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1.
BMC Nephrol ; 23(1): 170, 2022 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-35509038

RESUMEN

BACKGROUND: Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter's syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo). CASE PRESENTATION: We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS. CONCLUSIONS: We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.


Asunto(s)
Alcalosis , Síndrome de Gitelman , Adulto , Alcalosis/genética , Calcio/metabolismo , Femenino , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Humanos , Magnesio , Masculino , Mutación/genética , Renina/genética , Miembro 3 de la Familia de Transportadores de Soluto 12/genética
2.
Int J Mol Sci ; 23(1)2021 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-35008629

RESUMEN

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)-regular diet with a FR < 3%; F10 (n = 6)-regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)-60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.


Asunto(s)
Dieta , Túbulos Renales/lesiones , Síndrome Metabólico/etiología , Urolitiasis/etiología , Animales , Ingestión de Alimentos , Electrólitos/orina , Fructosa , Túbulos Renales/patología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/orina , Estado Nutricional , Ratas Wistar , Factores de Riesgo , Urinálisis , Urolitiasis/sangre , Urolitiasis/orina
3.
Kidney Blood Press Res ; 43(3): 1042-1052, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29940595

RESUMEN

BACKGROUND/AIMS: Cardiovascular complications are responsible for increased mortality and morbidity in chronic kidney disease (CKD) patients. Functional and structural changes of peritoneal membrane are reported in CKD patients both on conservative treatment and on renal replacement therapy (RRT). The aim of the study was to assess the structure of peritoneal membrane small arteries (precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients before initiation of peritoneal dialysis (PD) and evaluate its relationship with heart and large arteries abnormalities and with selected biochemical parameters. METHODS: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic (n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane samples were taken during Tenckhoff catheter insertion. Histopathological evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio was performed in each patients. Echocardiography, intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH), hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P), transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each participant. RESULTS: There were no statistically significant differences in peritoneal membrane arteriolar indices - wall thickness (WT) and L/V ratio between investigated groups. There was statistically significant higher PWV value in diabetic patients. There were no statistically significant differences in echocardiographic indices, IMT, laboratory data in analyzed groups. There were some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP (R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age (R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in diabetic group. CONCLUSION: Peritoneal membrane arteriolar damage seems to be an integrated part of cardiovascular system damage in CKD stage 5 patients.


Asunto(s)
Arteriolas/patología , Enfermedades Cardiovasculares/diagnóstico , Membranas/irrigación sanguínea , Peritoneo/ultraestructura , Insuficiencia Renal Crónica/complicaciones , Adulto , Anciano , Arteriolas/lesiones , Arteriolas/ultraestructura , Enfermedades Cardiovasculares/mortalidad , Grosor Intima-Media Carotídeo , Diabetes Mellitus , Humanos , Persona de Mediana Edad , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica/mortalidad
4.
Nephrol Dial Transplant ; 32(suppl_2): ii209-ii218, 2017 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-28339709

RESUMEN

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.


Asunto(s)
Enfermedades Renales/patología , Riñón/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Preescolar , Femenino , Humanos , Lactante , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Estudios Prospectivos , Sistema de Registros , Distribución por Sexo , Adulto Joven
5.
BMC Nephrol ; 16: 68, 2015 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-25935771

RESUMEN

BACKGROUND: Fructose acutely raises serum uric acid in normal subjects, but the effect in subjects with metabolic syndrome or subjects with chronic kidney disease is unknown. The aim of the study was to evaluate changes in serum uric acid during the fructose tolerance test in patients with chronic kidney disease, metabolic syndrome with comparison to healthy controls. METHODS: Studies were performed in 36 subjects with obesity (body mass index >30) and metabolic syndrome, 14 patients with stage 3 chronic kidney disease, and 25 healthy volunteers. The fructose tolerance test was performed in each patient. The change in serum uric acid during the fructose challenge was correlated with baseline ambulatory blood pressure, serum uric acid, metabolic, and inflammatory markers, and target organ injury including carotid intima media thickness and renal resistive index (determined by Doppler). RESULTS: Absolute serum uric acid values were highest in the chronic kidney disease group, followed by the metabolic syndrome and then healthy controls. Similar increases in serum uric acid in response to the fructose tolerance test was observed in all three groups, but the greatest percent rise was observed in healthy controls compared to the other two groups. No significant association was shown between the relative rise in uric acid and clinical or inflammatory parameters associated with kidney disease (albuminuria, eGFR) or metabolic syndrome. CONCLUSIONS: Subjects with chronic kidney disease and metabolic syndrome have higher absolute uric acid values following a fructose tolerance test, but show a relatively smaller percent increase in serum uric acid. Changes in serum uric acid during the fructose tolerance test did not correlate with changes in metabolic parameters, inflammatory mediators or with target organ injury. These studies suggest that acute changes in serum uric acid in response to fructose do not predict the metabolic phenotype or presence of inflammatory mediators in subjects with obesity, metabolic syndrome or chronic kidney disease. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov. Identifier : NCT01332526. www.register.clinicaltrials.gov/01332526.


