The pathogenetic role of infections in nephrotic syndrome

G. Ardissino, M. Belingheri, U.O. di Nefrologia e Dialisi Pediatrica, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italia

Steroid sensitive idiopathic nephrotic syndrome (INS) is a common disease in childhood (2-7 cases/year/100.000 [1]) for which there is no specific treatment except for immunosuppressive therapy. The incidence of relapses presents a growth-related decrease. In particular the number of relapses per year decreases from 1.07 to 0.79 and 0.56 moving from childhood to teenage and adulthood [2]. The disease then could be regarded to as a transient maturation disturbance of the immune response rather the a hyperactivity of the immune system in need of immunosuppression.
Infections are important stimuli for inducing the development of the immune system in young children towards the adult condition. It has been well documented an inverse correlation between rate of infections early in life and risk of allergic diseases [3].
Based on these considerations and with analogies with allergic diseases, it can be hypothesized that children who suffer of INS might have been exposed to few infections and that this low exposure might have played a role in the immune system derangement and in the genesis of the nephrotic syndrome itself. It can be useful to emphasize that an increase in IgE level in patients with INS [4] and the association with atopy [5] has been documented and this might, indirectly, support the analogy with allergic diseases and a possible common pathophysiological pathway.
In this theoretical setting, immunosuppression with steroids, although necessary, might oppose the natural process of immune system maturation and would maintain the condition responsible for the disease. Moreover, the overprotection of children from any source of infections, typically characterizing the caregivers of children with INS (sometimes supported by suggestions from pediatricians) would also be responsible for maintaining the underlying disease process.
If the present working hypothesis would be confirmed new therapeutical strategies based upon immunostimulation might provide a faster course of the disease.
We would like to explore the possibility to promote an epidemiological investigation (case-control design), among interested researchers on the working hypothesis that patients with INS have been expose to fewer common infections compared to controls by means of a very simple ad hoc questioner (see attached) to be administered to parents of children with INS at onset (first event) investigating how many infective episodes the child has had prior to INS onset.

  1. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003; 362: 629-639.
  2. Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P, Lesavre P, Chauveau D, Knebelmann B, Broyer M, Grünfeld JP, Niaudet P. Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis. 2003 Mar;41(3):550-7.
  3. Lluis A, Schaub B. Lesson from the farm environment. Curr Opin Allergy Clin Immunol. 2012 Apr;12(2):158-63.
  4. Shao YN, Chen YC, Jenq CC, Hsu HH, Chang MY, Tian YC, Fang JT, Yang CW. Serum immunoglobulin E can predict minimal change disease before renal biopsy. Am J Med Sci. 2009 Oct;338(4):264-7
  5. Abdel-Hafez M, Shimada M, Lee PY, Johnson RJ, Garin EH. Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis. 2009 Nov;54(5):945-53.


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