Femoral neck fracture is common in the elderly population. Acute kidney injury (AKI) is an important risk factor for mortality in patients who have had such fracture. We evaluated the incidence of AKI in patients who had femoral neck fracture and identified risk factors for AKI and mortality.This was an observational cohort study including 285 patients who were ≥ 65 years of age and who underwent femoral neck fracture surgery between 2013 and 2017.The mean age was 78.63 ± 6.75 years. A total of 67 (23.5%) patients developed AKI during the hospital stay: 57 (85.1%), 5 (7.5%), and 5 (7.5%) patients were classified as having stage 1, 2, and 3 AKI, respectively. Patients with AKI had a lower baseline estimated glomerular filtration rate and higher left atrial dimension, left ventricular mass index, pulmonary artery pressure, and the ratio of early mitral inflow velocity to early diastolic mitral annulus velocity (E/e') and were more likely to have diabetes or hypertension (HTN) (P < 0.05). The presence of HTN (odds ratio [OR], 4.570; 95% confidence interval [CI], 1.632-12.797) higher E/e' (OR, 1.105; 95% CI, 1.019-1.198), and lower hemoglobin (OR, 0.704; 95% CI, 0.528-0.938) were independently associated with a higher risk for developing AKI. Severe AKI (OR, 24.743; 95% CI, 2.822-212.401) was associated with a higher risk of mortality.Elderly patients with femoral neck fracture had a high incidence of AKI. Diastolic dysfunction was associated with AKI. Severe AKI was associated with in-hospital mortality.
Emerging evidence suggests that intestinal dysbiosis is associated with diverse pathological processes. In this study we demonstrated intestinal barrier disruption and aberrant mucosal immunity in 5/6 nephrectomized mice and the effect of probiotics on chronic kidney disease (CKD). CKD was induced in 6-week-old mice by 5/6 nephrectomy. They were fed a lactobacilli mixture for 8 weeks. Serum, urine and stool samples were collected for renal function assessments and gut microbiome analyses. Gut permeability, colon heat shock protein 70 (HSP70) and colon epithelial integrity were evaluated and cytokine levels in colon and kidney were measured. Colon leukocytes were analyzed by flow cytometry and bone marrow–derived cells were cocultured with lactobacilli mixture. In CKD mice, 'leaky gut' was accompanied by decreased colon HSP70 and claudin-1 expression, whereas it increased pore-forming claudin-2 expression and apoptosis. Although the percentage of regulatory T cells did not differ between CKD and control mice, cytokine expression and the ratio of CX3CR1intermediate:CX3CR1high pro-inflammatory/resident macrophages increased in the colon of CKD mice. Orally administered lactobacilli partially mitigated the CKD-induced 'leaky gut'; restored colon epithelial HSP70, claudin-1 and claudin-2 expression and decreased apoptosis. Probiotic treatment also restored the CX3CR1intermediate:CX3CR1high macrophage ratio and increased circular dichroism (CD)103+CD11c+ regulatory dendritic cells in the colon. These changes suppressed systemic inflammation and kidney fibrosis. Our results suggest that intestinal dysbiosis-associated gut barrier disruption and aberrant mucosal immunity are important for the systemic inflammation and progressive fibrosis of CKD. Targeting the intestine might provide novel therapeutic opportunities for CKD.
Thrombotic microangiopathy is not a rare complication of kidney transplantation and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury with extensive thrombosis of the arterioles and capillaries.Various factors can cause thrombotic microangiopathy after kidney transplantation, including surgery, warm and cold ischemia-reperfusion injury, exposure to immunosuppressants, infection, and rejection.Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway.The affected patients' genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway.Although clinical studies have provided a better understanding of the pathogenesis of diseases, the diverse triggers present in the transplant environment can lead to thrombotic microangiopathy, along with various genetic predispositions, and it is difficult to identify the genetic background in various clinical conditions.Given the poor prognosis of posttransplant thrombotic microangiopathy, further research is necessary to improve the diagnosis and treatment protocols based on risk factors or genetic predisposition, and to develop new therapeutic agents.
