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Studies have highlighted the significant involvement of kidney pericytes in renal fibrosis. Kidney pericytes, classified as interstitial mesenchymal cells, are extensively branched, collagen-producing cells that closely interact with endothelial cells. This article aims to provide an overview of the recent advancements in understanding the physiological functions of pericytes and their roles in kidney diseases. In a healthy kidney, pericytes have essential physiological function in angiogenesis, erythropoietin (EPO) production, and the regulation of renal blood flow. Nevertheless, pericyte-myofibroblast transition has been identified as the primary cause of disease progression in acute kidney injury (AKI)-to-chronic kidney disease (CKD) continuum. Our recent research has demonstrated that hypoxia-inducible factor-2α (HIF-2α) regulates erythropoietin production in pericytes. However, this production is repressed by EPO gene hypermethylation and HIF-2α downregulation which were induced by transforming growth factor-β1-activated DNA methyltransferase and activin receptor-like kinase-5 signaling pathway during renal fibrosis, respectively. Additionally, AKI induces epigenetic modifications in pericytes, rendering them more prone to extracellular matrix production, cell migration and proliferation, thereby contributing to subsequent capillary rarefaction and renal fibrosis. Further investigation into the specific functions and roles of different subpopulations of pericytes may contribute for the development of targeted therapies aimed at attenuating kidney disease and mitigating their adverse effects., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD)., Method: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison., Result: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients., Conclusion: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Aging is inevitable in life. It is defined as impaired adaptive capacity to environmental or internal stresses with growing rates of disease and death. Aging is also an important risk factor for various kidney diseases such as acute kidney injury and chronic kidney disease. Patients older than 65 years have nearly 28% risk of failing recovery of kidney function when suffering from acute kidney injury. It is reported that more than a third of population aged 65 years and older have chronic kidney disease in Taiwan, and the occurrence of multiple age-related disorders is predicted to increase in parallel. Renal aging is a complex, multifactorial process characterized by many anatomical and functional changes. Several factors are involved in renal aging, such as loss of telomeres, cell cycle arrest, chronic inflammation, activation of renin-angiotensin system, decreased klotho expression, and development of tertiary lymphoid tissues. These changes can also be observed in many other different types of renal injury. Recent studies suggested that young blood may rejuvenate aged organs, including the kidneys. In order to develop new therapeutic strategies for renal aging, the mechanisms underlying renal aging and by which young blood can halt or reverse aging process warrants further study., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: End-stage renal disease (ESRD) is a growing global health concern with increased disease burden and high medical costs. Utilization of the emergency department (ED) among dialyzed patients and the associated risk factors remain unknown., Methods: Participants of this study, selected from the National Health Insurance Database in Taiwan, were aged 19-90 years and received maintenance hemodialysis from January 1, 2010, to December 31, 2010. A control group consisting of individuals who did not receive dialysis, selected from the same data source, were matched for age, sex, and the Charlson Comorbidity Index (CCI). Subgroup analysis with hemodialysis frequency was also performed. ED utilization among enrolled individuals was assessed in 2012. Generalized estimating equations with multiple variable adjustments were used to identify risk factors associated with resuscitation during ED visits., Results: One group of 2985 individuals who received maintenance hemodialysis, and another group of 2985 patients that did not receive hemodialysis, between January 1, 2010, and December 31, 2010, were included in this study. There were 4822 ED visits in the hemodialysis group, and 1755 ED visits in the non-dialysis group between January 1, 2012, and December 31, 2012. Analysis of multivariable generalized estimating equations identified the risk associated with resuscitation during ED visits to be greater in individuals who were receiving maintenance hemodialysis, aged older than 55 years, hospitalized in the past year, and assigned first and second degree of triage., Conclusion: Patients receiving maintenance hemodialysis had higher ED utilization and a significantly higher risk of resuscitation during ED visits than those without hemodialysis., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Substantial progress was made in acute kidney injury (AKI) over the past 10 years, but no therapeutic interventions have been shown to prevent AKI or accelerate functional recovery after injury. A large number of preclinical studies supports the use of recombinant human erythropoietin (rHuEPO) to prevent AKI, but the clinical trial data are inconclusive. To address concerns about preclinical study design and reporting in AKI, we here presented our rigorous experiments on the use of rHuEPO in a mouse model simulating the most common post-ischemic AKI in patients., Methods: Use of saline vehicle or rHuEPO (100 or 1000 U/KgBW) in mice subjected to AKI induced by ischemia-reperfusion injury of left kidney 2 weeks after right nephrectomy (NX + IRI)., Results: NX + IRI resulted in a reproducible AKI model. Use of rHuEPO as a pretreatment or posttreatment did not affect AKI severity, functional recovery, and mouse survival regardless of gender, injury severity, or doses of rHuEPO. Administering rHuEPO with 1000 U/KgBW did increase hematocrit and modulate AKI kidney macrophages by Nos2 downregulation and Ccl17 upregulation. Active expression of erythropoietin receptor (EPOR) was not identified in renal cells by lineage tracing study, whereas expression of colony-stimulating factor 2 receptor β (CSF2Rβ) was identified in kidney macrophages and upregulated after AKI. Both EPOR and CSF2Rβ were identified in cultured bone marrow derived macrophages, possibly mediated the robust inhibition of cytokine-induced phenotype switching by rHuEPO., Conclusion: Use of rHuEPO can modulate macrophage function but not the post-ischemic AKI severity, functional recovery and survival in mice., (Copyright © 2018 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Anemia is a common complication and contributes to increased morbidity and mortality in chronic kidney disease (CKD) patients. Whereas there has been a significant improvement of understanding the underlying mechanism of erythropoiesis, the treatment of renal anemia is still restricted to erythropoietin (EPO)-stimulating agents. The purpose of this article is to review the physiology of erythropoiesis, functional role of EPO and underlying molecular and cellular basis that regulate EPO production. Regulation of EPO production is at mRNA level. When anemia or hypoxia occurs, transcriptional factor, hypoxia-inducible factor (HIF), binds to EPO 5' hypoxic response element and EPO gene transcription increases. The renal EPO is mainly produced by pericytes. In CKD, pericytes transdifferentiate to myofibroblasts, and subsequently the ability of EPO production decreases, leading to renal anemia. Recent experimental and clinical studies show the promising efficacy of prolyl hydroxylase inhibitors in renal anemia through increasing EPO production by stabilizing HIF. Recent advances on epigenetics create a new field to study EPO gene expression at chromatin level. We will discuss the role of demethylating agent on restoring EPO expression, providing a novel approach to the treatment of renal anemia., (Copyright © 2018. Published by Elsevier B.V.)

