Background and objectives High BP variability may cause AKI because of inappropriate kidney perfusion. This study aimed to investigate the association between intraoperative BP variability and postoperative AKI in patients who underwent noncardiac surgery. Design, setting, participants, & measurements We performed a cohort study of adults undergoing noncardiac surgery in hospitals in South Korea. We studied three cohorts using the following recording windows for intraoperative BP: discovery cohort, 1-minute intervals; first validation cohort, 5-minute intervals; and second validation cohort, 2-second intervals. We calculated four variability parameters (SD, coefficient of variation, variation independent of mean, and average real variability) based on the measured mean arterial pressure values. The primary outcomes were postoperative AKI (defined by the Kidney Disease Improving Global Outcomes serum creatinine cutoffs) and critical AKI (consisting of stage 2 or higher AKI and post-AKI death or dialysis within 90 days). Results In the three cohorts, 45,520, 29,704, and 7435 patients were analyzed, each with 2230 (443 critical), 1552 (444 critical), and 300 (91 critical) postoperative AKI events, respectively. In the discovery cohort, all variability parameters were significantly associated with risk of AKI, even after adjusting for intraoperative hypotension. For example, average real variability was associated with higher risks of postoperative AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.07 to 1.19) and critical AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.02 to 1.26). Associations were evident predominantly among patients who also experienced intraoperative hypotension. In the validation analysis with 5-minute-interval BP records, all four variability parameters were associated with the risk of postoperative AKI or critical AKI. In the validation cohort with 2-second-interval BP records, average real variability was the only significant variability parameter. Conclusions Higher intraoperative BP variability is associated with higher risks of postoperative AKI after noncardiac surgery, independent of hypotension and other clinical characteristics. Visual Abstract

Background and Aims: No medication has been found to reduce liver-related events. We evaluated the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) on liver-related outcomes. Approach and Results: Single nucleotide polymorphisms associated with SGLT2 inhibition were identified, and a genetic risk score (GRS) was computed using the UK Biobank data (n=337,138). Two-sample Mendelian randomization (MR) was conducted using the FinnGen (n=218,792) database and the UK Biobank data. In parallel, a nationwide population-based study using the Korean National Health Insurance Service (NHIS) database was conducted. The development of liver-related complications (ie, hepatic decompensation, HCC, liver transplantation, and death) was compared between individuals with type 2 diabetes mellitus and steatotic liver diseases treated with SGLT2i (n=13,208) and propensity score–matched individuals treated with dipeptidyl peptidase-4 inhibitor (n=70,342). After computing GRS with 6 single nucleotide polymorphisms (rs4488457, rs80577326, rs11865835, rs9930811, rs34497199, and rs35445454), GRS-based MR showed that SGLT2 inhibition (per 1 SD increase of GRS, 0.1% lowering of HbA1c) was negatively associated with cirrhosis development (adjusted odds ratio=0.83, 95% CI=0.70–0.98, p=0.03) and this was consistent in the 2-sample MR (OR=0.73, 95% CI=0.60–0.90, p=0.003). In the Korean NHIS database, the risk of liver-related complications was significantly lower in the SGLT2i group than in the dipeptidyl peptidase-4 inhibitor group (adjusted hazard ratio=0.88, 95% CI=0.79–0.97, p=0.01), and this difference remained significant (adjusted hazard ratio=0.72–0.89, all p<0.05) across various sensitivity analyses. Conclusions: Both MRs using 2 European cohorts and a Korean nationwide population-based cohort study suggest that SGLT2 inhibition is associated with a lower risk of liver-related events.

Sehoon Park , Soojin Lee , Yaerim Kim , Yeonhee Lee , Min Woo Kang , Kyungdo Han , Hajeong Lee , Jung Pyo Lee , Kwon Wook Joo , Chun Soo Lim , Yon Su Kim , Dong Ki Kim. Kidney Res Clin Pract 2020;39:180-91. https://doi.org/10.23876/j.krcp.20.016

With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST‐C scores of the patients. The main study outcome was death‐censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using Cox regression analysis. Three hundred and thirty‐three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end‐stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST‐C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST‐C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD.

The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death‐censored graft failure. In total, 1256 IgAN patients in both pre‐ and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time‐dependent risk factor for worse prognosis (adjusted hazard ratio = 5.009 [3.610‐6.951]; P < .001) during a median of 8.1 years of follow‐up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with >10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time‐dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.

Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.