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1.
Indian J Pediatr ; 90(1): 76-78, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36057032

RESUMO

Identification of volume status in nephrotic syndrome (NS) is important but clinically challenging. Urinary and serum indices can be helpful in assessing the volume status and so can be inferior vena cava collapsibility index (IVCCI). This study was done to assess the serum and urinary indices in children with nephrotic edema and to correlate them with IVCCI for intravascular volume assessment. Fifty children with nephrotic edema and 47 children in remission were analyzed for blood and urine indices. Volume status was defined as overfilling or underfilling based on the biochemical indices and also by IVCCI. Eighty-four percent individuals among cases and 23% among controls had sodium retention (FENa < 0.5%). Among cases, 54% had primary sodium retention compared to 17% among controls (p = 0.0002). Hypovolemia was observed among 36% cases based on biochemical indices and in 20% cases as per IVCCI. Hypovolemia was significantly associated with low urinary sodium and low serum albumin.


Assuntos
Edema , Nefrose , Veia Cava Inferior , Criança , Humanos , Ecocardiografia , Edema/etiologia , Edema/fisiopatologia , Hipovolemia/diagnóstico , Hipovolemia/etiologia , Sódio/sangue , Sódio/urina , Ultrassonografia , Veia Cava Inferior/diagnóstico por imagem , Nefrose/complicações , Nefrose/fisiopatologia
2.
BMC Nephrol ; 21(1): 346, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795277

RESUMO

BACKGROUND: Nephrotic syndrome (NS) is associated with a hypercatabolic state expressed as an exacerbated degradation of muscle mass. However, the clinical significance of this phenomenon has not yet been investigated. The aim of the study was to evaluate the nutritional status of patients with severe NS (defined as nephrotic range proteinuria with hypoalbuminemia ≤2.5 g/dL) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2 in comparison to patients in different stages of chronic kidney disease (CKD). METHODS: Twenty men with severe NS (NS group) and 40 men without proteinuria similar in term of serum creatinine (control group) were included into the study. A retrospective cohort of 40 men with CKD stage G4 (PreD group) and 20 haemodialysis men (HD group) were added to the analysis after matching for age, height and weight using propensity score matching. The bioimpedance spectroscopy and biochemical nutritional markers were evaluated. RESULTS: Nephrotic patients had a significantly lower lean tissue mass (LTM; p = 0.035) and index (a quotient of LTM over height squared, LTI; p = 0.068), with an expected deficiency of LTM by 3.2 kg, and LTI by 0.9 kg/m2 when compared to the control group. A significant lean tissue deficit (defined as LTI below the lower limit of the reference range by 1.0 kg/m2) was observed in 12.5% of patients in the control group in comparison to 31.7% with advanced CKD (PreD+HD; p = 0.032) and 50% with NS (p = 0.003). NS group presented with higher phosphorus (p = 0.029), uric acid (p = 0.002) and blood urea (p = 0.049) than the control group. Blood urea was strongly negatively correlated with LTM in NS (r = - 0.64, p = 0.002). Nine nephrotic patients (45%) were identified as hypercatabolic based on severe hyperphosphatemia (> 5.0 mg/dL) and/or hyperuricemia (> 8.0 mg/dL), and were characterized by higher blood urea and lower prealbumin, as well as LTM lower by 5.6 kg than in less catabolic individuals. CONCLUSIONS: In term of lean tissue amount, NS group was more similar to advanced CKD than to the control group. We concluded that specific metabolic pattern with elevated phosphorus, uric acid and blood urea, and lean tissue deficiency may be defined as protein-energy wasting associated with nephrotic syndrome (neph-PEW).


