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1.
Exp Clin Transplant ; 16(2): 216-218, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27364115

RESUMEN

We report a case of recurrent tubulointerstitial nephritis without uveitis in a patient with previous tubulointerstitial nephritis and uveitis syndrome after transplant. A 26-year-old male patient who had been diagnosed with tubulointerstitial nephritis and uveitis syndrome at 8 years of age developed end-stage renal failure and subsequently underwent living-donor related renal transplant at 17 years old. The 1st recurrence of tubulointerstitial nephritis and uveitis occurred 36 months after transplant, which was treated with increased immunosuppressive drugs. Graft function worsened again to estimated glomerular filtration rate of 25 mL/min/1.73 m² at 76 months after transplant. Transplant ultrasonography was unremarkable. Virology tests (including cytomegalovirus, BK virus, and Epstein-Barr virus tests) were all negative, with negative donor-specific antibodies. Urine protein creatinine ratio was unremarkable. A biopsy showed chronic allograft rejection and graft sclerosis, and immunosuppressive medications were subsequently decreased. The patient's renal function continued to decline over the next 3 months, with estimated glomerular filtration rate showing 18 mL/min/1.73 m², prompting a further renal biopsy that showed granulomatous interstitial nephritis and moderate interstitial fibrosis. This was consistent with a further relapse of tubulointerstitial nephritis but without uveitis. His renal function improved over the next few months after tacrolimus was reintroduced.


Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Nefritis Intersticial/cirugía , Uveítis/cirugía , Adulto , Autoanticuerpos/sangre , Biopsia , Tasa de Filtración Glomerular , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/inmunología , Rechazo de Injerto/fisiopatología , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Trasplante de Riñón/métodos , Donadores Vivos , Masculino , Nefritis Intersticial/complicaciones , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/inmunología , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Uveítis/complicaciones , Uveítis/diagnóstico , Uveítis/inmunología
2.
Exp Clin Transplant ; 10(4): 332-43, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22845765

RESUMEN

OBJECTIVES: Chronic allograft nephropathy remains one of the main causes of late graft loss after kidney transplant owing to multifactorial development of kidney scarring. Chronic allograft nephropathy is characterised by an excess accumulation of extracellular matrix. A key system regulating extracellular matrix homeostasis are matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases. This study sought to determine if a change in the matrix metalloproteinases/tissue inhibitors of matrix metalloproteinases system contributes to chronic allograft nephropathy-associated progressive kidney scarring. MATERIALS AND METHODS: Examination of sequential renal biopsies was done at implantation, acute rejection, and subsequent chronic allograft nephropathy. In situ localisation of matrix metalloproteinase activity was assessed with a high-resolution in situ zymography technique using gelatin and collagen 1 substrates. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases were localised using immunohistochemistry. RESULTS: In situ zymography showed over a 50% reduction in matrix metalloproteinase activity against both collagen 1 and gelatin substrates in chronic allograft nephropathy biopsies. A similar loss of matrix metalloproteinase activity was seen in the glomerular and tubulointerstitial compartments. Immunoreactive matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases were observed intracellularly in mesangial and tubular epithelial cells. Matrix metalloproteinases-1, -2, -3, and -9 were significantly reduced in acute rejection and later in chronic allograft nephropathy. However, glomerular matrix metalloproteinases 1 and 9 and tubulointerstitial matrix metalloproteinase-2 were reduced at implantation. Tissue inhibitors of matrix metalloproteinase-2 and -3 were elevated from implantation onwards. We were unable to stain reproducibly for tissue inhibitors of matrix metalloproteinase-1. CONCLUSIONS: Kidney scarring underlying chronic allograft nephropathy is associated with a reduction in matrix metalloproteinases activity that may be due to reduced expression of matrix metalloproteinases -1, -2, -3, and -9, and up-regulation of tissue inhibitors of matrix metalloproteinases -2 and -3. Some of these changes originate from implantation.


