Kidney Disease in Special Populations: Adolescents
Does your adolescent patient have kidney disease or hypertension?
- What can I expect to find in an adolescent with kidney disease?
- What are the causes of kidney disease in children and adolescents?
- How do I determine if my adolescent patient has hypertension? What else should I be looking for?
- What is a normal blood pressure in an adolescent?
- Why does my adolescent patient have hypertension?
- What tests to perform?
How should adolescent patients with hypertension be managed?
What happens to children with hypertension?
What happens to children with kidney disease?
- Are there special considerations in adolescents with kidney transplants?
- How to utilize team care?
Are there clinical practice guidelines to inform decision making?
Does your adolescent patient have kidney disease or hypertension?
Kidney disease is relatively uncommon in the general pediatric population at large. On the other hand, treatment for chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children has improved dramatically in the past 20-30 years and increasing numbers of these patients are surviving well into adulthood. For this reason, internists and other adult providers are likely to come into contact with adult survivors of pediatric illnesses with which they may be unfamiliar. Adolescents and young adults with known chronic kidney disease and end-stage renal disease can now expect to transition to adult providers for ongoing care. They may also present with previously undiagnosed pediatric kidney disease or with new onset of other forms of kidney disease commonly seen in adults.
The incidence and prevalence of hypertension among children and adolescents has increased in recent years, in part due to more widespread screening and recognition, but also likely secondary to the increased prevalence of overweight and obesity in the general population. Some pediatric patients with hypertension may present with specific complaints suggestive of a renal etiology, such as gross hematuria, but in most, the signs and symptoms may be subtle, absent or non-specific.
What can I expect to find in an adolescent with kidney disease?
In adolescent patients with childhood-onset renal disease, the diagnosis is known, but the adult clinician may be unfamiliar with features unique to the patient's primary disease. In patients with undiagnosed or new onset kidney disease, signs and symptoms may be subtle. Problems such as hypertension or proteinuria may even be picked up incidentally. Specific complaints may include gross hematuria, edema, dysuria, recurrent urinary tract infections, abdominal or flank pain, headaches or other neurologic symptoms suggestive of hypertension. Because of the insidious nature of chronic kidney disease, associated sequelae such as poor linear growth, enuresis, and polyuria may go unnoticed for years.
What are the causes of kidney disease in children and adolescents?
The spectrum of kidney disease in children and adolescents differs significantly from that in adult patients, with the major causes including congenital malformations, glomerulonephritis, and cystic kidney disease. Acquired kidney disease from hypertension or diabetes is exceedingly rare in childhood, which is in striking contrast to the distribution of renal disease in adults. Additionally, the prevalence of kidney disease in children has remained relatively stable over the past several decades, unlike in adults, for whom numbers have increased greatly. The etiology of pediatric ESRD among North American patients 13-20 years old receiving a transplant using 2008 NAPRTCS data can be broken down generally into the following categories (
Table 1. Etiology of Pediatric ESRD
|Disease category||%of patients|
Structural malformations: This is the largest category and represents diseases that are congenital in origin. There is a broad clinical spectrum among patients with congenital renal and urinary tract malformations: some may require renal replacement therapy in the neonatal period, whereas others may proceed to ESRD sometime during childhood or even reach adulthood with minimal medical intervention.
The largest group of disorders in this category include renal dysplasia, hypoplasia and obstructive nephropathy. These patients are sometimes referred to as having "high-output" renal failure, because they often produce large volumes of dilute urine. Hypertension is rare and patients can crave salt and drink large volumes of water to keep up with the high urine output. Because of the continued high urine output, patients with renal dysplasia occasionally go undiagnosed for a long period of time. Subtle clues that should raise concern include: poor growth (especially linear growth/height), salt-craving, nocturnal enuresis because of the high urine output, preference for water over other beverages, waking up at night to drink water and constipation.
Glomerulonephritis:This category of disease includes those that are also commonly seen in adults. All forms of glomerulonephritis are more common as a cause of kidney disease among adolescents than among younger children. Diseases in this category include: membranoproliferative glomerulonephritis (MPGN), lupus nephritis, idiopathic glomerulonephritis, Henoch-Schlonlein purpura (HSP), Wegener's granulomatosis, membranous nephropathy, and IgA nephropathy. As in adults, typical presenting symptoms in adolescent patients with glomerulonephritis include: gross hematuria, hypertension, proteinuria, edema. Diseases with a systemic component, such as lupus and vasculitis will often be accompanied by additional symptoms, such as fever, malaise, joint complaints, rash and respiratory complaints.
