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Cerebrovascular disease accounts for major neurologic disabilities in patients with type 2 diabetes mellitus (DM). A potential association of mitochondrial DNA (mtDNA) and inflammation with cerebral vessel remodeling in patients with type 2 DM was evaluated. A cohort of 150 patients and 30 healthy controls were assessed concerning urinary albumin/creatinine ratio (UACR), synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), N-acetyl-ß-(D)-glucosaminidase (NAG), interleukins IL-17A, IL-18, IL-10, tumor necrosis factor-alpha (TNFα), intercellular adhesion molecule-1 (ICAM-1). MtDNA-CN and nuclear DNA (nDNA) were quantified in peripheral blood and urine by qRT-PCR. Cytochrome b (CYTB) gene, subunit 2 of NADH dehydrogenase (ND2), and beta 2 microglobulin nuclear gene (B2M) were assessed by TaqMan assays. mtDNA-CN was defined as the ratio of the number of mtDNA/nDNA copies, through analysis of the CYTB/B2M and ND2/B2M ratio; cerebral Doppler ultrasound: intima-media thickness (IMT)-the common carotid arteries (CCAs), the pulsatility index (PI) and resistivity index (RI)- the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), the breath-holding index (BHI). The results showed direct correlations of CCAs-IMT, PI-ICAs, PI-MCAs, RI-ICAs, RI-MCAs with urinary mtDNA, IL-17A, IL-18, TNFα, ICAM-1, UACR, synaptopodin, podocalyxin, KIM-1, NAG, and indirect correlations with serum mtDNA, IL-10. BHI correlated directly with serum IL-10, and serum mtDNA, and negatively with serum IL-17A, serum ICAM-1, and NAG. In neurologically asymptomatic patients with type 2 DM cerebrovascular remodeling and impaired cerebrovascular reactivity may be associated with mtDNA variations and inflammation from the early stages of diabetic kidney disease.
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ADN Mitocondrial , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Inflamación , Humanos , ADN Mitocondrial/genética , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Persona de Mediana Edad , Inflamación/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Anciano , Remodelación Vascular/genética , Estudios de Casos y ControlesRESUMEN
Immune mechanisms play an important role in the pathogenesis of glomerulonephritis (GN), with autoimmunity being the main underlying pathogenetic process of both primary and secondary GN. We present three autoimmune diseases mediated by different autoimmune mechanisms: glomerulonephritis in vasculitis mediated by anti-neutrophil cytoplasmic antibodies (ANCAs), glomerulonephritis mediated by anti-glomerular basement membrane antibodies (anti-GBM antibodies), and immune complex-mediated glomerulonephritis. Some of these diseases represent a common clinical and histopathologic scenario, namely rapidly progressive crescentic glomerulonephritis. This is a severe illness requiring complex therapy, with the main role being played by therapy aimed at targeting immune mechanisms. In the absence of immune therapy, the crescents, the characteristic histopathologic lesions of this common presentation, progress toward fibrosis, which is accompanied by end-stage renal disease (ESRD). The fact that three diseases mediated by different immunopathologic mechanisms have a common clinical and histopathologic picture reveals the complexity of the relationship between immunopathologic mechanisms and their clinical expression. Whereas most glomerular diseases progress by a slow process of sclerosis and fibrosis, the glomerular diseases accompanied by glomerular crescent formation can progress, if untreated, in a couple of months into whole-nephron glomerulosclerosis and fibrosis. The outcome of different immune processes in a common clinical and histopathologic phenotype reveals the complexity of the relationship of the kidney with the immune system. The aim of this review is to present different immune processes that lead to a common clinical and histopathologic phenotype, such as rapidly progressive crescentic glomerulonephritis.
