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1.
Clin Nephrol ; 96(5): 297-301, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34448699

RESUMEN

A 33-year-old Japanese man with no significant past medical history was admitted to our hospital for evaluation of weight gain and pitting edema. A laboratory test confirmed nephrotic-range proteinuria. Renal biopsy showed subepithelial deposits, and membranous nephropathy (MN) was diagnosed. Closer examination clarified an active syphilis infection. After renal biopsy, we prescribed amoxicillin for 8 weeks to treat the syphilis infection. Three weeks later, the patient's proteinuria dramatically decreased. This case is of interest because syphilis can become a cause of acute-onset MN in younger adults, and the incidence of syphilis is increasing in Japan.
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Asunto(s)
Glomerulonefritis Membranosa , Sífilis , Adulto , Amoxicilina/uso terapéutico , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/etiología , Humanos , Japón , Masculino , Proteinuria , Sífilis/complicaciones , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico
2.
Clin Exp Nephrol ; 23(10): 1202-1210, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31240503

RESUMEN

INTRODUCTION: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. CONCLUSION: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.


Asunto(s)
24,25-Dihidroxivitamina D 3/sangre , Hipercalcemia/sangre , Enfermedades Renales/sangre , Sarcoidosis/sangre , Adulto , Anciano , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Biopsia , Calcio/sangre , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Hipercalcemia/etiología , Riñón/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/patología , Macrófagos/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/sangre , Nefritis Intersticial/patología , Estudios Retrospectivos , Sarcoidosis/complicaciones , Sarcoidosis/tratamiento farmacológico , Esteroides/uso terapéutico , Adulto Joven
3.
Clin Exp Nephrol ; 23(10): 1181-1187, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31161263

RESUMEN

BACKGROUND: Cholesterol crystal embolism (CCE) causes renal damage, and there is an extremely high risk of end-stage renal disease. However, the time course of CCE-related renal deterioration varies and little is known about the subsequent risk of dialysis among patients with biopsy-proven CCE. METHODS: We performed a retrospective cohort study of 38 Japanese patients in whom a histological diagnosis of CCE was made from September 1992 to July 2005. Competing risk regression analysis was used to investigate the association between declining renal function ( ≥ 1.5 elevation of serum creatinine within 26 weeks after CCE) or its subtypes (acute [ < 1 week after CCE], subacute [1 to < 6 weeks], and chronic [6 to < 26 weeks]) and the risk of dialysis, with adjustment for age, baseline serum creatinine, and the precipitating event (iatrogenic or spontaneous). RESULTS: During a median follow-up period of 25.9 weeks, 14 patients (35.9%) started dialysis. Multivariable analysis showed that patients with declining renal function had a higher risk of commencing dialysis than those without declining function (subdistribution hazard ratio [SHR] 9.47; 95% confidence interval [CI] 1.34-66.8). Patients with different renal presentations had a similarly increased risk of commencing dialysis, with the risk being significantly higher for the subacute and chronic patterns of declining renal function (adjusted SHR [95% CI] for acute, subacute, and chronic declining renal function[vs. no decline]: 7.36 [0.85-63.6], 11.9 [1.36-101], and 10.7 [1.49-77.0], respectively). CONCLUSION: Declining renal function after CCE, even later than 6 weeks, was significantly associated with the subsequent risk of dialysis.


Asunto(s)
Embolia por Colesterol/terapia , Anciano , Pueblo Asiatico , Biopsia , Estudios de Cohortes , Creatinina/sangre , Embolia por Colesterol/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Fallo Renal Crónico/etiología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Diálisis Renal , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
4.
Clin Nephrol ; 89(3): 223-228, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29162218

RESUMEN

We investigated a 25-year-old Japanese man who had polycystic kidneys and end-stage renal failure without a positive family history. Ultrasonography revealed enlarged kidneys with increased echogenicity and multiple cystic lesions. MRI showed replacement of both kidneys by cystic lesions without definite walls. Renal biopsy demonstrated interstitial fibrosis, especially at the corticomedullary junction. The residual tubular system showed starfish-like disruption. Tubules with cystic dilation were mainly the distal loop of Henle and the distal tubules since immunohistochemical staining was positive for cytokeratin 7 (the distal loop of Henle and the distal tubule) and Tamm-Horsfall protein (the distal loop of Henle), while being negative for aquaporin 3 (the collecting duct) and CD10 (proximal tubule). Comprehensive genetic analysis identified compound heterozygous missense mutations of NPHP4 with autosomal recessive inheritance since his asymptomatic parents each had a single heterozygous missense mutation of NPHP4. In conclusion, MRI and immunohistochemical analysis of renal biopsy specimens may be useful for evaluation of this disease.
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Asunto(s)
Enfermedades Renales Quísticas/diagnóstico por imagen , Enfermedades Renales Quísticas/patología , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/patología , Imagen por Resonancia Magnética , Adulto , Humanos , Inmunohistoquímica , Enfermedades Renales Quísticas/genética , Túbulos Renales/metabolismo , Túbulos Renales/patología , Masculino , Proteínas/genética
5.
Clin Nephrol ; 89(6): 438-444, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29648530

