The authors report the cases of two young children with almost simultaneous onset of SRNS and IDDM in early childhood. This could not be explained by diabetic microangiopathy as it usually takes several years to develop.1 2
Furthermore, both children initially presented with nephrotic syndrome and 2 weeks after commencing prednisolone, they were diagnosed with diabetes mellitus. There have been reports in adults of rare cases of glomerulopathies that are not diabetic nephropathies in the early phases of IDDM but rather immune complex glomerulonephritis such as IgA nephropathy and C1q nephropathy, which are often associated with significant proteinuria and nephrotic syndrome resistant to immune-suppressor treatment.11 12
However, renal biopsies in our cases did not show immune complex glomerulonephritis.
There are several reports in the literature of SSNS coexisting with IDDM in children,5–9
but in none of the reports was treatment influenced by renal biopsy results which all showed MCD.5–9
However, daily steroid tapering was suggested in preference to alternate day steroids to allow better glycaemic control. Therefore, the indications for renal biopsy in nephrotic children with and without IDDM were suggested to be similar.13
Similarly, SSNS with MCD was reported in a patient with type 2 diabetes mellitus.14
It was accompanied by mild worsening of renal function. Steroid treatment induced complete remission of the nephrotic syndrome and recovery to normal renal function. The reported patient experienced two relapses, but was sensitive to steroid14
and eventually achieved persistent remission after a course of chlorambucil.
Interestingly, in a report of two young women who developed nephrotic syndrome within 2 weeks of presenting with IDDM, neither received steroids; in one of them the oedema resolved spontaneously while the other required diuretics.15
One of these patients had a renal biopsy which showed changes consistent with MCD on electron microscopy but no evidence of diabetic glomerulosclerosis.
The occurrence of MCD causing SSNS is rarely seen in IDDM patients presenting with nephrotic syndrome. Furthermore, in a search for an explanation of the coexistence of MCD in IDDM patients, the pathogenesis was linked to the shared human leucocyte antigen (HLA) typing in both IDDM and renal disease.5 6 16
In our cases we did not test for HLA typing, however, our patients were negative for the genetic mutations underlying SRNS (podocin NPHS2 and WT1). The coexistence of the two diseases may be due to chance but could perhaps be caused by as yet undiscovered underlying genetic predisposing factors.
Our patients’ pathology initially showed MCD but both had SRNS. It is generally accepted that SRNS is usually caused by non-MCD and is mostly due to focal segmental glomerulosclerosis (FSGS).17
In our cases the diagnosis of FSGS was not made on the first biopsies and so could have been missed or not present at all. The follow-up biopsy in the second case demonstrated more prominent glomerular changes which were consistent with class IIa diabetic nephropathy according to the 2010 classification of diabetic nephropathy of the Research Committee of the Renal Pathology Society.10
It is important to distinguish changes arising from diabetic nephropathy from other primary glomerular diseases developing on top of diabetic nephropathy in situations such as the second biopsy of case 2 where the changes were similar to early features of FSGS. It could not be distinguished at this stage whether the glomerular sclerotic lesions were caused by idiopathic FSGS or diabetic nephropathy.18
In another case series, a patient with juvenile onset IDDM presented with SRNS and associated mild diabetic glomerulosclerosis, and later developed Grave's disease.8
The association between IDDM and thyroid disease could be explained by an immunomediated underlying disease. Both of our cases had normal thyroid function tests. However, they did not have long duration of follow-up.
The observed poor control of diabetes mellitus in our two patients could be attributed to corticosteroid therapy. In both patients steroid treatment was accompanied by hyperglycaemia and glycosuria but not academia or ketonuria. However, the diagnosis of IDDM was confirmed as the diabetes did not resolve after tapering prednisolone therapy.
As mentioned earlier, diabetic microangiopathy was unlikely in our cases at presentation, although diabetes causes mostly glomerular disease. IDDM is associated with progressive increase in urinary albumin excretion to a nephrotic range proteinuria over 5–12 years, followed by hypertension and a decline in glomerular filtration rate (GFR) after a mean duration of 17 years of diabetes in patients at risk. The pathological lesions of diffuse glomerular sclerosis or nodular intercapillary glomerular sclerosis are typically seen in biopsies from patients with advanced diabetic nephropathy. There is a close correlation between the expansion of the glomerular mesangium and the declining filtration surface area, as well as the declining GFR in affected patients.19
Inadequate glycaemic control during the first 5 years of diabetes seems to accelerate time to occurrence, whereas a young age at diabetes onset seems to prolong the time to the development of microvascular complications.1
Therefore, the occurrence of nephrotic syndrome at presentation in both patients could not be explained by IDDM. However, in the second case the presence of proteinuria could have accelerated the appearance of early diabetic changes which was controlled by the immune suppression and ACE inhibitor used for the nephrotic status.
- The authors report two cases of almost simultaneous incidence of steroid resistance nephrotic syndrome and insulin-dependent diabetes mellitus in two young children.
- To our knowledge this is the first report of such concurrence in young children.