Aristolochic Acid Nephropathy - Symptoms, Diagnosis, and Treatment

Introduction:

Aristolochic acid nephropathy (AAN) is a fast-progressing interstitial nephritis that can cause end-stage renal disease and urothelial cancer. It was first discovered in a group of individuals who had taken Chinese herb-infused diet pills in Belgium. Since both herbs have the same common name in PinYin (Han Fang Ji and Guang Fang Ji), and since one herb can be used in place of the other in traditional Chinese medicine regardless of their botanical classification. This nephropathy was initially known as Chinese-herb nephropathy (CHN), appeared to be the dramatic consequence of the substitution of Stephania tetrandra by Aristolochia fangchi rich in aristolochic acid (AA). New cases of AAN were frequently reported following the release of the index cases, not just in Belgium but also internationally.

What Is Aristolochic Nephropathy?

Aristolochic acid nephropathy (AAN) refers to any type of toxic interstitial nephropathy that results from ingesting plants that contain aristolochic acids (AA) or by environmental pollutants found in food. It frequently occurs in conjunction with urothelial cancers. Although most nations have outlawed the sale of items containing aristolochic acid, AAN (aristolochic acid nephropathy) incidents are nevertheless often reported worldwide. Additionally, the prevalence of AAN is probably significantly underreported due to the extensive usage of AA in conventional herbal treatments and the low level of public awareness of the ailment.

Aristolochic acid nephropathy cases have been documented despite the removal of aristolochic acid-producing plants. These patients are found to develop severe interstitial nephritis that can be associated with end-stage renal disease (ESRD). Other cases also include the development of urothelial malignancies due to the intake of Chinese herbs containing aristolochic acid.

What Are the Symptoms of Aristolochic Acid Nephropathy?

• Nephrotoxicity: Most cases of aristolochic acid nephropathy present with renal failure. It rapidly progresses into end-stage renal disease. Certain cases present moderate hypertension, severe anemia, and increased levels of serum creatinine, along with proteinuria and glycosuria. The amount of urinary neutral endopeptidase (NEP), a 94 kDa ectoenzyme of the proximal tubule brush border, serves as a reliable indicator of the severity of the renal disease. The kidneys become microscopically smaller, asymmetrical, and irregular in cortical form.

• Urothelial Malignancies: Patients suffering from aristolochic acid nephropathy present with upper tract urothelial carcinoma and bladder endothelial cancer. Urothelial cancer is found to be associated with ESRD (end-stage renal disease). Therefore, in most cases of aristolochic acid nephropathy, urothelial carcinoma is found to be a late complication.

How Is Aristolochic Acid Nephropathy Diagnosed?

There are currently no rigid diagnostic standards to help the practitioner diagnose this condition.

The majority of patients have been found to have the following symptoms.

• Renal insufficiency.

• Anemia.

• A low erythrocyte and leukocyte count in the urine sediment.

• Minor proteinuria (usually less than 1.5 grams per day).

The diagnosis of AAN is typically made based on:

• Clinical features.

• Laboratory tests.

• Kidney biopsy.

A history of exposure to Aristolochia-containing products, characteristic signs and symptoms of kidney disease, and laboratory tests showing evidence of kidney dysfunction and specific markers of AAN, such as the presence of aristolactam-DNA adducts in the urine.

• Kidney Ultrasound - Ultrasonography of the renal tract reveals undersized kidneys, which can have an uneven and asymmetric cortical contour.

• Microscopic Findings - Histological findings include:

1. Fibrous hyperplasia of arteriolar walls.

2. Low numbers of chronic inflammatory cells decreasing from the outer to the inner cerebral labyrinth.

3. Severe interstitial fibrosis accompanied by tubular atrophy.

Nearly all patients have multifocal urothelial atypia, and 40 % to 46 % of patients have multifocal, frequently bilateral transitional cell carcinoma in situ, typically found in the upper urinary tract. DNA adduct analysis and phytochemical analysis can both confirm that an individual consumed aristolochic acid.

• Kidney Biopsy - In AAN, a kidney biopsy will show the following characteristic findings-

1. Tubular atrophy.

2. Interstitial fibrosis.

3. Chronic inflammation.

The biopsy may also show other features, such as glomerular abnormalities, that can help distinguish AAN from other types of kidney disease.

How Is Aristolochic Acid Nephropathy Treated?

• Aristolochic acid nephropathy (AAN) is a serious kidney disease caused by the ingestion of aristolochic acid, which is found in certain plants used in traditional medicine and herbal remedies.

• Treatment options for AAN are limited and include measures to manage symptoms and slow the progression of kidney disease, such as blood pressure control and restriction of dietary protein and salt.

• Medications to reduce proteinuria and delay the need for dialysis or kidney transplantation.

Treatment for AAN may involve a combination of approaches, including:

• Discontinuing Aristolochic Acid-Containing Products: The first step in treating AAN is to stop using any herbal remedies or supplements that contain aristolochic acid.

• Removal of the Affected Kidney- Patients suffering from urothelial cancer related to aristolochic acid intoxication and being treated with dialysis or kidney transplant are advised for removal of the native kidneys and ureters.

• Supportive Care: Patients with AAN may require supportive care, such as medications to control high blood pressure or diuretics to manage fluid retention.

• Dialysis: In some cases, patients with AAN may require dialysis, which involves using a machine to filter waste products from the blood when the kidneys are unable to function properly.

• Kidney Transplant: For patients with end-stage kidney disease due to AAN, a kidney transplant is a treatment option. However, it is important to note that transplant recipients must avoid aristolochic acid-containing products to prevent the recurrence of the disease.

• Management of Associated Complications: Patients with AAN may be at increased risk for developing bladder cancer, so regular monitoring and screening may be necessary.

Conclusion:

Aristolochic acid nephropathy is any type of toxic interstitial nephropathy caused by the ingestion of plants containing aristolochic acid (AA). Aristolochic acid nephropathy (AAN) is caused by exposure to aristolochic acid, a natural compound found in certain plants of the Aristolochia family. This disease is characterized by progressive renal fibrosis and eventually leads to end-stage kidney failure. Exposure to aristolochic acid can occur through the consumption of contaminated herbal remedies or food products or through environmental exposure to Aristolochia plants. AAN can also occur as a result of occupational exposure to aristolochic acids, such as in the case of Chinese herbalists who handle Aristolochia plants.