Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.

BACKGROUND: No reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies. CASE PRESENTATION: A 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening. CONCLUSIONS: This is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Renal and cardiac biopsy findings in an adolescent patient with the 3243A>G mitochondrial DNA mutation: Favorable renal prognosis post renal transplantation from the mother.

We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory to steroid therapy, and at the second kidney biopsy, abnormal mitochondrial proliferation was newly observed in the podocytes. The patient also developed late-onset hearing loss and had a family history of diabetes, and genetic testing confirmed the mitochondrial DNA mutation 3243A>G (48%). Eight months after hemodialysis was started, encephalopathy occurred presumably due to rapid dehydration. After changing dialysis into continuous ambulatory peritoneal dialysis, encephalopathy was resolved, but the patient developed myocardial hypertrophy, probably because of the myocardial overreaction to congestion. A myocardial biopsy showed mitochondrial proliferation in the myocardium. After renal transplantation from his mother with a heteroplasmy of 4%, the cardiomyopathy improved, and the renal function has remained stable for 4 years. We speculated that the abnormal mitochondrial morphology in the kidney and heart may be characteristic of mitochondrial genetic disease, and renal transplantation from the mother with a low heteroplasmy was considered desirable for mitochondrial nephropathy with poor prognosis.

Long-term clinicopathological characteristics of TAFRO syndrome and its relapse: a case series study.

Introduction: This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission. Methods: This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization. Results: Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment. Conclusions: This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors.

Efficacy and safety of first-line biological DMARDs in rheumatoid arthritis patients with chronic kidney disease.

OBJECTIVE: To evaluate the efficacy and safety of first-line biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with chronic kidney disease (CKD), including those undergoing haemodialysis (HD). METHODS: This retrospective cohort study included 425 patients with RA prescribed their first bDMARDs at two hospitals from 2004 to 2021. Patients were categorised by kidney function and bDMARD modality (TNFα inhibitors (TNFαis), interleukin-6 inhibitors (IL-6is), cytotoxic T-lymphocyte antigen-4 immunoglobulin (CTLA4-Ig)). The primary outcome was the 36-month drug retention rate, with secondary outcomes including changes in Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate (ESR), prednisolone dosage and reasons for discontinuation. RESULTS: The 36-month drug retention rates by estimated glomerular filtration rate (eGFR) (≥60, 30-60, <30 mL/min/1.73 m2) were as follows: all bDMARDs (45.2%, 32.0%, 41.4%), TNFαis (45.3%, 28.2%, 34.0%), IL-6is (47.4%, 66.7%, 71.4%) and CTLA-4Ig (50.0%, 31.3%, 33.3%). Even in groups with lower kidney function, the drug retention rate of bDMARDs was generally maintained. However, the retention rate of TNFαis was significantly lower in patients with eGFR <30 mL/min/1.73 m2. IL-6is showed the highest retention rate and the lowest discontinuation rate due to ineffectiveness in this group (HR 0.11, 95% CI 0.02 to 0.85, p=0.03). All bDMARDs improved DAS28-CRP/ESR and reduced prednisolone dosage across all groups. CONCLUSION: bDMARDs demonstrated effective and safe profiles in patients with RA with CKD, even among patients on HD. In particular, IL-6is had a significantly higher drug retention rate in patients with an eGFR of <30 mL/min/1.73 m2 and fewer discontinuations due to ineffectiveness. IL-6is were more efficacious as monotherapy compared with the other bDMARDs.

A case of renal limited myeloperoxidase anti-neutrophil cytoplasmic antibody-positive vasculitis treated with maintenance avacopan monotherapy.

A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333 IU/mL), proteinuria (1.21 g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1 year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.

Genetic Analysis of Severe Polycystic Liver Disease in Japan.

BACKGROUND: Polycystic liver disease (PLD) is present in most patients with autosomal dominant polycystic kidney disease (ADPKD). PLD can alternatively be found with few, if any, kidney cysts as a diagnosis of isolated polycystic liver disease (ADPLD). Several genes are identified as causative for this spectrum of phenotypes, however, the relative incidence of genetic etiologies amongst patients with severe PLD is unknown. METHODS: Patients with ADPKD or ADPLD having severe PLD defined as height-adjusted total liver volume (hTLV) over 1,800mL/m were recruited. Subsequent clinical care was followed. Genetic analysis was performed using whole exome sequencing. RESULT: We enrolled and sequenced 49 patients (38 females, 11 males). Pathogenic or suspected pathogenic variants in polycystic disease genes were found in 44 out of 49 patients (90%). The disease gene was PKD1 in 20/44 (45%), PKD2 in 15/44 (34%), PRKCSH in 5/44 (11%), GANAB in 2/44 (5%), SEC63 in 1/44 (2%), and ALG8 in 1/44 (2%). The median hTLV was no different between genetically-defined ADPKD and ADPLD groups (4431 (range 1817-9148) versus 3437 (range 1860-8211) mL, p=0.77), whereas height-adjusted kidney volume (hTKV) was larger as expected in ADPKD than ADPLD (607 (range 190-2842) versus 179 (range 138-234) mL/m, p<0.01). Of the clinically-defined ADPKD cases, 20/38 (53%) were PKD1, 15/38 (39%) were PKD2, and 3 (8%) remain genetically unsolved. Among patients with a pathogenic PKD1 or PKD2 variant, we found three cases with a liver-dominant ADPKD (severe PLD with hTKV <250mL/m). CONCLUSION: ADPLD-related genes represent 20% of severe PLD patients in our cohort. Of those enrolled with ADPKD, we observed a higher frequency of PKD2 carriers than in any previously reported ADPKD cohorts. While there was no significant difference in the hTLV between PKD1 versus PKD2 patients in this cohort, our data suggests that enrollment on the basis of severe PLD may enrich for PKD2 patients.

