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1.
Transplant Proc ; 56(8): 1752-1756, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232925

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories. METHODS: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group. RESULTS: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036). CONCLUSIONS: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal , Sobrevivência de Enxerto , Falência Renal Crônica , Transplante de Rim , Recidiva , Humanos , Glomerulosclerose Segmentar e Focal/cirurgia , Glomerulosclerose Segmentar e Focal/etiologia , Transplante de Rim/efeitos adversos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Falência Renal Crônica/cirurgia , Falência Renal Crônica/etiologia , Resultado do Tratamento , Rejeição de Enxerto , Biópsia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38738277

RESUMO

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

3.
Sci Rep ; 14(1): 4002, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369626

RESUMO

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Transplantados , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Aloenxertos , Biópsia , Rim/patologia
4.
Mol Biol Rep ; 50(11): 8915-8923, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37704932

RESUMO

BACKGROUND: Sepsis is a major cause of acute kidney injury (AKI). Recent studies have demonstrated that ß-hydroxybutyrate (ß-HB) alleviates renal ischemia-reperfusion injury and cisplatin-induced renal injury in murine models. This study aimed to investigate whether ß-HB ameliorates sepsis-induced AKI (SIAKI) in a lipopolysaccharide (LPS)-induced mouse sepsis model. METHODS AND RESULTS: SIAKI was induced by intraperitoneally injecting LPS to C57BL/6 male mice. ß-HB was administrated intraperitoneally before LPS injection. The mice were divided into sham, ß-HB, LPS, and ß-HB + LPS groups. The histological damage score and serum creatinine level were significantly increased in the LPS group mice, but attenuated in the ß-HB + LPS group mice. The expression of phosphorylated nuclear factor-κB tumor necrosis factor-α/interleukin-6 and the number of F4/80-positive macrophages in the ß-HB + LPS group mice were lower than those in the LPS group mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells, cleaved caspase-3 expression, and Bax/Bcl-2 ratio in the ß-HB + LPS group mice were lower than those in the LPS group mice. CONCLUSION: ß-HB pre-treatment ameliorates SIAKI by reducing tubular apoptosis and inflammatory responses. Thus, ß-HB pre-treatment could be a potential prophylactic strategy against SIAKI.


Assuntos
Injúria Renal Aguda , Sepse , Masculino , Camundongos , Animais , Ácido 3-Hidroxibutírico/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/induzido quimicamente , Rim/metabolismo , Apoptose , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/metabolismo
5.
Exp Cell Res ; 424(2): 113509, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36773738

RESUMO

Maladaptive repair after acute kidney injury (AKI) can predispose patients to chronic kidney disease (CKD). However, the molecular mechanism underlying the AKI-to-CKD transition remains unclear. The Akt signaling pathway has been reported to be involved in the pathological processes of both AKI and CKD. In this study, we investigated the role of Akt1 in a murine model of the AKI-to-CKD transition. Wild-type (WT) and Akt1-/- mice were subjected to unilateral ischemia-reperfusion injury (UIRI), with their kidneys harvested after two days and two, four, and six weeks after UIRI. The dynamic changes in tubulointerstitial fibrosis, markers of tubular epithelial-mesenchymal transition (EMT), and tubular apoptosis were investigated. Akt1 of the three Akt isoforms was activated during the AKI-to-CKD transition. After UIRI, tubulointerstitial fibrosis and tubular EMT were significantly increased in WT mice, but were attenuated in Akt1-/- mice. The expression of the transforming growth factor (TGF)-ß1/Smad was increased in both WT and Akt1-/- mice, but was not different between the two groups. The levels of phosphorylated glycogen synthase kinase (GSK)-3ß, Snail, and ß-catenin in the Akt1-/- mice were lower than those in the WT mice. The number of apoptotic tubular cells and the expression of cleaved caspase-3/Bax were both lower in Akt1-/- mice than in WT mice. Genetic deletion of Akt1 was associated with attenuation of tubulointerstitial fibrosis, tubular EMT, and tubular apoptosis during the AKI-to-CKD transition. These findings were associated with TGF-ß1/Akt1/GSK-3ß/(Snail and ß-catenin) signaling independent of TGF-ß1/Smad signaling. Thus, Akt1 signaling could serve as a potential therapeutic target for inhibiting the AKI-to-CKD transition.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Modelos Animais de Doenças , Insuficiência Renal Crônica/metabolismo , Rim/metabolismo , Injúria Renal Aguda/metabolismo , Fibrose , Apoptose , Transição Epitelial-Mesenquimal
6.
PLoS One ; 17(12): e0279561, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36574383

