Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts

Pathologic diagnosis of antibody-mediated rejection (ABMR) in ABO-incompatible (ABOi) transplantation patients is often challenging because patients without ABMR are frequently immunopositive for C4d. The aim of this study was to determine whether C4d positivity with microvascular inflammation (MVI), in the absence of any detectable donor-specific antibodies (DSAs) in ABOi patients, could be considered as ABMR. Methods: A retrospective study of 214 for-cause biopsies from 126 ABOi kidney transplantation patients was performed. Patients with MVI score of ≥2 and glomerulitis score of ≥1 (n = 62) were divided into three groups: the absolute ABMR group (DSA-positive, C4d-positive or C4d-negative; n = 36), the C4d-positive group (DSA-negative, C4d-positive; n = 22), and the C4d-negative group (DSA-negative, C4d-negative; n = 4). The Banff scores, estimated glomerular filtration rates (eGFRs), and graft failure rates were compared among groups. Results: C4d-positive biopsies showed higher glomerulitis, peritubular capillaritis, and MVI scores compared with C4d-negative specimens. The C4d-positive group did not show significant differences in eGFRs and graft survival compared with the absolute ABMR group. Conclusion: The results indicate that C4d positivity, MVI score of ≥2, and glomerulitis score of ≥1 in ABOi allograft biopsies may be categorized and treated as ABMR cases.

Hepatocellular carcinoma and cancer-related mortality after kidney transplantation with rituximab treatment

Purpose@#There are increased therapeutic usages of rituximab in kidney transplantation (KT). However, few studies have evaluated the effect of rituximab on cancer development following KT. This study aimed to evaluate the effect of rituximab on the cancer occurrence and mortality rate according to each type of cancer. @*Methods@#Five thousand consecutive recipients who underwent KT at our center were divided into era1 (1990–2007) and era2-rit– (2008–2018), and era2-rit+ (2008–2018) groups. The era2-rit+ group included patients who received single-dose rituximab (200–500 mg) as a desensitization treatment 1–2 weeks before KT. @*Results@#The 5-year incidence rates of malignant tumors after KT were 3.1%, 4.3%, and 3.5% in the era1, era2-rit–, and era2-rit+ group, respectively. The overall incidence rate of cancer after transplantation among the 3 study groups showed no significant difference (P = 0.340). The overall cancer-related mortality rate was 17.1% (53 of 310). Hepatocellular carcinoma (HCC) had the highest mortality rate (61.5%) and relative risk of cancer-related death (hazard ratio, 8.29; 95% confidence interval, 2.40–28.69; P = 0.001). However, we found no significant association between rituximab and the incidence of any malignancy. @*Conclusion@#Our results suggest that single-dose rituximab for desensitization may not increase the risk of malignant disease or cancer-related mortality in KT recipients. HCC was associated with the highest risk of cancer-related mortality in an endemic area of HBV infection.

Clinical features and outcomes in kidney transplant recipients with renal cell carcinoma: a single-center study

BACKGROUND: Previous studies have recommended a 2- to 5-year waiting time prior to kidney transplantation (KT) in patients with end-stage renal disease (ESRD) and symptomatic renal cell carcinoma (RCC) and no delay for incidental early-stage RCC. Data on Asian KT recipients are unavailable.METHODS: This is a Korean single-center retrospective study on 35 KT recipients with ESRD and RCC. Patients were classified into two groups: early KT (KT performed within 1 year after nephrectomy for RCC, including KT with simultaneous nephrectomy) and delayed KT (KT performed over than 1 year after nephrectomy for RCC). Patient survival, graft survival, and cancer recurrence were compared between both groups.RESULTS: There were no statistically significant differences in patient survival (P = 0.388), graft survival (P = 0.317), or graft rejection rate (P = 0.207) between the early and delayed KT groups. Additionally, there were no differences in pathological characteristics or RCC stage other than cancer histology: acquired cystic disease-associated RCC (47.4%) was the most common RCC type in the early KT group, whereas clear cell type (62.5%) was the most common RCC type in the delayed KT group. No RCC recurrence was observed.CONCLUSION: Patients with early-stage and asymptomatic RCC do not require a mandatory observational period prior to KT after curative nephrectomy

