Enfermedad renal cronica

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• #9: Figure 2. Incidence of Progression to Diabetic Nephropathy during Treatment with 150 mg of Irbesartan Daily, 300 mg of Irbesartan Daily, or Placebo in Hypertensive Patients with Type 2 Diabetes and Persistent Microalbuminuria. The difference between the placebo group and the 150-mg group was not significant (P=0.08 by the log-rank test), but the difference between the placebo group and the 300-mg group was significant (P<0.001 by the log-rank test). The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.08] for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/ 83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02). Conclusions Irbesartan is renoprotective independently of its blood-pressure–lowering effect in patients with type 2 diabetes and microalbuminuria. (N Engl J Med 2001;345:870-8.)
• #10: Figure 3. Geometric Mean Rate of Urinary Albumin Excretion (Panel A), Estimated Mean Creatinine Clearance (Panel B), and Trough Mean Arterial Blood Pressure (Panel C) in Hypertensive Patients with Type 2 Diabetes and Persistent Microalbuminuria, According to Treatment Group. The average urinary albumin excretion rate (geometric mean) was significantly reduced in both irbesartan groups (P<0.001). There were no significant differences among the three groups in the initial or the sustained (3-to-24-month) rate of decline in creatinine clearance. The average trough mean arterial blood pressure during the study was 103 mm Hg in the placebo group, 103 mm Hg in the 150-mg group, and 102 mm Hg in the 300-mg group (P=0.005 for the comparison between the 300-mg group and the placebo group).
• #12: A pesar de los efectos beneficiosos del bloqueo del sistema renina-angiotensina en la nefropatía diabética (ND), albuminuria y la progresión de la enfermedad renal no está completamente detenido por estos agentes. Por lo tanto, es necesario explorar el potencial efectos antiproteinúrico y renoprotector de innovadores enfoques terapéuticos. El estudio probó la hipótesis de que la combinación de pentoxifilina (PTF) con los bloqueadores del receptor de angiotensina II en pacientes normotensos con diabetes tipo 2 produce un efecto aditivo antiproteinúrico. Sesenta y un pacientes con DN y albuminuria residual, a pesar del tratamiento con el las dosis recomendadas de ARB por más de 1 año fueron asignados aleatoriamente para recibir la adición de 1200 mg de PTF al día (n? 30) o un grupo control (n? 31). Las características basales fueron similares entre los grupos, y mostró un análisis de correlación significativa asociación entre la excreción urinaria de albúmina (EUA) y urinarios de TNF-? (R? 0,53, P <0,001). Después de 4 meses, albuminuria mostró una disminución significativa en los pacientes que recibieron PTF, de 900 mg/24 h (466 a 1542 mg / d) a 791 mg/24 h (309 a 1400 mg / d, p <0,001), mientras que no se observaron cambios significativos en el grupo control: 920 mg/24 h (450 a 1489 mg / d) en línea de base, y 900 mg/24 h (428 a 1800 mg / d) al final del estudio. La variación porcentual media de los Emiratos Árabes Unidos en el tratamiento y el grupo control fue? 16,7 y 5,5%, respectivamente (entre los grupos de comparación, P <0,001). Este aditivo antiproteinúrico efecto no fue dependiente de los cambios de la presión arterial o el control metabólico. No obstante, ambos niveles séricos y urinarios de TNF-? también disminuida en los pacientes que recibieron PTF, de 6,4 pg / ml (2,1 a 9,7) y 16 pg / mg (8 a 29) al inicio del estudio a 4,6 pg / ml (0,4 a 9) y 14,2 pg / mg (3 a 26) al final del estudio, respectivamente (P <0,01), sin variaciones significativas en el grupo control. Por otra parte, análisis de regresión al final del estudio mostraron una correlación entre el cambio en los Emiratos Árabes Unidos y el cambio en urinaria TNF-? en pacientes que fueron tratados con PTF (R? 0,49, P <0,001). En conclusión, la administración de PTF a los pacientes que tienen el tipo 2 diabetes y está bajo tratamiento a largo plazo con un ARA produce un significativo efecto aditivo antiproteinúrico asociados  Patients A previous sample size calculation to detect a 25% relative difference in the change in UAE rate with an value of 0.05 and a value of 0.80 showed a need for a minimum of 26 patients. The criteria for the selection of patients were diabetic nephropathy, defined by persistent albuminuria 300 mg/24 h in two consecutive determinations, no other kidney or renal tract disease, and presence of diabetic retinopathy (20,21) and normal BP (140/90 mmHg); treatment with the recommended doses of ARB for 1 yr; normal renal function, defined as a GFR 90 ml/min (calculated using the Modification of Diet in Renal Disease study equation) (22); and insufficient response to conventional therapy, defined as albuminuria 400 mg/24 h in three consecutive measurements in the 3 mo before inclusion in the study. All of the patients received treatment with ARB at the recommended dosage (irbesartan 300 mg, 31 patients; losartan 100 mg, 26 patients; and candesartan 16 mg, 18 patients). The baseline demographic, clinical, and laboratory characteristics of the two groups were similar (Table 1). There were no significant differences in BP, renal function, or metabolic control. All patients showed residual albuminuria despite treatment with ARB at the maximal dosage for 1 yr. UAE was similar in both groups: 900 mg/d (range 466 to 1542 mg/d) in the treatment group and 910 mg/d (range 450 to 1489 mg/d) in the control group. Likewise, the serum and urinary levels of TNF- were similar between groups.
