Seok Hui Kang

The Oxford classification as a predictor of prognosis in patients with IgA nephropathy.

BACKGROUND In 2009, the Oxford classification was developed as a pathological classification system for immunoglobulin A nephropathy (IgAN) to predict the risk of disease progression. The aim of this retrospective study was to evaluate the clinical and pathologic relevance of the Oxford classification in Korean patients with a pathologic diagnosis of IgAN. PATIENTS AND METHODS We reviewed the renal pathology archives from January 2000 to December 2006 at Seoul St Marys Hospital in Korea and identified 273 patients, who were diagnosed as having IgAN. We enrolled 197 patients who were available for further clinicopathologic analysis. All cases of IgAN were categorized according to the WHO classification, the semiquantitative classification and the Oxford classification. These pathologic classifications were compared. The clinical and laboratory findings at the time of biopsy were compared with those at the end of the follow-up according to the Oxford classification. RESULTS When three pathologic classifications were compared, M1, S1, E1, T1 or T2 were associated with a higher score in the activity index. S1, T1 or T2 were associated with a higher score in the chronicity index and a higher grade in the WHO classification. The clinical and laboratory findings were compared according to the Oxford classification. At the time of biopsy, the proteinuria in patients with M1 was more than that of M0 (P = 0.035). At the end of follow-up, the number of antihypertensive drugs taken among patients with M1 was greater than that of patients with M0 (P = 0.001). At the time of biopsy, the proteinuria of patients with S1 was greater than that of S0 patients (P = 0.009). At the end of follow-up, the number of patients who received immunosuppressants was increased as the grade of T increased (P = 0.000). At the end point of the follow-up, the estimated glomerular filtration rate (eGFR) decreased as the grade of T increased (P = 0.008). The time-average proteinuria after adjusting the initial proteinuria increased significantly with increasing degree of T (P = 0.000). Levels of tubular atrophy/interstitial fibrosis were predictive for survival from end-stage renal disease or of having a 50% reduction of eGFR. CONCLUSION The pathologic variables of the Oxford classification correlated significantly with other classifications (the WHO classification and the semiquantitative classification). The Oxford classification is a simple method for predicting renal outcome and differentiating between active and chronic lesions. We suggest that the Oxford classification offers an advantage for determining treatment policy for patients with IgAN.

Comparison of Clinical Outcome between High and Low Baseline Anti-ABO Antibody Titers in ABO-Incompatible Kidney Transplantation

High baseline anti-ABO antibody titer is still an important obstacle for successful ABO-incompatible kidney transplantation (ABO IKT). This study aims to investigate the clinical outcome of ABO IKT in patients with a high baseline titer in comparison with patients with a low baseline titer. Fourteen patients who received ABO IKT at our center were classified as the high-titer group (≥1:256, n = 8) or the low-titer group (≤1:128, n = 6). We used a protocol composed of rituximab, plasmapheresis, and intravenous immunoglobulin (RTX/PP/IVIG). We compared the intensity of preparation, complications, and clinical outcome between the two groups. The high-titer group required more sessions of pretransplant (10.5 ± 3.5 vs. 6.0 ± 1.3 times, p = 0.01) and posttransplant (1.6 ± 1.8 vs. 0 ± 0 times) PP/IVIG than the low-titer group did. All patients from both groups showed immediate recovery of graft function. The antibody titer and allograft function in the high-titer group were stable and did not differ significantly from those of the low-titer group up to 1 year after kidney transplantation. There was no antibody-mediated rejection in either group during follow-up, but three cases of acute cellular rejection developed in the high-titer group. The high-titer group showed two cases of opportunistic viral infection (herpes gingivitis and cytomegalovirus viremia) and one case of graft loss due to postoperative bleeding. ABO IKT can be safely performed even in patients with a high baseline anti-ABO antibody titer, but the risk for infection and bleeding should be considered before transplantation.

Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy

Dexmedetomidine has been shown to reduce pro‐inflammatory cytokine levels in rats with sepsis and in severely ill patients. The aim of this study was to document the effects of dexmedetomidine on inflammatory responses during and after surgery.

