Sun Ryoung Choi

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.

Fenofibrate Improves Renal Lipotoxicity through Activation of AMPK-PGC-1α in db/db Mice

Peroxisome proliferator-activated receptor (PPAR)-α, a lipid-sensing transcriptional factor, serves an important role in lipotoxicity. We evaluated whether fenofibrate has a renoprotective effect by ameliorating lipotoxicity in the kidney. Eight-week-old male C57BLKS/J db/m control and db/db mice, divided into four groups, received fenofibrate for 12 weeks. In db/db mice, fenofibrate ameliorated albuminuria, mesangial area expansion and inflammatory cell infiltration. Fenofibrate inhibited accumulation of intra-renal free fatty acids and triglycerides related to increases in PPARα expression, phosphorylation of AMP-activated protein kinase (AMPK), and activation of Peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)-estrogen-related receptor (ERR)-1α-phosphorylated acetyl-CoA carboxylase (pACC), and suppression of sterol regulatory element-binding protein (SREBP)-1 and carbohydrate regulatory element-binding protein (ChREBP)-1, key downstream effectors of lipid metabolism. Fenofibrate decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and FoxO3a phosphorylation in kidneys, increasing the B cell leukaemia/lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) ratio and superoxide dismutase (SOD) 1 levels. Consequently, fenofibrate recovered from renal apoptosis and oxidative stress, as reflected by 24 hr urinary 8-isoprostane. In cultured mesangial cells, fenofibrate prevented high glucose-induced apoptosis and oxidative stress through phosphorylation of AMPK, activation of PGC-1α-ERR-1α, and suppression of SREBP-1 and ChREBP-1. Our results suggest that fenofibrate improves lipotoxicity via activation of AMPK-PGC-1α-ERR-1α-FoxO3a signaling, showing its potential as a therapeutic modality for diabetic nephropathy.

Clinical usefulness of BK virus plasma quantitative PCR to prevent BK virus associated nephropathy

The present study investigated the clinical usefulness of plasma real‐time polymerase chain reaction (PCR) (plasma‐PCR) in the prevention of BK virus‐associated nephropathy (BKVAN). First, we investigated the diagnostic value of plasma BK‐PCR, urine BK‐PCR, and urine cytology for the prediction of BKVAN retrospectively. Then we designed a prospective study of regular plasma‐PCR monitoring and pre‐emptive immunosuppression (IS) reduction based on the result. In the retrospective cohort, the prevalence of BKVAN was 3.7% (14/379) and the positive rate of decoy cells, urine‐PCR (>1 × 1010 copies/ml), and plasma‐PCR (>1 × 104 copies/ml) was 18.6%, 11.1%, and 5.5%, respectively. Plasma‐PCR was superior to urine‐PCR or urine cytology in specificity and positive predictive value for detection of BKVAN. In prospective study, regular monitoring of plasma‐PCR detected significant BKV viremia in 8.3% (12/145) and BKVAN in 1 patient (0.6%). After IS reduction, BKV viremia was eliminated in 91.6% (11/12) within 103 days (25–254). In patients with viremia, the frequency of acute rejection did not increase and allograft function did not differ significantly compared with those in patients without viremia during the first year post‐transplant (P > 0.05, in both). Plasma‐PCR is useful to predict an increased risk for BKVAN, and regular monitoring is effective to prevent the development of BKVAN.

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.

Increased interleukin-17 producing effector memory T cells in the end-stage renal disease patients

Patients with end-stage renal disease (ESRD) exhibit immune dysregulation, but the precise immunological profile and the effect of hemodialysis (HD) on it has not been investigated fully. Thirty-eight ESRD patients (22 on HD and 16 in pre-dialysis) and 24 healthy volunteers were included. We compared the T cell immune profiles as in these patients. Among the effector T cell subset, the percentages of Th17 and Th2 cells were significantly higher in the ESRD group than in the healthy controls (P<0.05). The percentage of Th1 cells did not differ significantly between these groups. The percentages of Th1, Th2 and Th17 cells did not differ significantly (P>0.05) between the two subgroups within the ESRD group. The CCR4(-)CCR6(+)/CD4(+) T cell percentage was also significantly higher in the ESRD group. The naïve T cell (T(naïve)) percentage was significantly lower in the ESRD group, and the difference between patients and controls was greater in the pre-dialysis patients than in the HD patients (P<0.05, for each comparison). By contrast, the percentages of central memory T cells (T(CM)) and effector memory T (T(EM)) cells were significantly higher in the ESRD group. Interleukin-17 production by T(EM) cells was significantly higher in the ESRD group. The severity of uremia was related negatively to the T(naïve) cell percentage but positively to the T(CM) and T(EM) cell percentages. The percentages of T(EM) and CD45RA(+) T effector memory subsets of CD8(+) T cells were significantly higher in the ESRD group (P<0.05). The result of this study showed significantly altered T cell-associated immunity and that it could not be corrected with hemodialysis.

