RESUMEN
BACKGROUND: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. METHOD: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. RESULTS: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). CONCLUSION: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.
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Ácido Fólico , Homocisteína , Preeclampsia , Centros de Atención Terciaria , Vitamina B 12 , Humanos , Femenino , Preeclampsia/sangre , Preeclampsia/epidemiología , Embarazo , Homocisteína/sangre , Ácido Fólico/sangre , Vitamina B 12/sangre , Nepal/epidemiología , Adulto , Estudios Transversales , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/epidemiología , Índice de Severidad de la Enfermedad , Proteinuria/sangreRESUMEN
OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.
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Factor Activador de Células B , Progresión de la Enfermedad , Glomerulonefritis Membranosa , Proteinuria , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral , Humanos , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/diagnóstico , Factor Activador de Células B/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Pronóstico , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/sangre , Proteinuria/sangre , Proteinuria/etiología , Modelos de Riesgos Proporcionales , Receptores de Fosfolipasa A2/inmunología , Receptores de Fosfolipasa A2/sangre , Estudios de Casos y Controles , Anciano , Tasa de Filtración Glomerular , Riñón/fisiopatología , Riñón/patologíaAsunto(s)
Metaboloma , Proteinuria , Insuficiencia Renal Crónica , Humanos , Niño , Proteinuria/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Masculino , Femenino , Adolescente , Estudios Longitudinales , Riñón/fisiopatología , Tasa de Filtración Glomerular , Preescolar , Biomarcadores/sangreRESUMEN
Fabry disease (FD) is associated with inflammation, proteinuria, and chronic kidney disease. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) plays an important role in inflammation in diabetic nephropathy and lupus nephritis. Since there is a close relationship linking serum TWEAK (sTWEAK), inflammation, and carotid intima-media thickness (CIMT) in various kidney diseases, we aimed to determine the relationship between sTWEAK levels and CIMT in subjects with and without proteinuria in a cross-sectional study involving 15 FD patients (seven females, eight males) and seven healthy controls (four females, three males). There were no differences in age, sex, estimated glomerular filtration rate, and biochemical parameters (serum glucose, albumin, creatinine, uric acid, C-reactive protein (CRP), low-density lipoprotein, and high-density lipoprotein) between FD patients and healthy controls. The spot urine protein-creatinine ratios of healthy controls and FD patients were 90 mg/g and 185 mg/g, respectively (P = 0.022). STWEAK levels were higher in FD patients than in healthy controls (P = 0.007). The CIMT of FD patients and healthy controls was 0.55 ± 0.14 mm and 0.42 ± 0.04 mm, respectively (P = 0.007). STWEAK was positively correlated with CRP and CIMT, and negatively with proteinuria (P = 0.005, P = 0.013, and P = 0.018, respectively). In the multivariate analysis, only sTWEAK was an independent variable of increased CIMT. We demonstrated that sTWEAK and CIMT were increased in FD patients. STWEAK might have a role in the pathogenesis of subclinical atherosclerosis in FD.
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Biomarcadores , Grosor Intima-Media Carotídeo , Citocina TWEAK , Enfermedad de Fabry , Humanos , Citocina TWEAK/sangre , Femenino , Masculino , Estudios Transversales , Adulto , Enfermedad de Fabry/sangre , Enfermedad de Fabry/complicaciones , Estudios de Casos y Controles , Biomarcadores/sangre , Persona de Mediana Edad , Proteinuria/etiología , Proteinuria/sangre , Adulto Joven , Valor Predictivo de las Pruebas , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , Factores de RiesgoRESUMEN
Chronic kidney disease (CKD) is generally regarded as a final common pathway of several renal diseases, often leading to end-stage kidney disease (ESKD) and a need for renal replacement therapy. Estimated GFR (eGFR) has been used to predict this outcome recognizing its robust association with renal disease progression and the eventual need for dialysis in large, mainly cross-sectional epidemiological studies. However, GFR is implicitly limited as follows: (1) GFR reflects only one of the many physiological functions of the kidney; (2) it is dependent on several non-renal factors; (3) it has intrinsic variability that is a function of dietary intake, fluid and cardiovascular status, and blood pressure especially with impaired autoregulation or medication use; (4) it has been shown to change with age with a unique non-linear pattern; and (5) eGFR may not correlate with GFR in certain conditions and disease states. Yet, many clinicians, especially our non-nephrologist colleagues, tend to regard eGFR obtained from a simple laboratory test as both a valid reflection of renal function and a reliable diagnostic tool in establishing the diagnosis of CKD. What is the validity of these beliefs? This review will critically reassess the limitations of such single-focused attention, with a particular focus on inter-individual variability. What does science actually tell us about the usefulness of eGFR in diagnosing CKD?
