Most cited article - PubMed ID 17631016
Improved control of hypertension in children after renal transplantation: results of a two-yr interventional trial
BACKGROUND: Isolated nocturnal hypertension (INH) is associated with increased prevalence of left ventricular hypertrophy (LVH) and cardiovascular morbidity and mortality in adult patients. Unlike in adults, data illustrating the possible association between INH and cardiac target organ damage is lacking in children. This study aimed to investigate whether INH is associated with increased left ventricular mass index (LVMI) and LVH in children. METHODS: Retrospective data from all untreated children with confirmed ambulatory hypertension (HT) in our center was reviewed. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed concurrently. Ambulatory normotensive children served as controls. LVH was defined as LVMI ≥ 95th percentile. RESULTS: There were 102 ABPM studies; of these, 79 children had renal HT, and 23 had primary HT. Median age of children was 13.2 years (3.8-18.9). Nineteen children had INH, 9 children had isolated daytime HT, 54 had daytime and nighttime HT, and 20 were normotensive. The LVMI adjusted for age (patient's LVMI/95th percentile of the LVMI) was significantly higher in children with INH than in normotensive children (0.83 ± 0.03 vs. 0.74 ± 0.03, p = 0.03). Left ventricular hypertrophy was present in 11% of children with INH; this was not significantly higher than in normotensive children (0%, p = 0.23). CONCLUSIONS: This study investigated the association between INH and cardiac structure in children with primary and renal HT and showed children with INH had higher LVMI adjusted for age than normotensive children and children with INH had similar LVMI adjusted for age to children with isolated daytime HT.
- Keywords
- Ambulatory blood pressure monitoring, Children, Echocardiography, Isolated nocturnal hypertension, LVMI, Left ventricular hypertrophy,
- MeSH
- Blood Pressure Monitoring, Ambulatory * MeSH
- Child MeSH
- Hypertension * complications epidemiology MeSH
- Hypertrophy, Left Ventricular diagnostic imaging epidemiology MeSH
- Blood Pressure MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Retrospective Studies MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.
- Keywords
- Angiotensin-converting enzyme inhibitors, Calcium channel blockers, Children, Graft function, Hypertension, Proteinuria, Renal transplantation,
- MeSH
- Antihypertensive Agents pharmacology therapeutic use MeSH
- Calcium Channel Blockers pharmacology therapeutic use MeSH
- Child MeSH
- Adult MeSH
- Hypertension * drug therapy etiology MeSH
- Angiotensin-Converting Enzyme Inhibitors pharmacology therapeutic use MeSH
- Blood Pressure drug effects MeSH
- Humans MeSH
- Proteinuria drug therapy etiology MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antihypertensive Agents MeSH
- Calcium Channel Blockers MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
BACKGROUND: Variable effects of steroid minimization strategies on blood pressure in pediatric renal transplant recipients have been reported, but data on the effect of steroid withdrawal on ambulatory blood pressure and circadian blood pressure rhythm have not been published so far. METHODS: In a prospective, randomized, multicenter study on steroid withdrawal in pediatric renal transplant recipients (n = 42) on cyclosporine, mycophenolate mofetil, and methylprednisolone, we performed a substudy in 28 patients, aged 11.2 ± 3.8 years, for whom ambulatory blood pressure monitoring (ABPM) data were available. RESULTS: In the steroid-withdrawal group, the percentage of patients with arterial hypertension, defined as systolic and/or diastolic blood pressure values recorded by ABPM > 1.64 SDS and/or antihypertensive medication, at month 15 was significantly lower (35.7%, p = 0.002) than in controls (92.9%). The need of antihypertensive medication dropped significantly by 61.2% (p < 0.000 vs. control), while in controls, it even rose by 69.3%. One year after steroid withdrawal, no patient exhibited hypertensive blood pressure values above the 95th percentile, compared to 35.7% at baseline (p = 0.014) and to 14.3% of control (p = 0.142). The beneficial impact of steroid withdrawal was especially pronounced for nocturnal blood pressure, leading to a recovered circadian rhythm in 71.4% of patients vs. 14.3% at baseline (p = 0.002), while the percentage of controls with an abnormal circadian rhythm (35.7%) did not change. CONCLUSIONS: Steroid withdrawal in pediatric renal transplant recipients with well-preserved allograft function is associated with less arterial hypertension recorded by ABPM and recovery of circadian blood pressure rhythm by restoration of nocturnal blood pressure dipping.
