not (gray dashed line). Data are presented as Mean Standard error of the Mean (SeM). a clear separationbetween groups is observed from day 2 onwards. note: Day 10 was excluded from the visualization to minimize vari-ability due to discharge or censorship. Table 2. unadjusted and multivariate logistic regression analysis of the association between hemoglobin correction andclinical outcomes. | unadjusted analysis | adjusted analysis | | - | - | | Primary outcome | | OR | 95% Ci | P-value | OR | 95% Ci | P-value | | MaKe10 | 1.15 | [0.47–2.80] | 0.758 | 1.04 | [0.41–2.62] | 0.931 | | Secondary outcomes | | Mortality | 0.68 | [0.29- .56] | 0.360 | 0.59 | [0.25–1.40] | 0.232 | | new KRT Requirement | 1.09 | [0.57–2.09] | 0.797 | 1.17 | [0.60–2.31] | 0.642 | | Decrease in eGFR >25% | 1.36 | [0.61–3.02] | 0.455 | 1.22 | [0.52–2.86] | 0.644 | | MaKe90 | 0.83 | [0.40–1.72] | 0.617 | 0.86 | [0.41–1.80] | 0.684 | | Crude OR: unadjusted bivariate association. | | adjusted OR: Multivariate model adjusted for age, sex, and baseline eGFR. | | MaKe10: Composite outcome of death, new requirement for KRT, or persistent renal dysfunction (defined as a decrease in eGFR >25% frombaseline) at 10 days or hospital discharge. MaKe90: Composite outcome assessed at 90 days. Ci: Confidence interval; OR: Odds Ratio. | ### Page 7 according to the strategy used to increase Hb levels, whether through blood transfusion alone or trans-fusion combined with ESas (). despite early correction of Hb to >10 g/dl, no improvement in MaKE was observed. this lack of ben-efit is consistent with the limited, though growing, body of evidence suggesting that aggressive anemiamanagement may not improve kidney outcomes in aKi. in a retrospective cohort of 212 patients, Huet al. evaluated whether anemia was associated with lower rates of kidney recovery and poorer survivalamong individuals with aKi by comparing patients with mild versus severe anemia. in their study, nei-ther kidney recovery nor survival differed between groups, regardless of whether anemia severity wasdefined by an Hb decline >2 versus ≤2 g/dl or by a nadir Hb >9 versus ≤9 g/dl (p > 0.5 for both) []. itis important to note that the characteristics of our cohort differ substantially from those of the afore-mentioned study, as we specifically focused on patients with aKi and severe anemia, defined as Hb<8 g/dl. this represents a more vulnerable clinical phenotype, potentially more susceptible to aKi-relatedcomplications and, therefore, theoretically more likely to benefit from Hb correction. in our cohort ofpatients with aKi and severe anemia, only approximately 20% achieved an Hb level >10 g/dl duringhospitalization. although the composite MaKE outcome was not significantly associated with Hb correction, bothmortality and KRt initiation remained frequent across groups, reflecting the high severity of illness of thiscohort. these findings suggest that, in patients with severe aKi and profound anemia, early Hb correc-tion alone may be insufficient to substantially modify short-term kidney-related outcomes. the markedattenuation of the unadjusted association after multivariable adjustment suggests that baseline clinicaldifferences and residual confounding likely contributed to the crude differences observed between groups. this lack of a statistically significant association is particularly noteworthy, given that our initial hypoth-esis was strongly supported by established pathophysiological mechanisms. at the cellular level, severeanemia may impair tubular epithelial cell and macrophage function, thereby promoting inflammationand fibrosis, whereas improvement in Hb levels has been shown to mitigate these abnormalities andenhance both structural and functional renal parameters []. in addition, severe anemia may increasesusceptibility to further tubular injury; thus, restoration of Hb to a near-normal range could theoretically ![Horizontal bar chart showing adjusted odds ratios for kidney outcomes related to hemoglobin correction. The bar chart illustrates the impact of hemoglobin correction on kidney outcomes, displaying adjusted odds ratios \(95% confidence intervals\) for MAKE-10, mortality, new RRT, dysfunction, and MAKE-90. A dashed vertical line at odds ratio 1 indicates no effect; MAKE-10 is slightly above 1, while other outcomes are below. The trend reflects no definitive favor toward correction or control across categories in a sample of 232.]