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Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/diagnóstico , Acidosis/sangre , Acidosis/fisiopatología , Fragilidad , Humanos , Riñón/irrigación sanguínea , Riñón/fisiología , Fósforo/sangre , Proteinuria/sangre , Proteinuria/fisiopatología , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapiaRESUMEN
Glomerular diseases (GD) lead to a variety of disorders of the vascular and the total body water volumes. Various pathomechanisms, including vascular underfill and overfill, have been suggested to explain these disturbances. Accordingly, the circulating renin-angiotensin-aldosterone system (cRAAS) is expected to be activated as either a cause or a result of these fluid disorders. The aim of this study was to characterize the activity of the cRAAS in dogs with GD and to evaluate its relationship with the vascular volume status. In a prospective study, we evaluated the plasma renin activity and the serum aldosterone concentration in 15 dogs with GD. Their fluid volume status was estimated with clinical variables reflecting volemia and hydration, echocardiographic volume assessment, N-terminal pro B-type natriuretic peptide, blood urea nitrogen:creatinine ratio, and the urinary fractional excretion of sodium. Ten dogs with chronic kidney disease (CKD) with matching degree of azotemia were recruited as controls. The activity of the cRAAS was low in 10 dogs, normal in 3 dogs, high in 1 dog and equivocal (high renin-low aldosterone) in 1 dog with GD. These dogs had a lower cRAAS activity than dogs with CKD (p = 0.01). The clinical evaluation showed 8 hypovolemic and 7 non-hypovolemic dogs; 3 dehydrated, 9 euhydrated and 3 overhydrated dogs. The cRAAS activity was not different between hypovolemic and non-hypovolemic dogs. The down-regulated cRAAS without obvious association with the clinical volume status of these dogs with GD, suggests different mechanisms of fluid volume dysregulation in dogs with GD than previously assumed. This finding however should be confirmed in a focused larger scale study, as it may influence the use of cRAAS blockers as part of the standard therapy of GD in dogs.
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Aldosterona/sangre , Azotemia/veterinaria , Enfermedades de los Perros/sangre , Glomerulonefritis/veterinaria , Proteinuria/veterinaria , Insuficiencia Renal Crónica/veterinaria , Renina/sangre , Animales , Factor Natriurético Atrial/sangre , Azotemia/sangre , Nitrógeno de la Urea Sanguínea , Perros , Regulación hacia Abajo , Femenino , Glomerulonefritis/sangre , Masculino , Estudios Prospectivos , Precursores de Proteínas/sangre , Proteinuria/sangre , Insuficiencia Renal Crónica/sangreRESUMEN
OBJECTIVES: Whether immunosuppressive therapy may be safely withdrawn in lupus nephritis (LN) is still unclear. We assessed rate and predictors of flare after IS withdrawal in patients with LN in remission. METHODS: Patients with biopsy-proven LN treated with immunosuppressants (IS) between 1980 and 2020 were considered. Remission was defined as normal serum creatinine, proteinuria <0.5 g/24 h, inactive urine sediment, and no extra-renal SLE activity on stable immunosuppressive and/or antimalarial therapy and/or prednisone ≤5mg/day. IS discontinuation was defined as the complete withdrawal of immunosuppressive therapy, flares according to SLEDAI Flare Index. Predictors of flare were analysed by multivariate logistic regression analysis. RESULTS: Among 513 SLE patients included in our database, 270 had LN. Of them, 238 underwent renal biopsy and were treated with IS. Eighty-three patients (34.8%) discontinued IS, 46 (30) months after remission achievement. During a mean (s.d.) follow-up of 116.5 (78) months, 19 patients (22.9%) developed a flare (8/19 renal) and were re-treated; 14/19 (73.7%) re-achieved remission after restarting therapy. Patients treated with IS therapy for at least 3 years after remission achievement had the lowest risk of relapse (OR 0.284, 95% CI: 0.093, 0.867; P = 0.023). At multivariate analysis, antimalarial maintenance therapy (OR 0.194, 95% CI: 0.038, 0.978; P = 0.047), age at IS discontinuation (OR 0.93, 95% CI: 0.868, 0.997; P = 0.040), remission duration >3 years before IS discontinuation (OR 0.231, 95% CI: 0.058, 0.920; P = 0.038) were protective against disease flares. CONCLUSIONS: Withdrawal of IS is feasible in LN patients in remission for at least 3 years and on antimalarial therapy. Patients who experience flares can re-achieve remission with an appropriate treatment.
