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BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
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Glomerulonefritis Membranosa , Trasplante de Células Madre Hematopoyéticas , Humanos , Glomerulonefritis Membranosa/inmunología , Glomerulonefritis Membranosa/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Adulto , Persona de Mediana Edad , Leucemia Mieloide Aguda/terapia , Síndrome Nefrótico/etiologíaRESUMEN
Although changes in dietary sodium intake alter blood pressure (BP) in salt-sensitive individuals, pathophysiological mechanisms are still unknown. It has been reported that uromodulin is involved in sodium tubular transport, and genome-wide association studies pointed to UMOD gene as one of the most important gene candidates for arterial hypertension. Our aim was to analyze urinary uromodulin, salt intake and BP in 326 young middle-aged subjects (mean age 36±8 years, 49.4% male). In a subgroup of 175 individuals, ambulatory blood pressure monitoring and echocardiogram were performed. Uromodulin was determined by ELISA. According to the JNC-7 criteria, subjects were classified as optimal BP (n=103, men 72%), prehypertension (PHT) (n=143, men 43%) and hypertension (HT) (n= 80, men 38%). There were no differences in age, salt intake, estimated glomerular filtration rate, sodium excretion and uromodulin among BP groups. However, in PHT subjects, uromodulin was positively associated with fractional sodium excretion and negatively with 24-h sodium excretion and diastolic BP dip. These findings point to the effect of uromodulin on sodium reabsorption along the nephron and consequently circadian BP alteration in prehypertensives.
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Hipertensión , Sodio , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Estudio de Asociación del Genoma Completo , Cloruro de Sodio Dietético , Uromodulina/genéticaRESUMEN
INTRODUCTION: The pandemic of obesity is strongly related to increase of chronic kidney disease (CKD) prevalence. The currently recommended CKD epidemiology collaboration (CKD EPI) equation has several serious limitations, particularly in obese subjects who have high body surface area (BSA). The aim of our study was to analyze differences in the prevalence of CKD between CKD EPI and de-indexed equations where individual BSA was used. METHODS: In a total of 2,058 subjects (random sample from a general rural population, 29.65% obese), BSA was estimated using DuBois and DuBois and Moesteller equations and included into the de-indexed equations (CKD DBi, CKD Mi). CKD was classified according to the KDIGO guidelines, and glomerular hyperfiltration (GHF) was defined as 95th percentile, according to the gender and age decade. RESULTS: In obese subjects, prevalence of CKD was significantly higher with CKD EPI than with CKD DBi and CKD Mi equations (9.5%, 6.1%, 5.3%, respectively; p < 0.001), while prevalence of GHF was significantly lower (3.8%, 12.3%, 12.8%, respectively; p < 0.001). Opposite results were observed in subjects with a body mass index <25 kg/m2 for CKD (5%, 7.1%, 7.2%; p = 0.07) and GHF prevalence (6.1%, 1%, 0.6%; p < 0.001). DISCUSSION/CONCLUSIONS: The prevalence of CKD is overestimated, and the prevalence of GHF is underestimated in obese subjects using the CKD EPI equation, i.e., the CKD EPI equation is unreliable in one-third of the population. De-indexed equations should be recommended instead of the CKD EPI equation in epidemiological studies until direct measurement of the glomerular filtration rate becomes more available.
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Insuficiencia Renal Crónica , Humanos , Tasa de Filtración Glomerular , Creatinina , Insuficiencia Renal Crónica/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa CorporalRESUMEN
The aims of the study were to provide data on chronic kidney disease (CKD) prevalence in rural population and to analyze the association with cardiovascular risk factors and aging. A random sample of 2193 farmers (1333 female (F) and 860 male (M), mean age 50.61±17.12) were enrolled. Questionnaire and clinical examination were conducted. Participants provided a spot urine and fasting blood sample. Estimated glomerular filtration rate (eGFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Subjects were classified according to the KDIGO guidelines. The overall prevalence of CKD (eGFR <60 mL/min/1.73 m2) was 8.83% (F vs. M 9.9% vs. 6.3%; p<0.001). Albuminuria (albumin-to-creatinine ratio >30 mg/g) was found in 8.45% (F vs. M p>0.05). Sharp increase in CKD prevalence was found to begin after the sixth decade (29.44% in subjects older than 65 years; F vs. M 30.9% vs. 26.8%; p<0.01). The strongest predictor factors for CKD were age >65 years (OR 22.12), hypertension (OR 6.53), albuminuria (OR 5.71), fasting blood glucose >7 mmol/L (OR 5.49), diabetes (OR 3.07), abdominal obesity (OR 2.05) and non-smoking (OR 0.41). In multivariate analysis, age (OR 1.13), female gender (OR 0.60) and diabetes (OR 1.75) were the independent predictor factors for CKD. In conclusion, CKD prevalence is high in rural population, being higher in women than in men. In both genders, eGFR significantly decreased with aging. Aging is a significant independent predictor of CKD.
