Pulse therapy

Application in rapidly progressive glomerulonephritis (RPGN)

Rapidly progressive glomerulonephritis is distinguished by an extremely unfavorable natural course with a fatal prognosis. Spontaneous remission is entirely impossible in this pathology. Therefore, clinicians are justified in using maximally aggressive therapy aimed at rapidly suppressing the activity of the destructive process in the kidneys.

The primary treatment method is pulse therapy—the administration of ultra-high doses of prednisolone combined with cytostatics.

In addition, the comprehensive management of RPGN includes:

• Plasmapheresis. The procedure is performed in full volume, removing up to five liters of plasma. A specific indication for plasmapheresis is the detection of high titers of specific anti-glomerular basement membrane antibodies in the patient's blood.
• The four-drug regimen. This is a potent combination consisting of cytostatics, glucocorticoids, heparin, and antiplatelet agents.

As replacement therapy in the acute period, parallel to active treatment, hemodialysis is performed to save the patient's life. Subsequently, kidney transplantation is considered a potential outcome and treatment option.

Treatment regimens for lipoid nephrosis

Lipoid nephrosis, also known as minimal change disease, is overwhelmingly a steroid-sensitive condition. This exact fact dictates a two-stage therapeutic approach.

Stage one — initial immunosuppression:

• Glucocorticoid pulse therapy is administered. Methylprednisolone is used, given as an intravenous drip.
• The dosage is 20 mg/kg per day, but the maximum allowable dose is capped at 1000 mg.
• Administrations are carried out for three consecutive days.
• Following the infusions, the patient is switched to maintenance oral therapy at a dose of 0.5–1.0 mg/kg per day.
• Courses of intravenous pulse therapy must be repeated every three to four weeks.

Stage two — in case of no effect or after diagnosis verification: If initial therapy fails to yield results, cytostatics, specifically cyclophosphamide, are strictly added to the glucocorticoids.

• Cyclophosphamide pulse therapy regimen: the drug is administered intravenously at a dose of 15 mg/kg per day. The first three administrations are given at two-week intervals, and all subsequent ones every three to four weeks.
• Alternative regimen: daily oral administration of cyclophosphamide at a dose of 2 mg/kg per day is prescribed. Treatment continues until a stable clinical improvement is achieved.

Alternative approaches and complication prevention

Clinical practice encounters steroid-resistant and steroid-dependent forms of diseases, as well as cases of individual intolerance to systemic glucocorticoids. In such situations (analogous to approaches used in IgA nephropathy), budesonide is prescribed.

This drug is distinguished by predominantly local (enterohepatic) metabolism, providing a significantly lower systemic steroid load on the body. Budesonide treatment requires gradual dose titration and very slow withdrawal, which must take place under strict monitoring of blood cortisol levels.

It is important to remember that with any glucocorticoid treatment—whether monotherapy or in combination with immunosuppressants—supportive preventive therapy is strictly mandatory. Its main goal is to prevent severe adverse events: the development and further progression of osteoporosis, as well as gastrointestinal tract injury.

When aggressive therapy is not indicated

Pulse therapy and other aggressive treatments are far from required for all immune pathologies. A striking example is the acute form of idiopathic thrombocytopenic purpura (ITP) in children.

According to the 2010 international consensus, if a child exhibits a mild decrease in platelet count, a watch-and-wait strategy is entirely permissible. In this case, physicians deliberately forego glucocorticoid pulse therapy, cytostatic therapy, and splenectomy.

However, there is a mandatory condition for using this tactic: it is only possible with a guarantee of round-the-clock patient access to qualified medical care and only after the complete diagnostic exclusion of any secondary causes of thrombocytopenia.

Class and exam questions

What else to study on this topic

• Rationale for the use of heparin and antiplatelet agents as part of the four-drug glomerulonephritis treatment regimen.
• Indications and technical features of plasmapheresis in high titers of anti-glomerular basement membrane antibodies.
• Rules for dose titration and the algorithm for safe budesonide withdrawal under cortisol level monitoring.
• Differential diagnosis of secondary causes of thrombocytopenia before choosing a watch-and-wait strategy in ITP.
• Indications for hemodialysis and kidney transplantation in the acute period of rapidly progressive glomerulonephritis.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.