Assuntos
Falência Renal Crônica/fisiopatologia , Músculo Esquelético/patologia , Síndrome Nefrótica/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Síndrome de Emaciação/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Nitrogênio da Ureia Sanguínea , Composição Corporal , Estudos de Casos e Controles , Espectroscopia Dielétrica , Humanos , Hiperfosfatemia/sangue , Hiperuricemia/sangue , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Nefrose/metabolismo , Nefrose/fisiopatologia , Síndrome Nefrótica/metabolismo , Tamanho do Órgão , Fósforo/sangue , Pré-Albumina/metabolismo , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Índice de Gravidade de Doença , Ácido Úrico/sangue , Síndrome de Emaciação/metabolismo , Adulto Jovem
3.
Medicine (Baltimore) ; 99(32): e21644, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769933

RESUMO

INTRODUCTION: The kidney is one of the common extraglandular sites involved in primary Sjögren syndrome (pSS), with chronic tubulointerstitial nephritis (TIN) the most common pathology type. Renal involvement in pSS often presents as chronic TIN accompanied by type 1 or 2 renal tubular acidosis (RTA). Description of renal involvement as acute TIN with type III RTA in pSS has been rarely reported. PATIENT CONCERNS: A 37-year-old woman was admitted with complaints of dry mouth, dry eyes, and progressive muscle weakness for 17 months. Two months before admission, the patient had a blood potassium level of 1.7 mmol/L. DIAGNOSIS: Further tests confirmed pSS and type III RTA. Renal biopsy demonstrated acute TIN and thin basement membrane nephropathy (TBMN). INTERVENTIONS: Full-dose corticosteroid (1 mg/kg/day) and cyclophosphamide (100 mg/day) were applied. OUTCOMES: The creatinine levels of the patient decreased 0.28 mg/dL (1.18-0.90 mg/dL) during 3-month follow-up. CONCLUSIONS: We reported a patient with pSS-associated kidney injury, presenting as acute TIN with type 3 RTA and TBMN. This case increases the awareness of a rare manifestation of pSS-associated kidney injury. In pSS-associated acute TIN, cyclophosphamide combined with full-dose corticosteroids may achieve good outcomes.


Assuntos
Acidose Tubular Renal/etiologia , Nefrite Intersticial/etiologia , Síndrome de Sjogren/complicações , Acidose Tubular Renal/fisiopatologia , Corticosteroides/uso terapêutico , Adulto , Creatinina/análise , Creatinina/sangue , Ciclofosfamida/uso terapêutico , Síndromes do Olho Seco/etiologia , Feminino , Humanos , Debilidade Muscular/etiologia , Nefrite Intersticial/fisiopatologia , Nefrose/etiologia , Nefrose/fisiopatologia , Potássio/sangue , Síndrome de Sjogren/fisiopatologia
4.
Am J Physiol Renal Physiol ; 318(5): F1284-F1294, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32200668

RESUMO

Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities. Mathematical deconvolution fit best to a three-component model that included saturable high- and low-affinity uptake sites for albumin and underlying nonsaturable uptake consistent with passive uptake of albumin in the fluid phase. Knockdown of cubilin or its chaperone amnionless selectively reduced the binding capacity of the high-affinity site, whereas knockdown of megalin impacted the low-affinity site. Knockdown of disabled-2 decreased the capacities of both binding sites. Additionally, knockdown of megalin or disabled-2 profoundly inhibited the uptake of a fluid phase marker, with cubilin knockdown having a more modest effect. We propose a novel model for albumin retrieval along the PT in which cubilin and megalin receptors have different functions in recovering filtered albumin in proximal tubule cells. Cubilin binding to albumin is tuned to capture normally filtered levels of the protein. In contrast, megalin binding to albumin is of lower affinity, and its expression is also essential for enabling the recovery of high concentrations of albumin in the fluid phase.


Assuntos
Albuminúria/metabolismo , Túbulos Renais Proximais/metabolismo , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Nefrose/metabolismo , Receptores de Superfície Celular/metabolismo , Albumina Sérica/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Albuminúria/genética , Albuminúria/fisiopatologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Endocitose , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Túbulos Renais Proximais/fisiopatologia , Cinética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/deficiência , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Knockout , Modelos Biológicos , Nefrose/genética , Nefrose/fisiopatologia , Gambás , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/genética
5.
Am J Physiol Renal Physiol ; 316(2): F382-F395, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30207166

