RESUMO
Many reports have shown the therapeutic efficacy of LDL apheresis (LDL-A) in drug-resistant nephrotic syndrome (NS) for improvement of heavy proteinuria and severely impaired renal function. To obtain comprehensive results in a large number of cases, a post hoc analysis of the Prospective Observational survey on the Long-Term Effects of the LDL-Apheresis on the Drug Resistant Nephrotic Syndrome (POLARIS) study was performed by stratifying enrolled cases according to the pretreatment estimated glomerular filtration rate (eGFR) levels indicating normal (N) (≥60 ml/min/1.73 m2 ), moderately impaired (M) (≥30 to <60 ml/min/1.73 m2 ), and severely impaired (S) (<30 ml/min/1.73 m2 ) renal function. Significant improvements of proteinuria and renal function were found in Group N and, most interestingly, in Group M. A tendency for improvement in proteinuria was found in Group S. Most cases in all groups had not entered end-stage renal disease at 2 years after LDL-A treatment. These results suggest that LDL-A has therapeutic efficacy even in cases in which renal function has declined to 30 ml/min/1.73 m2 .
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Remoção de Componentes Sanguíneos/métodos , Lipoproteínas LDL/sangue , Síndrome Nefrótica/complicações , Síndrome Nefrótica/terapia , Insuficiência Renal/complicações , Insuficiência Renal/terapia , Estudos de Coortes , Humanos , Síndrome Nefrótica/sangue , Estudos Prospectivos , Insuficiência Renal/sangue , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: LDL apheresis (LDL-A) is used for drug-resistant nephrotic syndrome (NS) as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was conducted to evaluate its clinical efficacy with high-level evidence. METHODS: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. RESULTS: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7%) showed remission of NS based on a urinary protein (UP) level <1.0 g/day. The UP level immediately after LDL-A and the rates of improvement of UP, serum albumin, serum creatinine, eGFR, and total and LDL cholesterol after the treatment session significantly affected the outcome. CONCLUSIONS: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.
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BACKGROUND: We conducted a randomized, open-label trial to determine which of the antihypertensive drugs was most beneficial for CKD patients with hypertension in spite of treatment with an angiotensin receptor blocker (ARB). METHODS: Patients 20-75 years of age who had CKD according to the definition in the K/DOQI Guidelines and hypertension (systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg) with the usual dose of an ARB were randomly assigned to receive losartan 50 mg plus 5 mg of the calcium channel blocker amlodipine (CCB group, n = 37), 5 mg of the angiotensin-converting enzyme inhibitor enalapril (ACEI group, n = 36), or 12.5 mg of the thiazide diuretic hydrochlorothiazide (HCTZ group, n = 36). The primary endpoints were changes in blood pressure (BP), ratio of urinary excretion of protein to creatinine (UPCR), tolerability, and eGFR during the 12-month treatment period compared with control period. RESULTS: There were no significant differences in BP and tolerability between the three groups. The percentage changes in UPCR at 12 months after start of the combination therapy were significantly different in the HCTZ group (-26.3 ± 11.1 %, mean ± SE) and CCB group (+46.7 ± 33.6 %, p < 0.05), while eGFR was significantly lower in the HCTZ group than in the ACEI group or CCB group at 4 months but not at 12 months. CONCLUSION: Addition of diuretics, CCB, or ACEI to ARB was equally effective for the control of hypertension in CKD, while, in terms of urinary excretion of protein, diuretics may be better than CCB.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Quimioterapia Combinada , Enalapril/efeitos adversos , Enalapril/uso terapêutico , Feminino , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/uso terapêutico , Hipertensão Renal/etiologia , Losartan/efeitos adversos , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
We present a case of idiopathic retroperitoneal fibrosis (IRF) complicated by severe renal failure and multiple intracranial lesions, which are probable results of cerebral vasculitis. IRF is an idiopathic hyperplasia of the retroperitoneal tissue that often entraps the ureters and causes post-renal failure. While the etiology of IRF is unclear, researchers consider IRF a systemic autoimmune disease complicated by immune-mediated vasculitides. The chief complaints of the patient were cognitive disorders, and brain MRI findings revealed multiple intracranial lesions with accompanying central degeneration. Given that vasogenic cerebral edemas derive from uremia, we speculated that the lesions in our case were related to more destructive changes such as aortic and periaortic inflammation. Details on this case manifesting rare cerebrovascular complications may help elucidate the pathogenesis of IRF.
