While diabetes mellitus is a fairly common and well understood disorder, few people know that diabetes may develop as a brand new bona fide complication in patients that get a kidney transplant. Anybody with kidney failure contemplating kidney transplantation as treatment for kidney disease needs to know about this risk, better known as new-onset diabetes following transplant (NODAT).
While the risk is there, it’s important to understand that not everybody is in danger, and those who are have treatment options should diabetes post-kidney transplantation develop.
Just How Common Is NODAT?
NODAT is a recognized problem in a significant number of individuals that get a kidney transplant. However, clear data on this number aren’t available. This is only because there was no standardized definition of NODAT for a long time, till 2003. Hence, based on how you define NODAT, the prevalence could change.
Some studies appear to imply that nearly 30 percentage of those who didn’t have diabetes before getting a kidney transplant might develop persistent elevation in blood glucose levels suggestive of NODAT by six months following their kidney transplantation. This is obviously a substantial number, indicating that counselling about NODAT ought to be an essential component of care of kidney failure patients interested in getting a kidney transplant.
What Is the Impact of NODAT?
Newly developed diabetes after receiving a kidney transplant has wide-ranging effects, some of which are also found from the typical person with diabetes.
Therefore, these folks are susceptible to develop certain complications. A Couple of examples include:
- Ketoacidosis: improved ketone and acid levels in blood found in patients with deficiency of insulin, which may cause profound dehydration and electrolyte disturbances, and elevated blood sugars. The affected patient is usually severely sick.
- Neuropathy: that “pins and needles” sensation in hands and feet that afflicts diabetes.
- Higher chance of infection as elevated blood glucose is a known source of suppression of the immune system. This then can manifest as increased frequency of urinary tract infections, skin infections, lung diseases, etc..
- More specifically, NODAT will have a negative effect on not just the individual’s lifespan and risk of death, but also survival of the transplanted kidney. To put it in other words, a kidney transplant recipient who develops NODAT may have a shorter lifespan and see the transplanted kidney fail earlier as well.
Why Can NODAT Develop? What Are the Risk Factors?
Although the effect is significant, notice that not each kidney failure patient who received a transplanted kidney develops diabetes because a post-transplant complication. Certain medications along with other risk factors do increase the likelihood of a specific patient developing NODAT. Some of them include:
- Medications: these include glucocorticoids (e.g., prednisone) and other drugs that we use to suppress the immune system of a transplant recipient to be able to avoid rejection of the transplanted kidney (because the receiver’s immune system sees that kidney as a “foreign entity”). Examples of these medications include a class of drugs known as “calcineurin inhibitors” (such as tacrolimus and cyclosporine, the former being more likely to trigger diabetes), and sirolimus. Please be aware that not all transplant rejection prophylaxis medications necessarily increase risk of NODAT (these include other common post transplant immunosuppression medicines like mycophenolate mofetil, also known as CellCept).
- Infections are a known trigger. These include Hepatitis C virus (HCV), cytomegalovirus (CMV) infection.
- Along with the aforementioned specific drug/infection related risk variables, African race, obesity, and a family history of diabetes do increase risk of NODAT.
Balancing the Risk of Rejection With the Risk of NODAT: A Catch 22 Situation
As might be evident from the above discussion, the same medications that we utilize to maintain adequate amount of suppression of the recipient’s immune system (so they do not reject the new transplanted kidney), also increase the risk of diabetes. To put it differently, would you rather risk rejecting the organ, or would you rather risk developing diabetes? In any event, you might feel like you’re putting the health of your transplant kidney, your new lease of life, also in peril. Balancing these two competing priorities is obviously significant, so how can you cope with it?
Here’s the take home message: Rejection of the transplanted kidney is still the biggest factor that determines its ability to survive and operate in a patient, more than risk of recently improved diabetes.
Therefore, most guidelines imply prioritizing adequate immunosuppression to prevent rejection, even if it means an increase in risk of the transplant recipient developing NODAT.
How Is NODAT Diagnosed?