Focal segmental glomerulosclerosis (FSGS): FSGS is the most common glomerular disease as a cause of ESRD in adolescents. Patients can present with steroid-resistant nephrotic syndrome or nephrotic-range proteinuria without edema and they are frequently hypertensive. FSGS is a disease that can be challenging to treat and the risk of recurrence in transplanted kidneys can be as high as 30-40%.
Other: The "other" category encompasses a list of diseases that are relatively rare, some of which are typically diagnosed early in life, such as aautosomal recessive polycystic kidney disease( ARPKD), cystinosis and Wilms tumor, as well as those that may be diagnosed in older children, such as hemolytic-uremic syndrome (HUS) and interstitial nephritis.
Practitioners caring for adolescents or young adults with ESRD (those with transplants and on dialysis) should become familiar with the patient's primary etiology of renal failure. This will help to identify which patients might be at risk of disease recurrence in a transplanted kidney, or development of systemic manifestions or other complications of the primary disease.
How do I determine if my adolescent patient has hypertension? What else should I be looking for?
Accurate blood pressure (BP) measurements are essential in determining the presence of hypertension. Blood pressure can be measured in the office ("casual BP"), at home ("self-measured BP") or by 24-hour ambulatory blood pressure monitoring (ABPM). Office or home readings should be taken after the patient has been resting in a seated position for at least 5-10 minutes.
Determining appropriate cuff size - It is important to ensure that the appropriate cuff size is used, as a cuff that is too small may give a falsely elevated reading. By contrast, a cuff that is too large will not give a reading that is too low. If there is a discrepancy between readings with two different cuff sizes, the reading with the larger cuff should be used. Cuff size is determined by measuring the arm circumference midway between the acromion process and the olecranon. This circumference should be compared with the length of the cuff bladder (the part that inflates), which is typically printed on the inside of the cuff. The bladder should encircle at least 80% of the arm circumference. Many overweight and obese adolescents require a large adult or even a thigh cuff for accurate blood pressure measurement. These are more commonly available in recent years as the prevalence of obesity has increased.
Patient position - The patient should be in a seated position with the arm elevated to the level of the heart. Measurements should be taken after the patient has been resting for at least 5 minutes. Repeat measurements should be 2-3 minutes apart.
Oscillometric measurement - Oscillometric devices are commonly available in most clinical settings and are often selected for their ease of use and convenience. A few points should be kept in mind when interpreting readings from such devices. First, an oscillometric monitor does not measure systolic blood pressure (SBP) and diastolic blood pressure (DBP) directly, but rather it measures the mean arterial pressure (MAP) and extrapolates SBP and DBP. This can result in an overestimation of SBP and an underestimation of DBP. Additionally, the device may initially inflate to a pressure far above the patient's true SBP, causing pain and a falsely elevated reading. However, repeated measurements accommodate to the patient. For this reason, at least 2-3 readings a few minutes apart are recommended. The first reading can often then be discarded.
Auscultatory measurement - Measuring the blood pressure by ausculation is the preferred method of BP measurement in pediatric patients according to the most recent consenus recommendations from the National High BP Education Program. Again, the appropriate cuff size should be selected and the patient should be in a seated position and resting quietly for at least 5 minutes. The brachial artery is auscultated with the bell of the stethoscope. SBP is estimated at the appearance of the Korotkoff sounds, and DBP at the 5th Korotkoff sound. It is advised to wait at least 2-3 minutes between cuff inflations.
Self-measured blood pressure (SMBP) - Many small, oscillometric devices are now available for home use. Devices with arm cuffs have been most extensively studied and are physiologically the most simliar to readings in other settings. Blood pressure taken in more distal arteries can vary from that centrally or in the arm, with systolic pressures typically higher and diastolic pressures lower. Devices measuring blood pressure more distally (at the wrist or finger) are available and remain potential options for obese patients, but have not been well-studied. Wrist devices must be used with the arm elevated to the level of the heart. Repeated or daily readings can then be recorded and reviewed by the practitioner.
