Sometimes, doctors choose to treat a certain condition with a specific medicine or class of medicines. But what happens when that medicine causes unintended and potentially harmful reactions? For example, doctors have occasionally used immune checkpoint inhibitors – including tyrosine kinase inhibitors such as sunitinib – to treat patients with metastatic renal cell carcinoma (mRCC). But according to Renal and Urology News, a study performed in China found that treating mRCC with immune checkpoint inhibitors could worsen proteinuria, or excess protein in the urine.
Interested in learning more? Take a look at the findings of the study published in Translational Andrology and Urology.
Immune Checkpoint Inhibitors and Proteinuria
To begin, let’s first unpack what immune checkpoint inhibitors are. The National Cancer Institute explains that an immune checkpoint inhibitor is:
a type of drug that blocks proteins called checkpoints that are made by some types of immune system cells, such as T cells, and some cancer cells. These checkpoints help keep immune responses from being too strong and sometimes can keep T cells from killing cancer cells [so by blocking] these checkpoints, T cells can kill cancer cells better.
In this particular study, researchers evaluated the impact of immune checkpoint inhibitors on proteinuria in those with mRCC. Altogether, 141 patients enrolled. Findings from the study show that:
- 52% of patients experienced increased proteinuria during the course of the study. Rates of Grade 1-3 proteinuria all rose. Additionally, an estimated 80% of patients enrolled had some signs of proteinuria.
- Treatment with tyrosine kinase inhibitors also reduced estimated glomerular filtration rate (eGFR), which measures kidney function. A significant decline in eGFR signifies a loss of kidney function.
- After a subgroup received additional treatment with a PD-1 inhibitor, approximately 50% of the subgroup saw significantly worsening proteinuria.
- Being treated with immune checkpoint inhibitors for over 12 months corresponded with heightened rates of proteinuria and significant declines in eGFR. Both of these also correspond with worse patient outcomes and more limited survival.
Overall, the researchers believe that those with mRCC receiving immune checkpoint inhibitors should be frequently monitored to assess kidney health and function.
Proteinuria: An Overview
As described above, proteinuria refers to protein in the urine. In healthy kidneys, proteins pass through the kidneys into the bloodstream. But for those with proteinuria, protein leaves the body through the urine. This can result from dehydration, stress, kidney stones, or inflammation. However, proteinuria can also be a sign of acute kidney inflammation, cancers like multiple myeloma, or chronic kidney disease. In situations like mRCC, proteinuria shows worsening kidney damage. Symptoms associated with proteinuria can include nausea and vomiting, appetite loss, muscle cramping, foamy or bubbly urine, fatigue, shortness of breath, and swelling of the face, abdomen, and lower extremities.
What is Renal Cell Carcinoma (RCC)?
Renal cell carcinoma (RCC) is a form of aggressive kidney cancer which may easily metastasize to other organs, such as the lungs. Despite the fact that RCC is a rare cancer, it is also considered to be the most common form of adult kidney cancer. Risk factors include being male, being between 50-70 years old, smoking cigarettes, having a history of kidney problems, or having TFE 3, VHL, or PRC gene mutations. In many cases, RCC is asymptomatic until it spreads. When symptoms appear, they can include:
- Fever
- Unintended weight loss
- Hematuria (blood in the urine) or rusty-colored urine
- Abdominal pain
- High blood pressure
- Fatigue
- Enlarged testicle
- Anemia
- Lower back pain on one side
- Vision abnormalities
