Amyloidosis is a rare but well-known complication of most of the long term illness. It is the deposition of abnormally folded proteins in the body compartments. However, we see a type of amyloidosis in patients with Chronic Kidney Diseases (CKD) and chronic hemodialysis. This is termed as dialysis related amyloidosis (Beta 2 Amyloidosis). Additionally This type of amyloidosis has found in patient with severe renal impairment, but has not undergone any dialysis.
Mechanism of Dialysis Related Amyloidosis
Our kidney is the most vital organ for the excretory functions of the body. Usually, it removes all the excess chemicals from the body. Beta 2 macroglobulin is also filtered out from the kidney. However, When someone has chronic kidney disease, they have to undergo regular hemodialysis to maintain regular kidney functions. But the artificial dialysis membrane fails to filter out the type of macroglobulin called beta 2 macroglobulin (a type of small protein) from the body.
The failure to remove the beta-amyloid associated macroglobulin can cause the accumulation of them in the body compartments. Some of the sites are the joints and synovium, heart, tongue, and some other organs.
Complications of Dialysis Associated Amyloidosis
Depending on the site of the deposition of the Beta 2 globulin, it cause different clinical signs and symptoms. Most often these patients presenting with chronic joint pains. However in addition to joint pains dialysis related amyloidosis causes lot of different clinical features.
Chronic joint pain
Carpal tunnel syndrome
Cardiomegaly
Heart failure
Macroglossia (large tongue)
Bone fractures
Carpal tunnel syndrome in a Chronic Dialysis patient.
How to Prevent Dialysis Related Amyloidosis
All the patients who undergo chronic dialysis are prone to get dialysis-associated amyloidosis. It is estimated to have 50% of patients getting dialysis related amyloidosis with in 10years of dialysis. Additionally most of the treatment methods for dialysis associated beta 2 amyloidosis fail to completely cure the complications like chronic joint pains, bone destructions and etc.
Therefore it is essential to take adequate precautions to prevent this conditions in all patients undergoing hemodialysis.
Young patients are more prone to get dialysis associated amyloidosis as they are getting more dialysis. Therefore it is better to transplant them early as possible. Longer the duration of dialysis , higher the risk of DAA.
Early kidney transplant is the best method to prevent dialysis related amyloidosis.
However some of the patient with End stage kidney failure may not fit enough to undergo kidney transplant. In such situations we have to take some other methods to prevent this condition.
Most importantly maintaining the residual kidney function is necessary. This will patient own kidneys to function with limitations. As a result, kidneys are able to remove some of the beta 2 macro globulins from the body.
The percentage of beta 2 amyloidosis increase when we use low flux dialyzers. Therefore it is advisable to use high flux dialyzers. When we use high flux dialyzers, a larger pore size allows the dialyzer to remove globulins from the blood.
In addition to the dialyzer, there is important role of dialysate solutions. Therefore always use high quality dialysis solutions in each dialysis.
Some centers also use beta 2 macroglobulin filters to remove beta 2 globulins from the blood. This also reduce the plasma level of beta 2 globulins. As a result there is less chance of accumulation of amyloids in the body tissues.
Related articles
Bardin T, Zingraff J, Kuntz D, Dru¨ eke T. Dialysis related amyloidosis. Nephrol Dial Transplant 1986; 1: 151–154
Zingraff J, Noe¨l LH, Bardin T, et al. Beta-2-microglobulin amyloidosis in chronic renal failure (letter). N Engl J Med 1990;323: 1070–1071
I often see incidents of hypoglycemia during dialysis sessions. This is a common complication of dialysis in most of the hemodialysis centers. Although hypoglycemia is one of the very common complication during haemodialysis, more often inexperienced clinicians may miss these incidents. This article is mainly focus on how to detect hypoglycemia early, how to manage hypoglycaemia and how to prevent it.
Why is the hypoglycemia very common complication during dialysis?
It is true that we often see the patient undergoing clinical and subclinical hypoglycemia during dialysis. But why the dialysis patients are more proven to get hypoglycemic attacks. Is it the dialysis which causing the hypoglycemia? Or some other cause.
Diabetes mellitus can make you hypoglycemic
We know that one of the most common cause for CKD is the diabetes. Patients with diabetes often has high blood sugar levels. This is due to the insulin insensitivity or lack of insulin. So can these patients undergo hypoglycemia during hemodialysis?
Some of these CKD patients on Metformin, some are on other oral hypoglycemic agents like Gliclacide. Even if the metformin do not cause significant hypoglycemia, some other medications can cause the hypoglycemia. In addition Insulin can cause on and off hypoglycaemic events.
Kidney disease can also cause hypoglycemia
Gluconeogenesis is the process of creating glucose inside the body. This mainly occurs when you are in a fasting state. The kidneys are the second most vital organ for this mechanism. It is second only to the liver. When you have CKD, structure of your kidney get damaged and ability of gluconeogenesis is also get reduced. As a result body fails to maintain the adequate amount of the blood sugar levels during dialysis or even at the day to day settings.
