RESUMO
INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.
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Remoção de Componentes Sanguíneos , Diabetes Mellitus , Nefropatias Diabéticas , Hipercolesterolemia , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Qualidade de Vida , Estudos Prospectivos , Remoção de Componentes Sanguíneos/métodos , Lipoproteínas LDL , Proteinúria/terapia , Nefropatias Diabéticas/terapia , Resultado do Tratamento , Diabetes Mellitus/terapiaRESUMO
BACKGROUND: Minimal change nephrotic syndrome (MCNS) is a common type of nephrotic syndrome in adults, though evidence regarding its clinical and histopathological features related to time to complete remission (CR) is limited. METHODS: This was a retrospective study of biopsy-proven, first-onset, adult MCNS patients who achieved CR after undergoing corticosteroid treatment. Body weight (BW) change rate was calculated as follows: (BW at admission - BW at discharge)/BW at discharge × 100. Histopathological examinations were performed, with particular attention given to tubulointerstitial lesions. RESULTS: Fifty-seven patients (median 41 years old, range 22-63 years; 37 males) were diagnosed with MCNS from 2007 to 2020. Time to CR was a median 11 (8-21) days. In addition to serum creatinine and urinary protein, BW change rate also showed a positive correlation with time to CR (rs = 0.438, p < 0.001; rs = 0.280, p = 0.035; rs = 0.544, p < 0.001; respectively), while multivariate Cox proportional hazards models also revealed those factors as significant predictors for longer time to CR. In MCNS patients with a higher BW change rate (n = 28), serum creatinine, urinary protein, histopathological score, and time to CR were significantly greater as compared to those with a lower BW change rate (n =29). Also, in those patients, histopathological interstitial edema was significantly associated with longer time to CR after adjustments for serum creatinine and urinary protein. CONCLUSION: The present results indicate that BW change rate can predict time to CR in adult-onset MCNS patients. Histopathologically, interstitial edema is also an important factor for time to CR in MCNS patients with greater BW increase.
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Nefrose Lipoide , Síndrome Nefrótica , Corticosteroides/uso terapêutico , Adulto , Creatinina , Humanos , Masculino , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/tratamento farmacológico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVE: Infection is related to a higher rate of hospitalization and subsequent death in patients undergoing hemodialysis. Limited data are available about factors associated with death after hospitalization for infection. Nutritional disorder also known as protein energy wasting is profoundly associated with poor consequences. The Geriatric Nutritional Risk Index (GNRI) is a simple but useful nutritional screening tool to predict mortality. We examined whether the GNRI could predict hospitalization for infection and subsequent death. DESIGN AND METHODS: This was a prospective cohort study on patients undergoing hemodialysis. The predictor was the GNRI. The patients were divided into tertiles of the GNRI (T1 to T3), with the highest tertile of T3 as the referent. The outcomes of interest were all-cause mortality, hospitalization for infection, and subsequent death. RESULTS: Of 518 patients, 107 patients died (median follow-up period: 5.0 years; interquartile range: 3.6-5.0) and 169 patients experienced new hospitalization for infection (median follow-up period: 4.5 years; interquartile range: 3.4-5.0) during the follow-up period from December 2004 to December 2009. A lower GNRI was a significant predictor for all-cause mortality in multivariable Cox models (hazard ratio [HR]: 2.9, 95% confidential interval [CI]: 1.5-5.5, P < .001 for T1 vs. T3). However, the GNRI was not associated with hospitalization for infection in multivariable Fine-Gray models with death as a competing risk (subdistributional HR: 1.5, 95% CI: 1.0-2.3, P = .056 for T1 vs. T3). After hospitalization for infection, 38 patients died during the subsequent 2.5-year follow-up period. The GNRI was a significant predictor of death after hospitalization for infection in multivariable Cox models (HR: 2.7, 95% CI: 1.3-5.6, P = .006 for T1 vs. T2+T3). CONCLUSIONS: A lower GNRI predicted a higher risk of all-cause mortality but not hospitalization for infection. However, a lower GNRI was significantly associated with a higher risk of mortality after hospitalization for infection. These findings suggest that long-term mortality after hospitalization for infection was predicted by nutritional disorder evaluated by the GNRI.