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Inmunosupresores/uso terapéutico , Nefritis Lúpica/tratamiento farmacológico , Adulto , Biopsia , Creatinina/sangre , Femenino , Humanos , Inmunosupresores/administración & dosificación , Riñón/patología , Modelos Logísticos , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Proteinuria/sangre , Recurrencia , Inducción de RemisiónRESUMEN
The fatty acid profiles of patients with idiopathic nephrotic syndrome (INS) are different from that of healthy controls, even during remission, revealing an increase of the pro-inflammatory omega 6 series. It is still unknown whether the concomitance of nephrotic syndrome affects the potential positive effects of the Mediterranean diet on the levels of omega 3 and 6 fatty acids. We performed a cross-sectional study to evaluate the association between the adherence to the Mediterranean diet and fatty acid profile in 54 children with INS. The dietary habits were assessed through the validated Kidmed questionnaire. Patients with higher adherence had lower levels of linoleic acid and total omega-6. Moreover, a negative correlation between proteinuria and the anti-inflammatory omega-3 series was found. In conclusion, patients with INS with proteinuria and low adherence to the Mediterranean diet have an imbalance in the omega-6/omega-3 ratio that may benefit from following the Mediterranean diet.
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Dieta Mediterránea/estadística & datos numéricos , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Adhesión a Directriz/estadística & datos numéricos , Síndrome Nefrótico/dietoterapia , Niño , Estudios Transversales , Encuestas sobre Dietas , Conducta Alimentaria , Femenino , Humanos , Masculino , Síndrome Nefrótico/sangre , Síndrome Nefrótico/complicaciones , Política Nutricional , Estado Nutricional , Proteinuria/sangre , Proteinuria/congénito , Proteinuria/dietoterapia , Resultado del TratamientoRESUMEN
Diabetic kidney disease (DKD) is a highly heterogenous disease, including the proteinuric and the nonproteinuric pattern. Oxidized low-density lipoprotein (ox-LDL) is progressively increased in DKD and causes direct damage to kidney tubular epithelial cells through a mechanism similar to that underlying the deleterious effect of lipid peroxides in the vascular endothelium. We aimed to examine the association between plasma ox-LDL cholesterol and clinical endpoints in DKD patients. Ninety-one patients with established proteinuric DKD and diabetic retinopathy were enrolled and prospectively followed for 10 years or the occurrence of death, or at least 30% decline in eGFR, or progression to end-stage kidney disease (ESKD) requiring renal replacement therapy (primary outcome). At the end of the study, both eGFR and proteinuria were reassessed. Secondary outcomes of the study were the percentage change in eGFR and proteinuria over time for each patient. At baseline, patients were divided into 2 groups according to the median ox-LDL value (i.e., below or equal and above 66.22 U/L). Both Kaplan-Meier curves (p = 0.001, log-rank test) and univariate Cox regression analysis showed that high ox-LDL was associated with the primary outcome (HR = 3.42, 95%CI = 1.55 - 7.56, p = 0.002). After adjustment for various well-known cofounders, multivariate Cox analysis showed that the association between increased circulating ox-LDL levels and the composite kidney endpoint remained significant (HR = 2.87, 95%CI = 1.14-7.20, p = 0.025). Regarding the secondary outcome of eGFR decline, the assessment of areas under the curves (AUC) showed that ox-LDL outperformed several cofounding factors (AUC 71%, 95%CI = 0.59 - 0.83, p = 0.001) and had better accuracy to predict deterioration of eGFR over time than baseline proteinuria (AUC 67%, 95%CI = 0.54 - 0.79, p = 0.014). Increased ox-LDL might be associated with disease progression in proteinuric DKD.
