CKD after AKI in the ICU

I give a regular talk to the residents in the ICU on CRRT and one of the things that I focus on is prognosis. We all know that the outcomes of patients requiring CRRT in the ICU are poor. Multiple studies have shown that the mortality is 40-60% and that this mortality rate has not changed in the last 20 years. However, something that residents are less aware of is that, in the event that a patient survives their stay in the ICU, the majority will not require long term dialysis - approximately 80%. This is sometimes difficult to appreciate when you see patients on HD at discharge from the ICU but most of these will recover at least some renal function. One question, however, is how much function they recover and if this has any bearing on their overall mortality.

A paper recently published in CJASN goes a long way towards answering these questions. This was a retrospective cohort study of all 1220 patients admitted to the ICU requiring CRRT in a single center in the Netherlands between 1994 and 2010. As expected, the in-hospital mortality was high (55%). Of those who survived, 12% did not recover enough renal function to come off dialysis after discharge.

The commonest reasons for admission were thoracic surgery and sepsis. 20% of patients had pre-existing CKD, 48% had normal baseline renal function. There was no baseline in the remainder. At the time of discharge from hospital, 60% of patients had some degree of renal dysfunction (30% eGFR 30-60, 15% eGFR 15-30, 15% eGFR 0-15 including the 12% on HD). Of note, more than half of the patients with an eGFR <15 at discharge had pre-existing CKD. Unadjusted patient and renal survival is shown in the table:

The independent predictors of long term mortality were age, a surgical diagnosis, malignancy and an eGFR < 30. Similarly, the predictors of future need for dialysis were pre-existing CKD, and an eGFR < 30 at discharge. Interestingly, an eGFR between 30 and 60 was not associated with an increased risk of mortality or need for RRT in the future, relative to those with normal renal function at discharge.

This study adds to our knowledge of the predictors of outcomes after an episode of AKI requiring CRRT. No-one should be surprised that patients with significantly reduced GFR at discharge at are increased risk of mortality and need for eventual dialysis. However, it is reassuring that, in those patients who have an eGFR >60 at discharge, the likelihood of them requiring dialysis in the future is very low. It would be interesting to know if the presence of proteinuria modified the relationship between eGFR and mortality/need for dialysis, particularly in those with an eGFR between 30 and 60 at discharge but unfortunately, these data were not available.

Gassy

When putting a patient on CRRT, the choice of buffer these days is largely dependent on whether or not you want to use citrate for anticoagulation. Most of our patients get either citrate or bicarbonate. However, not so long ago, the main buffer was lactate. When bicarbonate was first being used as a buffer for CRRT, it had to be added separately to each bag and, in our institution at least, it came in a glass bottle next to the CVVH fluid.

More recently, the bicarbonate comes in a separate compartment of the same replacement fluid bag and just prior to use, a valve is broken and the bicarbonate-rich fluid is mixed with the rest. I had previously assumed that this was because you do not want to mix bicarbonate with calcium because of the risk of precipitation. However, in our institution, we currently use calcium-free replacement fluid and so there is no risk of precipitation (the calcium is given intravenously to the patient based on a sliding scale).

It turns out that the reason for the separate bicarbonate bags is much more interesting. Most i.v. fluid bags are gas permeable. Therefore, if you leave bicarbonate in the bag for a prolonged period of time, CO2 will leach out of the bags. By a passive process, the bicarbonate in the fluid will then be converted to CO2 which will come out of solution and will in turn leach. You will, in the end be left with very little bicarbonate in the bags. To get around this, the manufacturers of dialysate fluids used put the bicarbonate in a separate glass bottle, This is expensive and cumbersome and is prone to errors if somebody forgets to add it to the solution. Instead, now the bicarbonate-containing dialysate fluids are double-bagged. The inner bag contains the solution and is gas-permeable as before. The outer bag is constructed of a thicker, non-permeable plastic that keeps the CO2 inside. Also, to reduce diffusion further, the air between the two bags has a relatively high CO2 concentration. 

Mercury rising

A patient who had been working in a recycling company that handled thermometers presented with fever, dry cough, fatigue and rash. Based on imaging (CXR showed massive radio-opaque material in the lungs, right atrium and right ventricle; skeletal survey showed radio-opaque deposits in the kidneys, bowel wall, and bladder wall), symptoms, and a positive history of exposure, a diagnosis of mercury intoxication was made. The patient developed multi-organ failure including anuric acute renal failure, and nephrology was consulted. Further background details on the case can be found here. What is the treatment and the role of dialysis in mercury intoxication? 


Metallic mercury has a widespread use both within industry and in many everyday objects such as thermometers, dental amalgams, batteries, fluorescent light bulbs, and many others. Mercury intoxication can result from vapor inhalation, resulting in severe respiratory symptoms, or from injection, usually in cases of attempted suicide. 


The chelating agents 2,3- dimercaptopropanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are central to the management of mercury toxicity. DMSA is given orally, and can cause leucopenia and elevated liver enzymes. DMPS is an intravenous medication and its use is associated with hypotension. In our patient, DMSA 500 mg po q 8hrs was given for 4 days, before it was discontinued because of elevated LFTs and leucopenia. We then started DMPS with CRRT but unfortunately, after two weeks of supportive treatment, the patient died. 


Chelators such as DMPS and DMSA work by mobilizing mercury and facilitating its excretion through the kidneys. This creates a management conundrum in the anuric patient, as this route of excretion is not available. Consistent with this, our patient’s blood mercury levels rose dramatically during chelator treatment, despite CRRT. We hypothesize that the administration of DMPS mobilized mercury from extracellular deposits and redistributed it to the blood and organs, but it failed to be adequately eliminated from the body because of anuria. For this reason, intensive CRRT with a high-flux dialyzer is a critical adjunct to chelator therapy. If this is not available, continuous renal replacement therapy with chelators have showed better mercury clearance than conventional dialysis, whereas peritoneal dialysis has been shown to be ineffective at clearing mercury. These principles should be borne in mind in other heavy metal poisonings also. Other management pearls I took from this unusual case were to initiate dialysis early and to give DMSA at a lower and more frequent dose to avoid serious side effects. 


Tarek Alhamad M.D.