- Keywords
- Ambulatory blood pressure, Nocturnal blood pressure dipping, Pediatric renal transplantation, Randomized controlled trial, Steroid withdrawal,
- MeSH
- Allografts immunology physiopathology MeSH
- Blood Pressure Monitoring, Ambulatory MeSH
- Circadian Rhythm physiology MeSH
- Cyclosporine administration & dosage adverse effects MeSH
- Child MeSH
- Glucocorticoids administration & dosage adverse effects MeSH
- Glomerular Filtration Rate physiology MeSH
- Transplantation, Homologous adverse effects MeSH
- Hypertension chemically induced diagnosis prevention & control MeSH
- Immunosuppressive Agents administration & dosage adverse effects MeSH
- Blood Pressure drug effects MeSH
- Mycophenolic Acid administration & dosage adverse effects MeSH
- Kidney immunology physiopathology MeSH
- Humans MeSH
- Methylprednisolone MeSH
- Adolescent MeSH
- Withholding Treatment * MeSH
- Prospective Studies MeSH
- Graft Rejection immunology physiopathology prevention & control MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Cyclosporine MeSH
- Glucocorticoids MeSH
- Immunosuppressive Agents MeSH
- Mycophenolic Acid MeSH
- Methylprednisolone MeSH
Proteinuria is a relatively frequent complication in children after renal transplantation (40-80 %). It is usually mild and non-nephrotic in nature and predominantly tubular in origin. The major causes of post-transplant proteinuria are recurrence of primary glomerulonephritis [mostly focal segmental glomerulosclerosis (FSGS)], rejection (acute and chronic), mTOR inhibitors or hypertension. Proteinuria is a risk factor for graft loss and patient death in adults, and even a mild proteinuria (0.1-0.2 g/day) is associated with impaired graft and patient survival. In children, proteinuria seems to be associated with graft but not patient survival. Proteinuria (protein/creatinine ratio) should be assessed regularly in all children. In children with prior chronic kidney disease due to idiopathic FSGS, proteinuria should be assessed daily during the first month after transplantation to enable early diagnosis of recurrence. The cause of proteinuria should be identified, and graft biopsy should be considered in children with unexplained proteinuria, especially with new onset proteinuria or deterioration of previously mild proteinuria. Treatment must be primarily targeted at the cause of proteinuria, and in normotensive children symptomatic antiproteinuric therapy with angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists should also be initiated. Other antihypertensive drugs should be used to achieve target blood pressure of <75th percentile. Target proteinuria should be <20 mg/mmol creatinine.
- MeSH
- Angiotensin Receptor Antagonists therapeutic use MeSH
- Antihypertensive Agents therapeutic use MeSH
- Time Factors MeSH
- Kidney Failure, Chronic diagnosis etiology surgery MeSH
- Glomerulosclerosis, Focal Segmental complications diagnosis MeSH
- Hypertension complications diagnosis drug therapy MeSH
- Immunosuppressive Agents adverse effects MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use MeSH
- Humans MeSH
- Graft Survival MeSH
- Proteinuria diagnosis etiology physiopathology therapy MeSH
- Recurrence MeSH
- Graft Rejection diagnosis etiology therapy MeSH
- Renin-Angiotensin System drug effects MeSH
- Risk Factors MeSH
- TOR Serine-Threonine Kinases antagonists & inhibitors MeSH
- Kidney Transplantation adverse effects MeSH
- Age Factors MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Angiotensin Receptor Antagonists MeSH
- Antihypertensive Agents MeSH
- Immunosuppressive Agents MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- MTOR protein, human MeSH Browser
- TOR Serine-Threonine Kinases MeSH
Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and adverse cardiovascular outcomes. Blood pressure (BP) in transplanted children should be measured not only by clinic BP (cBP) measurement, but also by ambulatory blood pressure monitoring (ABPM), because ABPM has distinct advantages over cBP, specifically the ability to reveal nocturnal, masked or white-coat hypertension. These types of hypertension are common in transplanted children (nocturnal hypertension 36-71 %, masked hypertension 24-45 %). It may also reveal uncontrolled hypertension in treated children, thereby improving control of hypertension. Regular use of ABPM and ABPM-guided therapy of hypertension may help to decrease cardiovascular and renal target organ damage in transplanted children. Therefore, ABPM should be routinely performed in all transplanted children at least once a year, regardless of the values of cBP.
