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1.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892431

RESUMEN

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.


Asunto(s)
Receptores de Orexina , Orexinas , Polimorfismo de Nucleótido Simple , Humanos , Orexinas/metabolismo , Orexinas/genética , Masculino , Femenino , Persona de Mediana Edad , Receptores de Orexina/metabolismo , Receptores de Orexina/genética , Adulto , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPP/metabolismo , Riñón Poliquístico Autosómico Dominante/metabolismo , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/sangre , Estudios de Casos y Controles , Anciano , Presión Sanguínea , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/metabolismo , Enfermedades Renales Poliquísticas/sangre
2.
Clin Nephrol ; 93(1): 34-49, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31746731

RESUMEN

BACKGROUND: To determine the role of E-selectin gene S128R polymorphism on the enlargement of renal cysts in patients with polycystic kidney disease (PKD). MATERIALS AND METHODS: 76 PKD patients with no comorbidity were enrolled in the study. Serum E-selectin levels were analyzed by enzyme-linked immunoabsorbent assay (ELISA). E-selectin gene S128R (561 A>C, rs: 5361) polymorphism was examined by polymerase chain reaction restriction fragment length (PCR-RFLP). Magnetic resonance imaging was performed at baseline evaluation and at the end of the 1st year to determine cyst enlargement and total kidney volume (TKV). RESULTS: No significant difference was identified between AA genotype and AC or CC variants of E-selectin gene S128R polymorphism in terms of age, disease duration, baseline cyst volume, cyst volume at the 12th month, baseline dominant cyst volume, and dominant cyst volume at the 12th month. In contrast, a significant difference was determined between the groups with regard to the change of TKV (2.9 ± 13.4 vs. 5.2 ± 16.3 mm3; respectively, p = 0.01). In the correlation analysis, the serum E-selectin level was significantly correlated to glucose, alanine transaminase, creatinine, calcium, phosphorus, total protein, albumin, and end diastolic volume (p = 0.0001, p = 0.001, p = 0.03, p = 0.021, p = 0.023, p = 0.002, p = 0.003, and p = 0.047, respectively). Multivariate logistic regression analysis demonstrated a 1.32-fold higher risk of cyst enlargement in patients with CC polymorphism when compared to AA genotype (p = 0.052), but not between AA and AC genotypes or CC and AC genotypes. CONCLUSION: PKD patients with CC variants of the E-selectin gene S128R polymorphism are at greater risk of cyst enlargement. The results of the present study should be confirmed with further studies with large sample size and longer duration of follow-up.


Asunto(s)
Quistes/patología , Selectina E/genética , Riñón/patología , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/patología , Adulto , Quistes/sangre , Quistes/diagnóstico por imagen , Quistes/genética , Selectina E/sangre , Femenino , Antecedentes Genéticos , Genotipo , Humanos , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/diagnóstico por imagen , Polimorfismo de Longitud del Fragmento de Restricción
3.
Sci Rep ; 9(1): 14525, 2019 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-31601841

RESUMEN

Identifying the key toxic players within an in-vivo toxic syndrome is crucial to develop targeted therapies. Here, we established a novel method that characterizes the effect of single substances by means of an ex-vivo incubation set-up. We found that primary human spermatozoa elicit a distinct motile response on a (uremic) toxic milieu. Specifically, this approach describes the influence of a bulk toxic environment (uremia) as well as single substances (uremic toxins) by real-time analyzing motile cellular behavior. We established the human spermatozoa-based toxicity testing (HSTT) for detecting single substance-induced toxicity to be used as a screening tool to identify in-vivo toxins. Further, we propose an application of the HSTT as a method of clinical use to evaluate toxin-removing interventions (hemodialysis).


Asunto(s)
Motilidad Espermática , Espermatozoides/efectos de los fármacos , Pruebas de Toxicidad , Toxinas Biológicas/toxicidad , Uremia/terapia , Anciano , Anciano de 80 o más Años , Diabetes Mellitus Tipo 1/sangre , Femenino , Humanos , Hidronefrosis/sangre , Técnicas In Vitro , Cinética , Masculino , Persona de Mediana Edad , Nefroesclerosis/sangre , Enfermedades Renales Poliquísticas/sangre , Diálisis Renal , Solventes/química
4.
PLoS One ; 14(3): e0207461, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30870430