Ambulatory blood pressure monitoring (ABPM) - The use of ambulatory blood pressure monitoring to diagnose and characterize hypertension in children and adolescents has increased in recent years. There is evidence to suggest that, at least in children with kidney disease, ABPM is more sensitive in diagnosing hypertension than SMBP. ABPM is especially helpful in ruling out white coat hypertension, diagnosing abnormal nocturnal dipping in diabetic patients (an early sign of diabetic nephropathy), and identifying masked hypertension in patients for whom this condition is suspected. It is also useful in determining the effectiveness of prescribed antihypertensive therapy. Several studies have also suggested that specific BP patterns on ABPM may be useful in discriminating between primary and secondary hypertension.
The majority of adolescent patients seen in the outpatient setting for hypertension will be asymptomatic, or may have non-specific symptoms. Symptomatic hypertension requires prompt treatment and evaluation and all patients should be screened for common symptoms associated with elevated blood pressure. These include:
Headache - may be acute or chronic
Chest pain or shortness of breath
Nausea and vomiting
Seizure - Patients with severe hypertension, particularly those with a rapid increase in blood pressure over a short period of time, can experience symptoms of hypertensive encephalopathy when the cerebrovascular autoregulatory system fails to adapt to the extremely elevated blood pressure.
What is a normal blood pressure in an adolescent?
Blood pressure is dependent on body size; this must be taken into account when assessing children for hypertension. As a result, there is no single cut-point BP value to define hypertension as in adult patients. Children are classified as hypertensive based on comparisons to population-based norms subcategorized by age, sex and height percentile. These values can be found in charts published in The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents (PUBMED:15286277) or online at
Table 2. Blood pressure Stages in Children and Adolescents
|Prehypertensve||BP >=90th percentile and <95 percentile OR >=120/80 and <95th percentile|
|Stage 1 hypertension||BP >95th percentile but <99th percentile + 5 mmHg|
|Stage 2 hypertension||BP >99th percentile + 5 mmHg|
Why does my adolescent patient have hypertension?
Recent studies have shown that not all children and adolescents with hypertension have secondary hypertension. A good history and physical can aid the physician in determining whether the patient may be at risk for secondary hypertension. The following factors increase the likelihood that a patient has primary hypertension: adolescent, obese, positive family history, pre-hypertension or stage 1 hypertension. Unless there are futher clues on the history or physical exam that point to another disease process, the patient most likely has primary hypertension and an extensive work-up is unlikely to be helpful and may not be necessary.
Causes of secondary hypertension in adolescents:
Intrinsic renal disease: This category includes undiagnosed chronic kidney disease secondary to glomerulonephritis, congenital malformations and vesicoureteral reflux (VUR). In the case of VUR, it is thought that repeated episodes of pyelonephritis lead to renal scarring, which can predispose to hypertension. In adolescence, the VUR may have resolved, but scarring from prior infections is associated with both hypertension and chronic kidney disease. Hypertension may be the initial presenting sign of a patient with undiagnosed intrinsic renal disease.
Renovascular disease: Renal artery stenosis, most often due to fibromuscular dysplasia in this age group, renal vein thrombosis (typically accompanied by gross hematuria), or stenosis of a branch vessel, as can be found in patients with Williams syndrome and neurofibromatosis, will often present with severe (Stage 2) or symptomatic hypertension. Hypertension is due to high production of renin by the affected kidney(s).
Cardiac disease (coarctation): Although less common to go undetected until adolescence, a coarctation of the aorta can cause upper extremity hypertension.
Malignancy: A rare form of secondary hypertension in both children and adults, pheochromocytomas may be diagnosed in isolation or as part of an endocrine syndrome (MEN Type 2 and Von Hippel Lindau disease). Patients may present with severe hypertension that may be labile in nature. Associated symptoms include tachycardia, facial flushing and headache. Other malignancies associated with hypertension, such as Wilms tumor and neuroblastoma, are diseases of infants and younger children.
Other endocrine causes: Cushing syndrome, hyperthyroidism are rare forms of secondary hypertension. Patients would be expected to exhibit other signs and symptoms in addition to hypertension.