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Desnutrição , Distúrbios Nutricionais , Humanos , Idoso , Avaliação Nutricional , Estudos Prospectivos , Estado Nutricional , Avaliação Geriátrica , Diálise Renal , Fatores de Risco , Desnutrição/epidemiologiaRESUMO
INTRODUCTION: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. METHODS: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57-75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. RESULTS: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3-122] vs. 25.7 [13.4-45.8] pmol/h/mL, p < 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. CONCLUSIONS: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events.
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Glicemia/análise , Insuficiência Renal Crônica/sangue , Xantina Desidrogenase/sangue , Idoso , Estudos Transversais , Diálise , Feminino , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Acute kidney injury (AKI) is a common complication of minimal change nephrotic syndrome (MCNS), particularly in adults. To predict development of AKI, as defined by the Kidney Disease Improving Global Outcomes classification, we investigated clinical and histopathological features of adult-onset MCNS patients. METHODS: A retrospective study was conducted with biopsy-proven adult-onset MCNS patients treated with corticosteroids. RESULTS: A total of 58 MCNS patients [49 (24-71) years old, 38 males] were diagnosed using kidney biopsy findings from 2005 to 2018 at Osaka City University Hospital, of whom 24 (41.4%) were found to be complicated with AKI. Age, urinary protein, increased body weight (difference from admission to discharge), and histopathological scores were significantly greater in patients with as compared to without AKI, while urinary protein, increased body weight, and interstitial edema score were significantly associated with AKI development [OR 1.55 (95% CI 1.04-2.31), 1.37 (95% CI 1.03-1.81), 20.7 (95% CI 1.76-243), respectively]. Of the 24 MCNS patients with AKI, 10 underwent transient hemodialysis treatment. Although histopathological features were not different, the time interval between disease onset and kidney biopsy was significantly longer for MCNS patients complicated with AKI requiring hemodialysis as compared to those for whom that was not required [32 (24-46) vs. 13 (10-23) days, p = 0.034]. CONCLUSION: These results indicate that urinary protein, increased body weight, and interstitial edema score are important information for predicting development of AKI in adult-onset MCNS patients.
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Injúria Renal Aguda/patologia , Rim/patologia , Nefrose Lipoide/patologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Corticosteroides/uso terapêutico , Adulto , Idoso , Biópsia , Progressão da Doença , Edema/etiologia , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/complicações , Nefrose Lipoide/tratamento farmacológico , Proteinúria/etiologia , Sistema de Registros , Diálise Renal , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Aumento de Peso , Adulto JovemRESUMO
BACKGROUND: Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. METHODS: This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6 months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24 months after therapy initiation. RESULTS: LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6 months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. CONCLUSION: Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. TRIAL REGISTRATION: Trial registration number: jRCTs042180076.