RESUMO

Proteinuria, the most common symptom of renal injury, is an independent factor for renal tubular injury. However, the underlying mechanism remains to be fully elucidated. Mitochondrion is an important target for proteinuria-induced renal tubular cell injury. Insufficient mitophagy exacerbates cell injury by initiating mitochondrial dysfunction-related cell apoptosis. In the experiment, the role of NIP3-like protein X (NIX)-mediated mitophagy was investigated in proteinuria-induced renal injury. In this study, we demonstrated that NIX expression was reduced in renal tubules and correlated with the decline of estimated glomerular filtration rate and increase of the proteinuria in patients. In proteinuric mice, NIX-mediated mitophagy was significantly suppressed. Meanwhile, the proteinuric mice exhibited renal dysfunction, increased mitochondrial fragmentation, and tubular cell apoptosis. Overexpression of NIX attenuated those disruptions in proteinuric mice. In cultured renal tubular epithelial cells, albumin induced a decrease in NIX-mediated mitophagy and an increase in cell apoptosis. Overexpression of NIX attenuated albumin-induced cell apoptosis, whereas NIX siRNA aggravated these perturbations. These results indicate that proteinuria suppresses NIX-mediated mitophagy in the renal tubular epithelial cell, which triggers the cell undergoing mitochondria-dependent cell apoptosis. Collectively, our finding suggests that restoration of NIX-mediated mitophagy might be a novel therapeutic target for alleviating proteinuria-induced kidney injury.


Assuntos
Albuminúria/metabolismo , Apoptose , Células Epiteliais/metabolismo , Túbulos Renais/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mitofagia , Nefrose/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/genética , Albuminúria/patologia , Albuminúria/fisiopatologia , Animais , Estudos de Casos e Controles , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Túbulos Renais/patologia , Túbulos Renais/fisiopatologia , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Nefrose/genética , Nefrose/patologia , Nefrose/fisiopatologia , Proteínas Proto-Oncogênicas/genética , Transdução de Sinais , Proteínas Supressoras de Tumor/genética , Adulto Jovem
6.
BMC Med Genet ; 18(1): 121, 2017 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-29073906

RESUMO

BACKGROUND: Hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is challenging and requires a high index of suspicion as well as genetic analysis. CASE PRESENTATION: A 14-month-old boy, with sensorineural hearing loss in both ears, showed typical radiological features of X-linked stapes gusher on preoperative temporal bone computed tomography (CT) for cochlear implantations. Then after his discharge from hospital, he suffered a hypocalcemic seizure and we discovered a renal cyst during investigation of hypocalcemia. He was finally diagnosed with HDR syndrome by clinical findings, which were confirmed by molecular genetic testing. Direct sequencing of the GATA3 gene showed a heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a frameshift of the reading frame (p.Met401Valfs*106). CONCLUSIONS: To our knowledge, this is the first case of HDR syndrome with a novel de novo variant mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the diversity of clinical manifestations expand the genotypic and phenotypic spectrum of HDR syndrome. Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis for children with a wide range of clinical manifestations including hypocalcemia induced seizures and deafness. We hope that this case will contribute to further understanding and studies of HDR-associated GATA3 mutations.


Assuntos
Cromossomos Humanos Par 10/química , Implante Coclear , Mutação da Fase de Leitura , Fator de Transcrição GATA3/genética , Perda Auditiva Neurossensorial/diagnóstico , Hipoparatireoidismo/diagnóstico , Nefrose/diagnóstico , Diagnóstico Diferencial , Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Haploinsuficiência , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/genética , Perda Auditiva Condutiva/fisiopatologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/cirurgia , Heterozigoto , Humanos , Hipoparatireoidismo/genética , Hipoparatireoidismo/fisiopatologia , Hipoparatireoidismo/cirurgia , Lactente , Masculino , Nefrose/genética , Nefrose/fisiopatologia , Nefrose/cirurgia , Tomografia Computadorizada por Raios X
7.
Am J Med Genet A ; 170A(5): 1268-73, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26762557

