Residency · Residency · Medicine Pediatrics

Chronic Kidney Disease: Pediatric Considerations and Adult Progression

Overview

Chronic kidney disease (CKD) in children and adults differs in etiology, complications, and management priorities. Growth failure, bone development, and neurocognitive outcomes are unique pediatric concerns, while cardiovascular risk dominates adult CKD management. GFR estimation using pediatric (Schwartz) versus adult (CKD-EPI) equations has limitations in each population. The Med-Peds physician plays a critical role in CKD transition and lifelong management.

Definition and Staging (KDIGO, Universal)

CKD: kidney damage or GFR <60 mL/min/1.73m2 for >=3 months. Kidney damage: structural or functional abnormalities (proteinuria, hematuria, imaging abnormalities, histologic changes)

Albuminuria staging: A1 (<30 mg/g), A2 (30-300 mg/g), A3 (>300 mg/g) Combined GFR + albuminuria staging predicts risk of progression and cardiovascular events.

Etiology

Pediatric CKD

Congenital anomalies of the kidney and urinary tract (CAKUT): 40-50% of pediatric CKD; includes renal dysplasia, obstructive uropathy (posterior urethral valves), vesicoureteral reflux with reflux nephropathy. Hereditary nephropathies: Alport syndrome (COL4A3/4/5 mutations, progressive GN with hearing loss), polycystic kidney disease (ARPKD and ADPKD), nephronophthisis (ciliopathy, leading genetic cause of ESRD in children), cystinosis. Glomerular diseases: FSGS, lupus nephritis, IgA nephropathy, congenital nephrotic syndrome. HUS sequelae: particularly atypical HUS. Other: Wilms tumor post-nephrectomy, chemotherapy nephrotoxicity.

Adult CKD

Diabetes mellitus: approximately 40% of adult CKD/ESRD (diabetic kidney disease) Hypertension: approximately 25% (hypertensive nephrosclerosis) Glomerulonephritis: IgA nephropathy, FSGS, membranous, lupus. Polycystic kidney disease: ADPKD; most common genetic cause in adults. Other: interstitial nephritis, reflux nephropathy (childhood VUR), obstruction, renovascular disease.

GFR Estimation

Pediatric

Bedside Schwartz equation: eGFR = 0.413 x height (cm) / serum creatinine (mg/dL) Simple and widely used; reasonable accuracy for screening. Limitations: inaccurate in extremes of body habitus, low muscle mass, acute kidney injury. CKiD equation (Updated Schwartz): includes cystatin C, BUN, height; more accurate. eGFR = 39.1 x [height(m)/creatinine]^0.516 x [1.8/cystatin C]^0.294 x [30/BUN]^0.169 x 1.099^male x [height(m)/1.4]^0.188. Cystatin C-based equations: less affected by muscle mass; useful in children with neuromuscular disease or malnutrition. Nuclear GFR scan (99mTc-DTPA or iothalamate clearance): gold standard when precise GFR needed (transplant evaluation, drug dosing)

Adult

CKD-EPI 2021 equation: recommended standard; uses creatinine and/or cystatin C; RACE COEFFICIENT REMOVED in 2021 update. Removal of race coefficient: addresses structural racism concern that race-adjusted equations may have delayed referral and transplant listing for Black patients. Combined creatinine-cystatin C equation is most accurate. Cockcroft-Gault: still used for drug dosing in some settings; not recommended for CKD staging. Cystatin C: more accurate than creatinine-based estimates in elderly, sarcopenic patients, and extremes of body size.

Complications and Management

Growth and Development (Pediatric-Specific)

Growth failure: 30-50% of children with CKD have height below the 3rd percentile. Mechanisms: inadequate nutrition, metabolic acidosis, CKD-MBD (renal osteodystrophy), GH resistance (uremia-induced IGF-1 resistance), anemia, inflammation. Recombinant human growth hormone (rhGH): indicated for children with CKD and growth failure; 0.05 mg/kg/day SC; can increase height velocity by 2-3 cm/year; continue until final adult height or transplant. Nutritional optimization: adequate caloric intake (may need supplemental feeds via NG tube or gastrostomy); protein restriction is NOT recommended in growing children (unlike adults) Psychosocial and neurocognitive: CKD affects school performance, IQ, and social development; regular developmental assessment.