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Diabetes Mellitus , Hipertensión , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Albuminuria/epidemiología , Albuminuria/etiología , Albuminuria/orina , Población Rural , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Hipertensión/complicaciones , Prevalencia , Factores de Riesgo , Creatinina/orinaRESUMEN
We report the case of 39-year-old Caucasian man presenting in emergency department with new onset of severe hypertension with hypokalaemia eight weeks after renal colic. Patient was referred to a hypertension unit for further investigation. Hormonal analysis confirmed secondary aldosteronism and slightly impaired kidney function. Imaging revealed smaller right kidney, 'string of beads appearance' of distal part of right renal artery, a short zone of dissection and renal infarction. Renal scintigraphy showed significant blood flow reduction and severe functional damage of the right kidney. Despite multidrug antihypertensive treatment patient's hypertension was resistant and target organ damage evolved. After initial patient's refusal, he was later successfully treated with laparoscopic simple nephrectomy. Histopathological analysis confirmed renal artery dissection and medial fibroplasia. Thereafter, hypertension was controlled with trandalopril monotherapy. This is a first case report of the patient with renovascular multifocal fibromuscular dysplasia, dissection and renal infarction whose diagnosis of the disease was confirmed by angiography and histopathologic analysis. Resistant hypertension was successfully treated with nephrectomy.
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Displasia Fibromuscular , Hipertensión Renovascular , Hipertensión , Enfermedades Renales , Adulto , Displasia Fibromuscular/complicaciones , Humanos , Hipertensión/complicaciones , Infarto/etiología , Masculino , Arteria Renal/diagnóstico por imagen , Arteria Renal/cirugíaRESUMEN
Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.
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Lesión Renal Aguda , COVID-19 , Trasplante de Riñón , Aloinjertos , Biopsia , Rechazo de Injerto/etiología , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Nefrectomía , SARS-CoV-2RESUMEN
AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.
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Disección Aórtica/epidemiología , Displasia Fibromuscular/epidemiología , Adulto , Factores de Edad , Anciano , Disección Aórtica/diagnóstico por imagen , Argentina/epidemiología , Asia/epidemiología , Angiografía por Tomografía Computarizada , Europa (Continente)/epidemiología , Femenino , Displasia Fibromuscular/diagnóstico por imagen , Humanos , Incidencia , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores Sexuales , Túnez/epidemiologíaRESUMEN
Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. AA initially was involved in the outbreak of cases of rapidly progressive renal fibrosis reported in Belgium after intake of root extracts of Aristolochia fangchi imported from China. A high prevalence of UTUC was found in these patients. The common molecular link between Balkan and Belgian nephropathy cases was the detection of aristolactam-DNA adducts in renal tissue and UTUC. These adducts are not only biomarkers of prior exposure to AA, but they also trigger urothelial malignancy by inducing specific mutations (A:T to T:A transversion) in critical genes of carcinogenesis, including the tumor-suppressor TP53. Such mutational signatures are found in other cases worldwide, particularly in Taiwan, highlighting the general public health issue of AA exposure by traditional phytotherapies.