RESUMEN

The anti-diuretic hormone arginine vasopressin is thought to be a detrimental factor in polycystic kidney disease (PKD). We previously reported that high water intake (HWI) reduced urine osmolality and urinary arginine vasopressin, improved renal function, and reduced the kidney/body weight ratio in PCK rats, an orthologous model of human PKD. In PKD patients, however, it is reported that HWI increases total kidney volume, urine volume, and urine sodium excretion, which could be a consequence of high salt intake. In the current study, we loaded PCK rats with high salt concurrently with HWI to determine whether this human-imitated condition exacerbates disease progression. PCK rats were assigned into 4 groups: control group (CONT: distilled water), HWI group (HWI: 5% glucose in water), HWI with 0.2% NaCl group (HWI+0.2%NaCl), and HWI with 0.45% NaCl group (HWI+0.45%NaCl). Total water intake during the experimental period was increased by 1.86-, 2.02-, and 2.42-fold in HWI, HWI+0.2%NaCl, and HWI+0.45%NaCl, and sodium intake was increased by 2.55- and 5.83-fold in HWI+0.2%NaCl and HWI+0.45%NaCl, respectively, compared with CONT. Systolic blood pressure was higher in HWI+0.2%NaCl and HWI+0.45%NaCl than in both CONT and HWI. Serum urea nitrogen, kidney/body weight ratio, cAMP, cystic area, and fibrosis index were significantly lower in HWI compared with CONT, and these ameliorative effects were not abrogated in either HWI+0.2%NaCl or HWI+0.45%NaCl. The amount of sodium excreted into the urine was increased by 2.50- and 8.38-fold in HWI+0.2%NaCl and HWI+0.45%NaCl, respectively, compared with HWI. Serum sodium levels were not different between the groups. These findings indicate that the beneficial effect of HWI against the progression of cystic kidney disease was not affected even by high salt-overload in this rodent model of PKD.


Asunto(s)
Enfermedades Renales Poliquísticas/dietoterapia , Cloruro de Sodio Dietético/administración & dosificación , Agua/administración & dosificación , Animales , Presión Sanguínea , Nitrógeno de la Urea Sanguínea , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Masculino , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/orina , Ratas , Ratas Sprague-Dawley , Sodio/orina , Cloruro de Sodio Dietético/efectos adversos
5.
BMC Nephrol ; 20(1): 104, 2019 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-30909873

RESUMEN

BACKGROUND: Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD. METHODS: A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline. RESULTS: Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (ß = - 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, ß = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007). CONCLUSIONS: High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.


Asunto(s)
Angiotensinógeno/orina , Homeostasis/fisiología , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/orina , Potasio/sangre , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Cohortes , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/diagnóstico , Hiperpotasemia/orina , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/diagnóstico , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
6.
J Hypertens ; 37(1): 109-115, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30015755

RESUMEN

BACKGROUND: Hypertension and baroreflex dysfunction confer poorer outcomes in patients with polycystic kidney disease (PKD). METHOD: We examined whether hypothalamic paraventricular nucleus (PVN) activation or circulating vasopressin contribute to hypertension and baroreflex dysfunction in the Lewis polycystic kidney (LPK) rat. RESULTS: Bilateral PVN inhibition with muscimol reduced SBP further in urethane-anaesthetized adult LPK rats than in control Lewis rats (-43 ±â€Š4 vs. -18 ±â€Š3 mmHg; P < 0.0001, n = 14), but was not associated with a greater reduction in sympathetic nerve activity (SNA) or improvement in HR or SNA baroreflex function. Blockade of ionotropic glutamatergic input to the PVN with kynurenic acid also reduced SBP (P < 0.001), but not SNA, further in both adult and juvenile LPK rats. No differences in AMPA or NMDA receptor mRNA expression were noted. Systemic V1A receptor antagonism using OPC-21268 reduced SBP in adult LPK rats only (P < 0.001) and had no effect on the depressor response to PVN inhibition (P = 0.39). Combined peripheral V1A receptor antagonism and PVN inhibition, however, normalized SBP in adult LPK rats (122 ±â€Š11 vs. 115 ±â€Š6 mmHg; LPK vs. Lewis, P > 0.05, n = 10). CONCLUSION: Our data show that in the LPK rat model of PKD, hypertension is contributed to by increased PVN neuronal activity and, through an independent mechanism, systemic V1A receptor activation. Treatments that reduce PVN neuronal activity and/or inhibit peripheral V1A receptors may provide novel treatment strategies to ameliorate hypertension in individuals with PKD and limit overall disease progression.