Monogenic hypertension:This is a small group of single-gene disorders often associated with low renin and electrolyte abnormalities. A strong family history of hypertension, particularly starting in childhood or early adulthood, should raise suspicion for a monogenic disorder. Diseases include: Gordon syndrome, Liddle syndrome, glucocorticoid-remediable hyperaldosteronism (GRA) and apparent mineralocorticoid excess (AME). Knowledge gained from the genetic basis of these disorders has improved our understanding of renal tubular physiology and salt-handling in the kidney.
Drugs/substances:Medications known to increase blood pressure include corticosteroids, calcineurin inhibitors (tacrolimus and cyclosporin), oral contraceptive pills and stimulants used to treat ADHD.
Obstructive sleep apnea (OSA): The association between OSA and hypertension is well-established. Adolescent patients, particularly those who are obese, presenting with hypertension should be screened for signs and symptoms of OSA and referred for polysomnography if deemed appropriate. While hypertension in these patients may be multifactorial, there is evidence to suggest that treatment of OSA will reduce blood pressure.
What tests to perform?
The following testing would be recommended for adolescent patients undergoing evaluation for hypertension:
Urinalysis (UA): Urinalysis with microscopic exam should be performed on all patients with suspected kidney disease or hypertension. The presence of microscopic hematuria or proteinuria may be an indication of intrinsic renal disease.
Electrolytes, Blood urea nitrogen (BUN), creatinine:Renal function should be tested in all patients for whom intrinsic renal disease is suspected. Adolescent patients with pre-hypertension, suspected white coat hypertension or Stage 1 hypertension are likely to have normal renal function. In these cases, testing could be deferred until further evaluation of the elevated BPs has taken place.
Fasting serum glucose: Given the association of obesity with hypertension, type 2 diabetes and metabolic syndrome, a fasting serum glucose would be appropriate in overweight or obese patients (if not already done) to evaluate for co-morbid conditions.
Fasting lipid panel: The American Academy of Pediatrics (AAP) currently recommends testing of serum lipids at least one time in adolescents. All adolescent patients with hypertension should have serum lipids tested if not already done in the past 12 months.
Additional lab testing
In patients for whom renal disease or secondary hypertension is suspected, the following laboratory tests should be considered:
C3, C4: Serum complements can aid in diagnosing certain forms of glomerulonephritis. Low complements are associated with lupus nephritis, post-infectious glomerulonephritis (typically an isolated decrease in C3), membranoproliferative glomerulonephritis (MPGN) and shunt nephritis.
Antinuclear antibody (ANA): If the patient has clinical signs and symptoms suggestive of lupus, an ANA may be helpful.
Thyroid-stimulating hormone (TSH) : Hypertension can be one of the signs of hyperthyroidism. If this is the etiology for the patient's elevated blood pressure, there will usually be other signs and symptoms present. A screening TSH can rule out thyroid disease if suspected.
Plasma free metanephrines: If a pheochromocytoma is suspected, measurement of plasma free metanephrines is the most sensitive test. The specificity is lower, however, which may lead to
Renin: Can be abnormally high in renovascular disease. The affected kidney will increase renin production in response to a perceived low blood flow or hypotensive state when a stenosis is present. Plasma renin activity can also be low in certain forms of monogenic hypertension.
Aldosterone: Can help distinguish among some forms of low-renin hypertension.
Complete blood count (CBC): Patients with chronic kidney disease will often be anemic, with other cell lines intact. Patients with HUS have low platelets and varying degrees of anemia due to intravascular hemolysis.
Parathyroid hormone (PTH): Patients with previously undiagnosed chronic kidney disease may have elevated PTH levels. In a patient with (untreated) advanced kidney disease it would not be uncommon for the PTH to be several fold higher than normal.
Renal US - should be obtained in any adolescent with stage 2 hypertension, or in any patient with suspected kidney disease. A renal US can help assess any evidence of anatomic abnormality and kidney size. A size discrepancy may be present with a dysplastic or scarred kidney. Small kidneys indicate chronic kidney disease. Patients with an acute inflammatory process, such as post-infectious glomerulonephritis (PIGN) or pyelonephritis may have enlarged kidneys. A doppler study is useful to determine the presence of thrombosis, but is not recommended to rule out renovascular disease (see below under CT angiogram).
Echocardiogram - should be obtained as part of the initial evaluation of patients with confirmed hypertension in order to screen for left ventricular hypertrophy (LVH), which is an indication to initiate or intensify antihypertensive therapy. LVH can be assess subjectively, but the standard for determining the presence of LVH is to measure the left ventricular mass index. This index can then be compared to age- and sex-specific norms. A LVMI >95th percentile is indicative of LVH.
