Last Friday I started teaching third year medical students. This is the first time I have taught medical students (in isolation, there are always medical students at my lectures for the residents) since 2003, when I ran a teaching section for renal physiology for first year medical students at Pritzker School of Medicine, University of Chicago with John Asplin.
I am now teaching the medical students two lectures every rotation, the first on sodium and the second on potassium and calcium. I hope to expand this to ABGs and another electrolyte lecture so I can isolate potassium and spend an entire hour on it.
I modified my Don’t Panic handout for the students. During the lecture I realized that the SIADH section was weak and too complex for the students. I will probably change it to focus on the fact that ADH reduces water excretion and that this can be adaptive (early CHF, volume depletion, hyperosmolar) or maladaptive (SIADH). I will change the section on the dilution of urine to a background box as I think it is important but only interesting to nephrologists and similar wierdos.
I will add a focus on a few clinical scenarios with increased ADH.
July first. The ultimate deer in the headlights day.
I spent much of my day pointing out where the bathrooms were and telling the new residents that, “Yes. You do need to do the admission on the patient that you were called about at 3 pm.”
I am attending on the Nephrology consult service and we have a neat case. Bevacizumab induced thrombotic microangiopathy with acute renal failure. The patient is recovering renal function and the only thing I am going to add to the case at this point is removing the Quinton, but its interesting seeing a rare(?) complication on the bleeding edge of medicine.
Vascular endothelial growth factor or VEGF is a critical factor in the growth of blood vessels. I once saw Dr. Judah Folkman, the father of anti-angiogenesis treatment speak at IUPUI. Bevacizumab is a humanized mouse antibody targeted against VEGF. It was the first anti-angiogenesis drug licensed in the U.S. (I guess thalidomide doesn’t count).
Funny thing is, the kidney is pretty vascular and this drug causes proteinuria in 21 to 64% and hypertension in 3 to 36%.
Eremina Et al. published a 6 patient series inwhich patients developed proteinuria and renal failure following exposure to bevacizumab. All 6 patients had a renal biopsies consistant with thrombotic microangiopathy (TMA). TMA is most commonly associated with TTP but these patients did not have systemic signs of this: no fever, no mental status changes. Hematologically only one patient had schistocytes, only one patient had thrombocytopenia and anemia was found in only 2 of the 6 cases. TMA is also seen in pregnancy related renal failure, hypertensive emergency, and scleroderma renal crisis. Pre-eclampsia, one form of pregnancy related renal failure that causes TMA is also associated with decreased VGEF. Patients with pre-eclampsia have decreased due to metabolism by increased sFlt (soluble fms-like tyrosine kinase) produced in the placenta.
In addition to the case series, the authors performed an animal study where they created a mouse inwhich they could turn off the VEGF gene by feeding it tetracycline. When they did this they were able to produce an identical renal lesion.
Lastly they took the mice who were tetracycline to shut down the VEGF gene, and supplemented them with human VEGF. This failed to ameliorate the renal pathology.
In addition to demonstrating a new, and severe side effect of a powerful new anti-cancer weapon, Eremina Et al have demonstrated a previously unknown aspect of renal physiology. The importance of VEGF to capillary endothelial cell health. A remaining puzzle is how a protein made in the renal podocytes (epithelial cells) traverses across the basement membrane (against the primary flow from capillary to the urinary space) to protect the glomerular capillary endothelium.
Interestingly, in the NEJM series, none of the patients required dialysis. Additionally there was no consensus on how to treat this condition. One patient received plasmapheresis, as is required with TTP. One received cyclophosphamide and prednisone as is done with all glomerular lesions that look scary. Our patient received both dialysis for a few days and two plasmapheresis sessions. The dialysis was needed for her renal failure and the plasmapheresis seems right as the half life of monoclonal antibodies is long (Bevacizumab has a half-life of 20 days).
The authors finish their discussion talking about how their animal model in does not match the human condition: 100% of the mice were affected versus a small minority of humans; the human lesion is reversible while it is not in mice.
Only a nephrologist ever capitalizes Fluids and Electrolytes.
I am so excites. I get to give the first lecture on July 1. I love the nervous energy that comes with fresh second years and new interns still getting used to the length of their newly lengthened coats.
I am working over my standard F&E Emergencies. I am putting together a new handout designed to be kept in the pocket. While working on the talk I re-found this classic review of diuretic therapy by Craig Brater. Dr. Brater was elevated to Dean of Indiana University Medical School right before I got married at the end of my residency. We had our rehearsal dinner at this Columbia Club on the Circle. I bumped into Dr. Brater right before dinner and congratulated him on becoming the dean.