Mechanism of dialysis
Dialysis is a complicated process. There is a 15g to 20g of glucose loss during each dialysis session. This loss of plasma glucose can lead to subclnical hypoglycemia in most of the patients. However in some patients they are not fit enough to maintain this loss of glucose during dialysis. Therefore they can get a significant hypoglycemia during dialysis.
Therefore hypoglycemia during dialysis is a multifactorial complication. Although loss of glucose during dialysis do not cause significant symptoms, failure to maintain the gluconeogenesis causing the significant damage to the patient.
How to identify the hypoglycemia during dialysis?
In a usual setting an experienced healthcare professional can identify the hypoglycemic events easily. But during dialysis it is very difficult to identify the hypoglycemic events. As an experienced clinician I have met patients with blood sugar levels of 20mg/dl but they were almost normal except few symptoms. But this is not a viable blood sugar level in a normal patient. Therefore you need to have clear understanding about hypoglycemia during dialysis. If you are not specifically look it, you can’t identify most of the hypoglycemia during haemodialysis.
Symptoms of hypoglycemia during dialysis sessions
Hypotensive attacks Hypotension is the main symptom of low blood sugar levels during dialysis. If a patient develop a hypotension during dialysis, 1st thing to look is the hypoglycemia. Most of the times it is low blood sugar levels than the depletion of volume or some other cause.
Failure to maintain blood pressure with inotropes This is a common issue with patients undergoing the urgent hemodialysis due to Acute Kidney injuries. Most of they are critically ill and on inotrope support. But if a patient do not improve with proper inotrope support, we have to look for the hypoglycemia.
Altered level of consciousness Level of consciousness is a broad term. It include the orientation, the way of talking, level of intelligence and lot of other factors. In some instances I have met CKD patient with less than 20mg/dl blood sugar level with no significant alteration of consciousness.
Case 1. 27years old patient came to regular hemodialysis. He maintained his blood pressure levels and saturation well. No complaints too. But when I talk to him, I found some irrelevance of his sentence to each. I had some suspicion and checked the blood sugar level. It was 17mg/dl and immediate actions were taken.
Case 2. 54years old patient was in his regular haemodialysis. He was given a cup of tea while he was on dialysis. But the staff member noted that he failed to take his tea. He informed me. Then I asked for a blood sugar level. It was 27mg/dl and he was collapsed in few second. Immediate resuscitation was conducted and successfully recovered the patient.
Sweating during dialysis Sweating is a very common symptom of hypoglycemia. You can see it even in patients taking medication for diabetes. However surprisingly I rarely met hypoglycemic patients with sweating during dialysis. So I think you have a clear understanding on symptoms of hypoglycaemia during dialysis sessions. Then the next question is how to manage the hypoglycaemia during dialysis.
How to manage hypoglycemia during dialysis?
As I mentioned events of hypoglycemia is common and subclinical most of the times. However there are times you have to attend on events of hypoglycemia. Even if the pre dialysis and intradialysis blood sugar monitoring can be done, it is not a good and presence experience to patients. Even though the basic management of hypoglycemia is same in each complication, you have to attend the case depend on the symptoms too.
Hypoglycemia with hypotention.
Here the management of both hypoglycaemia and the hypotension should be done simultaneously.Soon as you note there is a hypotension the next action is to check the hypoglycemia.
Start bolus of 100cc normal saline
Give 1 vial of dextrose
Reduce the blood flow rate and position the patient
Repeat the blood pressure and blood sugar in 10 minutes
If blood sugar is not enough repeat the dextrose infusion
Hypoglycemia with no response to inotropes
Inotropes are the medications to improve the blood pressure in critical patients. They have different actions. It is common that patient face significant reduction of blood pressure soon as they are connected to the dialysis machines. But it can be picked up with these medications. But if these patients do not improve the blood pressure with inotrope, it is worth to check the blood sugar level than next inotrope.
Hypoglycemia with altered level of consciousness
Hypoglycemia is not the only cause for altered level of consciousness during dialysis. There are lot of cause like electrolyte imbalance, stoke and etc. In addition there is a very important condition called Dialysis disequilibrium syndrome.
But before thinking of anything else, you should focus on hypoglycemia during dialysis. Because it is easily preventable cause for altered level of consciousness during dialysis.
Whenever a patient has a reduce level of consciousness;
Check the blood pressure
Check the blood sugar levels
Look at the other neurological features
Give bolus of dextrose irrespective of blood sugar levels unless it is too high
Then only you can exclude other causes of altered level of consciousness.
Hypoglycemia with sweating during dialysis
Sweating is another presentation of hypoglycemia. But when someone has the sweating, it myocardial infarction should be ruled out.
Check all vital parameters
Give dextrose
Check urgent ECG
How to prevent hypoglycemia during dialysis
Although hypoglycemia is commonly missed as subclinical incidents, we have to be prepared and look into it properly.
