Chronic Kidney Disease (CKD) in Children

MD Pediatrics 10-mark Answer

DEFINITION

ETIOLOGY

Age-based Pattern (Key Exam Point):

• CAKUT (Congenital Anomalies of the Kidney and Urinary Tract) - most common overall
  • Renal hypoplasia/dysplasia
  • Obstructive uropathy (posterior urethral valves, UPJ obstruction)
  • Reflux nephropathy (chronic vesicoureteral reflux)
• Prune belly syndrome
• Autosomal recessive polycystic kidney disease (ARPKD)
• Cortical necrosis
• Congenital nephrotic syndrome (Finnish type)
• Renal vein thrombosis
• Hemolytic uremic syndrome (HUS)

• Glomerulonephritis (15-20%):
  • Focal segmental glomerulosclerosis (FSGS) - most common cause in steroid-resistant nephrotic syndrome
  • IgA nephropathy
  • Lupus nephritis (SLE)
  • MPGN, Henoch-Schonlein purpura nephritis
• Hereditary nephropathies (10-15%):
  • Alport syndrome (COL4A3/4/5 mutation)
  • Nephronophthisis (most common genetic cause of ESRD in children/adolescents)
  • Autosomal dominant PKD (ADPKD)
  • Cystinosis, primary hyperoxaluria

Pathophysiology of Progression:

1. Adaptive hyperfiltration in surviving nephrons
2. Compensatory mechanisms maintain homeostasis until ~60-70% nephron loss
3. Secondary progression driven by: systemic and intraglomerular hypertension, proteinuria, metabolic acidosis, hyperlipidemia, anemia, tubulointerstitial fibrosis, and systemic inflammation

CLINICAL FEATURES

Symptoms by System:

• Pallor, fatigue, exercise intolerance
• Poor appetite, nausea, vomiting
• Growth failure (hallmark in children - height velocity decreases)
• Polyuria/polydipsia (especially in tubulopathies/dysplasia)

• Oliguria or polyuria depending on stage
• Hematuria, proteinuria
• Hypertension (present in >50% at diagnosis)

• Hypertension
• Left ventricular hypertrophy (LVH) - present in ~50% of pediatric CKD
• Increased arterial stiffness
• Accelerated atherosclerosis

• Normochromic normocytic anemia (EPO deficiency)
• Bleeding tendency (platelet dysfunction)

• Renal osteodystrophy (rickets-like picture): bone pain, fractures, deformities
• Secondary hyperparathyroidism (elevated PTH)
• Hyperphosphatemia, hypocalcemia
• Vascular calcification

• Uremic encephalopathy (late): confusion, seizures
• Peripheral neuropathy
• Sleep disturbances, poor school performance

• Short stature - most clinically visible feature in children
• Growth hormone resistance (despite normal/elevated GH levels)
• Delayed puberty
• Hypothyroidism may coexist

• Metabolic acidosis (normal anion gap initially)
• Hyperkalemia
• Hyponatremia
• Hyperuricemia

• Pallor, sallow yellow appearance
• Pruritis (uremic)

INVESTIGATIONS

eGFR (mL/min/1.73 m²) = k × Height (cm) / Serum Creatinine (mg/dL)

• k = 0.413 (revised bedside Schwartz formula, 2009)

MANAGEMENT

1. Treating the primary cause where possible
2. Slowing CKD progression
3. Managing complications
4. Preparing for renal replacement therapy (RRT)

1. Hypertension Control

• Target BP < 50th percentile for age, sex, and height (or < 130/80 mmHg if adolescent)
• First-line: ACE inhibitors (e.g., enalapril, ramipril) or ARBs (e.g., losartan) - have antiproteinuric and renoprotective effects; preferred in proteinuric CKD
• Avoid dehydration; maintain adequate hydration especially in salt-losing nephropathies

2. Anemia Management

• Target hemoglobin: 10-12 g/dL (avoid >13 g/dL)
• Iron supplementation (oral or IV) - ensure adequate iron stores first
• Erythropoiesis-stimulating agents (ESA): Recombinant EPO (epoetin alfa/darbepoetin alpha)
  • Typically started when Hb < 10 g/dL with adequate iron stores

3. CKD-MBD (Renal Osteodystrophy)

• Restrict dietary phosphorus
• Phosphate binders: Calcium carbonate (with meals), sevelamer in older children
• Active Vitamin D: Calcitriol or alfacalcidol to suppress PTH and correct hypocalcemia
• Target: PTH 2-9x upper normal for stage (KDOQI targets vary by CKD stage)

4. Metabolic Acidosis

• Oral sodium bicarbonate or sodium citrate supplementation
• Target serum bicarbonate ≥ 22 mEq/L
• Treating acidosis also improves growth and reduces muscle catabolism

5. Growth Failure

• Optimize nutrition, treat acidosis, and manage CKD-MBD first
• Protein intake: At least 100% of DRI; limit to 140% (stages 2-3) and 120% (stages 4-5)
• Recombinant Growth Hormone (rGH): 0.05 mg/kg/day SC
  • Indicated if growth failure persists despite optimal management
  • Best response in predialytic CKD; initiate early
  • Final height improved by 10-15 cm with adequate therapy
  • Response superior before dialysis

6. Nutritional Management

• Calories: Age-appropriate, supplemented via NG tube or PEG if needed
• Sodium/water: Restrict in oliguric CKD; supplement in salt-losing nephropathy
• Potassium: Restrict when hyperkalemic
• Phosphorus: Dietary restriction
• Low protein diet NOT recommended in children (risk of growth impairment)

7. Dyslipidemia

• Dietary measures first; statins considered in adolescents if persistent

8. Renal Replacement Therapy (RRT) - Stage 5/GFR < 15

• Preparation begins at Stage 4 (GFR < 30)
• Options:
  • Peritoneal dialysis (PD): Preferred in infants and younger children; easier home management
  • Hemodialysis (HD): For older children, technical/compliance issues
  • Renal transplantation: Goal of management - preemptive transplantation (before starting dialysis) is ideal; best outcomes
• Living related donor transplant preferred

9. Recent Updates (UpToDate 2024-2025)

• SGLT2 inhibitors (dapagliflozin, empagliflozin): Emerging evidence for renoprotection in adolescents with CKD and proteinuria; Lava et al. 2024 systematic review shows promise but pediatric data still limited
• KDIGO 2024 reinforces albuminuria as a key CKD progression marker alongside GFR staging
• Cardiovascular risk reduction (early RAAS blockade, BP control) emphasized from CKD stage 2 onwards
• Growth hormone therapy response: Initiating rGH during predialytic phase maximizes final adult height

COMPLICATIONS SUMMARY (Mnemonics for Quick Recall)

• H - Hypertension / cardiovascular disease
• A - Anemia
• G - Growth failure
• E - Electrolyte disturbances (K⁺, Na⁺, HCO₃⁻)
• C - CKD-MBD (renal osteodystrophy)
• A - Acidosis (metabolic)
• N - Neurological (uremic encephalopathy, peripheral neuropathy)

PROGNOSIS

• Pediatric CKD has better outcomes than adult CKD due to reduced cardiovascular comorbidity
• Growth failure and cardiovascular disease are chief sources of morbidity
• Preemptive renal transplantation offers best long-term outcome
• Patients on long-term dialysis have a significantly increased morbidity and mortality compared to transplant recipients