Predictive performance of the new race-free Chronic Kidney Disease Epidemiology Collaboration equations for kidney outcome in Korean patients with chronic kidney disease

The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.

Clinical outcomes and effects of treatment in older patients with idiopathic membranous nephropathy

BACKGROUND/AIMS@#Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN.@*METHODS@#The outcomes of 135 patients with histologically proven MN were analyzed. ‘Older’ was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients.@*RESULTS@#The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients.@*CONCLUSIONS@#Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome / 감염과화학요법

Because primary antifungal prophylaxis is widely used for immunocompromised hosts, the incidences of unusual fungal infections have increased. Trichosporon asahii has emerged as an important life-threatening opportunistic systemic pathogen because of the increased use of cytotoxic or immunosuppressant agents, along with high mortality rates. Here, we describe a case of catheter-related T. asahii bloodstream infection with multiple septic skin nodules in both the arms and legs of the patient who was in the neutropenic period after allogeneic stem cell transplantation for myelodysplastic syndrome treated with prophylactic ciprofloxacin and itraconazole. We successfully treated her with intravenous voriconazole for more than a month without any complications. Clinicians should consider breakthrough Trichosporon infections when clinical progress in an immunocompromised patient with unexplained infection signs and symptoms does not improve despite proper treatment with antibiotics or various antifungal agents. In addition, voriconazole can be a good treatment choice for achieving better treatment results and prognosis.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome / 감염과화학요법

Because primary antifungal prophylaxis is widely used for immunocompromised hosts, the incidences of unusual fungal infections have increased. Trichosporon asahii has emerged as an important life-threatening opportunistic systemic pathogen because of the increased use of cytotoxic or immunosuppressant agents, along with high mortality rates. Here, we describe a case of catheter-related T. asahii bloodstream infection with multiple septic skin nodules in both the arms and legs of the patient who was in the neutropenic period after allogeneic stem cell transplantation for myelodysplastic syndrome treated with prophylactic ciprofloxacin and itraconazole. We successfully treated her with intravenous voriconazole for more than a month without any complications. Clinicians should consider breakthrough Trichosporon infections when clinical progress in an immunocompromised patient with unexplained infection signs and symptoms does not improve despite proper treatment with antibiotics or various antifungal agents. In addition, voriconazole can be a good treatment choice for achieving better treatment results and prognosis.

Response to comment on “New therapeutic agents in diabetic nephropathy”

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New therapeutic agents in diabetic nephropathy

Studies investigating diabetic nephropathy (DN) have mostly focused on interpreting the pathologic molecular mechanisms of DN, which may provide valuable tools for early diagnosis and prevention of disease onset and progression. Currently, there are few therapeutic drugs for DN, which mainly consist of antihypertensive and antiproteinuric measures that arise from strict renin-angiotensin-aldosterone system inactivation. However, these traditional therapies are suboptimal and there is a clear, unmet need for treatments that offer effective schemes beyond glucose control. The complexity and heterogeneity of the DN entity, along with ambiguous renal endpoints that may deter accurate appraisal of new drug potency, contribute to a worsening of the situation. To address these issues, current research into original therapies to treat DN is focusing on the intrinsic renal pathways that intervene with intracellular signaling of anti-inflammatory, antifibrotic, and metabolic pathways. Mounting evidence in support of the favorable metabolic effects of these novel agents with respect to the renal aspects of DN supports the likelihood of systemic beneficial effects as well. Thus, when translated into clinical use, these novel agents would also address the comorbid factors associated with diabetes, such as obesity and risk of cardiovascular disease. This review will provide a discussion of the promising and effective therapeutic agents for the management of DN.

Adenosine monophosphate-activated protein kinase in diabetic nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 5' adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

Current Issues in ABO-Incompatible Kidney Transplantation / 대한이식학회지

Organ shortage is a critical issue in Korea as well as in other countries. In Korea, in 2013, the number of end-stage renal disease patients on the waiting list was 14,600; however, only 1,759 patients received transplantation during 2013. Recent advances in immunosuppression and antibody removal protocols have made ABO-incompatible kidney transplantation (ABO IKT) feasible, and have increased the opportunities for patients to undergo transplantation, especially for patients who do not have an ABO-compatible donor. The first ABO IKT was reported in 1955, but was unsuccessful due to the absence of an effective preparation protocol for antibody removal. In the 1980s, Alexandre used a protocol for removal of anti-ABO antibodies for the first time; however, the outcome was still inferior to that of ABO-compatible KT. Since 2000, with the advancement of immunosuppression and plasmapheresis, the outcome of ABO IKT has shown significant improvement and is now comparable to that of ABO-compatible KT. However, there are still several undetermined issues in ABO IKT. For example, issues regarding anti-ABO antibody titer, pretransplant desensitization method, immune suppressant regimen, and the role of C4d have still not been established. In this article, we reviewed the current status and protocol of ABO IKT and addressed to the undetermined issues in this field.