Asunto(s)
Hipertensión , Núcleo Hipotalámico Paraventricular/metabolismo , Enfermedades Renales Poliquísticas , Vasopresinas/sangre , Animales , Modelos Animales de Enfermedad , Hipertensión/sangre , Hipertensión/etiología , Hipertensión/metabolismo , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/complicaciones , Enfermedades Renales Poliquísticas/metabolismo , Ratas
7.
Clin J Am Soc Nephrol ; 12(11): 1787-1794, 2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-28971980

RESUMEN

BACKGROUND AND OBJECTIVES: Causes of CKD differ in prognosis and treatment. Metabolomic indicators of CKD cause may provide clues regarding the different physiologic processes underlying CKD development and progression. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Metabolites were quantified from serum samples of participants in the Modification of Diet in Renal Disease (MDRD) Study, a randomized controlled trial of dietary protein restriction and BP control, using untargeted reverse phase ultraperformance liquid chromatography tandem mass spectrometry quantification. Known, nondrug metabolites (n=687) were log-transformed and analyzed to discover associations with CKD cause (polycystic kidney disease, glomerular disease, and other cause). Discovery was performed in Study B, a substudy of MDRD with low GFR (n=166), and replication was performed in Study A, a substudy of MDRD with higher GFR (n=423). RESULTS: Overall in MDRD, average participant age was 51 years and 61% were men. In the discovery study (Study B), 29% of participants had polycystic kidney disease, 28% had glomerular disease, and 43% had CKD of another cause; in the replication study (Study A), the percentages were 28%, 24%, and 48%, respectively. In the discovery analysis, adjusted for demographics, randomization group, body mass index, hypertensive medications, measured GFR, log-transformed proteinuria, and estimated protein intake, seven metabolites (16-hydroxypalmitate, kynurenate, homovanillate sulfate, N2,N2-dimethylguanosine, hippurate, homocitrulline, and 1,5-anhydroglucitol) were associated with CKD cause after correction for multiple comparisons (P<0.0008). Five of these metabolite associations (16-hydroxypalmitate, kynurenate, homovanillate sulfate, N2,N2-dimethylguanosine, and hippurate) were replicated in Study A (P<0.007), with all replicated metabolites exhibiting higher levels in polycystic kidney disease and lower levels in glomerular disease compared with CKD of other causes. CONCLUSIONS: Metabolomic profiling identified several metabolites strongly associated with cause of CKD.


Asunto(s)
Glomerulonefritis/sangre , Metaboloma/fisiología , Enfermedades Renales Poliquísticas/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/etiología , Adulto , Citrulina/análogos & derivados , Citrulina/sangre , Desoxiglucosa/sangre , Femenino , Glomerulonefritis/complicaciones , Guanosina/análogos & derivados , Guanosina/sangre , Hipuratos/sangre , Ácido Homovanílico/sangre , Humanos , Ácido Quinurénico/sangre , Masculino , Persona de Mediana Edad , Ácidos Palmíticos/sangre , Enfermedades Renales Poliquísticas/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto
9.
BMC Nephrol ; 17(1): 196, 2016 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-27899079

RESUMEN

BACKGROUND: In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease. METHODS: We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up. RESULTS: At baseline, median eGFR was 69 mL/min./1.73 m2, mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44-75) mL/min./1.73 m2, 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p < 0.001), ΔFMD (0.599, p < 0.001), ΔcIMT (0.562, p < 0.001) and ΔPWV (0.27, p < 0.001) also after linear regression modeling to correct for confounders. Finally, ROC analysis was done for a high baseline copeptin with ΔeGFR [cut-off:≤59], ΔFMD [cut-off: ≤7.08], ΔcIMT [cut-off:>0.76], and ΔPWV [cut-off:≤7.80]. CONCLUSIONS: Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.


Asunto(s)
Endotelio/fisiopatología , Tasa de Filtración Glomerular , Glicopéptidos/sangre , Enfermedades Renales Poliquísticas/sangre , Adulto , Biomarcadores/sangre , Grosor Intima-Media Carotídeo , Ecocardiografía , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/fisiopatología , Análisis de la Onda del Pulso , Volumen Sistólico , Vasodilatación , Vasopresinas/fisiología
10.
Kidney Int ; 90(1): 192-202, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27178833

RESUMEN

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.


