Chronic Kidney Disease in Children

MD Pediatrics — 10 Marks Presentation

1. Definition & Staging

2. Etiology

Non-Glomerular (predominates <5 years)

• CAKUT — congenital anomalies of kidney & urinary tract (renal hypoplasia, dysplasia, obstructive uropathy): most common cause overall, ~28% of ESKD
• Cystic kidney disease (ARPKD, ADPKD, nephronophthisis/ciliopathies): ~12%
• Cystinosis, oxalosis, metabolic disorders
• Pyelonephritis, reflux nephropathy, interstitial nephritis

Glomerular (predominates >5 years)

• Focal segmental glomerulosclerosis (FSGS)
• Membranoproliferative GN (MPGN)
• IgA nephropathy
• Lupus nephritis (SLE)
• Hemolytic uremic syndrome (HUS)
• Alport syndrome (hereditary nephritis)
• Congenital nephrotic syndrome

Key point for exam: CAKUT most common in infants; glomerular disease dominates in school-age children and adolescents.

3. Pathogenesis

Primary Mechanism — Hyperfiltration Injury

Additional Pathologic Drivers

Key: Tubulointerstitial fibrosis is the primary determinant of CKD progression, regardless of etiology.

4. Clinical Manifestations

Symptoms (depend on etiology and CKD stage):

• Growth failure, vomiting, polyuria, polydipsia
• Salt wasting (renal dysplasia)
• Recurrent UTI

• Edema, hypertension, hematuria, proteinuria
• Malnutrition in severe forms

• Fatigue, weakness, nausea, vomiting, anorexia
• Poor sleep patterns, fluid overload

Key Physical Signs:

• Growth retardation, pallor (anemia)
• Hypertension, peripheral edema
• Bony deformities of rickets (renal osteodystrophy)

5. Complications (Pathophysiology Table)

6. Diagnosis & Monitoring

GFR Estimation

eGFR (mL/min/1.73 m²) = 0.413 × height (cm) / serum creatinine (mg/dL) Validated for age 1–16 years, GFR 15–90 mL/min/1.73 m²

Key Investigations

• Serum: creatinine, BUN, electrolytes, calcium, phosphorus, albumin, PTH, 25-OH vitamin D, FGF-23, CBC, lipid profile
• Urine: spot protein/creatinine ratio or 24-hr protein, UA (microscopy)
• Imaging: renal ultrasound (structural abnormalities, scarring, cysts)
• Ambulatory Blood Pressure Monitoring (ABPM): gold standard; detects masked hypertension (seen in up to 35% of predialysis CKD) — carries 4× risk of LVH
• Renal biopsy: when etiology unclear

7. Management

A. Nutrition

• 100% of estimated energy requirement for age (individualized for BMI, activity)
• Protein: not restricted in children — 100% DRI for ideal weight (growth concern)
• Nasogastric/gastrostomy feeds if oral intake insufficient
• Water-soluble vitamin supplementation for dialysis patients
• Low-phosphorus diet; low-phosphorus formula (Similac PM 60/40) in infants

B. CKD–Mineral Bone Disorder (CKD-MBD)

1. Low-phosphorus diet + phosphate binders at meals (calcium carbonate/acetate or sevelamer; avoid aluminum-based)
2. 25-OH vitamin D supplementation (goal ≥30 ng/mL) — ergocalciferol/cholecalciferol
3. Active vitamin D sterols (calcitriol/paricalcitol) — when PTH rises above stage-appropriate goals
4. Goals: normalize Ca, PO₄, PTH; prevent vascular calcification and osteodystrophy

C. Anemia

• Investigate iron deficiency → oral/IV iron if TSAT ≤20% + ferritin ≤100 ng/mL
• Erythropoiesis-stimulating agents (ESAs): erythropoietin or darbepoetin alfa, once iron-replete
• Target Hb: 11 g/dL (0.5–5 yr), 11.5 g/dL (5–12 yr), 12 g/dL (females >12 yr/males 12–15 yr), 13 g/dL (males >15 yr)