Asunto(s)
Fructosa/administración & dosificación , Síndrome Metabólico/diagnóstico , Obesidad/diagnóstico , Insuficiencia Renal Crónica/diagnóstico , Ácido Úrico/sangre , Adulto , Anciano , Índice de Masa Corporal , Progresión de la Enfermedad , Femenino , Fructosa/sangre , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Síndrome Metabólico/sangre , Persona de Mediana Edad , Obesidad/sangre , Valores de Referencia , Insuficiencia Renal Crónica/sangre , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
6.
Ren Fail ; 37(7): 1105-10, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26156686

RESUMEN

INTRODUCTION: Chronic kidney disease (CKD) is an independent factor for cardiovascular system complications, such as arterial hypertension, left ventricular hypertrophy (LVH), heart failure or accelerated atherosclerosis progression. The aim of the paper was to analyze left ventricular and arterial remodeling in patients with CKD stages 1-3 to identify the subclinical marker of cardiovascular system damage which changes first in the course of CKD. METHODS: The examined group consisted of 90 patients with CKD stage 1-3 and 30 subjects constituting the control group. Left ventricular mass index (LVMI), left ventricular relative wall thickness (RWT) and ejection fraction (EF) were determined by echocardiographic examination. Pulse wave velocity (PWV) between the carotid and femoral arteries as well as common carotid artery intima-media thickness (IMT) was measured. 24-h ambulatory blood pressure monitoring was performed in all subjects. RESULTS: No differences were found between blood pressure values in the examined groups of patients with CKD1, CKD2 and CKD3. Concentric remodeling was found in 20.0%, concentric hypertrophy in 22.2% and eccentric hypertrophy in 18.9% of patients. LVMI values in patients with CKD2 and 3 were higher than in the control group. IMT values in patients with CKD3 were higher than in patients with CKD2. PWV in patients with stage 3 CKD was significantly higher than in the control group (p < 0.05). CONCLUSIONS: In the course of CKD, the left ventricle undergoes remodeling earlier than large arterial vessels. Echocardiographic assessment of LVH in early stages of CKD may identify patients at increased cardiovascular risk.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Hipertensión/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Insuficiencia Renal Crónica/complicaciones , Rigidez Vascular/fisiología , Adulto , Anciano , Presión Sanguínea/fisiología , Grosor Intima-Media Carotídeo , Ecocardiografía , Femenino , Humanos , Hipertensión/etiología , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica/clasificación , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Remodelación Ventricular
7.
Postepy Hig Med Dosw (Online) ; 69: 830-7, 2015 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-26206996