RESUMO

Monosomy 10p is a rare chromosomal disorder with a prevalence <1/1,000,000, in which a terminal or interstitial distal region of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. Two main phenotypes have been defined depending on the location of the deletion: HDR syndrome (Hypoparathyroidism, sensorineural Deafness, and Renal disease), and DGS2 (DiGeorge syndrome type 2). The vast majority of cases reported so far have resulted from de novo events. Here, we present the first familial presentation of this contiguous gene deletion syndrome, affecting two family members in different generations: a child and his maternal uncle. In both cases, the deletion was due to a malsegregation of a maternal balanced rearrangement, ins(16;10)(q22;p13p15.2). The identification and characterization of this rearrangement was possible using a combination of different genetic analyses such as karyotype, MLPA, FISH, and array CGH. We underline the importance of the present results in terms of genetic and reproductive counseling for the carriers of the balanced rearrangement within the family, and demonstrate again the utility of expanding the genetic studies to the relatives of the affected patients.


Assuntos
Transtornos Cromossômicos/genética , Cromossomos Humanos Par 10/genética , Síndrome de DiGeorge/genética , Perda Auditiva Neurossensorial/genética , Hipoparatireoidismo/genética , Nefrose/genética , Adulto , Criança , Deleção Cromossômica , Transtornos Cromossômicos/fisiopatologia , Hibridização Genômica Comparativa , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/fisiopatologia , Síndrome de DiGeorge/fisiopatologia , Deleção de Genes , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Hipoparatireoidismo/fisiopatologia , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Nefrose/fisiopatologia
8.
Nephrology (Carlton) ; 21(9): 765-73, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26560070

RESUMO

AIM: Mutations of LMX1B cause nail-patella syndrome, a rare autosomal dominant disorder. Recently, LMX1B R246Q heterozygous mutations were recognised in nephropathy without extrarenal manifestation. The aim of this study was to clarify characteristics of nephropathy caused by R246Q mutation. METHODS: Whole exome sequencing was performed on a large family with nonsyndromic autosomal dominant nephropathy without extrarenal manifestation. Clinical and histological findings of patients with LMX1B mutation were investigated. RESULTS: LMX1B R246Q heterozygous mutation was identified in five patients over three generations. Proteinuria or haematoproteinuria was recognized by urinary screening from all patients in childhood. Proteinuria gradually increased to nephrotic levels and renal function decreased in adolescence. Two patients progressed to end-stage renal disease in adulthood. Renal histology demonstrated minimal change in childhood and focal segmental glomerulosclerosis in adulthood. Using electron microscopy, focal collagen deposition could be detected in glomeruli even when a "moth-eaten appearance" was not apparent in the glomerular basement membrane. In addition, podocin expression in glomerular podocytes was significantly decreased, even in the early stages of disease progression. CONCLUSION: Comprehensive genetic analyses and collagen or tannic acid staining may be useful for diagnosis of LMX1B-associated nephropathy. While renal prognosis of R246Q may be worse than that of typical NPS nephropathy, signs of podocytopathy can be detected during the infantile period; thus, childhood urinary screening may facilitate early detection.


Assuntos
Glomerulosclerose Segmentar e Focal/genética , Falência Renal Crônica/genética , Rim/patologia , Proteínas com Homeodomínio LIM/genética , Mutação , Nefrose Lipoide/genética , Nefrose/genética , Proteinúria/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Colágeno/metabolismo , Análise Mutacional de DNA , Progressão da Doença , Feminino , Imunofluorescência , Marcadores Genéticos , Predisposição Genética para Doença , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Heterozigoto , Humanos , Lactente , Rim/metabolismo , Rim/fisiopatologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Masculino , Nefrose/patologia , Nefrose/fisiopatologia , Nefrose Lipoide/metabolismo , Nefrose Lipoide/patologia , Linhagem , Fenótipo , Proteinúria/patologia , Proteinúria/fisiopatologia , Fatores de Tempo , Adulto Jovem
9.
J Clin Ultrasound ; 44(3): 175-81, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26402850

