The severity and treatment of congenital nephrosis vary depending on the causative mutation [8]. Congenital nephrotic syndrome of the Finnish type is caused by two truncating mutations in the NPHS1 gene leading to massive proteinuria which is unresponsive to conservative treatment. In Finland, the treatment modality has traditionally been daily albumin infusions until bilateral nephrectomy at the body weight of about 7 kg, followed by peritoneal dialysis and kidney transplantation when body weight has reached 10 kg. The present study compares the outcome and prevalence of disease and treatment-related complications in infants treated with the traditional method and those treated with delayed nephrectomy, short period of hemodialysis and KT. Patients with delayed nephrectomy had better neurocognitive development and they required enteral tube feeding less frequently than infants with early nephrectomy. We found no difference in the number infection episodes, thromboembolic events, surgical complications, or growth between the two groups. These findings favor delayed nephrectomy. To the best of our knowledge, this is the first study comparing different CNS treatment protocols within one center.
Massive proteinuria and nephrotic syndrome are known to increase the risk for infections and thromboembolic events [9, 10]. These complications have been connected to urinary loss immunoglobulins and factors involved in the coagulation system, especially antithrombins, and the need for central venous line [11]. The reported prevalence of infections and thrombotic complications among nephrotic infants is around 13 to 54% depending on patient material [9–13]. In the present study, thrombosis was diagnosed in four patients in each group (0.19 and 0.29 per patient year). The relatively low prevalence of thrombosis complications may be partly explained by routine use of warfarin as an antithrombotic prophylaxis and omega-3 fish oil both during nephrosis and dialysis. The latter is used predominantly to improve to lower triglyceride levels; however, it has been shown to affect the coagulation system and that way, reduce the risk for thrombosis [14].
Peritoneal dialysis has previously been recommended as primary dialysis modality after nephrectomy as it preserves the central venous access and is thought to decrease the number of infections and thrombosis compared to hemodialysis [8]. Hölttä et al. have reported the largest CNS material so far, showing 68.3% on PD in non-Finnish type patients and 100% in infants with CNS of the Finnish type [15]. In the present study, hemodialysis was successfully used in almost all the patients in group 2. Our protocol was planned to include only a short period of dialysis, which probably explains the low number of dialysis-related complications. Despite our encouraging results, if delayed access to KT is expected, for example, due to lacking potential living donation, we would still recommend peritoneal dialysis as the primary dialysis modality.
Eating difficulties are a well-known problem among children with chronic kidney disease in all age groups, but the influence of uremia-induced nausea and vomiting on growth and development is most detrimental during infancy [16]. In the present study, we found that the need for enteral tube feeding was more common in the group with early nephrectomy, which suggests that the reason for poor eating is the prolonged dialysis and uremia rather than other CNS-related factors. Although the infants with delayed nephrectomy had significantly higher P-Crea at nephrectomy, none of them had developed severe uremia despite prolonged massive proteinuria. This may at least partly explain their better ability to eat without enteral tube support when compared to group 1. Many oral motor skills that are necessary for development of normal feeding skills mature during the first year of life [17]. Disturbances in this developmentary process may lead to long-lasting problems and delay in the development of eating skills [17]. We did not find any differences in physical growth between the groups up to one year after KT, since the hypercaloric diet and the use of NGT or G-tube tube ensure the growth of the infants. However, the need for NGT or G-tube feeding has a great influence on quality of life and parental coping.
We have previously reported delayed motor development in 26.6% of the CNF patients during their early childhood [18]. The possible factor affecting early motor development include long-lasting hypoproteinemia and altered muscle structure regarding CKD. In the present study, motor development was assessed to be better in the group with late nephrectomy. This finding suggests that the delay in motor development and possible impaired physical performance capacity may be more affected by a long dialysis period and CKD rather than nephrosis.
A clear caveat of the study is its retrospective nature and the small number of patients. The strength of the study, however, is that a single-center study enables adherence to uniform protocols. Previous retrospective studies in bigger patient materials have shown comparable long-term outcome in CNS patients treated with early nephrectomy compared to patients with conservative treatment or delayed nephrectomy [11, 15]. The studies have compared infectious complications and growth during dialysis and the overall survival. However, they have mainly compared infants with severe form of NPHS1 gene mutation and patients with other CNS causing mutations. The severity of CNS symptoms and the patient outcome is likely to be affected by the underlaying mutation. In the present study, all patients had either Fin-major or Fin-minor mutation in NPHS1 gene and therefore we presume that the patient outcome is mainly affected by the given treatment.
In conclusion, according to the present results, CNF patients treated with delayed nephrectomy and short dialysis prior to KT preserve their ability to eat and have shorter dependence on NGT/G-tube-assisted feeding. Longer period of nephrosis did not increase the risk for thromboembolic events, infections, or growth problems compared to patients with early nephrectomy. These findings should be interpreted with caution due to the relatively small study population.