Ask patient to have proper meal prior to dialysis
Arrange a mid-dialysis snack or refreshment
Monitor CBS in high risk patients
Reference:
Vadakedath, S., & Kandi, V. (2017). Dialysis: A Review of the Mechanisms Underlying Complications in the Management of Chronic Renal Failure. Cureus, 9(8), e1603. https://doi.org/10.7759/cureus.1603
Abe, M., & Kalantar-Zadeh, K. (2015). Haemodialysis-induced hypoglycaemia and glycaemic disarrays. Nature reviews. Nephrology, 11(5), 302–313. https://doi.org/10.1038/nrneph.2015.38
Have you ever experienced a sudden headache or confusion during your dialysis as a patient? Have you ever experienced a sudden neurological deterioration in your patient during or soon after the dialysis as a physician? The dialysis disequilibrium syndrome can be the reason for the unexplained neurological issues like headache, confusion, seizures, nausea and some of the other symptoms in dialysis patients. So what is this Dialysis Disequilibrium Syndrome (DDS)?
Basic mechanism of dialysis
Before understating the dialysis disequilibrium syndrome, it is good to know the basics of dialysis and how it works on your body.
If your kidney get Acute Kidney Injury (AKI) or Chronic Kidney Disease (CKD), you may have to undergo a process called dialysis. What we do as dialysis is the providing of natural kidney functions by an artificial kidney attached to machine. The most important function of dialysis is the removal of waste products from the body like urea. In addition it help to maintain acid base balance and electrolyte balance of the body.
If you have understood this basic of dialysis, you might understand that urea is removed in each session of the dialysis.
Mechanism of dialysis disequilibrium syndrome (DDS)?
Osmotic pressure of our body is basically maintain by two particles. One is the Sodium (Na+). Other one is the Urea. Even though other electrolytes are affecting this process, only these two can give significant contribution to oncotic pressure.
As we mentioned we remove some amount of the urea with each dialysis. Therefore there is a reduction of osmotic pressure in the blood. When plasma osmotic pressure reduced, it can cause cells to take some fluid from plasma and keep the balance between them.
Same process occurs in the brain too. This will ultimately result in increased size (edema) in the brain cells. This cerebral edema can cause lot of neurological issues simply from headache to death at last. When the amount of removed urea is higher, the edema is higher and risk of dialysis disequilibrium syndrome is higher.
Who get the disequilibrium syndrome?
Dialysis induced disequilibrium syndrome (DDS) is commonly seen in patient who undergoes their 1st series of dialysis. However it can also be seen in other CKD patients too. Some studies show that it is common in patients who miss their dialysis sessions.In addition it can present in some patients who undergoes dialysis or CRRT following acute kidney injury.
Symptoms and signs of disequilibrium syndrome
Headache
Nausea
Dizziness
Confusion
Visual disturbance
Tremor
Seizures
Coma
How to prevent disequilibrium syndrome
Few decades ago, DDS is one of the common issues during dialysis. However with the development of the Nephrology and dialysis care, the disequilibrium syndrome has become a rare condition among the patients with Chronic Kidney Disease. Even though the dialysis disequilibrium syndrome is a rare complication, this should be considered as on of the serious complication of dialysis.
Initiate the dialysis with short cycles Usual hemodialysis session are continue upto 4 to 5 hours. However at the initiation of the dialysis, it is advice to limit the duration of dialysis for few hours. Usually 2.5hours – 3hours as maximum. As a result the risk of sudden reduction of urea is rare.
Use low blood flow rate When you dialysis, you can adjust the blood flow rate though the machine. Higher the rate of blood purification, higher the risk dialysis disequilibrium syndrome. Therefore you can try with a blood flow rate of 100 – 150 in initial dialysis sessions.
Monitor the Urea Reduction Ratio Usually you can monitor the urea reduction rate with pre and post dialysis blood urea samples. So if the URR is high, you can reduce the other parameters in future dialysis.
Initiate with low Ultrafiltrate (UF) In each dialysis session, we remove some amount of water from the body. When the volume of blood reduced, it cause sudden imbalance on osmolality. This also can lead to DDS. Therefore use low UF in early dialysis sessions.
Summery
As a summery dialysis disequilibrium syndrome (DDS) is not a common complication in novel Nephrology and dialysis care. However it was a common complication in history of hemodialysis. Why is this so important? Importance of dialysis disequilibrium syndrome is that its severe neurological complication. These can cause even sudden death. Therefore we have to take necessary precautions to prevent this condition during dialysis.
Reference articles
Zepeda-Orozco, D., & Quigley, R. (2012). Dialysis disequilibrium syndrome. Pediatric nephrology (Berlin, Germany), 27(12), 2205–2211. https://doi.org/10.1007/s00467-012-2199-4
S.M.Silver MD, R.H.Sterns MD, M.L.Halperin MD, Brain swelling after dialysis: Old urea or New Osmoles? American Journal of Kidney Diseases, Volume 28, Issue 1, July 1996, Pages 1-13 https://doi.org/10.1016/S0272-6386(96)90124-9
