Congenital Chronic Kidney Disease

Congenital chronic kidney disease is chronic kidney disease caused by abnormalities of kidney or urinary tract development that are present from birth. It is the leading cause of end stage kidney disease in children, accounting for about half of paediatric chronic kidney disease.

Most cases are congenital anomalies of the kidney and urinary tract: renal hypoplasia and dysplasia, multicystic dysplastic kidney, obstructive uropathy (posterior urethral valves, pelvi ureteric junction obstruction, vesico ureteric junction obstruction), vesico ureteric reflux with dysplasia, and bilateral or solitary kidneys with reduced nephron number.

Genetic basis. Monogenic causes account for 10 to 20% of cases and include HNF1B (renal cysts and diabetes syndrome), PAX2 (renal coloboma syndrome), SIX2 and SALL1 (branchio-oto-renal and Townes-Brocks), nephronophthisis ciliopathy genes, and Alport and tubulopathy genes. Maternal diabetes, prematurity, intrauterine growth restriction and drugs taken in pregnancy (ACE inhibitors, angiotensin receptor blockers, NSAIDs, mycophenolate) reduce nephron endowment.

Natural history. Low nephron number produces glomerular hyperfiltration, proteinuria and progressive sclerosis; decline often accelerates at puberty and in the second decade. Children with severe dysplasia may start renal replacement in infancy; others are diagnosed in adulthood with hypertension, proteinuria or a single small kidney.

Antenatal and neonatal

• Antenatal ultrasound: hydronephrosis, echogenic or cystic kidneys, bladder distension with keyhole sign (posterior urethral valves), oligohydramnios (lethal pulmonary hypoplasia, Potter sequence with flat facies and limb contractures).
• Neonatal: poor urinary stream, palpable bladder or kidneys, pneumothorax, respiratory distress, failure to pass urine within 24 hours, urinary tract infection.

Infants and children

• Failure to thrive, short stature, vomiting, polyuria and polydipsia, salt wasting with hyponatraemia and dehydration, recurrent urinary tract infection, enuresis, hypertension, rickets and bone deformity, anaemia, developmental delay.
• Associated anomalies: hearing loss, coloboma, cardiac, skeletal and genital abnormalities.

Red flags

• Anuria or no urine within 24 hours of birth, or bladder distension in a male infant.
• Febrile urinary tract infection with hydronephrosis, uraemic acidosis or hyperkalaemia in the neonate.
• Hypertension with a serum creatinine that does not fall within 2 weeks after birth.
• Failure to thrive with polyuria (salt wasting) in the first year.

• Antenatal ultrasound with measurement of renal length, parenchymal thickness, bladder, amniotic fluid; foetal MRI where the picture is unclear.
• Postnatal ultrasound: first scan after day 2 to 3 (early scan underestimates hydronephrosis because of oliguria), repeated at 4 to 6 weeks.
• Creatinine: neonatal creatinine reflects maternal values and normalises in term infants by 1 to 2 weeks (preterm infants later); use serial values and the nadir. Bedside Schwartz equation: eGFR (mL/min/1.73 m²) = 0.413 x height (cm) divided by creatinine (mg/dL), or 36.5 x height (cm) divided by creatinine (micromol/L). Cystatin C where muscle mass is abnormal.
• Urinalysis, urine protein:creatinine ratio, electrolytes, bicarbonate, calcium, phosphate, parathyroid hormone, alkaline phosphatase, haemoglobin, ferritin, blood pressure by age appropriate cuff.
• Micturating cystourethrogram: boys with bilateral hydronephrosis (posterior urethral valves), recurrent infection or high grade reflux suspected.
• Isotope renography: MAG3 with diuretic for obstruction (drainage half time above 20 minutes suggests obstruction); DMSA for scarring and split function, performed at least 4 to 6 months after infection.
• Genetic testing: gene panel or exome when extra-renal features, family history, cystic kidneys or progression; the result changes counselling and transplant donor choice.

Differential diagnosis

• Acquired renal failure of the neonate (perinatal asphyxia, renal vein thrombosis, nephrotoxins).
• Autosomal recessive polycystic kidney disease (large echogenic kidneys, hepatic fibrosis).
• Tubulopathies (Bartter, Gitelman, cystinosis) presenting with polyuria and growth failure.
• Congenital nephrotic syndrome.

First line: protect residual function

• Posterior urethral valves: bladder drainage with a urethral catheter or feeding tube at birth, then valve ablation when stable. Vesicostomy if the urethra is too small. Follow renal function and bladder function (valve bladder syndrome) throughout childhood.
• Antibiotic prophylaxis for high grade reflux, hydronephrosis and valves: trimethoprim 2 mg/kg at night from 6 weeks of age (amoxicillin 10 mg/kg once daily before 6 weeks); alternative nitrofurantoin 1 mg/kg at night from 3 months of age, avoided when eGFR is under 45. Treat breakthrough infection promptly and culture before antibiotics.
• Avoid nephrotoxins and dehydration. Treat hypertension: ramipril 1.25 to 2.5 mg daily started in older children and titrated, with potassium and creatinine checked in 1 to 2 weeks; avoid ACE inhibitors in infants under 1 month.

Growth and nutrition

• Energy intake 100 to 120% of requirement for age. Early nasogastric or gastrostomy tube feeding in infants with vomiting or poor intake; do not restrict protein in infants and young children.
• Sodium chloride supplements for salt wasting: 2 to 4 mmol/kg daily in divided doses, titrated to sodium and blood pressure. Free water must not be restricted in polyuric dysplasia.
• Sodium bicarbonate to keep bicarbonate at least 22 mmol/L (dose 1 to 2 mmol/kg daily, increasing as needed).
• Growth hormone: somatropin 0.045 to 0.05 mg/kg daily subcutaneously, started when height is under the 3rd centile after nutrition, acidosis and mineral disorder are corrected, and continued until transplantation or growth ends. Monitor for slipped femoral epiphysis, intracranial hypertension and glucose.

Complications

• Mineral and bone: cholecalciferol to keep 25-hydroxyvitamin D above 75 nmol/L; alfacalcidol 0.25 to 0.5 microg daily when parathyroid hormone is rising despite normal calcium and phosphate; phosphate control with dietary advice then calcium carbonate with feeds.
• Anaemia: epoetin alfa 50 to 100 units/kg three times weekly, with iron, target haemoglobin 100 to 120 g/L.
• Hypertension: aim for 24-hour ambulatory mean pressure under the 75th centile (under the 50th centile if proteinuric).

Kidney replacement therapy

• Peritoneal dialysis is the preferred modality in infants and young children. Pre-emptive transplantation when the child weighs about 8 to 10 kg and eGFR is under 15; living donor preferred. Obstructive uropathy needs bladder assessment before transplantation (urodynamics, clean intermittent catheterisation, bladder augmentation).

Referral and escalation. All infants with antenatal hydronephrosis of anteroposterior diameter 15 mm or more, bilateral disease, or abnormal bladder need paediatric nephrology and urology referral. Urgent review for anuria, bladder distension, febrile infection or hyperkalaemia above 6.0 mmol/L.

Special groups

• Adolescents: structured transition to adult care by 16 to 18 years, with adherence support. Pubertal growth spurt may require extra growth hormone before transplantation.
• Women with congenital kidney disease planning pregnancy: pre-conception counselling, stop ACE inhibitors and mycophenolate before conception, higher risk of pre-eclampsia and preterm delivery when eGFR is under 60.
• Genetic counselling: autosomal dominant inheritance with variable penetrance in HNF1B and PAX2; screen first degree relatives with ultrasound.