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Ácidos Aristolóquicos/toxicidad , Nefropatía de los Balcanes/inducido químicamente , Carcinoma de Células Transicionales/inducido químicamente , Exposición a Riesgos Ambientales/efectos adversos , Neoplasias Renales/inducido químicamente , Neoplasias Ureterales/inducido químicamente , Animales , Aristolochia , Nefropatía de los Balcanes/diagnóstico , Nefropatía de los Balcanes/patología , Nefropatía de los Balcanes/terapia , Carcinógenos/toxicidad , Aductos de ADN , Humanos , Tamizaje MasivoRESUMEN
Balkan endemic nephropathy (BEN), an environmental form of aristolochic acid nephropathy is characterized with later onset and milder forms of hypertension (HT). Thus, we hypothesized that arterial stiffness progresses slower in BEN patients resulting in lower CV mortality. A total of 186 hemodialysed (HD) patients (90 BEN, 96 non-BEN; 67.3 + 13.0 years) were enrolled and followed-up for 25 months. Brachial blood pressure (BP) and pulse wave velocity (PWV) were determined before mid-week dialysis. BEN patients were older (72.1 ± 37.1 vs. 62.8 ± 15.1; p < 0.001), had shorter duration of HT prior commencement of HD than non-BEN patients (36 vs. 84 months; p < 0.001). There were no differences in BP, but BEN patients were treated with less antihypertensive drugs (p < 0.01). BEN patients had lower PWV values at baseline and at the end of follow-up period despite being chronologically older (p < 0.001). Baseline PWV > 10 m/s was associated with higher risk for CV mortality (aHR 1.8 [1.4, 2.4]). In multivariate analyses BEN was predictor of lower PWV. During the follow-up period significantly less CV deaths were observed in BEN vs. on-BEN patients (12 vs. 31; p = 0.001). CV mortality adjusted for other risk factors was significantly lower in BEN group (aHR 0.2 [0.1, 0.5]). Overall BEN patients had longer mean survival time on HD (22.3 vs. 18.2 months; p < 0.001). Observed slower vascular aging (i.e., lower PWV) in BEN patients compared to other ESRD patients is related to the later onset of HT and milder stages of HT during predialytic clinical course and better control of BP and phosphate during HD.
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Regardless of having a similar antihypertensive effect, different antihypertensive drug classes have a different effect on albuminuria. Patients with albuminuria will usually need more than one drug to achieve blood pressure control, particularly if the aim is also to reduce albuminuria. Albuminuria is independently associated with cardiovascular and renal risk regardless of diabetes status. The recent ESC/ESH guidelines listed microalbuminuria among the hypertension-mediated organ damages. Albumin-to-creatinine ratio was suggested to be included in routine workup for evaluation of every hypertensive patient and changes in albuminuria were considered to have moderate prognostic value. Because of its specific effects on renal hemodynamic and glomerular structure, the ACEIs and ARBs should be prescribed in maximum tolerated doses. The MRAs can be considered in uncontrolled hypertensive patients. The CCBs can be used in addition to the RAAS blockade. Data on antialbuminuric effect of the new CCBs generation (T-type and N-type calcium channel blockers) is promising and they might be preferential CCBs when available. In case of resistant hypertension, thiazide or thiazide-like diuretic has to be added into the combination with RAAS blockers and other antihypertensive drugs. Low-salt intake has to be recommended for all hypertensive patients, particularly those with albuminuria. A multifactorial and early antialbuminuric approach should be started even when albuminuria values are below the cut-off value for microalbuminuria.
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Albuminuria/tratamiento farmacológico , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , HumanosRESUMEN
INTRODUCTION: Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. MATERIALS AND METHODS: A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. CONCLUSIONS: eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN.
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Algoritmos , Insuficiencia Renal Crónica/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Croacia/epidemiología , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Endemic nephropathy (EN) is a chronic tubulointerstitial aristolochic acid nephropathy (AAN) affecting residents of the certain villages in the valleys of the major tributaries of the Danube river in the south-east Europe including Croatia. Patients with EN have a significantly higher incidence of transitional cell carcinoma of the ureter than the general population. A-T transversion of the p53 gene is now considered to be a mutational "signature" of aristolochic acid, which is a cause of endemic nephropathy. Currently used diagnostic criteria for EN are outdated, uneven (three types of criteria) and are not in agreement with proposed new guidelines for kidney diseases. Therefore, based on current knowledge and expertise of a group of scientists and experts from all countries with EN as well as world where AAN has been reported, new diagnostic criteria and the new classification of the population of endemic villages were created at a symposium on EN. EN presents a major public health problem and current knowledge about this disease as well as new diagnostic criteria should help us in its early detection and treatment and maybe in a near future its eradication.