RESUMEN

BACKGROUND: Antithyroid drugs such as propylthiouracil and methimazole have been reported to cause antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but little is known about long-term outcomes. MATERIALS AND METHODS: We identified AAV patients who underwent renal biopsy and retrospectively assessed their clinical and histological findings. Patients with AAV who had received propylthiouracil or methimazole were defined as having antithyroid drug-associated AAV (ATD-AAV), and the other patients were defined as having primary AAV. RESULTS: Seven patients with ATD-AAV and 83 patients with primary AAV were identified. Compared with the primary AAV group, the patients with ATD-AAV were significantly younger (mean ± standard deviation; 45.4 ± 21.4 years vs. 65.9 ± 13.8 years, p < 0.01), and had lower serum creatinine (median [interquartile range]; 0.7 mg/dL [0.6 - 1.5] vs. 2.3 mg/dL [1.0 - 4.0], p = 0.02), as well as a higher frequency of positivity for MPO--ANCA/PR3-ANCA (42.9 vs. 4.8%, p < 0.01). While glomerular crescents varied, interstitial fibrosis and tubular atrophy were milder in ATD-AAV patients. Kaplan-Meier analysis showed a significantly higher kidney survival rate in patients with ATD-AAV than in those with primary AAV (p = 0.05). CONCLUSION: Patients with ATD-AAV were younger and had milder kidney involvement, resulting in a better long-term outcome compared with primary AAV.
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Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Antitiroideos/efectos adversos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inducido químicamente , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Humanos , Estudios Retrospectivos
6.
Nephrology (Carlton) ; 23(11): 1007-1012, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28834647

RESUMEN

AIM: Kidney biopsy is the gold standard for diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but it is unknown whether vasculitis can be detected from AAV patients with minor urinary abnormalities. METHODS: Ninety ANCA-positive patients undergoing kidney biopsy were evaluated retrospectively after being divided into two groups, which were group A (minor urinary abnormalities with both proteinuria <0.5 g/day and red blood cells ≤5/high power field) and group B (major urinary abnormalities except group A). RESULTS: Thirteen patients were included in group A and 77 patients were in group B. Crescentic glomeruli were detected less frequently in group A than in group B (61.5% vs. 92.2%, P < 0.01). The percentage of crescentic glomeruli relative to total glomeruli was significantly lower in group A than in group B (median [interquartile range]; 2.7% [0-5.2%] vs. 27.3% [8.1-56.1%], P < 0.01). Vasculitis of the small renal arteries was detected more frequently in group A than in group B without significant difference (30.8% vs. 19.5%, P = 0.46). Overall renal vasculitis (crescentic glomeruli and/or small renal artery vasculitis) was detected less frequently in group A than in group B (69.2% vs. 92.2%, P = 0.03). CONCLUSIONS: These findings indicate that renal biopsy can be a useful tool for histological diagnosis of ANCA-associated vasculitis in ANCA-positive patients with minor urinary abnormalities, even though the rate of renal vasculitis to the total number of glomeruli sampled is lower in patients with minor urinary abnormalities than patients with major abnormalities.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Riñón/patología , Adulto , Anciano , Anciano de 80 o más Años , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
7.
BMC Nephrol ; 19(1): 272, 2018 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-30340529

