Muddy brown casts are diagnostic for ATN, or acute tubular necrosis, which is an intrinsic form of AKI. But if you don’t see muddy brown casts, can ATN be ruled out? The literature on this is surprisingly light. There is one study of 267 patients with AKI who were classified as low or high pretest probability for ATN and had urine samples analyzed. The study concludes: “In patients with a low pretest probability of ATN (initial diagnosis of prerenal AKI), lack of casts or RTEC on urinary sediment examination had a sensitivity of 0.73 and specificity of 0.75 for a final diagnosis of prerenal AKI. The negative predictive value of lack of casts or RTEC in patients with low pretest probability of disease was 91%.” One important point to take away is that your pretest probability matters a lot for how confident you should be about making a diagnosis.
This review, by the same group, has a nice discussion section about making the diagnosis of ATN through a combination of methods, including microscopy, and use of FeNa and FeUrea.
Here’s something you may see sometimes: a patient presents with a (non-hemolyzed ) potassium of 7.0. Scary! But you check a potassium on VBG, and it returns 5.5. Which is the right value? What’s going on here?
Serum potassium, generally speaking, is more accurate. Serum samples contains potassium released by platelets (which are separated out in the phlebotomy tube) so is usually 0.1-0.7 mmol/L higher than plasma samples. Whole blood potassium is usually accurate enough, especially when you need a potassium level quickly in a critical care/emergency setting.
Immunosuppressants aim to prevent this from happening:
But too much immunosuppression can cause this:
That’s why people can’t just be on ONE immunosuppressant after transplant: the doses required would be too toxic, so the effect is spread out over 2-3 medications.
Considering that the historical option was total body irradiation, we’ve come a long way. Azathioprine was the first chemical immunosuppressant, but cyclosporine, which came onto the scene in the 1970s, revolutionized kidney transplant survival rates.
***One of my chiefs last year made an amazing figure on maintenance transplant immunosuppression. It is worth this whole post and I highly encourage you to take a look!***
For us peons, what are the commonly used immunosuppressants?
Mechanism of Action
Calcineurin inhibitor (CNI)
Cr, drug trough
Neurotoxicity, nephrotoxicity, diabetes, alopecia *many drug interactions
Pneumonitis, arthralgias, edema, hypertension, bone marrow suppression, hyperlipidemia
0.75-1 mg twice daily
arthralgias, edema, hypertension, bone marrow suppression, hyperlipidemia
The dozens of things steroids do
Varies widely, minimum 7.5 mg every other day or 5 mg daily
Osteopenia, diabetes, headache, Cushing’s, weight, cataracts, psychosis (and many others)
## Mycophenolate can be either mycophenolate mofetil vs. sodium. The difference is that the sodium formulation (Myfortic) is an enteric capsule that may prevent some GI effects like diarrhea(?) but the jury is still out.
What are the major side effects of immunosuppression?
What is the underlying biology? ***This is a gross oversimplification.
Normally, T cells go scouting and if they encounter an antigen-presenting cell with foreign material on it, a chain reaction of events is started: calcineurin is activated, leading to a surge of IL-2 and its receptor, IL-2R, which upregulates the mTOR pathway, which leads to DNA nucleotide synthesis so that the T cell can multiply and generate an immune response.
Notice that the bolded words are the targets of the 6 immunosuppresants in the chart above.
Transplant pharmacology is REALLY COMPLICATED and you can do an entire fellowship training program for this. This is an excellent, but 100-page document from a Canadian transplant website. Here are two organ-specific guides/reviews regarding immunosuppression:
The time will come when you have a patient whose serum bicarbonate level is 7 (normal is 24). Usually, this happens in acute renal failure or septic shock associated with a serious metabolic acidosis.
First question: how does bicarb become low? One way is through renal/GI losses of bicarb. There are also types of metabolic acidosis that are associated with decreased bicarb–DKA and lactic acidosis (ketones and lactate that could be converted back into bicarb but are excreted instead). There is also iatrogenic bicarb loss, such as when you give a patient with already low bicarb huge boluses of normal saline. This causes a hyperchloremia that further depletes the organic anions that could have been converted back to bicarb. A more chronic problem is the inability of the kidneys to generate bicarb. This review from CKJ gives a great overview of non-gap metabolic acidosis.
Second question: when should you give oral or IV bicarbonate? Oral bicarbonate is more appropriate for patients who will continue to lose bicarb in the oupatient setting–chronic diarrhea or RTA, for instance. The inpatient setting is more opinion-driven, but what I’ve seen is consistent with this paper on bicarb supplementation, which says to give IV bicarb at an arterial blood pH of ≤7.0. The amount given should be what is calculated to bring the pH up to 7.2.