RESUMEN

Interstitium - the renal tubulointerstitial compartment - is located between the renal tubule basement membrane and microcirculation vessels. Interstitial fibroblasts produce the extracellular matrix and constitute the structure's cellular skeleton, regulating spatial relationships between its components (microenvironment). The tubular epithelium and endothelium cooperate within an integrated microenvironment. Structural or functional impairment of the extracellular matrix, microcirculation vessels or tubular epithelium results in disturbances of tubulointerstitial compartment components. In the course of glomerular kidney diseases, the intrarenal RAA system becomes activated and inflammatory mediators are released. Interstitial inflammation and microcirculatory disorders develop, inducing adverse consequences, manifested mainly through the process of hypoxia and inflammation. Inflammation-induced increase in interleukin-1 (TNF-α) expression leads to increased concentrations of VEGF, ICAM-1, angiotensin II, IL-6 and IL-8. Cytokines activate fibroblasts, myofibroblasts and endothelial cells. Fibrosis is also triggered by HIF-1alpha pathway activation, resulting in vascular growth and fibroblast proliferation. This reaction likewise occurs through activation of NF-ĸß, EPO, GLUT-1, IGF-1 and INOS. Interstitial fibrosis is one of the factors determining the clinical course of kidney diseases. Apart from inducing fibrosis, microcirculatory disorders lead to the progression of hypoxia. Angiogenesis is a part of the repair process accompanying fibrosis. Its determinant is the normal function and structure of endothelial cells manifested by their ability to migrate and proliferate in response to, inter alia, angiopoietins, VEGF and nitric oxide synthase. Administering a three-drug RAAS-inhibiting therapy to patients with chronic glomerulopathies improves tubular function, measured by the decrease in excretion of NAG and propeptide of type III procollagen fibres, and contributes to the improvement in microcirculation functioning.


Asunto(s)
Proliferación Celular/fisiología , Progresión de la Enfermedad , Células Endoteliales/fisiología , Fibroblastos/fisiología , Insuficiencia Renal Crónica/fisiopatología , Humanos
8.
Semin Dial ; 27(4): E48-50, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24796505

RESUMEN

A 65-year-old female patient with chronic kidney disease stage 5 and a history of spleen neoplasm with dissemination within peritoneum is presented. During 5 years of hemodialysis therapy, bilateral occlusion of brachiocephalic and iliac vein developed as a consequence of vein catheterization. An attempt to cannulate inferior vena cava was unsuccessful. A cannulation of dilated collateral abdominal veins with dialysis needles allowed to perform several hemodialysis sessions in the patient.


Asunto(s)
Abdomen/irrigación sanguínea , Venas Braquiocefálicas/patología , Cateterismo Venoso Central/métodos , Circulación Colateral , Fallo Renal Crónico/terapia , Diálisis Renal/métodos , Vena Subclavia/patología , Anciano , Constricción Patológica , Femenino , Humanos , Enfermedades Vasculares/patología
9.
Kidney Blood Press Res ; 38(1): 83-91, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24577260

RESUMEN

BACKGROUND/AIMS: Analysis of gene expression in renal tissue is considered to be a diagnostic tool predicting the clinical course of glomerulonephritis. The present study quantified the relative transcript levels of VEGF, CTGF and HIF-1α in renal tissue to establish their relationship with some clinical variables in patients suffering from chronic glomerulonephritis (CGN). METHODS: 28 patients (6F and 22M, mean age 51.2±15.0) with CGN were enrolled. Type of CNG recognized by kidney biopsy (histopatological evaluation) was as follows: minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts, lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology was taken as control. Mean clinical follow-up of patients was 12 months after biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of biopsy and then in 6 months intervals. Real-time PCR was used to determine relative gene expression. The housekeeping gene GAPDH was used as normalization control. RESULTS: At the time of the biopsy relative expression of 3 analyzed genes was diminished in comparison to control. There were statistically significant differences in VEGF gene relative expression level in patients which varied according to eGFR and tendency in patients which varied according to DPE. HIF-alfa and CTGF gene showed only a tendency. CONCLUSIONS: Overexpression of the VEGF gene in subjects with DPE>3,5 g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.


Asunto(s)
Factor de Crecimiento del Tejido Conjuntivo/biosíntesis , Glomerulonefritis/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genética , Anciano , Enfermedad Crónica , Factor de Crecimiento del Tejido Conjuntivo/genética , Femenino , Estudios de Seguimiento , Expresión Génica , Glomerulonefritis/patología , Humanos , Hipertensión Renal/genética , Hipertensión Renal/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Riñón/metabolismo , Riñón/patología , Masculino , Persona de Mediana Edad
10.
Nephrol Dial Transplant ; 27(2): 608-12, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21613382

