Ethnic Differences in Incidence and Outcomes of Childhood Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Ethnic differences in outcomes among children with nephrotic syndrome are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a longitudinal study at a single regional pediatric center comparing ethnic differences in incidence from 2001 to 2011 census data and longitudinal outcomes, including relapse rates, time to first relapse, frequently relapsing disease, and use of cyclophosphamide. Among 711 children, 24% were European, 33% were South Asian, 10% were East/Southeast Asian, and 33% were of other origins. RESULTS: Over 10 years, the overall incidence increased from 1.99/100,000 to 4.71/100,000 among children ages 1-18 years old. In 2011, South Asians had a higher incidence rate ratio of 6.61 (95% confidence interval, 3.16 to 15.1) compared with Europeans. East/Southeast Asians had a similar incidence rate ratio (0.76; 95% confidence interval, 0.13 to 2.94) to Europeans. We determined outcomes in 455 children from the three largest ethnic groups with steroid-sensitive disease over a median of 4 years. South Asian and East/Southeast Asian children had significantly lower odds of frequently relapsing disease at 12 months (South Asian: adjusted odds ratio; 0.55; 95% confidence interval, 0.39 to 0.77; East/Southeast Asian: adjusted odds ratio; 0.42; 95% confidence interval, 0.34 to 0.51), fewer subsequent relapses (South Asian: adjusted odds ratio; 0.64; 95% confidence interval, 0.50 to 0.81; East/Southeast Asian: adjusted odds ratio; 0.47; 95% confidence interval, 0.24 to 0.91), lower risk of a first relapse (South Asian: adjusted hazard ratio, 0.74; 95% confidence interval, 0.67 to 0.83; East/Southeast Asian: adjusted hazard ratio, 0.65; 95% CI, 0.63 to 0.68), and lower use of cyclophosphamide (South Asian: adjusted hazard ratio, 0.82; 95% confidence interval, 0.53 to 1.28; East/Southeast Asian: adjusted hazard ratio, 0.54; 95% confidence interval, 0.41 to 0.71) compared with European children. CONCLUSIONS: Despite the higher incidence among South Asians, South and East/Southeast Asian children have significantly less complicated clinical outcomes compared with Europeans.

Pharmacological interventions for hypertension in children.

BACKGROUND: Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. OBJECTIVES: To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. SELECTION CRITERIA: The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. MAIN RESULTS: A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies. Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. AUTHORS' CONCLUSIONS: Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Cochrane in context: pharmacological interventions for hypertension in children.

BACKGROUND: Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end-organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is increasing, most likely owing to a concurrent rise in obesity. In children with hypertension, nonpharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end-organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. OBJECTIVES: To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared with placebo; as combination therapy compared with placebo or as a single medication; or in comparisons of various doses within the same class on systolic or diastolic blood pressure (or both) in children with hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013,Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. SELECTION CRITERIA: The selection criteria were deliberately broad as there are only few clinical trials in children. We included randomized controlled trials of at least 2 weeks duration comparing antihypertensive agents either as monotherapy or as combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95th percentile or above for age, height and gender. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarized data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. MAIN RESULTS: A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from 3 to 24 weeks. There were five randomized controlled trials comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting ..-blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomized trial was identified that evaluated the effectiveness of antihypertensive medications on target end-organ damage. The trials were of variable quality and most were funded by pharmaceutical companies. Among the angiotensin receptor blockers, candesartan (one trial, n=240), when compared with placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval .9.44 to .3.56) and diastolic blood pressure by 5.50 mmHg (95% confidence interval .9.62 to .1.38) (low-quality evidence). High dose telmisartan (one trial, n=76), when compared with placebo, reduced systolic blood pressure by .8.50 (95% confidence interval .13.79 to .3.21) but not diastolic blood pressure (.4.80, 95% . .9.50 to 0.10) (low-quality evidence). ..-Blocker (metoprolol, one trial, n=140), when compared with placebo, significantly reduced systolic blood pressure by 4.20 mmHg (95% confidence interval .8.12 to .0.28) but not diastolic blood pressure (.3.20 mmHg 95% confidence interval .7.12 to 0.72) (low-quality evidence). ..-Blocker-diuretic combination (bisoprolol/hydrochlorothiazide, one trial, n=94) when compared with placebo did not result in a significant reduction in systolic blood pressure (.4.0 mmHg, 95% confidence interval .8.99 to .0.19), but did have an effect on diastolic blood pressure (.4.50 mmHg, 95% confidence interval .8.26 to .0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine, one trial, n=133) was not effective in reducing systolic blood pressure (.0.62 mmHg, 95% confidence interval .2.97 to 1.73) or diastolic blood pressure (.1.86 mmHg, 95% confidence interval .5.23 to 1.51) when compared with placebo. Further, there was no consistent dose-response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. AUTHORS' CONCLUSIONS: Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end-organ damage. Most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose­response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Pharmacological interventions for hypertension in children.