Outcomes of living donor kidney transplantation in diabetic patients: age and sex matched comparison with non-diabetic patients

BACKGROUND/AIMS: Kidney transplantation (KT) reportedly provides a significant survival advantage over dialysis in diabetic patients. However, KT outcome in diabetic patients compared with that in non-diabetic patients remains controversial. In addition, owing to recent improvements in the outcomes of KT and management of cardiovascular diseases, it is necessary to analyze outcomes of recently performed KT in diabetic patients. METHODS: We reviewed all diabetic patients who received living donor KT between January 2008 and December 2011. Each patient was age- and sex-matched with two non-diabetic patients who received living donor KT during the same period. The outcomes of living donor KT were compared between diabetic and non-diabetic patients. RESULTS: Among 887 patients, 89 diabetic patients were compared with 178 non-diabetic patients. The incidence of acute rejection was not different between the diabetic and non-diabetic patients. Urinary tract infection and other infections as well as cardiovascular events occurred more frequently in diabetic patients. However, diabetes, cardiovascular disease, and infection were not significant risk factors of graft failure. Late rejection (acute rejection after 1 year of transplantation) was the most important risk factor for graft failure after adjusting for diabetes mellitus (DM), human leukocyte antigen mismatch, rejection and infection (hazard ratio, 56.082; 95% confidence interval, 7.169 to 438.702; p < 0.001). Mortality was not significantly different between diabetic and non-diabetic patients (0 vs. 2, p = 0.344 by log-rank test). CONCLUSIONS: End-stage renal disease patients with DM had favorable outcomes with living donor kidney transplantation.

Predictors of Avascular Necrosis after Kidney Transplantation / 대한이식학회지

BACKGROUND: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. METHODS: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. RESULTS: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P < 0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). CONCLUSIONS: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.

Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy

BACKGROUND/AIMS: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.

Rapidly resolved IgG4-related retroperitoneal fibrosis after steroid pulse therapy / 영남의대학술지

Retroperitoneal fibrosis (RF) is a disorder characterized by the presence of a retroperitoneal mass and concurrent systemic inflammation. Some cases of RF are recognized as belonging to the spectrum of immunoglobulin G4-related disease (IgG4-RD). Glucocorticoids are highly effective for treatment of retroperitoneal fibrosis, although the optimal dose and duration of therapy have not been established. An initial dose of prednisone (40-60 mg) daily is usually administered with a tapering scheme. We report on a 55-year-old man diagnosed with IgG4-related RF and successfully treated with a 3-day course of daily 250 mg (4 mg/kg) intravenous methylprednisolone, which resulted in the prompt resolution of urinary obstruction and systemic symptoms.

Secondary amyloidosis complication of Crohn disease treated with infliximab / 영남의대학술지

Secondary systemic (AA) amyloidosis is a severe complication of progressed Crohn disease (CD) characterized by the deposition of amyloid A in body organs and tissues. Various therapeutic approaches have been recommended, however there is still no effective treatment. Recently, several case reports have demonstrated the effects of anti-tumor necrosis factor-alpha therapy in patients with AA amyloidosis associated with CD. We report on a 35-year-old female patient with CD complicated by AA amyloidosis in the gastrointestinal tract and renal involvement, who was treated with infliximab. The infliximab therapy improved the gastrointestinal symptoms and decreased the serum creatinine.