A case of hypertensive emergency with alveolar hemorrhage and thrombotic microangiopathy.

A 28-year-old woman with a 5-year history of untreated hypertension was admitted for respiratory distress, hemoptysis, and retinopathy. Computed tomography showed diffuse plaques in both lung fields. Acute kidney injury, hemolytic anemia, and thrombocytopenia were noted. Kidney biopsy showed thrombosis with fibrinoid necrosis and edematous intimal thickening and luminal narrowing of the small renal artery, indicating thrombotic microangiopathy; the majority of glomeruli were collapsed. After 8 weeks of treatment with antihypertensive drugs, serum creatinine decreased to 1.0 mg/dL, and the patient recovered. In the absence of any other underlying disease, malignant nephrosclerosis associated with a hypertensive emergency was diagnosed.

Trajectory of GFR Decline and Fluctuation in Albuminuria Leading to End-Stage Kidney Disease in Patients With Biopsy-Confirmed Diabetic Kidney Disease.

Introduction: Data on longitudinal trajectory of kidney function decline and fluctuation in albuminuria leading to end-stage kidney disease (ESKD) is sparse in patients with type 2 diabetes. Methods: Using data from an observational study of patients with type 2 diabetes and biopsy-confirmed diabetic kidney disease (DKD), generalized additive mixed models (GAMMs) were performed to quantify patterns of longitudinal trajectory of estimated glomerular filtration rate (eGFR) decline to ESKD associated with repeated measures of urine albumin-to-creatinine ratio (ACR). Results: Over a median follow-up period of 3.3 years, 155 of 319 patients progressed to ESKD. Among these patients, 91.6% exhibited a curvilinear pattern in their eGFR trajectory. The median coefficient of variation for ACR, representing the variability in ACR measurements, was 48.9 (interquartile range: 36.9, 68.2). The median compound annual growth rate (CAGR) for ACR, reflecting the variation in ACR progression over time, was 43.6% (interquartile range: 0.0, 102.5); and 84.5% of patients developed nephrotic-range albuminuria, with a majority remaining nephrotic and subsequently progressing to ESKD. There was a positive association between the instantaneous speed of eGFR decline and ACR. Conclusion: The observed curvilinear pattern in eGFR trajectory, high variability in ACR progression over time, and positive correlation between the speed of eGFR decline and ACR highlight the complex dynamics of disease progression and emphasize close monitoring of ACR fluctuation over time in patients with DKD.

Percutaneous Perirenal Mass Biopsy in a Sitting Position Revealed Extramedullary Relapse of Acute Lymphoblastic Leukemia.

Background/Aim: Acute lymphoblastic leukemia (ALL) is a blood malignancy characterized by a rapid proliferation of lymphoid progenitor cells. Extramedullary relapse (EMR) is the recurrence of leukemia that occurs outside the bone marrow. The central nervous system is the most prevalent site of EMR in ALL, whereas other organs, particularly the renal organs, are less commonly involved. Case Report: A 49-year-old man diagnosed with Philadelphia chromosome-negative ALL (Ph-negative ALL) received a second umbilical cord blood transplant (uCBT) and was confirmed to be in his third hematological complete remission. However, the perirenal mass lesion emerged after two weeks, and was difficult to detect on echography in the prone position. We successfully performed a percutaneous biopsy of the mass in a sitting position and pathologically identified it as EMR. After the diagnosis, chemotherapy was restarted, and the patient was scheduled to receive a third uCBT. Conclusion: This is the first report of EMR in a perirenal lesion of ALL and shows that this novel biopsy can be performed as a renal biopsy, even in a sitting position. This case is the first to describe a biopsy technique in detail and demonstrates the value of collaboration between hematologists and nephrologists in diagnosing EMR of the kidneys.

A Case of Glomerular Microangiopathy-like Nephropathy Caused by Hyperthyroidism.