RESUMEN

BACKGROUND: Cyst infection is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD) that is often refractory. Carbapenems are frequently needed to treat to patients with refractory cyst infection, but little is known about the penetration of newer water-soluble carbapenems into cysts. This study investigated the penetration of meropenem (MEPM) into infected cysts in patients with ADPKD. METHODS: Between August 2013 and January 2014, 10 ADPKD patients (14 infected cysts) receiving MEPM at Toranomon Hospital underwent drainage of infected cysts and definite cyst infection was confirmed through detection of neutrophils by cyst fluid analysis. The serum concentration of MEPM was measured just after intravenous administration and was compared with that in fluid aspirated from infected cysts. RESULTS: In the patients undergoing cyst drainage, the mean serum MEPM concentration was 35.2 ± 12.2 µg/mL (range: 19.7 to 59.2 µg/mL, while the mean cyst fluid concentration of MEPM in the drained liver cysts (n = 12) or kidney cysts (n = 2) was 3.03 ± 2.6 µg/mL (range: 0 to 7.3 µg/mL). In addition, the mean cyst fluid/serum MEPM concentration ratio was 9.46 ± 7.19% (range: 0 to 18.8%). There was no relationship between the cyst fluid concentration of MEPM and the time until drainage after MEPM administration or between the cyst fluid/serum MEPM concentration ratio and the time until drainage. CONCLUSION: These findings suggest that MEPM shows poor penetration into infected cysts in ADPKD patients. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN) as "Penetration of meropenem into cysts in patients with autosomal dominant polycystic kidney disease (ADPKD)", UMIN ID 000011292 on July 26th, 2013.


Asunto(s)
Antibacterianos/uso terapéutico , Quistes/tratamiento farmacológico , Meropenem/uso terapéutico , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antibacterianos/metabolismo , Quistes/complicaciones , Quistes/metabolismo , Drenaje/métodos , Femenino , Humanos , Masculino , Meropenem/metabolismo , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/metabolismo , Estudios Prospectivos
8.
Mod Rheumatol ; 28(3): 570-574, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-26743943

RESUMEN

A 63-year-old Japanese woman with Sjögren's syndrome and peripheral neuropathy was admitted for evaluation of purpura on her lower extremities. Skin biopsy revealed leukocytoclastic vasculitis with the deposition of IgM, and serum cryoglobulin was positive. Accordingly, cryoglobulinemic vasculitis was diagnosed. There was no response to high-dose steroid therapy and plasmapheresis, but intravenous cyclophosphamide pulse therapy was effective for 4 years. Thereafter, proteinuria and hematuria developed, with cryoglobulinemic glomerulopathy being diagnosed by renal biopsy. Because the total dose of cyclophosphamide had reached 8000 mg, treatment with rituximab was selected. While rituximab was initially effective for her skin lesions and nephropathy, relapse occurred within 2 years and additional administration of this agent was required. The long-term efficacy of treatment for cryoglobulinemic vasculitis remains uncertain in patients with Sjögren's syndrome.


Asunto(s)
Crioglobulinemia/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Síndrome de Sjögren/complicaciones , Vasculitis/tratamiento farmacológico , Crioglobulinemia/complicaciones , Crioglobulinemia/patología , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Rituximab/administración & dosificación , Rituximab/efectos adversos , Síndrome de Sjögren/patología , Vasculitis/complicaciones , Vasculitis/patología
9.
Mod Rheumatol ; 28(2): 369-372, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26942857

RESUMEN

A 69-year-old Japanese man was presented with hypertensive crisis. Renal histology revealed malignant nephrosclerosis, including an onion skin pattern with fibrinoid necrosis of the small arteries from arterioles up to interlobular arteries. Immunological investigation clarified positive anti-RNA polymerase (RNAP) III antibody, and limited cutaneous systemic sclerosis (Lc SSc) was diagnosed by skin biopsy as the underlying disease causing scleroderma renal crisis (SRC). Angiotensin covering enzyme (ACE) inhibitor therapy and calcium antagonist were effective for his renal condition. Although an association between SRC and anti-RNAP III antibody has already been reported in patients with diffuse cutaneous SSc (Dc SSc), this case indicates that SRC with hypetensive emergency with malignant nephrosclerosis can also be diagnosed on patients with Lc SSc patients by the examination of anti-RNAP III antibody.


Asunto(s)
Nefroesclerosis/etiología , Nefrosis/etiología , ARN Polimerasa III/inmunología , Esclerodermia Sistémica/complicaciones , Anciano , Anticuerpos/inmunología , Humanos , Masculino , Nefroesclerosis/inmunología , Nefrosis/inmunología , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/patología , Piel/patología
10.
Nephrol Dial Transplant ; 32(7): 1176-1183, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28873973

