Long-term survival in patients with septic acute kidney injury is strongly influenced by renal recovery

<div><p>Background</p><p>Several studies have shown that long-term survival after acute kidney injury (AKI) is reduced even if there is clinical recovery. However, we recently reported that in septic shock patients those that recover from AKI have survival similar to patients without AKI. Here, we studied a cohort with less severe sepsis to examine the effects of AKI on longer-term survival as a function of recovery by discharge.</p><p>Methods</p><p>We analyzed patients with community-acquired pneumonia from the Genetic and Inflammatory Markers of Sepsis (GenIMS) cohort. We included patients who developed AKI (KDIGO stages 2–3) and defined renal recovery as alive at hospital discharge with return of SCr to within 150% of baseline without dialysis. Our primary outcome was survival up to 3 years analyzed using Gray’s model.</p><p>Results</p><p>Of the 1742 patients who survived to hospital discharge, stage 2–3 AKI occurred in 262 (15%), of which 111 (42.4%) recovered. Compared to recovered patients, patients without recovery were older (75 ±14 vs 69 ±15 years, p<0.001) and were more likely to have at least stage 1 AKI on day 1 (83% vs 52%, p<0.001). Overall, 445 patients (25.5%) died during follow-up, 23.4% (347/1480) for no AKI, 28% (31/111) for AKI with recovery and 44.3% (67/151) for AKI without recovery. Patients who did not recover had worse survival compared to no AKI (HR range 1.05–2.46, p = 0.01), while recovering patients had similar survival compared to no AKI (HR 1.01, 95%CI 0.69–1.47, p = 0.96). Absence of AKI on day 1, no in-hospital renal replacement therapy (RRT), higher Apache III score and higher baseline SCr were associated with recovery after AKI.</p><p>Conclusions</p><p>In patients with sepsis, recovery by hospital discharge is associated with long-term survival similar to patients without AKI.</p></div

Proteomics Reveals Age-Related Differences in the Host Immune Response to Sepsis

Sepsis is commonly caused by community-acquired pneumonia (CAP) and may develop into severe sepsis, characterized by multiple organ failure. The risk of severe sepsis among CAP patients and subsequent mortality increases sharply after the age of 65. The molecular mechanisms associated with this age-related risk are not fully understood. To better understand factors involved with increased incidence and mortality of severe sepsis in the elderly, we used a nested case-control study of patients enrolled in a multicenter observational cohort of 2320 participants with CAP. We identified a total of 39 CAP patients 50–65 and 70–85 years old who did or did not develop severe sepsis. Plasma samples were obtained on presentation to the emergency department and prior to therapeutic interventions. A semi­quantita­tive plasma proteomics workflow was applied which incorporated tandem immuno­affinity depletion, iTRAQ labeling, strong cation exchange fractionation, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 772 proteins were identified, of which 58 proteins exhibit statistically significant differences in expression levels among patients with severe sepsis as a function of age. Differentially expressed proteins are involved in pathways such as acute phase response, coagulation signaling, atherosclerosis signaling, lipid metabolism, and production of nitric oxide and reactive oxygen species. This study provides insight into factors that may explain age-related differences in incidence of severe sepsis in the elderly

Flow chart of study population.

<p>Flow chart of study population.</p

Post-hospitalization ESRD.

<p>Post-hospitalization ESRD.</p

Factors associated with recovery of renal function after AKI in survivors to hospital discharge (n = 262⁺).

<p>Factors associated with recovery of renal function after AKI in survivors to hospital discharge (n = 262<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198269#t004fn002" target="_blank">⁺</a>).</p

Kaplan-Meier survival curves stratified by recovery status.

<p>The three groups are significantly different overall, p < 0.001 (Peto-Peto-Prentice test).</p

Time-varying covariate effects with 95% confidence intervals of renal recovery at hospital discharge in Gray’s model.

<p>Hazard ratios (HR) of Non-recovery vs No AKI from the Gray’s model are reported as the minimum to maximum covariate effect during 10 time intervals. AKI: Acute kidney injury; PSI: Pneumonia Severity Index (on day 1, without age).</p

Baseline characteristics and hospital outcomes of the study population.

<p>Baseline characteristics and hospital outcomes of the study population.</p

Unadjusted outcomes for the propensity-matched cohort of patients transferred to long-term acute care hospitals.

<p>ICU = intensive care unit; LTAC = long-term acute care hospital</p><p>Unadjusted outcomes for the propensity-matched cohort of patients transferred to long-term acute care hospitals.</p

Long-term acute care hospital characteristics by type.

<p>Values are median [interquartile range], frequency (percent) or mean ± standard deviation.</p><p>MedPAR = Medicare Provider Analysis and Review File.</p><p>*The total number of 2005 admissions in MedPAR independent of eligibility for this study.</p><p>Long-term acute care hospital characteristics by type.</p