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Córtex Cerebral/patologia , Fibrose Retroperitoneal/complicações , Vasculite do Sistema Nervoso Central/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fibrose Retroperitoneal/patologia , Vasculite do Sistema Nervoso Central/patologiaRESUMO
BACKGROUND: Hyperlipidemia is not merely a complication but a major exacerbating factor in longstanding nephrotic syndrome (NS). Low-density lipoprotein apheresis (LDL-A) has been reported to ameliorate dyslipidemia and induce rapid remission of NS. Several clinical studies have suggested the therapeutic efficacy of LDL-A, but the level of clinical evidence is insufficient. Therefore, a multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome), was initiated in Japan. METHOD: Patients with drug-resistant NS were prospectively recruited into the study and treated with LDL-A in facilities that were registered in advance. In the POLARIS study design, the clinical data are to be followed up for 2 years. In the current study, we aimed at evaluating the short-term efficacy based on the treatment outcome of LDL-A immediately after completion of treatment. RESULTS: Along with rapid improvement of hyperlipidemia, LDL-A significantly improved proteinuria and hypoproteinemia after treatment. More than half of the patients showed remission of NS based on the urinary protein level at the completion of LDL-A. The duration of NS before the start of treatment was significantly shorter in patients who responded to LDL-A. CONCLUSIONS: An analysis of patients registered in the POLARIS study indicated that LDL-A has short-term efficacy for drug-resistant NS. Rapid relief of dyslipidemia by LDL-A may provide early remission in about half of the NS patients who are resistant to conventional medication. Completion of the POLARIS study may reveal additional long-term effects of LDL-A in these patients.
Assuntos
Remoção de Componentes Sanguíneos , Hiperlipidemias/terapia , Lipoproteínas LDL , Síndrome Nefrótica/terapia , Adulto , Idoso , Resistência a Medicamentos , Feminino , Humanos , Hiperlipidemias/etiologia , Hipoproteinemia/etiologia , Hipoproteinemia/terapia , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/urina , Estudos Prospectivos , Proteinúria/etiologia , Proteinúria/terapia , Albumina Sérica/metabolismo , Fatores de TempoRESUMO
BACKGROUND: AN69 dialyzer, a plate type dialyzer with a polyacrylonitrile membrane (PAN membrane) is reported to reduce symptoms in hemodialysis (HD) patients with complications such as poor nutritional status and peripheral arterial disease (PAD). Yet very few studies have investigated the long-term use of the PAN membrane or compared the solute-removal properties of the PAN membrane with those of the Type IV polysulfone membrane (PS membrane), the dialysis membrane most widely used. In the present study we compared the contaminant-removal properties of the AN69 membrane dialyzer with those of a Type IV PS membrane dialyzer and investigated the clinical effects of the long-term use of the former for elderly hemodialysis patients with mild PAD. METHODS: Cross-over trials with 2 week intervals for solute were conducted in 6 patients to compare the performance of the membranes in removing small molecular weight substances, ß2 microglobulin (ß2MG), amino acid (AA), and serum albumin (Alb). Next, the AN69 membrane was used for dialysis over a period of 72 weeks in 8 patients. The time course changes of Alb, the geriatric nutritional risk index (GNRI), the % creatinine generation rate (%CGR), the normalized protein catabolic rate (nPCR) and the dry weight (DW) were observed to evaluate the nutritional status. The time course changes of ß2MG, C-reactive proteins (CRP), LDL cholesterol (LDL), fibrinogens (Fib), nitrogen oxide (NOx), hemoglobin (Hb), ferritins, transferrin saturation (TSAT), dose of erythropoiesis-stimulating agents (ESA), and dose of iron were observed to evaluate the therapeutic effects of long-term use. Skin perfusion pressure (SPP) was measured at two points: once at the switchover to the AN69 membrane and once 72 weeks later. RESULTS: In cross-over trials, the AN69 membrane showed basically the same dialysis efficiency as the PS membrane in removing small molecular weight substances, but it removed significantly lower amounts of ß2MG. The AN69 membrane also showed significantly lower rates of AA removal rate and Alb leakage. The nutritional status was stably maintained during long-term use after the switchover to the AN69 membrane, and no significant increase of ß2MG was observed. Fib and NOx were both reduced, the latter to a significant degree. The Hb values showed a good time course, with relatively high TSAT levels and low ferritin levels overall. SPP remained generally stable for 72 weeks. CONCLUSION: The cross-over trial show the AN69 membrane eliminates less AA and Alb compared with the PS membrane. Judging from the therapeutic effects of the long-term use of the AN69 membrane, the membrane is effective for dialysis and has good biocompatibility in the treatment of elderly HD patients with mild PAD.