RESUMEN

BACKGROUND: Currently, there are few strategies for improving the quality of life (QOL) in patients with autosomal dominant polycystic kidney disease (ADPKD) and massive kidneys. Renal transcatheter arterial embolization (TAE) reduces kidney volume, but its impact on QOL in ADPKD patients on hemodialysis is unknown. This study investigated the influence of renal TAE on QOL in ADPKD patients with massive kidneys receiving hemodialysis. METHODS: This prospective observational study enrolled 188 ADPKD patients on hemodialysis (92 men and 96 women; mean age 56.7 ± 9.1 years) who underwent renal TAE at Toranomon Hospital between August 2010 and July 2014. The 36-item Short Form Health Survey (SF-36) and our original 15-item questionnaire were used to evaluate QOL. RESULTS: Using a linear mixed model, the least squares mean values of the SF-36 physical component summary (PCS), mental component summary (MCS) and role/social component summary (RCS) before renal TAE were calculated as 38.21 [95% confidence interval (CI) 36.50-39.91], 48.45 (47.05-49.86) and 43.04 (40.70-45.37), respectively. These values improved to 42.0 (40.22-43.77; P < 0.001 versus before TAE), 51.25 (49.78-52.71; P = 0.001) and 49.67 (47.22-52.12; P < 0.001), respectively, 1 year after renal TAE. Scores for abdominal fullness, poor appetite and heartburn showed marked improvement after renal TAE, while scores for fever, bodily pain and sleep disorder also improved slightly, but significantly. Scores for constipation and use of analgesics/sleeping medications/laxatives did not improve significantly. All of the SF-36 scores and the scores for specific symptoms (except bodily pain, snoring and constipation) were significantly correlated with the sequential decrease of the height-adjusted total kidney volume. CONCLUSIONS: In ADPKD patients on hemodialysis, renal TAE was effective in improving abdominal fullness, appetite, heartburn and SF-36 scores (MCS and RCS scores), but not for sleep disturbance, constipation and physical strength (PCS score).


Asunto(s)
Cateterismo , Embolización Terapéutica , Riñón Poliquístico Autosómico Dominante/terapia , Calidad de Vida , Arteria Renal/cirugía , Diálisis Renal , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Selección de Paciente , Riñón Poliquístico Autosómico Dominante/patología , Estudios Prospectivos , Encuestas y Cuestionarios , Adulto Joven
11.
Clin Nephrol ; 88(11): 292-297, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28933340

RESUMEN

A 37-year-old Japanese man with a serum creatinine level of 2.5 mg/dL and hepatomegaly was admitted to our hospital for investigation of renal failure. Magnetic resonance imaging (MRI) showed hepatomegaly with small cystic lesions that had high signal intensity on T2-weighted images. There was no splenomegaly, and the kidneys were nearly normal in size with a few small cystic lesions. Renal biopsy revealed that interstitial fibrosis and tubular atrophy affected 60% of the cortex. There was cystic tubular dilation, mainly affecting the distal loop of Henle and distal tubules, since immunohistochemical staining of the dilated tubules was positive for cytokeratin 7 and Tamm-Horsfall protein but was negative for aquaporin 3 and CD10. Immunofluorescence microscopy and electron microscopy did not demonstrate any immune deposits. Genetic analysis identified two different heterozygous missense variants of PKHD1, while the patient's asymptomatic parents were each heterozygous for a single PKHD1 mutation. Accordingly, autosomal recessive polycystic kidney disease (-ARPKD) due to compound heterozygous PKHD1 mutation was diagnosed. The renal biopsy findings of this patient may be nonspecific, but they were different from the typical renal histology of infantile ARPKD. In conclusion, the renal features of adult-onset ARPKD may differ from those of infantile disease.
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Asunto(s)
Riñón/patología , Imagen por Resonancia Magnética/métodos , Riñón Poliquístico Autosómico Recesivo/patología , Adulto , Humanos , Masculino , Mutación , Riñón Poliquístico Autosómico Recesivo/diagnóstico por imagen , Riñón Poliquístico Autosómico Recesivo/genética , Receptores de Superficie Celular/genética
12.
J Am Soc Nephrol ; 27(7): 2177-87, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26620095