RESUMO

Procalcitonin (PCT) is a biomarker for diagnosing infections and guiding antibiotic therapy. In this study, we investigated whether PCT can predict survival and recovery at 28 days in critically ill patients with sepsis-induced acute kidney injury (SIAKI) receiving continuous renal replacement therapy (CRRT). We examined 649 patients with SIAKI who underwent CRRT in our intensive care unit. In a multivariable Cox regression analysis, a single PCT level at CRRT initiation was not associated with survival in all patients. However, the higher % PCT decrease over 72 hours after CRRT initiation was independently associated with the higher chance of 28-day survival (per 10% decrease, hazard ratio [HR] for mortality: 0.87, 95% confidence interval [CI]: 0.85-0.89; P < 0.001). Among the survivors, the % PCT decrease over 72 hours after CRRT initiation, not a single PCT level at CRRT initiation, was independently associated with recovery from dialysis (per 10% decrease, HR for renal recovery: 1.28, 95% CI:1.21-1.36; P < 0.001). This study demonstrated that the higher % PCT decrease was independently associated with the higher chance of survival and recovery from dialysis at 28 days in critically ill patients with SIAKI receiving CRRT. Thus, a decrease in the PCT level, not a single PCT level at CRRT initiation, could be a valuable tool for predicting prognosis in these patients.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Sepse , Humanos , Diálise Renal , Pró-Calcitonina , Terapia de Substituição Renal , Estado Terminal , Sepse/complicações , Sepse/terapia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/complicações , Estudos Retrospectivos
7.
BMC Emerg Med ; 22(1): 138, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915412

RESUMO

BACKGROUND: During the COVID-19 pandemic, maintenance of essential healthcare systems became very challenging. We describe the triage system of our institute, and assess the quality of care provided to critically ill non-COVID-19 patients requiring continuous renal replacement therapy (CRRT) during the pandemic. METHODS: We introduced an emergency triage pathway early in the pandemic. We retrospectively reviewed the medical records of patients who received CRRT in our hospital from January 2016 to March 2021. We excluded end-stage kidney disease patients on maintenance dialysis. Patients were stratified as medical and surgical patients. The time from hospital arrival to intensive care unit (ICU) admission, the time from hospital arrival to intervention/operation, and the in-hospital mortality rate were compared before (January 2016 to December 2019) and during (January 2021 to March 2021) the pandemic. RESULTS: The mean number of critically ill patients who received CRRT annually in the surgical department significantly decreased during the pandemic in (2016-2019: 76.5 ± 3.1; 2020: 56; p < 0.010). Age, sex, and the severity of disease at admission did not change, whereas the proportions of medical patients with diabetes (before: 44.4%; after: 56.5; p < 0.005) and cancer (before: 19.4%; after: 32.3%; p < 0.001) increased during the pandemic. The time from hospital arrival to ICU admission and the time from hospital arrival to intervention/operation did not change. During the pandemic, 59.6% of surgical patients received interventions/operations within 6 hours of hospital arrival. In Cox's proportional hazard modeling, the hazard ratio associated with the pandemic was 1.002 (0.778-1.292) for medical patients and 1.178 (0.783-1.772) for surgical patients. CONCLUSION: Our triage system maintained the care required by critically ill non-COVID-19 patients undergoing CRRT at our institution.


Assuntos
Injúria Renal Aguda , COVID-19 , Terapia de Substituição Renal Contínua , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , COVID-19/epidemiologia , COVID-19/terapia , Cuidados Críticos , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Pandemias , Terapia de Substituição Renal , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 100(42): e27572, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34678898

