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Introduction Dotinurad is being developed as a selective uric acid reabsorption inhibitor. However, its effect on lowering serum uric acid (UA) levels in chronic kidney disease (CKD) patients with severe renal dysfunction is unknown. Therefore, the purpose of this study was to determine the effect of dotinurad on renal function in CKD patients with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73 m2. Methods Seven patients with CKD who received dotinurad 0.5 mg to 4 mg per day were studied retrospectively. Changes in UA, eGFR, and urine protein-to-creatinine ratio (UPCR) were analyzed. The observation period was 10.9±2.1 months. Results Serum UA levels were decreased and maintained with dotinurad administration. Nevertheless, there were no improvements noted in renal function. Additionally, no serious adverse effects were identified in any of the patients throughout the observation period. Conclusion Although the sample size in this study was small, our findings demonstrate the efficacy of dotinurad in individuals with advanced CKD who have an eGFR lower than 25 mL/min/1.73 m2.
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OBJECTIVE: Tirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight-loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported. METHODS: Nine patients with CKD undergoing HD received weekly tirzepatide doses (2.5-7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years. RESULTS: Tirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (-1.0 kg, p = 0.024) and body mass index (-0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (- 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (-1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period. CONCLUSION: Tirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.
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Diabetes Mellitus Tipo 2, Controle Glicêmico, Diálise Renal, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Pessoa de Meia-Idade, Masculino, Feminino, Estudos Retrospectivos, Controle Glicêmico/métodos, Adulto, Idoso, Composição Corporal, Insuficiência Renal Crônica/terapia, Insuficiência Renal Crônica/complicações, Glicemia/metabolismo, Estudos Longitudinais, Hipoglicemiantes/administração & dosagemRESUMO
BACKGROUND/AIM: Sacubitril/valsartan (SV), a novel pharmacological class of angiotensin receptor neprilysin inhibitors, is effective in treating heart failure (HF) by inhibiting the degradation of natriuretic peptides and the renin-angiotensin-aldosterone system. However, no studies have observed the long-term effects of SV on patients with HF and preserved left ventricular ejection fraction (LVEF) undergoing hemodialysis (HD) over a long period. PATIENTS AND METHODS: This single-center retrospective study of 21 months duration involved consecutive patients with HF and preserved LVEF undergoing HD, who received 50-200 mg/day. All patients were followed up regularly, and clinical, biochemical, and echocardiographic parameters were recorded at baseline and during follow-up. The efficacy and safety of SV were also analyzed. RESULTS: This longitudinal study included nine patients, with a median age of 76 years. The median HD duration was 7 years. At baseline, the mean brain natriuretic peptide (BNP) was 133±73.6 pg/ml and that of LVEF was 66%±9%. After SV therapy, the systolic blood pressure, diastolic blood pressure, and heart rate decreased, albeit without statistical significance. BNP levels, LVEF, left atrial anteroposterior dimension, and left ventricular mass index did not change, compared to baseline values. No adverse effects were observed in any of the patients. CONCLUSION: SV tended to decrease blood pressure and heart rate in patients with HF and preserved LVEF undergoing HD but did not alter cardiac function assessments, such as BNP or echocardiography.
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Aminobutiratos, Compostos de Bifenilo, Combinação de Medicamentos, Insuficiência Cardíaca, Diálise Renal, Volume Sistólico, Valsartana, Humanos, Valsartana/uso terapêutico, Masculino, Feminino, Compostos de Bifenilo/uso terapêutico, Idoso, Insuficiência Cardíaca/fisiopatologia, Insuficiência Cardíaca/tratamento farmacológico, Insuficiência Cardíaca/terapia, Aminobutiratos/uso terapêutico, Volume Sistólico/efeitos dos fármacos, Antagonistas de Receptores de Angiotensina/uso terapêutico, Idoso de 80 Anos ou mais, Função Ventricular Esquerda/efeitos dos fármacos, Pessoa de Meia-Idade, Resultado do Tratamento, Estudos Retrospectivos, Tetrazóis/uso terapêutico, EcocardiografiaRESUMO
BACKGROUND: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. METHODS: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. RESULTS: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups. CONCLUSION: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146).