Assuntos
Resinas Acrílicas/uso terapêutico , Membranas Artificiais , Doença Arterial Periférica/terapia , Diálise Renal , Idoso , LDL-Colesterol/metabolismo , Fibrinogênio/metabolismo , Humanos , Masculino , Peso Molecular , Polímeros/uso terapêutico , Albumina Sérica/metabolismo , Sulfonas/uso terapêutico , Fatores de Tempo , Transferrina/metabolismo , Resultado do Tratamento , Microglobulina beta-2/metabolismoRESUMO
BACKGROUND: The long-term prognosis of immunoglobulin A nephropathy is poor. Treatment is intended to achieve complete remission in the early stage or to preserve renal function in the advanced stages. In Japan, aggressive steroid pulse therapy following tonsillectomy (tonsillectomy-pulse therapy) has recently been used to treat early IgA nephropathy and has achieved favorable outcomes. However, steroid doses are sometimes limited because of adverse reactions s and the efficacy of tonsillectomy-steroid pulse therapy has not been established in patients with renal dysfunction. In our current treatment protocol, the total steroid dose has been significantly reduced through the use of the immunosuppressant mizoribine in combination with tonsillectomy-steroid pulse therapy for the treatment of active IgA nephropathy in patients with renal impairment. METHODS: The subjects were 18 patients with active IgA nephropathy who were younger than 70 years and had an estimated glomerular filtration rate ≥20 and <60 mL/min/1.73 m(2). After giving informed consent, the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone in combination with mizoribine (100 to 150 mg/day). A renin-angiotensin system inhibitor was used before tonsillectomy in all cases. One year after tonsillectomy, the safety of this protocol and its effects on hematuria, proteinuria, and the progression of renal dysfunction were assessed. RESULTS: The mean patient age was 48.4 years, and the mean time from disease onset to tonsillectomy was 8.4 years. After 1 year, urinary protein had decreased (1.80 ± 1.36 to 0.47 ± 0.75 g/g · Cr) in all cases but 1 and had resolved completely in 38.9% of cases. Hematuria had decreased in all cases and had resolved completely in 61.1% of cases. The estimated glomerular filtration rate also improved in all cases and the mean increased significantly from 42.4 ± 11.9 to 50.1 ± 15.9 mL/min/1.73 m(2). No serious complications were found during follow-up. Steroid acne that required treatment occurred in 2 cases (11.1%) but was transient and mild. CONCLUSION: Steroid pulse therapy in combination with mizoribine following tonsillectomy is effective in improving urinary findings and preserving renal function in the treatment of IgA nephropathy, which remained active in patients with renal impairment (estimated glomerular filtration rate ≥20 and <60 mL/min/1.73 m(2)).