The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI.We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined.Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 ± 18.5 years and the mean peak creatinine level was 8.2 ± 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery.The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Purpose: Diffusion-weighted MRI (DWI) is well known to be sensitive in the detection of hyperacute infarct, but has not been systematically investigated in patients with acute or subacute infarct. We evaluated the usefulness of diffusion-weighted MRI in assessing the various stages of brain infarct. Materials and Methods: Fifty-five consecutive patients with symptoms of brain infarct underwent fast spin-echo T2-weighted MRI (T2W1) and DWI. Using only a brief clinical history, two radiologists first attemptelto detect the lesion using T2W1, which was then compared with DWI. The usefulness of the latter was then evaluated in terms of the following criteria: 1) Its abilility to detect a lesion not seen at T2WI (detection); 2) localization of the responsible ischemic focus among multiple high-signal intensities seen at T2WI (localization); 3) conspicuity of a lesion which was subtle at T2WI (conspicuity); 4) detection of multiple lesions (multiplicity). Results: DWI was useful in 44 of 55 patients (80%), including 9 of 9 (100%) with hyperacute infarct (
Abstract Background : Although recipients and donors in living kidney transplantation are exposed to psychological distress, including depression and anxiety during the pre-operative period, only a few studies have evaluated their psychological relationship. This study aimed at determining the psychological characteristics and correlation between transplant recipients and donors as well as at investigating it in relation to biologically related and unrelated donors. Methods : This retrospective study on living kidney transplantation at the Korea University Anam Hospital was conducted from April 2008 to June 2019. While participants’ personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2(MMPI-2), their mood states before transplantation were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using a paired t-test and Spearman’s correlation analyses. Results : The recipient group showed a significantly higher sub-score in hypochondriasis (t =-4.49, P=.0001), depression (t =-3.36, P=.0015), hysteria (t =-3.30, P=.0018), STAI-T (t =-2.14, P=0.0372), and CES-D (t =-3.93, P=.0003) than donor group. A comparison of the psychological association between the recipient and donor groups revealed a significant positive correlation in the STAI-S (r=.357, P=.009) and CES-D (r=.362, P=.008). When assessing the difference in correlation based on the biological relationship between the recipients and donors, there is a positive correlation in CES-D (r=.415, P=.0202) in biologically related donors and recipients. In biologically unrelated but emotionally related group, recipients’ STAI-S score and donors’ STAI-S (r=0.413, P=.163), STAI-T (r=.559, P=009) score is positively correlated, and recipients’ STAI-T score and donors’ STAI-S (r=.466, P=.033), STAI-T (r=.520, P=.016) score is also positively correlated. Besides, recipients’ CES-D and donors’ STAI-S (r=.529, P=.014) and STAI-T (r=.560, P=.008) score show a positive correlation. Conclusions : The study indicated that transplantation recipients suffered from a higher level of depression and anxiety compared to the donors before transplantation. The findings suggest that recipients are more depressive and anxious than donors, and psychological problems like depression and anxiety can be shared in living kidney transplantation donors and recipients, especially in biologically unrelated but emotionally related groups.
Acute rejection (AR) is a major complication of kidney transplantation (KT). Although advances in immunosuppressive therapy have reduced the incidence of AR, the effect of AR on allograft dysfunction remains an important issue. The number of AR episodes, their severity and type, patient responses to the treatment, and the timing of AR are all potential determinants of graft outcomes [1,2]. Of special interest to many researchers is the role of timing of AR episodes, and what effects timing has on graft outcomes. The primary reason for this interest is that the physiological environment of the allograft changes gradually with time. After KT, dosing of immunosuppressive therapy decreases over time, and graft function gradually declines because of immunologic damage, infection, aging, and chronic exposure to calcineurin inhibitors. Additionally, immune responses to the allograft might be mediated by different mechanisms related to how much time has passed after transplantation [3,4].
