Overview
Definition:
Hypertension in pediatric chronic kidney disease (CKD) is defined as persistently elevated blood pressure (BP) above the 90th percentile for age, height, and sex
It is a common complication and a significant contributor to the progression of CKD and cardiovascular morbidity
Angiotensin-converting enzyme (ACE) inhibitors are cornerstone therapy, but their use requires careful consideration of growth effects.
Epidemiology:
Hypertension is present in up to 70% of children with CKD, with the prevalence increasing with CKD stage
Early-onset CKD and specific etiologies like congenital anomalies of the kidney and urinary tract (CAKUT) are associated with higher rates
Left ventricular hypertrophy (LVH) and microalbuminuria are frequent accompanying findings.
Clinical Significance:
Uncontrolled hypertension in pediatric CKD accelerates kidney damage, leading to faster decline in glomerular filtration rate (GFR) and increased risk of end-stage renal disease (ESRD)
It also significantly elevates the risk of cardiovascular complications, including stroke, myocardial infarction, and heart failure, even in childhood and adolescence
Furthermore, it can adversely impact linear growth.
Clinical Presentation
Symptoms:
Often asymptomatic
May present with headache
Visual disturbances like blurred vision
Nausea and vomiting
Epistaxis (nosebleeds)
Irritability or lethargy
Poor feeding in infants
Seizures in severe cases.
Signs:
Elevated systolic and/or diastolic blood pressure on multiple readings
Funduscopic examination may reveal hypertensive retinopathy (e.g., arteriolar narrowing, hemorrhages, exudates)
Signs of fluid overload (edema, pulmonary rales)
Signs of cardiac dysfunction (e.g., gallop rhythm, loud P2).
Diagnostic Criteria:
Diagnosis relies on serial BP measurements using appropriate cuff size and technique, plotted on age-, sex-, and height-specific BP nomograms
Hypertension is defined as BP >90th percentile for age and height on at least three separate occasions
Pediatric guidelines from organizations like the American Academy of Pediatrics (AAP) and the Kidney Disease: Improving Global Outcomes (KDIGO) provide detailed criteria and thresholds.
Diagnostic Approach
History Taking:
Detailed birth history (prematurity, perinatal insults)
Family history of hypertension or renal disease
History of urinary tract infections or voiding dysfunction
Symptoms suggestive of underlying CKD (e.g., polyuria, polydipsia, failure to thrive)
Medication history (including over-the-counter drugs).
Physical Examination:
Accurate BP measurement in all four limbs using an appropriately sized cuff
Assess for edema, auscultate for cardiac murmurs and rubs, listen for pulmonary crackles
Funduscopic examination
Palpate kidneys for enlargement or masses
Assess growth parameters (height, weight, BMI).
Investigations:
Urinalysis (proteinuria, hematuria, specific gravity)
Urine protein-to-creatinine ratio (UPCR) or albumin-to-creatinine ratio (UACR) to assess proteinuria
Serum creatinine for estimated GFR (eGFR)
Electrolytes (sodium, potassium, bicarbonate)
Complete blood count (CBC)
Renal ultrasound to evaluate kidney structure and rule out obstructive uropathy
Echocardiogram to assess for LVH and cardiac function
Serum calcium, phosphate, parathyroid hormone (PTH) levels in established CKD.
Differential Diagnosis:
Secondary hypertension due to renovascular disease (e.g., renal artery stenosis), coarctation of the aorta, endocrine disorders (e.g., pheochromocytoma, Cushing's syndrome), or parenchymal renal disease not yet diagnosed as CKD
Essential hypertension in older children, although less common
White coat hypertension.
Management
Initial Management:
Lifestyle modifications: salt restriction (target <3 g/day), DASH diet principles, regular physical activity as tolerated
Management of underlying CKD cause and associated complications (anemia, bone mineral disorder).
Medical Management:
Pharmacological therapy is initiated when BP remains elevated despite lifestyle measures
First-line agents in pediatric CKD include ACE inhibitors (e.g., enalapril, ramipril) or angiotensin II receptor blockers (ARBs) (e.g., losartan, valsartan) due to their antiproteinuric and renoprotective effects
Dosing is critical and adjusted based on BP response and renal function
Calcium channel blockers (e.g., amlodipine) and beta-blockers (e.g., metoprolol) are often used as second- or third-line agents or in combination therapy
Diuretics (e.g., furosemide, hydrochlorothiazide) may be needed for volume management.
