Lithium and Renal Failure: Role of Corrected Creatinine Clearance

Lithium can affect renal function in several ways:
- The most common complication of chronic lithium therapy is nephrogenic diabetes insipidus.
- Lithium may also be responsible for a distal tubular acidification defect.
- The role of lithium in the production of acute renal failure is well accepted.
- However, controversy exists over its role in chronic renal failure.

Q: How do you monitor patient chronically on Lithium for early signs of renal failure?

Answer: 24 hour urine should be collected for corrected creatinine clearance

Serum Creatinine Levels alone are an insufficient measure of renal function. By the time it's above normal or even at the high end of normal, it's too late. The patient is already in renal failure, defined by GFR.



Estimated GFR (eGFR) is only fairly accurate below 59 ml/min, but it's with eGFR's above that level that we want to be making decisions about discontinuing lithium. Nephrologists use the eGFR extensively for following their patients, but their patients are people who are already in renal failure and usually do have eGFR's below 59.

urine creatinine (mg/dl)/serum creatinine (mg/dl) x 24-hr urine volume (ml)/1440 minutes x 1.73/BSA = corrected creatinine clearance (ml/min), which minus 20% = GFR.

Case examples reported by Dr. Jean Aycock, M.D.:

(1) One patient had been referred to me by her retiring psychiatrist who had obtained an annual serum creatinine level, which had gradually crept up from 0.9 to 1.3. I did a 24-hr urine collection & found she had a corrected creatinine clearance of 39 ml/min, GFR of 31 ml/min.
(2) The other was my patient, on whom I was obtaining a baseline 24-hour urine prior to starting lithium therapy (she'd never taken it before), who had a serum creatinine level of 1.1 mg/dl. Her corrected creatinine clearance was 76 ml/min, for a GFR of 61 ml/min.
I referred both patients to nephrologists, who confirmed stage 3 and 2 renal failure, respectively.


Physicians can provide following information to patients for accurately doing 24 hour urine collection.

Instructions for 24-hour urine collection prior to starting lithium therapy:

1. Pick up the urine container(s) from the lab.

Make sure the container lid is properly seated and screwed on firmly after each use and before re-transport to the lab. All urine has to make it or you'll need to repeat the entire collection.

You will also need to repeat the collection if you don't remember to collect every single drop of urine during the timed 24-hour period, as otherwise you may falsely appear to be in renal failure.

You will also need a large wide-mouthed flexible plastic drink cup.

2. You may choose to start your collection at either of these times: at (10 AM) (4 PM), empty your bladder as usual into the toilet (DO NOT COLLECT THIS URINE).

Your 24-hour collection starts with a just-emptied bladder. Record the exact time.

3. Choose the one toilet in your home you're going to use for the next 24 hours and tape a large sign to it or in front of it to remind yourself to collect all urine. Place the plastic cup to collect your urine and the collection bottle on the toilet lid. Put them back on the lid after each use.

Tape other toilets shut and/or put signs on them to yourself to use only the toilet you've designated; ask family members not to use "yours". If there is one toilet for the household, others will need to remember to replace your cup and container on the lid.

4. For the next 24 hours, you will be collecting every drop in your bladder in the plastic cup and pouring from it into the large container.

5. Continue collecting all urine until (10 AM) (4 PM) (or the exact time you noted yesterday as the beginning of the collection), when YOU WILL COLLECT THE LAST DROPS in your bladder in the cup, pouring from that into the collection bottle. This ends the collection.

6. Take the collection bottle(s) and your lab order and go immediately to the lab to have your blood drawn and to turn in the urine collection.


Instructions for 24-hour urine collection for those who are taking lithium:

1. Pick up the urine container(s) from the lab. As taking lithium may have increased your total urine volume, if you think you may fill more than one, be sure to request two containers. DO NOT OVERFILL.

Make sure the container lid is properly seated and screwed on firmly after each use and before re-transport to the lab. All urine has to arrive at the lab or you'll need to repeat the entire collection.

You will also need to repeat the collection if you don't remember to collect every single drop of urine during the timed 24-hour period, as otherwise you may falsely appear to be in renal failure.

You will also need a large wide-mouthed flexible plastic drink cup.

2. You may choose to start your collection at either of these times: at (10 AM) (4 PM) take your (morning) (evening) lithium, ( _____________, and ___________) and then empty your bladder as usual into the toilet. DO NOT COLLECT THIS URINE.

Your 24-hour collection starts with a just-emptied bladder. Record the exact time.
Take other medications at your usual times.

3. Choose the one toilet in your home you're going to use for the next 24 hours and tape a large sign to it to remind yourself to collect all urine. Place the plastic cup to collect your urine and the collection bottle on the toilet lid. Put them back on the lid after each use.

Tape other toilets shut and/or put signs on them to yourself to use only the commode you've designated; ask family members not to use "yours". If there is one toilet for the household, others will need to remember to replace your cup and container on the lid.

4. For the next 24 hours, you will be collecting every drop in your bladder in the plastic cup and pouring from it into the large container.


5. Take your usual (PM) (AM) lithium and other meds as directed (__________, ___________) at (10 AM) (4 PM). Take other meds on your usual schedule.

6. Continue collecting all urine until (10 AM) (4 PM) (or the exact time you recorded yesterday as the beginning of the collection), when YOU WILL COLLECT THE LAST DROPS in your bladder in the cup, pouring those into the collection bottle. This ends the collection.

7. Take the collection bottle(s) and your lab order and go immediately to the lab to have your blood drawn and to turn in the urine collection.


Note: This information including this amazing patient information notes are made by Dr. Jean Aycock, M.D. Posted after his approval. Thanks again Dr. Jean Aycock.