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Nefropatía de los Balcanes/epidemiología , Ácidos Aristolóquicos/genética , Nefropatía de los Balcanes/diagnóstico , Nefropatía de los Balcanes/genética , Croacia/epidemiología , Genes p53/genética , Humanos , Incidencia , MutaciónRESUMEN
BACKGROUND AND OBJECTIVES: Improvements in agricultural practices in Croatia have reduced exposure to consumption of aristolochic acid-contaminated flour and development of endemic (Balkan) nephropathy. Therefore, it was hypothesized that Bosnian immigrants who settled in an endemic area in Croatia 15-30 years ago would be at lower risk of developing endemic nephropathy because of reduced exposure to aristolochic acid. To test this hypothesis, past and present exposure to aristolochic acid, proximal tubule damage as a hallmark of endemic nephropathy, and prevalence of CKD in Bosnian immigrants were analyzed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional observational study from 2005 to 2010, 2161 farmers were divided into groups: indigenous inhabitants from endemic nephropathy and nonendemic nephropathy villages and Bosnian immigrants; α-1 microglobulin-to-creatinine ratio >31.5 mg/g and eGFR<60 ml/min per 1.73 m(2) were considered to be abnormal. RESULTS: CKD and proximal tubule damage prevalence was significantly lower in Bosnian immigrants than inhabitants of endemic nephropathy villages (6.9% versus 16.6%; P<0.001; 1.3% versus 7.3%; P=0.003, respectively); 20 years ago, Bosnian immigrants observed fewer Aristolochia clematitis in cultivated fields (41.9% versus 67.8%) and fewer seeds among wheat seeds (6.1% versus 35.6%) and ate more purchased than homemade bread compared with Croatian farmers from endemic nephropathy villages (38.5% versus 14.8%, P<0.001). Both Croatian farmers and Bosnian immigrants observe significantly fewer Aristolochia plants growing in their fields compared with 15-30 years ago. Prior aristolochic acid exposure was associated with proximal tubule damage (odds ratio, 1.64; 95% confidence interval, 1.04 to 2.58; P=0.02), whereas present exposure was not (odds ratio, 1.31; 95% confidence interval, 0.75 to 2.30; P=0.33). Furthermore, immigrant status was an independent negative predictor of proximal tubule damage (odds ratio, 0.40; 95% confidence interval, 0.19 to 0.86; P=0.02). CONCLUSIONS: Bosnian immigrants and autochthonous Croats residing in endemic areas are exposed significantly less to ingestion of aristolochic acid than in the past. The prevalence of endemic nephropathy and its associated urothelial cancers is predicted to decrease over time.
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Enfermedades de los Trabajadores Agrícolas/inducido químicamente , Agricultura , Ácidos Aristolóquicos/efectos adversos , Nefropatía de los Balcanes/inducido químicamente , Dieta/efectos adversos , Emigrantes e Inmigrantes , Contaminación de Alimentos , Túbulos Renales Proximales/efectos de los fármacos , Exposición Profesional/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Trabajadores Agrícolas/diagnóstico , Enfermedades de los Trabajadores Agrícolas/etnología , Enfermedades de los Trabajadores Agrícolas/fisiopatología , Enfermedades de los Trabajadores Agrícolas/prevención & control , alfa-Globulinas/orina , Nefropatía de los Balcanes/diagnóstico , Nefropatía de los Balcanes/etnología , Nefropatía de los Balcanes/fisiopatología , Nefropatía de los Balcanes/prevención & control , Biomarcadores/sangre , Biomarcadores/orina , Bosnia y Herzegovina/etnología , Creatinina/sangre , Creatinina/orina , Croacia/epidemiología , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Exposición Profesional/prevención & control , Oportunidad Relativa , Prevalencia , Características de la Residencia , Factores de Riesgo , Factores de Tiempo , Adulto JovenRESUMEN
Glomerular diseases may be classified as acute or chronic, primary or secondary, hereditary or acquired, proliferative or non-proliferative etc. The most commonly used is the classification according to the histopathological finding. For certain types of glomerulonephritides histopathological image, as well as clinical presentation, may vary widely. A while ago there was no classification based on the pathogenesis of certain types of glomerular diseases. However, as scientists ellucidate the underlying pathogenetic mechanism, current classifications change. The latter is best shown at the example of membranoproliferative glomerulonephritis.