RESUMO

RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal-dominant neurocutaneous disorder that affects the skin, bones, and nervous system. The most common manifestation of kidney involvement is renal artery stenosis; glomerulonephritis is extremely rare. In this case report, we present a patient with NF-1 and immunoglobulin A nephropathy (IgAN). PATIENT CONCERNS: A 51-year-old Korean man previously diagnosed with NF-1 presented with persistent proteinuria and hematuria identified during a routine medical check-up. He had no history of hypertension or diabetes, and denied a history of alcohol use or smoking. DIAGNOSIS: The contrast-enhanced computed tomography scan revealed normal-sized kidneys and no evidence of renal artery stenosis. On the day of the kidney biopsy, laboratory tests showed a serum creatinine level of 1.1 mg/dL, urine protein/creatinine ratio of 1.3 g/g, and urine red blood cell count of >10 to 15/HPF. The kidney biopsy sample revealed IgAN grade III, according to Lee glomerular grading system. INTERVENTION: The patient was advised to take 4 mg of perindopril. OUTCOME: Three months after the treatment, the urine protein/creatinine ratio decreased to 0.6 g/g, with no change in the serum creatinine level (1.03 mg/dL). LESSONS: A genetic link between NF-1 and IgAN or other glomerular diseases is not established. However, activation of the mTOR pathway may explain this association.


Assuntos
Glomerulonefrite por IGA/complicações , Neurofibromatose 1/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Perindopril/uso terapêutico
9.
Korean J Intern Med ; 36(4): 962-974, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33322851

RESUMO

BACKGROUND/AIMS: Acute kidney injury (AKI) is an underestimated yet important risk factor for the development of chronic kidney disease (CKD), characterized by tubulointerstitial fibrosis and tubular dedifferentiation. Tubular dedifferentiation, which is associated with the loss of epithelial markers and the gain of mesenchymal features, is thought to be involved in tubulointerstitial fibrosis. As protein kinase B/Akt is involved in the development of CKD, we investigated the role of Akt1, one of the three Akt isoforms, in a murine model of AKI-to-CKD progression. METHODS: We subjected C57BL/6 male mice to unilateral ischemia-reperfusion injury (UIRI) and harvested their kidneys after 6 weeks. Mice were divided into four groups, namely, wild-type (WT) UIRI, Akt1-/- UIRI, WT sham, and Akt1-/- sham. RESULTS: Akt1 (but not Akt2 or Akt3) was markedly activated in WT UIRI mice than in WT sham mice. Tubulointerstitial fibrosis and tubular dedifferentiation significantly increased in WT UIRI mice, but were attenuated in Akt1-/- UIRI mice. Both WT UIRI and Akt1-/- UIRI mice showed markedly upregulated transforming growth factor-ß1 (TGF-ß1)/Smad signaling compared with WT sham mice. However, TGF-ß1/Smad expression did not differ between the two groups. The levels of phosphorylated GSK-3ß, ß-catenin, and Snail were attenuated in Akt1-/- UIRI mice compared with those in WT UIRI mice. CONCLUSION: Deletion of Akt1 results in the attenuation of renal fibrosis and tubular dedifferentiation, independent of TGF-ß1/Smad signaling, during AKI-to-CKD progression in a UIRI without contralateral nephrectomy model. Thus, Akt1 may serve as a therapeutic target in AKI-to-CKD progression.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Injúria Renal Aguda/genética , Animais , Fibrose , Glicogênio Sintase Quinase 3 beta , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica/genética
10.
Biomed Res Int ; 2020: 6143542, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299873

RESUMO

We investigated the role of Akt1, one of the three isoforms of Akt, in renal fibrosis using the murine model of unilateral ureteral obstruction (UUO). We subjected wild type and Akt1 -/- mice to UUO. The Akt1 gene was silenced in vitro using short hairpin RNA delivered via a lentiviral vector in human proximal tubular cells (HK2 cells) and kidney fibroblasts (NRK-49F cells). The obstructive kidneys of Akt1 -/- mice showed more severe tubulointerstitial fibrosis than those of wild type mice. The expression of fibronectin and type I collagen was significantly increased in obstructed kidneys of Akt1 -/- mice compared to those of wild type mice. The important finding was that the expression of transforming growth factor ß1 (TGFß1) was significantly increased in the Akt1 -/- mice compared to the wild type mice. The knockdown of Akt1 enhanced the expression of TGFß1 in HK2 cells. Interestingly, the upregulation of TGFß1 due to genetic knockdown of Akt1 was associated with activation of signal transducer and activator of transcript 3 (STAT3) independently of the Smad pathway in NRK-49F and HK2 cells. Immunohistochemical staining also showed that expression of phosphorylated STAT3 was more increased in Akt1 -/- mice than in wild type mice after UUO. Additionally, the deletion of Akt1 led to apoptosis of the renal tubular cells in both in vivo and in vitro studies. Conclusively, these results suggest that the deletion of Akt1 may contribute to renal fibrosis via induction of the TGFß1/STAT3 pathway in a murine model of UUO.