CKD-Mineral Bone Disorder (CKD-MBD)

Pathophysiology

Phosphate retention --> elevated FGF23 --> decreased 1,25(OH)2D --> hypocalcemia --> secondary hyperparathyroidism --> bone disease. FGF23 rises early (CKD stage 2-3) before PTH or phosphorus changes.

Pediatric Considerations

Renal osteodystrophy affects growing bones and growth plates. High-turnover bone disease (osteitis fibrosa): excess PTH causing bone resorption; rachitic changes at growth plates. Growth retardation, skeletal deformities, bone pain, fractures. Target PTH varies by CKD stage; avoid oversuppression (adynamic bone disease)

Adult Considerations

Osteoporosis, fracture risk, vascular calcification. Cardiovascular mortality: the leading cause of death in CKD; vascular calcification from phosphate-calcium product deposition. Calciphylaxis: rare but devastating ischemic skin necrosis.

Management (All Ages)

Phosphate binders: calcium carbonate/acetate (caution: vascular calcification risk), sevelamer (non-calcium based, preferred in adults), lanthanum, iron-based binders (sucroferric oxyhydroxide) Active vitamin D: calcitriol or alfacalcidol; to suppress PTH and treat hypocalcemia. Native vitamin D: ergocalciferol or cholecalciferol; maintain 25-OH vitamin D >30 ng/mL. Calcimimetics: cinacalcet (activates calcium-sensing receptor, suppresses PTH); FDA-approved for adults with secondary hyperparathyroidism; limited pediatric data. Parathyroidectomy: refractory severe hyperparathyroidism.

Anemia of CKD

Mechanism: decreased erythropoietin production, iron deficiency, chronic inflammation, uremic toxins. Target hemoglobin: 10-11.5 g/dL (avoid >13 g/dL per CHOIR and CREATE trials) Iron supplementation: IV iron preferred in CKD-4/5 and dialysis; target ferritin >100 (>200 in dialysis), TSAT >20%. Erythropoiesis-stimulating agents (ESAs): epoetin alfa, darbepoetin alfa; used after iron optimization; lowest effective dose. HIF-PHI (HIF-prolyl hydroxylase inhibitors): roxadustat, daprodustat; oral agents; approved for adults; stimulate endogenous EPO production; emerging role.

Cardiovascular Risk (Adult-Predominant)

CKD is an independent cardiovascular risk factor (equivalent to diabetes in risk) Management: aggressive BP control (<130/80, or <120/80 per SPRINT), ACEi/ARB (renoprotective, reduce proteinuria), statin (KDIGO: all adults >=50 with CKD should receive statin), SGLT2 inhibitors (dapagliflozin, empagliflozin -- renoprotective AND cardioprotective)

SGLT2 Inhibitors: A Paradigm Shift

Dapagliflozin (DAPA-CKD) and empagliflozin (EMPA-KIDNEY): reduce CKD progression and cardiovascular events regardless of diabetes status. Now standard of care for adults with CKD and proteinuria (eGFR 20-90 with UACR >=200 mg/g) Mechanism: reduce intraglomerular pressure, natriuresis, reduce inflammation. Pediatric use: not yet established; trials pending.

Other CKD Management

Metabolic acidosis: sodium bicarbonate supplementation to maintain serum bicarbonate >=22 mEq/L; slows CKD progression. Hyperkalemia: dietary restriction, patiromer, sodium zirconium cyclosilicate. Volume management: sodium restriction, diuretics. Vaccination: hepatitis B (higher doses may be needed), pneumococcal, influenza; avoid live vaccines if immunosuppressed.