Asunto(s)
Anemia/tratamiento farmacológico , Resistencia a Medicamentos , Hematínicos/farmacología , Hemodiafiltración , Hemoglobinas/análisis , Fallo Renal Crónico/terapia , Diálisis Renal , Administración Intravenosa , Anciano , Estudios de Cohortes , Darbepoetina alfa/administración & dosificación , Darbepoetina alfa/farmacología , Darbepoetina alfa/uso terapéutico , Eritropoyetina/administración & dosificación , Eritropoyetina/farmacología , Eritropoyetina/uso terapéutico , Femenino , Hematínicos/uso terapéutico , Humanos , Inyecciones Subcutáneas , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/terapia , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico
11.
Ther Apher Dial ; 20(1): 73-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26482029

RESUMEN

Patients with autosomal dominant polycystic kidney disease and polycystic liver disease (PLD) often have elevated serum levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). Ursodeoxycholic acid (UDCA) is used to treat biliary tract diseases, but its effect on PLD remains unclear. UDCA was administered for 1 year at a dose of 300 mg daily to seven PLD patients with elevated ALP or GGT levels who were selected for this treatment by experienced clinicians. Laboratory data and liver volumes were compared among three time points: 1 year before UDCA treatment, at the start of UDCA therapy, and 1 year after the start of therapy. Median GGT did not show a significant change between 1 year before UDCA (180 IU/L) and the start of UDCA therapy (209 IU/L), but it decreased significantly to 98 IU/L after 1 year of UDCA therapy (P = 0.015 vs. the start of therapy). ALP showed a significant increase from 1 year before UDCA (456 IU/L) to the start of UDCA therapy (561 IU/L), and then decreased significantly after 1 year of UDCA therapy (364 IU/L). Median liver volume did not show any significant changes among these three time points of assessment. UDCA may be effective for reducing biliary enzyme levels and inhibiting the growth of liver cysts in patients with PLD.


Asunto(s)
Quistes , Hepatopatías , Hígado , Enfermedades Renales Poliquísticas , Ácido Ursodesoxicólico/administración & dosificación , Anciano , Fosfatasa Alcalina/sangre , Colagogos y Coleréticos/administración & dosificación , Quistes/sangre , Quistes/diagnóstico , Quistes/terapia , Monitoreo de Drogas/métodos , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hepatopatías/sangre , Hepatopatías/diagnóstico , Hepatopatías/terapia , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/diagnóstico , Enfermedades Renales Poliquísticas/terapia , Diálisis Renal/métodos , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , gamma-Glutamiltransferasa/sangre
12.
PLoS One ; 10(11): e0143430, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26599216

RESUMEN

BACKGROUND/AIMS: Monitoring of serum ferritin levels is widely recommended in the management of anemia among patients on dialysis. However, associations between serum ferritin and mortality are unclear and there have been no investigations among patients undergoing peritoneal dialysis (PD). METHODS: Baseline data of 191,902 patients on dialysis (age, 65 ± 13 years; male, 61.1%; median dialysis duration, 62 months) were extracted from a nationwide dialysis registry in Japan at the end of 2007. Outcomes, such as one-year mortality, were then evaluated using the registry at the end of 2008. RESULTS: Within one year, a total of 15,284 (8.0%) patients had died, including 6,210 (3.2%) cardiovascular and 2,707 (1.4%) infection-related causes. Higher baseline serum ferritin levels were associated with higher mortality rates among patients undergoing hemodialysis (HD). In contrast, there were no clear associations between serum ferritin levels and mortality among PD patients. Multivariate Cox regression analysis of HD patients showed that those in the highest serum ferritin decile group had higher rates of all-cause and cardiovascular mortality than those in the lowest decile group (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.31-1.81 and HR, 1.44; 95% CI, 1.13-1.84, respectively), whereas associations with infection-related mortality became non-significant (HR, 1.14; 95% CI, 0.79-1.65). CONCLUSIONS: Using Japanese nationwide dialysis registry, higher serum ferritin values were associated with mortality not in PD patients but in HD patients.