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Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Tasa de Filtración Glomerular , Riñón/fisiopatología , Lipoproteínas LDL/sangre , Proteinuria/sangre , Anciano , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteinuria/diagnóstico , Proteinuria/mortalidad , Proteinuria/fisiopatología , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver.
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Insuficiencia Multiorgánica/enzimología , Urato Oxidasa/deficiencia , Animales , Peso Corporal , Dieta , Heces , Femenino , Intestinos/patología , Masculino , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/patología , Insuficiencia Multiorgánica/fisiopatología , Especificidad de Órganos , Proteinuria/sangre , Proteinuria/complicaciones , Proteinuria/fisiopatología , Ratas Sprague-Dawley , Urato Oxidasa/metabolismo , Ácido Úrico/sangreRESUMEN
BACKGROUND: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19). METHODS: We examined the associations between laboratory markers and urinary levels of N-acetyl-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen. RESULTS: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uß2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uß2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.
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Lesión Renal Aguda/sangre , COVID-19/sangre , Citocinas/sangre , Mediadores de Inflamación/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , COVID-19/complicaciones , COVID-19/diagnóstico , Proteínas de Unión a Ácidos Grasos/orina , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Proteinuria/sangre , Proteinuria/etiología , Proteinuria/orina , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Regulación hacia Arriba , Microglobulina beta-2/orinaRESUMEN
OBJECTIVE: We aimed to evaluate the association between baseline plasma zinc and the development of proteinuria as well as possible effect modifiers in hypertensive patients. METHODS: This is a subset of the China Stroke Primary Prevention Trial (CSPPT) Renal Sub-Study. In the CSPPT, participants were randomized to receive a daily oral dose of 1 tablet containing 10 mg enalapril and 0.8 mg folic acid or 1 tablet containing 10 mg enalapril only. A total of 783 participants with plasma zinc measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria during the follow-up, defined as a urine dipstick reading of trace or ≥1+ at the exit visit. RESULTS: During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9 %) participants. There was an inverse relation of baseline plasma zinc with the development of proteinuria (per SD increment; OR, 0.74, 95 % CI: 0.55-0.99), p for trend of quartiles = 0.005. CONCLUSIONS: In Chinese hypertensive patients, there was a significant inverse association between baseline plasma zinc and the development of proteinuria, although plasma zinc remained in the reference range.
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Proteinuria/sangre , Zinc/sangre , Anciano , Antihipertensivos/uso terapéutico , Pueblo Asiatico , Femenino , Ácido Fólico/uso terapéutico , Humanos , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteinuria/tratamiento farmacológicoRESUMEN
BACKGROUND: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. METHODS: This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. RESULTS: During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03-1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92-1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. CONCLUSION: SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.
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Insuficiencia Renal Crónica/sangre , Ácido Úrico/sangre , Anciano , Pueblo Asiatico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteinuria/sangre , Estudios RetrospectivosRESUMEN
BACKGROUND: To find new diagnostic markers for idiopathic membranous nephropathy (IMN) and also conduct preliminary explorations into the possible pathogenesis of IMN by comparing the expression of microRNA-451a (miR-451a), miR-106a, miR-19b, miR-17, and phosphatase and tensin homolog (PTEN) protein in the serum of patients with IMN and healthy controls. METHODS: The expression levels of miR-451a, miR-106a, miR-19b, and miR-17 in the serum of patients in the IMN group (n = 55, age: 50.2 ± 12.1 years) and the control group (n = 58, age 47.4 ± 13.1 years) were measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the concentration of serum PTEN protein was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the control group, the expression of miR-106a, miR-19b, and miR-17 was decreased significantly in the IMN group, whereas PTEN protein concentration was increased significantly in the IMN group. The areas under the receiver operating characteristic curve (AUC) of serum miR-106a, miR-19b, miR-17, and PTEN were 0.66 (95% confidence interval [CI], 0.56-0.76), 0.81 (95% CI, 0.73-0.89), 0.69 (95% CI, 0.59-0.79), and 0.86 (95% CI, 0.79-0.93), respectively. The level of serum PTEN protein was negatively correlated with the expression of miR-106a and miR-19b. PTEN concentration was positively correlated with serum urea (Urea), creatinine (Crea), cystatin C (Cysc), 24 h urine total protein (24 h-UP) and negatively correlated with albumin (Alb) and estimated glomerular filtration rate (eGFR). CONCLUSIONS: MiR-106a, miR-19b, miR-17, and PTEN are involved in the pathogenesis of IMN and may become new biomarkers for the diagnosis of IMN.