D. Hypertension & Proteinuria

• ACE inhibitors (enalapril, lisinopril) or ARBs (losartan): first-line for ALL children with CKD regardless of proteinuria level — renoprotective
• Target BP <50th percentile MAP (ABPM) especially with proteinuria (ESCAPE trial: 35% lower risk of reaching composite endpoint)
• Add thiazide or loop diuretics, calcium channel blockers (amlodipine), β-blockers as needed

E. Metabolic Acidosis

• Maintain serum bicarbonate ≥22 mEq/L
• Oral sodium bicarbonate or Bicitra (sodium citrate)

F. Fluid & Electrolyte Management

• Infants with renal dysplasia: high-volume feeds + sodium supplementation
• Hyperkalemia: restrict dietary K⁺ → alkalinizing agents → cation exchange resins (patiromer preferred over SPS in ≥12 yr)
• Fluid restriction for severe nephrotic syndrome or advanced CKD

G. Growth — Recombinant Human Growth Hormone (rHuGH)

• Indication: height <−2 SD and/or growth velocity <25th percentile for ≥6 months despite optimal medical management
• Daily subcutaneous injections; continue until 50th percentile for mid-parental height, final adult height, or transplantation

H. Immunizations

• All standard immunizations; pneumococcal (PPSV-23) + annual influenza
• Avoid live virus vaccines in immunosuppressed patients (post-transplant)
• Give MMR + varicella before transplantation

I. Drug Dosing

• Dose-adjust renally excreted drugs (lengthen interval, reduce dose, or both)

8. Progression of Disease

• Median GFR loss: 1.5 mL/min/1.73 m²/year (non-glomerular) vs 4.3 mL/min/1.73 m²/year (glomerular)
• Non-modifiable risk factors: older age, glomerular etiology, CKD severity, puberty onset
• Modifiable risk factors: elevated BP, persistent nephrotic proteinuria, anemia, dyslipidemia, no ACE-I/ARB use

9. End-Stage Kidney Disease (ESKD) & Renal Replacement Therapy

• Diuretic-resistant fluid overload
• Uncontrolled electrolyte abnormalities (hyperkalemia, metabolic acidosis, hyperphosphatemia)
• Fluid restriction limiting adequate nutrition for growth
• Uremic symptoms (fatigue, nausea, vomiting, poor school performance)
• Typically considered as GFR approaches 10–15 mL/min/1.73 m²

Dialysis Modalities

Kidney Transplantation

• Optimal therapy for all children with ESKD (Nelson, Ch. 573)
• Life expectancy post-transplant substantially better than on dialysis
• Preemptive transplantation (no prior dialysis) in ~25%; preferred when possible
• Immunosuppression: tacrolimus + MMF ± steroids (most common regimen); >90% on tacrolimus-based maintenance in the US
• Post-transplant complications: acute/chronic rejection, infections (CMV, EBV → PTLD), hypertension, dyslipidemia, malignancy, growth failure
• 5-year death-censored graft survival: 85.2% (deceased donor) vs 93.1% (living donor)

10. Prognosis

• Pediatric-onset ESKD carries 30-fold increased mortality compared with healthy peers
• Death rate on dialysis: 30× higher than general pediatric population
• Leading causes of mortality: cardiovascular disease (primary) and infections
• Successful transplantation allows normal schooling, catch-up growth, near-normal quality of life
• Early identification, multidisciplinary care, and aggressive management of modifiable risk factors are critical to improving outcomes

Summary for Exam

CKD in children = sustained loss of nephron mass → hyperfiltration → progressive fibrosis. The most common etiology is CAKUT in young children, glomerular disease in older children. Key complications are anemia, osteodystrophy, growth failure, and cardiovascular disease. Management is multidisciplinary: nutrition, BP control (ACE-I/ARB first-line), CKD-MBD management, ESAs, and ultimately dialysis/transplantation. Kidney transplantation is the treatment of choice for ESKD.