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

Urinary Tract Infections in Children: Classification and Management of First Episode

MD Pediatrics - 10-mark Answer

DEFINITION

CLASSIFICATION

A. By Site of Infection

B. By Severity / Risk

C. By Episode

D. By Fever (Clinically Practical - Nelson/EAU 2025)

• Febrile UTI - fever, implies upper tract involvement, requires full evaluation
• Afebrile UTI - no fever, implies cystitis; lower evaluation threshold

E. By Age (Piyush Gupta / Indian Context)

• Neonates (< 1 month): Hematogenous spread common; male preponderance; often septicemia; urgent evaluation
• Infants (1-24 months): Most common age for first UTI presentation with non-specific symptoms (fever, irritability, poor feeding)
• Preschool (2-5 years): Girls > boys; cystitis symptoms begin to appear
• School age (> 5 years): Similar to adult pattern; girls >> boys; symptomatic UTI predominates

EPIDEMIOLOGY

• UTI is the most common serious bacterial infection in children < 2 years with fever
• Cumulative incidence: ~8% in girls, ~2% in boys (Shaikh et al., meta-analysis)
• E. coli accounts for ~80% of cases; others include Klebsiella, Proteus, Enterococcus, Pseudomonas (latter two often in complicated UTI)
• Proteus is more common in boys (associated with prepuce colonization)

CLINICAL FEATURES

DIAGNOSIS

Urine Collection:

• Toilet-trained: Clean-catch midstream urine (preferred)
• Non-toilet-trained, stable: Clean-catch attempt first; if not possible - catheterization
• Sick infants: Suprapubic aspiration (SPA) or catheterization (any growth on SPA is significant)
• Bag specimen: Not acceptable for culture due to high contamination rate

Diagnostic Criteria (ISPN 2023 / Bagga):

• Urine culture ≥ 10⁵ CFU/mL (clean catch) OR ≥ 10⁴ CFU/mL (catheter) of single organism
• Positive dipstick (LE or nitrite) OR microscopy (≥ 5 WBC/HPF)
• Both culture AND urinalysis required for definitive diagnosis (AAP 2011)

Supporting Investigations:

• CBC, CRP/ESR (elevated suggest pyelonephritis)
• Serum creatinine/BUN (assess renal function, especially if toxic/atypical)
• Urine R&M, culture and sensitivity

ALGORITHM FOR MANAGEMENT OF FIRST EPISODE UTI

CHILD PRESENTS WITH FIRST EPISODE UTI
               |
    ┌──────────┴──────────┐
  FEBRILE UTI          AFEBRILE UTI
(pyelonephritis)       (cystitis)
    |                      |
    ▼                      ▼
URINE SAMPLE          URINE SAMPLE
(catheter/SPA in     (clean catch)
 infants)
    |
    ▼
STEP 1: ASSESS SEVERITY
    ├── TOXIC / UNABLE TO TAKE ORALS / < 3 months
    │         → ADMIT + IV ANTIBIOTICS
    │
    └── NON-TOXIC, TOLERATING ORALS, > 3 months
              → ORAL ANTIBIOTICS (OUTPATIENT)

Step 1 - Antibiotic Treatment

• Age < 3 months
• Toxic, high fever, unable to tolerate orals
• Septicemia / urosepsis
• Obstructive uropathy (urgent drainage needed)
• Failed oral therapy after 48-72 hours

• Ceftriaxone: 50-75 mg/kg/day once daily (first-line)
• Ampicillin + Gentamicin: neonates (covers Enterococcus)
• Piperacillin-tazobactam: for Pseudomonas/resistant organisms

• 3rd generation cephalosporins: Cefixime 8 mg/kg/day OD or Cefpodoxime 10 mg/kg/day BD (first-line for febrile UTI, ISPN 2023)
• Amoxicillin-clavulanate: 30-40 mg/kg/day in 2-3 doses (alternative)
• 1st/2nd gen cephalosporins (cephalexin): for cystitis only in adolescents
• Avoid: amoxicillin alone (high E. coli resistance); trimethoprim-sulfamethoxazole (significant resistance in India)
• Duration (ISPN 2023): Acute pyelonephritis - 7-10 days; Cystitis - 3-5 days

Key update: Oral antibiotics are equally effective as parenteral for non-toxic febrile UTI (AAP 2011, ISPN 2023 - Strong recommendation, Level I evidence)