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BACKGROUND/AIM: In the SUSTAIN-6 trial, semaglutide reduced the risk of worsening nephropathy in patients with type 2 diabetes. The objective of this retrospective study was to elucidate the effect and safety of oral semaglutide (Rybelsus®) in patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: Six patients with DKD received 3 mg/day semaglutide orally. The observation period was 9.0±5.0 months. Changes in estimated glomerular filtration rate (eGFR), urinary protein, fasting blood glucose, and hemoglobin A1c were studied from 6 months before the administration of oral semaglutide until 6 months after administration. RESULTS: The change in eGFR over the 6 months prior to semaglutide administration was -1.2±1.6 ml/min/1.73 m2, showing a trend for a decrease; although not statistically significant, the change at 6 months after oral semaglutide initiation showed improved eGFR (1-50.7±1.8 ml/min/1.73 m2). Proteinuria was not reduced after treatment with oral semaglutide. No significant adverse effects (including retinopathy) were observed in any patient during the study. CONCLUSION: Despite the small sample size and short observation period, oral semaglutide was found to be a relatively well-tolerated drug for patients with DKD.
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Diabetes Mellitus Tipo 2, Nefropatias Diabéticas, Humanos, Nefropatias Diabéticas/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/tratamento farmacológico, Estudos Retrospectivos, Rim/metabolismoRESUMO
Immunoglobulin G4 (IgG4)-related disease is a systemic inflammatory disorder characterized by tubulointerstitial nephritis with IgG4-positive plasma cell infiltration. We report the case of an 84-year-old male who presented with a history of dyspnea on exertion and cough. The lymph nodes were palpated in the axilla. Urinalysis revealed mild proteinuria and increased levels of NAG and ß2-microglobulin. Blood tests showed hyperglobulinemia with a marked elevation of serum IgG4 levels. Chest computed tomography showed bilateral ground-glass and reticular opacities in the lower and peripheral portions of the lungs. Ga-67 scintigraphy showed kidney uptake. The patient was diagnosed with IgG4-related kidney disease based on the renal pathology indicative of typical tubulointerstitial nephritis with extensive IgG4-positive plasma cell infiltration. The patient was treated with prednisolone and showed a prompt response in his clinical condition. The patient achieved normalization of serum IgG4 levels 6 months after the initiation of treatment. Although IgG4-related disease is thought to be potentially associated with organ fibrosis, there are few reports on combination of interstitial pneumonia and IgG4-related kidney disease. Our case report presents a possible pattern of IgG4-related disease.
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Background: In the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease trial, finerenone reduced the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes, while in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial, it improved renal and cardiovascular outcomes in patients with advanced CKD. However, no previous studies have assessed patients with CKD and type 2 diabetes with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73 m2. Methods: Nine patients with CKD and type 2 diabetes who received finerenone 10 mg/day were analyzed retrospectively. Changes in eGFR, urinary protein, and serum potassium levels were studied from 1 year before administration of finerenone until 6 months after administration. Results: The mean baseline eGFR slope was -7.63 ± 9.84 (mL/min/1.73 m2/year). After finerenone treatment, the mean eGFR slope significantly improved -1.44 ± 3.17 (mL/min/1.73 m2/6 months, P=0.038). However, finerenone treatment did not significantly reduce proteinuria. Furthermore, finerenone did not increase serum potassium levels. Conclusions: Patients treated with finerenone showed a significantly slower decline in eGFR. Furthermore, aside from the present study, no reports have indicated the effectiveness of finerenone in patients with advanced CKD with an eGFR below 25 mL/min/1.73 m2. As confirmed in our clinical trials, the finding that finerenone is effective in a wide range of renal functions can be generalized to clinical practice. However, sample size in this study was small. Thus, further large-scale investigations will be needed.
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Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease (CKD), leading end-stage renal disease. Thus, DKD is one of the most important diabetic complications. Incretin-based therapeutic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonizts and dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to elicit vasotropic actions, suggesting a potential for effecting reduction in DKD. Glucose-dependent insulinotropic polypeptide (GIP) is also classified as an incretin. However, the insulin action after GIP secretion is known to be drastically reduced in patients with type 2 diabetes. Therefore, GIP has been formally considered unsuitable as a treatment for type 2 diabetes in the past. This concept is changing as it has been reported that resistance to GIP can be reversed and its effect restored with improved glycemic control. The development of novel dual- or triple- receptor agonizts that can bind to the receptors, not only for GLP-1 but also to GIP and glucagon receptors, is intended to simultaneously address several metabolic pathways including protein, lipid, and carbohydrate metabolism. These led to the development of GIP receptor agonist-based drugs for type 2 diabetes. The possibility of combined GIP/GLP-1 receptor agonist was also explored. The novel dual GIP and GLP-1 receptor agonist tirzepatide has recently been launched (Mounjaro®, Lilly). We have revealed precise mechanisms of the renoprotective effect of GLP-1 receptor agonizts or DPP-4 inhibitors, while the long-term effect of tirzepatide will need to be determined and its potential effects on kidneys should be properly tested.