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(1) Introduction and Aims: Little is known about the relationship between renal pathology and gallbladder pathology, although the two organs (the gallbladder and the right kidney) are in close proximity to one another. If a renal abscess disseminates, the gallbladder would be one of the secondary organs involved. As the bile provides a favorable environment for the development of pathogenic germs, it allows for the development of acute cholecystitis, even if calculi are absent, thus resulting in the development of acute acalculous cholecystitis. The aim of our study was to analyze the association between acute acalculous cholecystitis (AAC) and renal abscesses. (2) Methods: A department-wide retrospective cohort observational study including 67 patients with renal abscesses, with a mean age of 34.5+/-16.21 years and with five males and 62 females, was conducted. All of the patients were examined by an abdominal ultrasound. The lab tests included CBC with differential liver enzymes and serum bilirubin (in order to assess alterations in the liver function which can be associated with AAC) and serum creatinine (in order to assess the renal function). Blood culture and urine culture tests were also performed. (3) Results: Of the 67 patients with renal abscesses, eight (11.94%) were associated with acute cholecystitis: four cases (5.97%) of acalculous cholecystitis and four cases (5.97%) of calculous cholecystitis, two of which presented biliary sludge (acute micro-calculous cholecystitis). All four cases of acute acalculous cholecystitis presented with sepsis, and there was one case of septic shock at onset. We did not observe an impairment in renal function in the patients presenting with acute acalculous cholecystitis, and hepatic impairment was inconstant and moderate. All of the cases had a favorable outcome after a prompt initiation of intensive antibiotic therapy; both the renal abscess and the acute acalculous cholecystitis receded without further complications. (4) Conclusions: The association of acute acalculous cholecystitis with renal abscesses could be related to the possibility of germ dissemination from the infectious focus. In the case of a renal abscess, careful clinical, lab, and imaging exams of the gallbladder are recommended in order to ensure early therapeutic intervention in the event of an association with acute acalculous cholecystitis.
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Background: Endoscopic retrograde cholangiopancreatography (ERCP) represents a major pivotal point in gastrointestinal endoscopy. Little is known about acute kidney injury (AKI) post-ERCP. This study analyses the incidence, risk factors, and prognosis of post-ERCP AKI. Methods: A total of 396 patients were prospectively studied. AKI was defined by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL or by an increase in SCr ≥ 50% in the first 48 h post-ERCP. Logistic regression analysis was used to identify the predictors of AKI and in-hospital mortality. A two-tailed p value < 0.05 was considered significant. Results: One hundred and three patients (26%) developed post-ERCP AKI. Estimated glomerular filtration rate (adjusted odds ratio (aOR) = 0.95, 95% confidence interval (CI): 0.94−0.96, p < 0.001), nonrenal Charlson Comorbidity Index (Aor = 1.19, 95% CI: 1.05−1.35, p = 0.006), choledocholithiasis (aOR = 4.05, 95% CI: 1.98−8.29, p < 0.001), and bilirubin (aOR = 1.1, 95% CI: 1.05−1.15, p < 0.001) were associated with post-ERCP AKI. Post-ERCP AKI was associated with longer hospital stay (p < 0.001) and with increased in-hospital mortality (7.76% versus 0.36%, p < 0.001). Moderate-to-severe (stage 2 and 3) AKI was independently associated with in-hospital mortality (aOR = 6.43, 95% CI: 1.48−27.88, p < 0.013). Conclusions: Post-ERCP AKI represented an important complication associated with longer hospital stay. Moderate-to-severe post-ERCP AKI was an independent risk factor for in-hospital mortality.
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Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Túbulos Renales Proximales/fisiopatología , Podocitos/fisiología , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Regulación de la Expresión Génica/fisiología , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Factores Protectores , ARN Largo no Codificante/orina , Factores de Riesgo , Adulto JovenRESUMEN
Aim: An advanced proteomics platform for protein biomarker discovery in diabetic chronic kidney disease (DKD) was developed, validated and implemented. Materials & methods: Three Type 2 diabetes mellitus patients and three control subjects were enrolled. Urinary peptides were extracted, samples were analyzed on a hybrid LTQ-Orbitrap Velos Pro instrument. Raw data were searched using the SEQUEST algorithm and integrated into Proteome Discoverer platform. Results & discussion: Unique peptide sequences, resulted sequence coverage, scoring of peptide spectrum matches were reported to albuminuria and databases. Five proteins that can be associated with early DKD were found: apolipoprotein AI, neutrophil gelatinase-associated lipocalin, cytidine deaminase, S100-A8 and hemoglobin subunit delta. Conclusion: Urinary proteome analysis could be used to evaluate mechanisms of pathogenesis of DKD.