Key update: Treatment should be initiated within 48-72 hours of fever onset to reduce risk of renal scarring (ISPN 2023)

Step 2 - Imaging Algorithm After First UTI

ALL CHILDREN WITH FIRST FEBRILE UTI
              |
              ▼
    RENAL BLADDER ULTRASOUND (RBUS)
    (within 1-2 weeks; urgently if toxic)
              |
    ┌─────────┴─────────┐
  NORMAL RBUS        ABNORMAL RBUS
       |            (hydronephrosis, dilated
       ▼             ureter, small/dysplastic
  AGE < 2 YEARS?    kidney, thick bladder wall)
  Non-E. coli UTI?        |
  Recurrent UTI?          ▼
       |            MCU / VCUG INDICATED
    ┌──┴──┐
   YES   NO
    |      |
    ▼      ▼
   MCU   NO FURTHER
(after  IMAGING
 UTI    ROUTINE
treat-   VCUG NOT
 ment    REQUIRED
 2-3 wk) (AAP/ISPN)

1. Abnormal RBUS (hydronephrosis, ureteral dilation, scarring)
2. Age < 2 years with non-E. coli UTI
3. Recurrent febrile UTI (≥ 2 episodes)
4. Atypical UTI features
5. Clinical suspicion of VUR (bilateral renal abnormality, family history)
6. Poor response to treatment at 48-72 hours

• Acute-phase DMSA is NOT recommended routinely (ISPN 2023 - Strong recommendation)
• Indicated only in: recurrent UTI with high-grade VUR (grades 3-5) to assess scarring
• Late DMSA (4-6 months after UTI) to detect permanent scarring if clinically needed

Step 3 - VUR Management

• Indicated in: BBD (Bladder-Bowel Dysfunction), high-grade VUR (IV-V), recurrent UTI with anatomic risk
• NOT indicated after first UTI with normal urinary tract (ISPN 2023, AAP 2011)
• Agents: Nitrofurantoin 1-2 mg/kg/day nocte (> 1 month), or Trimethoprim 1-2 mg/kg/day nocte

Step 4 - Follow-up

• Repeat urine culture at 48-72 hours if clinically not improving (to assess treatment failure/resistance)
• After treatment completion: urine culture NOT routinely required if asymptomatic
• Emphasize fever testing with subsequent febrile illnesses (not routine monthly cultures - AAP)
• Bladder-bowel dysfunction (BBD) - constipation, dysfunctional voiding - must be identified and treated as it is a major risk factor for recurrent UTI

RECENT UPDATES (UpToDate / 2024-2026)

COMPLICATIONS

• Renal scarring → Hypertension (long-term)
• Chronic kidney disease (from repeated scarring with high-grade VUR)
• Xanthogranulomatous pyelonephritis (rare, chronic)
• Perinephric abscess
• Septicemia/Urosepsis (especially neonates, immunocompromised)

MNEMONIC: "FACTS" for First UTI Management

• F - Find cause (culture before antibiotics, collect urine correctly)
• A - Antibiotics (oral if non-toxic; IV if < 3 months/toxic/unable to tolerate)
• C - Check RBUS (all children after first febrile UTI)
• T - Target imaging selectively (MCU only if RBUS abnormal, < 2 yr, non-E. coli, recurrent)
• S - Surveillance (follow up; treat BBD; prophylaxis only for high-risk)

• Nelson's Textbook of Pediatrics 22nd Ed., Ch. 575 (Urinary Tract Infections)
• Piyush Gupta Textbook of Pediatrics, 3rd Ed.
• Hari P, Meena J, Bagga A et al. ISPN Evidence-based CPG for UTI and VUR. Pediatr Nephrol 2024 [PMID: 37897526]
• AAP Clinical Practice Guideline for febrile UTI in children 2-24 months. Pediatrics 2011 (reaffirmed 2016)
• Yang S et al. Kidney USG after first febrile UTI - meta-analysis. JAMA Pediatrics 2023 [PMID: 37252727]
• Gnech M et al. EAU/ESPU paediatric UTI guidelines 2025. J Pediatr Urol 2026 [PMID: 40615247]
• Nelson Z et al. WikiGuidelines UTI consensus. JAMA Netw Open 2024 [PMID: 39495518]