Asunto(s)
Enfermedades Renales/enzimología , Trasplante de Riñón/efectos adversos , Riñón/enzimología , Metaloproteinasas de la Matriz/metabolismo , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Enfermedad Aguda , Adulto , Biopsia , Enfermedad Crónica , Regulación hacia Abajo , Inglaterra , Femenino , Fibrosis , Rechazo de Injerto/enzimología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Inmunohistoquímica , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/patología , Modelos Lineales , Masculino , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Resultado del Tratamiento , Regulación hacia Arriba
3.
Nephron Clin Pract ; 119(4): c348-54, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22135795

RESUMEN

BACKGROUND/AIMS: Renin-angiotensin system (RAS) inhibitors are considered first-line agents for hypertensive patients with progressive chronic kidney disease (CKD). In a previous study, we showed that stopping RAS inhibitors increased estimated glomerular filtration rate (eGFR) in a significant number of advanced CKD patients. The present study tries to address who would benefit and whether this benefit is predictable. METHODS: Forty-three CKD stage 4 patients had RAS inhibitors stopped and were followed for at least 24 months. Compared outcome groups were 'alive', 'renal replacement therapy (RRT)' or 'died'. Improvement in eGFR was used in a receiver-operating characteristic curve and finds the best predictor for surviving without RRT. RESULTS: Patients who survived without RRT were all hypertensive and had a higher eGFR increment after stopping the drugs. Those with eGFR improvement ≥5 ml/min/1.73 m(2) were the most likely to survive long term without RRT (log-rank test, p = 0.03). They had a significant increment in blood pressure that correlated with eGFR improvement (r = 0.403, p = 0.013). CONCLUSION: A significant increase in eGFR after stopping RAS inhibitors suggests that long-term survival without RRT is more likely. Our findings question the universal preemptive indication of RAS inhibitors in advanced CKD and suggest that they can be safely stopped, at least in some patients.


Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Enfermedades Renales/complicaciones , Sistema Renina-Angiotensina/efectos de los fármacos , Factores de Edad , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Enfermedad Crónica , Creatinina/sangre , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/terapia , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hiperpotasemia/inducido químicamente , Hipertensión/complicaciones , Estimación de Kaplan-Meier , Enfermedades Renales/fisiopatología , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Resultado del Tratamiento
4.
Saudi J Kidney Dis Transpl ; 21(5): 835-41, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20814116

RESUMEN

The majority of patients diagnosed with chronic kidney disease (CKD) are elderly and CKD is linked with poor cardiovascular, cognitive, and disability outcomes in these people. Only a minority of these patients will progress to end stage renal disease (ESRD) while the majority will die due to cardiovascular disease. Thus, only a small number of these patients with CKD will benefit from specialist nephrologist assessment. The priority for the remainder should be cardiovascular disease prevention. We have reviewed specific issues relevant to older people to determine high-risk groups with CKD that are likely to benefit from a more intensive risk reduction intervention and to allow identification of clinically relevant renal disease.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Renales/epidemiología , Fallo Renal Crónico/epidemiología , Factores de Edad , Albuminuria/epidemiología , Albuminuria/etiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedad Crónica , Progresión de la Enfermedad , Humanos , Enfermedades Renales/complicaciones , Enfermedades Renales/mortalidad , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Medición de Riesgo , Factores de Riesgo
5.
Nephrol Dial Transplant ; 25(12): 3977-82, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19820248