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Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/diagnóstico , Anciano , Albuminuria/diagnóstico , Albuminuria/orina , Biomarcadores/orina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/orina , Femenino , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/orina , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Péptidos , Proyectos Piloto , Proteoma/análisis , Proteómica/métodosRESUMEN
AIMS: To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction. METHODS: In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed. RESULTS: In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (pâ¯<â¯0.0001, R2=â¯0.57); urinary IL-8 correlated directly with synaptopodin, NAG, nephrin, and KIM-1 (pâ¯<â¯0.0001, R2â¯=â¯0.67); urinary IL-18 correlated directly with synaptopodin, NAG, and nephrin (pâ¯<â¯0.0001, R2â¯=â¯0.59). Serum IL-1 alpha correlated positively with nephrin, synaptopodin, NAG (Pâ¯<â¯0.0001, R2â¯=â¯0.68); serum IL-8 correlated directly with synaptopodin and NAG (pâ¯<â¯0.0001, R2â¯=â¯0.66); serum IL-18 correlated directly with NAG, KIM-1, and podocalyxin (pâ¯<â¯0.0001, R2=0.647). CONCLUSIONS: Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.
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Citocinas/inmunología , Diabetes Mellitus Tipo 2/inmunología , Nefropatías Diabéticas/inmunología , Nefropatías Diabéticas/patología , Túbulos Renales Proximales , Podocitos/patología , Anciano , Albuminuria , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Humanos , Inflamación/inmunología , Interleucina-18/inmunología , Interleucina-1alfa/inmunología , Interleucina-8/inmunología , Túbulos Renales Proximales/inmunología , Túbulos Renales Proximales/patología , Persona de Mediana Edad , Podocitos/inmunologíaRESUMEN
Background: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.Methods: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.Results: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.Conclusions: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.
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Trastornos Cerebrovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatías Diabéticas/metabolismo , Nefropatías Diabéticas/metabolismo , MicroARNs/metabolismo , Remodelación Vascular/fisiología , Adulto , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/orina , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/etiología , Angiopatías Diabéticas/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/orina , Femenino , Humanos , Túbulos Renales/fisiopatología , Masculino , MicroARNs/sangre , MicroARNs/orina , Persona de Mediana Edad , Podocitos/patologíaRESUMEN
Aim: The involvement of proinflammatory interleukins (IL) in diabetic kidney disease of Type 2 diabetes mellitus (DM) patients was studied in relation to a particular miRNA profile. Materials & methods: A total of 117 patients with Type 2 DM and 11 controls were enrolled in a case series study. Serum and urinary ILs and miRNAs were assessed. Results: IL-1α correlated with miRNA21, 124, estimated glomerular filtration rate (eGFR) and negatively with miRNA125a and 192; IL-8 with miRNA21, 124, eGFR and negatively with miRNA125a, 126 and 146a; IL-18 with miRNA21, 124 and negatively with miRNA146a, 192, eGFR. Conclusion: There is an association between specific serum and urinary ILs and serum and urinary miRNAs profiles in the inflammatory response in Type 2 DM patients with diabetic kidney disease.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Interleucinas/sangre , Interleucinas/orina , MicroARNs/sangre , MicroARNs/orina , Adulto , Anciano , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/genética , Femenino , Humanos , Interleucina-18/sangre , Interleucina-18/orina , Masculino , MicroARNs/genética , Persona de Mediana Edad , Adulto JovenRESUMEN