CT angiogram - useful as a screen for renal artery stenosis when renovascular hypertension is suspected. This modality is more sensitive than Doppler ultrasound, particularly when there is a stenosis in a smaller, branch vessel.
Nuclear renal scans - can be used to evaluate for urinary obstruction (MAG-3 scan with lasix), or for parenchymal scarring (DMSA scan). Parenchymal scarring may be evidence of undiagnosed vesicoureteral reflux.
Kidney biopsy: A kidney biopsy may be required to make a specific diagnosis, and would typically be arranged with the consultation of a nephrologist.
Interpretation of test results
Testing on an adolescent patient with suspected hypertension or kidney disease should be done with aim of arriving at a diagnosis as well as assessing for complications of the disease.
How should adolescent patients with hypertension be managed?
How should I approach an adolescent patient with hypertension?
The first decision point in treating any patient with hypertension is to assess for the presence of symptoms. Asymptomatic hypertension can generally be managed on a outpatient basis, whereas those with associated symptoms require more immediate intervention.
How do I approach symptomatic hypertension?
A patient with symptomatic hypertension requires prompt intervention. Symptomatic hypertension with evidence of end-organ dysfunction is termed Hypertensive Emergency. In children and adolescents, manifestations of end-organ dysfunction most often include: seizure or hypertensive encephalopathy, heart failure, retinopathy and renal failure. A patient with hypertensive emergency should be treated immediately, either with a continuous IV infusion or with IV bolus medications. Severe symptomatic hypertension without evidence of end-organ dysfunction is termed Hypertensive Urgency. These patients may still require IV medication, but they may also be safely managed with po medication, depending on the clinical scenario.
Should I use IV or PO medication?
There are some oral medications that are relatively short-acting and can be used to quickly lower the blood pressure. The onset of action will be slower than for IV medications, allowing for absorption, and the effect may be unpredictable. The use of short-acting nifedipine is no longer recommended for children or adolescents, due to its unpredictable effects on lowering blood pressure and risk of arrhythmia. IV medications may be given as a bolus or continuous infusion. The latter allows for the most control in titrating the blood pressure to the desired range. Some commonly used IV and short-acting PO medications are listed in
Table 3. PO and IV Medications
MEDICATION CLASS DOSE (per kg) DOSE (adult) PO Isradipine Calcium channel blocker 0.05-0.1 mg/kg (max 5 mg) q6 hours 2.5-5 mg q6 hours Hydralazine Direct vasodilator 0.25 mg/kg (max 25 mg) q 6-12 hours 10 mg q 6-12 hours Clonidine Central α agonist 0.05-0.1mg/dose q 6-12 hours Minoxidil Direct vasodilator 0.1-0.2 mg/kg (max 10 mg) q 8-24 hours 2.5-5 mg q 8-24 hours IV Hydralazine Direct vasodilator 0.1-0.2 mg/kg (max 20mg) q4-6 hours 10-20 mg/dose q4-6 hours (max = 40 mg/dose) Labetalol α- and β- blocker Bolus: 0.2-1 mg/kg/dose (max 40mg) q10 minutes
Infusion: 0.25-3 mg/kg/hr
Bolus: 20mg, may give 40-80 mg q10 minutes (max 300 mg total dose)
Esmolol β- blocker 100-500 mcg/kg/min Nicardipine Calcium channel blocker 0.5-4 mcg/kg/min Nitroprusside Direct vasodilator 0.5-10 mcg/kg/min
Does the patient require hospitalization?
Generally speaking, most patients presenting with symptomatic hypertension or for whom IV medications have been administered should be admitted for observation and further management/evaluation. Intensive care unit (ICU)-level care is appropriate for any patient requiring a continuous infusion to lower the blood pressure in a controlled manner. A patient who has received bolus medications or po medications with improvement may be appropriately managed on the floor.
Patients with asymptomatic hypertensive can be safely treated with long-acting oral agents. Unlike with adult evidence-based recommendations, there are relatively few comparative pediatric studies from which to build consensus guidelines on antihypertensive prescribing practices. In general, anfiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are effective and well-tolerated by children and adolescents. The practitioner should provide appropriate counseling on the risk of teratogenicity to adolescent females for whom they are prescribing these classes of medication.