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Diabetes Mellitus Tipo 2, Nefropatias Diabéticas, Inibidores da Dipeptidil Peptidase IV, Humanos, Incretinas/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/metabolismo, Nefropatias Diabéticas/tratamento farmacológico, Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico, Polipeptídeo Inibidor Gástrico/uso terapêutico, Peptídeo 1 Semelhante ao Glucagon/farmacologia, Inibidores da Dipeptidil Peptidase IV/farmacologia, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Glicemia/metabolismo, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêuticoRESUMO
Background: Immunoglobin A nephropathy (IgAN) is one of the most common forms of chronic glomerulonephritis and has been shown to occur in association with vaccinations. While various vaccines against COVID-19 have become widely used, their side effects, especially on IgAN following COVID-19 vaccines are still unclear. In this report, we describe the clinical courses and histopathologic findings of a newly diagnosed case of IgAN after receiving the mRNA-1273 (Moderna) COVID-19 vaccination. Methods: This study presents a case of new-onset IgAN following mRNA-1273 COVID-19 (Moderna) vaccination. In addition, we review and analyze similar cases previously reported in the literature up to October 2022. Results: Of the 52 cases reviewed, including our own, the majority of patients were female, and 64% of patients had initial onset IgAN. The most common manifestation was gross hematuria (87%), other associated symptoms were fever (44%), myalgia (8%), arthralgia (4%), and edema (4%). Many of these cases occurred after receiving Pfizer products as the second vaccination. Oral corticosteroids were used to 16 cases, and steroid pulse therapy was used to treat 7 cases. Conclusion: While this is not a controlled study, it is important for physicians to consider the possibility that COVID-19 vaccines may provoke a flare of IgAN. Several therapeutic agents may be useful for treating COVID-19 vaccine-induced IgAN, although a specific mechanism or pathophysiological association cannot be confirmed without further research.
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BACKGROUND/AIM: Imeglimin is a novel small molecular tetrahydrotriazine that has been shown to improve hyperglycemia in clinical trials among patients with type 2 diabetes. Nevertheless, its pharmacokinetics in patients with renal dysfunction remain unclear. The objective of this study was to elucidate the safety and effects of imeglimin in patients with type 2 diabetes undergoing dialysis. PATIENTS AND METHODS: Six patients with type 2 diabetes undergoing hemodialysis (HD) or peritoneal dialysis (PD) received imeglimin 500 mg/day. The observation period was 3.3±2.3 months. RESULTS: Fasting blood glucose was significantly decreased, compared to baseline after imeglimin treatment (126.2±32.0 mg/dl, p=0.037, vs. baseline). Furthermore, levels of alanine aminotransferase were decreased (10.3±6.3 IU/l, p=0.006, vs. baseline). Glycated hemoglobin A1c and triglyceride tended to be decreased, albeit without statistical significance. Levels of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and aspartate aminotransferase were not changed compared to baseline values. CONCLUSION: Despite the small sample size, imeglimin was found to be an effective and relatively well-tolerated agent for the treatment of patients with type 2 diabetes undergoing both HD and PD. During the observation period, adverse events such as hypoglycemia, diarrhea, nausea, or vomiting were not recognized in any patient.
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Diabetes Mellitus Tipo 2, Falência Renal Crônica, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diálise Renal/efeitos adversos, Triazinas/efeitos adversos, Hemoglobinas Glicadas, Falência Renal Crônica/tratamento farmacológicoRESUMO
Background: In rodents, glomerular expression of insulin receptor substrate 1 (IRS1) is decreased in diabetic kidney disease (DKD) and reduced associated functioning is involved in the development and progression of DKD. This study aimed to evaluate the significance of glomerular IRS1 expression in DKD patients, and investigated whether glomerular IRS1 expression can reflect renal pathology and predict renal outcomes. Methods: This study included 10 patients who underwent renal biopsy and were diagnosed with DKD or minor glomerular abnormality (MGA). IRS1-positive cells were determined based on renal biopsy and immunostaining, and the associations of the number of these cells with baseline and prognostic parameters were analyzed. Results: IRS1-positive cells were significantly decreased in DKD than in MGA. IRS1 positivity tended to be negatively correlated with global glomerulosclerosis and tubulointerstitial fibrosis. The rate of change in estimated glomerular filtration rate before and 12 months after renal biopsy was positively correlated to the number of IRS1-positive cells. Furthermore, a tendency towards negative correlation was observed between the number of glomerular IRS1-positive cells and the proteinuria. Conclusions: This study shows the glomerular IRS1-positive cell count was significantly decreased in DKD, and that the degree IRS1 positivity was partially correlated with renal pathology and function.