Assuntos
Deleção de Genes , Rim/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Obstrução Ureteral/complicações , Obstrução Ureteral/enzimologia , Animais , Apoptose , Caspase 3/metabolismo , Modelos Animais de Doenças , Fibrose , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo
11.
Mol Biol Rep ; 47(12): 9511-9520, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33247386

RESUMO

Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). Although Akt is involved in renal IRI, it is unclear as to which Akt isoform plays an important role in renal IRI. In this study, we investigated the role of Akt1 in renal IRI. We subjected the C57BL/6 male mice to unilateral IRI with contralateral nephrectomy. Two days after IRI, IRI-kidneys were harvested. The mice were divided into four groups: wild type (WT) IRI, Akt1-/- IRI, WT sham, and Akt1-/- sham. We found that Akt1, not Akt2 or Akt3, was markedly activated in WT IRI than in WT sham mice. The histologic damage score and serum creatinine level significantly increased in WT IRI mice, the increase being the highest in Akt1-/- IRI mice. The number of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells and expression of cleaved caspase-3/Bax were higher in Akt1-/- IRI mice than in WT IRI mice. The expression of Bcl-2 was lower in Akt1-/- IRI mice than in WT IRI mice. The expression of tumor necrosis factor-α/interleukin-6/interleukin-1ß and number of F4/80-positive macrophages were markedly higher in Akt1-/- IRI than in WT IRI mice. The expression of phosphorylated nuclear factor-κB p65 was also higher in Akt1-/- IRI mice than in WT IRI mice. Our results show that Akt1 deletion exacerbates kidney damage as it increases tubular apoptosis and inflammatory response during renal IRI. Akt1 could be a potential therapeutic target for developing treatments against IRI-induced AKI.


Assuntos
Apoptose/genética , Regulação da Expressão Gênica , Túbulos Renais/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Traumatismo por Reperfusão/genética , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Túbulos Renais/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nefrectomia/métodos , Proteínas Proto-Oncogênicas c-akt/deficiência , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
12.
Anatol J Cardiol ; 21(3): 134-141, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30821713

RESUMO

OBJECTIVE: Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. Serum creatinine and estimated glomerular filtration rate have some limitations to predict the early stage of acute kidney injury (AKI). We investigated the changes of early inflammatory biomarkers in AKI following the RDN procedure. METHODS: Twenty-five female swine were divided into three groups: normal control (Normal, n=5), sham-operated (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into three subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. Renal cortical tissue was harvested, and clinical parameters and inflammatory biomarkers were checked. RESULTS: There were no significant changes in the clinical parameters between the normal control and sham-operated groups using contrast media. Inflammatory interleukin (IL)-1ß, IL-18, IL-6, tumor necrosis factor-α, and anti-inflammatory IL-10 increased immediately and then decreased at week 2 after RDN in the renal cortical tissue. Leaderless protein, IL-1α level, increased at week 1 and then decreased at week 2 after RDN. Caspase-1 increased immediately after RDN until week 2. Apoptosis-associated speck-like protein containing a caspase recruitment domain and NLRP3 expressions increased immediately and then decreased at week 2 after RDN. CONCLUSION: The RDN could induce acute renal inflammation through the activation of caspase-1 and NLRP3 inflammasome.


Assuntos
Caspase 1/metabolismo , Hipertensão/cirurgia , Rim/inervação , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Insuficiência Renal Crônica/cirurgia , Animais , Modelos Animais de Doenças , Feminino , Hipertensão/sangue , Hipertensão/fisiopatologia , Interleucina-1beta/sangue , Rim/patologia , Suínos , Simpatectomia
13.
PLoS One ; 13(10): e0205848, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30325973

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD. METHODS: This study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables (age, sex, diabetes, hypertension, eGFR, albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein, intact parathyroid hormone (PTH), the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses. RESULTS: In multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH (OR: 1.02, 95% CI: 1.01-1.02), P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL (OR: 1.02, 95% CI: 1.01-1.02, P < 0.001) was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis (area under the curve: 0.835, 95% CI: 0.792-0.879) showed the best cutoff value of plasma NGAL for identifying LVDD was ≥ 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%. CONCLUSION: Plasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients.


