RESUMO
The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN.
Assuntos
Albuminúria , Claudina-1 , Nefropatias Diabéticas , Epigênese Genética , NAD , Sirtuína 1 , Inibidor Tecidual de Metaloproteinase-1 , Animais , Humanos , Albuminúria/genética , Claudina-1/genética , Claudina-1/metabolismo , Citocinas/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Fibrose , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NAD/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Nicotinamida Fosforribosiltransferase/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Podócitos/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/genética , Sirtuínas/genética , Sirtuínas/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genéticaRESUMO
BACKGROUND: IVC diameter on expiration (IVCdexp) is measured by echocardiography routinely. It is used to estimate volume status and designated as a definitive marker for determining dry weight (DW) in patients undergoing hemodialysis (HD). METHODS: A cross-sectional study. Outpatients (n = 107), and inpatients (n = 35) undergoing HD were enrolled. IVCdexp was measured on non-dialysis days in outpatients and dialysis days before and after the dialysis session in inpatients. In outpatients, the relationship of IVCdexp with echocardiography findings and clinical characteristics was analyzed. IVCdexp was compared with the other DW markers as a predictive factor for intradialytic hypotension. In inpatients, IVCdexp was analyzed by dividing inpatients with or without fluid in extravascular space. RESULTS: IVCdexp ranged from 5.4 to 16.9 mm in outpatients who had optimal DW. IVCdexp could reflect on volume status, but not predictive for intradialytic hypotension and not suggestive of fluid in extravascular space. CONCLUSIONS: IVCdexp was a rough marker to estimate volume status and only useful in suggesting apparent hypervolemia or hypovolemia. We should know that the IVCdexp value is affected by a lotof factors and not a definitive marker for estimating practical DW. J. Med. Invest. 66 : 172-177, February, 2019.
Assuntos
Veia Cava Inferior/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Veia Cava Inferior/diagnóstico por imagemRESUMO
Thromboembolism is a major complication of nephrotic syndrome, with the renal vein being the most frequent site. However, the incidence of portal vein thrombosis (PVT) in patients with nephrotic syndrome is rare. We report a case of a relapsed steroid-dependent minimal change disease with incidental PVT. A 38-year-old man presented with anasarca. Elevated liver enzymes were discovered during routine blood testing within days after commencing treatment. Although drug-induced liver injuries are frequently observed with mild aminotransferase abnormality during therapy with steroid or immune-suppressive agents, imaging revealed a massive thrombus of the portal vein, which was treated by anticoagulant therapy with edoxaban. Treatment with anticoagulant therapy could normalize liver function. Two months after the initiation of treatment with edoxaban, the follow-up CT scan and ultrasound showed the disappearance of PVT. Our case suggests that much attention should be paid to PVT as a cause of liver enzyme elevation when treating patients with nephrotic syndrome.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Síndrome Nefrótica/complicações , Veia Porta/patologia , Trombose Venosa/tratamento farmacológico , Administração Oral , Adulto , Anticoagulantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Inibidores do Fator Xa/uso terapêutico , Humanos , Masculino , Piridinas/uso terapêutico , Tiazóis/uso terapêutico , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagemRESUMO
Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection. The standard therapy of a chronic HCV infection is IFN monotherapy or IFN combined with ribavirin; however, after the introduction of direct-acting antivirals (DAAs), the standard therapy for patients with HCV genotype 1 has dramatically changed. We report a case of HCV-associated cryoglobulinemic membranoproliferative glomerulonephritis (MPGN) successfully treated by daclatasvir and asunaprevir, which are IFN-free DAAs for HCV, in combination with angiotensin II receptor blocker without immunosuppressive therapy. The patient developed severe nephrotic syndrome with progressive kidney dysfunction. Blood examination revealed a high copy number of HCV-RNA (6.4 log IU/mL, type 1), cryoglobulinemia, paraproteinemia of IgM-κ, and hypocomplementemia. Histological analysis showed MPGN type 1. These findings were compatible with those observed in HCV-associated cryoglobulinemic MPGN. This case offers original evidence for the application of newer generation of IFN-free DAAs in the treatment of HCV-associated cryoglobulinemic nephropathy.
RESUMO
For the first time, a 15-year-old boy was found to have a slight degree of proteinuria and microscopic hematuria during annual school urinalysis screening. His kidney function had already severely deteriorated. A kidney biopsy revealed tubulointerstitial nephritis (TIN) with diffuse inflammatory cell infiltration. His medical records showed his serum creatinine level to be 0.98 mg/dL two years ago, which was abnormally high considering his age. Although the etiology of slowly progressive TIN was unclear, glucocorticoid and immunosuppressant therapy improved his kidney function. This case report suggests that all doctors should recognize the reference range for the serum creatinine level in teenagers.
Assuntos
Creatinina/sangue , Nefrite Intersticial/diagnóstico , Adolescente , Envelhecimento/sangue , Biomarcadores/sangue , Biópsia , Progressão da Doença , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Hematúria/etiologia , Humanos , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Nefrite Intersticial/complicações , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Proteinúria/etiologia , Valores de Referência , UrináliseRESUMO
BACKGROUND: Serum albumin concentration (SAC) is a prognostic factor that is affected by many factors such as postural change, liver function and food intake. Chronic kidney disease (CKD) patients excrete proteinuria, have low-protein diet, and receive glucocorticoid therapy. No one has evaluated the most influential factors on SAC in CKD patients. METHODS: A retrospective study. Hospitalized CKD patients with less than 1 g/gCreatinine proteinuria receiving glucocorticoid therapy (n=28), with 1 or more g/gCreatinine proteinuria not receiving glucocorticoid therapy (n=36), and with 1 or more g/gCreatinine proteinuria receiving glucocorticoid therapy (n=39) were enrolled. SAC, hemoglobin, proteinuria and blood pressure at the last outpatient check-up before hospitalization, on the second day of hospitalization, at the last laboratory examination before discharge, as well as at the first outpatient follow-up after discharge were analyzed. RESULTS: SAC decreased on the second day of hospitalization and increased at the first outpatient follow-up significantly in all groups. Unexpectedly, the change of SAC was irrelevant to the amount of proteinuria. CONCLUSIONS: SAC was affected by not only proteinuria, but also postural change, physical activity, and food in CKD patients. SAC should be analyzed by standardizing a patient's condition during phlebotomy. J. Med. Invest. 64: 146-152, February, 2017.