RESUMEN

BACKGROUND: Fructose has been strongly linked with hypertension, hyperuricemia and inflammation in experimental models and humans. However, the effect of low-fructose diet on inflammation, hyperuricemia and the progression of renal disease has not yet been evaluated in patients with chronic kidney disease (CKD). METHODS: Twenty-eight patients (age 59 ± 15 years, 17 males/11 females) with Stages 2 and 3 CKD were switched from a regular (basal) (60.0 g/24 h) to a low (12.0 g/24 h) fructose diet for 6 weeks, followed by a resumption of their regular diet for another 6 weeks. Diet was monitored by a dietician. At the baseline, low- and regular-fructose diet ambulatory blood pressure (BP) was measured and blood sampled for renal function (creatinine), inflammatory markers, fasting glucose and insulin and serum uric acid. Twenty-four-hour urine collections were also obtained for creatinine, uric acid, monocyte chemotatic protein-1, transforming growth factor-beta and N-acetyl-beta-D-glucosaminidase. RESULTS: The low-fructose diet tended to improve BP for the whole group (n = 28), while significant reduction of BP was only seen in dippers (n = 20) but not in non-dippers (n = 8). No effects on estimated glomerular filtration rate (eGFR) or proteinuria were observed. Serum uric acid was lowered non-significantly with low-fructose diet (7.1 ± 1.3 versus 6.6 ± 1.0 mg/dL, P < 0.1), whereas a significant decrease in fasting serum insulin was observed (11.2 ± 6.1 versus 8.2 ± 2.9 mIU/mL, P < 0.05) and the reduction persisted after return to the regular diet. A slight but not significant reduction in urinary uric acid and fractional uric acid excretion was observed while the patients were on the low fructose diet. The low-fructose diet also decreased high sensitivity C-reactive protein (hsCRP) (4.3 ± 4.9 versus 3.3 ± 4.5 mg/L; P < 0.01) and soluble intercellular adhesion molecule (sICAM) (250.9 ± 59.4 versus 227 ± 50.5 ng/mL; P < 0.05). The hsCRP returned to baseline with resumption of the regular diet, whereas the reduction in sICAM persisted. CONCLUSION: Low-fructose diet in subjects with CKD can reduce inflammation with some potential benefits on BP. This pilot study needs to be confirmed by a larger clinical trial to determine the long-term benefit of a low-fructose diet compared to other diets in subjects with CKD.


Asunto(s)
Dieta Baja en Carbohidratos , Fructosa , Inflamación/prevención & control , Insuficiencia Renal Crónica/dietoterapia , Insuficiencia Renal Crónica/diagnóstico , Anciano , Análisis de Varianza , Determinación de la Presión Sanguínea , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/prevención & control , Inflamación/fisiopatología , Resistencia a la Insulina/fisiología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Proyectos Piloto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ácido Úrico/sangre
11.
Kidney Blood Press Res ; 35(3): 161-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22116260

RESUMEN

BACKGROUND: Elevated serum uric acid experimentally stimulates renal vasoconstriction and activation of the renin- angiotensin system and consequently modulates erythropoietin (EPO) production. We used a dopamine-induced glomerular filtration response test (DIR) to assess whether elevated uric acid is associated with dopamine response and EPO levels in IgA patients. METHODS: In 46 non-nephrotic IgA patients (age: 33.7 ± 8.9 years) and 15 controls (age: 33.5 ± 6.9 years) with a glomerular filtration rate of 86.7 ± 17.4 and 118.1 ± 17.2 ml/min, respectively, renal vascular function was estimated based on DIR. DIR was measured using two 120-min creatinine clearances (before and after i.v. administration of 2 µg/kg/min dopamine) and at the same points EPO was measured. Uric acid, cholesterol, triglycerides, urinary uric acid and N-acetyl-ß-D-glucosaminidase were measured. RESULTS: Basal EPO was the same in IgA patients and controls (13.5 ± 9.5 vs. 10.6 ± 4.3 mU/ml, respectively; NS); however, EPO correlated with uric acid clearance in IgA patients but not in controls (r = 0.45, p < 0.002 vs. r = 0.25, p < 0.361, respectively), and DIR tended to be lower in IgA nephropathy (p < 0.06). A more pronounced slope between EPO and DIR as well as lower DIR/EPO was found in IgA patients. CONCLUSIONS: These results are consistent with greater renal vasoconstriction in IgA nephropathy that would stimulate EPO and reduce urate clearance.