A Case of Delayed Recovery from Antibody-Mediated Rejection / 대한내과학회지

Antibody-mediated rejection (ABMR) in kidney transplant recipients is mediated by donor-specific antibodies. It is the major cause of graft failure in noncompliant patients and is associated with reduced long-term graft survival. We present a case of delayed recovery of renal function despite aggressive therapy after acute ABMR. A 49-year-old male on triple-drug maintenance immunosuppression (prednisolone, cyclosporine, and azathioprine), who underwent cadaveric donor renal transplantation 14 years earlier, visited our clinic with a serum creatinine level (SCr) of 1.9 mg/dL. The kidney biopsy revealed acute ABMR with diffuse C4d immunopositivity. We started steroid pulse therapy and bortezomib with plasmapheresis. Nevertheless, the SCr increased. Consequently, antithymocyte globulin (ATG) and intravenous immunoglobulin were administered. The SCr increased further to 4.1 mg/dL. Therefore, we performed a second kidney biopsy, which showed no change. Finally, we used rituximab. Fortunately, the SCr decreased gradually and returned to baseline.

Ipsilateral leg swelling after renal transplantation as an alarming sign of Iliac vein stenosis

Iliac vein stenosis is a rare vascular complication of renal transplantation that may compromise allograft function if not recognized and corrected in a timely fashion. Because chronic venous stenosis may remain undiagnosed for several years, a high index of suspicion should be maintained until diagnosing this rare disease. A 56-year-old renal transplant recipient presented with unilateral leg swelling and renal dysfunction 16 years after transplantation. Computed tomography excluded deep vein thrombosis and revealed tight iliac vein stenosis on the side of the renal transplant. Following angiographic confirmation of the stenosis, endovascular treatment was successfully performed with a purposefully designed, self-expanding, venous stent. Ipsilateral leg swelling is an alarming sign for the diagnosis of iliac vein stenosis after renal transplantation. Percutaneous intervention with venous stent placement seems to be a safe and effective treatment of this rare condition.

A Case of Pleural Endometriosis Presented as Right Sided Hemothorax in a Patient Who Underwent Kidney Transplantation / 영남의대학술지

Thoracic endometriosis is an uncommon disease that has four main forms: catamenial pneumothorax, hemothorax, hemoptysis, and pulmonary nodules. Since the growth of endometrial tissue depends on the presence of estrogen, thoracic endometriosis usually occurs in menstruating women between 25 and 35 years of age. Menstrual disturbances are common in women with chronic kidney disease (CKD). However, they could be reversed after kidney transplantation. Therefore, previously asymptomatic endometriosis may become symptomatic after kidney transplantation. A 49-year-old woman with CKD underwent kidney transplantation. A month later, she experienced dyspnea, and hemothorax in her right hemithorax. However, there was no evidence of infectious diseases and malignancy in thoracentesis, pleural biopsy, and computed chest tomography (CT). The serum and pleural fluid levels of his carbohydrate antigen 125 were elevated. Hemothorax secondary to pleural endometriosis was suspected. We tried hormonal therapy, and the hemothorax disappeared. At the sixth-month follow-up, there was no recurrence of hemothorax.

Asymptomatic Bacteriuria Caused by Haemophilus influenzae in a Kidney Transplant Recipient

Haemophilus influenzae has rarely been implicated as the causative agent of urinary tract infections (UTIs). However, cases of UTIs caused by H. influenza in patients with anatomical or functional urinary tract abnormalities have been steadily reported. We report a case of asymptomatic bacteriuria caused by H. influenzae in a kidney transplant recipient. The patient was a 61-yr-old woman who visited the hospital for a routine follow-up after receiving a kidney transplant from a living-related donor; the patient showed no symptoms. Urine microscopy revealed white blood cell (WBC) count of >30/high power field (HPF). Urine culture on blood agar showed non-hemolytic, tiny, translucent, grayish colonies with satellitism around beta-hemolytic colonies of Staphylococcus epidermidis. The organism in the satellite colonies was identified as H. influenzae by using VITEK Neisseria/Haemophilus Identification Card (bioMerieux, Marcy L'Etoile, France) and found to require both X and V factors for growth. The organism did not produce beta-lactamase. Urine culture performed 1 week later revealed H. influenza again. The patient was not treated with antimicrobials. Urine culture performed using chocolate agar 7 weeks later did not reveal H. influenzae. Since H. influenzae does not grow in the media commonly used for urine culture such as blood agar, the use of these media could lead to underestimation of the true frequency of H. influenzae. If UTI is suspected in a patient with anatomical or functional urinary tract abnormality, chocolate agar should be considered for urine culture.