MicroRNAs (miRNAs) are short non-coding RNA species that are important post-transcriptional regulators of gene expression. The aim of the study was to establish a potential explanation of podocyte damage and proximal tubule (PT) dysfunction induced by deregulated miRNAs expression in the course of type 2 diabetes mellitus (DM). A total of 68 patients with type 2 DM and 11 healthy subjects were enrolled in a cross-sectional study and assessed concerning urinary albumin:creatinine ratio (UACR), urinary N-acetyl-ß-D-glucosamininidase (NAG), urinary kidney injury molecule-1, urinary nephrin, podocalyxin, synaptopodin, estimated glomerular filtration rate (eGFR), urinary miRNA21, miRNA124, and miRNA192. In univariable regression analysis, miRNA21, miRNA124, and miRNA192 correlated with urinary nephrin, synaptopodin, podocalyxin, NAG, KIM-1, UACR, and eGFR. Multivariable regression analysis yielded models in which miRNA192 correlated with synaptopodin, uNAG, and eGFR (R2=0.902; P<0.0001), miRNA124 correlated with synaptopodin, uNAG, UACR, and eGFR (R2=0.881; P<0.0001), whereas miRNA21 correlated with podocalyxin, uNAG, UACR, and eGFR (R2=0.882; P<0.0001). Urinary miRNA192 expression was downregulated, while urinary miRNA21 and miRNA124 expressions were upregulated. In patients with type 2 DM, there is an association between podocyte injury and PT dysfunction, and miRNA excretion, even in the normoalbuminuria stage. This observation documents a potential role of the urinary profiles of miRNA21, miRNA124, and miRNA192 in early DN. Despite their variability across the segments of the nephron, urinary miRNAs may be considered as a reliable tool for the identification of novel biomarkers in order to characterize the genetic pattern of podocyte damage and PT dysfunction in early DN of type 2 DM.
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Albuminuria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Perfilación de la Expresión Génica , Túbulos Renales Proximales/fisiopatología , MicroARNs/genética , MicroARNs/orina , Podocitos/patología , Anciano , Albuminuria/genética , Albuminuria/fisiopatología , Albuminuria/orina , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Humanos , Túbulos Renales Proximales/patología , Persona de Mediana Edad , Análisis Multivariante , Podocitos/metabolismoRESUMEN
INTRODUCTION: Acute kidney injury (AKI) increases the risk of death in acute ischemic stroke (AIS) patients. Intravenous thrombolytic therapy (iv. rt-PA) seems to be the most effective treatment for AIS patients. The effects of AKI on iv. rt-PA treated AIS cases is less studied. Our paper addresses this issue. METHODS: 45 consecutive stroke patients treated with iv. rt-PA (median age = 64 years; 29 male) and 59 age and sex matched controls not eligible for iv. rt-PA have been enrolled in our study. Subjects were followed-up until hospital release or death (median follow up time = 12 days). RESULTS: The prevalence of AKI did not differ between iv. rt-PA treated patients and controls (35.5% vs. 33.89%). In both groups, AKI was associated with increased in-hospital mortality: 50.0% vs. 3.4% p<0.0001 (in the rt-PA treated), and 45% vs. 30.7% (in controls). AKI iv. rt-PA treated patients had a significantly higher risk of in hospital mortality as compared to the no-AKI iv. rt-PA treated (HR = 15.2 (95%CI [1.87 to 124.24]; P = 0.011). In a Cox-multivariate model, the presence of AKI after iv. rt-PA remained a significant factor (HR = 8.354; p = 0.041) influencing the in-hospital mortality even after correction for other confounding factors. The independent predictors for AKI were: decreased eGFR baseline and elevated serum levels of uric acid at admission, (the model explained 60.2% of the AKI development). CONCLUSIONS: The risk of AKI was increased in AIS patients. Thrombolysis itself did not increase the risk of AKI. In the iv. rt-PA patients, as compared to non-AKI, those which developed AKI had a higher rate of in-hospital mortality. The baseline eGFR and the serum uric acid at admission were independent predictors for AKI development in the iv. rt-PA treated AIS patients.
