Basics
Description
- The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 clinical practice guidelines defines chronic kidney disease (CKD) as abnormalities of kidney structure or function, present for >3 months (except in infants <3 months of age) with implications for health.
- Criteria for CKD include the following:
- Markers of kidney damage such as albuminuria, urine sediment abnormalities, electrolyte and other abnormalities due to tubular disorders, abnormalities detected by histology, structural abnormalities detected by imaging, and history of kidney transplantation
- Decreased glomerular filtration rate (GFR) <60 mL/min/1.73 m2
- CKD is classified based on cause, GFR category, and albuminuria category.
- GFR categories
- G1: GFR ≥90
- G2: GFR 60-89
- G3a: GFR 45-59
- G3b: GFR 30-44
- G4: GFR 15-29
- G5: GFR <15
- Albuminuria categories-albumin to creatinine ratio in mg/g
Epidemiology
Incidence
~5-12 cases per year per million of age-related population
Prevalence
Prevalence of CKD has been reported to be between 21 and 74 cases per million of age-related population from various studies in Europe and Latin America.
Risk Factors
- Risk factors for congenital renal disease include genetic and environmental factors (maternal diabetes, exposure to medications such as ACE inhibitor/NSAIDs)
- Low birth weight, prematurity, and rapid weight gain in early childhood increase risk of CKD.
- Hypertension and proteinuria increase risk of CKD progression.
Pathophysiology
- Low nephron mass: leads to hyperfiltration injury
- Cardiovascular: Hypertension secondary to activation of renin-angiotensin system, fluid overload, and anemia from erythropoietin deficiency contribute to cardiovascular morbidity.
- Bone and mineral bone disorder of CKD: Decreased synthesis of vitamin D1,25 OHD leads to hyperparathyroidism and bone disease.
- Growth: Metabolic acidosis, anemia, and perturbations in the growth hormone insulin-like growth factor-1 (GH-IGF-1) axis lead to poor growth.
Etiology
- Congenital anomalies of kidney and urinary tract (CAKUT) constitute ~60% of cases of childhood CKD and include the following:
- Renal dysplasia/hypoplasia
- Obstructive uropathy (posterior urethral valves, prune belly syndrome)
- Cystic and hereditary disorders
- Autosomal recessive and dominant polycystic kidney disease
- Juvenile nephronophthisis (cystic)
- Alport syndrome, cystinosis, oxalosis, congenital nephrotic syndrome (hereditary)
- Glomerular diseases
- Focal segmental glomerulosclerosis (FSGS)
- Hemolytic uremic syndrome (HUS)
- Systemic lupus erythematosus (SLE)
- IgA nephropathy
- Others-membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, pauci-immune glomerulonephritis
Commonly Associated Conditions
Several syndromes have associated anomalies of the kidney and urinary tract such as DiGeorge syndrome, Alport syndrome, Alagille syndrome, branchio-oto-renal syndrome, Townes-Brocks syndrome, and Bardet-Biedl syndrome.
Diagnosis
History
- Past history
- Birth history for oligohydramnios, perinatal events
- Recurrent urinary tract infections (UTIs)
- Enuresis
- Family history
- Renal disease
- Hearing impairment
Signs and Symptoms
- Poor growth
- Poor appetite
- Fatigue, malaise
- Headache (if hypertensive)
- Polyuria (in congenital abnormalities)
- Oliguria
Physical Exam
- General
- Short stature
- Decreased weight for age
- Pallor
- Fetid breath
- Elevated blood pressure (BP)
- Head, ears, eyes, nose, and throat
- Retinal changes
- Presence of preauricular tags, branchial cysts
- Hearing deficit
- Chest
- Heart
- Flow murmur
- Gallop
- Pericardial rub
- Abdomen
- Palpable kidneys
- Suprapubic mass
- Extremities
- Neurologic system
- Developmental delay
- Altered mental status
- Hypotonia
- Irritability
Diagnostic Tests & Interpretation
Lab
- Serum chemistries: azotemia, hyperkalemia, acidemia, hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase
- CBCs: normocytic anemia with low reticulocyte count (CKD stage 3, GFR <60)
- Urinalysis: isosthenuria, proteinuria, hematuria
- Intact parathyroid hormone: elevated
- 25-vitamin D: often low
- GFR measurement
- Inulin clearance is the gold standard for GFR measurement but is not practical. A simple and commonly used method to estimate GFR in children >1 year of age with CKD is the CKiD bedside equation, an update to the traditional Schwartz formula.
- The calculation is already corrected for surface area and does not require a urine collection: height (cm) — 0.413 correction factor/Pcreat in mg/dL.
Imaging
- Chest x-ray: pulmonary edema, cardiomegaly
- Bone films: delayed bone age, rickets, osteomalacia, osteitis fibrosa
- Renal ultrasound: small echogenic kidneys, cystic kidneys, hydronephrosis
Diagnostic Procedures/Other
A renal biopsy is indicated for diagnosis of acquired or glomerular kidney diseases such as FSGS. It is not necessary when there is radiologic evidence of structural/congenital cause of CKD such as small or echogenic kidneys.
Differential Diagnosis
- Differentiate acute kidney injury from CKD
- Usually, CKD is insidious and associated with poor growth, delayed puberty, rickets, polyuria, and anemia. The kidneys may be small on renal ultrasound.
Treatment
Medication
- Phosphate binders (e.g., calcium carbonate, calcium acetate, sevelamer; avoid aluminum)
- 1,25-dihydroxy vitamin D and/or 25-hydroxy vitamin D
- Alkali therapy (e.g., sodium bicarbonate/citrate)
- Antihypertensive therapy
- ACE inhibitors (renoprotection)
- Recombinant erythropoietin
- Ferrous sulfate (if iron deficient)
- Recombinant human growth hormone
Additional Therapies
Renal replacement therapy (dialysis/renal transplantation) is indicated when GFR is <10 mL/min/1.73 m2 or when medical management fails to control signs/symptoms of CKD.