Asunto(s)
Dopamina , Eritropoyetina/sangre , Tasa de Filtración Glomerular/fisiología , Glomerulonefritis por IGA/sangre , Ácido Úrico/sangre , Vasoconstricción/fisiología , Adulto , Biomarcadores/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Glomerulonefritis por IGA/diagnóstico , Humanos , Masculino , Vasoconstricción/efectos de los fármacos , Adulto Joven
12.
Kidney Blood Press Res ; 35(6): 608-18, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22948748

RESUMEN

BACKGROUND/AIMS: Hypoxia-inducible factor (HIF)-1α is responsible for increased expression of genes engaged in angiogenesis. Our previous study indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in locomotor muscles of uremic animals. Perhaps these changes are secondary to disturbances of HIF-1α in skeletal muscles. METHODS: Expression of HIF-1α at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls). RESULTS: For CKD5/6 versus controls, mRNA levels for HIF-1α, VEGF-A, VEGFR-1 and VEGFR-2 were significantly reduced only in MG, while eNOS was significantly decreased and iNOS was significantly increased only in ML. Western blot analysis indicated significantly increased HIF-1α protein levels in MG and ML from CKD1/2 animals versus controls, whereas in the CKD5/6 group, the level of HIF-1α protein decreased significantly in MG and increased significantly in ML versus controls and CKD1/2. CONCLUSION: The reduced expression of HIF-1α mRNA and protein in locomotor muscle from CKD5/6 animals may be involved in the pathogenesis of uremic myopathy. Increased expression of iNOS in the postural muscles may act as a protective factor through HIF-1α stabilization.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Músculo Esquelético/metabolismo , Insuficiencia Renal Crónica/metabolismo , Animales , Masculino , Músculo Esquelético/patología , ARN Mensajero/biosíntesis , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/patología
13.
Kidney Blood Press Res ; 36(1): 335-43, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23235363

RESUMEN

BACKGROUND/AIMS: Pharmacological inhibition of renin-angiotensin-aldosteron system (RAAS) may reduce proteinuria and the rate of chronic kidney disease progression. The aim was to compare the effects on albuminuria of the therapy with either: (i) telmisartan 80 mg and aliskiren 300 mg, (ii) telmisartan 80 mg and eplerenone 50 mg, (iii) telmisartan 160 mg as monotherapy. DESIGN AND PATIENTS: Randomized, double-center, double-blind, cross-over, three treatments-three periods of 8 weeks each study. 18 patients with non-diabetic proteinuric CKD stage 1-3 completed the protocol. RESULTS: There was significant difference in albuminuria between studied therapies (ANOVA; p<0.01). The combination therapy with telmisartan plus aliskiren decreased albuminuria more effectively than the treatment with telmisartan plus eplerenone and monotherapy with telmisartan 160 mg OD [376 mg/g creatinine (286-686) vs. 707 (502-1204) vs. 525 (318-763); post-hoc p<0.01 and p<0.05, respectively]. CONCLUSIONS: The study demonstrated that the combination therapy with angiotensin receptor blocker (ARB) and renin inhibitor was more effective in albuminuria lowering than the concomitant usage of ARB and mineralocorticoid receptor antagonist as well as than ARB in doses two-fold higher than usually used in treatment of hypertension in patients with non-diabetic CKD and that this higher antiproteinuric efficacy was independent on changes in blood pressure.


Asunto(s)
Amidas/uso terapéutico , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Progresión de la Enfermedad , Fumaratos/uso terapéutico , Hipertensión/tratamiento farmacológico , Proteinuria/prevención & control , Insuficiencia Renal Crónica/tratamiento farmacológico , Sistema Renina-Angiotensina/fisiología , Espironolactona/análogos & derivados , Adulto , Albuminuria/epidemiología , Albuminuria/prevención & control , Amidas/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Antagonistas de Receptores de Angiotensina/uso terapéutico , Bencimidazoles/farmacología , Benzoatos/farmacología , Comorbilidad , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Eplerenona , Femenino , Fumaratos/farmacología , Humanos , Hipertensión/epidemiología , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacología , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Estudios Prospectivos , Proteinuria/epidemiología , Insuficiencia Renal Crónica/epidemiología , Renina/antagonistas & inhibidores , Sistema Renina-Angiotensina/efectos de los fármacos , Índice de Severidad de la Enfermedad , Espironolactona/farmacología , Espironolactona/uso terapéutico , Telmisartán , Resultado del Tratamiento
14.
Int Urol Nephrol ; 54(4): 937-947, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34312814