Beta blockers have also been widely used in children and adolescents and studies have demonstrated their efficacy in lowering blood pressure in this population. They are contraindicated in patients with asthma and may not be well-tolerated by adolescent athletes. They are useful in patients taking stimulants for ADHD who are also hypertensive because these patients are often also tachycardic.
Calcium channel blockers are widely used in children and adolescents, are effective and have relatively few associated side effects. Diuretics have not traditionally been extensively used as first-line agents in children and adolescents. Studies in adults have demonstrated their effectiveness at lowering blood pressure compared to more expensive, newer medications. In adolescents with essential hypertension, they may be an appropriate choice for a first line agent. Dosing recommendations for oral medications are shown in
Table 4. Dosing Recommendations for Oral Medications
MEDICATION STARTING DOSE MAXIMUM DOSE ACE inhibitors Enalapril 0.8mg/kg/day up to 2.5-5mg/day in 1-2 doses 0.6mg/kg/day up to 40mg/day Captopril 0.3-0.5 mg/kg/dose up to 12.5-25 mg given BID-TID 6mg/kg/day up to 450mg/day Lisinopril 0.07mg/kg/day up to 5-10mg/day 0.6 mg/kg/day up to 40 mg/day Angiotensin Receptor Blockers (ARBS) Losartan 0.75 mg/kg/day up to 50 mg/day given QD-BID 1.4 mg/kg/day up to 100 mg/day Valsartan 1.3 mg/kg/day up to 40 mg/day 2.7 mg//kg/day up to 160 mg/day Calcium-channel Blockers Amlodipine 0.1 mg/kg/day up to 2.5-5mg/day 0.3mg/kg/day up to 10-20 mg/day ER-Nifedipine 0.25-0.5 mg/kg/day up to 30-60 mg/day QD-BID 3 mg/kg/day up to 120 mg/day Beta-Blockers Atenolol 0.5-1 mg/kg/day up to 50 mg/day QD-BID 2 mg/kg/day up to 100 mg/day Propranolol 1 mg/kg/day up to 80 mg/day QD-TID 16 mg/kg/day up to 640 mg/day Metoprolol 1-2 mg/kg/day up to 100 mg/day divided BID 6 mg/kg/day up to 200 mg/day Diuretics Hydrochlorothiazide 0.5-1 mg/kg/day up to 12.5-25 mg/day 3 mg/kg/day up to 50 mg/day Direct Vasodilators Minoxidil 0.1-0.2 mg/kg/day up to 5 mg/day divided QD-TID 1 mg/kg/day up to 50 mg/day
What should be the follow-up plan for an adolescent with asymptomatic hypertension? Does he/she need a nephrologist?
A patient with asymptomatic hypertension who will be discharged from the clinic or emergency department should have a clear plan for follow up, both to monitor the blood pressure and review any test results from the visit that are outstanding.
Most pediatricians are not specifically trained or experienced in managing hypertension, and it is common in the pediatric population for nephrologists to see these patients. Adult primary care practitioners may be more comfortable, particularly in the case of essential hypertension.
There is evidence to suggest that patients with pre-hypertension are at risk for developing hypertension later in life. Pharmacologic therapy is not necessary at this stage, but patients should be advised to institute therapeutic lifestyle changes (TLC). This primarily includes increased physical activity and weight loss. A low sodium diet should be recommended. Because studies in adults have demonstrated a lowering effect on blood pressure with a diet rich in fruits and vegetables, the DASH (Dietary Approaches to Stop Hypertension) is also often recommended.
What happens to children with hypertension?
There are no long-term studies in the pediatric population to assess mortality risk. Since studies have shown that children with elevated BP or hypertension are at risk of becoming adults with hypertension, the assumption is made that these patients are at increased lifetime risk of the complications of hypertension well-reported in the adult literature.
Pathophysiologic considerations - The typical complications that are seen in adults with long-standing hypertension, such as stroke and renal failure, are extremely rare in children and adolescents. Rather, most pediatric studies focus on intermediate end-points. The most common site of target organ damage among children and adolescents with hypertension is the heart and the development of left ventricular hypertrophy.