- MeSH
- Blood Pressure Monitoring, Ambulatory methods MeSH
- Time Factors MeSH
- Child MeSH
- Hypertension diagnosis MeSH
- Humans MeSH
- Masked Hypertension diagnosis MeSH
- Postoperative Complications diagnosis MeSH
- Graft Survival MeSH
- White Coat Hypertension diagnosis MeSH
- Kidney Transplantation * MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Proteinuria is a common complication after renal transplantation (RTx). In adults, tubular proteinuria prevails and is associated with impaired graft survival. In the absence of studies on proteinuria profiling in transplanted children, we aimed at analyzing the types of proteinuria in transplanted children. Fifty-three children (11.8 years) were analyzed in a cross-sectional study. Morning urine was tested for total protein (PROT), albumin (ALB) and alpha-1-microglobulin (AMG). The type of proteinuria was assessed by the alpha-1-microglobulin/albumin algorithm (AAA): [AAA = AMG x 100/(AMG+ALB]. Median PROT, ALB, and AMG (in mg/mmol creatinine) were 20.0, 3.8, and 4.9, respectively. Pathological total proteinuria (>22 mg protein/mmol creatinine) was found in 47% of children (25/53). Only 20% of patients with pathological total proteinuria (5/25) had glomerular proteinuria, whereas 80% (20/25) had tubular proteinuria. Three of five children with glomerular proteinuria had chronic allograft nephropathy. Both AMG and albuminuria negatively correlated with the estimated glomerular filtration rate (eGFR) (p = 0.021 and 0.003, respectively). In conclusion, tubular proteinuria was present in 80% of children post-RTx and may be associated with impaired graft function; glomerular proteinuria is associated mainly with chronic allograft nephropathy.
- MeSH
- Albuminuria physiopathology urine MeSH
- Alpha-Globulins analysis MeSH
- Algorithms MeSH
- Child MeSH
- Kidney Glomerulus physiopathology MeSH
- Transplantation, Homologous pathology MeSH
- Kidney Tubules physiopathology MeSH
- Humans MeSH
- Proteinuria complications physiopathology urine MeSH
- Cross-Sectional Studies MeSH
- Graft Rejection urine MeSH
- Serum Albumin analysis MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- Alpha-Globulins MeSH
- alpha-1-microglobulin MeSH Browser
- Serum Albumin MeSH
Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and morbidity and mortality of transplanted children. The etiology of posttransplant hypertension is multifactorial: native kidneys, immunosuppressive therapy, renal-graft artery stenosis, and chronic allograft nephropathy are the most common causes. Blood pressure (BP) in transplanted children should be measured not only by casual BP (CBP) measurement but also regularly by ambulatory BP monitoring (ABPM). The prevalence of posttransplant hypertension ranges between 60% and 90% depending on the method of BP measurement and definition. Left ventricular hypertrophy is a frequent type of end-organ damage in hypertensive children after transplantation (50-80%). All classes of antihypertensive drugs can be used in the treatment of posttransplant hypertension. Hypertension control in transplanted children is poor; only 20-50% of treated children reach normal BP. The reason for this poor control seems to be inadequate antihypertensive therapy, which can be improved by increasing the number of antihypertensive drugs. Improved hypertension control leads to improved long-term graft and patient survival in adults. In children, there is a great potential for antihypertensive treatment that could also result in improved graft and patient survival.
- MeSH
- Algorithms MeSH
- Blood Pressure Monitoring, Ambulatory MeSH
- Antihypertensive Agents therapeutic use MeSH
- Kidney Failure, Chronic physiopathology surgery MeSH
- Blood Pressure MeSH
- Humans MeSH
- Postoperative Complications * MeSH
- Hypertension, Renal drug therapy etiology physiopathology MeSH
- Kidney Transplantation adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antihypertensive Agents MeSH