A 49-year-old Japanese woman was admitted to our hospital with weight loss of 15 kg, nephrotic-range proteinuria (4.5 g/g.Cre), and hematuria over a 6-month period. She had received two doses of the COVID-19 vaccine one year before the onset of the disease, after which the estimated glomerular filtration rate increased. Laboratory tests and other tests led to a diagnosis of hyperthyroidism, and a kidney biopsy showed thrombotic microangiopathy-like glomerular microangiopathy comprising mainly glomerular endothelial cell damage. Thiamazole (30 mg) was started for the hyperthyroidism. Three months later, the thyroid function normalized, and two months later, the proteinuria and hematuria disappeared, suggesting that COVID-19 vaccination and these events were related.

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report.

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations.

Four Cases of Serum Copper Excess in Patients with Renal Anemia Receiving a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor: A Possible Safety Concern.

Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel approach for renal anemia management. Many intestinal genes, including divalent metal transporter 1, duodenal cytochrome B, and copper transporter ATPase7A, related to iron absorption are transactivated by HlF-α, during iron deficiency. We first report 4 cases of patients with renal anemia who showed excess in serum copper level during roxadustat or daprodustat treatment, which were decreased to the normal level after discontinuing HIF-PHIs and changing the drug to darbepoetin alfa, suggesting that HIF-PHI is associated with serum copper excess. HIF-PHI modulates iron metabolism, such as iron absorption, sequestration, and mobilization, and may increase serum copper levels by increasing copper absorption and/or redistribution of copper in tissues. Therefore, it is urgent to examine the correlation between HIF-PHI use and serum copper levels because copper excess might be involved in several acute or chronic adverse events.

A case of a hemodialysis patient with secondary hyperparathyroidism who was resistant to etelcalcetide treatment but not to cinacalcet hydrochloride.

Although both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75-100 mg of cinacalcet and 4.5 µg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to < 700 pg/mL, etelcalcetide was switched to 50 mg/day of cinacalcet, which reduced the levels to 208 pg/mL at 2 months after the switch. Genomic sequencing test using whole blood revealed no mutation in the portion including Cys 482 of CaSR gene. The patient was resistant to etelcalcetide treatment but not to cinacalcet, suggesting the possibility that the enlarged parathyroid gland has some change in the portion including Cys 482 in the CaSR gene. Therefore, considering the possibility of etelcalcetide resistance during SHPT treatment should be kept in mind.

Oral administration of cystine and theanine attenuates 5-fluorouracil-induced intestinal mucositis and diarrhea by suppressing both glutathione level decrease and ROS production in the small intestine of mucositis mouse model.

BACKGROUND: Chemotherapy is frequently used in cancer treatment; however, it may cause adverse events, which must be managed. Reactive oxygen species (ROS) have been reported to be involved in the induction of intestinal mucositis and diarrhea, which are common side effects of treatment with fluoropyrimidine 5-fluorouracil (5-FU). Our previous studies have shown that oral administration of cystine and theanine (CT) increases glutathione (GSH) production in vivo. In the present study, we hypothesized that CT might inhibit oxidative stress, including the overproduction of ROS, and attenuate 5-FU-induced mucositis and diarrhea. METHODS: We investigated the inhibitory effect of CT administration on mucositis and diarrhea, as well as its mechanism, using a mouse model of 5-FU-induced intestinal mucositis. RESULTS: CT administration suppressed 5-FU-induced diarrhea and weight loss in the studied mice. After 5-FU administration, the GSH level and the GSH/GSSG ratio in the small intestine mucosal tissue decreased compared to normal control group; but CT administration improved the GSH/GSSG ratio to normal control levels. 5-FU induced ROS production in the basal region of the crypt of the small intestine mucosal tissue, which was inhibited by CT. CT did not affect the antitumor effect of 5-FU. CONCLUSIONS: CT administration suppressed intestinal mucositis and diarrhea in a mouse model. This finding might be associated with the antioxidant characteristics of CT, including the improved rate of GSH redox and the reduced rate of ROS production in the small intestine mucosal tissue. CT might be a suitable candidate for the treatment of gastrointestinal mucositis associated with chemotherapy.

Cystine and Theanine as Stress-Reducing Amino Acids-Perioperative Use for Early Recovery after Surgical Stress.

