Congenital and infantile nephrotic syndrome

NS presenting at birth or within 1st 3 mo of life can be defined as congenital NS (CNS). Late onset, between 3 mo-one y of age = called infantile NS.

Congenital & infantile nephrotic syndrome (NS)

 

NS presenting at birth or within 1^st 3 mo of life can be defined as congenital NS (CNS). Late onset, between 3 mo-one y of age = called infantile NS. Most cases with congenital or infantile NS have genetic background of renal disease with poor outcome.

 

Genetic-mutations responsible for most cases of congenital/infantile NS include:

·         NPHS1, that encodes nephrin (Nph) (key component of the podocyte slit diaphragm) & responsible for Finnish-type congenital NS.  

·         NPHS2, encoding podocin (protein that interacts with Nph at slit diaphragm) & responsible for familial FSGS.  

·         WT1, encoding transcription tumour suppressor (protein engaged in renal/gonadal growth) & responsible for Denys-Drash syndrome.  

Other aetiologies of congenital/infantile NS include less common genetic mutations, idiopathic NS, & secondary causes e.g., infections (e.g., syphilis or toxoplasmosis), toxins e.g., mercurial intoxications.  As cases of congenital/infantile NS mostly caused by genetic mutation + failure to respond to immunosuppressive (Im/m) agents, genetic screening is suggested to confirm the Dgx before commencing such therapy.

 

 

Treatment:  NS in CNF is usually resistant to steroids + im/m agents, as CNF is NOT an immunologic disease. Moreover, these agents could be detrimental due to the high liability to infection. Study: 21 CNF infants, found 63 verified & 62 suspected septic episodes seen over one y. follow-up. Standard ttt includes daily or EOD albumin infusion + gamma globulin replacement + nutritional high-protein + low-salt diet+vitamin + thyroxine replcement, & infection prophylaxis + anti- thrombotic measures. Diet provided via tube feeding or parenteral nutrition. The rate of intercurrent sequelae still high, with growth & developmental retardation. A variety of interventions to limit protein excretion including unilateral nephrectomy (Nc)+ combined (ACEi + indomethacin), that decreases intraglomerular pressure > declined protein excretion. Bilateral Nc may be resorted to limit persistent massive protein losses before the evolution of RF.

If Nc is performed, DX is provided until ptn the weight of 8-9 kg, when RTx can be considered. The European Registry for Children on RRT (ESPN/ERA-EDA) documented an excellent 5-y ptn (91 %) & graft (89 %) survival for Finnish & non-Finnish NPHS1 ptns that was comparable to ptn & graft survival for CAKUT (congenital anomalies of kidney & UT). NS may develop in the allograft. Series: 65 ptns received 77 KTx, 23 episodes of recurrent NS seen in 13 ptns e 19 grafts. All 13 ptns had Fin-major/Fin-maj genotype that’s associated with absent Nph. 8 had a circulating anti-Nph AB. Recurrent NS leads lost allograft. Plasmaephresis + cyclophosphamide + anti-CD20 AB > successful in controlling the recurrent nephrosis due to anti- Nph AB.