A great case of hyponatremia that is in a patient with CNS disease and leading to a Cerebral Salt Wasting vs SIADH picture. Hard to differentiate both when the patient is already on 3% saline. Usually the volume status can give the clue if seen initially before the treatment is started.
Main topic of discussion was an approach to deal with this via a tonicity balance method.
A nice paper by Dr. Mitch Halperin et al in Intensive Care Medicine in 2001 reviewed this topic with a nice example.
When we treat someone with natremias, we account for mostly either free water excess or free water loss and adjust our rate of fluid choices accordingly. A different approach is of using the simple WHAT IS GOING IN ( salt and water) and WHAT IS COMING OUT( salt and water) and calculate the total net NA excess or loss and free water excess and loss and adjust based on that.
Take a look at that paper: Its titled Tonicity Balance and not electrolyte free water calculations guides therapy for acute changes in natremias. A must read!
Wednesday, December 30, 2009
Monday, December 28, 2009
JOURNAL CLUB: ASTRAL
There has been a lot of debate regarding renovascular hypertension/kidney disease and the benefits of revascularization vs. medical therapy. The much anticipated ASTRAL trial has just been published in the NEJM November 12, 2009. However, many questions remain unanswered.
Briefly, this was a randomized, multi-center, unblinded trial of 806 patients with atherosclerotic renovascular disease assigned to either medical therapy or revascularization with medical therapy (403 in each arm) followed over an average of 34months. Primary outcome was renal function as measured by reciprocal of creatinine and secondary outcomes were BP, time to renal and CV events, an mortality. No significant difference was found between the two arms in any outcomes, but 23 patients had complications associated with revascularization, including 2 deaths and 3 amputations.
The study design was based on "equipoise", or true uncertainty about which arm would do better. This, of course, is very subjective. Those thought to benefit from revascularization were excluded. The problem with this is that no one clearly knows who would benefit. Such assumptions are based on small studies looking at such things as degree of stenosis, resistive indices on duplex, hypertension control, renin/aldo levels, degree and rate of decline of renal function, and so forth. To have these patients undergo revascularization may therefore be considered "standard of care", and perhaps this is why a design of this nature was performed (ie. to include these patients would be "unethical").
It should also be noted that ~40% of patients had stenosis less than 70% in both arms, and unilateral RAS was included in a study where the primary outcome looked at renal function (although their posthoc analysis of severe bilateral stenosis or severe unilateral stenosis of solitary kidney also showed no difference).
We must be careful on how we interpret studies. This is a step in the right direction to draw a conclusion, but by no means should this be seen as anything definitive...
Briefly, this was a randomized, multi-center, unblinded trial of 806 patients with atherosclerotic renovascular disease assigned to either medical therapy or revascularization with medical therapy (403 in each arm) followed over an average of 34months. Primary outcome was renal function as measured by reciprocal of creatinine and secondary outcomes were BP, time to renal and CV events, an mortality. No significant difference was found between the two arms in any outcomes, but 23 patients had complications associated with revascularization, including 2 deaths and 3 amputations.
The study design was based on "equipoise", or true uncertainty about which arm would do better. This, of course, is very subjective. Those thought to benefit from revascularization were excluded. The problem with this is that no one clearly knows who would benefit. Such assumptions are based on small studies looking at such things as degree of stenosis, resistive indices on duplex, hypertension control, renin/aldo levels, degree and rate of decline of renal function, and so forth. To have these patients undergo revascularization may therefore be considered "standard of care", and perhaps this is why a design of this nature was performed (ie. to include these patients would be "unethical").
It should also be noted that ~40% of patients had stenosis less than 70% in both arms, and unilateral RAS was included in a study where the primary outcome looked at renal function (although their posthoc analysis of severe bilateral stenosis or severe unilateral stenosis of solitary kidney also showed no difference).
We must be careful on how we interpret studies. This is a step in the right direction to draw a conclusion, but by no means should this be seen as anything definitive...