Pharmacologic considerations - There are no long-term studies looking at antihypertensive use in children. Short-term studies of antihypertensive medications commonly used in children and adolescents have demonstrated both safety and efficacy, and most practitioners agree that the cardiovascular benefits of treatment outweigh any unknown risks of long-term pharmacotherapy.
What happens to children with kidney disease?
Children and adolescents diagnosed with chronic kidney disease and ESRD have an excellent prognosis in terms of survival from their kidney disease, thanks to improvements in dialysis and transplant care. Epidemiologic studes done in several countries over the past decade have shown an alarmingly high mortality rate among adult survivors of pediatric ESRD, up to 300 times higher than that of their peers in the general population. The leading causes of death were cardiovascular. Although the pathophysiology behind this finding is not entirely clear, researchers believe that risk factors include hypertension, hyperlipidemia, abnormal metabolism of calcium and phosphorus, and chronic inflammation.
Now that children with kidney disease are living well into adulthood, attention has also turned to quality of life aspects. Questions about mental health, social functioning, sexual health and others have yet to be fully answered.
Are there special considerations in adolescents with kidney transplants?
Issues related to medications
Immunosuppression: Because of the side effect profile, many of the newer pediatric protocols avoid exposure to steroids entirely. However, there are some patients for whom steroid regimens remain the most suitable choice. As patients are further out from transplant, the amount of immunosuppression prescribed is minimized, but they remain at increased risk for infection.
Teratogenicity: The most commonly prescribed teratogenic medications for transplant recipients are: MMF (Cellcept), ACE inhibitors, and ARBs. Patients are counseled to notify their provider if a pregnancy is planned or has occurred so that a suitable substitute can be prescribed.
Many studies have documented an increased risk of malignancy in transplant recipients, although evidence-based screening guidelines have yet to be developed. Some increased risk is thought to arise from de novo viral infection or re-activation of a prior infection. Screening is appropriate for:
Post-transplant lymphoproliferative disorder (PTLD) This is most commonly EBV related, but not in all cases. Many children are EBV negative prior to transplantation and are therefore at increased for primary EBV infection while immunosuppressed
Genital/cervical cancer – impact of HPV vaccine is not yet known
Other cancer screening should be done as recommended for all patients
All kidney transplant recipients remain on immunosuppressive medications for the life of their allograft. Along with an increased risk of infection, many are associated with other risks and side effects. Nephrologists often use medication trough levels to guide immunosuppression dosing (
Table 5. Common immunosuppressive medications used for kidney transplantation, associated adverse effects and medication level goals.
|Drug||Adverse Effects||Trough goals|
|Cyclosporin||Hirsutism, nephrotoxicity, hyperlipidemia, gingival hyperplasia||75-200|
|Tacrolimus (Prograf)||Tremor, diabetes, nephrotoxicity, hyperlipidemia||3-10|
|Sirolimus (Rapamycin)||Diabetes, hyperlipidemia, myelosuppression, impaired wound healing||5-12|
|Steroids||Hyperlipidemia, diabetes, osteoporosis||n/a|
|MMF (Cellcept)||Diarrhea, Myelosuppression||Not|
Age-appropriate counseling regarding safe sex practices, contraception and reproductive health remain important
During the treatment phase of their primary disease, patients may have had exposure to medications affecting fertility, particularly cyclophosphamide.
Transplant patients should be counseled that their increased susceptibility to infection includes sexually transmitted infections.
Genetic counseling may be indicated in patients with an inherited form of renal disease.Female patients are likely to have questions about risks involved with pregnancy
Cervical cancer screening
How to utilize team care?
Nephrology: An adolescent patient with suspected chronic kidney disease should be referred to a pediatric nephrologist. A patient with a more acute process, such as glomerulonephritis, HUS or other acute kidney injury should also have a pediatric nephrologist involved in their care. Unlike in adult medicine, most pediatric patients with hypertension are managed by nephrologists as well, particularly in the initial phases when ruling out secondary causes and starting antihypertensive medications.
Urology: Adolescent patients with chronic kidney disease secondary to genitourinary malformations may need care from a urologist.
Other specialities: Patients with secondary hypertension or comorbidities (diabetes, hyperlipidemia) may need input from other specialists as well, including endocrinology, rheumatology and cardiology. Patients with suspected monogenic hypertension may be referred to a geneticist if genetic testing is deemed appropriate.