Assuntos
Remoção de Componentes Sanguíneos , Nefropatias Diabéticas/terapia , Hipercolesterolemia/terapia , Proteinúria/terapia , Proteinúria/urina , Idoso , Remoção de Componentes Sanguíneos/efeitos adversos , LDL-Colesterol/sangue , Creatinina/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria/sangue , Proteinúria/etiologia , Taxa de SobrevidaRESUMO
Background We developed a novel high-sensitive assay for plasma xanthine oxidoreductase (XOR) activity that is not affected by the original serum uric acid level. However, the association of plasma XOR activity with that level has not been fully examined. Methods This cross-sectional study included 191 subjects (91 males, 100 females) registered in the MedCity21 health examination registry. Plasma XOR activity was determined using our assay for plasma XOR activity with [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Serum levels of uric acid and adiponectin, and visceral fat area (VFA) obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results The median values for uric acid and plasma XOR activity were 333 µmol/L and 26.1 pmol/h/mL, respectively. Multivariable linear regression analysis showed a significant and positive association of serum uric acid level (coefficient: 26.503; 95% confidence interval: 2.06, 50.945; p = 0.035) with plasma XOR activity independent of VFA and HOMA-IR, and also age, gender, alcohol drinking habit, systolic blood pressure, estimated glomerular filtration rate (eGFR), glycated hemoglobin A1c, triglyceride, and adiponectin levels. The "gender*XOR activity" interaction was not significant (p = 0.91), providing no evidence that gender modifies the relationship between plasma XOR activity and serum uric acid level. Conclusions Plasma XOR activity was found to be positively associated with serum uric acid level independent of other known confounding factors affecting that level, including gender difference, eGFR, adiponectin level, VFA, and HOMA-IR.
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Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Ácido Úrico/sangue , Xantina Desidrogenase/sangue , Xantina/metabolismo , Idoso , Estudos Transversais , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal , Marcação por Isótopo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Xantina/química , Xantina Desidrogenase/metabolismoRESUMO
BACKGROUND: Cr is secreted by the proximal tubules and thus Cr clearance (Ccr) can overestimate inulin clearance (Cin). However, in some cases, Ccr can even underestimate Cin. This suggests that Cr could be reabsorbed in the tubuli. We examined the clinical parameters that are associated with tubular Cr reabsorption. METHODS: In 80 kidney donor candidates (53.9 ± 13.2 years, 29 males), Cin and para-aminohippuric acid clearance were measured simultaneously. Intrarenal hemodynamic parameters were calculated by Gomez's formulae. To quantify the secretory component of Ccr (SFcr), it was calculated as follows: SFcr = (Ccr - Cin)/Ccr. RESULTS: Twenty-five subjects (31.3%) showed SFcr values <0. SFcr that correlated significantly and negatively with efferent arteriolar resistance (Re) and glomerular hydrostatic pressure (Pglo) (Re: r = -0.30, p = 0.008; Pglo: r = -0.28, p = 0.025). In multiple regression analyses, Re and Pglo were significantly and negatively associated with SFcr after adjustment for other confounders. CONCLUSIONS: These findings suggest that tubular reabsorption of Cr can occur in some cases. Intrarenal glomerular hemodynamic burden may be related to tubular creatinine reabsorption, which possibly leads to lower Ccr values.
Assuntos
Creatinina/metabolismo , Glomérulos Renais/fisiologia , Túbulos Renais/fisiologia , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Voluntários Saudáveis , Hemodinâmica , Humanos , Pressão Hidrostática , Masculino , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
BACKGROUND: Sarcopenia has become a serious disorder in modern society. Chronic kidney disease requiring dialysis and diabetes are some of the disorders that accelerate the onset and progression of sarcopenia. We, therefore, investigated the prevalence of sarcopenia in patients undergoing hemodialysis (HD) and confirmed the impact of diabetes mellitus (DM) on this population. METHODS: This study included 308 patients whose muscle strength and mass had been evaluated using handgrip strength and dual-energy X-ray absorptiometry, respectively. Sarcopenia was defined according to the criteria established by the Asian Working Group on Sarcopenia. In addition, this cohort had been followed up for 9 years. RESULTS: The prevalence of sarcopenia was 40% (37% in males and 45% in females) with gender differences being insignificant (p = 0.237). The DM morbidity rate was significantly higher in those with sarcopenia than in those without sarcopenia (41% vs. 27%, p = 0.015). Multivariate regression analyses showed that the presence of DM was an independent contributor to sarcopenia in patients undergoing HD (odds ratio 3.11; 95% confidence interval 1.63-5.93; p < 0.001). During the follow-up of 76 ± 35 months, 100 patients died. Patients with sarcopenia demonstrated significantly higher rates of all-cause mortality than those without sarcopenia (p < 0.001 using the log-rank test). Multivariate Cox proportional hazards analyses revealed that the presence of DM was significantly associated with higher all-cause mortality (adjusted hazard ratio: 2.39; 95% confidence interval 1.51-3.81; p < 0.001). CONCLUSIONS: The prevalence of sarcopenia among this cohort of patients undergoing HD was determined to be 40%. Moreover, the presence of DM was an independent contributor to sarcopenia and an independent predictor of all-cause mortality in this population.