Perioperative nutritional therapy requires the consideration of metabolic changes, and it is desirable to reduce stress aiming at early metabolic normalization. Glutathione (GSH) is a tripeptide composed of glutamic acid, cysteine, and glycine. It is one of the strongest antioxidants in the body and important for adjusting immune function. Cystine and theanine (γ-glutamylethylamide) provide substrates of GSH, cysteine and glutamic acid, promoting the synthesis of GSH. It has been reported that the ingestion of cystine (700 mg) and theanine (280 mg) exhibits inhibitory effects against excess inflammation after strong exercise loads in athletes, based on which its application for invasive surgery has been tried. In patients undergoing gastrectomy, ingestion of cystine (700 mg) and theanine (280 mg) for 10 days from 5 days before surgery inhibited a postoperative increase in resting energy expenditure, promoted recovery from changes in interleukin-6, C-reactive protein, lymphocyte ratio, and granulocyte ratio and inhibited an increase in body temperature. In a mouse small intestine manipulation model, preoperative 5-day administration of cystine/theanine inhibited a postoperative decrease in GSH in the small intestine and promoted recovery from a decrease in behavior quantity. Based on the above, cystine/theanine reduces surgical stress, being useful for perioperative management as stress-reducing amino acids.

Congestive hepatopathy and acute pancreatitis as severe complications of mixed connective tissue disease.

Mixed connective tissue disease (MCTD) causes multiple organ dysfunctions, such as joint swelling, pulmonary fibrosis and hypertension, and serositis, but hepatopancreatic complications are rare. Here, we report a case of young man who exhibited acute severe liver dysfunction. He also had impaired cardiac function: both ventriculi were hypokinetic, but pulmonary hypertension and pericarditis were not observed. Since his liver and cardiac function markedly improved after commencing furosemide and carperitide, we considered congestive hepatopathy due to MCTD and accompanying heart failure. Heart failure and congestive hepatopathy recurred and he was treated with diuretics and prednisolone, but he passed away by co-occurrence of acute hemorrhagic pancreatitis. Necropsy revealed chronic hepatic congestion but not accompanying autoimmune hepatitis and hepatic vasculitis. We should consider congestive hepatopathy and hemorrhagic pancreatitis as serious complications of MCTD.

Nephrotic Syndrome due to Focal Segmental Glomerulosclerosis Complicating Sjögren's Syndrome: A Case Report and Literature Review.

BACKGROUND: Renal tubular acidosis and tubulointerstitial nephritis constitute the primary renal complications associated with Sjögren's syndrome (SjS), and glomerulonephritis and nephrotic syndrome are rare. CASE PRESENTATION: A 79-year-old Japanese woman presented with bilateral leg edema and weight gain and was diagnosed with nephrotic syndrome. In addition, she reported a 5-year history of dryness of mouth and was diagnosed with SjS. Renal biopsy revealed segmental glomerulosclerosis, with some specimens showing collapse of the glomerular capillary loops, proliferation of glomerular epithelial cells, and sclerotic lesions at the tubular poles, without spike formation, double contour lesions, or any other changes of the glomerular basement membrane. Immunofluorescence staining showed no immune complex (immunoglobulin IgG, IgA, or IgM) or complement (C3) deposition in the glomerular capillary walls. Based on these findings, she was diagnosed with focal segmental glomerulosclerosis (FSGS). The administration of steroid and cyclosporine achieved complete remission of nephrotic syndrome. CONCLUSION: Although glomerular diseases are rare, a variety of glomerular lesions including FSGS are reported in patients with SjS. Therefore, renal biopsy is warranted in patients with SjS presenting with severe urinary abnormalities.

Cystine and Theanine Improve Survival after Gut Ischemia-Reperfusion.

BACKGROUND AND AIM: Oral administration of cystine and theanine (CT) may modulate antioxidant glutathione (GSH) metabolism, thereby improving outcomes after gut ischemia reperfusion. METHODS: Experiment 1: Institute of Cancer Research mice (n = 35) were assigned to a Vehicle (n = 11), a CT140 (n = 14), or a CT280 (n = 10) group. The CT140 and 280 groups were given CT at respective dosages of 140 and 280 mg/kg (cystine: theanine = 5: 2) once daily via gavage for 5 days. All mice underwent 75-min occlusion of the superior mesenteric artery (SMA). Survival after reperfusion was observed. Experiment 2: Mice (n = 67) were pretreated for 5 days (Vehicle: n = 24, CT280: n = 20, vehicle/sham: n = 23). The Vehicle and CT280 groups underwent 60-min SMA occlusion. Levels of GSH, the oxidized form of GSH, Glutathione-S-S-Glutathione (GSSG), and GSH-related amino acids (cysteine and glutamic acid) in the small intestine, and plasma cytokine (IL-6, IL-1ß, TNFα) levels, were evaluated before (0 h), 3, 6, or 9 h after reperfusion. RESULTS: Experiment 1: The CT280 group showed significantly better survival than the Vehicle group. Experiment 2: Gut GSSG, cysteine, and glutamic acid levels were higher in the CT280 than in the Vehicle group after reperfusion. Plasma IL-6 and TNFα levels rose more rapidly in the CT280 than in the Vehicle group. CONCLUSION: Oral administration of CT improves survival after gut I/R, possibly through the modulation of the GSH-redox cycle and cytokine responses.