Da Rae Kim

Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy. Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence. Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group. Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.

Syndrome of inappropriate antidiuretic hormone secretion associated with seronegative neuromyelitis optica spectrum disorder

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potential cause of hyponatremia of the central nervous system (CNS). Although SIADH has been reported to be associated with many other central nervous disorders, its association with neuromyelitis optica (NMO) or NMO spectrum disorders are rare. NMO is a demyelinating disorder characterized by optic neuritis and transverse myelitis. Aquaporin-4 (AQP4), which is the target antigen for a NMO autoantibody, is the predominant CNS water channel. However, some NMO patients show seronegative AQP4 antibody results. The spectrum of NMO has been changed, and new findings about the disease have been reported. Here, we report a case of seronegative NMO spectrum disorder associated with SIADH.

A case of Ramsay Hunt syndrome diagnosed after kidney transplantation.

We report the first case of Ramsay Hunt syndrome (RHS) diagnosed after kidney transplantation in Korea. RHS is a disease caused by latent varicella-zoster characterized to involve geniculate ganglion of the seventh cranial nerve. Patients who have undergone kidney transplantation can be easily affected by viral infections because of their immune-compromised status. A 35-year-old man with hypertensive end-stage renal disease underwent kidney transplantation. Two months after surgery, the recipient was diagnosed with RHS and treated with antivirals and steroids. However, after using the antiviral agents for the recommended duration, facial paralysis occurred as a new presentation and he required further treatment. Otalgia and periauricular vesicles improved, but the facial palsy remained.

Update of aristolochic acid nephropathy in Korea

Background/Aims The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. Methods We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. Results Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. Conclusions Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Fabry disease with lenticular degeneration without pulvinar sign

A 38-year-old man visited the neurology department with a tingling sensation in both the upper and lower extremities in 2016. He had been on hemodialysis since 2009 due to end-stage renal disease (ESRD). He was diagnosed with Fabry disease (FD) via GLA gene testing [c.902G[A (p.Arg301Gln) hemizygote]. The patient had been stable with regular hemodialysis. His blood chemistry results including electrolyte and liver function testing were within normal range, and cardiac function was normal on his most recent transthoracic echocardiography results. Enzyme replacement therapy was not performed. Neurologic examination showed no abnormal findings except decreased deep tendon reflexes. Brain MRI revealed high signal intensity (HSI) in the bilateral lentiform nuclei on T1-weighted imaging (T1WI), of which the core lesion was iso-intense. The core of the lesion showed low signal intensity (LSI) on T2-weighted imaging (T2WI) and diffusion-weighted imaging. There were no abnormal signal intensities in either thalamus. No other significant findings, such as cerebral atrophy or periventricular white matter changes suggesting cerebral small vessel disorders, were observed. Cerebral and carotid MR angiography was normal except for an angulated basilar artery (Fig. 1). Brain computed tomography was not performed. Nerve conduction studies revealed sensorimotor mixed axonal and demyelinating-type polyneuropathy. The tingling sensation improved without medication. FD is an X-linked lysosomal storage disorder caused by a GLA gene mutation. Neuroimaging abnormalities can be found in 37.5–70.3% of individuals with FD [1, 2]. The most frequent neuroimaging finding is non-specific T2 HSI in the periventricular white matter [1, 2]. The most specific MRI sign of brain involvement in FD is HSI in the bilateral pulvinar on T1WI, which is frequently seen in men with cardiac and renal involvement [3, 4]. In the present case, lesions were unexpectedly found in the lentiform nuclei with a similar appearance to the pulvinar signs observed in previous studies [3, 4]. T1 HSIs of the bilateral lentiform nuclei need to be differentiated from hepatolenticular degeneration, hyperglycemic hemichorea, occupational exposure to manganese and long-term parenteral nutrition [5]. As the patient had no such conditions, the T1 HSI lesions in the lentiform nuclei were more likely associated with FD. Selective microvascular calcification was the suspected mechanism of pulvinar sign in previous studies [3, 4]. On brain MRI, a calcified lesion could be observed as a hyperintensity on T1WI due to the T1 shortening effect [6]. However, at higher concentrations of calcium (over 30%), susceptibility effect can be dominated, resulting LSIs [6]. Those findings were evidenced by a previous report on FD with pulvinar sign with more intense calcifications of the globus pallidum, which were not detected on T1WI [3]. Therefore, in the early stages of FD, there could be a chance that the T1 shortening effect only impacts the globus pallidum. Therefore, the neuroimaging findings of the present case might be an early neuroimaging feature of FD. The lesion core in the present case might reflect greater calcification. & Sung Sang Yoon hsyoon96@khu.ac.kr

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy.

Background Immunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). Methods We included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m2/mo) or (2) a rise in serum creatinine to an absolute level of ≥ 1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. Results A total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. Conclusion The serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.

ISH NIA PS 02-02 The different predictive role of serum triglyceride to high-density lipoprotein cholesterol ratio according to kidney function in patients with acute myocardial infarction (from the Korea Acute Myocardial Infarction Registry)

Objective: High serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic effect of the TG/HDL-C ratio on patients with kidney dysfunction is unclear. We examined the association of TG/HDL-C ratio and major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) according to kidney function. Design and Method: This study was based on a retrospective cohort, the Korean Acute Myocardial Infarction Registry (KAMIR) database. Among 13,897 patients who diagnosed AMI from November 2005 to July 2008, we studied 8,225 patients who had baseline TG/HDL-C ratio. Patients were categorized into three groups by estimated glomerular filtration (eGFR) and the TG/HDL-C ratio was categorized into tertiles based on the quantity of the study population and the distribution of TG/HDL-C ratio. The primary end point was 12-month MACEs including cardiac death, MI, and repeated PCI or coronary artery bypass grafting. Results: During 12-month follow up period, 686 patients (8.3%) had MACEs. The log-rank test identified a significant association between the TG/HDL-C ratio and MACEs (p < 0.001) in the whole study cohort. In patients with normal kidney function (eGFR > 60 ml/min per 1.73 m2) and mildly reduced kidney function (eGFR = 60–89 ml/min per 1.73 m2), higher TG/HDL-C ratio was associated with increased risk of MACEs (hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.01–2.69, p = 0.018; HR 1.46, 95% CI 1.06–1.99, p = 0.02, respectively). However, in patients with moderately reduced kidney function (eGFR < 60 ml/min per 1.73 m2), higher TG/HDL-C ratio did not associated with increased risk of MACEs (HR 1.42, 95% CI 0.93–2.17, p = 0.104). Conclusions: A higher serum TG/HDL-C ratio is associated with increased risk of MACEs in patients with normal and mildly reduced kidney function. However, in patients with moderately reduced kidney function, the TG/HDL-C ratio did not revealed significant association with MACEs.