Introduction: Acute Kidney Injury (AKI) is common in critical ill populations and its association with high short-term mortality is well established. However, long-term risks of death and renal dysfunction are poorly understood and few studies exclude patients with pre-existing renal disease, meaning outcome for de novo AKI has been difficult to elicit. We aimed to compare the long-term risk of Chronic Kidney Disease (CKD), End Stage Renal Disease (ESRD) and mortality in critically ill patients with and without severe de novo AKI.Method: This cohort study was conducted between 2005 and 2011 in Swedish intensive care units (ICU). Data from 130134 adult patients listed on the Swedish intensive care register-database was linked with other national registries. Patients with pre-existing CKD (4192) and ESRD (1389) were excluded, as were cases (26771) with incomplete data. Patients were classified according to AKI exposure during ICU admission. Outcome in the de novo AKI group was compared to the non-exposed (no-AKI) intensive care control group. Primary outcome was all-cause mortality. Follow-up ranged from one to seven years (median 2.1 years). Secondary outcomes were incidence of CKD and ESRD and median follow-up was 1.3 years.Results: Of 97 782 patients, 5273 (5.4%) had de novo AKI. These patients had significantly higher crude mortality at one (48.4% vs. 24.6%) and five years (61.8% vs. 39.1%) compared to the control group. The first 30% of deaths in AKI patients occurred within 11 days of ICU admission whilst the 30-centile in the no-AKI group died by 748 days. CKD was significantly more common in AKI survivors at one year (6.0% vs. 0.44%) than in no-AKI group (adjusted incidence rate ratio (IRR) 7.6). AKI patients also had significantly higher rates of ESRD at one (2.0% vs. 0.08%) and at five years (3.9% vs. 0.3%) than those in the comparison group (adjusted IRR 22.5).Conclusion: This large cohort study demonstrated that de novo AKI is associated with increased short and long-term risk of death. AKI is independently associated with increased risk of CKD and ESRD as compared to an ICU control population. Severe de novo AKI survivors should be routinely followed-up and their renal function monitored.
Introduction: Prevalence of chronic kidney disease (CKD) amongst intensive care unit (ICU) admissions is rising. How mortality and risk of end-stage renal disease (ESRD) differs between those with and without CKD and with acute kidney injury (AKI) is unclear. Determining factors that increase the risk of ESRD is essential to optimise treatment, identify patients requiring nephrological surveillance and for quantification of dialysis provision. Method: This cohort study used the Swedish intensive care register 2005–2011 consisting of 130,134 adult patients. Incomplete cases were excluded (26,771). Patients were classified (using diagnostic and intervention codes as well as admission creatinine values) into the following groups: ESRD, CKD, AKI, acute-on-chronic disease (AoC) or no renal dysfunction (control). Primary outcome was all-cause mortality. Secondary outcome was ESRD incidence. Results: Of 103,363 patients 4,192 had pre-existing CKD; 1389 had ESRD; 5273 developed AKI and 998 CKD patients developed AoC. One-year mortality was greatest in AoC patients (54 %) followed by AKI (48.7 %), CKD (47.6 %) and ESRD (40.3 %) (P < 0.001). Five-year mortality was highest for the CKD and AoC groups (71.3 % and 68.2 %, respectively) followed by AKI (61.8 %) and ESRD (62.9 %) (P < 0.001). ESRD incidence was greatest in the AoC and CKD groups (adjusted incidence rate ratio (IRR) 259 (95 % confidence interval (CI) 156.9–429.1) and 96.4, (95 % CI 59.7–155.6) respectively) and elevated in AKI patients compared with controls (adjusted IRR 24 (95 % CI 3.9–42.0); P < 0.001). Risk factors independently associated with ESRD in 1-year survivors were, according to relative risk ratio, AoC (356; 95 % CI 69.9–1811), CKD (267; 95 % CI 55.1–1280), AKI (30; 95 % CI 5.98–154) and presence of elevated admission serum potassium (4.6; 95 % CI 1.30–16.40) (P < 0.001). Conclusions: Pre-ICU renal disease significantly increases risk of death compared with controls. Subjects with AoC disease had extreme risk of developing ESRD. All patients with CKD who survive critical care should receive a nephrology referral. Trial registration: Clinical trials registration number: NCT02424747 April 20th 2015.
Maternal diet modifies epigenetic programming in offspring, a potentially critical factor in the immune dysregulation of modern societies. We previously found that prenatal fish oil supplementation affects neonatal T-cell histone acetylation of genes implicated in adaptive immunity including PRKCZ, IL13, and TBX21. In this study, we measured H3 and H4 histone acetylation levels by chromatin immunoprecipitation in 173 term placentas collected in the prospective birth cohort, ALADDIN, in which information on lifestyle and diet is thoroughly recorded. In anthroposophic families, regular olive oil usage during pregnancy was associated with increased H3 acetylation at FOXP3 (p = 0.004), IL10RA (p = 0.008), and IL7R (p = 0.007) promoters, which remained significant after adjustment by offspring gender. Furthermore, maternal fish consumption was associated with increased H4 acetylation at the CD14 gene in placentas of female offspring (p = 0.009). In conclusion, prenatal olive oil intake can affect placental histone acetylation in immune regulatory genes, confirming previously observed pro-acetylation effects of olive oil polyphenols. The association with fish consumption may implicate ω-3 polyunsaturated fatty acids present in fish oil. Altered histone acetylation in placentas from mothers who regularly include fish or olive oil in their diets could influence immune priming in the newborn.
Nephron-sparing surgery (NSS) remains gold standard for the treatment of localised renal cell cancer (RCC), even in case of a normal contralateral kidney. Compared to radical nephrectomy, kidney failure and cardiovascular events are less frequent with NSS. However, the effects of different surgical approaches and of zero ischaemia on the postoperative reduction in renal function remain controversial. We aimed to investigate the relative short- and long-term changes in estimated glomerular filtration rate (eGFR) after ischaemic or zero-ischaemic open (ONSS) and laparoscopic NSS (LNSS) for RCC, and to analyse prognostic factors for postoperative acute kidney injury (AKI) and chronic kidney disease (CKD) stage ≥3. Data of 444 patients (211 LNSS, 233 ONSS), including 57 zero-ischaemic cases, were retrospectively analysed. Multiple regression models were used to predict relative changes in renal function. Natural cubic splines were used to demonstrate the association between ischaemia time (IT) and relative changes in renal function. IT was identified as significant risk factor for short-term relative changes in eGFR (ß = − 0.27) and development of AKI (OR, 1.02), but no effect was found on long-term relative changes in eGFR. Natural cubic splines revealed that IT had a greater effect on patients with baseline eGFR categories ≥G3 concerning short-term decrease in renal function and development of AKI. Unlike LNSS, ONSS was significantly associated with short-term decrease in renal function (ß = − 13.48) and development of AKI (OR, 3.87). Tumour diameter was associated with long-term decrease in renal function (ß = − 1.76), whereas baseline eGFR was a prognostic factor for both short- (ß = − 0.20) and long-term (ß = − 0.29) relative changes in eGFR and the development of CKD stage ≥3 (OR, 0.89). IT is a significant risk factor for AKI. The short-term effect of IT is not always linear, and the impact also depends on baseline eGFR. Unlike LNSS, ONSS is associated with the development of AKI. Our findings are helpful for surgical planning, and suggest either the application of a clampless NSS technique or at least the shortest possible IT to reduce the risk of short-time impairment of the renal function, which might prevent AKI, particularly regarding patients with baseline eGFR category ≥G3.