A new connecting technique in partial replantation of a ruptured peritoneal dialysis catheter

Peritoneal dialysis catheter ruptures have been managed by immediate removal and subsequent reinsertion of the catheter which inevitably entails interruption in peritoneal dialysis and a need for vascular access. A 36-year-old man on continuous ambulatory peritoneal dialysis complaining of dialysate leakage was found to have a small rupture near the outer cuff of the peritoneal dialysis catheter. Rather than employing the traditional method of exchanging the whole catheter, a partial replantation procedure to salvage the still-functioning conduit was performed. Two peritoneal dialysis adaptors were used to connect the end of the remaining old catheter to a new extraperitoneal segment of a new catheter and a piece of a transfer set to connect the adaptors. A novel, yet simple and safe, means of partial peritoneal dialysis catheter replantation when managing catheter injuries is suggested.

An Inverse Relationship between the Expression of the Gastric Tumor Suppressor RUNX3 and Infection with Helicobacter pylori in Gastric Epithelial Dysplasia

BACKGROUND/AIMS: This study was performed to determine the association between RUNX3 expression and Helicobacter pylori infection in premalignant gastric lesions. METHODS: We examined 107 patients with gastric epithelial dysplasia who had undergone endoscopic mucosal resection or submucosal dissection. All tissue samples were evaluated by RUNX3 staining and subclassified by immunophenotype. H. pylori infection in dysplastic lesions and the normal surrounding tissue was examined by silver staining, and cagA status was assessed by polymerase chain reaction. RESULTS: The loss of RUNX3 expression was observed in 62 cases (57.9%), and an association with H. pylori infection was found in 54 cases (50.5%). The infection rate with the cagA-positive H. pylori strain was 63.0%. In RUNX3-negative lesions, the rate of H. pylori infection (p=0.03) and the frequency of category 4 lesions (according to the revised Vienna classification) were high (p=0.02). In addition, the gastric mucin phenotype was predominant. In RUNX3-negative category 4 lesions, the rate of cagA-positive H. pylori infection rate was high but not significantly increased (p=0.08). CONCLUSIONS: Infection with H. pylori is associated with inactivation of RUNX3 in early gastric carcinogenesis. This mechanism was prominent in gastric cancer with a gastric mucin phenotype.

De novo glomerulitis associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: A single-center experience

BACKGROUND: Nephrotic syndrome (NS) and proteinuria are uncommon, often unrecognized manifestations of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Only a few isolated case reports and case series involving smaller number of patients who developed NS after HSCT have been published. METHODS: We reviewed the renal histopathological examination findings and clinical records of 15 patients who developed proteinuria after HSCT at Seoul and Yeouido St. Mary's Hospital (Seoul, Korea). We also measured the anti-PLA2 Rantibodies (M-type phospholipase A2 receptor) in the serum samples from the seven patients at the time of renal biopsy. RESULTS: All patients had GVHD. The most common indication for biopsy was proteinuria ( > 1 g/day), with nine patients having nephrotic range proteinuria. The most common histopathological finding was membranous nephropathy (MN; n = 12).Other findings were membranoproliferative glomerulonephritis, C1q nephropathy, and diabetic nephropathy. Eleven patients were treated with immunosuppressive agents, and three patients were treated only with angiotensin II receptor blocker. The overall response rate, including complete remission (urinary protein level < 0.3 g/day) and partial remission (urinary protein level = 0.31-3.4 g/day), was 73%. The mean follow-up period was 26 months, and none of the patients developed end-stage renal disease. All of the seven patients with MN had negative findings for anti-PLA2R antibodies, measured using an enzyme-linked immunosorbent assay kit. CONCLUSION: In this study the findings of 15 renal biopsies were analyzed and to our knowledge this is the largest clinicopathological study of GVHD-related biopsy-proven nephropathy. Approximately 80% of the patients were MN and 73% responded either partially or completely to immunosuppressive treatment. Currently, there is an increase in the incidence of GVHD-mediated renal disease, and therefore, renal biopsy is essential for diagnosing the nephropathy and preventing the progression of renal disease.

A Case of Steroid Dependent Eosinophilic Gastroenteritis Presenting as a Huge Gastric Ulcer

Eosinophilic gastroenteritis is defined as primary eosinophilic infiltration of the gastrointestinal tract. Endoscopic findings of this disease entity are non-specific, and huge gastric ulceration as initial presentation is extremely rare. We experienced a case of eosinophilic gastroenteritis presenting with abdominal pain in a 38 year-old-woman. Deep and huge ulceration in gastric antrum and body looked like advanced gastric cancer. Surgical resection was performed and histopathological examination showed dense infiltration of eosinophil without malignant cells. 5 years after surgery, diffuse abdominal pain and generalized edema developed and computed tomography showed entire wall thickening of the gastrointestinal tract. Random mucosal biopsy of the remnant stomach and terminal ileum showed mucosal eosinophilic infiltrations. She was treated with steroids and azathioprine but experienced frequent relapses and was dependent on steroids to maintain remissions. After 3 years, she died from infective endocarditis due to the prolonged use of immunosuppressive agents.