Asunto(s)
Ferritinas/sangre , Diálisis Peritoneal/mortalidad , Diálisis Renal/mortalidad , Diálisis Renal/métodos , Anciano , Anemia/sangre , Estudios de Cohortes , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/terapia , Femenino , Glomerulonefritis/sangre , Glomerulonefritis/terapia , Humanos , Japón , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Nefroesclerosis/sangre , Nefroesclerosis/terapia , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/terapia , Modelos de Riesgos Proporcionales , Sistema de Registros , Transferrina/metabolismo , Resultado del Tratamiento
13.
Int J Toxicol ; 34(6): 479-90, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26503599

RESUMEN

PCK rats develop age-related polycystic kidney disease (PKD) and liver disease and have been used to investigate pharmacotherapies to ameliorate hepatorenal lesions for patients with PKD. The PCK rat may be useful to understand the possible susceptibility to hepatotoxicity observed in the patient with PKD having hepatic polycystic lesions. Therefore, the purpose of this study was to investigate the background blood biochemical changes that reflect the hepatorenal function of PCK rats as well as the terminal histopathology in order to determine whether this model would be suitable for extrapolating the susceptibility of hepatotoxicity in patients. The blood biochemical parameters of hepatorenal function and histopathology were investigated in PCK rats at ages 5 to 19 weeks and compared to those outcomes in the Sprague Dawley (SD) rat. There were notable blood biochemical changes possibly due to biliary dysgenesis in the PCK rat as early as 5 weeks of age. High levels of γ-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and total bile acids persisted throughout the study compared to the SD rat. Increased aspartate aminotransferase, total bilirubin, and hyperlipidemia and a decrease in albumin were also evident at 10 to 19 weeks of age possibly due to progression of cholestatic liver dysfunction secondary to age-related liver cystic progression. Increased liver weights generally correlated with the severity of biliary and hepatic histopathological changes. In male PCK rats, age-related increases in blood urea nitrogen and creatinine at 10 to 19 weeks of age were observed, and the cystic progression was more severe than that in females. These data indicate that the PCK rat showed notable blood biochemical changes reflecting alteration of the liver function compared to the SD rat. Also, there was a large individual variation in these parameters possibly due to variable progression rate of biliary dysgenesis and subsequent liver damages in PCK rats.


Asunto(s)
Envejecimiento/sangre , Riñón/fisiopatología , Hígado/fisiopatología , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/fisiopatología , Animales , Sistema Biliar/patología , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Progresión de la Enfermedad , Femenino , Ictericia Obstructiva/fisiopatología , Riñón/patología , Pruebas de Función Renal , Hígado/patología , Pruebas de Función Hepática , Masculino , Tamaño de los Órganos , Enfermedades Renales Poliquísticas/patología , Ratas , Ratas Sprague-Dawley
14.
Eur J Endocrinol ; 172(4): 343-50, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25572388

RESUMEN

BACKGROUND: Controversies exist whether disturbances in mineral and bone disorder (MBD) normalise or persist after kidney transplantation. We assessed markers of MBD in patients with well-functioning kidney transplants to minimise confounding by reduced transplant function. METHODS: In this cross-sectional study, 40 patients aged ≥18 years who received a first kidney transplant more than 10 years ago were included. A well-functioning transplant was defined as an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m(2). RESULTS: Median time since transplantation was 18.3 years (inter quartile range (IQR) 12.2-26.2). Albumin-corrected serum calcium levels were above upper limit of normal in 15% of the transplanted patients, and serum phosphate levels below lower limit of normal in 31%. The median levels of intact parathyroid hormone (iPTH) and intact fibroblast growth factor 23 (iFGF23) were significantly higher than that in a group of healthy volunteers (11.3 pmol/l (IQR: 8.7-16.2) vs 4.4 pmol/l (IQR: 3.8-5.9), P<0.001 and 75.0 pg/ml (IQR: 53.3-108.0) vs 51.3 pg/ml (IQR: 36.3-67.6), P=0.004 respectively). There was a non-significant reduction in soluble Klotho (sKlotho) levels (605 pg/ml (IQR: 506-784) vs 692 pg/ml (IQR: 618-866)). When compared with a control group matched for eGFR, levels of iPTH were significantly higher (P<0.001), iFGF23 had a non-significant trend towards higher levels and sKlotho towards lower levels. CONCLUSIONS: In long-term kidney transplant patients with well-functioning kidney transplants, we found inappropriately high levels of iPTH and iFGF23 consistent with a state of persistent hyperparathyroidism. We speculate that the primary defect, FGF23 resistance, has evolved in the parathyroid gland before transplantation, and persists due to long half-life of the parathyroid cells.