RESUMEN

PURPOSE: Besides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage. METHODS: Assessment of 45 chronic kidney disease (CKD) patients stage 1-4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD-EPI equation: eGFR < 60 ml/min, eGFR > 60 ml/min) and different daily protein excretion (DPE): (DPE < 3.5 g; DPE > 3.5 g). RESULTS: Increased relative expression of hsa-miR-29-5p, hsa-miR-21-5p, and hsa-miR-196a-5p and decreased expression of hsa-miR-155-5p, hsa-miR-214-5p, hsa-miR-200a-5p, and hsa-miR-93-5p was demonstrated in urine of analyzed CKD patients. In subpopulation of chronic glomerulonephritis (CGN) patients, there was higher level of expression in urine of hsa-miR-155-5p, hsa-miR 214-3p, hsa-miR-93-5p, and hsa-miR-196a-5p in CGN with DPE < 3.5 g. CGN patients with eGFR < 60 ml/min showed higher expression level of miRNAs such as hsa-miR-214-3p, hsa-miR-29-5p, hsa-miR-93-5p, and hsa-miR-196-5p in urine. There was increase in hsa-miR 155-5p, hsa-miR-214-3p, and hsa-miR-200a-5p serum expression level in CKD population and reduction of hsa-miR-29a-5p, hsa-miR-21-5p, and hsa-miR-93-5p expression. Increased level of expression of hsa-miR-155-5p; hsa-miR-214-3p, hsa-miR-200a-5p, and hsa-miR-29-5p was found in CGN patients with eGFR > 60 ml/min. CONCLUSION: Increased relative expression of profibrogenic miRNAs in urine or serum of CKD patients with eGFR > 60 ml/min and DPE < 3.5 g may indicate higher degree of fibrosis at early CKD stages.


Asunto(s)
MicroARNs , Insuficiencia Renal Crónica , Humanos , Riñón/patología , Proteinuria , Reacción en Cadena en Tiempo Real de la Polimerasa , Insuficiencia Renal Crónica/metabolismo
15.
Med Sci Monit ; 17(2): CR117-21, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21278688

RESUMEN

BACKGROUND: CD14 is a membrane glycoprotein that acts as a co-receptor for the detection of bacterial lipopolysaccharide (LPS). Mutual interaction between CD14 and LPS plays an important role in the innate immune system. Increased serum soluble CD14 levels have been described in hemodialysis (HD) patients, and linked to increased mortality risk, inflammation and protein-energy wasting. The expression of CD14 may be influenced by CD14 promoter gene C-159T polymorphism. This study aimed to clarify the possible association between CD14 promoter gene C-159T polymorphism and nutritional status in hemodialysis patients. MATERIAL/METHODS: The study population consisted of 185 (104 males; 81 females) long-term HD patients treated in 5 dialysis centers. The control group consisted of 112 apparently healthy volunteers (32 males and 80 females). Nutritional status was assessed using a modified SGA scale, and anthropometric methods (BMI, WHR, waist, hip and mid-arm circumferences, biceps, triceps, subocular and subscapular skinfolds). Biochemical parameters evaluated included: CRP, albumin, creatinine, urea, cholesterol, triglycerides and TIBC. CD14 promoter gene C-159T polymorphism was determined by restriction fragment length polymorphism, after digestion of the PCR product with Hae III restriction endonuclease. RESULTS: Genotype and allele frequencies were similar to controls and compliant with Hardy-Weinberg equilibrium. No between-group differences were detected in measured variables with the exception of lower triglyceride levels in carriers of C allele in comparison to TT genotype. CONCLUSIONS: CD14 promoter gene C-159T polymorphism does not seem to be associated with nutritional status parameters in HD patients. It does seem, however, to influence triglyceride blood levels.


