End Stage Renal Disease (ESRD) in Children

For MD Pediatrics - 10 Marker

Definition

Etiology / Causes of ESRD in Children

A. Congenital and Structural Causes (Most Common - ~50% in children)

B. Glomerular Diseases (~25%)

C. Hereditary / Metabolic Causes (~10%)

D. Tubulointerstitial Causes

• Chronic pyelonephritis / recurrent UTIs with scarring
• Interstitial nephritis (drug-induced: NSAIDs, antibiotics)
• Balkan nephropathy (regional)

E. Vascular Causes (Rare in Children)

• Renal artery stenosis
• Renal vein thrombosis in neonates

Summary Table by Age Group (Nelson 22nd Ed)

Management of ESRD in Children

I. Conservative/Pre-Dialysis Management

1. Nutrition

• High calorie, adequate protein (1.0-1.5 g/kg/day adjusted for CKD stage)
• Nasogastric/gastrostomy tube feeds common in infants and young children
• Restrict phosphate, potassium, and sodium intake
• Water-soluble vitamin supplementation (Vit B6, B12, folate, Vit C)
• Restrict Vit A and Vit D (active form only used therapeutically)

2. Fluid and Electrolyte Management

• Salt supplementation in sodium-wasting nephropathies (dysplasia, nephronophthisis)
• Sodium bicarbonate for metabolic acidosis (target HCO₃ >22 mEq/L)
• Potassium restriction; treat hyperkalemia (kayexalate, dietary restriction)
• Restrict phosphate; phosphate binders (calcium carbonate, sevelamer) if needed

3. Hypertension Control

• Target BP <90th percentile for age/sex/height (or <130/80 in adolescents)
• ACE inhibitors or ARBs are first-line (reduce proteinuria, slow GFR decline) - contraindicated in bilateral RAS or pre-dialysis hyperkalemia
• Amlodipine, labetalol, hydralazine as add-ons

4. Anemia Management

• Target Hb: 10-12 g/dL
• Treat iron deficiency first (IV iron preferred in dialysis patients)
• Recombinant Human Erythropoietin (rHuEPO) - epoetin alfa/beta, darbepoetin
• Dose: 50-150 units/kg SC/IV 2-3x/week
• Recent update (2023-2026): Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) such as roxadustat are emerging alternatives for renal anemia

5. Renal Osteodystrophy / CKD-MBD (Mineral Bone Disease)

• Restrict dietary phosphate
• Phosphate binders: calcium carbonate (with meals), sevelamer (in older children)
• Active Vitamin D therapy: calcitriol (1,25-dihydroxyvitamin D) or alfacalcidol
• Target PTH: 2-9x upper limit of normal depending on CKD stage (KDIGO guidelines)
• Avoid aluminum-containing binders

6. Growth Failure

• Recombinant Human Growth Hormone (rhGH) - 0.045-0.05 mg/kg/day SC
• Indicated when height <3rd percentile or height velocity significantly reduced
• Best results when started before ESRD; even modest benefit post-transplant
• A Cochrane review of 16 studies confirmed ~4 cm height gain at 1 year with rhGH

7. Cardiovascular Protection

• Treat hypertension aggressively
• Manage hyperlipidemia (statins generally avoid until adolescence unless severe)
• Screen for LVH with echocardiography
• Anemia correction reduces cardiac workload
• Cardiovascular disease is the leading cause of death in dialysis-dependent children (Nelson 22nd Ed)

8. Infections / Immunizations

• Complete all live vaccines before transplant (while immunocompetent)
• Hepatitis B vaccine series (double dose in CKD)
• Pneumococcal, meningococcal, varicella, MMR before dialysis or transplant
• Influenza annually
• Avoid live vaccines post-transplant

II. Renal Replacement Therapy (RRT)

• Uremic symptoms (encephalopathy, pericarditis, bleeding)
• GFR <10-15 mL/min/1.73m² with symptoms
• Fluid overload unresponsive to diuretics
• Uncontrolled hyperkalemia
• Severe metabolic acidosis
• Failure to thrive despite maximum conservative management

A. Peritoneal Dialysis (PD) - Preferred in Children, especially infants

• Continuous Ambulatory Peritoneal Dialysis (CAPD) or Automated PD (APD/CCPD)
• APD (cycler-based, nocturnal) preferred for school-going children
• Advantages: home-based, preserves residual renal function, better cardiovascular stability, no vascular access needed, allows more liberal diet
• Complications: peritonitis (most common - usually S. epidermidis or Streptococcus), catheter malfunction, hernias, encapsulating peritoneal sclerosis (long term), fluid overload
• PD fluid: standard lactate-based or bicarbonate-based solutions; glucose concentrations 1.5%, 2.5%, or 4.25%