Assuntos
Diabetes Mellitus/mortalidade , Força Muscular/fisiologia , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia , Sarcopenia/mortalidade , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Feminino , Seguimentos , Força da Mão/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Diálise Renal/tendências , Insuficiência Renal Crônica/diagnóstico , Sarcopenia/diagnósticoRESUMO
BACKGROUND/AIMS: Megalin mediates the uptake of glomerular-filtered iron in the proximal tubules. Urinary full length megalin (C-megalin) excretion has been found to be increased in association with megalin-mediated metabolic load to the endo-lysosomal system in proximal tubular epithelial cells (PTECs) of residual nephrons. In the present study, we investigated the association between urinary iron and C-megalin in chronic kidney disease (CKD) patients, and the possible harmful effect of iron in renal tubules. METHODS: Urinary levels of iron and C-megalin were measured in 63 CKD patients using automatic absorption spectrometry and a recently-established sandwich ELISA, respectively. RESULTS: Although both urinary C-megalin and urinary total protein levels were correlated with urinary iron (C-megalin: ρ = 0.574, p <0.001; total protein: ρ = 0.500, p <0.001, respectively), urinary C-megalin alone emerged as an independent factor positively associated with urinary iron (ß = 0.520, p <0.001) (R2 = 0.75, p <0.001). Furthermore, urinary iron was significantly and positively associated with urinary 8-hydroxydeoxyguanosine, an oxidative stress marker, while no association with other markers of renal tubular injury, i.e., ß2-microglobulin and N-acetyl-ß-D-glucosaminidase, was noted. CONCLUSIONS: Our findings suggest that renal iron handling may be associated with megalin-mediated endo-lysosomal metabolic load in PTECs of residual nephrons and oxidative stress in renal tubules.
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Ferro/urina , Túbulos Renais Proximais/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/análise , Estresse Oxidativo , Insuficiência Renal Crônica/metabolismo , Biomarcadores/análise , Feminino , Humanos , Ferro/efeitos adversos , Ferro/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/sangue , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/ultraestrutura , MasculinoRESUMO
BACKGROUND: Diabetic nephropathy is a leading cause of end-stage kidney disease in the world. Although various types of treatment for diabetes, hypertension and dyslipidemia have improved prognosis and quality of life in patients with diabetic nephropathy, there still exist some diabetic patients with severe proteinuria showing poor prognosis. This clinical trial, LICENSE, aims to confirm the impact of LDL apheresis on proteinuria exhibiting hyporesponsiveness to treatment. METHODS: This ongoing trial is a multicenter, prospective study of diabetic patients with severe proteinuria. The objective is to examine the impact of LDL apheresis on proteinuria in patients with diabetic nephropathy. The other subject is to investigate safety of LDL apheresis in these patients. RESULTS: The subjects consist of diabetic patients with serum creatinine (Cr) levels below 2 mg/dL who present severe proteinuria above 3 g/g Cr or 3 g/day and LDL cholesterol above 120 mg/dL. The target number of registered patients will be 35 patients. Urinary protein excretion and renal function will be observed for 24 weeks after the treatment of LDL apheresis. CONCLUSION: This study will determine the effectiveness and safety of LDL apheresis for diabetic nephropathy patients with severe proteinuria and dyslipidemia.
