RESUMO
In 1992, we published the results of a prospective, controlled trial of aggressive therapy (high-dose prednisone plus oral cyclophosphamide alone or with plasmapheresis) in 86 patients with severe lupus nephritis. During this study, remission (serum creatinine < or =1.4 mg/dL [< or =123 micromol/L] and proteinuria < or =330 mg/d of protein) in renal disease occurred in 37 patients (43%). To assess the long-term effect of remission on patient and renal survival, we now report the results of our extended follow-up of these patients. After an average of 10 years of follow-up in the 86 patients, patient survival rates at both 5 and 10 years were 95% in the group that had a remission and 69% at 5 years and 60% at 10 years in the no-remission group (P < 0.001). Renal survival rates were 94% at both 5 and 10 years in the remission group compared with 46% at 5 years and 31% at 10 years in the no-remission group (P < 0. 0001). Features predictive of remission included stable renal function after 4 weeks on therapy, category IV lesion, lower chronicity index, white race, lower urine protein excretion level at baseline, and lower baseline serum creatinine level. The features predictive of end-stage renal disease were higher baseline serum creatinine level, presence of anti-Ro antibodies, and failure to attain a remission. Thus, in patients with the most severe forms of lupus nephritis, a remission of clinical renal abnormalities is associated with dramatic improvement in long-term patient and renal survival.
Assuntos
Nefrite Lúpica/terapia , Adulto , Feminino , Seguimentos , Humanos , Nefrite Lúpica/mortalidade , Masculino , Análise Multivariada , Prognóstico , Indução de Remissão , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria = 1.0 g/24 h of protein). Remission was significantly associated with captopril therapy and control of systolic blood pressure. The present study describes the status of these eight patients during a follow-up of 7.7 +/- 0.3 years. Since our previous report, one patient has been lost to follow-up and one patient progressed to end-stage renal disease (ESRD) 3.7 years after completion of the Captopril Study. The remaining six patients remain in remission of nephrotic syndrome (mean 24-hour proteinuria, 1.03 +/- 0.3 g of protein) and have stable serum creatinine levels (mean, 1.58 +/- 0.3 mg/dL) and body weights (mean, 69.8 +/- 5.3 kg). Of the six patients, one has discontinued angiotensin-converting enzyme inhibitor (ACEi) therapy because of hypotension. Excluding the patient who progressed to ESRD, the current mean systolic blood pressure is 135 +/- 6 mm Hg and mean diastolic blood pressure is 78 +/- 4 mm Hg. We conclude that long-term remission of nephrotic syndrome and preservation of renal function is achievable in some patients with type 1 diabetes. Control of blood pressure and ACEi therapy appear to be important in achieving long-term remission.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Captopril/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Síndrome Nefrótica/fisiopatologia , Estudos Prospectivos , Proteinúria , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de RemissãoRESUMO
We evaluated 100/serum creatinine, 24-hour creatinine clearance, and simultaneously measured creatinine clearance or creatinine clearance estimated by the formula devised by Cockcroft and Gault in comparison with measurements of glomerular filtration rate (GFR) using iothalamate among 136 patients with diabetic nephropathy. We also evaluated 100/serum creatinine, simultaneously measured creatinine clearance or creatinine clearance estimated by the Cockcroft and Gault formula in comparison with measurements of GFR using inulin among 88 healthy adults, 21 hypercalciuric kidney stone formers and their hypercalciuric relatives, and one man with chronic nephritis. Creatinine clearances measured simultaneously were closely correlated to GFR (r = 0.93) as were creatinine clearances, estimated by the Cockcroft and Gault formula (r = 0.84) when GFR ranged from 16 to 175 mL/min (0.27 to 2.92 mL/s). These observations confirm the clinical use of either creatinine clearances during water diuresis or estimates of creatinine clearance by the Cockcroft and Gault formula in the assessment of kidney function.
Assuntos
Creatinina/sangue , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Adulto , Biomarcadores/sangue , Nefropatias Diabéticas/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Valores de ReferênciaRESUMO
Traditionally, creatinine clearance is used as an estimation of the glomerular filtration rate (GFR) because of its relative ease and low cost. Errors in collection limit its usefulness. Estimation of GFR using 99mTc diethylene-triamine pentaacetic acid (Tc-DTPA) by direct scintigraphic determination of fractional radionuclide accumulation within each kidney does not require blood or urine sampling, takes 10 to 15 minutes to perform, and has been reported to give a GFR that correlates with 24-hour urinary creatinine clearance (CC) in hospitalized patients (r = 0.95). To assess its usefulness in the outpatient diabetic with nephropathy, 24 patients with type I diabetes underwent 56 iothalamate clearances during water diuresis and 56 simultaneous Tc-DTPA GFR estimations. GFR was also estimated from 24-hour urinary CC, 100/creatinine, and by the formula of Cockcroft and Gault. Tc-DTPA GFR estimation by direct renal scanning correlated relatively poorly with iothalamate GFR (r = 0.74) in this patient population when all levels of iothalamate GFR were compared (n = 56), but improved (r = 0.80) when iothalamate GFR values greater than or equal to 120 mL/min were excluded from analysis (n = 45). Given all levels of iothalamate GFR, the best correlation was obtained with the estimation using the equation of Cockcroft and Gault (r = 0.86).