() Figure 3. Forest plot of adjusted odds ratios for primary and secondary kidney outcomes. Visual summary of the mul-tivariate logistic regression analysis (N = 232). The markers represent the adjusted Odds Ratio (aOR) for the effect ofachieving Hb correction >10 g/dl on each outcome. Horizontal bars indicate 95% Confidence intervals (95% Ci). PrimaryOutcome: MaKe10. Secondary Outcomes: individual components of MaKe10 (Mortality, new RRT, ≥25% decline in eGFRfrom baseline) and MaKe90. Model adjustment; all models were adjusted for age, sex, and baseline eGFR (CKD-ePi2021). The vertical dashed line at 1.0 represents the line of no effect. Values to the left favor hemoglobin correction.abbreviations: RRT, Renal Replacement Therapy; eSa, erythropoiesis-Stimulating agents. ### Page 8 reestablish intracellular homeostasis and confer protection against ongoing renal damage []. Based onthis robust physiological evidence, we hypothesized that, in the setting of aKi and severe anemia,improvement in Hb levels might also confer a medium-term survival benefit, potentially independent ofits effects on kidney function. Consistent benefits related to kidney physiology have been describedwhen severe anemia is corrected, including prevention of the transition from aKi to CKd [], enhancedtissue oxygenation [], improved nephron metabolism [], preservation of kidney function [], andimproved quality of life []. in our study, nearly nine out of ten patients received at least one blood transfusion during hospital-ization, with transfusions occurring more frequently in the correction group (p = 0.019). despite this, noclinical benefit was observed with respect to MaKE outcomes. Blood transfusion remains common incritically ill patients, although its use has gradually declined with the adoption of more restrictive trans-fusion strategies []. Because nearly all patients in the correction group received blood transfusions, itis possible that transfusion-related adverse effects, including volume overload, inflammatory responses,and transfusion-related immunomodulation, may have partially offset the potential physiological benefitsof hemoglobin correction, contributing to the neutral outcomes observed. the absence of benefit inMaKE outcomes among patients with aKi and severe anemia, despite receiving a median of five units ofpacked red blood cells, is consistent with findings from a meta-analysis of 31 clinical trials, which demon-strated no mortality benefit when comparing liberal versus restrictive transfusion strategies, the lattertypically defined by transfusion thresholds of hemoglobin levels below 7 g/dl [,]. a cochrane reviewincluding 48 clinical trials found that 30-day mortality was not affected by adopting a restrictive trans-fusion strategy, defined as transfusion at Hb <8 g/dl, compared with a liberal strategy (<9 g/dl); however,MaKE outcomes were not evaluated in that analysis []. Restrictive transfusion strategies have also beenexamined in critically ill populations with a specific focus on renal outcomes, and similarly, no favorableeffects have been demonstrated []. importantly, restrictive approaches reduce the likelihood of receiv-ing a red blood cell transfusion by approximately 40% []. notably, current american College of ChestPhysicians guidelines consider certain comorbidities on an individual basis when issuing recommenda-tions on liberal versus restrictive transfusion thresholds, yet provide no specific guidance regarding trans-fusion practices in the setting of aKi []. Studies such as ours may help address this gap in the evidence. ![Flowchart illustrating hemoglobin levels in AKI and related clinical outcomes with statistical values. The figure shows a flowchart about Acute Kidney Injury \(AKI\), featuring a human silhouette and kidneys. It branches into hemoglobin levels: "Hemoglobin >10 g/dL" in green and "Hemoglobin >8 g/dL" in blue. Outcome metrics are outlined in panels labeled MAKE10 and MAKE90. MAKE10 lists mortality, KRT, or decline in eGFR \(aOR 0.93\), while MAKE90 shares associated metrics with aOR of 0.68. Individual outcomes include mortality \(aOR 0.23\), KRT \(aOR 0.64\), and eGFR decline =25% \(aOR 0.64\). "ESA" and "Blood Transfusion" are compared.]() Figure 4. Central image. ### Page 9 during aKi, increased erythropoietin (EPO) production has been observed across multiple organs, aneffect that appears to occur independently of oxygen tension []. in parallel, EPO receptors are upreg-ulated within the kidney parenchyma [], suggesting that activation of these receptors may promotecellular repair processes [,]. Experimental studies have demonstrated that administration of high-doseEPO attenuates aKi severity []. accordingly, it was biologically plausible to hypothesize that increas-ing Hb levels during aKi through EPO administration could confer clinical benefit. For this reason, weperformed an exploratory analysis examining the use of ESas. despite ESa administration, Hb trajectoriesdid not differ between groups, and no clinical benefit was observed among patients who received EPO.importantly, current KdiGO anemia guidelines do not support ESa use for rapid correction of anemiaduring acute illness, and the delayed hematologic response of ESas likely limits their short-term impactduring aKi hospitalization. these findings are consistent with the lack of effect reported in prior clinical trials, including EPO-tBi[] and EaKi []. this observation may