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Glomerulonefritis/clasificación , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/patología , HumanosRESUMEN
Considerable progress in understanding of the pathogenesis of a number of primary glomerular diseases is evident. Scientific achievements in this field led to reclassification of certain types of glomerulonephritides, development of new diagnostic tests, as well as new therapeutic approaches. These new findings will enable us to treat primary glomerulopathies more efficiently thus reducing incidence of resistant disease. Novelties in diagnostics, treatment algorithm, characteristics of the resistant disease and the possibilities of specific treatment are shown in this review.
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Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Pruebas Diagnósticas de Rutina , Glomerulonefritis/patología , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/terapia , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/terapia , Humanos , Incidencia , Glomérulos Renales/patologíaRESUMEN
OBJECTIVE: Arterial stiffness is an independent cardiovascular risk factor. Aging, high blood pressure and increased renin-angiotensin system activity contribute to increased arterial stiffness in patients with atherosclerotic renovascular hypertension (aRVH). A literature search failed to identify any study related to this topic. Therefore, our aim was to determine the arterial stiffness in patients with aRVH and analyze whether stenting in addition to multifactorial drug therapy has beneficial effects on markers of stiffness and the clinical course. METHODS: In this 6-month longitudinal study, 37 patients with refractory hypertension and unilateral aRVH were enrolled. After stenting, all patients received multifactorial dug therapy including 80âmg of telmisartan. Arterial stiffness indices were determined using Arteriograph. The control group consisted of 44 patients with essential hypertension. RESULTS: There were no differences in brachial blood pressure values between the two groups (Pâ>â0.05). At baseline, adjusted pulse wave velocity (PWV) was higher in aRVH patients than that of essential hypertensive patients (12.8â±â0.4 vs. 11.6â±â0.3âm/s; Pâ=â0.029). In the aRVH group, at the end of the follow-up, a significant decrease in the aortic augmentation index (37.7â±â9.9 vs. 33.7â±â11.4; Pâ=â0.02) without changes in PWV was observed (Pâ>â0.05). CONCLUSION: This study is the first to show that arterial stiffness is higher in patients with refractory aRVH than in those with essential hypertension. Multifactorial therapy based on stenting and intensive medical treatment reduced central blood pressure and augmentation index. Failure to obtain PWV reduction is likely a consequence of the present irreversible structural vessel changes. Longer follow-up might enable us to resolve whether arterial stiffness indices have better predictive ability in patients with aRVH than brachial blood pressure.
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Hipertensión Renovascular/fisiopatología , Rigidez Vascular , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Aorta/fisiopatología , Aterosclerosis/complicaciones , Bencimidazoles/uso terapéutico , Benzoatos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Determinación de la Presión Sanguínea , Hipertensión Esencial , Femenino , Humanos , Hipertensión/fisiopatología , Hipertensión/terapia , Hipertensión Renovascular/etiología , Hipertensión Renovascular/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Sistema Renina-Angiotensina , Factores de Riesgo , Stents , TelmisartánRESUMEN
Diagnosis of endemic nephropathy (EN) is based on the combination of several clinical and laboratory criteria. Despite extensive research no specific diagnostic biomarker for EN has yet been identified. The aim of the study was to evaluate the diagnostic significance of the variables previously proposed as diagnostic criteria, but also new ones. After an extended questionnaire, the clinical and laboratory examination population in EN villages was classified according to the modified WHO criteria. The urinary active form of TGF-ß was measured with a bioassay using a cell line which expresses luciferase activity. In the study we used ROC analysis to examine the predictive value of the tested variables. In the study there was no difference in haemoglobin level between the study subgroups. Leucine aminopeptidase (LAP) in urine and active urinary TGF-ß levels were increased in the EN diseased group when compared to other subgroups, but they did not fulfil the statistical criteria needed for differentiating a diseased form from other study subgroups. Both kidney length and parenchima thickness, alfa1-microglobulinuria, and kidney function assessed by MDRD formula were the variables that differentiated the study subgroups well. Based on our results the cut-off value of alfa1-microglobulin for screening should be 23.5 mg/g creatinine instead of 15 mg/g creatinine in the present criteria, and for making a diagnosis of EN 31,5 mg/g creatinine. Persons with a positive family history for EN had a 5.8 times greater risk of developing EN when compared to a negative one. Taken together, the above-mentioned variables should be implemented in new uniform diagnostic criteria for EN.
