Henoch-Schönlein Purpura and Peroneal Nerve Palsy after Hemorrhagic Fever with Renal Syndrome

In the course of hemorrhagic fever with renal syndrome (HFRS), mild neurological symptoms such as headache, vertigo and nausea are common. Peripheral neuropathy in HFRS is very rare. Henoch- Schönlein purpura (HSP) is an immunologically medicated systemic vasculitis of small blood vessels affecting the skin, gastrointestinal tract, joints and kidneys, predominantly. Neurological complications in HSP include headache, focal cerebral deficit, coma, convulsion, subarachnoid hemorrhage and chorea. Peripheral neuropathy is also very rare. However there was no case report about HSP and peroneal nerve palsy after HFRS. With a brief review of the literature, we report a case of HSP and peroneal nerve palsy following HFRSope

Neo-Fs Index: A Novel Immunohistochemical Biomarker Panel Predicts Survival and Response to Anti-Angiogenetic Agents in Clear Cell Renal Cell Carcinoma

Background: Frameshift indels have emerged as a predictor of immunotherapy response but were not evaluated yet to predict anti-angiogenetic agent (AAA) response or prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Here, to develop biomarkers that predict survival and response to AAA, we evaluated the immunohistochemical expression of proteins whose genes frequently harbor frameshift indels in 638 ccRCC patients and correlated the individual and integrated markers with prognosis and AAA response. The mutational landscape was evaluated using targeted next-generation sequencing in 12 patients concerning protein markers. Immune gene signatures were retrieved from TCGA RNA seq data. Results: Five proteins (APC, NOTCH1, ARID1A, EYS, and filamin A) were independent adverse prognosticators and were incorporated into the Neo-fs index. Better overall, disease-specific and recurrence-free survival were observed with high Neo-fs index in univariate and multivariate survival analyses. Better AAA responses were observed with a high Neo-fs index, which reflected increased MHC class I, CD8+ T cell, cytolytic activity, and plasmacytoid dendritic cell signatures and decreased type II-IFN response signatures, as well as greater single-nucleotide variant (SNV) and indel counts. Conclusions: Neo-fs index, reflecting antitumor immune signature and more SNVs. and indels, is a powerful predictor of survival and AAA response in ccRCC.ope

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE)

Backgrounds: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods: The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion: Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration: NCT03929887 .ope

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

Interleukin-4 (IL-4) expression is implicated in the pathogenesis of nephrotic syndrome (NS). This study aimed to investigate the changes in the transcriptomes of human podocytes induced by IL-4 treatment and to analyze whether these changes could be affected by simultaneous steroid treatment. Three groups of human podocytes were treated with control, IL-4, and IL-4 plus dexamethasone (DEX), respectively. We performed whole-transcriptome sequencing to identify differentially expressed genes (DEGs) between the groups. We investigated relevant biological pathways using Gene Ontology (GO) enrichment analyses. We also attempted to compare and validate the DEGs with the genes listed in PodNet, a literature-based database on mouse podocyte genes. A total of 176 genes were differentially expressed among the three groups. GO analyses showed that pathways related to cytoskeleton organization and cell signaling were significantly enriched. Among them, 24 genes were listed in PodNet, and 12 of them were previously reported to be associated with IL-4-induced changes in human podocytes. Of the 12 genes, the expression levels of BMP4, RARB, and PLCE1 were reversed when podocytes were simultaneously treated with DEX. In conclusion, this study explored changes in the transcriptome profiles of human podocytes treated with IL-4. Few genes were reported in previous studies and were previously validated in experiments with human podocytes. We speculate that IL-4 may exert pathogenic effects on the transcriptome of human podocytes, and a few genes may be involved in the pathogenesis.ope

Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury

Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 (HIF1) and associated proteins. Dapagliflozin improved renal function. Dapagliflozin reduced renal expression of Bax, renal tubule injury and TUNEL-positive cells and increased renal expression of HIF1 in IR-injured mice. HIF1 inhibition by albendazole negated the renoprotective effects of dapagliflozin treatment in IR-injured mice. In vitro, dapagliflozin increased the expression of HIF1, AMP-activated protein kinase (AMPK), and ERK and increased cell survival of hypoxic HK2 cells in a dose-dependent manner. In conclusion, dapagliflozin attenuates renal IR injury. HIF1 induction by dapagliflozin may play a role in renoprotection against renal IR injury.ope