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BACKGROUND/AIM: Renal anemia is a major complication in patients with chronic kidney disease (CKD), leading to morbidity and mortality. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHI), also called HIF stabilizers, increase endogenous erythropoietin production and are expected to be novel orally administrated agents for renal anemia in CKD. Enarodustat is being developed as an oral HIF-PHI. It was recently approved in Japan and clinical development is ongoing in the USA and South Korea. Therefore, there are only a few real-world data regarding treatment of renal anemia using enarodustat. This study evaluated the efficacy of enarodustat in patients with non-dialysis CKD. PATIENTS AND METHODS: Nine patients (78±11 years old, male=6, female=3) were enrolled in this study. Patients received enarodustat as first-line therapy or changed from erythropoiesis stimulating agents (2-6 mg). The observation period was 4.8±2.0 months. RESULTS: Levels of hemoglobin were effectively increased and maintained with enarodustat administration. C-reactive protein and serum ferritin were significantly decreased, but no change in renal function was observed. Furthermore, no serious adverse effects were recognized in all patients during the study. CONCLUSION: Enarodustat is an effective and relatively well-tolerated agent for the treatment of renal anemia in patients with non-dialysis CKD.
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Anemia, Insuficiência Renal Crônica, Humanos, Feminino, Masculino, Idoso, Idoso de 80 Anos ou mais, Doença Crônica, Insuficiência Renal Crônica/complicações, Insuficiência Renal Crônica/tratamento farmacológico, Piridinas, Anemia/tratamento farmacológico, Anemia/etiologiaRESUMO
Background: This meta-analysis was conducted to investigate the effects of incretin-based therapeutic agents, including the latest agent tirzepatide, on renal outcomes in patients with type 2 diabetes. Methods: MEDLINE (via PubMed) and Cochrane databases were searched for studies involving incretin-based therapeutic agents up to July 2022. Randomized and controlled trials comparing incretin-based therapeutic agents with placebo or other antidiabetic agents, and reporting renal outcomes were selected. The inclusion criteria were items related to the effects on albuminuria and the kidney-specific composite outcomes. A network meta-analysis was conducted to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Twelve trials consisting of 75,346 participants were included in this meta-analysis. Glucagon-like peptide-1 (GLP-1) receptor agonists reduced the risk of the kidney-specific composite outcome by 21% (HR 0.79, 95% CI 0.75-0.85), and worsening albuminuria by 24% (HR 0.76, 95% CI 0.71-0.82). In particular, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide remarkably reduced the risk of the kidney-specific composite outcome by 45% (HR 0.55, 95% CI 0.40-0.77), and worsening albuminuria by 62% (HR 0.38, 95% CI 0.24-0.61). Conclusions: Among incretin-based therapeutic agents, tirzepatide was associated with a significantly reduced risk of diabetic kidney disease.
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BACKGROUND/AIM: To date, no reports of interleukin (IL)-5-producing Castleman disease with nephrotic syndrome and moreover no reports of relapse after remission with rituximab treatment, have been published. CASE REPORT: A 67-year-old male presented to the Osaka Medical and Pharmaceutical University Hospital with a history of low-grade fever, papules, and nephrotic syndrome. Lymph nodes were palpated in the inguinal region. The patient showed anemia, eosinophilia, polyclonal hypergammaglobulinemia, and elevated interleukin (IL)-6 levels. Patient's serum IL-5 and IL-6 levels were measured using ELISA and immunohistochemical staining of lymph nodes was performed with antibodies specific to CD134. Histological examination confirmed diagnosis of a plasma cell variant of Castleman disease. After a total of four weekly doses of rituximab, urinary protein disappeared, and skin symptoms improved. However, one month after rituximab treatment, the skin rash worsened again, and eosinophils and IL-5 were elevated significantly. CONCLUSION: This is the first report of recurrent Castleman disease with direct evidence of increased serum IL-5. It may be reasonable to use rituximab, an anti-CD20 antibody for treating the disease, however, for IL-5-producing cases the effect of rituximab may be partial.