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Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/cirurgia , Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Metilprednisolona/administração & dosagem , Ribonucleosídeos/administração & dosagem , Tonsilectomia , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Terapia Combinada , Quimioterapia Combinada , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/fisiopatologia , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Pulsoterapia , Estudos Retrospectivos , Ribonucleosídeos/efeitos adversos , Fatores de Tempo , Tonsilectomia/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Hemodialysis is a treatment in which uremic toxins and excess water content are removed from the blood with a dialyzer and dialysis fluid. The efficiency of hemodialysis is strongly influenced by the following 3 parameters: the blood flow rate (QB), the dialysis fluid flow rate (QD), and the overall mass transfer area coefficient (K0A), an index of a dialyzer's performance. The flow ratio (QB : QD) to obtain a well-balanced dialysis efficiency is generally said to be 1 : 2. In Japan, the QB is controlled independently (from 200 to 250 mL/min) depending on individual conditions. However, the QD is usually set at around 500 mL/min regardless of the QB. MATERIALS AND METHODS: To investigate the effect on dialysis efficiency of decreasing the QD from 500 to 400 mL/min, 12 patients were divided into two groups: one in which the QB was 150 mL/min, with 1.3-m(2) membranes; and another in which the QB was 200 mL/min, with 1.6-m(2) membranes. We defined the conditions with the QD of 500 mL/min as condition A, and that with the QD of 400 mL/min as condition B. Each operating condition was assigned for 2 weeks as crossover trials. To evaluate solute removal, we calculated clearance, reduction rate, removal amount, clear space, the clear space rate, and albumin leakage. Furthermore, when dialysis efficiency decreased in condition B, we performed a supplementary test: we calculated the QB with the K0A equation to achieve a dialysis efficiency equivalent to that in condition A, defined as condition B', as the operating condition with the calculated QB and a QD of 400 mL/min, and re-evaluated. RESULTS: In condition B, a QB of 150 mL/min had no effect on the dialysis efficiency;whereas with a QB of 200 mL/min, slight yet significant differences were observed in the clearance of small molecular weight solutes. Condition B' (QB=210 mL/min) showed an equivalent or greater dialysis efficiency and demonstrated an association with theoretical values. CONCLUSIONS: In hemodialysis, the flow ratio (QB : QD) should be maintained at 1 : 2 to obtain a well-balanced dialysis efficiency. The present study has shown that the QD can be decreased while maintaining this flow ratio. A well-balanced QD setting can be financially and environmentally conscious. In addition, use of the K0A equation is a highly effective method to calculate a QB that allows an expected dialysis efficiency to be achieved in case the QD needs to be decreased uniformly, as when dialysis fluid is in short supply during times of disaster.
Assuntos
Soluções para Diálise/farmacologia , Diálise Renal , Reologia , Idoso , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Sístole/efeitos dos fármacosRESUMO
Focal segmental glomerulosclerosis (FSGS) is associated with various clinicopathological conditions, including hypertension. We report here a case of secondary FSGS associated with malignant hypertension. A 33-year-old man with a 1-month history of visual impairment and headache visited the Department of Ophthalmology at our hospital and was found to have hypertensive retinopathy and severe hypertension (230/160 mmHg). He was referred to our department based on suspected renal dysfunction. His blood pressure on admission was 250/130 mmHg. Physical examination and laboratory tests revealed hypertensive cardiac dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07 mg/dl, blood urea nitrogen, BUN 49.9 mg/dl), massive proteinuria (10.7 g/day), and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and papilledema. The cause of secondary hypertension could not be identified. He was treated for primary malignant hypertension, but required hemodialysis 3 days after admission due to anuria. Treatment with antihypertensive agents resulted in the gradual recovery of renal function, although heavy proteinuria continued with nephrotic syndrome. Renal biopsy performed 1 month after admission showed features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was discontinued following further improvement in renal function and the most recent laboratory tests showed proteinuria 1.8 g/day and persistent renal dysfunction (BUN 36.5 mg/dl, Cr 3.14 mg/dl). Malignant hypertension may cause various injuries, including glomerular endothelial and epithelial cell injuries in glomerular hypertension and hyperfiltration, increase of the renin-angiotensin-aldosterone system, and endothelial-epithelial interaction, resulting in the development of secondary FSGS and heavy proteinuria.