Issues for Referral
Pediatric primary care physicians should observe patients with CKD in consultation and with assistance from a pediatric nephrologist.
Complementary & Alternative Therapies
Treatment of hypertension, proteinuria (with ACE inhibitor/angiotensin receptor blocker [ARB]), and dyslipidemia delays progression of CKD.
Alert
During episodes of gastroenteritis, infants with CKD may be prone to dehydration because they have obligatory polyuria due to a concentrating defect. Do not use urine output level or specific gravity of urine as indices for hydration. If hospitalized, fluid levels considered "maintenance"¯ may be insufficient due to polyuria.
Surgery/Other Procedures
- Transplantation: In some cases, a preemptive transplant may be offered instead of dialysis.
- Consider arteriovenous fistula or graft placement for patients who will require long-term hemodialysis.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
Children with CKD need close outpatient follow-up every 1-3 months, depending on the level of GFR to monitor BP, growth, and lab tests.
Diet
Restrictions mandated by condition
- Phosphate
- Potassium
- Sodium (indicated if patient has edema/hypertension)
- Fluid (indicated in conditions related to oliguria)
Prognosis
Prognosis of CKD depends on the cause of CKD. CKD progression leads to need for renal replacement therapy. Prognosis of children with renal transplantation is excellent with 5-year survival of >85%.
Complications
- Growth retardation is particularly severe when CKD develops in the 1st year of life. Growth failure may be secondary to poor nutrition, bone disease, acidosis, or a direct effect on the GH-IGF-1 axis.
- Mineral and bone disorders may be seen early in association with CKD, manifesting with growth failure, bowing of the lower extremities, and slipped epiphysis. Vitamin D deficiency and secondary hyperparathyroidism are the major factors leading to bone disease.
- Anemia develops secondary to decreased erythropoietin secretion and decreased erythrocyte survival. The anemia is a normocytic variant associated with a low reticulocyte count.
- Cardiovascular disease including left ventricular hypertrophy (LVH) and coronary artery disease often develops in early adulthood. Uncontrolled hypertension, anemia, hyperlipidemia, and hyperparathyroidism all contribute to this leading cause of death in adults with CKD.
- Neurodevelopmental delay increases in children with CKD. This is probably due to uremic effects on the development of the brain.
- Hypertension may be seen in some patients with CKD due either to hyperreninemia or hypervolemia.
- Platelet abnormalities, protein-calorie malnutrition, and immunologic disturbances are also seen in patients with uremia.
Additional Reading
- Friedman AL. Etiology, pathophysiology, diagnosis, and management of chronic renal failure in children. Curr Opin Pediatr. 1996;8(2):148-151. [View Abstract]
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Inter Suppl. 2013;3:1-150.
- Schwartz GJ, Mu ±oz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629-637. [View Abstract]
- Staples A, Wong C. Risk factors for progression of chronic kidney disease. Curr Opin Pediatr. 2010;22(2):161-169. [View Abstract]
Codes
ICD09
- 585.9 Chronic kidney disease, unspecified
- 753.3 Other specified anomalies of kidney
- 585.3 Chronic kidney disease, Stage III (moderate)
- 753.15 Renal dysplasia
- 585.5 Chronic kidney disease, Stage V
- 753.1 Cystic kidney disease, unspecified
- 585.1 Chronic kidney disease, Stage I
- 585.4 Chronic kidney disease, Stage IV (severe)
- 585.2 Chronic kidney disease, Stage II (mild)
- 585.6 End stage renal disease
- 753.16 Medullary cystic kidney
ICD10
- N18.9 Chronic kidney disease, unspecified
- Q63.9 Congenital malformation of kidney, unspecified
- N18.3 Chronic kidney disease, stage 3 (moderate)
- Q61.4 Renal dysplasia
- N18.2 Chronic kidney disease, stage 2 (mild)
- N18.5 Chronic kidney disease, stage 5
- Q61.8 Other cystic kidney diseases
- N18.1 Chronic kidney disease, stage 1
- N18.6 End stage renal disease
- Q61.5 Medullary cystic kidney
- N18.4 Chronic kidney disease, stage 4 (severe)
SNOMED
- 236425005 Chronic renal impairment (disorder)
- 44513007 Congenital anomaly of the kidney (disorder)
- 433144002 Chronic kidney disease stage 3 (disorder)
- 204949001 Renal dysplasia (disorder)
- 431857002 Chronic kidney disease stage 4 (disorder)
- 204958008 Nephronophthisis (disorder)
- 431855005 Chronic kidney disease stage 1 (disorder)
- 46177005 End stage renal disease (disorder)
- 431856006 Chronic kidney disease stage 2 (disorder)
- 433146000 Chronic kidney disease stage 5 (disorder)
- 82525005 Congenital cystic kidney disease (disorder)
FAQ
- Q: Which OTC medications should be avoided in children with CKD?
- A: NSAIDs, pseudoephedrine (if patient hypertensive), enemas containing phosphate, and antacids containing magnesium or aluminum should not be taken.
- Q: Can children with CKD receive immunizations?
- A: Children with CKD should especially receive all necessary immunizations because some vaccines are contraindicated after transplantation. In some cases, booster immunizations are necessary because of an inadequate response to the initial series (e.g., hepatitis B virus, measles, mumps, rubella; varicella). Additionally, children with CKD should receive the polyvalent pneumococcal vaccine after age 2 years.
- Q: When is recombinant human erythropoietin indicated?
- A: Generally, this medication should be considered when the hematocrit level is <33% (Hgb <11.0 g/dL).