Renal Replacement Therapy

Pediatric

Peritoneal dialysis: preferred modality for infants and young children; allows home-based treatment, better preservation of residual renal function. Hemodialysis: for larger children; requires vascular access (AV fistula preferred >20 kg) Transplantation: treatment of choice for pediatric ESRD. Preemptive transplant (before dialysis) associated with best outcomes. Living donor preferred (better graft survival, shorter wait time) Growth improves post-transplant but may not reach full genetic potential. Immunosuppression: tacrolimus, mycophenolate, corticosteroids (steroid minimization protocols)

Adult

Hemodialysis: most common modality in the US; in-center or home HD. Peritoneal dialysis: underutilized; comparable outcomes; better quality of life; preferred in selected patients. Transplantation: treatment of choice; significantly improves survival compared to dialysis. Waitlist management, donor matching, post-transplant care. Immunosuppression: similar agents; long-term complications include malignancy (PTLD, skin cancer), infection, cardiovascular disease, metabolic syndrome.

Transition of CKD Care

Adolescents with CKD face a critical transition period. Mortality spike in 18-24 year age group with ESRD (often related to non-adherence during transition) Structured transition programs: readiness assessment, self-management skills, medication knowledge, appointment scheduling. Med-Peds physicians are uniquely suited to bridge this transition gap.

<image>A comparative diagram showing the etiologies of CKD in pediatric versus adult populations. The pediatric panel shows CAKUT as the dominant cause (40-50%) with a schematic of renal dysplasia and obstructive uropathy, followed by hereditary nephropathies (Alport, PKD, cystinosis) and glomerular diseases. The adult panel shows diabetes (40%) and hypertension (25%) as dominant, with corresponding kidney pathology illustrations. A timeline arrow connects pediatric CAKUT to adult CKD, showing how childhood kidney disease progresses through adolescence into adult ESRD.</image>

<image>An infographic showing the unique complications of CKD in growing children versus adults. The pediatric panel highlights growth failure (declining growth chart with GH resistance mechanism), renal osteodystrophy at the growth plate (histologic illustration showing widened, irregular growth plate), neurocognitive effects, and pubertal delay. The adult panel shows cardiovascular disease (vascular calcification, LVH), anemia management, and dialysis modality selection. A central column shows shared complications: CKD-MBD, anemia, metabolic acidosis, hyperkalemia, and fluid overload.</image>

<image>A treatment timeline showing the evolution of renoprotective therapies across ages. Starting with ACE inhibitors and ARBs (established since the 1990s for both children and adults), progressing to the addition of SGLT2 inhibitors (2020s, transformative for adult CKD, pediatric trials pending), and emerging therapies (finerenone/non-steroidal MRA, GLP-1 agonists for diabetic kidney disease). Each therapy shows its mechanism of action at the glomerular level, landmark trial name, and magnitude of benefit. The bottom timeline shows the progressive adoption of these agents into CKD guidelines.</image>

Clinical Pearls

In children, CAKUT (congenital anomalies) is the leading cause of CKD, while diabetes and hypertension dominate in adults -- the workup priorities are completely different. Growth failure may be the first sign of CKD in children -- plot height velocity at every visit. The Schwartz equation (0.413 x height/creatinine) is the standard pediatric GFR estimation; the CKD-EPI 2021 equation (without race coefficient) is the adult standard. Protein restriction slows CKD progression in adults but is NOT recommended in growing children -- adequate protein is essential for growth. SGLT2 inhibitors are now standard of care for proteinuric CKD in adults regardless of diabetes status (DAPA-CKD, EMPA-KIDNEY) -- a paradigm shift in nephrology. Recombinant growth hormone is indicated for children with CKD-related growth failure and can significantly improve final adult height. The mortality spike in 18-24 year olds with ESRD is largely attributable to failed transition and medication non-adherence -- structured transition programs save lives. Preemptive kidney transplantation (before dialysis) achieves the best outcomes in both children and adults -- timely referral for transplant evaluation is essential. FGF23 rises before PTH or phosphorus in CKD -- it is the earliest biomarker of CKD-MBD.

References

• KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117-S314.
• Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629-637.
• Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737-1749.
• Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease (DAPA-CKD). N Engl J Med. 2020;383(15):1436-1446.
• Warady BA, Chadha V. Chronic kidney disease in children: the global perspective. Pediatr Nephrol. 2007;22(12):1999-2009.
• Mak RH, Cheung WW, Zhan JY, et al. Cachexia and protein-energy wasting in children with chronic kidney disease. Pediatr Nephrol. 2012;27(2):173-181.

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