Most children with NS experience relapses that need treatment with prednisolone. This treatment is normally given as a full dose of 60 mg/m² until the child has been free of protein in the urine for 3 days and then 40 mg/m² every other day for a further 4 weeks. This is normally not a major problem if the children respond reasonably quickly to the treatment and the dose can thus be rapidly changed to an alternate-day regimen. The steroid toxicity can be managed in most of these cases. Some 30 % of children will, however, have frequent relapses resulting in many courses of prednisolone every year. These children are at high risk of developing intolerable steroid toxicity. They are often treated with alternate-day steroids at as low a dose as possible to keep them in remission. The alternate-day treatment was shown to be more successful than treatment during 3 consecutive days per week [6]. An alternate-day dose of up to 1 mg/kg did not have any long-term side effects on children’s growth [7]. However, treatment with other immunosuppressive drugs is often needed to achieve the aim of minimizing the number of relapses and of full steroid courses.

A further somewhat overlapping group of children will develop steroid-dependent NS. They relapse while still on, or immediately after, a weaning dose of the drug. This can often be managed by keeping the child on an alternate-day dose that is low enough to keep them well but that does not have any discernible side effects [6, 7]. Many of these children will also need treatment with another drug to reduce their tendency to relapse.

A small group of children with NS do not respond to the initial dose of prednisolone; they are defined as having steroid-resistant NS (SRNS) [1]. A common definition is there is no reduction in urinary losses of protein despite a 4-week course of prednisolone. Three pulses of intravenous methylprednisolone are often given to ensure the child has received the drug. In some cases it is suspected that the absorption of the drug has been inadequate owing to the often-occurring massive edema including intestinal edema. Further treatment protocols of SRNS usually include several doses of methylprednisolone [8, 9].

Patients with SRNS are in a far more difficult subgroup of NS than those who respond to steroids. They will need a kidney biopsy. The two most common biopsy diagnoses are minimal-change nephropathy (i.e., nothing significant is seen) and focal and segmental glomerulosclerosis. Children with focal and segmental glomerulosclerosis have a much more severe disease that often leads to end-stage renal disease requiring renal transplantation. Many of these children unfortunately have disease recurrence after the transplant, which can lead to rapid loss of the transplanted kidney [10].

A number of other immunosuppressive drugs are used in these children to try to achieve remission and to prevent the development of renal failure. This treatment can sometimes convert the condition of the children into being steroid sensitive.

The most common form of postinfectious GN is poststreptococcal GN. These children typically present with hematuria, often macroscopic, mildly impaired kidney function, and somewhat raised blood pressure 1–2 weeks after a streptococcal infection [11]. The diagnosis is strengthened by the confirmation of the streptococcal infection, by the presence of rising streptococcal antibodies in serum, or a positive throat culture. Patients develop reduced complement C3 and C4 levels in blood, which should normalize within a few months.

Poststreptococcal GN is a self-limiting disease that should heal without any long-term sequelae [11]. Treatment with steroids is thus not needed in a vast majority of cases. A small minority will develop a rapidly progressing GN where the biopsy will show crescentic nephritis. These rare children might benefit from treatment with steroids (see next section).

Lupus nephritis is the most common severe nephritis in childhood. Its onset is mainly in prepubertal or pubertal girls who develop severe systemic symptoms over the course of a few weeks with fatigue, loss of appetite, weight loss, joint pain, and rash (typically malar). More than 50 % of children with lupus will develop nephritis characterized by microscopic hematuria and proteinuria and some impairment of the kidney function [12]. Many present with overt nephrotic syndrome with massive proteinuria, low serum albumin, and edema.

All these children should have a kidney biopsy to classify the degree of kidney involvement from Class I to V, and those with Class III–V nephritis should receive treatment focusing on the nephritis [13].

Treatment of lupus nephritis is generally done in two phases, induction and maintenance treatment, and steroids have always played a major role in both. Treatment of lupus nephritis is normally initiated with three infusions of high-dose methylprednisolone and then continued with a high dose of oral prednisolone; 2 mg/kg/day capped at 60 mg/day [13].

No consensus exists on how quickly to wean the steroid dose or on how low the dose should be during the maintenance phase. Some centers continue daily steroids at doses around 15 mg/day, while others aim for alternate-day dosing, and yet other centers try to stop the prednisolone when the child is well. Aggressive treatment with other immunosuppressive drugs, such as mycophenolate mofetil, cyclophosphamide, azathioprine, and rituximab, is essential so as to use as few steroids as possible [14].

Severe side effects from steroids are clearly a major problem for children and young people with lupus. Because of this, a relative steroid-free induction treatment of lupus nephritis has been attempted in adult patients with seemingly good results. Treatment started with three pulses of methylprednisolone together with two infusions of the CD20 antibody rituximab and oral mycophenolate mofetil [15]. No further steroid treatment was given. A randomized trial of this regimen is now underway including both adults and children.