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Hiperplasia do Linfonodo Gigante, Síndrome Nefrótica, Masculino, Humanos, Idoso, Hiperplasia do Linfonodo Gigante/complicações, Hiperplasia do Linfonodo Gigante/diagnóstico, Hiperplasia do Linfonodo Gigante/tratamento farmacológico, Rituximab/uso terapêutico, Síndrome Nefrótica/diagnóstico, Síndrome Nefrótica/tratamento farmacológico, Síndrome Nefrótica/etiologia, Interleucina-5/uso terapêutico, AnticorposRESUMO
INTRODUCTION: Daily burden of patients with chronic kidney disease (CKD) who have not received maintenance dialysis or renal transplantation has not been well reported compared with patients receiving dialysis. We conducted a patient survey and an advisory board in Japan to investigate the experience and perception of CKD and its treatments from the patient's perspective. METHODS: An anonymous web survey (n = 342) was conducted in October and November 2020. Participants, who were recruited through multiple panels, aged 20 years or older, diagnosed with any stage of CKD, and who had neither received nor planned maintenance dialysis or renal transplantation were included. A questionnaire prepared under the medical advisor's guidance was used to collect the background information, burden of disease and treatments, and needs and expectations for future treatments. An advisory board with five patients nominated from a patient group was conducted in December 2020. Additional insights to interpret the results of the preceding survey were collected using pre-identified discussion topics. RESULTS: Establishing a diagnosis of CKD generally took a long time; approximately 20% of the patients waited more than 5 years before diagnosis. In daily life, patients were burdened with CKD-related symptoms (e.g., tinnitus, leg cramps) and behavioral restrictions, including diet. They also felt psychological burdens, such as concerns about possible future dialysis and/or renal transplantation, lack of awareness and understanding of disease among the other people in their lives, and financial burdens related to medical expenses. Furthermore, they felt a lack of communication in daily interactions with health care professionals and others around them, and they desired interaction with patients with CKD. CONCLUSION: Understanding the burdens and the thoughts of patients with CKD could inform discussions about the ways to improve communication with patients in daily practice, the role of the patient community, and new therapeutic options to address patients' expectations. TRIAL REGISTRATION: UMIN000042300.
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Transplante de Rim, Insuficiência Renal Crônica, Humanos, Diálise Renal, Insuficiência Renal Crônica/complicações, Insuficiência Renal Crônica/terapia, ComunicaçãoRESUMO
The number of patients with diabetic kidney disease (DKD) has been rising significantly over the last several decades and is one of the most frequent causes of chronic kidney disease (CKD) in the United States. Hyperglycemia accelerates development of DKD, a direct result of increased intracellular glucose availability. Two large clinical studies, the Diabetes Control and Complications Trial in type 1 diabetes and the United Kingdom Prospective Diabetes Study in type 2 diabetes showed that intensive glycemic control delayed the onset and the progression of DKD. On the other hand, it is reported that glycemic control alone is not sufficient to control DKD progression. Recent data support that insulin signaling and its associated signaling contribute significantly to preserve glomerular function. However, little is known about the key regulators of insulin signaling in glomerular component cells. In this review, we summarize the novel knowledge regarding the reno-protective effects of insulin signaling or its associated signaling in glomerular constituent cells on DKD.
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Diabetes Mellitus Tipo 2, Nefropatias Diabéticas, Humanos, Insulina, Estudos Prospectivos, Glomérulos RenaisRESUMO
Cell therapies using human induced pluripotent stem cell (hiPSC)-derived nephron progenitor cells (NPCs) are expected to ameliorate acute kidney injury (AKI). However, using hiPSC-derived NPCs clinically is a challenge because hiPSCs themselves are tumorigenic. LIN28A, ESRG, CNMD and SFRP2 transcripts have been used as a marker of residual hiPSCs for a variety of cell types undergoing clinical trials. In this study, by reanalyzing public databases, we found a baseline expression of LIN28A, ESRG, CNMD and SFRP2 in hiPSC-derived NPCs and several other cell types, suggesting LIN28A, ESRG, CNMD and SFRP2 are not always reliable markers for iPSC detection. As an alternative, we discovered a lncRNA marker gene, MIR302CHG, among many known and unknown iPSC markers, as highly differentially expressed between hiPSCs and NPCs, by RNA sequencing and quantitative RT-PCR (qRT-PCR) analyses. Using MIR302CHG as an hiPSC marker, we constructed two assay methods, a combination of magnetic bead-based enrichment and qRT-PCR and digital droplet PCR alone, to detect a small number of residual hiPSCs in NPC populations. The use of these in vitro assays could contribute to patient safety in treatments using hiPSC-derived cells.