Early gastric cancer associated with gastritis cystica polyposa in the unoperated stomach treated by endoscopic submucosal dissection

Gastritis cystica polyposa (GCP) is an uncommon hyperplastic benign lesion, which is histologically characterized by hyperplastic foveolar epithelia and multicystically dilated glands inside the lesion. GCP is also called gastritis cystica profunda when the cystic lesion locates within the submucosa. GCP was at first described as polypoid tumors developed in the gastric mucosa adjacent to Billroth-II stoma. This relatively rare lesion usually develops in patients who previously underwent gastroenterostomy, especially for treatment of a benign lesion, eg, gastric ulcer. GCP is infrequently found in an unoperated stomach. Because GCP is usually found in the operated stomach, its etiology and pathogenesis have been considered to be chronic inflammation after surgical treatment. Mucosal prolapse or duodenogastric reflux of intestinal contents into the gastric remnant may be inferred to be a cause of GCP. Subsequent reports brought up some similar findings in various synonyms, and some of the cases reported were with accompanying carcinoma. However, the mechanism of GCP developing in the unoperated stomach is unclear. In some cases reported, it was suggested that GCP at a gastroenterostomy site may be a precancerous lesion because carcinoma is frequently found at old gastrojejunostomy stoma and the histologic features of GCP resemble the experimental stomal polyps preceding carcinoma after partial gastrectomy in rats. Herein, we report 2 cases of early gastric cancer (EGC) that accompanied GCP, which occurred in patients who had never undergone stomach surgery. The patients were treated with the endoscopic submucosal dissection (ESD) technique. The carcinoma cells were confined to the mucosal layer.

Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 ± 12.2 cells/mm2 and 5.6 ± 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 ± 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.

Influence of N-acetylcysteine on Klotho expression and its signaling pathway in experimental model of chronic cyclosporine nephropathy in mice.

Background Cyclosporine A (CsA)–associated oxidative stress has been proposed as an important mechanism of renal injury. This study was designed to examine whether N-acetylcysteine (NAC), a well-known antioxidant, affects Klotho, antiaging gene, expression and its signaling pathway in an experimental model of chronic CsA nephropathy. Methods Mice maintained on a low-sodium diet were given vehicle (olive oil, 1 mL/kg/day), CsA (30 mg/kg/day), NAC (150 mg/kg/day), or a combination of CsA and NAC for 4 weeks. The effect of NAC on CsA-induced renal injury was evaluated with basic parameters, histopathology, and markers of oxidative stress [8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion and manganese superoxide dismutase (MnSOD) expression]. The influence of NAC on Klotho and its signal pathway (p-AKT and p-FoxO1) in CsA-treated mouse kidney was evaluated with immunohistochemistry and/or immunoblot. Results Concomitant administration of CsA and NAC significantly improved renal function and attenuated tubulointerstitial fibrosis, and these changes were accompanied by decreased urinary 8-OHdG level and increased MnSOD expression. NAC treatment preserved Klotho gene expression compared with CsA treatment alone (P<0.05), and this correlated with urinary 8-OHdG excretion (r=–0.934) and MnSOD expression (r=0.873, P<0.001 for both). Concomitant treatment of CsA and NAC translocated FoxO1 from the cytoplasm to the nucleus, implicating dephosphorylation of FoxO1 by NAC in p-AKT/p-FoxO1 pathway. Conclusion NAC treatment preserves Klotho expression and modifies p-AKT/p-FoxO1 pathway in chronic CsA nephropathy.

Clinical Significance of Early-Onset Hyperuricemia in Renal Transplant Recipients

Background/Aims: It is undetermined whether the effect of uric acid (UA) on graft outcome is independent of graft dysfunction. This study was designed to explore whether early-onset hyperuricemia has clinical significance regardless of graft function. Methods: This study was conducted based on a retrospective chart review. We calculated time-averaged UA and estimated glomerular filtration rate from the values at 3, 6, and 9 months after transplantation. Cardiovascular complications during follow-up and long-term graft survival were assessed according to UA levels and graft function. Results: 351 patients were enrolled into this study. Hyperuricemia increased the risk of cardiovascular complications (HR = 2.8, 95% CI 1.1–7.1; p = 0.02), but reduced graft function did not. In the hyperuricemia group, 5- and 10-year graft survival was significantly lower than in the normouricemia group (89 and 81% vs. 96 and 92%, respectively; p = 0.02). In the reduced graft function group, these values were also lower than in the normal graft function group (89 and 81% vs. 96 and 93%, respectively; p = 0.02). In the multivariate analysis, both hyperuricemia and reduced graft function were independent risk factors for graft failure and the presence of both factors presented the highest risk. Conclusion: Early-onset hyperuricemia is a significant predictor of cardiovascular complications and graft survival independently of graft function.