Since we do have a fair understanding of risk factors that increase the risk of NODAT, tracking high risk patients is recommended. A good transplant center will advise you about the risk of NODAT before they get the kidney so you are able to make an informed choice.
However, as soon as you are being tracked after getting the transplanted kidney, the following definitions will apply to be able to diagnose new-onset diabetes after transplantation. These definitions have been set forth by an international expert panel:
- Symptoms of diabetes in addition to random plasma glucose level greater than 200 mg/dL
- Fasting plasma glucose greater than or equal to 126 mg/dL
- 2-hour plasma glucose greater than or equal to 200 mg/dL during an oral glucose tolerance test
- You could also be familiar with a common evaluation called , which we use for identification of diabetes in the general population. Its usage as a diagnostic tool isn’t advisable during the initial three months following a kidney transplant. However, then, the exact same definition for identification of diabetes as used in the overall population employs. This would be a hemoglobin A1c levels greater than or equal to 6.5 precent in order to diagnose NODAT.
Approach to Handling NODAT: The First Conservative Management
In the event you develop NODAT (particularly in the setting of the above mentioned risk factors), a conservative strategy is first instituted in order to treat elevated blood sugars. Here are some things to understand:
- Active surveillance for NODAT is obviously part of standard maintenance of the kidney transplant recipient. Blood glucose is measured as frequently as once per week for your first month, even though the frequency of testing can be decreased later.
- One of the techniques to decrease the risk of NODAT, in addition to decrease its severity once it has already developed, is to aim for a reduction in the dose of steroids (one of the linchpins of rejection prophylaxis medications). However, as the risk of rejecting a transplanted organ goes up significantly if steroids are stopped completely, complete cessation is usually not recommended.
- Similarly, the dose of tacrolimus (another common immunosuppression drug), as permitted by rejection risk, may be considered for reduction. If everything else fails and the patient is having additional signs/symptoms of NODAT, then a switch to a similar medication called cyclosporine may become necessary.
Approach to Handling NODAT: Definitive Medical Therapy
If the above described conservative management does not help and diabetes continues to develop and worsen following kidney transplantation, the transplant recipient with recently developed diabetes might require specific management with diabetes medicines. The same as any other person having diabetes, we normally begin with oral medications.
Common examples include a drug known as glipizide (sometimes favored because its excretion in the body does not rely too much on the kidneys’ function; if that weren’t the case, diabetes medicines could accumulate to high levels in kidney disease patients and lead to dangerously low blood glucose levels). If one medication isn’t adequate, other medicines are inserted until finally, subcutaneous insulin shots might become necessary to control the blood sugar levels adequately.
Can You Stop NODAT From Growing?
Knowing the risk, you’re probably also wondering if there’s anything you can do to lessen it. As a side note, some institutions do transplant the pancreas (the organ where insulin is produced and whose abnormalities may lead to diabetes) simultaneously with the kidney in patients that have end-stage diabetic kidney disease. They are a few studies that show that such a procedure leads to a better and a longer lifespan.
This is related in a huge way to improved control of type 1 diabetes (which borders almost on a complete “cure” of this disease as a consequence of the transplanted pancreas), but there are nevertheless no cases of this kind of approach having been tried in the event of NODAT, for the apparent reason that by definition, a NODAT patient would not have diabetes pre-transplant.
A Word From Verywell
Overall, the risk of developing NODAT may be difficult to accept and may cast doubt over if you should go through the procedure. Make sure that you bring up and discuss your concerns with your doctor. He or she will assist you in making the best choice for you. Oftentimes, provided the management options if diabetes has been developed, the quality of lifestyle post-transplant can outweigh the risk of NODAT.
New-onset diabetes after transplantation (NODAT): a test of definitions in clinical trials. First MR, et al.. Transplantation. 2013.
New onset diabetes after transplantation (NODAT): a summary. Phuong-Thu T Pham. Diabetes Metab Syndr Obes. 2011.
New-Onset Diabetes after Kidney Transplantation: Risk Factors. Emilio Rodrigo. Journal of American Society of Nephrology. 2006.