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Regulación de la Expresión Génica , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/genética , MicroARNs/sangre , Fosfohidrolasa PTEN/sangre , Albúminas/metabolismo , Estudios de Casos y Controles , Creatinina/sangre , Cistatina C/sangre , Femenino , Tasa de Filtración Glomerular , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/fisiopatología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Fosfohidrolasa PTEN/genética , Proteinuria/sangre , Proteinuria/complicaciones , Urea/sangreRESUMEN
PURPOSE OF REVIEW: Albuminuria is associated with progression of kidney disease and is the accepted gold standard for screening, staging, and prognostication of chronic kidney disease. This review focuses on current literature that has explored applications of albuminuria as a surrogate outcome, variable used in kidney failure risk prediction for novel populations, and variable that may be predicted by other proteinuria measures. RECENT FINDINGS: Change in albuminuria shows promise as a surrogate outcome for kidney failure, which may have major implications for trial design and conduct. The kidney failure risk equation (KFRE) has been validated extensively to date and has now been applied to pediatric patients with kidney disease, advanced age, different causes of kidney disease, various countries, and those with prior kidney transplants. As albumin-to-creatinine ratios (ACRs) are not always available to clinicians and researchers, two recent studies have independently developed equations to estimate ACR from other proteinuria measures. SUMMARY: The utility of albuminuria and the KFRE continues to grow in novel populations. With the ability to convert more widely available (and inexpensive) proteinuria measures to ACR estimates, the prospect of incorporating kidney failure risk prediction into routine care within economically challenged healthcare jurisdictions may finally be realized.
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Albuminuria , Proteinuria , Insuficiencia Renal Crónica , Albuminuria/sangre , Albuminuria/diagnóstico , Creatinina , Tasa de Filtración Glomerular , Humanos , Proteinuria/sangre , Proteinuria/diagnóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , RiesgoRESUMEN
BACKGROUND: The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic. METHOD: Relevant studies on this topic were searched in PubMed, Embase, and Web of Science databases from July to August 2020. RESULTS: Serum creatinine, the estimated glomerular filtration rate, and 24-h proteinuria are the 3 main tests used for the monitoring in daily practice. Regarding the timing, several monitoring strategies have been proposed and guidelines are available too, but they provide conflicting information. To date, there is no medical evidence-based that one strategy is better than another. Comorbidities, chronic renal disease, use of nephrotoxic drugs or concomitant steroid therapy also impact the nephrotoxicity risk. Based on the literature review we proposed a kidney function monitoring strategy to guide physicians in clinical practice. CONCLUSION: A baseline assessment should be performed in all patients treated with 5-ASA. The monitoring should be carried out according to the other nephrotoxic factors. A tight monitoring may reduce morbidity and mortality of drug nephrotoxicity.