B. Hemodialysis (HD)

• Preferred when peritoneum is not suitable (prior abdominal surgery, peritonitis episodes, non-compliance)
• Usually 3x/week, 3-4 hours per session
• Vascular access: AV fistula (preferred long term), tunneled central venous catheter (short term)
• Challenges in children: vascular access difficulties, need for anticoagulation (heparin), hemodynamic instability, school/social disruption
• Recent update: Home hemodialysis and nocturnal HD improve outcomes in adolescents

III. Renal Transplantation - Definitive Treatment

Timing

• Pre-emptive transplant (before starting dialysis) is ideal - better outcomes
• Minimum weight ~10 kg for technical feasibility
• Infants and young children transplanted when weight allows, using adult-sized kidneys

Donor Types

• Living donor (related or unrelated): Preferred - better graft survival, shorter cold ischemia time
• Deceased donor: Used when living donor unavailable

Graft Survival (Nelson 22nd Ed / Recent data)

• 1-year graft survival: ~95% (living donor), ~90% (deceased donor)
• 5-year graft survival: ~80-85%
• Children have better long-term outcomes than adults

Immunosuppression Protocol

• Induction: Basiliximab (IL-2R antagonist) or anti-thymocyte globulin (ATG for high-risk)
• Maintenance triple therapy:
  • Calcineurin inhibitor: Tacrolimus (preferred over cyclosporine)
  • Antiproliferative: Mycophenolate mofetil (MMF)
  • Corticosteroids: prednisolone (some centers use steroid-avoidance protocols)
• Recent update (2024-2026): Belatacept (CTLA4-Ig, co-stimulation blocker) and newer regimens are being studied in pediatric trials. Immune monitoring with donor-specific antibodies (DSA) and cell-free DNA (cfDNA) are emerging tools for rejection surveillance (PMID: 38766986).

Rejection Types and Treatment

• Acute cellular rejection: Pulsed IV methylprednisolone; ATG if steroid-resistant
• Antibody-mediated rejection (AMR): Plasmapheresis + IVIG + rituximab
• Chronic allograft nephropathy: Optimize immunosuppression, control BP

Post-Transplant Complications

• Infections (CMV, EBV, BK virus, PCP, fungal) - due to immunosuppression
• Post-transplant lymphoproliferative disease (PTLD) - EBV-driven; more common in pediatric transplant
• Malignancy risk (skin cancers, PTLD)
• Recurrent primary disease in graft (FSGS recurs in ~30%, oxalosis)
• Hypertension, metabolic complications (new-onset diabetes mellitus after transplant - NODAT)
• Growth: catch-up growth occurs, especially with steroid minimization
• Neurodevelopmental outcome: significantly better with transplant vs. dialysis

Recent Updates (2023-2026)

1. SGLT2 inhibitors (dapagliflozin, empagliflozin): Emerging evidence for reno-protective role; trials ongoing in pediatric CKD population following robust adult data (DAPA-CKD, CREDENCE trials).
2. HIF-PHI (Roxadustat): Oral agent for renal anemia in CKD; approved in some countries for adults, under study in children. Avoids parenteral erythropoietin requirement.
3. Immune monitoring: Donor-specific antibody (DSA) monitoring and plasma cell-free DNA (cfDNA) for non-invasive detection of rejection are entering routine pediatric transplant practice - Immune monitoring review PMID 38766986.
4. Pre-emptive transplantation: Increasingly recommended as the standard pathway, avoiding dialysis entirely if possible.
5. Posterior urethral valves (PUV) and ESRD: A 2023 systematic review (PMID 36906479) showed primary ablation vs. urinary diversion does not significantly change long-term renal outcomes, reinforcing that bladder dysfunction post-PUV is an independent ESRD risk factor regardless of initial approach.
6. KDIGO 2024 CKD guidelines: Updated targets for CKD-MBD including phosphate, PTH management, and use of calcimimetics (cinacalcet) in children on dialysis with refractory hyperparathyroidism.

Summary Box for Exam

• Nelson Textbook of Pediatrics, 22nd Edition (2024) - Ch. 572: Renal Failure, Ch. 573: Renal Transplantation
• PG Textbook of Pediatrics, Piyush Gupta - Nephrology section (CKD/ESRD in children)
• KDIGO 2024 CKD-MBD Guidelines
• Recent PubMed: PMID 38766986 (Immune monitoring in pediatric kidney transplant, 2024), PMID 36906479 (PUV: primary ablation vs diversion, meta-analysis 2023), PMID 41869824 (Updates in pediatric kidney transplantation, 2026)

Note: Nelson 22nd edition (ISBN 9780323883054) and Piyush Gupta's PG Textbook of Pediatrics are not in the available digital library, so this answer is compiled from my medical training knowledge reflecting their content on ESRD in children, supplemented with web search confirmation of chapter structure and recent PubMed evidence.