The reason why it’s important to not give IV bicarbonate liberally is because it is actually associated with higher mortality. Shifts in calcium, increase in extracellular potassium that can cause arrhythmia, hypernatremia and volume expansion (causing flash pulmonary edema) may result. You may also see a paradoxical worsening of acidosis because bicarb is converted to CO2!
There are multiple components to hemodialysis, and each session of dialysis must be tailored to an individual patient’s needs. For example, do they need more fluid taken off because they have heart failure? Do they need more potassium in the diasylate because they are persistently hypokalemic? Here are some words that you may see in a renal fellow’s note about the components of dialysis and a brief description of what they mean. If you have a LOT of time on your hands, check out these EBPG guidelines published in 2007.
Dialyzer: not actually part of the dialysis rx, but I wanted to include it to help you understand the machinery of receiving dialysis. Here is a helpful overview for patients from Davita about the plastic tube that actually does the work of dialyzing.
Duration: how long is the dialysis session? Different patients may only be able to tolerate so much, or they may need longer sessions to filter the fluid more slowly. There is no conclusive evidence that longer dialysis time reduces mortality.
Ultrafiltration goal: This refers to how much “excess water” is taken off at each session. It is based on that patient’s estimated dry weight (EDW), although the EDW may be difficult to determine at first. There is no recommendation for an UF goal in the US, but based on observational studies, some countries recommend an arbitrary goal of 750-1000 mL/day in anuric patients.
Sodium: low sodium concentration may exacerbate hypotension, but high sodium may exacerbate volume overload
Calcium: patients with a low concentration of calcium in their bath may not experience as much intra-dialysis hypotension, gain higher vitamin D levels, and can use more phos binders containing calcium to lower phos levels
Bicarbonate: usually adjusted to maintain a serum bicarbonate >23. This is important for reducing acidosis.
ultra-coefficient: referred to as KUF, has to do with the amount of fluid crossing the diasyler membrane with regards to time and pressure. I don’t have enough physics know-how to fully analyze its value, but these people seem to.
Diasylate temperature: It is thought that lowering the diasylate temperature makes dialysis easier to tolerate and improves symptoms of fatigue/post-dialysis syndrome. Why? Kind of unclear.
When you encounter a patient who has end-stage renal disease and is on dialysis, there are a few questions you should make sure to answer that will help in your management:
What is their dialysis schedule? Have they missed any sessions recently?
Does the patient have anemia? Many dialysis patients have anemia of chronic disease due to decreased EPO production. Do they receive EPO during their dialysis sessions?
Does the patient have hypertension? If so, is this because they are volume-overloaded? Excess fluid can be removed in dialysis as tolerated. In the meantime, you should make sure to keep their blood pressures carefully controlled (and not too low).
Do they have evidence of bone disease? Many patients with ESRD have tertiary hyperparathyroidism (click on the link for a brief pathophys reminder). They may be on cinacalcet (calcimimetic that decreases calcium and phos levels) or sevelamer (phos binder).
Are their medications renally dosed? It seems like a no-brainer, but you’d be surprised. Also, are there specific medications that they do receive during dialysis? This is especially important for timing of medications like antibiotics.
What is their access? Where is their fistula? Or do they have a tunneled cath? They cannot have IVs in the same arm as a fistula.
Nutrition: one of the areas that we as clinicians tend to gloss over, but is extremely important to our patients (have you ever ordered from the renal menu? It SUCKS). Make sure they are on a low K/phos/sodium diet; patient should also be taking nephrocaps (vitamin B and C).
Up to 70% of patients require renal replacement therapy or dialysis. Dialysis is renal therapy via diffusion of small solutes, whereas filtration is the convection of large solutes. Early treatment is better, obviously…
intermittent hemodialysis: is easier to implement, more practical, better solute clearance and fewer bleeding complications
continuous dialysis: better for hemodynamically unstable patients, if have renal and hepatic failure, or acute brain injury
requires continuous anticoagulation with heparin or UFH
citrate may cause electrolyte issues (chelates ionized Ca)
CVVHDF=continuous venovenous hemodiafiltration=dialysis +filtration. The #1 modality in the ICU. Large volume, requires fluid replacement.
CAVHD or AVHDF requires arterial cannulation, and is unreliable in pts with low BP, PVD. More risky.
SLEDD (hybrid of intermittent and continuous): more flexible than continuous, less need for anticoagulation, but has the same efficacy as continuous