RESUMO

PURPOSE: To evaluate the carotid artery diameter, and wall thickness and stiffness in patients with glomerulopathy and proteinuria without severely reduced kidney function. METHODS: We compared 30 control subjects to 30 patients with glomerular disease, proteinuria, and glomerular filtration rate > 30 ml/min/1.73 m(2) : membranous glomerulonephritis (n = 13), minimal change disease (n = 2), focal and segmental glomerulosclerosis (n = 3), IgA nephropathy (n = 5), lupus nephritis (n = 5), antiphospholipid antibody nephropathy (n = 1), cryoglobulinemic glomerulonephritis (n = 1). The laboratory evaluations included carotid artery diameter, intima-media thickness, and stiffness measurements. RESULTS: Carotid cross-sectional area of intima-media complex was thicker in patients (18.6 ± 1.4 [x ± SEM]) than in controls (14.8 ± 0.6 mm(2) , p = 0.014), as was carotid artery wall stiffness (8.96 ± 0.86 versus 5.65 ± 0.38, [x ± SEM], p < 0.01). This difference remained significant after adjustment for age, sex, and metabolic cardiovascular risk factors: carotid stiffness was 9.19 ± 0.67 (99% confidence interval [CI] 7.40-10.98)] in patients and 4.80 ± 0.75 (99% CI 2.79-7.11) in controls; adjusted mean difference 4.40 (99% CI 1.46-7.34); p <0.001. CONCLUSIONS: This study showed, for the first time, signs of altered structural and elastic properties of the arterial wall in patients with proteinuria and glomerular disease without severely reduced kidney function.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Proteinúria/fisiopatologia , Ultrassonografia/métodos , Espessura Intima-Media Carotídea , Elasticidade , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose/complicações , Nefrose/diagnóstico por imagem , Nefrose/fisiopatologia , Proteinúria/complicações , Fatores de Risco
10.
Exp Clin Transplant ; 13 Suppl 3: 156-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26640940

RESUMO

OBJECTIVES: Proteinuria is a major cause of glomerulosclerosis progression in glomerular diseases, and the development of end-stage renal disease is more rapid in nephrotic patients than in nonnephrotic ones. The renal parenchyma is less regenerable because it is a tissue consisting of renal cells. Thus, stem cells obtained from fetal kidney tissue might be effective for reducing proteinuria and delaying glomerulosclerosis in these patients. MATERIALS AND METHODS: This report presents preliminary data from a prospective cohort study that included 17 patients with chronic glomerulonephritis in stage 2 to 4 chronic kidney disease who completed 3 visits during 1 year of follow-up. Fetal renal stem cells (multiple cells in suspension) were injected into the patient every 6 months. Patients were divided into 2 groups according to their nephrotic status, and 24-hour maximal proteinuria was recorded for at least 6 months (first group with proteinuria < 3.5 g/24 h, and second group with proteinuria > 3.5 g/24 h). RESULTS: During follow-up, group 1 was observed to have stable hemoglobin and total protein levels but significantly decreased albumin levels and glomerular filtration rates. In group 2, total protein with serum albumin significantly increased, and proteinuria and glomerular filtration rates significantly decreased. There was no significant difference in glomerular filtration rate decline between groups. CONCLUSIONS: Treatment with fetal renal stem cells significantly decreased proteinuria in nephrotic patients. However, this outcome also might have resulted from a reduction in glomerular filtration rate. Further studies with a larger number of patients and a control group would help to achieve better results that measure the efficacy of this treatment.


Assuntos
Células-Tronco Fetais/transplante , Taxa de Filtração Glomerular , Glomerulonefrite/cirurgia , Transplante de Rim/métodos , Rim/cirurgia , Nefrose/cirurgia , Proteinúria/cirurgia , Insuficiência Renal Crônica/cirurgia , Transplante de Células-Tronco/métodos , Adulto , Progressão da Doença , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/fisiopatologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrose/diagnóstico , Nefrose/fisiopatologia , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Clin Exp Nephrol ; 19(6): 1037-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25680889

RESUMO

BACKGROUND: Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. METHODS: 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. RESULTS: In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. CONCLUSION: Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Nefrose/fisiopatologia , Proteinúria/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose/urina , Proteinúria/urina , Diálise Renal , Estudos Retrospectivos , Fatores de Risco
13.
Am J Hum Genet ; 95(6): 637-48, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25466283

RESUMO

Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment. Through a combination of autozygosity mapping and whole-exome sequencing, we identified WDR73 as a gene in which mutations cause Galloway-Mowat syndrome in two unrelated families. WDR73 encodes a WD40-repeat-containing protein of unknown function. Here, we show that WDR73 was present in the brain and kidney and was located diffusely in the cytoplasm during interphase but relocalized to spindle poles and astral microtubules during mitosis. Fibroblasts from one affected child and WDR73-depleted podocytes displayed abnormal nuclear morphology, low cell viability, and alterations of the microtubule network. These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features. WDR73 is another example of a gene involved in a disease affecting both the kidney glomerulus and the CNS.