reflect a state of ESa resistance. although the mechanismsunderlying ESa hyporesponsiveness in aKi remain incompletely understood, prior studies suggest thatpoor Hb responsiveness to high doses of EPO may promote endothelial dysfunction and reduced nitricoxide bioavailability, thereby increasing cardiovascular risk []. alternatively, this pattern may reflect amore severely ill and pro-inflammatory patient population. Our findings contribute to the ongoing clinical debate regarding aggressive anemia correction in aKi.Specifically, our results are consistent with the conservative approach recommended by current KdiGOguidelines, which caution against routine ‘normalization’ of Hb levels in patients with aKi, particularlywhen targeting values above 10 g/dl []. the narrow therapeutic window between potential benefits,such as avoidance of KRt, reduced transfusion requirements, and alleviation of anemia-related symptoms;and potential harms, including cardiovascular events and increased mortality, underscores the impor-tance of individualized decision-making when prescribing ESas. the strengths of our study include the uniqueness of the cohort, which comprised patients with aKiand severe anemia, and its direct relevance to everyday clinical practice. We applied robust statisticalmethods with multivariable adjustment and relied on a validated clinical database with clearly definedoutcomes. nevertheless, these strengths should be interpreted in light of several inherent methodological limita-tions. a post-hoc power analysis for MaKE10, based on the observed group sizes and effect estimate,showed limited statistical power (approximately 6.1%), indicating that the study was underpowered todetect small differences between groups; therefore, a type ii error cannot be excluded. the retrospectiveobservational design allows for the identification of associations but precludes causal inference. the rel-atively small number of patients achieving Hb correction limits statistical power, the robustness of mul-tivariable analyses, and the generalizability of our findings. although daily Hb values were available, theexact timing of MaKE components was not consistently recorded; therefore, Hb correction could not bemodeled as a time-dependent exposure. Baseline kidney function was defined using the most recentstable sCr value within 6 months before hospitalization, which may not fully reflect kidney functionimmediately prior to aKi onset. Because most patients had KdiGO stage 3 aKi, the findings primarilyreflect a population with severe kidney injury and may not be generalizable to patients with milder aKi(stages 1–2). the relatively small number of patients with less severe aKi precluded robust subgroupanalyses according to aKi stage. Because the cohort included only patients who received nephrologyconsultation, the study may be subject to severe-case selection bias, limiting generalizability to patientswith milder aKi managed without nephrology involvement. the definition of severe anemia (Hb <8 g/dl),the target hemoglobin level used to define correction (>10 g/dl), and the timing of anemia diagnosis inrelation to aKi onset were arbitrarily chosen. Pre-hospitalization hemoglobin values were not consistentlyavailable, limiting evaluation of the magnitude and chronicity of anemia before aKi onset. Becausehemoglobin correction strategies were based on physician clinical judgment rather than a standardizedprotocol, confounding by indication and residual selection bias cannot be excluded. it is possible thatsome patients in the non-correction group were perceived as either too critically ill or clinically stable towarrant aggressive hemoglobin correction, which may have introduced treatment-selection bias. BecauseHb correction was defined as any value >10 g/dl within the first 10 days, temporal overlap betweenexposure and MaKE10 assessment cannot be completely excluded. the specific etiology of anemia could ### Page 10 not be consistently determined. information regarding active bleeding, recent surgical procedures, orinvasive interventions was not consistently available, limiting evaluation of the potential impact of ongo-ing blood loss on treatment response and outcomes. the absence of detailed hematologic and inflammatory biomarkers limited characterization of anemiaphenotypes and precluded subgroup analyses according to specific anemia mechanisms. the retrospec-tive design prevented reliable differentiation between isolated ESa therapy and combined transfusionplus ESa treatment. Because detailed ESa dosing data and iron/inflammatory biomarkers were not con-sistently available, the potential influence of inflammation and iron-restricted erythropoiesis on ESaresponsiveness could not be adequately evaluated. additionally, we lacked access to ancillary parametersthat could further characterize anemia, such as iron deficiency status and bleeding events. these omis-sions may have confounded