Asunto(s)
Receptores de Lipopolisacáridos/genética , Estado Nutricional/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Diálisis Renal , Alelos , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad
16.
Acta Radiol ; 52(4): 422-9, 2011 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-21498279

RESUMEN

BACKGROUND: Percutaneous endovascular examinations and interventions require significant amounts of iodinated contrast media (CM) and have been reported to be complicated by an increased incidence of post-contrast nephropathy. PURPOSE: To evaluate renal function, the incidence of post-contrast nephropathy, and risk factors after interventional procedures in neurosurgical patients after intra-arterial administration of a low-osmolar contrast medium (LOCM) versus an iso-osmolar contrast medium (IOCM). MATERIAL AND METHODS: This single-center, prospective, randomized, double-blinded study included 92 patients in its final analysis (mean age 49.6 ± 12.6 years, 29.3% men, mean eGFR 97.8 ± 26.3 mL/min/1.73 m(2)). LOCM was used in 48 patients (52.2%) and IOCM in 44 patients (47.8%). The patients were given an average of 151.2 ± 52.1 mL of contrast medium intra-arterially. Serum creatinine (SCr), urinary N-acetyl-ß-glucosaminidase (NAG) excretion, and creatinine clearance (CCr) were measured at baseline, and on days 1 and 3 after the procedure. RESULTS: Baseline risk factors, renal functional parameters, and average CM doses were not statistically different between the two groups. SCr, NAG, and CCr values did not differ significantly between the LOCM and IOCM groups on days 1 and 3 after CM administration. Nephropathy developed in 21 cases (22.8%): 13 (27.1%) after LOCM use and 8 (18.2%) after IOCM; (P = NS). The only significant risk factors of CIN were the diabetes (P = 0.0466) and atherosclerosis (P = 0.0498). CONCLUSION: We found a high incidence of nephropathy in neurosurgical patients after intra-arterial CM administration. The renal function values and incidence of nephropathy following LOCM administration were not statistically different from those following IOCM administration.


Asunto(s)
Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Complicaciones de la Diabetes/inducido químicamente , Método Doble Ciego , Femenino , Humanos , Inyecciones Intraarteriales , Yohexol/efectos adversos , Yohexol/análogos & derivados , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Concentración Osmolar , Estudios Prospectivos , Factores de Riesgo , Ácidos Triyodobenzoicos/efectos adversos
17.
Blood Press Monit ; 26(1): 22-29, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33234809

RESUMEN

OBJECTIVE: Chronic kidney disease (CKD) is associated with high cardiovascular risk. Prevalence of hypertension and hypertension-mediated organ damage (HMOD) increases with CKD progression. Nocturnal blood pressure (BP) is a strong predictor of cardiovascular complications. This cross-sectional study investigated the link between the diurnal BP profile and HMOD in nondiabetic CKD G1-G3b patients. METHODS: We investigated 109 CKD patients and 41 apparently healthy persons as controls. All subjects underwent 24-ambulatory blood pressure monitoring (ABPM), echocardiography with left ventricular mass index (LVMI) calculation and pulse wave velocity (PWV) measurement. RESULTS: Hypertension was present in 84% of CKD patients. SBP-24 and DBP-24, SBP-day and DBP-day did not differ between CKD and controls. Significant differences were found in SBP-night and DBP-night. The nondipping BP profile (SBP-night/SBP-day ratio ≥0.9) was found in 62% of CKD patients and 32% of controls (P < 0.005). Nocturnal hypertension was found in 56% of CKD patients. LVMI was higher in CKD compared to controls, higher in nondipping than dipping CKD patients, and higher in patients with nocturnal hypertension than without nocturnal hypertension. Abnormal left ventricular geometry was found in 72% nondipping and 43% dipping CKD patients. PWV was higher in CKD than in controls, in patients with nocturnal hypertension than without nocturnal hypertension but did not differ between CKD nondippers and dippers. CONCLUSION: The nondipping BP profile and nocturnal hypertension are associated with HMOD in G1-G3b CKD patients. Hence, there is a need for more extensive use of ABPM for individual risk assessment and personalization of antihypertensive treatment in CKD patients.