RESUMEN

In patients with autosomal dominant polycystic kidney disease (ADPKD), massive renal enlargement is a serious problem. Renal transcatheter arterial embolization (TAE) can reduce renal volume (RV), but effectiveness varies widely, and the reasons remain unclear. We investigated factors affecting renal volume reduction rate (RVRR) after renal TAE in all 449 patients with ADPKD who received renal TAE at Toranomon Hospital from January of 2006 to July of 2013, including 228 men and 221 women (mean age =57.0±9.1 years old). One year after renal TAE, the RVRR ranged from 3.9% to 84.8%, and the least squares mean RVRR calculated using a linear mixed model was 45.5% (95% confidence interval [95% CI], 44.2% to 46.8%). Multivariate analysis using the linear mixed model revealed that RVRR was affected by the presence of large cysts with wall thickening (regression coefficient [RC], -6.10; 95% CI, -9.04 to -3.16; P<0.001), age (RC, -0.82; 95% CI, -1.03 to -0.60; P<0.001), dialysis duration (RC, -0.10; 95% CI, -0.18 to -0.03; P<0.01), systolic BP (RC, 0.39; 95% CI, 0.19 to 0.59; P<0.001), and the number of microcoils used for renal TAE (RC, 1.35; 95% CI, 0.83 to 1.86; P<0.001). Significantly more microcoils were needed to achieve renal TAE in patients with younger age and shorter dialysis duration. In conclusion, cyst wall thickening had an important effect on cyst volume reduction. Renal TAE was more effective in patients who were younger, had shorter dialysis duration, or had hypertension, parameters that might associate with cyst wall stiffness and renal artery blood flow.


Asunto(s)
Cateterismo , Embolización Terapéutica/métodos , Selección de Paciente , Riñón Poliquístico Autosómico Dominante/terapia , Arteria Renal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Riñón Poliquístico Autosómico Dominante/patología , Estudios Retrospectivos
13.
Am J Pathol ; 185(8): 2118-31, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26072030

RESUMEN

Intracapillary foam cell infiltration with podocyte alterations is a characteristic pathology of focal segmental glomerulosclerosis (FSGS). We investigated the possible role of podocyte injury in glomerular macrophage and foam cell infiltration in a podocyte-selective injury model (NEP25 mice) and hypercholesterolemic model [low-density lipoprotein receptor deficiency (LDLR(-/-)) mice] with doxorubicin-induced nephropathy. Acute podocyte selective injury alone failed to induce glomerular macrophages in the NEP25 mice. However, in the doxorubicin-treated hypercholesterolemic LDLR(-/-) mice, glomerular macrophages/foam cells significantly increased and were accompanied by lipid deposition and the formation and ingestion of oxidized phospholipids (oxPLs). Glomerular macrophages significantly correlated with the amount of glomerular oxPL. The NEP25/LDLR(-/-) mice exhibited severe hypercholesterolemia, glomerular lipid deposition, and renal dysfunction. Imaging mass spectrometry revealed that a major component of oxidized low-density lipoprotein, lysophosphatidylcholine 16:0 and 18:0, was present only in the glomeruli of NEP25/LDLR(-/-) mice. Lysophosphatidylcholine 16:0 stimulated mesangial cells and macrophages, and lysophosphatidylcholine 18:0 stimulated glomerular endothelial cells to express adhesion molecules and chemokines, promoting macrophage adhesion and migration in vitro. In human FSGS, glomerular macrophage-derived foam cells contained oxPLs accompanied by the expression of chemokines in the tuft. In conclusion, glomerular lipid modification represents a novel pathology by podocyte injury, promoting FSGS. Podocyte injury-driven lysophosphatidylcholine de novo accelerated glomerular macrophage-derived foam cell infiltration via lysophosphatidylcholine-mediated expression of adhesion molecules and chemokines in glomerular resident cells.


Asunto(s)
Células Espumosas/patología , Glomeruloesclerosis Focal y Segmentaria/patología , Glomérulos Renales/patología , Peroxidación de Lípido/fisiología , Podocitos/patología , Animales , Movimiento Celular/fisiología , Modelos Animales de Enfermedad , Células Espumosas/metabolismo , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Humanos , Glomérulos Renales/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones , Ratones Noqueados , Podocitos/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo
14.
BMC Nephrol ; 17(1): 170, 2016 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-27829402

RESUMEN

BACKGROUND: The purpose of this study was to investigate the usefulness of intracystic MRI features for detection of severe cyst infection that is usually refractory to antibiotic therapy alone in patients with autosomal dominant polycystic kidney disease. METHODS: Seventy-six patients (88 episodes) with positive cyst cultures treated from January 2006 to December 2013 were enrolled as the cases for this case-control study, while 147 patients who continued to attend our hospital from January 2011 to December 2013 and did not have cyst infection diagnosed during that period were enrolled as the controls. Intracystic MRI findings were investigated. RESULTS: At least one of four intracystic MRI features (high signal intensity (SI) on diffusion-weighted images (DWI), fluid-fluid level, wall thickening, or gas) was found in all of the cases, but such findings were also detected in some controls. Intracystic gas was specific for cyst infection, but its sensitivity was only 1.1 %. A high intracystic SI on DWI showed a sensitivity of 86.4 %, but its specificity was lower at 33.3 %. Both the specificity and sensitivity of a fluid-fluid level or wall thickening were about 80 %. However, the specificity of these MRI features decreased as total liver and kidney volume (TLKV) increased, falling to 65.8 % in patients with organomegaly (TLKV > 8500 cm3). A cyst diameter > 5 cm was useful for detecting severely infected cysts that needed drainage, and specificity was increased by combining the other four MRI findings with a cyst diameter > 5 cm. CONCLUSIONS: MRI with DWI was useful for detecting severe cyst infection in ADPKD. While the specificity of MRI alone was not high enough in patients with organomegaly, combining the four MRI features with abdominal pain, sequential MRI changes, or cyst diameter > 5 cm improved detection of severely infected cysts in these patients.