Th17 Cells Are Not Directly Associated with Renal Ischemia-Reperfusion Injury

Purpose: Interleukin-17-producing T cell (Th17 cell) is a newly discovered subtype of helper T cell. Its function and importance in the pathogenesis of a broad range of immune diseases are under active investigation. However, little is currently known about the role of Th17 cells in ischemia-reperfusion (IR) injury of the kidney, a common pathophysiologic occurrence in various renal disease processes. Methods: We measured the number of infiltrated T lymphocytes and Th17 cells in C57Bl/6 mouse kidneys in sham-operated controls and following varying degrees of renal IR injury induced by renal pedicle clamping and reperfusion. The cell count results were compared to accompanying histologic damage and serum creatinine levels after 35 min and 45 min of ischemia, and following reperfusion of 48, 72, 96, and 168 hrs. Results: The number of T lymphocytes increased as ischemia time increased. However, the number of Th17 cells was not significantly affected by prolonged ischemia and reperfusion. Furthermore, the degree of histologic damage and serum creatinine levels did not correlate with the T lymphocyte and Th17 cell count numbers. Conclusion: We did not observe any evidence that Th17 cells are directly linked to renal tissue damage caused by IR injury. The role and importance of helper T cells in renal IR injury need to be evaluated further in the light of the interaction with Th1, Th2, and regulatory T cells rather than Th17 alone.ope

A Case of Lupus-like Glomerulonephritis in an HIV-infected Patient

Many types of glomerulonephritis are associated with human immunodeficiency virus (HIV) infection. We present a case of a 50-year-old Korean man with an HIV infection, who developed nephrotic syndrome and progressive renal failure. Renal biopsy showed lupus-like glomerulonephritis without clinical or serologic evidence of systemic lupus erythematosus. After the administration of antiretroviral agents and steroids, there was reduction in the amount of proteinuria and improvement in renal functionope

The spectrum of biopsy-proven renal diseases in Korea

ope

Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

BACKGROUND/AIMS: Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. METHODS: Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-alpha, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy. RESULTS: Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-alpha, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells. CONCLUSIONS: DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effectsope

Antihypertensive and Renal Protective Effects of Oryeongsan in Spontaneously Hypertensive Rats

Oryeongsan (ORS), a traditional medicine used to regulate body fluids, has a long history of use as a diuretic in Korea, China, and Japan. ORS is commonly thought to lower blood pressure, but high-quality data on its effects are sparse. The purpose of this study was to determine the antihypertensive and renal protective effects of ORS in rats with hypertension. Spontaneously hypertensive rats (SHR) were divided into two groups with similar mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP). Then, 10 mL/kg of vehicle (distilled water) or 200 mg/kg of ORS extract were administered orally once a day for 3 weeks. SBP and DBP were measured at weeks 1, 2, and 3. At the end of the experiment, blood was collected, and kidneys were removed for histology. By the 2nd and 3rd week after initiation of treatment, the ORS-treated group had significantly lower SBP than control-treated rats (191.3 ± 6.5 vs. 206.3 ± 9.8 mmHg, p = 0.022 at the 2nd week; 195.8 ± 7.8 vs. 217.0 ± 8.1 mmHg, p = 0.003 at the 3rd week, respectively). The ORS-treated group trended toward having a lower DBP than control, but there was no significant difference. Blood urea nitrogen (BUN) and serum creatinine (Cr) were not different between the ORS-treated and control groups (BUN: 23.7 ± 1.1 vs. 22.7 ± 2.8 mg/dL, p = 0.508; Cr: 19.0 ± 2.2 vs. 21.6 ± 2.1 μM, p = 0.083, respectively). The percentage of renal tissue affected by tubulointerstitial fibrosis was significantly lower in the ORS-treated group (1.68 ± 0.60) compared to controls (3.17 ± 0.96, p = 0.019). These findings suggest that treatment with ORS reduces SBP and ameliorates renal damage in SHR.ope