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We investigated the long-term effects of maintaining high hemoglobin (Hb) on renal function in patients with chronic kidney disease not on dialysis. Subjects (Hb < 10 g/dL and serum creatinine (Cr) 2-6 mg/dL) were randomized to either a high Hb group (N = 161, 11.0 ≤ Hb < 13.0 g/dL) receiving darbepoetin alfa or to a low Hb group (N = 160, 9.0 ≤ Hb < 11.0 g/dL) with epoetin alfa, stratified according to baseline Hb and serum Cr levels, comorbidity of diabetes, and study centers. Primary endpoints were composites of the following events: doubling of serum Cr, initiation of dialysis, renal transplantation, or death. Three-year cumulative renal survival rates (95% CI) were 39.9% (30.7-49.1%) and 32.4% (24.0-40.8%) in the high and low Hb groups, respectively (log-rank test; P = 0.111). A Cox proportional-hazards model adjusted by age, sex and the randomization factors showed a significantly lower event rate in the high Hb group (P = 0.035). The estimated hazard ratio (95% CI) for the high versus the low Hb group was 0.71 (0.52-0.98), the risk reduction was 29% in the high Hb group. Incidences of serious adverse cardiovascular events did not differ significantly between the high and low Hb groups (3.1% and 4.4%, respectively). No safety issues were noted in either group. Maintaining higher Hb levels with darbepoetin alfa better preserved renal function in patients with chronic kidney disease not on dialysis.
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Eritropoetina/análogos & derivados , Hematínicos/uso terapêutico , Hemoglobinas/metabolismo , Falência Renal Crônica/tratamento farmacológico , Idoso , Creatinina/sangue , Darbepoetina alfa , Epoetina alfa , Eritropoetina/efeitos adversos , Eritropoetina/uso terapêutico , Feminino , Humanos , Incidência , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is a recently described disease entity, characterized by nonorganized electron-dense deposits in glomeruli and immunofluorescence findings indicating monoclonal immunoglobulin G deposits. The pathogenesis of many cases of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits remains unknown. We herein report 2 patients with parvovirus B19 infection who developed acute nephritic syndrome with hypocomplementemia (patient 1) or persistent proteinuria and congestive heart failure (patient 2); however, neither patient had detectable levels of serum monoclonal immunoglobulin G. Renal biopsy in both patients showed diffuse endocapillary proliferative glomerulonephritis with monoclonal immunoglobulin G3κ deposits, and electron microscopy showed nonorganized electron-dense deposits mainly in the subendothelial and mesangial areas. Clinical symptoms, abnormal laboratory findings, and urinary abnormalities recovered spontaneously in both cases within 4 weeks. Our 2 cases may be the first reported patients with proliferative glomerulonephritis with monoclonal immunoglobulin G deposits possibly associated with parvovirus B19 infection. Virus infection-associated immune disorders could be implicated in the pathogenesis of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits.
Assuntos
Glomerulonefrite/imunologia , Imunoglobulina G , Glomérulos Renais/imunologia , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/imunologia , Adulto , Feminino , Glomerulonefrite/patologia , Glomerulonefrite/virologia , Humanos , Glomérulos Renais/patologia , Glomérulos Renais/virologia , Masculino , Pessoa de Meia-Idade , Paraproteinemias/imunologia , Infecções por Parvoviridae/patologia , Infecções por Parvoviridae/virologiaRESUMO
Chronic kidney disease (CKD) is defined as either kidney damage or an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 for more than 3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine tests or imaging studies. CKD is classified as stage 1 to 5 on the basis of eGFR. Cardiovascular disease (CVD) carries a reciprocal risk of loss of kidney function in patients with chronic kidney disease (CKD) and with the development of kidney disease. CVD is a major cause of morbidity and mortality in patients with CKD. Blood pressure control in patients with CKD aims to prevent CVD and provide renoprotection. The renin-angiotensin system (RAS) is involved in every stage of the progression of CKD and is, therefore, a critical link in the pathologic relationship between hypertension and renal disease. The first-line agents for controlling blood pressure are inhibitors of the RAS: angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. These agents have been shown to have renoprotective effects in addition to their ability to control blood pressure. In CKD, the target blood pressure is less than 130/80 mm Hg, or 125/75 mm Hg, if amount of urinary protein is more than 1 g/day. To achieve the target blood pressure, other classes of antihypertensive agents, such as diuretics and calcium channel blockers, should be administered in addition to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.