Asunto(s)
Infecciones Bacterianas/diagnóstico por imagen , Quistes/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Hepatomegalia/complicaciones , Riñón/patología , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Adulto , Anciano , Estudios de Casos y Controles , Quistes/microbiología , Gases , Humanos , Persona de Mediana Edad , Tamaño de los Órganos , Riñón Poliquístico Autosómico Dominante/complicaciones , Estudios Retrospectivos , Sensibilidad y Especificidad
15.
Am J Physiol Renal Physiol ; 308(6): F614-26, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25587125

RESUMEN

Podocyte-endothelial cell cross-talk is paramount for maintaining the filtration barrier. The present study investigated the endothelial response to podocyte injury and its subsequent role in glomerulosclerosis using the podocyte-specific injury model of NEP25/LMB2 mice. NEP25/LMB2 mice showed proteinuria and local podocyte loss accompanied by thrombotic microangiopathy on day 8. Mice showed an increase of glomerular plasminogen activator inhibitor type 1 (PAI-1) mRNA and aberrant endothelial PAI-1 protein already on day 1, before thrombosis and proteinuria. A PAI-1-specific inhibitor reduced proteinuria and thrombosis and preserved podocyte numbers in NEP25/LMB2 mice by stabilization of ß1-integrin translocation. Heparin loading significantly reduced thrombotic formation, whereas proteinuria and podocyte numbers were unchanged. Immortalized podocytes treated with PAI-1 and the urokinase plasminogen activator (uPA) complex caused significant cell detachment, whereas podocytes treated with PAI-1 or uPA alone or with the PAI-1/uPA complex pretreated with an anti-uPA receptor (uPAR) antibody failed to cause detachment. Confocal microscopy and cell surface biotinylation experiments showed that internalized ß1-integrin was found together with uPAR in endocytotic vesicles. The administration of PAI-1 inhibitor or uPAR-blocking antibody protected cultured podocytes from cell detachment. In conclusion, PAI-1/uPA complex-mediated uPAR-dependent podocyte ß1-integrin endocytosis represents a novel mechanism of glomerular injury leading to progressive podocytopenia. This aberrant cross-talk between podocytes and endothelial cells represents a feedforward injury response driving podocyte loss and progressive glomerulosclerosis.


Asunto(s)
Endocitosis , Cadenas beta de Integrinas/metabolismo , Inhibidor 1 de Activador Plasminogénico/metabolismo , Podocitos/fisiología , Receptores del Activador de Plasminógeno Tipo Uroquinasa/metabolismo , Animales , Línea Celular , Heparina , Humanos , Ratones Endogámicos C57BL , Distribución Aleatoria , Trombosis/metabolismo , Regulación hacia Arriba , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo
16.
Diabetes Metab Res Rev ; 31(6): 572-81, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25533683

RESUMEN

BACKGROUND: The effect of clinical and pathological parameters on the estimated glomerular filtration rate (eGFR) decline has not been investigated in patients with type 2 diabetes and overt proteinuric biopsy-proven diabetic nephropathy. METHODS: Among 198 patients with type 2 diabetes who underwent renal biopsy and were confirmed to have pure diabetic nephropathy according to the recent classification, 128 patients with overt proteinuria were enrolled. Receiver operating characteristic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) analyses were performed using models adjusted for various clinical and pathological covariates to determine the best predictors of rapid eGFR decline [defined as >14.9%/year (median eGFR decline)]. RESULTS: A model that incorporated proteinuria showed the largest area under the curve (AUC) among clinical models, which suggested that proteinuria was the best clinical predictor. Although a model incorporating interstitial fibrosis and tubular atrophy (IFTA) score did not display a significantly larger AUC than the model with proteinuria (0.843 vs 0.812, respectively, p = 0.47), a model with both IFTA score and proteinuria had a significantly larger AUC than the model with proteinuria alone (0.875 vs 0.812, respectively, p = 0.014). Similarly, the addition of IFTA score resulted in a significantly greater net reclassification improvement and integrated discrimination improvement than the model with proteinuria alone [NRI: 0.78 (95% CI: 0.43-1.13; p < 0.001), IDI: 0.13 (95% CI: 0.07-0.19; p < 0.001)]. CONCLUSIONS: Our results suggest that not only proteinuria but also tubulointerstitial lesions should be assessed to predict rapid eGFR decline in patients with type 2 diabetes who have overt proteinuria and biopsy-proven diabetic nephropathy.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Riñón/fisiopatología , Proteinuria/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Anciano , Atrofia/patología , Atrofia/fisiopatología , Biomarcadores , Biopsia con Aguja , Estudios de Cohortes , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Progresión de la Enfermedad , Femenino , Fibrosis/patología , Fibrosis/fisiopatología , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Pronóstico , Proteinuria/etiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/fisiopatología , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
17.
Am J Nephrol ; 41(4-5): 337-44, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26067713