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Remoção de Componentes Sanguíneos , LDL-Colesterol/isolamento & purificação , Nefropatias Diabéticas/terapia , Hipercolesterolemia/terapia , Proteinúria/terapia , Nefropatias Diabéticas/complicações , Humanos , Hipercolesterolemia/complicações , Proteinúria/complicações , Projetos de PesquisaRESUMO
Hyperuricemia has been reported to affect renal hemodynamics. In a recent study, both low and high levels of serum uric acid (SUA) were found to be associated with loss of kidney function. The goal of this study was to evaluate the relationship between SUA levels and intrarenal hemodynamic parameters in healthy subjects, using plasma clearance of para-aminohippurate (CPAH) and inulin (Cin). Renal and glomerular hemodynamics were evaluated by simultaneous measurements of CPAH and Cin in 48 healthy subjects (54.6 ± 13.4 yr). Intrarenal hemodynamic parameters, including efferent and afferent (Ra) arteriolar resistance, were calculated using Gómez's formulas. Relationships of SUA levels with these intrarenal hemodynamic parameters were examined. In quadratic regression analysis, SUA levels had a significant inverse U-shaped relationship with Cin (P < 0.0001, R2 = 0.350) and CPAH (P = 0.0093, R2 = 0.188) and a U-shaped relationship with Ra (P = 0.0011, R2 = 0.262). In multiple regression analysis with normal (3.5-6.0 mg/dl) and mildly low or high (<3.5 or >6.0 mg/dl) SUA levels entered as dummy variables of zero and one, respectively, mildly low or high SUA levels were significantly and independently associated with Ra (ß = 0.230, P = 0.0403) after adjustment for several factors (R2 = 0.597, P < 0.0001). Both mild hyperuricemia and mild hypouricemia are significantly associated with increased Ra, although weakly. The increase in Ra in subjects with mild hyperuricemia or hypouricemia may be related to renal hemodynamic abnormalities, possibly leading to a decline in renal function.
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Hemodinâmica , Hiperuricemia/sangue , Hiperuricemia/fisiopatologia , Rim/irrigação sanguínea , Circulação Renal , Ácido Úrico/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular , Voluntários Saudáveis , Humanos , Infusões Intravenosas , Inulina/administração & dosagem , Inulina/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Análise de Regressão , Fluxo Plasmático Renal , Ácido p-Aminoipúrico/administração & dosagem , Ácido p-Aminoipúrico/metabolismoRESUMO
BACKGROUND/AIMS: We have reported that the eGFR overestimates renal function when glycemic control is poor. It has been reported that eGFR calculated by serum creatinine underestimates GFR in living kidney donors. We compared the utility of the eGFR in diabetic patients, non-diabetic patients and living kidney donors. Forty diabetic patients, 40 non-diabetic patients, and 40 living kidney donors were enrolled. METHODS: GFR was measured by inulin clearance (C(in)). eGFR was calculated based on serum creatinine (eGFR(cr)) or serum cystatin C (eGFR(cys)). We compared the agreements between each of the eGFR and C(in) in each group. RESULTS: There were significant and positive correlations between each eGFR and C(in) in diabetic patients and non-diabetic patients. However, the intraclass correlation coefficients (ICC) between each eGFR and C(in) in diabetic patients (ICC: eGFR(cr) 0.699, eGFR(cys) 0.604) were weaker than those in non-diabetic patients (ICC: eGFR(cr) 0.865, eGFR(cys) 0.803). The correlation coefficients between each eGFR and C(in) (eGFR(cr); r = 0.422, p = 0.0067 and eGFR(cys); r = 0.358, p = 0.0522) in living kidney donors were significantly weaker than those in non-diabetic patients. The ICCs between each eGFR and C(in) (ICC: eGFR(cr) 0.340, eGFR(cys) 0.345) in living kidney donors were significantly weaker than those in non-diabetic patients. CONCLUSIONS: Based on C(in), eGFR was accurate in non-diabetic patients. However, eGFR was inaccurate in living kidney donors and relatively inaccurate in diabetic patients.
