Glucocorticoids and Control of Glomerular Filtration Rate

Introduction

Adrenocortical glucocorticoid is a steroid hormone used for treating renal diseases due to its immunomodulatory and immunosuppressive effects. It is a preferred treatment for immunosuppression in transplant patients. Studies have shown acutely or chronically glucocorticoids can increase the glomerular filtration rate (GFR). This article reviews the effect of glucocorticoid therapy on the glomerular filtration rate.

What Is the Glomerular Filtration Rate?

Glomerular filtration rate refers to the amount of filtrate formed in renal corpuscles of both kidneys per minute. The filtration rate is directly related to the pressure gradient within the glomerulus. Therefore, any pressure changes could alter the glomerular filtration rate. An increase in GFR can increase urine production.

The estimated glomerular filtration rate is a test to detect individuals with chronic kidney disease. The test usually detects waste products like creatinine within the urine.

What Are Glucocorticoids and Their Types?

Glucocorticoids are naturally occurring or man-made steroids that have specific uses. One of its functions is to interrupt inflammation by moving into cells to suppress proteins that promote inflammation. Additionally, they aid in the body’s response to stress and regulate the utilization of fat and sugar. The types of glucocorticoids are:

Natural: Cortisol.

Man-Made Drugs:

1. Prednisone.

2. Methylprednisolone.

3. Cortisone.

4. Hydrocortisone.

How Are Glucocorticoids Metabolized in the Kidney?

Glucocorticoid metabolism is a two-step process. Firstly, the hydrogen and or oxygen atoms are added. The second process includes conjugation. The kidney releases hydrophilic inactive metabolites through urinary excretion. Around 1 to 20 percent of unchanged glucocorticoids get excreted.

Intracellular metabolism by the enzyme controls the availability of glucocorticoids to bind with receptors. The enzymes are widely distributed in the glucocorticoid target tissue and are more prominent in the liver. The enzyme functions as a reductase by converting inactive cortisone to active cortisol.

How Do Glucocorticoids Exert Their Effect on the Kidney?

Cortisol is a naturally occurring glucocorticoid released by adrenal glands. The circulating level of cortisols is low at sleep onset and increases between 2 to 4 AM, reaching a peak a few minutes after awakening. The cortisol level declines throughout the day and reaches its low between 11 at night and 1 in the morning. However, synthetic glucocorticoids have longer half-life due to their low hepatic metabolism.

The glucocorticoids regulate electrolyte excretion in the kidneys. It increases water, diuresis, glomerular filtration rate, and renal plasma flow. There is also an increase in potassium excretion. The effect exerted by glucocorticoids is classified as genomic and or non-genomic. The genomic effects develop after a delay of hours and days, but non-genomic effects develop within minutes or seconds.

Glucocorticoids treat various renal disorders by suppressing the immune system or exerting its action on glomerulus function. But, the direct action of glucocorticoids on the kidney has yet to be adequately researched.

How Do Glucocorticoids Increase GFR?

According to animal studies, glucocorticoids cause vasodilatation of both preglomerular and efferent resistances, resulting in increased glomerular plasma flow, an essential factor for increasing GFR. However, the mechanism through which alteration to glomerular microcirculation develops remains unclear.

But, based on a recent hypothesis, a glucocorticoid may increase GFR by exerting effects on the protein catabolism to increase amino acid production. Due to this, glucocorticoids increase water and electrolyte delivery to the nephron. Glucocorticoids can also influence the sensitivity of the nephron to regulatory influences by determining the hemodynamic kidney state and its fluid delivery rate. The profound effect of glucocorticoids is the modification of immunological and cellular mechanisms responsible for glomerular injury.

What Are the Renal Disorders Treated With Glucocorticoids?

Glucocorticoids are not effective in managing all renal diseases. However, in some renal conditions, glucocorticoids may induce a short-term benefit. The efficacy of glucocorticoid on renal disorder depends on the dose, duration, and type of drug administered. Some of the renal disorders treated with glucocorticoids are:

• Minimal Change Disease: Prednisone treatment is the first line of therapy for children with minimal change disease. The dosage is gradually tapered and stopped when the disease reaches remission.

• Idiopathic Focal Segmental Glomerulosclerosis: Patients are treated with prednisone for at least 16 weeks, and the doses are gradually tapered after six months. Individuals developing glomerular sclerosis due to genetic, toxic, or viral causes must not be treated with glucocorticoids.

• IgA Nephropathy: A six-month therapy with glucocorticoids in patients with eGFR of more than 50 mL/min and proteinuria can reduce the deterioration of kidney function. Patients with impaired kidney function can be treated with low doses of glucocorticoid.

• Membranous Nephropathy: There is no evidence of glucocorticoid therapy curing membranous nephropathy. However, alternating treatment with glucocorticoids and alkylating agents for six months can increase remission and improve kidney function in the long term.

• Lupus Nephritis: Intravenous methylprednisolone and Cyclophosphamide or other drugs are used as the first line of therapy for treating flares. Oral prednisone is used as maintenance therapy.

What Is the Potential Adverse Effect Resulting From Glucocorticoid Use for Renal Disease?

The adverse effects related to glucocorticoids can range from benign to potentially life-threatening. Higher doses and prolonged glucocorticoid treatment can increase the incidence of side effects. Some of the side effects are:

• Hypertension.

• Hyperglycemia.

• Osteoporosis.

• Infections.

• Mood changes.

• Cushing syndrome.

Is Glucocorticoid Treatment a Double-Edged Sword for Renal Diseases?

Glucocorticoids have therapeutic effects on renal diseases like glomerulonephritis, nephrotic syndrome, and lupus nephritis. It also decreases immune-mediated response, inflammation, and proteinuria and improves renal outcomes. But in some cases, prolonged glucocorticoid therapy can induce apoptosis of renal cells that contribute to the development and progression of chronic kidney disease. Therefore, this results in declined kidney function and enhanced cardiovascular complications.

Hence, it can be concluded that glucocorticoid therapy is a double-edged sword that has beneficial and harmful influences on kidney function. The healthcare provider must carefully determine the benefits and possible risks of glucocorticoid use before initiating the therapy.

Conclusion

Glucocorticoids are used in the management of various diseases. The drugs have anti-inflammatory and immunosuppression effects and are also associated with adverse effects with prolonged use. In kidneys, glucocorticoid treatment has caused a reduction in glomerular filtration rate in human and animal studies, but the exact mechanism of this remains unclear and needs further research.