Asunto(s)
Factores de Crecimiento de Fibroblastos/sangre , Glucuronidasa/sangre , Trasplante de Riñón , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Factor-23 de Crecimiento de Fibroblastos , Tasa de Filtración Glomerular , Glomerulonefritis/sangre , Glomerulonefritis/fisiopatología , Glomerulonefritis/terapia , Humanos , Trasplante de Riñón/estadística & datos numéricos , Proteínas Klotho , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/fisiopatología , Enfermedades Renales Poliquísticas/terapia , Factores de Tiempo
15.
Hematology ; 20(1): 48-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24580134

RESUMEN

OBJECTIVE AND IMPORTANCE: The use of argatroban during hemodialysis in a patient receiving warfarin is not established. We present a case of heparin-induced thrombocytopenia in a patient on hemodialytic therapy who successfully received argatroban concomitantly to warfarin during renal replacement therapy. CLINICAL PRESENTATION: A 46-year-old male patient with autosomal dominant polycystic kidney disease presented with heparin-induced thrombocytopenia (HIT) arised during dialytic procedures. Intervention After the acute episode requiring argatroban and warfarin therapy, the patient continued to receive argatroban during the hemodialytic session concomitantly to warfarin. CONCLUSION: The administration of argatroban in the dialytic circuit of a patient on oral anticoagulant therapy can be considered an effective and safe approach.


Asunto(s)
Anticoagulantes/administración & dosificación , Heparina/efectos adversos , Ácidos Pipecólicos/administración & dosificación , Diálisis Renal/métodos , Trombocitopenia/tratamiento farmacológico , Warfarina/administración & dosificación , Arginina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/terapia , Sulfonamidas , Trombocitopenia/inducido químicamente
17.
Am J Physiol Regul Integr Comp Physiol ; 307(10): R1207-15, 2014 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-25209412

RESUMEN

Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney.


Asunto(s)
Hipoxia/sangre , Riñón/metabolismo , Oxígeno/sangre , Enfermedades Renales Poliquísticas/sangre , Animales , Hipoxia de la Célula , Modelos Animales de Enfermedad , Hemodinámica , Hipoxia/fisiopatología , Riñón/irrigación sanguínea , Masculino , Consumo de Oxígeno , Presión Parcial , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/fisiopatología , Ratas Endogámicas Lew , Circulación Renal , Reabsorción Renal , Sodio/sangre
18.
Kidney Int ; 85(6): 1340-50, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24402093

RESUMEN

Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis and is linked to cardiovascular disease and all-cause mortality in chronic kidney disease. FGF23 rises in patients with CKD stages 2-3, but in patients with autosomal dominant polycystic kidney disease, the increase of FGF23 precedes the first measurable decline in renal function. The mechanisms governing FGF23 production and effects in kidney disease are largely unknown. Here we studied the relation between FGF23 and mineral homeostasis in two animal models of PKD. Plasma FGF23 levels were increased 10-fold in 4-week-old cy/+ Han:SPRD rats, whereas plasma urea and creatinine concentrations were similar to controls. Plasma calcium and phosphate levels as well as TmP/GFR were similar in PKD and control rats at all time points examined. Expression and activity of renal phosphate transporters, the vitamin D3-metabolizing enzymes, and the FGF23 co-ligand Klotho in the kidney were similar in PKD and control rats through 8 weeks of age, indicating resistance to FGF23, although phosphorylation of the FGF receptor substrate 2α protein was enhanced. In the kidneys of rats with PKD, FGF23 mRNA was highly expressed and FGF23 protein was detected in cells lining renal cysts. FGF23 expression in bone and spleen was similar in control rats and rats with PKD. Similarly, in an inducible Pkd1 knockout mouse model, plasma FGF23 levels were elevated, FGF23 was expressed in kidneys, but renal phosphate excretion was normal. Thus, the polycystic kidney produces FGF23 but is resistant to its action.


Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Riñón/metabolismo , Enfermedades Renales Poliquísticas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Biomarcadores/sangre , Calcitriol/metabolismo , Calcio/sangre , Creatinina/sangre , Modelos Animales de Enfermedad , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/genética , Glucuronidasa/metabolismo , Riñón/patología , Proteínas Klotho , Masculino , Ratones Noqueados , Hormona Paratiroidea/sangre , Fosfatos/sangre , Fosforilación , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/patología , ARN Mensajero/metabolismo , Ratas , Transducción de Señal , Canales Catiónicos TRPP/deficiencia , Canales Catiónicos TRPP/genética , Regulación hacia Arriba , Urea/sangre
19.
Turk Psikiyatri Derg ; 24(3): 213-6, 2013.
Artículo en Turco | MEDLINE | ID: mdl-24049011

RESUMEN

Lithium remains to be the gold standard in the treatment of mood disorders. This study presents a case treated with lithium for an extended period with a good response. Following an increase in creatinine levels, further investigation of renal dysfunction revealed polycystic kidney disease. Lithium was used prior to the diagnosis of polycystic kidney disease, resulting in the unique opportunity to examine the effects of lithium on kidneys with polycystic kidney disease. Within this context, this study also discusses the pharmacokinetics of lithium, and its possible relation to cyst formation in polycystic kidney disease.


Asunto(s)
Litio/administración & dosificación , Trastornos del Humor/tratamiento farmacológico , Enfermedades Renales Poliquísticas/diagnóstico , Creatinina/sangre , Humanos , Litio/efectos adversos , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/inducido químicamente
20.
J Investig Med ; 61(3): 597-603, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23360844

RESUMEN

BACKGROUND: Autosomal-dominant polycystic kidney disease (ADPKD) demonstrates cardiovascular manifestations, such as hypertension, myocardial infarction, and increased carotid intimae-media thickness. These complications are the main cause of morbidity and mortality in patients with ADPKD. Platelet activation and arterial stiffness are important manifestations that independently predict cardiovascular events. In the present study, we aimed to investigate the relation between arterial stiffness, mean platelet volume (MPV), and highly sensitive C-reactive protein (hs-CRP) in patients with normotensive polycystic kidney disease. METHODS: We included 30 normotensive subjects with ADPKD with an estimated glomerular filtration rate (eGFR) of 60 mL or more per minute per 1.73 m, 30 normotensive subjects with ADPKD with eGFR from 30 to 60 mL/min per 1.73 m, and 30 healthy controls in our study. Pulse wave velocity (PWV), eGFR, spot urine protein-creatinine ratio, MPV, and hs-CRP levels were measured in all participants. In addition, transthoracic echocardiography and ambulatory blood pressure monitoring were performed. RESULTS: Age, sex, biochemical markers, eGFR, hemoglobin level, and platelet count were similar in the ADPKD subjects and the controls. There were significant differences in MPV (9.8 ± 0.7, 8.7 ± 0.8, and 8.0 ± 0.5 femtolitre; P < 0.001) and hs-CRP (6.8 ± 3.0, 5.3 ± 2.7, and 2.6 ± 0.52 mg/L; P < 0.001) in the groups. Additionally, PWV values were increased from healthy subjects to ADPKD patients who have decreased eGFR (5.5 ± 1.1, 8.8 ± 1.6, and 10.8 ± 1.2 m/s; P for trend <0.001). There were significant positive correlations between PWV and MPV (r = 0.401; P = 0.002) and hs-CRP (r = 0.343; P = 0.007) in the patients with ADPKD. Additionally, PWV was independently predicted by MPV (ß = 0.286; P = 0.007), proteinuria (ß = 0.255; P = 0.001), eGFR (ß = -0.479; P < 0.001), and hs-CRP (ß = 0.379; P < 0.001) in the patients with ADPKD. In addition, eGFR, as a sign of severity of disease, was independently predicted by MPV (ß = -0.325; P = 0.003), PWV (ß = -0.471; P < 0.001), and hs-CRP (ß = -0.269; P = 0.008). CONCLUSIONS: Our findings suggest that MPV and hs-CRP levels are associated with increased arterial stiffness in patients with early-stage ADPKD and those with late-stage ADPKD. Also, MPV and hs-CRP were independently associated with the severity of ADPKD.


Asunto(s)
Plaquetas/metabolismo , Presión Sanguínea , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/fisiopatología , Rigidez Vascular/fisiología , Adulto , Proteína C-Reactiva/metabolismo , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Enfermedades Renales Poliquísticas/complicaciones , Enfermedades Renales Poliquísticas/diagnóstico por imagen , Proteinuria/sangre , Proteinuria/complicaciones , Proteinuria/fisiopatología , Análisis de la Onda del Pulso , Ultrasonografía
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