Patients with minimal-change disease are characteristically of preschool age. Boys are more frequently affected; the male-to-female ratio is 6:4. Of these children, 23% have hematuria and 18% have hypertension. In most cases, the hematuria is microscopic. The cholesterol values are severely elevated, usually in the range of 300 to 500 mg/dL; serum cholesterol levels <250 mg/dL are unusual. The serum creatinine values may be elevated, although the elevations are usually mild. The hallmark of minimal-change disease is that this form of nephrotic syndrome responds to daily prednisone therapy with total clearing of the proteinuria. Furthermore, 90% of the patients with minimal-change disease who will respond to prednisone therapy do so within 4 weeks.

Once a patient has responded to daily prednisone therapy, the standard is to continue prednisone on alternate days for 4 weeks, then discontinue the steroid therapy. Unfortunately, relapse in minimal-change disease is the rule rather than the exception. Patients who have responded to prednisone therapy with total clearing of the proteinuria can be divided into three subgroups according to their course:

The first group poses little difficulty. Patients in the second group can be treated with daily prednisone therapy. Most pediatric nephrologists continue the daily therapy for 3 to 4 days after the proteinuria has cleared, after which alternate-day prednisone therapy is given for 2 to 3 weeks. For patients who relapse only one to three times each year, the prednisone exposure is acceptable, and side effects are minimal. Patients in the third group are difficult to manage. Because neither the side effects of steroid therapy nor the edema associated with nephrosis is acceptable, a number of alternative therapies are utilized. Cyclophosphamide or chlorambucil alone without other therapy offers a 70% chance of a 2.5- to 3-year remission. Likewise, daily cyclosporine therapy can be given instead of prednisone and
may maintain patients with minimal-change disease in remission. The advantages of these therapies must be weighed against their side effects.

The side effects of cyclophosphamide include:

The side effects of chlorambucil include:

The side effects of cyclosporine include:

The lymphomas associated with chlorambucil therapy for frequently relapsing nephrotic syndrome occurred in patients who had received a total dose of chlorambucil >14 mg/kg. The dosage currently administered is 0.01 mg/kg per day for 8 weeks, making a total dose of 8.4 mg/kg. No tumors have been reported since the standard therapy was lowered to this total dose.

The choice of agent depends on the patient’s ability to tolerate side effects. Most youngsters would rather not take cyclophosphamide because of the hair loss, but this is a temporary phenomenon, and the hair does grow back.

The long-term prognosis of patients with minimalchange disease is excellent. In most cases, the disease remits and the proteinuria and edema resolve.

Two important complications of this disease are worthy of note:

Patients in whom nephrotic syndrome recurs and ascites develops are susceptible to primary peritonitis. The most common organisms causing this are Streptococcus pneumoniae and Escherichia coli. This diagnosis must be excluded in any patient with nephrotic syndrome who is receiving steroid therapy and who presents with abdominal pain, with or without fever.

Vascular thromboses or pulmonary emboli may develop in patients with active nephrotic syndrome, who are in a hypercoagulable state. These entities must be considered in patients with nephrotic syndrome who present with pain in an extremity, a change in the color of an extremity, or a sudden onset of chest pain.

When the proteinuria does not clear totally after 4 weeks of daily steroid therapy, other diagnoses and renal biopsy must be considered. The continuation of daily prednisone therapy in such cases exposes patients to the side effects of steroid therapy without much hope of benefit, so that they simultaneously experience the worst of the disease and the worst of the treatment.

The most likely diagnosis in young patients who meet the criteria for minimal-change disease but fail to respond to prednisone therapy is FSGS. The clinical characteristics of patients with this histologic diagnosis are shown in Table 12.2. It is difficult to distinguish between FSGS and minimal-change disease on the basis of a patient’s clinical signs and symptoms at presentation. A large percentage of patients with FSGS have hematuria (33%) and hypertension (48%). As in minimal-change disease, the serum cholesterol is severely elevated in FSGS, and the creatinine level may also be elevated. The only consistent feature that distinguishes patients with FSGS is that their proteinuria persists despite prednisone therapy. Only 7% of patients with FSGS respond initially to prednisone therapy. The prognosis for patients with FSGS is poor, with 50% to 70% progressing to chronic renal failure during a 5- to 10-year time frame. Although a number of treatment options are available, including highdose cyclosporine and high-dose intravenous methylprednisolone, the success rates with these options do not exceed 50% to 60%.

Unfortunately, FSGS is increasing in importance because the incidence is rising, particularly in the adolescent and young adult African-American population. A study done in Houston, Texas, examined the incidence of FSGS in renal biopsies prior to 1990 and compared it with those done from 1990 to 1998. The percentage of biopsies that showed FSGS increased from 23% to 47% over this time frame. In children older than 8 years, the incidence of FSGS doubled from 33% to 67%. The incidence of FSGS in adults is also increasing, especially in young African-American men; the reasons for this sudden increase in this specific population are not clear.

Additionally, this disease recurs in a transplanted kidney in approximately 30% of patients who have undergone transplantation.