Assuntos
Hérnia Hiatal/genética , Deficiência Intelectual/genética , Microcefalia/genética , Nefrose/genética , Síndrome Nefrótica/genética , Proteínas/genética , Adolescente , Encéfalo/fisiopatologia , Linhagem Celular , Sobrevivência Celular , Criança , Pré-Escolar , Citosol/metabolismo , Exoma/genética , Hérnia Hiatal/fisiopatologia , Homozigoto , Humanos , Glomérulos Renais/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Microtúbulos/metabolismo , Mitose , Modelos Moleculares , Mutação , Nefrose/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Podócitos , Transporte Proteico , Proteínas/metabolismo , Polos do Fuso/metabolismo
14.
Am J Physiol Renal Physiol ; 307(5): F525-32, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24990894

RESUMO

Albuminuria in nephrotic states is thought to arise from the formation of large pores in the glomerular capillary wall as large hydrodynamic probes, like Ficoll, have increased fractional clearance. In the present study, we tested for large pore formation in a novel manner. We accounted for the rates of plasma elimination as determined for tritium-labeled tracers of uncharged polydisperse Ficoll (radii range: 35-85 Å) and two globular (14)C-labeled proteins, albumin (radius: 36 Å) and IgG (radius: 55 Å), in control and puromycin aminonucleoside nephrotic (PAN) Sprague-Dawley rats. The plasma elimination rates were then matched to the urinary excretion of these labeled materials (n = 7). Albumin and IgG plasma retention rates were identical and far enhanced compared with the retention rates of inert transport markers of equivalent hydrodynamic radius; their elimination rate corresponded to the elimination of a 75-Å radius Ficoll (n = 5) and >105-Å radius dextran (n = 5). In PAN, they were eliminated as ∼36- and ∼55-Å radii Ficoll, respectively, equivalent to their hydrodynamic radii. In contrast, there was no comparable increase in the elimination rate of Ficoll in PAN. The total plasma clearance of Ficoll in control and PAN rats and the urinary clearance in PAN rats were essentially the same for all radii. On the other hand, the urinary clearance of >45-Å radii Ficoll in controls was considerably lower with increasing radii, demonstrating a postfiltration cellular uptake in controls, which, when inhibited in nephrotic states, would account for apparent large pore formation.


Assuntos
Albuminúria/fisiopatologia , Capilares/fisiopatologia , Permeabilidade da Membrana Celular/fisiologia , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/fisiopatologia , Nefrose/fisiopatologia , Albuminúria/patologia , Animais , Capilares/patologia , Radioisótopos de Carbono , Modelos Animais de Doenças , Ficoll , Taxa de Filtração Glomerular/fisiologia , Hidrodinâmica , Imunoglobulina G/urina , Masculino , Nefrose/induzido quimicamente , Nefrose/patologia , Puromicina Aminonucleosídeo/efeitos adversos , Ratos , Ratos Sprague-Dawley
15.
Audiol Neurootol ; 19(2): 106-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24434941

RESUMO

We present the case of a Dutch family with a new mutation (c523_528dup) in GATA3 causing HDR syndrome. HDR syndrome is characterised by hypoparathyroidism, deafness and renal defects. In this study, we describe the audiometric characteristics of 5 patients from this family. Their hearing impairment was congenital, bilateral and symmetric. Audiograms showed mild-to-moderate hearing impairment with a flat audiogram configuration. Higher frequencies tended to be affected more strongly. Cross-sectional analyses showed no progression, and a mean audiogram was established. Psychophysical measurements in 3 HDR patients - including speech reception in noise, loudness scaling, gap detection and difference limen for frequency - were obtained to assess hearing function in greater detail. Overall, the results of the psychophysical measurements indicated characteristics of outer hair cell loss. CT scanning showed no anomalies in 3 of the HDR patients. Although 2 patients displayed vestibular symptoms, no anomalies in the vestibular system were found by vestibulo-ocular examination. Our results are in agreement with the theory that outer hair cell malfunctioning can play a major role in HDR syndrome.