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Lesión Renal Aguda/mortalidad , Isquemia Encefálica/mortalidad , Fibrinolíticos/uso terapéutico , Mortalidad Hospitalaria/tendencias , Accidente Cerebrovascular/mortalidad , Activador de Tejido Plasminógeno/uso terapéutico , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/orina , Administración Intravenosa , Anciano , Biomarcadores/orina , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/orina , Análisis de Supervivencia , Terapia Trombolítica/métodos , Resultado del Tratamiento , Ácido Úrico/orinaRESUMEN
AIM: The study assessed mRNA expression of podocyte-associated molecules in urinary sediments of patients with type 2 diabetes mellitus (DM) in relation to urinary podocytes, biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. METHODS: A total of 76 patients with type 2 DM and 20 healthy subjects were enrolled in a cross-sectional study, and assessed concerning urinary podocytes, urinary mRNA of podocyte-associated genes, urinary biomarkers of podocyte damage and of PT dysfunction. RESULTS: We found significant differences between urinary mRNA of podocyte-associated molecules in relation with albuminuria stage. In multivariable regression analysis, urinary mRNA of nephrin, podocin, alpha-actinin-4, CD2-associated protein, glomerular epithelial protein 1 (GLEPP1), ADAM 10, and NFκB correlated directly with urinary podocytes, albuminuria, urinary alpha1-microglobulin, urinary kidney-injury molecule-1, nephrinuria, urinary vascular endothelial growth factor, urinary advanced glycation end-products (AGE), and indirectly with eGFR (p < 0.0001, R2 = 0.808; p < 0.0001, R2 = 0.825; p < 0.0001, R2 = 0.805; p < 0.0001, R2 = 0.663; p < 0.0001, R2 = 0.726; p < 0.0001, R2 = 0.720; p < 0.0001, R2 = 0.724). CONCLUSIONS: In patients with type 2 DM there is an association between urinary mRNA of podocyte-associated molecules, biomarkers of podocyte damage, and of PT dysfunction. GLEPP1, ADAM10, and NFκB may be considered additional candidate molecules indicative of early diabetic nephropathy. AGE could be involved in this association.
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Objectives: Due to the shortage of living kidney donors and the current diabetes mellitus (DM) pandemic, studying the association of solitary kidney (SK) with DM is of paramount importance. Our aim was to assess the significance of the association between SK and DM. Materials and methods: Eighty-four patients with SK and DM (group A), with a mean age of 62.46±12.72 years, of whom 36 were males and 48 were females, were enrolled in the study. The control group (group B) comprised 84 SK patients without DM of similar age and duration of existence of a SK. Mean age: 61.58±8.22 years, 23 males and 61 females. Serum creatinine, GFR (CKD-EPI), glycaemia, cholesterol, triglycerides, uric acid, proteinuria/24h, systolic blood pressure (SBP), diastolic blood pressure (DBP) and BMI were assessed. Results: The group of patients with SK and DM (group A) had a higher BMI (p=0.0007), higher metabolic abnormalities (higher glycaemia [p<0.001], triglycerides [p=0.0004], uric acid [p=0.019] and proteinuria/24h [p=0.006]). The study group also had a higher prevalence of hypertension (p=0.003) and coronary artery disease (p=0.031). Conclusions: We found a higher value of proteinuria in the study group, significant metabolic abnormalities, as well as a higher prevalence of hypertension and coronary artery disease. However, no differences with respect to GFR were found, which could have significant implications for transplantation (AU)