In this issue of Kidney Research and Clinical Practice, Koo et al [5] investigated the impact of time of AR on long-term graft survival in a single-center cohort. They enrolled 709 patients who had undergone KT between 2000 and 2009 and found that both early- and late-onset AR significantly influences graft outcomes.
Previously, several studies examined the influence of timing of AR on graft outcomes. In 2003, Sijpkens et al [4] found that AR occurring more than 3 months after KT was associated with poorer graft outcomes than AR that occurred during the first 3 months. Interestingly, they also found that human leukocyte antigen (HLA) Class I mismatches predicted late AR, whereas HLA Class II mismatches were associated with early AR. This suggests that direct and indirect pathways of allorecognition may play a role in the pathophysiology of early and late AR, respectively. In 2008, Opelz and Dohler [6] found that late AR is more severe than early AR, as reflected by incomplete functional recovery. Late AR was more difficult to reverse by rejection treatment than early AR and therefore led to poorer long-term outcomes. Most recently, Krisl et al [7] examined how the type of AR, in addition to timing, affects graft outcomes. The authors found that late-onset antibody-mediated rejection was associated with significantly worse graft survival compared with other types and timing of AR, suggesting an important role of humoral immunity in graft outcomes.
Despite these results, it is difficult to conclude that the timing of AR is a critical factor determining graft outcomes. Recent immunosuppressive strategies using tacrolimus and mycophenolate mofetil have contributed to improvement of graft outcomes [8,9]; earlier studies, however, included many patients taking cyclosporine with azathioprine. Therefore, the results are not sufficiently informative about the effects of AR in the current era of immunosuppression. Additionally, 70–100% of donors in previous studies were deceased donors. However, living donors account for a large proportion of the donor population in Asian countries. In Korea, more than 50% of KTs use kidneys from living donors [10]. Different donor characteristics can lead to varied immunologic environments and thus influence the effect of AR on graft outcomes. In addition, we should consider the role of relatively short cold ischemic times in Korea because cold ischemia enhances the immune response to an allograft and affects clinical features of AR. Consequently, the impact of early and late AR on graft survival in Korea needs to be investigated using regional data.
In the present study, Koo et al [5] examined these issues with a cohort of recent KT patients in a single center. They found that there were no significant differences in graft survival according to the timing of AR, although both early and late AR had negative effects on outcomes compared with no AR. As a result, they conclude that both early and late AR present major barriers to improving long-term graft survival. Additionally, male sex and HLA mismatch were risk factors for early AR, whereas younger age of recipient and high panel-reactive antibody levels predicted late AR. However, this study has limitations in the analysis of the factors that may have affected the results, such as baseline renal function at rejection, AR severity, AR consequences, viral infections, de novo renal disease, and histological findings of microcirculatory inflammation and chronic changes.
The major conclusion of this study is that compared with nonimmunologic factors, AR was the most significant risk factor associated with poor graft survival. To improve graft survival, we should aim to reduce the number of AR episodes and their severity and enhance responses to treatment regardless of the timing of AR onset. In particular, an important issue raised by this study was whether early AR is a significant risk factor for graft failure, and the authors showed the importance of early AR in graft survival. Besides, antibody-associated graft injury needs to be considered a major risk factor of late-onset AR because high panel-reactive antibody was associated with late AR. Although there is a lack of precise data about the type of AR, implementing steps such as immunologic monitoring, early detection, and treatment of humoral immune response should be critical for improving prognosis. Finally, this study is valuable because the authors examined the influence of AR timing on graft survival in patients receiving the current standards of immunosuppressive therapy. We are encouraged by the recent establishment of the national database, Korean Organ Transplant Registry [10]. Comparable with the Scientific Registry of Transplant Recipient, the Collaborative Transplant Study, and the Australia and New Zealand Dialysis and Transplant Registry in other countries, we have our own transplantation database system that will be used for large-scale researches. The Korean Organ Transplant Registry data will be of help to more clearly define the impact of AR and related clinical features on patient outcomes.