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Diabetes Mellitus/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Testes de Função Renal/normas , Transplante de Rim/normas , Rim/fisiologia , Doadores Vivos , Adulto , Idoso , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND/AIMS: Hyperuricemia has been reported to affect renal hemodynamics in rat models. We evaluate the relationship between serum uric acid and intrarenal hemodynamic parameters in humans, utilizing the plasma clearance of para-aminohippurate (CPAH ) and inulin (Cin). METHODS: Renal and glomerular hemodynamics were assessed by simultaneous measurement of CPAH and Cin in 58 subjects. Of these, 19 subjects were planned to provide a kidney for transplantation; 26 had diabetes without proteinuria; and 13 had mild proteinuria. Renal and glomerular hemodynamics were calculated using Gomez`s formulae. RESULTS: Cin was more than 60 ml/min/1.73m(2) in all subjects. Serum uric acid levels correlated significantly with vascular resistance at the afferent arteriole (Ra) (r = 0.354, p = 0.006) but not with that of the efferent arteriole (Re). Serum uric acid levels (ß = 0.581, p = <0.001) were significantly and independently associated with Ra after adjustment for several confounders (R(2) = 0.518, p = <0.001). CONCLUSIONS: These findings suggest, for the first time in humans, that higher serum uric acid levels are associated significantly with Ra in subjects with Cin > 60 ml/min/1.73m(2). The increase in Ra in subjects with higher uric acid levels may be related to dysfunction of glomerular perfusion.
Assuntos
Hiperuricemia/sangue , Hiperuricemia/fisiopatologia , Circulação Renal , Ácido Úrico/sangue , Adulto , Idoso , Algoritmos , Pressão Sanguínea , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Inulina , Glomérulos Renais/irrigação sanguínea , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Resistência Vascular , Ácido p-Aminoipúrico/metabolismoRESUMO
To date, there is insufficient evidence regarding use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with autosomal-dominant polycystic kidney disease (ADPKD), as such cases have been excluded from previous clinical trials exploring the kidney protection effects of such medications. Here, findings of an ADPKD patient who received dapagliflozin, a selective SGLT2 inhibitor, for 1 year are presented. A 38-year-old woman with a family history of ADPKD wished for treatment with dapagliflozin. After starting administration at 10 mg/day, total kidney volume (TKV) continued to increase, from 1641 to 1764 mL after 84 days and then to 2297 mL after 340 days. The estimated glomerular filtration rate (eGFR) was also decreased from 67.3 to 56.2 mL/min/1.73 m2, and then to 51.4 mL/min/1.73 m2 at those times. Immediately after discontinuation of dapagliflozin, TKV and eGFR were slightly improved to 2263 mL and 55.1 mL/min/1.73 m2, respectively. Following a review of basic research studies, we consider that increased intratubular urinary osmotic pressure, compensatory glucose reabsorption by sodium-glucose cotransporter-1 in the late proximal tubule, and hypertrophy shown in collected cells caused by increased vasopressin may be associated with ADPKD disease progression. Caution may be needed when administering dapagliflozin to patients with ADPKD.