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Células-Tronco Pluripotentes Induzidas, Neuroblastoma, RNA Longo não Codificante, Humanos, Células-Tronco Pluripotentes Induzidas/metabolismo, Diferenciação Celular/genética, Técnicas In Vitro, Néfrons, RNA Longo não Codificante/metabolismo, Neuroblastoma/metabolismoRESUMO
Non-alcoholic fatty liver disease is the most common chronic liver disease and is associated with chronic kidney disease. The fibrosis-4 index and non-alcoholic fatty liver disease score are widely used as non-invasive diagnostic methods for non-alcoholic fatty liver disease. However, the relationship between these markers and specific renal histopathologies in chronic kidney disease remain unclear. This study included 179 patients aged between 16 and 80 years who underwent renal biopsy. We examined the association between the fibrosis-4 index or non-alcoholic fatty liver disease score and change in estimated glomerular filtration rate 12 months after kidney biopsy for each renal histopathology. Renal histopathologies were determined by renal biopsy. Our results showed that there was a significant negative correlation between the fibrosis-4 index and estimated glomerular filtration rate. In nephrosclerosis, the non-alcoholic fatty liver disease score and estimated glomerular filtration rate tended to have a negative correlation, albeit without significance. In IgA nephropathy, both the fibrosis-4 index and non-alcoholic fatty liver disease score were significantly negatively correlated with estimated glomerular filtration rate. Furthermore, the fibrosis-4 index was not associated with urinary protein-to-creatinine ratio or renal function markers such as urinary b2 microglobulin and urinary N-acetyl-D-glucosamine. Our kidney biopsy-based study showed that the liver fibrosis markers fibrosis-4 index and non-alcoholic fatty liver disease score were negatively correlated with the estimated glomerular filtration rate in nephrosclerosis and IgA nephropathy.
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Glomerulonefrite por IGA, Nefroesclerose, Hepatopatia Gordurosa não Alcoólica, Insuficiência Renal Crônica, Humanos, Adolescente, Adulto Jovem, Adulto, Pessoa de Meia-Idade, Idoso, Idoso de 80 Anos ou mais, Taxa de Filtração Glomerular, Nefroesclerose/patologia, Hepatopatia Gordurosa não Alcoólica/patologia, Glomerulonefrite por IGA/patologia, Creatinina, Acetilglucosamina, Fatores de Risco, Rim/patologia, Insuficiência Renal Crônica/patologia, Biópsia, Biomarcadores, Cirrose Hepática/patologia, FibroseRESUMO
BACKGROUND/AIM: Renal anemia is a major complication in patients with chronic kidney disease (CKD) and hemodialysis, increasing morbidity and mortality. Roxadustat is a novel oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (PHI), which is administrated for renal anemia. Different from erythropoiesis-stimulating agents (ESAs), Roxadustat could increase erythropoietin physiologically, improving the therapeutic effects. It has not been so long since Roxadustat was approved by the European Commission (EC). Thus, only a few studies have reported on the treatment of renal anemia using Roxadustat. PATIENTS AND METHODS: In this study, we evaluated the efficacy of Roxadustat in patients undergoing hemodialysis (HD). Nine patients under HD (72±10 years old) were enrolled in this study. Patients received Roxadustat first time or changed from ESAs (5-10 mg, 3 times a week after HD). Observation period was 5.3±2.9 months. RESULTS: Roxadustat treatment effectively increased and maintained hemoglobin levels. Levels of ferritin and C-reactive protein tended to decrease, but the difference was not statistically significant. No significant adverse effects were observed in all patients during the study. CONCLUSION: Roxadustat is effective and relatively tolerant for treating renal anemia in patients subjected to hemodialysis.
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Anemia, Hematínicos, Idoso, Idoso de 80 Anos ou mais, Anemia/tratamento farmacológico, Anemia/etiologia, Glicina/análogos & derivados, Hematínicos/efeitos adversos, Humanos, Hipóxia, Prolina Dioxigenases do Fator Induzível por Hipóxia/uso terapêutico, Isoquinolinas, Pessoa de Meia-Idade, Diálise Renal/efeitos adversosRESUMO
Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors; however, their efficacy was partial. Recently, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide 1, liraglutide (LEADER), and dipeptidyl peptidase 4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD "fantastic four".