Objetivos: Dada la reducción del número de los donantes vivos de riñones y la pandemia de diabetes mellitus (DM), estudiar la asociación del riñón único (RU) con la DM es de la mayor importancia. Nuestro objetivo fue evaluar la significación de la asociación entre el RU y la DM. Material y métodos: Han sido estudiados 84 pacientes con RU y DM (grupo A), con edad media de 62,46±12,72 años; eran 36 hombres y 48 mujeres. El grupo control (grupo B) ha estado compuesto por 84 pacientes con RU sin DM, de la misma edad y del mismo periodo de tiempo que el grupo A; la edad media de estos pacientes fue de 61,58±8,22 años; eran 23 hombres y 61 mujeres. Hemos evaluado la creatinina sérica, el FG (CKD-EPI), la glucemia, el colesterol, los triglicéridos, el ácido úrico, la proteinuria de 24 h, la tensión arterial sistólica (TAS), la tensión arterial diastólica (TAD) y el IMC. Resultados: El grupo de los pacientes con RU y DM (el grupo A) tuvo valores mayores del IMC (p=0,0007), anomalías metabólicas más elevadas (la glucemia [p<0,001], los triglicéridos [p=0,0004], el ácido úrico [p=0,019] y una proteinuria/24 h también más elevada [p=0,006]). El grupo de estudio tuvo también una prevalencia elevada de la TA (p=0,003) y de la enfermedad arterial coronaria (p=0,031). Conclusiones: Hemos encontrado un valor más elevado de la proteinuria en el grupo estudiado, anomalías metabólicas importantes y también prevalencia más alta de la TA y de la enfermedad arterial coronaria, pero ninguna diferencia entre los FG, lo que puede tener una implicación importante en el trasplante (AU)
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Humanos , Riñón/anomalías , Fenómenos Fisiológicos del Sistema Urinario , Diabetes Mellitus/epidemiología , Fenómenos Fisiológicos del Sistema Urinario , Factores de Riesgo , Estudios de Casos y Controles , Creatinina/sangre , Proteinuria/epidemiologíaRESUMEN
OBJECTIVES: Due to the shortage of living kidney donors and the current diabetes mellitus (DM) pandemic, studying the association of solitary kidney (SK) with DM is of paramount importance. Our aim was to assess the significance of the association between SK and DM. MATERIALS AND METHODS: Eighty-four patients with SK and DM (group A), with a mean age of 62.46±12.72 years, of whom 36 were males and 48 were females, were enrolled in the study. The control group (group B) comprised 84 SK patients without DM of similar age and duration of existence of a SK. Mean age: 61.58±8.22 years, 23 males and 61 females. Serum creatinine, GFR (CKD-EPI), glycaemia, cholesterol, triglycerides, uric acid, proteinuria/24h, systolic blood pressure (SBP), diastolic blood pressure (DBP) and BMI were assessed. RESULTS: The group of patients with SK and DM (group A) had a higher BMI (p=0.0007), higher metabolic abnormalities (higher glycaemia [p<0.001], triglycerides [p=0.0004], uric acid [p=0.019] and proteinuria/24h [p=0.006]). The study group also had a higher prevalence of hypertension (p=0.003) and coronary artery disease (p=0.031). CONCLUSIONS: We found a higher value of proteinuria in the study group, significant metabolic abnormalities, as well as a higher prevalence of hypertension and coronary artery disease. However, no differences with respect to GFR were found, which could have significant implications for transplantation.
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Diabetes Mellitus/fisiopatología , Nefropatías Diabéticas/fisiopatología , Riñón/fisiopatología , Riñón Único/fisiopatología , Nefropatías Diabéticas/complicaciones , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Riñón Único/complicacionesRESUMEN
AIMS: Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. METHODS: A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Urinary podocytes were examined in cell cultures by utilizing monoclonal antibodies against podocalyxin and synaptopodin. RESULTS: Podocytes were detected in the urine of 10% of the healthy controls, 24% of the normoalbuminuric, 40% of the microalbuminuric, and 82% of the macroalbuminuric patients. In multivariate logistic regression analysis, urinary podocytes correlated with urinary albumin:creatinine ratio (p=0.006), urinary nephrin/creat (p=0.001), urinary vascular endothelial growth factor/creat (p=0.001), urinary kidney injury molecule-1/creat (p=0.003), cystatin C (p=0.001), urinary advanced glycation end-products (p=0.002), eGFR (p=0.001). CONCLUSIONS: In patients with type 2 diabetes podocyturia parallels proximal tubule dysfunction independently of albuminuria and renal function decline. Advanced glycation end-products may impact the podocytes and the proximal tubule.