BACKGROUND: Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. OBJECTIVES: To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. SELECTION CRITERIA: The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender.  DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. MAIN RESULTS: A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies.Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. AUTHORS' CONCLUSIONS: Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.

Twenty four-hour ambulatory blood pressure profiles 12 months post living kidney donation.

Summary Small blood pressure (BP) elevations may occur post kidney donation. This prospective study determined 24-h ambulatory BP (ABP) and other cardiovascular risk factor changes in 51 living donors over 12 months postdonation. Donors also provided 24-h urine collections for monitoring protein and creatinine clearance, 75 g oral glucose tolerance tests (OGTT), and fasting lipids. Nondipping was defined as night-day systolic (SBP) ratio >or=0.9. Baseline and 12-month pre to postdonation comparisons were made both for dippers and nondippers. Of 51 donors, 35 were dippers and 16 nondippers. In these two groups, predonation 24-h SBP were 115.2 +/- 8 and 115.6 +/- 10 mmHg; serum creatinine (SCr) 69.3 +/- 12 and 71.1 +/- 13 micromol/l; and 24-h urine protein 0.12 +/- 0.05 and 0.09 +/- 0.03 g (all P = NS) while at 12 months, 24-h SBP were 111.4 +/- 11 and 114.3 +/- 8 mmHg (P = 0.384), SCr 97.9 +/- 16 and 97.7 +/- 21 micromol/l (P = 0.810); and 24-h urine protein 0.139 +/- 0.09 and 0.111 +/- 0.07 g/d (P = 0.360) respectively. The 24-h SBP was significantly lower in the dippers at 12 months as compared with predonation (P = 0.036). OGTT and lipid profiles remained normal in both groups. Predonation nocturnal nondipping does not carry adverse postdonation consequences over 12 months.

A prospective observational study of changes in renal function and cardiovascular risk following living kidney donation.

The effect of unilateral nephrectomy on the cardiovascular risk profile of living kidney donors has not been prospectively studied. We performed an observational cohort study of 58 living donors to 6 months postdonation for changes in 24-hr ambulatory blood pressure profiles, renal function, urine protein excretion, body mass index, glucose tolerance, and fasting lipid profiles. The 24-hr systolic blood pressure average and night-day ratio were unchanged from pre- to postdonation (118.9+/-11 vs. 118.1+/-14 mm Hg, P=0.77; 0.87+/-0.07 vs. 0.87+/-0.09, P=0.68, respectively). Estimated glomerular filtration rate declined from 91.9+/-16 to 61.6+/-12 mL/min/1.73 m2 (P<0.0001). Protein excretion, body mass index, glucose, and lipids were unchanged. No significant differences were noted between dippers and nondippers either pre- or postdonation. In summary, living kidney donation in the short term is safe. We suggest further observation of individuals with lower glomerular filtration rate for possible increased cardiovascular risk factors in the future.