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.

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.

Comparison of Patient Outcome According to Renal Replacement Modality after Renal Allograft Failure

The aim of this study is to investigate the clinical course of patients with failed allograft according to the type of renal replacement modality. Three hundred sixty-eight patients with failed allograft were included. Of these, 233 patients started hemodialysis (HD-PSKT), 64 patients started peritoneal dialysis (PD-PSKT), and 71 patients underwent second transplantation (ReKT). At baseline, age, sex, laboratory findings, and comorbidity did not differ significantly among three groups. Chronic rejection was the most common cause of allograft failure (81.6%) followed by acute rejection (10.7%). During the observation period, 96 patients died. The most common cause of death was cardiovascular disease (39.6%) followed by infection (34.4%) and malignancy (8.3%). Infection was important cause of death within 10 years from allograft failure, but cardiovascular disease and malignancy occupied significant portion of death after 10 years from allograft failure. Significant difference was not found among the three groups in the cause of allograft failure and the cause of death. The patient outcome was better in the ReKT than in the other two groups and it did not differ significantly between the PD-PSKT and HD-PSKT. In multivariate analysis, old age, hypoalbuminemia, and high comorbidity were proved to be the independent risk factors for mortality and the ReKT was still significantly superior to the HD-PSKT and PD-PSKT after adjustment for other confounding factors. In conclusion, second transplantation may result in survival benefit, and proper management of nutrition and comorbidity may help to improve outcome in patients with failed allograft.

Usefulness of continuous renal replacement therapy for correcting hypernatremia in a patient with severe congestive heart failure

Continuous renal replacement therapy (CRRT) is used as an alternative to intermittent hemodialysis (IHD) in patients who have acute kidney injury (AKI) and cannot tolerate IHD. Several studies have reported the usefulness of CRRT in treating sepsis, which is a non‐renal indication for CRRT. Recently, CRRT was also introduced as a useful tool for treating severe congestive heart failure (CHF). By using CRRT, we successfully treated hypernatremia in a patient with severe CHF, without observing any fluid overload. Therefore, we report this case to suggest that CRRT should be considered for the treatment of hypernatremia in patients with severe CHF.

Changes in Renal Function after Different Tandem Hematopoietic Stem-cell Transplantation Approaches in Patients with Multiple Myeloma

This study was done to observe the alteration of the estimated glomerular filtration rate (eGFR) in multiple myeloma patients according to type of tandem hematopoietic stem cell transplantation (HSCT). Forty-one patients were enrolled in this study. Twenty patients underwent autologous HSCT (auto-HSCT) and 21 patients underwent allogeneic HSCT (allo-HSCT). The changes in eGFR after the two tandem HSCT modalities were different between the two groups, according to the donor of stem cells (P = 0.016). In the auto-HSCT group, the eGFR, recorded 12 months after secondary HSCT, was significantly decreased compared with the eGFR recorded before stem cell mobilization (P = 0.005). Although there was no significant difference, the trend showed that the eGFR after allo-HSCT decreased from the previous HSCT until a month after secondary HSCT. In addition, after 6 months of secondary HSCT, the eGFR recovered to the level recorded prior to the HSCT (P = 0.062). This difference may be due to total body irradiation, a calcineurin inhibitor, or maintemance therapy. Changes in renal function would be monitored closely for these patients. The recovery of the eGFR would be a main focus for the patients treated with the total body irradiation or the calcineurin inhibitor, a progressive decline of the eGFR would be also crucial for the patients treated with maintenance therapy.