Asunto(s)
Hipertensión , Insuficiencia Renal Crónica , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Ritmo Circadiano , Estudios Transversales , Humanos , Hipertensión/complicaciones , Análisis de la Onda del Pulso , Insuficiencia Renal Crónica/complicaciones
18.
Med Sci Monit ; 16(6): CR301-6, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20512094

RESUMEN

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness. It was shown that PWV is related to increased cardiovascular risk in renal transplant recipients (RTR). Renal transplantation leads to decrease of arterial stiffness when compared with dialysis patients. Despite many studies, causes of increased arterial stiffness in RTR are not well defined. This study sought to investigate the association between cardiovascular risk factors, graft function, cardiovascular and immunosuppressive therapy, and carotid-femoral PWV in renal transplant recipients. MATERIAL/METHODS: Carotid-femoral PWV were measured with Complior device in 207 (73 female and 134 male) RTR aged 45+/-12 years, and in 21 healthy volunteers as controls. RESULTS: Pulse wave velocity was higher in RTR compared with controls: 9.2+/-2.1 m/s vs 8.3+/-1.5m/s (P<.05). In RTR group, significant correlations were found between PWV and age (r=0,55; P<.001), male sex (r=0.17; P<.02), body weight (r=0.23; P<.01), systolic (SBP) (r=0.36; P<.001), and diastolic blood pressure (DBP) (r=0.19; P<.01), pulse pressure (pulse pressure) (r=0.34; P<.001), mean arterial pressure (MAP) (r=0.28; P<.001), number of antihypertensive medication (r=0.17; P<.02), fasting glucose (r=0.24; P<.01), presence of diabetes (r=0.24; P<.01), eGFR (r=-0.19; P<.01), therapy with cyclosporine (r=0.29; P<.001), and therapy with tacrolimus (r=-0.22; P<.01). In stepwise multiple regression analysis, age, male sex, MAP, cyclosporine, and fasting glucose concentration were independently associated with increased PWV. CONCLUSIONS: Arterial stiffness is increased in RTR. Type of immunosuppressive regimen, high blood pressure, and glucose metabolism disturbances should be considered as potential targets to reduce increased arterial stiffness in RTR.


Asunto(s)
Arterias/fisiopatología , Fallo Renal Crónico/terapia , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/fisiología , Adulto , Anciano , Estudios Transversales , Ciclosporina/uso terapéutico , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis de Regresión
19.
Pol J Pathol ; 61(4): 229-33, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21290347

RESUMEN

Rheumatoid arthritis (RA) is an autoimmune disease also known as an example of connective tissue disease. There are no case-controlled studies to determine the frequency of renal disease in RA. Most of patients present slow progression of chronic kidney disease while acute renal failure is uncommon in rheumatoid arthritis. We report a case of a 40-year-old woman with established medical history of RA who presented with abrupt onset of severe hypertension with rapidly growing serum creatinine concentration and oliguria. Renal biopsy revealed oedematous intimal thickening of vessels and ischemic changes in glomeruli, and nonspecific lesions in tubules and interstitium. These pathological findings were consistent with the scleroderma nephropathy. Additionally, we provided a brief literature overview on coincidence of hypertension and different types of connective tissue diseases.


Asunto(s)
Lesión Renal Aguda/complicaciones , Artritis Reumatoide/complicaciones , Esclerodermia Difusa/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/fisiopatología , Adulto , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Riñón/patología , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/fisiopatología
20.
Artículo en Inglés | MEDLINE | ID: mdl-32957678

RESUMEN

Arterial hypertension (AH) is one of the most common cardiovascular diseases increasing mortality rates in Poland and worldwide. Due to its prevalence, complications and treatment costs, AH is a significant health-related, economic and social problem. The aim of this study was to assess the level of acceptance of illness and compliance with therapeutic recommendations in patients with AH. The study included 200 outpatient hypertensive patients, 85 men and 115 women aged 49.1 ± 11.6, and used the standardized acceptance of illness (AIS), the eight-item Morisky Medication Adherence Scale (MMAS-8) and author's design questionnaires. The level of acceptance of illness was found to be as follows: higher in men than in women, unaffected by comorbidities or sociodemographic factors such as residence and professional activity, decreasing with age, and correlating negatively with the duration of antihypertensive therapy. The level of adherence and compliance did not affect the AIS score and increased with the level of education. The study population demonstrated an overall good level of acceptance of illness. Men were characterized by lower levels of adherence and compliance. Patients with AH presented a moderate level of adherence and compliance, which indicates the need for providing active education, support and extensive cooperation facilitating their conformity to therapeutic recommendations.


Asunto(s)
Antihipertensivos , Hipertensión , Adulto , Antihipertensivos/uso terapéutico , Actitud Frente a la Salud , Estudios Transversales , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Polonia , Encuestas y Cuestionarios
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