Clinical Impacts of CD38+ B Cells on Acute Cellular Rejection With CD20+ B Cells in Renal Allograft

Background. There is an increasing evidence that the presence of CD20+ B cells is associated with poor clinical outcomes in acute cellular rejection (ACR), but clinical significance of CD38+ B cells is undetermined. We attempted to examine the clinical significance of the CD38+ B cells alone or in combination with CD20+ B cells in renal transplant recipients with ACR. Methods. Fifty-four patients with ACR were included. Biopsy specimens were stained for CD20 and CD38. The clinical outcomes of CD20 or CD38+ B cells were evaluated with late-onset and repeated ACR, steroid resistance, incomplete recovery after rejection treatment, and allograft survival. Results. Twenty-three patients (42.6%) had CD20+ and 25 (46.3%) patients had CD38+ B cells. Of these, 15 patients (27.8%) were positive for both CD20 and CD38 (CD20+CD38+). CD38+ patients had higher rates of late-onset or repeated ACR and incomplete recovery compared with CD38− patients (P<0.05). The patients with CD20+CD38+ had a higher incomplete recovery rate than did patients with only CD20+ or CD38+ (P<0.05). The 5-year allograft survival was lower in CD20+ and CD38+ patients than in CD20− or CD38− patients (P<0.05 for each). CD20+CD38+ patients had lower graft survival than did patients with CD20+ or CD38+ alone (P<0.05). Conclusion. Infiltration of CD38+ B cells alone or in combination with CD20+ B cells is a predictor for poor clinical outcomes of ACR in renal allograft.

Clinical significance of slow recovery of graft function in living donor kidney transplantation.

Background. The clinical significance of slow recovery of graft function (SGF) in living donor kidney transplantation is unclear. We evaluated the incidence, risk factors, and clinical outcome of SGF in living donor transplantation. Methods. Three hundred ten living donor kidney recipients were included and categorized into immediate recovery of graft function (IGF; n=239) and SGF (n=71), according to estimated glomerular filtration rate (60 mL/min/1.73 m2) at posttransplant day 14. We compared the clinical parameters, protocol biopsy findings, acute rejection (AR), and 10-year graft survival between the two groups. Results. The SGF group had an older recipient age, lower ratio of donor to recipient body mass index, and higher incidence of AR than IGF group, as shown by protocol biopsies. The SGF group had significantly more AR episodes than IGF group within 12 months (21.1% vs. 13.4%, P<0.05) and during follow-up period (32.4% vs. 20.1%, P<0.05). The 10-year graft survival rate did not differ between groups, but AR presence was significantly associated with a lower graft survival in the SGF group than the IGF group (64.9% vs. 78.9%, P<0.05). Conclusions. SGF in the early posttransplant period is immunologically active and should be considered as one of the risk factors for determining long-term graft survival in living donor kidney transplantation.

Comparison of the palindrome vs. step-tip tunneled hemodialysis catheter: a prospective randomized trial.

Numerous designs for tunneled hemodialysis catheter have been developed in an effort to improve catheter function and survival. In this prospective randomized controlled study, 97 patients were randomized into the palindrome catheter group (PC, n = 47) and step‐tip catheter group (SC, n = 50). Demographic characteristics were not different between the two groups. The effective blood flow rates at different pump speeds were comparable between the two groups. The recirculation was low within acceptable range in both types of catheter, and hemodialysis adequacy was not different between the two groups. However, when arterial and venous blood lines were reversed, while the recirculation was significantly increased in SC, it was not increased at all in PC. The catheter dysfunction‐free survival rate was significantly higher in PC than in SC (78.9% vs. 54.4% at 2 months, p = 0.008). The overall catheter survival rate was also higher in PC than in SC (90.6% vs. 68.8% at 2 months, p = 0.015). We conclude that both catheters are equally effective on the adequate hemodialysis and low recirculation. However, the PCs have advantages over the SCs in terms of lower catheter dysfunction rate, lower recirculation with reversed blood lines, higher short‐term catheter survival rate.