the assessment of anemia etiology, management, and prognosis. We wereunable to formally evaluate the presence of EPO resistance due to insufficient data, which may haveinfluenced the effectiveness of ESa therapy. decisions regarding blood transfusion or ESa use werebased on clinical judgment, introducing the possibility of unmeasured confounding inherent tonon-randomized study designs. detailed information regarding ESa dose, timing, duration, and adminis-tration frequency was not consistently available, limiting interpretation of the exploratory analyses involv-ing ESa therapy. although we adjusted for key covariates, residual confounding cannot be excluded.Finally, long-term follow-up data related to blood transfusions may be incomplete. although institutionalpolicy recommends transfusion at Hb levels <7 g/dl, consistent with the cohort’s median baseline Hb of7.2 g/dl (iQR, 6.5–7.6), detailed documentation of all transfusion events during the 90-day follow-upperiod may have been subject to incomplete recording. From a clinical perspective, our study provides valuable real-world evidence to inform therapeuticdecision-making in a highly vulnerable population, patients with aKi and severe anemia, in whom uncer-tainty regarding Hb correction strategies remains substantial. By demonstrating that early Hb correctionto levels >10 g/dl does not translate into a reduction in MaKE, our findings support a more conservativeand individualized approach to anemia management during aKi. Such an approach may help reduceunnecessary transfusions and avoid exposure to ineffective or potentially burdensome interventions.importantly, this study challenges long-standing assumptions regarding the benefits of Hb normalizationin acute illness and highlights that Hb correction alone should not be pursued as a surrogate marker ofkidney recovery. these insights may contribute to refining clinical protocols, optimizing resource utiliza-tion, and guiding future prospective studies aimed at identifying patient subgroups that may truly ben-efit from targeted Hb based interventions Conclusions in this retrospective cohort of patients with aKi and severe anemia, correction of Hb levels to >10 g/dl,compared with failure to achieve this target, was not associated with short- or medium-term MaKE. Acknowledgment to all the Social Service students of Medicine who have been in the nephrology Service, without you this articlewould have been not possible. GnB, JJZ and JSCi designed the study, analyzed the data, supervised, and wrote themanuscript. FCa, iFM, GCa, MFGP captured the data, reviewed the software. dP, aMGG, EMG, JaGF, laV, KRl, RMG,Man, GGG wrote and supervised the manuscript. Authors’ contributions CRedit: Guillermo Navarro-Blackaller: Conceptualization, data curation, Formal analysis, Funding acquisition,investigation, Methodology; Jose J. Zaragoza: Conceptualization, data curation, Formal analysis, Funding acquisition,investigation, Methodology, Project administration, Software, Supervision, Validation, Writing – original draft;Fernando Cruz-Aragón: data curation, Formal analysis, Funding acquisition, investigation; Daniela Ponce:Supervision, Validation, Visualization; Itzel Fong-Maravilla: data curation, Formal analysis, Software; GaelChávez-Alonso: data curation, Formal analysis, investigation, Methodology; María F. García-Peña: data curation,Formal analysis; Alejandro Martínez Gallardo-González: Software, Supervision, Validation, Visualization; EduardoMendoza-Gaitán: Supervision, Validation, Visualization; Juan A. Gómez-Fregoso: Conceptualization, Software, ### Page 11 Supervision, Validation; Luz Alcantar-Vallin: data curation, Supervision, Validation, Visualization, Writing – originaldraft; Karina Renoirte-López: Methodology, Supervision, Validation, Visualization; Ramón Medina-González:Conceptualization, Formal analysis, Funding acquisition, investigation, Methodology; Manuel Arizaga-Nápoles:Formal analysis, Software, Supervision, Validation; Guillermo García-García: Validation, Visualization, Writing – origi-nal draft, Writing – review & editing; Jonathan S. Chávez-Iñiguez: Conceptualization, data curation, Formal analysis,Funding acquisition, investigation, Methodology, Project administration, Resources, Software, Supervision, Validation,Visualization, Writing – original draft, Writing – review & editing. Disclosure statement the authors have no conflicts of interest to declare. Consent to participate Written informed consent was waived from participants. Statement of ethics the study was conducted in adherence with the declaration of Helsinki and was approved by the Hospital Civil deGuadalajara Fray antonio alcalde institutional Review Board (HCG/CEi-0550/15). Funding this study was funded by a grant from the Secretaria de Salud Jalisco y el Consejo nacional de Ciencia, Humanidadesy tecnología COnaHCyt number 1. ORCID Jonathan S. 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