Polycystic kidney disease and inherited nephropathies: Case

This neonate has the perinatal form of autosomal recessive polycystic kidney disease, confirmed by the homozygous PKHD1 mutation. The PKHD1 gene encodes fibrocystin, a protein found on the primary cilium of collecting duct and biliary epithelial cells, and its defect explains the simultaneous involvement of the kidneys and the biliary tract. The bilateral enlarged echogenic kidneys with oligohydramnios, the respiratory distress from pulmonary hypoplasia, and the severe hypertension are the classical presenting features. His thrombocytopenia, splenomegaly and portal hypertension on Doppler confirm congenital hepatic fibrosis, which is a defining feature of ARPKD that demands the same clinical attention as the kidney disease. [2]

Clinical findings

The clinical picture is one of multisystem disease from a single gene defect. The massively enlarged kidneys are palpable as bilateral flank masses and are distending his abdomen. The pulmonary hypoplasia from the oligohydramnios sequence has necessitated mechanical ventilation from birth, and the restricted lung capacity is compounded by the enlarged kidneys splinting the diaphragm. His blood pressure of 98 over 65 in a term neonate is significantly elevated, and severe hypertension is one of the most dangerous early complications of ARPKD because it can cause cardiac failure, intracranial haemorrhage and accelerated kidney damage. [1]

The hepatic involvement is already clinically apparent. The thrombocytopenia of 75 times 10 to the 9 per litre with palpable splenomegaly indicates hypersplenism from portal hypertension, and the Doppler findings confirm the congenital hepatic fibrosis that accompanies ARPKD because the fibrocystin defect affects the biliary epithelium. This is the dual challenge of ARPKD: the kidney disease causes hypertension, electrolyte disturbance and progressive renal failure, while the hepatic fibrosis causes portal hypertension that may result in life-threatening variceal bleeding. Management must address both simultaneously, with nephrology and hepatology working as one team. [1]

Investigations and staging

The diagnosis is confirmed by the homozygous PKHD1 mutation on genetic testing. The renal ultrasound shows the characteristic bilateral enlarged echogenic kidneys with loss of corticomedullary differentiation and a radial array of small cysts, as described in the international imaging consensus for cystic kidney diseases in children. The abdominal ultrasound with Doppler confirms the portal hypertension, and I would arrange upper gastrointestinal endoscopy to screen for oesophageal and gastric varices, because variceal bleeding is a leading cause of morbidity and mortality in children with congenital hepatic fibrosis. [4]

The renal function assessment uses the estimated GFR, which in neonates is based on creatinine interpreted with postnatal age and maternal renal function. The creatinine of 130 micromoles per litre at day 5 reflects the neonatal physiological elevation compounded by the kidney disease, and I would monitor the trend rather than rely on a single value. Blood pressure, electrolytes including sodium for salt wasting, and acid-base status need close monitoring. The full blood count tracks the thrombocytopenia and any developing anaemia, and liver function tests and coagulation profile monitor the hepatic synthetic function. [1]

Management and outcome

The immediate management prioritises the three threats to this neonate's survival: respiratory failure, severe hypertension and fluid and electrolyte disturbance. He needs continued mechanical ventilation with strategies that accommodate the restricted lung capacity, and I would involve the neonatal team in planning prolonged respiratory support. The hypertension requires treatment with intravenous antihypertensives, titrated carefully because neonates with ARPKD are exquisitely sensitive to volume and blood pressure changes. I would transition to oral antihypertensives, typically a calcium channel blocker, with an ACE inhibitor added cautiously once renal function and electrolytes are stable, because ACE inhibition is nephroprotective in cystic kidney disease. [1]

Fluid and electrolyte management must account for the polyuria and salt wasting. The diseased tubules cannot concentrate urine, so this neonate is at risk of dehydration and hypernatraemia if fluid losses are not replaced. I would use daily weights, strict input-output charting, and serum and urine electrolytes to guide sodium supplementation and fluid prescription. Adequate nutrition is essential for growth, and I would involve a renal dietitian and consider nasogastric feeding to ensure sufficient calories and sodium, because failure to thrive is a major problem in infantile ARPKD and growth in the first year is a strong predictor of long-term outcome. [2]

The hepatic fibrosis management runs in parallel. I would institute surveillance with regular platelet counts, liver function tests, abdominal ultrasound with Doppler, and endoscopic screening for varices, because portal hypertension may declare itself with variceal bleeding even as the kidney disease is being managed. Prophylactic beta-blocker therapy or endoscopic prophylactic treatment may be indicated if varices are found. The hepatology team must be involved from the outset, and the coordination between nephrology and hepatology is central to the long-term management of ARPKD. [1]

Looking ahead, if this child progresses to kidney failure with severe portal hypertension, combined liver-kidney transplantation is the definitive treatment that addresses both complications simultaneously. This approach corrects the portal hypertension by replacing the fibrotic liver and the kidney failure by providing a functioning graft, and it has been shown to have favourable outcomes in experienced centres, with the advantage of avoiding the risk of recurrent variceal bleeding after isolated kidney transplant. I would begin the conversation with the family early about the likely long-term trajectory, the role of transplantation, and the possibility of combined liver-kidney transplant, while emphasising that modern intensive care has substantially improved survival for neonates with ARPKD and that many children stabilise and grow before requiring renal replacement therapy. [3]

The family needs genetic counselling because ARPKD is autosomal recessive with a 25 percent recurrence risk in each pregnancy. Both parents are carriers of a PKHD1 mutation, and prenatal diagnosis and preimplantation genetic diagnosis are options for future pregnancies. I would refer the family to a clinical geneticist and offer cascade testing of siblings if applicable, ensuring that the counselling is sensitive, informative and supportive throughout what is a profoundly stressful experience for the family. [1]