RESUMEN

BACKGROUND: With the association between diabetic nephropathy (DN) and renal outcome being increasingly clear, we aimed at creating a new DN pathological scoring system that could predict the renal outcome. METHODS: We studied 205 patients with DN confirmed by renal biopsy, sometime between March 1985 and January 2010, who met the inclusion criteria. Renal biopsy included clinical parameters and Tervaert classifications. Hazard ratios (HRs) for death-censored end-stage renal disease (ESRD) were estimated by adjusted Cox proportional-hazards regression. The overall pathological risk score (D-score) was calculated by summing the products of beta coefficient and bootstrap-inclusion fractions, its predictive utility evaluated by Kaplan-Meier methods and c-statistics for a 10-year risk of ESRD. RESULTS: The D-scores of glomerular classes 1, 2A, 2B, 3, and 4 were, respectively, 0, 3, 4, 6, and 6. Those of interstitial fibrosis and tubular atrophy classes 0, 1, 2, and 3 were 0, 7, 9, and 11, and those of interstitial inflammation classes 0, 1, and 2 were 0, 3, and 4, respectively. The D-score of hyalinosis class 2 was 3 and that of arteriosclerosis class 2 was 1. So, a patient's D-score could be 0-25. HRs for ESRD in patients with D-score ≤14, 15-18, 19-21, and 22-25 were, respectively, 1.00 (reference) 16.21 (95% confidence interval (CI), 1.86-140.90), 19.78 (95% CI, 2.15-182.40), and 45.46 (95% CI, 4.63-446.68) after adjusting for clinical factors. The c-statistics suggested a better predictive ability for a 10-year renal death with models that included the D-score. CONCLUSION: Prediction of DN patients' renal outcome was better with the D-score than without it. Patients with a D-score ≤14 had excellent renal prognosis.


Asunto(s)
Arteriosclerosis/patología , Nefropatías Diabéticas/patología , Fallo Renal Crónico/patología , Riñón/patología , Proteinuria/patología , Adulto , Anciano , Atrofia , Biopsia , Estudios de Cohortes , Nefropatías Diabéticas/metabolismo , Progresión de la Enfermedad , Femenino , Fibrosis , Tasa de Filtración Glomerular , Humanos , Inflamación , Riñón/metabolismo , Fallo Renal Crónico/metabolismo , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Estudios Retrospectivos , Medición de Riesgo
18.
Am J Physiol Renal Physiol ; 306(1): F98-F104, 2014 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-24154691

RESUMEN

Focal segmental glomerulosclerosis (FSGS) is a podocyte disease. Among the various histologies of FSGS, active epithelial changes, hyperplasia, as typically seen in the collapsing variant, indicates disease progression. Using a podocyte-specific injury model of FSGS carrying a genetic podocyte tag combined with double immunostaining by different sets of podocytes and parietal epithelial cell (PEC) markers [nestin/Pax8, Wilms' tumor-1 (WT1)/claudin1, and podocalyxin/Pax2], we investigated the direction of epithelial phenotypic transition and its role in FSGS. FSGS mice showed progressive proteinuria and renal dysfunction often accompanied by epithelial hyperplasia, wherein 5-bromo-4-chloro-3-indoyl ß-d-galactoside (X-gal)-positive podocyte-tagged cells were markedly decreased. The average numbers of double-positive cells in all sets of markers were significantly increased in the FSGS mice compared with the controls. In addition, the average numbers of double-positive cells for X-gal/Pax8, nestin/Pax8 and podocalyxin/Pax2 staining in the FSGS mice were comparable, whereas those of WT1/claudin1 were significantly increased. When we divided glomeruli from FSGS mice into those with FSGS lesions and those without, double-positive cells tended to be more closely associated with glomeruli without FSGS lesions compared with those with FSGS lesions. Moreover, the majority of double-positive cells appeared to be isolated and very rarely associated with FSGS lesions (1/1,997 glomeruli). This study is the first to show the incidence and localization of epithelial cells with phenotypical changes in FSGS using a genetic tag. The results suggest that the major direction of epithelial phenotypic transition in cellular FSGS is from podocytes to PECs and that these cells were less represented in the active lesions of FSGS.