Assuntos
Pressão Sanguínea/fisiologia , Falência Renal Crônica/fisiopatologia , Progressão da Doença , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Falência Renal Crônica/complicações , Testes de Função Renal , Sistema Renina-AngiotensinaRESUMO
Renal fibrosis is a common finding in progressive renal diseases. Matrix metalloproteinases (MMPs) are involved in epithelial-to-mesenchymal transition (EMT). We investigated the role of MMP-2 and the effect of inhibition of MMPs on the development of renal fibrosis. Renal fibrosis was induced in MMP-2 wild-type (MMP-2âº/âº) mice by unilateral ureteral obstruction (UUO). Renal histopathology, EMT-associated molecules, and activity of MMP-2 and MMP-9 were examined during the development of interstitial fibrosis. UUO-renal fibrosis was also induced in MMP-2 deficient (MMP-2â»/â») and MMP-2âº/⺠mice treated with minocycline (inhibitor of MMPs). In MMP-2âº/⺠mice, MMP-2 and MMP-9 were expressed in damaged tubules, and their activities increased in a time-dependent manner after UUO. Interstitial fibrosis was noted at day 14, with deposition of types III and I collagens and expression of markers of mesenchymal cells (S100A4, vimentin, α-smooth muscle actin, and heat shock protein-47) in damaged tubular epithelial cells, together with F4/80+ macrophage infiltration. Fibrotic kidneys expressed EMT-associated molecules (ILK, TGF-ß1, Smad, Wnt, ß-catenin, and Snail). In contrast, the kidneys of MMP-2â»/â» mice and minocycline-treated MMP-2âº/⺠mice showed amelioration of renal fibrosis with reduced expression of markers of mesenchymal cells in tubular epithelial cells, inhibition of upregulated EMT-associated molecules, and suppression of macrophage infiltration. The results suggested that MMP-2 have a pathogenic role in renal interstitial fibrosis, possibly through the induction of EMT and macrophage infiltration. Inhibition of MMPs may be beneficial therapeutically in renal fibrosis.
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Transição Epitelial-Mesenquimal , Nefropatias/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Obstrução Ureteral/metabolismo , Animais , Colágeno/metabolismo , Células Epiteliais , Fibrose/enzimologia , Fibrose/genética , Fibrose/metabolismo , Fibrose/patologia , Regulação da Expressão Gênica , Histocitoquímica , Nefropatias/genética , Nefropatias/patologia , Túbulos Renais/química , Túbulos Renais/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Transgênicos , Minociclina , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100 , Obstrução Ureteral/genética , Obstrução Ureteral/patologiaRESUMO
A 63-year-old man with hepatitis C virus infection was admitted to our hospital for nephrotic syndrome. Light microscopic analysis of a percutaneous renal biopsy showed thickening of the glomerular capillary walls and spike formation. Immunofluorescence revealed granular deposition of monoclonal immunoglobulin G1-lambda and C3 complement along the glomerular basement membrane. Urinary protein excretion decreased slightly after combined treatment with steroid and an immunosuppressive agent. Monoclonal immunoglobulin deposition disease with membranous feature is rare. Additional reports of such cases are needed to elucidate the mechanisms and optimal therapy for this rare entity.