Assuntos
Fator de Transcrição GATA3/genética , Perda Auditiva Neurossensorial/genética , Hipoparatireoidismo/genética , Mutação , Nefrose/genética , Audiometria de Tons Puros , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Hipoparatireoidismo/fisiopatologia , Masculino , Nefrose/fisiopatologia , Países Baixos , Linhagem , Fenótipo , Percepção da Fala/fisiologia , Síndrome , Testes de Função Vestibular
16.
Nephrology (Carlton) ; 19(2): 94-100, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24171710

RESUMO

AIM: Henoch-Schoenlein nephritis (HSPN) is a severe disease in adults and may cause renal insufficiency in a large portion of patients. But its rarity has led to lack of data. There are few controlled studies on therapy with immunosuppressants in HSPN adults. This study aims to evaluate the effect of leflunomide on HSPN adults with nephrotic proteinuria. METHODS: We retrospectively studied 65 adult patients who had biopsy-proven HSPN with nephrotic proteinuria. Twenty-seven patients (Group P) only received steroids, and 38 (Group P + L) were treated with leflunomide in addition to steroids. The clinical features, laboratory data and pathological findings of both groups were analyzed. RESULTS: The two groups were well-matched at baseline. After 24 months of treatment, urinary protein excretion of both groups decreased significantly from the baseline, and the estimated glomerular filtration rate (eGFR) was higher in Group P + L. Four patients in Group P and three in Group P + L developed to end-stage renal disease at the most recent follow-up. Group P + L showed better renal outcome than Group P. The treatment group and the degree of mesangial hypercellularity were significantly related to renal prognosis. CONCLUSION: Leflunomide combined with steroids is effective for treating adult HSPN with nephrotic proteinuria.


Assuntos
Corticosteroides/administração & dosagem , Vasculite por IgA/tratamento farmacológico , Isoxazóis/administração & dosagem , Rim/fisiopatologia , Nefrose/tratamento farmacológico , Proteinúria/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Vasculite por IgA/fisiopatologia , Isoxazóis/efeitos adversos , Leflunomida , Masculino , Pessoa de Meia-Idade , Nefrose/fisiopatologia , Proteinúria/fisiopatologia , Estudos Retrospectivos
17.
Kidney Int ; 84(4): 745-55, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23636175

RESUMO

Two types of alternatively activated macrophages, M(2a) induced by IL-4/IL-13 and M(2c) by IL-10/TGF-ß, exhibit anti-inflammatory functions in vitro and protect against renal injury in vivo. Since their relative therapeutic efficacy is unclear, we compared the effects of these two macrophage subsets in murine adriamycin nephrosis. Both subsets significantly reduced renal inflammation and renal injury; however, M(2c) macrophages more effectively reduced glomerulosclerosis, tubular atrophy, interstitial expansion, and proteinuria than M(2a) macrophages. The M(2c) macrophages were also more effective than M(2a) in reduction of macrophage and CD4(+) T-cell infiltration in kidney. Moreover, nephrotic mice treated with M(2c) had a greater reduction in renal fibrosis than those treated with M(2a). M(2c) but not M(2a) macrophages induced regulatory T cells (Tregs) from CD4(+)CD25(-) T cells in vitro, and increased Treg numbers in local draining lymph nodes of nephrotic mice. To determine whether the greater protection with M(2c) was due to their capability to induce Tregs, the Tregs were depleted by PC61 antibody in nephrotic mice treated with M(2a) or M(2c). Treg depletion diminished the superior effects of M(2c) compared to M(2a) in protection against renal injury, inflammatory infiltrates, and renal fibrosis. Thus, M(2c) are more potent than M(2a) macrophages in protecting against renal injury due to their ability to induce Tregs.