RESUMEN

BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) has shown to slow chronic kidney disease (CKD) progression. This is most notable at the earlier stages of diabetic and proteinuric nephropathies. Objective. Here, we observed the impact of discontinuation of angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptors blockers (ARB) in patients with advanced kidney disease. METHODS: 52 patients (21 females and 31 males) with advanced CKD (stages 4 and 5), who attended our low clearance clinic (LCC) in preparation for renal replacement therapy (RRT). Mean age was 73.3 ± 1.8 years with an estimated glomerular filtration rate (eGFR) of 16.38 ± 1 ml/min/1.73 m(2). Baseline urine protein:creatinine ratio (PCR) was 77 ± 20 mg/mmol. 46% suffered from diabetes mellitus. Patients were followed for at least 12 months before and after ACEi/ARB were stopped. RESULTS: 12 months after discontinuation of ACEi/ARB eGFR increased significantly to 26.6 ± 2.2 ml/min/ 1.73 m(2) (p = 0.0001). 61.5% of patients had more than a 25% increase in eGFR, whilst 36.5% had an increase exceeding 50%. There was a significant decline in the eGFR slope -0.39 ± 0.07 in the 12 months preceding discontinuation. The negative slope was reversed +0.48 ± 0.1 (p = 0.0001). Mean arterial blood pressure (MAP) increased from 90 ± 1.8 mmHg to 94 ± 1.3 mmHg (p = 0.02), however ≥50% of patients remained within target. Overall proteinuria was not affected (PCR before = 77 ± 20 and after = 121.6 ± 33.6 mg/mmol). CONCLUSION: Discontinuation of ACEi/ARB has undoubtedly delayed the onset of RRT in the majority of those studied. This observation may justify a rethink of our approach to the inhibition of the RAAS in patients with advanced CKD who are nearing the start of RRT.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Progresión de la Enfermedad , Enfermedades Renales/prevención & control , Enfermedades Renales/fisiopatología , Sistema Renina-Angiotensina/fisiología , Privación de Tratamiento , Anciano , Presión Sanguínea/fisiología , Enfermedad Crónica , Contraindicaciones , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Enfermedades Renales/terapia , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Proteinuria/fisiopatología , Terapia de Reemplazo Renal , Estudios Retrospectivos
6.
Transplantation ; 77(5): 686-92, 2004 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15021830

RESUMEN

BACKGROUND: Renal warm ischemic injury and immunosuppression with cyclosporin A (CsA) may contribute to chronic allograft nephropathy after cadaveric transplantation. This study establishes whether CsA can sensitize the kidney to injury and fibrosis induced by renal warm ischemia (RWI). METHODS: The left kidney of Sprague-Dawley rats was subjected to 30 min of warm ischemia and/or intraperitoneal CsA (15 mg/kg/d) for 30 days (n=6 per group). Renal injury and fibrosis were assessed histologically together with immunohistochemistry for collagen III, transforming growth factor (TGF)-beta1, ED1 (macrophage marker), and alpha-smooth muscle actin. Renal mRNAs for collagen III, TGF-beta 1, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase-1 together with MMP enzyme activity were also determined. RESULTS: RWI or CsA alone produced only minor effects on renal injury and fibrosis. However, in CsA-treated rats, RWI produced a marked increase in tubulointerstitial fibrosis, as shown by the potentiation of collagen III and TGF-beta1 determined by immunochemistry and mRNA analysis. The up-regulation of tissue inhibitor of metalloproteinase-1 mRNA was associated with a decrease in MMP enzyme activity. In CsA-treated rats, RWI was also associated with an increase in inflammatory infiltrates, elevated immunostain for ED1 (indicating extensive macrophage influx), and elevated immunostain for alpha-smooth muscle actin (indicating myofibroblast activation). CONCLUSIONS: In the rat, CsA can sensitize the kidney to fibrosis induced by renal warm ischemia. In renal transplantation, when cadaveric donor kidneys have been subjected to a period of warm ischemia, CsA may be an inappropriate choice for immunosuppressive therapy.


Asunto(s)
Ciclosporina/farmacología , Inmunosupresores/farmacología , Isquemia/patología , Trasplante de Riñón , Riñón/efectos de los fármacos , Nefritis Intersticial/patología , Animales , Colágeno Tipo III/metabolismo , Fibrosis , Calor , Isquemia/fisiopatología , Riñón/patología , Riñón/fisiopatología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Nefritis Intersticial/fisiopatología , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1
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