Assuntos
Hipertrofia Ventricular Esquerda/sangue , Falência Renal Crônica/sangue , Lipocalina-2/sangue , Adulto , Idoso , Biomarcadores/metabolismo , Estudos Transversais , Diástole , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertrofia Ventricular Esquerda/complicações , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Ultrassonografia Doppler
14.
J Clin Invest ; 128(11): 5008-5017, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30179860

RESUMO

Preeclampsia remains a clinical challenge due to its poorly understood pathogenesis. A prevailing notion is that increased placental production of soluble fms-like tyrosine kinase-1 (sFlt-1) causes the maternal syndrome by inhibiting proangiogenic placental growth factor (PlGF) and VEGF. However, the significance of PlGF suppression in preeclampsia is uncertain. To test whether preeclampsia results from the imbalance of angiogenic factors reflected by an abnormal sFlt-1/PlGF ratio, we studied PlGF KO (Pgf-/-) mice and noted that the mice did not develop signs or sequelae of preeclampsia despite a marked elevation in circulating sFLT-1. Notably, PlGF KO mice had morphologically distinct placentas, showing an accumulation of junctional zone glycogen. We next considered the role of placental PlGF in an established model of preeclampsia (pregnant catechol-O-methyltransferase-deficient [COMT-deficient] mice) by generating mice with deletions in both the Pgf and Comt genes. Deletion of placental PlGF in the context of COMT loss resulted in a reduction in maternal blood pressure and increased placental glycogen, indicating that loss of PlGF might be protective against the development of preeclampsia. These results identify a role for PlGF in placental development and support a complex model for the pathogenesis of preeclampsia beyond an angiogenic factor imbalance.


Assuntos
Pressão Sanguínea , Modelos Biológicos , Fator de Crescimento Placentário/deficiência , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Glicogênio/genética , Glicogênio/metabolismo , Camundongos , Camundongos Knockout , Placenta/patologia , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
Int Urol Nephrol ; 50(12): 2255-2260, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30136086

RESUMO

PURPOSE: Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)2D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)2D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD. METHODS: This study included 409 patients with CKD [glomerular filtration rate (GFR) < 60 ml/min/1.73 m2] who were not on dialysis therapy. Patients on exogenous EPO therapy and patients with iron deficiencies were excluded. Endogenous EPO resistance was assessed by calculating the ratio of endogenous EPO to hemoglobin (Hb) (endogenous EPO/Hb ratio). The associations of Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio with clinical and laboratory variables were investigated by univariate and multivariate analyses. RESULTS: In univariate analysis, serum 1,25(OH)2D level was correlated with the Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio. Multiple regression analysis revealed that the serum 1,25(OH)2D level remained significantly associated with the Hb level (ß = 0.532, P < 0.001), endogenous EPO level (ß = 0.149, P = 0.010), and the endogenous EPO/Hb ratio (ß = - 0.187, P = 0.002), even after adjusting for other confounding factors, including the levels of parathyroid hormone and the inflammatory marker C-reactive protein. CONCLUSION: The serum 1,25(OH)2D level exhibited significant associations with anemia, EPO deficiency, and endogenous EPO resistance in CKD patients. These associations were independent of secondary hyperparathyroidism and inflammation status.


Assuntos
Anemia/sangue , Eritropoetina/sangue , Eritropoetina/deficiência , Insuficiência Renal Crônica/sangue , Vitamina D/análogos & derivados , Idoso , Anemia/etiologia , Feminino , Taxa de Filtração Glomerular , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Vitamina D/sangue
16.
Clin Exp Nephrol ; 22(6): 1411-1419, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29948445

RESUMO

INTRODUCTION: Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is the most severe form of AKI associated with poor short- and long-term patient outcomes. The aim of this study was to evaluate the variables associated with long-term patient survival in our clinic. METHODS: This was a single-center retrospective study with AKI survivors who received CRRT from March 2011 to February 2015. During the study period, all consecutive AKI survivors who underwent CRRT were included. Patients on maintenance dialysis prior to CRRT were excluded. Data were collected by reviewing the patients' medical charts. Long-term follow-up data were gathered through February 2018. RESULTS: A total of 430 patients were included, and 62.8% of the patients were male. The mean age of the patients was 63.4 ± 14.6 years. The mean serum creatinine level at the time of CRRT initiation was 3.5 ± 2.5 mg/dL. At the time of discharge, the mean eGFR and serum creatinine levels were 58.4 ± 46.7 and 1.7 ± 1.6 mg/dL, respectively. After 3 years, 44.9% of the patients had survived. When we investigated the factors associated with long-term patient mortality, a longer stay in the ICU [OR 1.034 (1.016-1.053), p < 0.001], a history of cancer [OR 3.830 (1.037-3.308), p = 0.037], a prolonged prothrombin time [OR 1.852 (1.037-3.308), p = 0.037] and a lower eGFR at the time of discharge [OR 0.988 (0.982-0.995), p = 0.001] were independently associated with long-term patient mortality. CONCLUSION: Our study demonstrates that long-term mortality after CRRT is associated with longer ICU stays and lower eGFRs at the time of hospital discharge. Our data imply the importance of renal recovery for long-term survival of AKI patients treated with CRRT.