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Nefropatía de los Balcanes/diagnóstico , Riñón/patología , Adolescente , Adulto , Ácidos Aristolóquicos/metabolismo , Nefropatía de los Balcanes/metabolismo , Biomarcadores/metabolismo , Diagnóstico Diferencial , Femenino , Humanos , Riñón/metabolismo , Masculino , Factor de Crecimiento Transformador beta/metabolismo , Adulto JovenRESUMEN
Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.
Asunto(s)
Nefropatía de los Balcanes , Consenso , Manejo de la Enfermedad , Tamizaje Masivo/métodos , Nefropatía de los Balcanes/clasificación , Nefropatía de los Balcanes/diagnóstico , Nefropatía de los Balcanes/terapia , HumanosRESUMEN
BACKGROUND: Hypertension is not considered to be a characteristic of endemic nephropathy (EN). Recent observations suggested that it might be more prevalent than it was reported before. AIM: The aim of our study was to analyze prevalence, treatment and control of hypertension in a Croatian endemic area. METHODS: In the present cross-sectional study, 1,602 farmers were enrolled, 1,246 from EN and 356 from control villages. Epidemiological and medical histories were taken and clinical and laboratory examinations performed for kidney function. Blood pressure was measured following the ESH/ESC guidelines. RESULTS: The prevalence of hypertension in EN villages was higher than in control (50.8 vs. 46.5%, p = 0.005). There was no difference in overall treatment, control of all and treated hypertensives between the villages. In all villages, women were treated more than men (EN 41.6 vs. 28.4%, p < 0.001; control 46.4 vs. 27.3%, p < 0.001), but better control of treated was achieved in men (EN 24.7 vs. 17.4%, p = 0.002; control 29.6 vs. 15.5%, p = 0.002). Women had lower income and level of education than men (p < 0.01). CONCLUSION: Hypertension is highly prevalent in endemic villages. In all villages, men had better blood pressure control despite being treated less. This finding could be explained by poorer education and income in women.
Asunto(s)
Enfermedades Endémicas/prevención & control , Hipertensión/epidemiología , Hipertensión/terapia , Enfermedades Renales/epidemiología , Enfermedades Renales/terapia , Adulto , Anciano , Croacia/epidemiología , Estudios Transversales , Femenino , Humanos , Hipertensión/diagnóstico , Enfermedades Renales/diagnóstico , Masculino , Persona de Mediana Edad , Prevalencia , Resultado del TratamientoRESUMEN
BACKGROUND: Tubular proteinuria and enzymuria are hallmarks of endemic nephropathy (EN). The role of I/D angiotensin convertase (ACE) gene polymorphism has not yet been elucidated in this peculiar chronic tubulointerstitial nephritis, and our aim was to investigate the role of this polymorphism in EN focusing on the urinary N-acetyl-ß-D-glucosaminidase (NAG) excretion, a biomarker of proximal tubular damage. METHODS: ACE genotype and allele frequencies were determined in 229 farmers (147 women and 82 men) from an endemic Croatian village. The farmers were stratified according to the WHO criteria into the following subgroups: those 'at risk' for EN (n = 37), 'suspected of having EN' (n = 57), and 'others' (n = 135). RESULTS: There were 74 (32.3%) subjects homozygous for the D allele, 99 (43.2%) heterozygous (ID genotype) and 56 (24.4%) homozygous for the I allele. No differences in allele frequency were found between the established WHO subgroups (p > 0.05). In the whole group, DD subjects had significantly higher values of diastolic blood pressure (p = 0.003) and urinary NAG than subjects with ID and II genotype (5.5 ± 1.2 vs. 4.0 ± 3.0 vs. 3.8 ± 4.2, respectively; p = 0.023). The highest values of serum creatinine (p = 0.02), proteinuria (p = 0.03) and urinary NAG (6.0 ± 3.7 vs. 3.7 ± 2.1 vs. 3.0 ± 1.6, respectively; p = 0.008) were observed in those suspected of having EN group with the DD genotype. CONCLUSION: ACE gene polymorphism is not a risk factor for EN. However, it might influence the clinical course of EN, and increased excretion of NAG might be a prognostic marker of this chronic tubulointerstitial nephritis.