Asymptomatic Bacteriuria Caused by Haemophilus influenzae in a Kidney Transplant Recipient

Haemophilus influenzae has rarely been implicated as the causative agent of urinary tract infections (UTIs). However, cases of UTIs caused by H. influenza in patients with anatomical or functional urinary tract abnormalities have been steadily reported. We report a case of asymptomatic bacteriuria caused by H. influenzae in a kidney transplant recipient. The patient was a 61-yr-old woman who visited the hospital for a routine follow-up after receiving a kidney transplant from a living-related donor; the patient showed no symptoms. Urine microscopy revealed white blood cell (WBC) count of >30/high power field (HPF). Urine culture on blood agar showed non-hemolytic, tiny, translucent, grayish colonies with satellitism around beta-hemolytic colonies of Staphylococcus epidermidis. The organism in the satellite colonies was identified as H. influenzae by using VITEK Neisseria/Haemophilus Identification Card (bioMerieux, Marcy L'Etoile, France) and found to require both X and V factors for growth. The organism did not produce beta-lactamase. Urine culture performed 1 week later revealed H. influenza again. The patient was not treated with antimicrobials. Urine culture performed using chocolate agar 7 weeks later did not reveal H. influenzae. Since H. influenzae does not grow in the media commonly used for urine culture such as blood agar, the use of these media could lead to underestimation of the true frequency of H. influenzae. If UTI is suspected in a patient with anatomical or functional urinary tract abnormality, chocolate agar should be considered for urine culture.

Comparison between CT Colonography and Double-Contrast Barium Enema for Colonic Evaluation in Patients with Renal Insufficiency

OBJECTIVE: To compare the CT colonography (CTC) and double-contrast barium enema (DCBE) for colonic evaluation in patients with renal insufficiency. MATERIALS AND METHODS: Two sequential groups of consecutive patients with renal insufficiency who had a similar risk for colorectal cancer, were examined by DCBE (n = 182; mean +/- SD in age, 51 +/- 6.4 years) and CTC (n = 176; 50 +/- 6.7 years), respectively. CTC was performed after colon cleansing with 250-mL magnesium citrate (n = 87) or 4-L polyethylene glycol (n = 89) and fecal tagging. DCBE was performed after preparation with 250-mL magnesium citrate. Patients with colonic polyps/masses of > or = 6 mm were subsequently recommended to undergo a colonoscopy. Diagnostic yield and positive predictive value (PPV) for colonic polyps/masses, examination quality, and examination-related serum electrolyte change were retrospectively compared between the two groups. RESULTS: Both the CTC and DCBE were positive for colonic polyps/masses in 28 (16%) of 176 and 11 (6%) of 182 patients, respectively (p = 0.004). Among patients with positive findings, 17 CTC and six DCBE patients subsequently underwent a colonoscopy and yielded a PPV of 88% (15 of 17 patients) and 50% (3 of 6 patients), respectively (p = 0.089). Thirteen patients with adenomatous lesions were detected in the CTC group (adenocarcinoma [n = 1], advanced adenoma [n = 6], and non-advanced adenoma [n = 6]), as compared with two patients (each with adenocarcinoma and advanced adenoma) in the DCBE group (p = 0.003). Six (3%) of 176 CTC and 16 (9%) of 182 DCBE examinations deemed to be inadequate (p = 0.046). Electrolyte changes were similar in the two groups. CONCLUSION: In patients with renal insufficiency, CTC has a higher diagnostic yield and a marginally higher PPV for detecting colorectal neoplasia, despite a similar diagnostic yield for adenocarcinoma, and a lower rate of inadequate examinations as compared with DCBE.