Assuntos
Injúria Renal Aguda/terapia , Terapia de Substituição Renal , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Int Urol Nephrol ; 50(10): 1887-1895, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29779118

RESUMO

PURPOSE: Glomerular filtration rate (GFR) has been reported to decrease after unilateral adrenalectomy in patients with primary aldosteronism (PA). The aim of this study was to identify clinical predictors for decreased GFR after adrenalectomy in patients with PA. METHODS: The records of 187 patients (98 patients with PA and 89 with non-PA adrenal disease) who were followed up for at least 6 months after unilateral adrenalectomy were retrospectively analyzed. Estimated GFR (eGFR) was investigated at 1, 3, and 6 months postoperatively. Preoperative risk factors for eGFR% decline at 1 month ([preoperative eGFR-eGFR at 1 month]/preoperative eGFR × 100) and postoperative CKD development were investigated. RESULTS: The eGFR decreased significantly at 1 month and remained stable in the PA group. However, there were no significant changes in eGFR in the non-PA group over the 6-month period. In the PA group, a high preoperative eGFR and high aldosterone to renin ratio (ARR) were independently associated with eGFR% decline at 1 month. In patients with PA but without preoperative CKD (n = 68), a low preoperative eGFR and high ARR were independent risk factors for developing postoperative CKD. The best preoperative cut-off values of eGFR and ARR for predicting the development of postoperative CKD were ≤ 102 ml/min/1.73 m2 and ≥ 448 ng/dl:ng/ml/h, respectively. CONCLUSIONS: Renal function deteriorated significantly after unilateral adrenalectomy in patients with PA. Clinicians must pay attention to postoperative renal function in PA patients at elevated risk of developing decreased kidney function.


Assuntos
Taxa de Filtração Glomerular , Hiperaldosteronismo/fisiopatologia , Hiperaldosteronismo/cirurgia , Insuficiência Renal Crônica/fisiopatologia , Adrenalectomia , Adulto , Aldosterona/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Curva ROC , Insuficiência Renal Crônica/etiologia , Renina/sangue , Estudos Retrospectivos , Fatores de Risco
18.
Iran J Kidney Dis ; 12(2): 132-134, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29507277

RESUMO

Preeclampsia is the most common cause of proteinuria with hypertension during pregnancy. Primary kidney disease and kidney disease secondary to systemic disorders may rarely occur during pregnancy, resulting in proteinuria. A 34-year-old woman was admitted to our hospital with abdominal distention and lower extremity edema. The pregnancy was terminated at the 24th week of gestation due to preterm labor. Even after the delivery, proteinuria and renal deterioration continued to progress. The M-peak was not found on serum and urine protein electrophoresis. The serum free light chains assay showed absolute elevation of lambda chains at 1013.9 mg/L with a decreased kappa to lambda ratio of 0.05. Kidney biopsy revealed light chain deposition disease with lambda light chain deposits on immunofluorescence. Bone marrow examination was compatible with multiple myeloma. To our knowledge, this is the first reported case of light chain deposition disease associated with multiple myeloma during pregnancy.