Asunto(s)
Diferenciación Celular , Células Epiteliales/citología , Glomeruloesclerosis Focal y Segmentaria/patología , Podocitos/citología , Animales , Anticuerpos Monoclonales/toxicidad , Biomarcadores , Claudina-1/genética , Claudina-1/metabolismo , Células Epiteliales/fisiología , Epitelio/patología , Exotoxinas/toxicidad , Regulación de la Expresión Génica , Marcadores Genéticos , Humanos , Subunidad alfa del Receptor de Interleucina-2 , Ratones , Ratones Transgénicos , Nestina/genética , Nestina/metabolismo , Factor de Transcripción PAX2/genética , Factor de Transcripción PAX2/metabolismo , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/metabolismo , Podocitos/fisiología , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo
19.
Kidney Int ; 83(6): 1065-75, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23447065

RESUMEN

Collapsing focal segmental glomerulosclerosis (cFSGS) is a progressive kidney disease characterized by glomerular collapse with epithelial hyperplasia. Here we used a transgenic mouse model of cFSGS with immunotoxin-induced podocyte-specific injury to determine the role for Notch signaling in its pathogenesis. The mice exhibited progressive loss of podocytes and severe proteinuria concomitant with histological features of cFSGS. Hyperplastic epithelium was negative for genetic podocyte tags, but positive for the parietal epithelial cell marker claudin-1, and expressed Notch1, Jagged1, and Hes1 mRNA and protein. Enhanced Notch mRNA expression induced by transforming growth factor-ß1 in cultured parietal epithelial cells was associated with mesenchymal markers (α-smooth muscle actin, vimentin, and Snail1). Notch inhibition in vitro suppressed these phenotypic transcripts and Notch-dependent cell migration. Moreover, Notch inhibition in vivo significantly decreased parietal epithelial cell lesions but worsened proteinuria and histopathology in our cFSGS model. Thus, aberrant Notch1-mediated parietal epithelial cell migration with phenotypic changes appears to underlie the pathogenesis of cFSGS. Parietal epithelial cell hyperplasia may also represent an adaptive response to compensate for a disrupted filtration barrier with progressive podocyte loss.


Asunto(s)
Células Epiteliales/metabolismo , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomérulos Renales/metabolismo , Podocitos/metabolismo , Receptor Notch1/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Animales , Anticuerpos Monoclonales , Apoptosis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Biomarcadores/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Línea Celular , Movimiento Celular , Proliferación Celular , Claudina-1/genética , Claudina-1/metabolismo , Dibenzazepinas/farmacología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Exotoxinas , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/patología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Hiperplasia , Integrasas/genética , Integrasas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Proteína Jagged-1 , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/patología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Podocitos/efectos de los fármacos , Podocitos/patología , Proteinuria/genética , Proteinuria/metabolismo , Proteinuria/patología , ARN no Traducido/genética , ARN no Traducido/metabolismo , Receptor Notch1/antagonistas & inhibidores , Proteínas Serrate-Jagged , Factores de Tiempo
20.
Nephrol Dial Transplant ; 27(2): 633-9, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21771754

RESUMEN

BACKGROUND: Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. METHODS: A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. RESULTS: Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. CONCLUSION: Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.


Asunto(s)
Amiloidosis/epidemiología , Amiloidosis/metabolismo , Artritis Reumatoide/epidemiología , Enfermedades Renales/epidemiología , Enfermedades Renales/metabolismo , Proteinuria/metabolismo , Proteína Amiloide A Sérica/metabolismo , Distribución por Edad , Anciano , Amiloidosis/patología , Amiloidosis/terapia , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/terapia , Biopsia con Aguja , Comorbilidad , Intervalos de Confianza , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Enfermedades Renales/patología , Enfermedades Renales/terapia , Pruebas de Función Renal , Persona de Mediana Edad , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Remisión Espontánea , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia
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