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Glomerulonefrite Membranosa/complicações , Hepatite C/complicações , Imunoglobulina G/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Síndrome Nefrótica/complicações , Membrana Basal Glomerular/patologia , Humanos , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteinúria/complicaçõesRESUMO
BACKGROUND/AIMS: Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI. METHODS: AKI was induced in MMP-2 wild-type (MMP-2(+/+)) and MMP-2-deficient (MMP-2(-/-)) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2(+/+) mice were also treated with MMP-2/MMP-9 inhibitor. RESULTS: In both MMP-2(+/+) and MMP-2(-/-) mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2(+/+) mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2(-/-) mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2(+/+) mice. CONCLUSION: MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI.
Assuntos
Injúria Renal Aguda/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Injúria Renal Aguda/patologia , Animais , Células Epiteliais/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/enzimologia , Túbulos Renais/patologia , Masculino , Metaloproteinase 2 da Matriz/deficiência , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologiaRESUMO
A 60-year-old man had experienced cough, bloody sputum, and a 38 °C fever for 1.5 months. He visited an outpatient clinic and received antibiotics and nonsteroidal anti-inflammatory drugs. However, because the symptoms continued, he visited our hospital. The past medical history included chronic sinusitis, hypertension, and diabetes mellitus. A chest x-ray film and computed tomography showed multiple pulmonary nodules with cavities. Macrohematuria had developed 3 days before admission, and renal function had deteriorated (creatinine, 2.45 mg/dL) in 2 weeks. He was admitted to our hospital because of rapidly progressive glomerulonephritis (RPGN) and multiple pulmonary nodules. On admission, the clinical diagnosis was suspected to be granulomatosis with polyangiitis (Wegener's) (GPA), although tests for proteinase-3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) were negative. Antibiotics were administered for 5 days. After renal biopsy, methylprednisolone pulse therapy and cyclophosphamide pulse therapy were performed. The pathological diagnosis on the basis of the renal biopsy was glomerular and interstitial hemorrhage, possibly associated with vasculitis. After the treatment, the pulmonary symptoms, multiple pulmonary nodules, and severe inflammatory reactions in the peripheral blood were resolved. However, renal dysfunction progressed to end-stage renal disease 1 month after renal biopsy. Hemodialysis was started, and the steroid therapy was continued. During hemodialysis, a second renal biopsy was performed and led to a diagnosis of pauci-immune focal segmental crescentic glomerulonephritis. Renal function gradually recovered, and hemodialysis was discontinued. This case was (double) ANCA-negative GPA which presented prominent glomerular and interstitial hemorrhage, may be associated with small vessel vasculitis, but without active necrotizing and crescentic glomerular lesions, in the rapidly progressive glomerulonephritis.
Assuntos
Adiponectina/sangue , Nefropatias Diabéticas/tratamento farmacológico , Imidazóis/uso terapêutico , Imidazolidinas/uso terapêutico , Lipoproteínas LDL/sangue , Malondialdeído/metabolismo , Selectina-P/sangue , Tetrazóis/uso terapêutico , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Nefropatias Diabéticas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: The diagnostic value of N-terminal pro-brain natriuretic peptide (NT-pro BNP) for heart failure with preserved ejection fraction (EF; HF-PEF) was evaluated in hemodialysis (HD) patients. METHOD: In total, 83 patients were analyzed. Left-ventricular (LV) function was assessed using trans-thoracic Doppler echocardiography, and indices of hydration status were assessed using bioelectrical impedance analysis. Plasma NT-pro BNP levels were measured simultaneously. RESULTS: A moderate negative correlation was found between NT-pro BNP and LVEF. Subsequently, 77 HD patients who maintained their LVEF (LVEF >50%) were analyzed. Patients with a clinical suspicion of LV diastolic dysfunction (LVDD; E/A ≤0.75) showed higher NT-pro BNP levels (p = 0.021), but no significant differences in hydration status were observed between the two groups. CONCLUSIONS: The NT-pro BNP level may be a very helpful biomarker in screening for LVDD and HF-PEF and determining the need for echocardiography or a sophisticated cardiac study, even in HD patients.