Assuntos
Compostos Benzidrílicos , Taxa de Filtração Glomerular , Glucosídeos , Rim , Rim Policístico Autossômico Dominante , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Rim Policístico Autossômico Dominante/tratamento farmacológico , Rim Policístico Autossômico Dominante/complicações , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/administração & dosagem , Feminino , Adulto , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Rim/patologia , Taxa de Filtração Glomerular/efeitos dos fármacosRESUMO
There is a close relationship between thyroid dysfunction and renal dysfunction. However, thyroid dysfunction can unfortunately result in inaccurate measurements of serum creatinine and cystatin C levels. The chronic decrease in cardiac output due to hypothyroidism can reduce renal plasma flow (RPF) resulting in renal dysfunction. We report the case of a 36-year-old male in whom renal dysfunction detected during a company health check-up was found to be caused by severe hypothyroidism. His serum creatinine levels showed poor results, but serum cystatin C levels were within the normal range. The physician thus prioritized serum cystatin C for assessing the patient's renal function, and concluded that his renal function was normal. He subsequently visited our hospital, aged 36 years, for a comprehensive examination. His serum creatinine level was 1.88 mg/dL and his serum cystatin C level was 0.75 mg/dL, indicating an unusual discrepancy between the two measurements. The patient also presented with fatigue, suggesting hypothyroidism, and we therefore evaluated his thyroid function. His free thyroxine level was below the sensitivity of the assay, while his thyroid-stimulating hormone level was > 100 µIU/mL. A renal biopsy was performed to further explore the underlying cause of his renal dysfunction, which suggested that reduced RPF could be the leading cause of his renal ischemia, with no indications of chronic glomerulonephritis or other abnormalities. His hypothyroidism and renal function improved after thyroid hormone replacement therapy. Given the limited reports of renal biopsy tissue examination during the acute phase of hypothyroidism, the current case provides important information regarding the diagnosis of renal dysfunction in patients with hypothyroidism.
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BACKGROUND/AIMS: In primary aldosteronism (PA), aldosterone could affect glomerular hemodynamics by elevating renal vascular resistance and glomerular capillary pressure. However, the relationship between plasma aldosterone concentrations (PAC) and glomerular hemodynamics including efferent arteriolar resistance (Re), afferent arteriolar resistance (Ra) in humans is still unclear. The aim of this study was to investigate the relationships of PAC with intraglomerular hemodynamic parameters in patients with PA. METHODS: An observational study of glomerular hemodynamics was performed using simultaneous measurements of plasma clearance of para-aminohippurate and inulin (Cin; glomerular filtration rate (GFR)) in 17 patients with PA. Kidney function was evaluated by Cin, estimated GFR based on serum creatine (eGFRcre) and serum cystatin C (eGFRcys) and creatine clearance (Ccr). Intraglomerular hemodynamic parameters, including Re, Ra, and intraglomerular hydrostatic pressure (Pglo) were calculated using Gomez's formulae. RESULTS: In the 17 PA cases, PAC was significantly correlated with Cin (rho=0.752, p=0.001) and eGFRcys (rho=0.567, p=0.018), but was not correlated witheGFRcreand Ccr. PAC was also significantly correlated with Pglo, Re, and urinary protein/day (rho=0.775, p=0.0004, rho=0.625, p=0.009, and rho=0.625, p=0.007, respectively). Multivariable regression analysis showed that PAC was significantly associated with Cin and Re. In comparing aldosterone producing adenoma (APA) and non-APA cases, Cin was significantly elevated in APA (p=0.037), whereas eGFRcre, eGFRcys, and Ccr were not. Re tended to be higher in APA (p=0.064). CONCLUSIONS: These results suggest high aldosterone cause glomerular hyperfiltration by constricting Re. Cin, but not eGFRcre and Ccr, may be useful for evaluating kidney function in PA.
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Thirteen years after kidney donation, a 70-year-old man was referred to a nephrologist because of proteinuria. The serum creatinine, albumin, and urinary protein levels were 2.39 mg/dL, 3.0 g/dL, and 6.72 g/gCr, respectively. A kidney biopsy revealed thickening of the glomerular basement membrane with sub-epithelial deposits, suggesting membranous nephropathy. Considering the apparent interstitial fibrosis and diffuse glomerulosclerosis, supportive treatment was chosen. However, 11 months after the kidney biopsy, hemodialysis was required. The present case constitutes an important teaching point, as glomerular disease can occur in living donors and require careful and long-term medical checkup examinations.
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Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman's capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient's paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.