Ace Inhibitor Considerations:
ACE inhibitors are preferred due to their ability to reduce proteinuria and slow CKD progression
However, they can be associated with hyperkalemia and acute kidney injury (AKI), especially in volume-depleted states or with concurrent NSAID use
Close monitoring of potassium and renal function is essential
In children with CKD, they may also impact growth, although the renoprotective benefits often outweigh potential growth concerns
Evidence suggests ACE inhibitors may mitigate growth suppression associated with proteinuria itself.
Growth Considerations:
Linear growth failure is a common problem in pediatric CKD and can be exacerbated by poorly controlled hypertension
ACE inhibitors, by improving renal function and reducing proteinuria, can indirectly improve growth
However, some studies suggest potential direct effects on growth, although this is less clear-cut and often dose-dependent
Careful monitoring of growth velocity is crucial
Nutritional support and management of endocrine factors (e.g., growth hormone deficiency) may be necessary if growth remains suboptimal despite BP control and optimal CKD management
Recombinant human growth hormone (rhGH) therapy may be considered in selected patients.
Supportive Care:
Regular BP monitoring at home and in clinic
Adherence to medication regimens
Nutritional counseling focusing on sodium and protein intake
Education of parents and child about the condition and management plan.
Complications
Early Complications:
Hypertensive encephalopathy
Hypertensive retinopathy
Acute kidney injury (AKI) precipitated by ACE inhibitors (especially in dehydrated states)
Electrolyte abnormalities (hyperkalemia).
Late Complications:
Progressive CKD and ESRD
Left ventricular hypertrophy (LVH)
Cardiovascular disease (e.g., stroke, myocardial infarction)
Chronic kidney disease-mineral bone disorder (CKD-MBD)
Impaired linear growth and delayed puberty.
Prevention Strategies:
Strict BP control to target <90th percentile for age/sex/height
Early initiation of ACE inhibitors or ARBs to reduce proteinuria
Regular monitoring of renal function and electrolytes
Adequate hydration
Judicious use of NSAIDs
Nutritional optimization
Growth monitoring and timely intervention.
Prognosis
Factors Affecting Prognosis:
The underlying cause of CKD
The severity of CKD at diagnosis
The degree of BP control achieved
The presence and severity of proteinuria
Adherence to treatment
Nutritional status.
Outcomes:
With aggressive management including BP control, ACE inhibitor therapy, and management of underlying CKD, progression to ESRD can be slowed
Cardiovascular risk can be mitigated
Growth can be optimized, although some degree of growth deficit may persist
Long-term outcomes depend on sustained adherence and optimal medical care.
Follow Up:
Lifelong follow-up is essential
Frequent monitoring of BP, GFR, electrolytes, and proteinuria
Regular growth assessment
Echocardiographic monitoring for LVH
Management of associated CKD complications
Transition to adult nephrology care is crucial.
Key Points
Exam Focus:
Hypertension is a common and critical complication in pediatric CKD, directly impacting renal and cardiovascular outcomes
ACE inhibitors are first-line agents due to antiproteinuric and renoprotective effects, but require careful monitoring of K+ and GFR
Growth failure is a significant concern, and BP control with ACE inhibitors can indirectly improve growth
KDIGO and AAP guidelines are essential references.
Clinical Pearls:
Always use appropriately sized BP cuffs in children
Plot BP readings on age/sex/height specific nomograms
Initiate ACE inhibitors with caution in dehydrated or hyperkalemic patients
Educate families on low-sodium diet and medication adherence
Consider rhGH for persistent growth failure despite optimal management
Remember ACE inhibitors can affect growth, but their renoprotective benefits often outweigh this risk in CKD.
Common Mistakes:
Underestimating the prevalence and impact of hypertension in pediatric CKD
Inadequate BP monitoring or use of incorrect cuff size
Failure to initiate antiproteinuric therapy (ACEi/ARB)
Inadequate monitoring of potassium and GFR when on ACEi/ARB
Neglecting growth monitoring and nutritional support
Delaying transition of care to adult services.