Kidney disease is an escalating burden all over the world. In addition to preventing kidney injury, regenerating damaged renal tissue is as important as to retard the progression of chronic kidney disease to end stage renal disease. Although the kidney is a delicate organ and has only limited regenerative capacity compared to the other organs, an increasing understanding of renal development and renal reprogramming has kindled the prospects of regenerative options for kidney disease. Here, we will review the advances in the kidney regeneration including the manipulation of renal tubular cells, fibroblasts, endothelial cells, and macrophages in renal disease. Several types of stem cells, such as bone marrow-derived cells, adipocyte-derived mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells are also applied for renal regeneration. Endogenous or lineage reprogrammed renal progenitor cells represent an attractive possibility for differentiation into multiple renal cell types. Angiogenesis can ameliorate hypoxia and renal fibrosis. Based on these studies and knowledge, we hope to innovate more reliable pharmacological or biotechnical methods for kidney regeneration medicine., (Copyright © 2014. Published by Elsevier B.V.)

Renal fibrosis is a disease affecting millions worldwide and is a harbinger of progressive renal failure. Understanding the mechanisms of renal fibrosis is important for discovering new therapies that are required to prevent loss of renal function. Recently, we identified pericytes that line the kidney microvasculature as the precursor cells of the scar-producing myofibroblasts during kidney injury. Kidney pericytes are extensively branched cells embedded within the capillary basement membrane and stabilize the capillary network through tissue inhibitor of metalloproteinase 3 and angiogenic growth factors. Pericytes detach from endothelial cells and migrate into the interstitial space where they undergo a transition into myofibroblasts after injury. Activation of endothelium, pericyte-myofibroblast transition, and recruitment of inflammatory macrophages lead to capillary rarefaction and fibrosis. Targeting endothelium-pericyte crosstalk by inhibiting vascular endothelial cell growth factor receptors and platelet-derived growth factor receptors in response to injury have been identified as new therapeutic interventions. Furthermore, targeting macrophage activation has also been proven as a novel and safe therapeutic approach for pericyte-myofibroblast transition. However, we are still far from understanding the interaction between pericytes and other cellular elements in normal physiology and during kidney fibrosis. Further studies will be required to translate into more specific therapeutic approaches., (Copyright © 2012. Published by Elsevier B.V.)

Background/purpose: Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients., Methods: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level., Results: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013)., Conclusion: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism., (Copyright © 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

Background/purpose: Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians., Methods: This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients., Results: Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055)., Conclusion: This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

Postpartum hemolytic uremic syndrome (HUS) is an unusual complication that presents with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure after delivery. In this report, we describe a 32-year-old patient (gravida 3, para 1, artificial abortion 1) who developed postpartum HUS following abruptio placenta. After cesarean delivery due to abruptio placenta, the patient developed acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia followed by hypertension. Plasma exchange led to recovery from thrombocytopenia and improvement in renal function. This case highlights the importance of observation of peripheral blood smears in patients with abruptio placenta who develop thrombocytopenia after delivery.

A rare case of thrombotic microangiopathy in a patient with hemophagocytic syndrome is reported. An 18-year-old girl was admitted following prolonged fever, watery diarrhea, abdominal discomfort, and a 2-week history of rhinorrhea, cough, and painful cervical lymph nodes. Anemia, thrombocytopenia, jaundice, hepatomegaly, and mild azotemia developed within 2 weeks of admission. The diagnosis of a reactive hemophagocytic syndrome, probably secondary to infection, was made based on the findings of bone marrow examination. Extensive investigation failed to identify a causative agent. The disease initially responded rapidly to intravenous steroids and high-dose immunoglobulin therapy but relapsed soon after tapering of the steroids. Although her condition improved again on resumption of treatment with high-dose steroids, nephrotic range proteinuria and microscopic hematuria developed after the steroids were tapered. Fragmented erythrocytes were seen in peripheral blood with elevated serum lactate dehydrogenase and decreased serum haptoglobin concentrations. The results of subsequent renal pathology examination were also compatible with thrombotic microangiopathy. The disease course finally stabilized after a course of pulse methylprednisolone therapy. Immune hyperactivity, particularly hypercytokinemia and monocyte hyperactivity, could have accounted for the development of thrombotic microangiopathy in this case. Only strong immunosuppressive therapy can control such disease activity.