ABO Incompatible Living Donor Kidney Transplantation with Rituximab and Plasmapheresis: A Single Center Experience / 대한신장학회지

PURPOSE: ABO incompatibility had long been an obstacle in kidney transplantation. However, recent reports showed excellent outcomes. In this study, we evaluated the outcomes of ABO incompatible kidney transplantation with preconditioning protocol using rituximab and plasmapheresis. METHODS: The recipients who had an ABO-incompatible donor and underwent living donor kidney transplantation were enrolled. Preconditioning protocol was pretransplant single dose rituximab with plasmapheresis at pretransplantation 7-10 days. Immune suppression regimen consisted of tacrolimus, mycophenolate mofetil and steroid. Anti-A or anti-B antibody titer was monitored during preconditioning and post transplantation period. RESULTS: 37 patients underwent living donor ABO incompatible kidney transplantation. Median pre-treatment antibody titer was 1:64 and pre transplant antibody titer after 1-6 times of plasmapheresis was 1:2. Median follow-up duration was 332 days (range 156-681). One episode of acute T cell mediated rejection was observed. Mean serum creatinine at 2 weeks was 1.00+/-0.27 mg/dL and at 24 weeks was 1.21+/-0.37 mg/dL. CONCLUSION: ABO incompatible kidney transplantation with rituximab and plasmapheresis can be safely performed. It is therefore a valuable option for expanding donor pool and should be actively performed in Korea.

Proteasome-Inhibitor-Based Primary Therapy for Antibody-Mediated Rejection in a Renal Transplant Recipient / 대한내과학회지

Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.

Proteasome-Inhibitor-Based Primary Therapy for Antibody-Mediated Rejection in a Renal Transplant Recipient / 대한내과학회지

Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.

Erratum to "Assessment of Deceased Donor Kidneys Using a Donor Scoring System" by Bang K, et al. (Yonsei Med J 2010;51:870-876)

No abstract available.

Erratum to "Assessment of Deceased Donor Kidneys Using a Donor Scoring System" by Bang K, et al. (Yonsei Med J 2010;51:870-876)

No abstract available.

Comparison of Drug-Eluting Stent and Bare Metal Stent in Reducing Adverse Cardiac Event after Coronary Stenting in Hemodialysis Patients / 대한신장학회지

PURPOSE: The patients treated with hemodialysis have been known to have a high 1-year mortality rate after percutaneous coronary intervention (PCI). We evaluated the clinical benefits of drug-eluting stent (DES), compared to bare-metal stent (BMS) in Korean hemodialysis patients. METHODS: We studied 72 hemodialysis patients (M:F=49:23, age 60+/-11 years) treated with percutaneous coronary intervention (PCI) from January, 1999 to February, 2006. Forty four patients (M:F=28: 16, age 60+/-11 years) treated with DES and 28 patients (M:F=21:7, age 60+/-12 years) with BMS were enrolled. A composite of major adverse cardiac and cerebral endpoints (MACCE) was defined as all-cause death, myocardial infarction, stroke, and target-vessel revascularization (TVR). We compared the incidence of MACCE between DES and BMS group. RESULTS: A composite of MACCE occurred in none in DES group (n=44) and 4 in BMS group (n=28) within 3 months after coronary stenting (Kaplan-Meier survival analysis: 0% vs 14%, respectively, p= 0.02). After 3 months, there was no difference in the incidence of primary end points between two groups. Multi-vessel disease (OR 2.47, 95% CI 1.02-6.11, p<0.05) was associated with a significant increase in the incidence of MACCE within 18 months after coronary artery stenting CONCLUSION: DES may be superior to BMS in reducing adverse cardiac outcome at early period after coronary stenting in HD patients. However, this study showed no significant difference with the lapse of time.