Asunto(s)
Albuminuria , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Túbulos Renales Proximales/fisiopatología , Podocitos/patología , Orina/citología , Albuminuria/complicaciones , Albuminuria/patología , Albuminuria/fisiopatología , Albuminuria/orina , Estudios de Casos y Controles , Células Cultivadas , Estudios Transversales , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/patología , Riñón/fisiopatología , Pruebas de Función Renal , Túbulos Renales Proximales/patología , Masculino , Persona de Mediana Edad , Urinálisis/métodosRESUMEN
BACKGROUND: Diabetic nephropathy is a severe complication of Type 2 diabetes. Tubular lesions may play an important role in its early stages. The aim of our study was to determine if atorvastatin protects the podocytes and the proximal tubule in patients with Type 2 diabetes. METHODS: A total of 63 patients with Type 2 diabetes completed this 6-months prospective pilot study. They were randomized to continue rosuvastatin therapy (control group) or to be administered an equipotent dose of atorvastatin (intervention group), and were assessed regarding urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. RESULTS: The patients from the intervention group presented a significant reduction in podocyturia (from 7.0 to 4.0 cells/ml, p < .05), urinary nephrin (from 1.7 to 1.3 mg/g, p < .001), urinary vascular endothelial growth factor (from 262.8 to 256.9, p < .01), urinary alpha1-microglobulin (from 10.0 to 8.3 mg/g, p < .01), urinary kidney injury molecule-1 (from 139.5 to 136.3 ng/g, p < .001), and urinary advanced glycation end-products (from 112.6 to 101.3 pg/ml, p < .001). Podocyturia correlated directly with the podocyte damage biomarkers, proximal tubule dysfunction biomarkers, albumin to creatinine ratio, and advanced glycation end-products, and inversely with the glomerular filtration rate. CONCLUSIONS: In patients with Type 2 diabetes, atorvastatin exerts favorable effects on the kidney. There is a correlation between the evolution of the podocytes and of the proximal tubule biomarkers, supporting the hypothesis that the glomerular changes parallel proximal tubule dysfunction in the early stages of diabetic nephropathy.
Asunto(s)
Atorvastatina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Podocitos/efectos de los fármacos , Rosuvastatina Cálcica/uso terapéutico , Anciano , Albuminuria/complicaciones , Biomarcadores , Femenino , Tasa de Filtración Glomerular , Productos Finales de Glicación Avanzada/orina , Humanos , Túbulos Renales Proximales/fisiopatología , Masculino , Proteínas de la Membrana/orina , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/orinaRESUMEN
The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7-day treatment with intravenous ciprofloxacin. Urinary N-acetyl-beta-d-glucosaminidase, alpha 1-microglobulin, and estimated glomerular filtration rate (eGFR) of these patients were measured at the initiation and at the end of treatment. In 47.37% patients NAG diminished under ciprofloxacin treatment. This observation has the significance of favourable evolution of the tubulointerstitial lesions caused by UTI and lack of nephrotoxic effects; 52.63% cases presented an increase of urinary NAG, a fact that suggests a nephrotoxic effect of ciprofloxacin. The evolution of urinary alpha 1-microglobulin was similar to that one of urinary NAG. Only one of three cases with chronic kidney disease (CKD) stage 5 presented acute kidney injury, associated with increase in the tubular markers. In spite of the high variability of the urinary biomarkers, UTI evolved favourably in these cases; eGFR increased in 16 out of 19 patients, a fact which is indicative of a good outcome of renal function, even in patients with elevated levels of the tubular damage biomarkers. This observation supports the hypothesis that eGFR may be dissociated from the biomarkers which assess tubular injury. In SK patients the occurrence of AKI is not frequent, although the urinary biomarkers rise in some patients treated with ciprofloxacin. This is related not only to the nephrotoxic effect of the drug, but probably to the association of other factors (allergy, individual susceptibility). In SK patients, renal tubular biomarkers, especially NAG, allow monitoring of tubular injury and impose caution in prescribing ciprofloxacin treatment, mainly to patients at risk. Ciprofloxacin is relatively safe regarding its nephrotoxicity, while caution is required in vulnerable patients.
Asunto(s)
Ciprofloxacina/uso terapéutico , Riñón/anomalías , Infecciones Urinarias/tratamiento farmacológico , Acetilglucosaminidasa/orina , alfa-Globulinas/orina , Ciprofloxacina/farmacología , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Infecciones Urinarias/patología , Infecciones Urinarias/fisiopatología , Infecciones Urinarias/orinaRESUMEN
Diabetic nephropathy (DN) is a frequent and severe complication of diabetes mellitus (DM). Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition-mainly cardiovascular ones-and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress) precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new "gold standard" biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin) are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.
