From the Guidelines
The acute kidney injury (AKI) in this 45-year-old female with Latent Autoimmune Diabetes in Adults (LADA) and recurrent Graves' disease is likely multifactorial, with carbimazole being a potential contributor, and management should prioritize monitoring kidney function, ensuring adequate hydration, and considering alternative anti-thyroid medications. The patient's condition is complex, involving multiple factors that could contribute to AKI, including the use of carbimazole, which can rarely cause drug-induced nephritis or vasculitis leading to kidney injury 1. Additionally, uncontrolled thyroid dysfunction itself can affect kidney function, as hyperthyroidism increases renal blood flow and glomerular filtration rate, and when treated, can appear as declining kidney function. Propranolol, although less likely to be the cause, can reduce renal perfusion. Other possibilities include diabetic nephropathy progression, volume depletion from hyperglycemia, or an unrelated kidney condition.
Given the potential for nephrotoxicity with certain medications, it is crucial to evaluate the necessity of each drug and consider alternatives with less nephrotoxic potential, especially in patients with compromised kidney function or at risk of AKI 1. The KDIGO guidelines recommend temporary discontinuation of potentially nephrotoxic and renally excreted drugs in people with a GFR < 60 ml/min/1.73 m2 who have serious intercurrent illness that increases the risk of AKI 1.
Key Considerations:
- Monitoring kidney function closely
- Ensuring adequate hydration
- Optimizing diabetes control
- Considering alternative anti-thyroid medications like propylthiouracil if kidney function continues to deteriorate
- A nephrology consultation if the AKI persists or worsens despite these interventions
- Urinalysis and kidney ultrasound to evaluate for other causes of kidney injury
The management strategy should be tailored to the individual patient's needs, taking into account the potential benefits and risks of each medication, and the patient's overall clinical condition, including the presence of other comorbidities that could influence kidney function 1.
From the FDA Drug Label
Renal Insufficiency: The pharmacokinetics of propranolol hydrochloride extended-release capsules have not been investigated in patients with renal insufficiency In a study conducted in 5 patients with chronic renal failure, 6 patients on regular dialysis, and 5 healthy subjects, who received a single oral dose of 40 mg of propranolol, the peak plasma concentrations (Cmax) of propranolol in the chronic renal failure group were 2 to 3-fold higher (161±41 ng/mL) than those observed in the dialysis patients (47±9 ng/mL) and in the healthy subjects (26±1 ng/mL).
Propranolol plasma clearance was also reduced in the patients with chronic renal failure.
The cause of the new AKI (eGFR 83-50) in this patient is unclear, but renal insufficiency can affect the pharmacokinetics of propranolol. The reduced clearance of propranolol in patients with chronic renal failure may lead to increased peak plasma concentrations and potentially increased toxicity 2. However, there is no direct information in the drug label that supports a causal relationship between propranolol and the development of AKI.
- Key points:
- Reduced propranolol clearance in renal insufficiency
- Increased peak plasma concentrations in chronic renal failure
- Potential for increased toxicity However, the FDA drug label does not provide sufficient information to determine the cause of the new AKI in this patient.
From the Research
Possible Causes of Acute Kidney Injury (AKI)
The patient's new AKI (eGFR 83-50) could be caused by various factors, including:
- Prerenal causes, such as dehydration or decreased blood flow to the kidneys 3, 4
- Intrinsic renal causes, such as acute tubular necrosis caused by ischemia or nephrotoxicity 5, 6
- Postrenal causes, such as obstruction of the urinary tract 3, 4
Medication-Related Causes
The patient is currently taking carbimazole and propranolol for Graves' disease. While there is no direct evidence linking these medications to AKI in the provided studies, it is essential to consider the potential nephrotoxic effects of certain medications 5, 4.
Underlying Medical Conditions
The patient's history of LADA (Latent Autoimmune Diabetes) and Graves' disease may also contribute to the development of AKI. However, there is no direct evidence in the provided studies to support this claim.
Importance of Early Diagnosis and Management
Early determination of the underlying cause of AKI and prompt management are crucial to prevent long-term consequences, such as chronic kidney disease and cardiovascular morbidity 3, 5, 4, 6. A thorough history, physical examination, laboratory work-up, and renal ultrasonography (if necessary) can help identify the cause of AKI and guide management decisions 3, 4.