Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia.

Oxidative stress, a hallmark pathophysiological feature in diabetic kidney disease (DKD), arises from the intricate interplay between pro-oxidants and anti-oxidants. While hyperglycemia has been well established as a key contributor, lipotoxicity emerges as a significant instigator of oxidative stress. Lipotoxicity encompasses the accumulation of lipid intermediates, culminating in cellular dysfunction and cell death. However, the mechanisms underlying lipotoxic kidney injury in DKD still require further investigation. The key role of cell metabolism in the maintenance of cell viability and integrity in the kidney is of paramount importance to maintain proper renal function. Recently, dysfunction in energy metabolism, resulting from an imbalance in oxygen levels in the diabetic condition, may be the primary pathophysiologic pathway driving DKD. Therefore, we aim to shed light on the pivotal role of oxidative stress related to lipotoxicity and renal hypoxia in the initiation and progression of DKD. Multifaceted mechanisms underlying lipotoxicity, including oxidative stress with mitochondrial dysfunction, endoplasmic reticulum stress activated by the unfolded protein response pathway, pro-inflammation, and impaired autophagy, are delineated here. Also, we explore potential therapeutic interventions for DKD, targeting lipotoxicity- and hypoxia-induced oxidative stress. These interventions focus on ameliorating the molecular pathways of lipid accumulation within the kidney and enhancing renal metabolism in the face of lipid overload or ameliorating subsequent oxidative stress. This review highlights the significance of lipotoxicity, renal hypoxia-induced oxidative stress, and its potential for therapeutic intervention in DKD.

The Correlation of Serum Osteoprotegerin with Non-Traditional Cardiovascular Risk Factors and Arterial Stiffness in Patients with Pre-Dialysis Chronic Kidney Disease: Results from the KNOW-CKD Study.

BACKGROUND: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. METHODS: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. RESULTS: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total CO2 content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. CONCLUSION: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01630486.

The Detection of Messenger RNA for Carcinoembryonic Antigen and Cytokeratin 20 in Peritoneal Washing Fluid in Patients with Advanced Gastric Cancer.

BACKGROUND/AIMS: Peritoneal micrometastasis is known to play an important role in the recurrence of gastric cancer. However, its effects remain equivocal. Herein, we examine the messenger RNA (mRNA) as tumor markers, carcinoembryonic antigen (CEA), and cytokeratin 20 (CK20), in peritoneal washing fluid. Moreover, we evaluate whether these results could predict the recurrence of gastric cancer following curative resection. METHODS: We prospectively enrolled 132 patients with gastric cancers, who had received an operation, between January 2010 and January 2013. The peritoneal lavage fluid was collected at the operation field and semi-quantitative PCR was performed using the primers for CEA and CK20. We excluded patients with stage IA (n=28) early gastric cancer, positive cytologic examination of peritoneal washings (n=7), and those who were lost during follow up (n=18). RESULTS: A total of 79 patients with gastric cancers were enrolled, and the mean follow-up period was 39.95±19.25 months (range, 5-72 months). According to the multivariate analysis, T4 stage at the initial diagnosis was significantly associated with recurrence. All cases of recurrence were CEA positive and 6 cases were CK20 positive. The positive and negative predictive values of CEA were 32.0% and 100%, respectively, whereas those of CK20 were 37.5% and 71.4%, respectively. Disease free survival of CK20-negative cases was 36.17±20.28 months and that of CK20-positive cases was 32.06±22.95 months (p=0.39). CONCLUSIONS: It is unlikely that the real time polymerase chain reaction results of mRNA for CEA and CK20 in peritoneal washing fluid can predict recurrence. However, negative results can convince surgeons to perform curative R0 resection.