Assuntos
Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Nefropatias/imunologia , Rim/imunologia , Mieloma Múltiplo/imunologia , Complicações Neoplásicas na Gravidez/imunologia , Adulto , Biópsia , Feminino , Imunofluorescência , Idade Gestacional , Humanos , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Rim/fisiopatologia , Rim/ultraestrutura , Nefropatias/diagnóstico , Microscopia Eletrônica , Mieloma Múltiplo/diagnóstico , Trabalho de Parto Prematuro/etiologia , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Proteinúria/etiologia , Proteinúria/fisiopatologia , Natimorto
19.
Clin Exp Nephrol ; 22(1): 28-34, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28389813

RESUMO

BACKGROUND: Iron deficiency anemia is common in patients with chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of acute kidney injury, is known to be associated with iron metabolism. We investigated whether plasma NGAL level is associated with iron status in pre-dialysis CKD patients with anemia. METHODS: This study included 419 patients who had anemia. The subjects were into categorized into a pre-dialysis group (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2, n = 288) and a non-CKD group (eGFR >60 ml/min/1.73 m2, n = 131). The associations between plasma NGAL and iron status (serum ferritin and transferrin saturation [TSAT]), eGFR, albumin, uric acid, total cholesterol, calcium, phosphate, and C-reactive protein (CRP) were assessed. RESULTS: In non-CKD group, plasma NGAL was not associated with any baseline variables including iron indices (TSAT and serum ferritin). In pre-dialysis group, univariate analysis showed plasma NGAL correlated with eGFR, CRP, TSAT, and serum ferritin. In multivariate analysis, plasma NGAL was independently associated with TSAT. However, serum ferritin lost its association with plasma NGAL. In ROC analysis for identifying iron deficiency, the plasma NGAL (best cut-off value ≤394 ng/ml) was superior to the serum ferritin (suggested cut-off value ≤500 ng/ml) in both sensitivity and specificity. CONCLUSIONS: Plasma NGAL is associated with iron status in anemic patients with pre-dialysis CKD. Further studies are needed to demonstrate the role of plasma NGAL in assessing the iron deficiency and in guiding the iron therapy for pre-dialysis CKD patients.


Assuntos
Anemia Ferropriva/sangue , Ferro/sangue , Lipocalina-2/sangue , Lipocalinas/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Ferritinas/análise , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Valor Preditivo dos Testes , Curva ROC , Diálise Renal , Transferrina/análise
20.
PLoS One ; 12(2): e0171625, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28178341

RESUMO

BACKGROUND: We recently reported on the enhanced expression of two isoforms of matrix metalloproteinase-2 (MMP-2) in human renal transplantation delayed graft function. These consist of the conventional secreted, full length MMP-2 isoform (FL-MMP-2) and a novel intracellular N-Terminal Truncated isoform (NTT-MMP-2) generated by oxidative stress-mediated activation of an alternate promoter in the MMP-2 first intron. Here we evaluated the effect of hyperglycemia and diabetes mellitus on the in vitro and in vivo expression of the two MMP-2 isoforms. METHODS: We quantified the abundance of the FL-MMP-2 and NTT-MMP-2 transcripts by qPCR in HK2 cells cultured in high glucose or 4-hydroxy-2-hexenal (HHE) and tested the effects of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). The streptozotocin (STZ) murine model of Type I diabetes mellitus and renal biopsies of human diabetic nephropathy were used in this study. RESULTS: Both isoforms of MMP-2 in HK2 cells were upregulated by culture in high glucose or with HHE. PDTC treatment did not suppress high glucose-mediated FL-MMP-2 expression but potently inhibited NTT-MMP-2 expression. With STZ-treated mice, renal cortical expression of both isoforms was increased (FL-MMP-2, 1.8-fold; NTT-MMP-2, greater than 7-fold). Isoform-specific immunohistochemical staining revealed low, but detectable levels of the FL-MMP-2 isoform in controls, while NTT-MMP-2 was not detected. While there was a modest increase in tubular epithelial cell staining for FL-MMP-2 in STZ-treated mice, NTT-MMP-2 was intensely expressed in a basolateral pattern. FL-MMP-2 and NTT-MMP-2 isoform expression as quantified by qPCR were both significantly elevated in renal biopsies of human diabetic nephropathy (12-fold and 3-fold, respectively). CONCLUSIONS: The expression of both isoforms of MMP-2 was enhanced in an experimental model of diabetic nephropathy and in human diabetic nephropathy. Selective MMP-2 isoform inhibition could offer a novel approach for the treatment of diabetic renal disease.


Assuntos
Nefropatias Diabéticas/genética , Regulação da Expressão Gênica , Metaloproteinase 2 da Matriz/genética , Animais , Glicemia , Linhagem Celular Transformada , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Humanos , Imuno-Histoquímica , Túbulos Renais Proximais/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Estresse Oxidativo , Isoformas de Proteínas
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