Assuntos
Transferência Adotiva/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Macrófagos/classificação , Macrófagos/fisiologia , Insuficiência Renal Crônica/terapia , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Gerenciamento Clínico , Modelos Animais de Doenças , Doxorrubicina/efeitos adversos , Técnicas In Vitro , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nefrose/induzido quimicamente , Nefrose/fisiopatologia , Nefrose/prevenção & controle , Fenótipo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/fisiologia
18.
Orv Hetil ; 154(11): 415-25, 2013 Mar 17.
Artigo em Húngaro | MEDLINE | ID: mdl-23477896

RESUMO

INTRODUCTION: The degree of glomerular filtration rate determines the stages of chronic renal disease and, therefore, knowledge on its estimation is essential. AIMS: Two standardized creatinine based estimated glomerular filtration rate equations and five equations based on the immunoturbidimetric determination of cystatin C were compared. METHODS: The distribution of the analytes and the equations, their relations, as well as the differences among the estimated glomerular filtration rates and their chronic kidney disease stages assignments were studied. RESULTS: The equations based on cystatin C classified more patient into stage 1, while the creatinine based ones more into stages 2, 3 and 4. The equations published as Grubb1, Grubb2 and Larsson classified more patients while the equations created by Tan and Sjöström classified fewer into stage 5 compared to the creatinine based equations. The equations of Grubb1 and Grubb2 resulted in the most similar stage assignment. The occurrence of stages between 3 and 5 was the lowest using the equation of Sjöström. CONCLUSIONS: The different equations for the estimation of glomerular filtration rate modify significantly the chronic kidney disease stage assignment which may have an influence on the treatment and outcome measures of the patients.


Assuntos
Taxa de Filtração Glomerular , Computação Matemática , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Comorbidade , Creatinina/sangue , Cistatina C/sangue , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Hipertensão Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nefrite/fisiopatologia , Nefrose/fisiopatologia , Análise Numérica Assistida por Computador , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/etiologia , Índice de Gravidade de Doença
19.
Am J Med Genet A ; 158A(4): 832-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22407589

RESUMO

Haploinsufficiency of a region located distal to 10p14 designated HDR1, is responsible for hypoparathyroidism, sensorineural deafness, and renal anomalies (HDR syndrome). Haploinsufficiency of a more proximal region, located on 10p13-10p14, designated as DGCR2 is associated with congenital heart defects and thymus hypoplasia/aplasia or T cell defect. We describe a patient showing facial dysmorphisms, delayed psychomotor development and bilateral sensorineural hearing loss and carrying a 10p14 deletion, the smallest deletion found in the literature so far. Our patient, carrying a partial deletion of the DGCR2 region and of the HDR1 region, including the GATA3 gene, showed, unexpectedly, only few of the clinical features of DiGeorge 2 syndrome (psychomotor retardation, palpebral ptosis, epicanthic folds, anteverted nares, cryptorchidism, hand/foot abnormalities) and did not show other typical signs, such as cardiac defect, cleft palate, and abnormal T cell levels. Of the three characteristic features of the HDR syndrome, our patient had only sensorineural deafness. On the basis of the revision of the other cases reported in the literature with a deletion including the 10p14 region, we suggest that GATA3 haploinsufficiency, although not recorded for each patient, is responsible for deafness. The present case shows that even this small 10p deletion is responsible for a specific phenotype. We also underline the importance of CGH-array, in order to obtain a more precise physical mapping of the 10p deletions and an accurate genotype-phenotype correlation.


Assuntos
Cromossomos Humanos Par 10/genética , Perda Auditiva Neurossensorial/genética , Hipoparatireoidismo/genética , Nefrose/genética , Deleção de Sequência , Pré-Escolar , Síndrome de DiGeorge/genética , Fator de Transcrição GATA3/genética , Estudos de Associação Genética , Haploinsuficiência , Perda Auditiva Neurossensorial/patologia , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Hipoparatireoidismo/patologia , Hipoparatireoidismo/fisiopatologia , Masculino , Nefrose/patologia , Nefrose/fisiopatologia
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