• #13: Despite the first-line use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), there is still a large need to improve the prevention and progression of diabetic nephropathy and its associated cardiovascular events. Endothelin antagonists have shown anti-inflammatory, antifibrotic, and antiproteinuric effects in experimental studies. This study was a randomized, placebo-controlled, double-blind, parallel-design, dosage-range study of the effect of the endothelin-A antagonist avosentan (SPP301) on urinary albumin excretion rate (UAER) in patients with diabetic nephropathy. We randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria (UAER 0.2 to 5.6 mg/min), and BP 180/110 mmHg to 12 wk of avosentan (5, 10, 25, and 50 mg) or placebo, in addition to standard ACEI/ARB therapy. Relative to baseline, all avosentan dosages decreased mean relative UAER (16.3 to 29.9%) compared with placebo (35.5%). Median relative UAER decreased with all avosentan dosages (28.7 to 44.8%) compared with placebo (12.1%). Creatinine clearance and BP were unchanged at 12 wk. The main adverse events were peripheral edema (12%), mainly with high (25 mg) dosages of avosentan; significant increases in liver enzymes did not occur. Twenty-one (7.3%) patients experienced adverse events that led to withdrawal from study medication. In summary, the endothelin-A antagonist avosentan given in addition to standard ACEI/ARB treatment decreases UAER in patients with diabetic nephropathy and macroalbuminuria. Despite the first-line use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), there is still a large need to improve the prevention and progression of diabetic nephropathy and its associated cardiovascular events. Endothelin antagonists have shown anti-inflammatory, antifibrotic, and antiproteinuric effects in experimental studies. This study was a randomized, placebo-controlled, double-blind, parallel-design, dosage-range study of the effect of the endothelin-A antagonist avosentan (SPP301) on urinary albumin excretion rate (UAER) in patients with diabetic nephropathy. We randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria (UAER 0.2 to 5.6 mg/min), and BP 180/110 mmHg to 12 wk of avosentan (5, 10, 25, and 50 mg) or placebo, in addition to standard ACEI/ARB therapy. Relative to baseline, all avosentan dosages decreased mean relative UAER (16.3 to 29.9%) compared with placebo (35.5%). Median relative UAER decreased with all avosentan dosages (28.7 to 44.8%) compared with placebo (12.1%). Creatinine clearance and BP were unchanged at 12 wk. The main adverse events were peripheral edema (12%), mainly with high (25 mg) dosages of avosentan; significant increases in liver enzymes did not occur. Twenty-one (7.3%) patients experienced adverse events that led to withdrawal from study medication. In summary, the endothelin-A antagonist avosentan given in addition to standard ACEI/ARB treatment decreases UAER in patients with diabetic nephropathy and macroalbuminuria.
• #14: Background Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. We evaluated the renoprotective effects of dual blockade of the renin−angiotensin− aldosterone system by adding treatment with aliskiren, an oral direct renin inhibitor, to treatment with the maximal recommended dose of losartan (100 mg daily) and optimal antihypertensive therapy in patients who had hypertension and type 2 diabetes with nephropathy. Methods We enrolled 599 patients in this multinational, randomized, double-blind study. After a 3-month, open-label, run-in period during which patients received 100 mg of losartan daily, patients were randomly assigned to receive 6 months of treatment with aliskiren (150 mg daily for 3 months, followed by an increase in dosage to 300 mg daily for another 3 months) or placebo, in addition to losartan. The primary outcome was a reduction in the ratio of albumin to creatinine, as measured in an earlymorning urine sample, at 6 months. Results The baseline characteristics of the two groups were similar. Treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-tocreatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). A small difference in blood pressure was seen between the treatment groups by the end of the study period (systolic, 2 mm Hg lower [P = 0.07] and diastolic, 1 mm Hg lower [P = 0.08] in the aliskiren group). The total numbers of adverse and serious adverse events were similar in the groups. Conclusions Aliskiren may have renoprotective effects that are independent of its bloodpressure− lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. (ClinicalTrials.gov number, NCT00097955.)
• #16: Few studies have directly compared the renoprotective effects of angiotensin II–receptor blockers and angiotensin-converting–enzyme (ACE) inhibitors in persons with type 2 diabetes. methods In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II–receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes. results After five years, the change in the glomerular filtration rate was ¡17.9 ml per minute per 1.73 m 2 of body-surface area, where the minus sign denotes a decrement, with telmisartan (in 103 subjects), as compared with ¡14.9 ml per minute per 1.73 m 2 with enalapril (in 113 subjects), for a treatment difference of ¡3.0 ml per minute per 1.73 m 2 (95 percent confidence interval, ¡7.6 to 1.6 ml per minute per 1.73 m 2 ). The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of ¡10.0 ml per minute per 1.73 m 2 , indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. conclusions Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II–receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events.
• #18: Background: The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled. Study Design: We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists. Setting & Population: Adult patients with chronic kidney disease and proteinuria. Selection Criteria for Studies: English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease. Intervention: MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. Outcomes: Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes. Results: 15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively. Limitations: Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias. Conclusions: Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function, routine use of MRBs as additive therapy in patients with chronic kidney disease cannot be recommended yet. However, the findings of this review promote interesting hypotheses for future study. Am J Kidney Dis 51:199-211. © 2008 by the National Kidney Foundation, Inc. INDEX WORDS: Aldosterone antagonists; renal insufficiency; chronic; renin-angiotensin-aldosterone system; angiotensin-converting enzyme inhibitors; angiotensin II type 1 receptor blockers.