Assuntos
Diabetes Mellitus Tipo 1/diagnóstico por imagem , Nefropatias Diabéticas/diagnóstico por imagem , Taxa de Filtração Glomerular/fisiologia , Radioisótopos do Iodo , Ácido Iotalâmico , Rim/diagnóstico por imagem , Pentetato de Tecnécio Tc 99m , Adulto , Creatinina/sangue , Creatinina/urina , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , CintilografiaRESUMO
BACKGROUND: Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy. METHODS: We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was < or = 2.5 mg per deciliter (221 mumol per liter). Blood-pressure goals were defined to achieve control during a median follow-up of three years. The primary end point was a doubling of the base-line serum creatinine concentration. RESULTS: Two hundred seven patients received captopril, and 202 placebo. Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0.007). The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 1.5 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter (88.4 mumol per liter). The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 0.03). Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 0.01). Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups. CONCLUSIONS: Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.
Assuntos
Captopril/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Adulto , Creatinina/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos ProspectivosRESUMO
Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Hipertensão Renal/tratamento farmacológico , Ramipril/administração & dosagem , Adulto , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 1/diagnóstico , Nefropatias Diabéticas/diagnóstico , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hipertensão Renal/diagnóstico , Recém-Nascido , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ramipril/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The prognosis of patients with systemic lupus erythematosus who have glomerulonephritis is poor, despite treatment with immunosuppressive therapy. Plasmapheresis therapy has been used, but there have been few controlled clinical observations of its efficacy. METHODS: We carried out a randomized, controlled trial comparing a standard-therapy regimen of prednisone and cyclophosphamide (standard therapy) with a regimen of standard therapy plus plasmapheresis in 86 patients with severe lupus nephritis in 14 medical centers. The patients underwent plasmapheresis three times weekly for four weeks. Drug therapy was standardized, with strict adherence to nine detailed medical-management protocols. RESULTS: Forty-six patients received standard therapy, and 40 patients received standard therapy plus plasmapheresis. The mean follow-up was 136 weeks. Six patients (13 percent) in the standard-therapy group and eight patients (20 percent) in the plasmapheresis group died. Renal failure developed in 8 patients (17 percent) in the standard-therapy group, as compared with 10 (25 percent) in the plasmapheresis group. Thirty patients (35 percent) reached stopping points--14 (30 percent) in the standard-therapy group and 16 (40 percent) in the plasmapheresis group. A similar number of patients in each group had a decrease in both the serum creatinine concentration and urinary protein excretion to approximately normal values. Patients treated with plasmapheresis had a significantly more rapid reduction of serum concentrations of antibodies against double-stranded DNA and cryoglobulins. CONCLUSIONS: Treatment with plasmapheresis plus a standard regimen of prednisone and cyclophosphamide therapy does not improve the clinical outcome in patients with systemic lupus erythematosus and severe nephritis, as compared with the standard regimen alone.
Assuntos
Nefrite Lúpica/terapia , Plasmaferese , Adulto , Autoanticorpos/análise , Terapia Combinada , Creatinina/sangue , Crioglobulinas/imunologia , Ciclofosfamida/administração & dosagem , DNA/imunologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Prednisona/administração & dosagemRESUMO
The purpose of this study was to determine the usefulness of a random urine specimen protein to creatinine (P/C) ratio in predicting 24-hour urine protein excretion (24 UP) in type 1 diabetic patients with overt nephropathy. Two hundred twenty-nine outpatient diabetic subjects enrolled in the Collaborative Study Group's multicenter clinical trial of "Angiotensin-Converting Enzyme Inhibition in Type 1 Diabetic Nephropathy" provided specimens for study, which encompassed a wide range of proteinuria (0.05 to 13.3 g/d). Twenty-four hour urine collections for total protein and creatinine (g/d) were obtained in the outpatient setting. This was followed shortly thereafter by an untimed single urine specimen for protein and creatinine (mg/dL). For longitudinal analysis, 33 patients provided two 24-hour urine collections with concomitant random urine specimens, separated by at least a 3-month period. Across the range of proteinuria that we studied, the log random urine P/C ratio correlated to log 24 UP (r = 0.90). The regression line was almost identical to the line of unity, which indicates that a patient's 24 U/P (in g/d) can be predicted directly from the random urine specimen P/C ratio (P/C = 24 UP in g/d). However, the standard deviations associated with these predictions were large, especially at the higher 24 UP values. Of the 33 patients who provided two time-separated specimens, the direction of change in P/C ratio was discordant with the direction of change in 24 UP in 14 of the 33 repeat specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Creatinina/urina , Diabetes Mellitus Tipo 1/urina , Nefropatias Diabéticas/urina , Proteinúria/urina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Captopril/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Adulto , Pressão Sanguínea , Creatinina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Feminino , Humanos , Falência Renal Crônica/prevenção & controle , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/sangue , Síndrome Nefrótica/complicações , Fatores de TempoRESUMO
BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world. Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the standard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria. The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined. The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial (IDNT), studying the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension. Here we report the study design and baseline patient characteristics. METHODS: To qualify, hypertensive type II patients, age 30-70 years, must have a 24 h urinary protein excretion of >900 mg and a serum creatinine 90-265 micromol/l (1.0-3. 0 mg/dl) in women and 110-265 micromol/l (1.2-3.0 mg/dl) in men. Three treatment arms include irbesartan, placebo and amlodipine, with every attempt made to achieve similar blood pressure levels in all treatment arms. A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide. The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine, end-stage renal disease or death. The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events. The average length of patient follow-up is expected to be approximately 36 months. RESULTS: The baseline characteristics of the study subjects are: age 59+/-8 years, duration of diabetes 15+/-9 years, height 168+/-11 cm (5 ft 6 in), weight 87+/-19 kg (192 lb), body mass index 31+/-7 kg/m(2), blood pressure 156+/-18 mmHg/85+/-11 mmHg, serum creatinine 150+/-53 micromol/l (1.7+/-0.6 mg/dl), creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day.