Nurses - Nurses remain an important point of contact between provider and patient, as in treatment for any patient with a chronic disease.
Pharmacists - Skilled pharmacists can play a key role in caring for a patient with complex medical disease. Tranpslant patients can have long lists of medications, pharmacokinetic considerations of immunosuppressive drug metabolism and drug-drug or drug-food interactions. Pharmacists can assist the physician as well as provide education for the patient. A special concern for adolescent and young adult transplant recipients is adherence to the medication regimen. Newer programs, such as text reminders when medications are due, can potentially be very helpful for this patient population.
Dietitians - Nutrition education and guidance is an essential part of the care plan for patients with chronic kidney disease. Dieticians can also provide education and counseling for patients with essential hypertension who need to institute therapeutic lifestyle changes.
Social work - A skilled social worker can be a valuable addition to the care team of patients with chronic disease. Adolescent patients with chronic kidney disease can now expect to become adult patients with chronic kidney disease and that transition is not often a smooth one. Issues that social work can assist with include: insurance options for adolescents and young adults, disability, education/work resources and support with assuming primary responsibility for one's own health care(often formerly under the purview of the patient's parents).
Are there clinical practice guidelines to inform decision making?
Pediatric guidelines for the diagnosis and treatment of hypertension can be found in the 4th Report (PUBMED:15286277)
There are numerous clinical guidelines for the treatment of dialysis patients. The Kidney Disease Outcomes Quality Initiative (KDOQI) provides both adult and pediatric-specific guidelines on dialysis therapy and management of the sequelae of chronic kidney disease. These can be found at: http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cfm#guidelines.
Kidney Disease: Improving Global Outcomes (KDIGO) is a global initiative to provide clinical guidelines for a broader scope of nephrology issues, including transplant care. There are not pediatric-specific guidelines at this time.
What is the evidence?
"National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents". Pediatrics. vol. 114. 2004. pp. 555-576.(Consensus recommendations on diagnosing and treating pediatric hypertension. Also includes age/sex/height normative values for BP in children.)
Urbina, E, Alpert, B, Flynn, J, Hayman, L, Harshfield, GA, Jacobson, M, Mahoney, L, McCrindle, B, Mietus-Snyder, M, Steinberger, J, Daniels, S. "Ambulatory blood pressure monitoring in children and adolescents: Recommendations for standard assessment". Hypertension. vol. 52. 2008. pp. 433-451.(Outlines the use of ABPM in the pediatric population.)
Pickering, TG, Hall, JE, Appel, LJ, Falkner, BE, Graves, J, Hill, MN, Jones, DW, Kurtz, T, Sheps, SG, Roccella, EJ. "Recommendations for Blood Pressure Measurement in Humans and Experimental animals: Part 1: Blood Pressure Measurement in Humans: A Statement for Professionals From the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research". Hypertension. vol. 45. 2005. pp. 142-161.(Detailed guidelines on proper techniques in obtaining blood pressure measurement. Compares the usefulness of different devices.)
Parekh, RS, Carroll, CE, Wolfe, RA, Port, FK. "Cardiovascular mortality in children and young adults with end-stage kidney disease". J Pediatr. vol. 141. 2002. pp. 162-164.(Epidemiologic study of high mortality rates in young adults with childhood-onset ESRD.)
Hanevold, C, Waller, J, Daniels, S, Portman, R, Sorof, J. "The effects of obesity, gender and ethnic group on left ventricular hypertrophy and geometry in hypertensive children: a collaborative study of the International Pediatric Hypertension Association". Pediatrics. vol. 113. 2004. pp. 328-333.(Demonstrates the association between hypertension and increased LV mass in children.)
Samuel, SM, Tonelli, MA, Foster, BJ, Alexander, RT, Nettel-Aguirre, A, Soo, A, Hemmelgarn, BR. "Survival in pediatric dialysis and transplant patients". Clin J Am Soc Nephrol. vol. 6. 2011. pp. 1094-1099.(Long-term outcomes of pediatric patient with ESRD in Canada.)
Flynn, JT, Tullus, K. "Severe hypertension in children and adolescents: pathophysiology and treatment". Pediatr Nephrol. vol. 24. 2009. pp. 1101-1112.(Review article in etiology and treatment of severe hypertension in pediatric patients.)
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