Renal Complications in Propionic Acidemia: Not as Rare as Previously Suspected
Oleg A. Shchelochkov, MD, and Charles Venditti, MD, PhD
Propionic acidemia (PA) is a serious metabolic disease which can impact many organs. For example, it has been known for some time, that propionic acidemia can cause poor heart function (cardiomyopathy) and inflammation of pancreas (pancreatitis). But what about other organs? Because PA is relatively rare, its low frequency makes it difficult to spot an uncommon complication or measure how often a complication happens. We are conducting a natural history study of PA at NIH (https://clinicaltrials.gov/ct2/show/NCT02890342 ). With the help of PA community, we were able to gain new insights into how PA can affect kidneys, and recently published a paper summarizing our findings (https://www.ncbi.nlm.nih.gov/pubmed/31249402). Below we share some important questions raised during the study:
Question: What prompted the study of kidney function in propionic acidemia?
Answer: It has been known for many decades that methylmalonic acidemia, a disease in many ways similar to propionic acidemia, can lead to poor kidney function. A loss of kidney function in methylmalonic acidemia (MMA) can significantly impact the quality of life and may require special treatments. In recent years, there have been isolated reports of patients with propionic acidemia who also developed kidney disease later in life. Our European colleagues had noticed that some older PA patients in their studies also had lower kidney function. Although kidney problems in PA were not as severe as in an isolated MMA, the frequency of this complication and the age of onset was not known. It prompted us to examine renal findings in patients, who were seen at NIH as part of the PA natural history study.
Question: What type of kidney problems did we find in PA patients?
Answer: We discovered that when we used the most common way to estimate renal function using blood creatinine, 50% of adult PA patients had some degree of the chronic kidney disease. We also found that a blood chemical called “cystatin C”, can be helpful to spot a renal function decline sooner. Importantly, patients who had chronic kidney disease had a higher chance of having cardiomyopathy. We don’t know yet, how exactly cardiomyopathy and chronic kidney disease are connected to each other. We are conducting additional studies to look into this association.
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Question: What would doctors do if they discover chronic kidney disease in a PA patient?
Answer: Patients with chronic kidney disease will benefit from establishing care with a renal doctor (a nephrologist). Nephrologists will order and review blood and urine labs, which help them come up with a better care plan. Interval renal ultrasounds can be helpful to follow the size and appearance of kidneys. Some patients may need to have their diet adjusted to control for how much water, calcium, phosphorus, vitamin D and other food ingredients they take each day. Doses of some medications will need to be adjusted in more advanced kidney disease. For example, doses of some anti-epileptic drugs may need to be adjusted if the kidney disease becomes severe.
Question: Can chronic kidney disease of PA be prevented?
Answer: At this point, we don’t know how to stop the chronic kidney disease of PA. But we believe that early diagnosis of chronic kidney disease, good control of blood pressure, avoidance of drugs toxic to kidneys, and prevention of chronic metabolic acidosis, may help slow down the progression of kidney disease.
We wanted to thank all families who participated in the study and we are looking forward to meeting new families at NIH. We are grateful for patients’ generous gift of time and efforts to make our protocol a reality. Every patient contributes in an important way. As we carefully study each patient, we gain new knowledge that we can share with patients, families, healthcare providers, and researchers. Please feel free to contact the team with questions or comments. You can email Dr. Oleg at oleg.shchelochkov@nih.gov or contact our research nurse Susan Ferry, RN at susan.ferry@nih.gov.
From the December 2019 OAA Newsletter
Question: What prompted the study of kidney function in propionic acidemia?
Answer: It has been known for many decades that methylmalonic acidemia, a disease in many ways similar to propionic acidemia, can lead to poor kidney function. A loss of kidney function in methylmalonic acidemia (MMA) can significantly impact the quality of life and may require special treatments. In recent years, there have been isolated reports of patients with propionic acidemia who also developed kidney disease later in life. Our European colleagues had noticed that some older PA patients in their studies also had lower kidney function. Although kidney problems in PA were not as severe as in an isolated MMA, the frequency of this complication and the age of onset was not known. It prompted us to examine renal findings in patients, who were seen at NIH as part of the PA natural history study.
Question: What type of kidney problems did we find in PA patients?
Answer: We discovered that when we used the most common way to estimate renal function using blood creatinine, 50% of adult PA patients had some degree of the chronic kidney disease. We also found that a blood chemical called “cystatin C”, can be helpful to spot a renal function decline sooner. Importantly, patients who had chronic kidney disease had a higher chance of having cardiomyopathy. We don’t know yet, how exactly cardiomyopathy and chronic kidney disease are connected to each other. We are conducting additional studies to look into this association.
'
Question: What would doctors do if they discover chronic kidney disease in a PA patient?
Answer: Patients with chronic kidney disease will benefit from establishing care with a renal doctor (a nephrologist). Nephrologists will order and review blood and urine labs, which help them come up with a better care plan. Interval renal ultrasounds can be helpful to follow the size and appearance of kidneys. Some patients may need to have their diet adjusted to control for how much water, calcium, phosphorus, vitamin D and other food ingredients they take each day. Doses of some medications will need to be adjusted in more advanced kidney disease. For example, doses of some anti-epileptic drugs may need to be adjusted if the kidney disease becomes severe.
Question: Can chronic kidney disease of PA be prevented?
Answer: At this point, we don’t know how to stop the chronic kidney disease of PA. But we believe that early diagnosis of chronic kidney disease, good control of blood pressure, avoidance of drugs toxic to kidneys, and prevention of chronic metabolic acidosis, may help slow down the progression of kidney disease.
We wanted to thank all families who participated in the study and we are looking forward to meeting new families at NIH. We are grateful for patients’ generous gift of time and efforts to make our protocol a reality. Every patient contributes in an important way. As we carefully study each patient, we gain new knowledge that we can share with patients, families, healthcare providers, and researchers. Please feel free to contact the team with questions or comments. You can email Dr. Oleg at oleg.shchelochkov@nih.gov or contact our research nurse Susan Ferry, RN at susan.ferry@nih.gov.
From the December 2019 OAA Newsletter