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Antiinflamatorios no Esteroideos/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Mesalamina/efectos adversos , Monitoreo Fisiológico/métodos , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Creatinina/sangre , Tasa de Filtración Glomerular/efectos de los fármacos , Mesalamina/administración & dosificación , Mesalamina/farmacología , Proteinuria/sangre , Proteinuria/inducido químicamente , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/prevención & controlRESUMEN
OBJECTIVE: To examine the therapeutic effects of camptothecin (CPT) and topotecan (TPT), inhibitors of transcription factor Fli-1 and topoisomerase, on lupus nephritis in (NZB × NZW)F1 (NZBWF1) mice, and to examine the effects of CPT and TPT on inflammatory mediators in human renal cells. METHODS: Female NZBWF1 mice were treated with vehicle, cyclophosphamide (CYC), CPT (1 mg/kg or 2 mg/kg), or TPT (0.03 mg/kg, 0.1 mg/kg, or 0. 3 mg/kg) by intraperitoneal injection twice a week, beginning at the age of 25 weeks (n = 8-10 mice per group). Blood and urine were collected for monitoring autoantibodies and proteinuria. Mice were euthanized at 40 weeks, and renal pathology scores were assessed. Human renal endothelial and mesangial cells were treated with CPT or TPT, and cytokine expression was measured. RESULTS: None of the NZBWF1 mice treated with 1 mg/kg or 2 mg/kg of CPT or 0.3 mg/kg of TPT had proteinuria >100 mg/dl at the age of 40 weeks. One of 8 mice treated with 0.1 mg/kg of TPT and 1 of 10 mice treated with CYC had proteinuria >300 mg/dl, whereas 90% of the mice treated with vehicle had proteinuria >300 mg/dl. Compared to vehicle control, mice treated with 1 mg/kg or 2 mg/kg of CPT, 0.1 mg/kg or 0.3 mg/kg of TPT, or CYC had significantly prolonged survival, attenuated renal injury, diminished splenomegaly, reduced anti-double-stranded DNA autoantibody levels, and reduced IgG and C3 deposits in the glomeruli (all P < 0.05). Human renal cells treated with CPT or TPT had reduced expression of Fli-1 and decreased monocyte chemotactic protein 1 production following stimulation with interferon-α (IFNα) or IFNγ. CONCLUSION: Our findings indicate that low-dose CPT and TPT could be repurposed to treat lupus nephritis.
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Camptotecina/farmacología , Nefritis Lúpica/tratamiento farmacológico , Proteína Proto-Oncogénica c-fli-1/antagonistas & inhibidores , Inhibidores de Topoisomerasa/farmacología , Topotecan/farmacología , Animales , Autoanticuerpos/sangre , Autoanticuerpos/orina , Citocinas/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Riñón/metabolismo , Riñón/patología , Nefritis Lúpica/genética , Proteinuria/sangre , Proteinuria/orinaRESUMEN
This study aims to explore the nephrotoxicity due to use of combination of cyclosporine A and hormone in the treatment of nephrotic syndrome. From January 2018 to November 2019, 100 patients with primary nephrotic syndrome were divided into experimental and control groups, with 50 patients per group. The experimental group took oral cyclosporine A and prednisone tablets, while the control group received oral cyclosporine A combined with shock therapy. The contents of white blood cells, triglycerides, urine protein and cholesterol in the experimental group were lower than those in the control group, while their albumin content was significantly higher than the control values. Blood concentrations of cyclosporine A were significantly lower in non-nephrotoxic patients than in nephrotoxic patients. The high blood cyclosporine A level in patients (>200ng/mL) may be a factor for inducement of nephrotoxicity. Basal serum creatinine levels in nephrotoxic patients were significantly higher than those in non-nephrotoxic patients. Therefore, high basal creatinine level may be a contributing factor to nephrotoxicity. The combination of cyclosporine A and hormone is effective in the treatment of nephrotic syndrome. Blood cyclosporine A levels greater than 200ng/ml or elevated basal serum creatinine may be the cause of nephrotoxicity.
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Ciclosporina/efectos adversos , Glucocorticoides/efectos adversos , Inmunosupresores/efectos adversos , Síndrome Nefrótico/tratamiento farmacológico , Prednisona/efectos adversos , Proteinuria/inducido químicamente , Administración Oral , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Creatinina/sangre , Ciclosporina/administración & dosificación , Ciclosporina/sangre , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Síndrome Nefrótico/sangre , Síndrome Nefrótico/diagnóstico , Prednisona/administración & dosificación , Proteinuria/sangre , Proteinuria/diagnóstico , Proteinuria/orina , Medición de Riesgo , Factores de Riesgo , Comprimidos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
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.