Asunto(s)
Albuminuria/orina , Biomarcadores/orina , Nefropatías Diabéticas/orina , Diagnóstico Precoz , HumanosRESUMEN
Chronic glomerulonephritis is related to focus infection. Odontogenic foci are frequently involved in glomerulonephritis. The relationship with the odontogenic focus infection can be demonstrated by the occurrence or aggravation of the symptoms of glomerulonephritis: proteinuria, haematuria, high blood pressure and oedema. Glomerular impairment in glomerulonephritis occurs together with inflammatory alterations of the tubulointerstitial compartment that can play an important part in the evolution of the disease. Tubular urinary markers can indicate the activation of this compartment during an infection of a focus, an odontogenic focus in our study.The paper aims at demonstrating the relationship between the odontogenic focus infection and tubulointerstitial lesions, assessed by a tubular urinary marker, N-acetyl beta-D glucosaminidase (NAG).We investigated the urinary N-acetyl beta-D glucosaminidase of 20 patients with chronic glomerulonephritis who presented odontogenic focus infections, comparing them with patients with chronic glomerulonephritis without odontogenic foci and of 20 controls, clinically healthy persons.Chronic glomerulonephritis patients with odontogenic focus infection presented clearly increased values as compared to clinically healthy control persons of urinary N-acetyl beta-D glucosaminidase.These patients underwent surgical intervention on the odontogenic focus under antibacterial prophylactic treatment. In 75% cases, the values of N-acetyl beta-D glucosaminidase diminished, indicating the favourable effect of the treatment of the odontogenic focus on the tubulointerstitial compartment in patients with chronic glomerulonephritis. In 25% cases this therapeutic treatment was associated with an increase of the values of urinary N-acetyl beta-D glucosaminidase, expressing its unfavourable effect on chronic glomerulonephritis.Urinary N-acetyl beta-D glucosaminidase indicated an etiopathogenetic relationship between the odontogenic focus and the tubulointerstitial compartment in chronic glomerulonephritis.
Asunto(s)
Acetilglucosaminidasa/orina , Infección Focal Dental/diagnóstico , Infección Focal Dental/orina , Glomerulonefritis/diagnóstico , Glomerulonefritis/orina , Adulto , Biomarcadores/orina , Femenino , Infección Focal Dental/etiología , Glomerulonefritis/complicaciones , Humanos , Túbulos Renales/enzimología , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The relationship between the kidney and other organs is notable. The best known is the relation with the cardiovascular system. Relationships with other organs are less studied, although their involvement sometimes dominates the clinical picture and the outcome of disease. The paper analyzes the kidney-liver relationship, namely chronic kidney disease and chronic liver disease from an immune viewpoint. The immune system operates as a unitary whole. There is an interdependence between the immune system of the liver, considered a lymphoid organ, and the kidney, whose participation in immune processes is well-known. The most important chronic liver diseases are viral hepatitis B and C. Infection with these viruses can lead to renal involvement, producing mainly glomerular disease. At the same time, secondary glomerulonephritis can cause an unfavorable outcome of the primary disease. The relationship between chronic liver disease and chronic kidney disease during chronic B and C hepatitis occurs via circulating immune complexes or complexes formed in situ. Cell-mediated immunity is also involved. The antiviral treatment of B and C hepatitis is also aimed at secondary glomerular disease. The participation of immune mechanisms raises the question of administering immunomodulating medication, a type of medication that influences viral replication--this is why it is associated with antiviral medication. Other two chronic liver diseases, namely liver cirrhosis, in which the main mechanism is a toxic one, and non-alcoholic steatohepatitis can produce via immune mechanisms glomerular involvement. In its turn, chronic kidney disease in advanced stages causes lipid metabolism disturbances with hypertriglyceridemia, which can influence fatty loading of the liver in the above-mentioned liver diseases. One can speak about a cross-talk between the liver and the kidney, in which immune mechanisms play an important role.