TOPIC DISCUSSION: NSF post transplant. theraputic challenge
A patient with history of Minimal Change disease and lupus nephritis who had renal transplant few years back. unfortunately immediately before transplant she had MRI with Gad. for years she had been complaining of a taught skin and immobility in her joints. recently she was seen by rhem and a skin biopsy showed NSF. her Cr 1.0. she is on prograf, cellcept prednison, what could we do to treat NSF? since we're able to diagnose it.
so NSF has been recently recognized as potentially a fatal disease. it is characterized by myofibroblasts depositions in internal organs such as liver, heart, kidneys etc as well as externally mainly the skin. it presents as painful,symmetrical thickening of the skin and the joints that can be misdiagnosed as scleroderma and alike,calciphylaxis, cellulitis. it follows a progressive unremitting coarse. major risk identified is exposure to gadolinium in dialysis patients or CKD patients with GFR<30. it maybe dose related.
all cases are retrospective, and all have been exposed to gad by history.
how?Free Gd3+ is poorly soluble, highly toxic, and can form precipitates with anions that tend to be elevated in renal failure. This has led to the hypothesis that excess exposure to free Gd3+ in patients with kidney disease leads to tissue damage.PD patient maybe at higher risk. Gad half life is dramatically increased to 1.3hrs in healthy to over 15 hours in CKD 5 patients.
Initiation of recombinant human erythropoietin (EPO) therapy or an increase in dose may be associated with NSF, but the true nature of the relationship between EPO and NSF remains incompletely understood.A case report described two patients without a history of exposure to gadolinium who developed NSF post-kidney transplantation ;the authors postulated that vascular manipulation or endothelial injury was a possible trigger.
treatment:case series. transplantation, Extracorporeal photopheresis ,Ultraviolet A1 (UV-A1) phototherapy, Plasmapheresis and more recently rapamune and gleevac have been proposed. all of these therapies have been inconsistent and disappointing.
back to the above case: options are either switching to rapamune based regimen. or addition to gleevac with special attention to infectious risks and significant edema developing in these patients.
JOURNAL CLUB: Is there anything we can do to prevent Contrast induced nephropathy?
Few weeks ago we discussed a new item on the many disappointing items that have been proposed to mitigate the risk for contrast nephropathy. the article in the Circulation 2009;120:1793-19-799, Iloprost-a prostacyclin analog- a vasodilator was noted in rat studies to attenuate the ischemic effects of contrast media. so a randomised, double blinded, placebo-controlled trial to see if Iloprost is up to the challenge. 208 patients, Cr 1.4 or more, cardiac angiograms were done +/- intervention. results: ??it may protect CIN.
obviously this is a small study, their placebo CIN rate was much higher than usual(23% vs 5-15%) which may have helped improve the data for the study drug. other issues were the inappropriate use of eGFR in a dynamic situation, the significant hypotention in the Iloprost arm is a concern, the bleeding tendencies from the platelet-inhibition property of Iloprost.
what do we know about CIN: 3-13% depending on definitions and patient populations, most significant risk factor is CKD, you can multiply Cr by ten and get an estimated risk score, it rarly leeds to dialysis, hyperosmolar contrast and >150cc increase the risk. other soft risk factors like low ef, anemia, diuretic use, chf, Htn, ?ace.
best treatment is prevention; Normal saline vs 0.5%saline 12 hours prior.
etilogies proposed: vasoconstriction, upregulation of the RAS system, dowenregulation of the vasodilators signaling, PH acidemic being worse.
??ischemic-reperfusion injury.
obviously this is a small study, their placebo CIN rate was much higher than usual(23% vs 5-15%) which may have helped improve the data for the study drug. other issues were the inappropriate use of eGFR in a dynamic situation, the significant hypotention in the Iloprost arm is a concern, the bleeding tendencies from the platelet-inhibition property of Iloprost.
what do we know about CIN: 3-13% depending on definitions and patient populations, most significant risk factor is CKD, you can multiply Cr by ten and get an estimated risk score, it rarly leeds to dialysis, hyperosmolar contrast and >150cc increase the risk. other soft risk factors like low ef, anemia, diuretic use, chf, Htn, ?ace.
best treatment is prevention; Normal saline vs 0.5%saline 12 hours prior.
etilogies proposed: vasoconstriction, upregulation of the RAS system, dowenregulation of the vasodilators signaling, PH acidemic being worse.
??ischemic-reperfusion injury.
IN THE NEWS- BONE DISEASE POST TRANSPLANTATION
After renal transplantation, a large percentage of patients lose bone. This loss of bone results from a combination of factors that include pre-existing renal osteodystrophy, immunosuppressive therapy, and the effects of chronically reduced renal function after transplantation. Many studies have found that the type of bone disease that pre dominates in the post transplantation world is Low turnover disease. Low bone volume and low bone turnover has been associated with cardiovascular calcifications. Do we use less Vitamin D in these patients, more of cinacalcet, the data is scant? This review might help answer few questions and stem more for further research.
Wednesday, December 23, 2009
IN THE NEWS- HIVAN CONCEPT CHANGE?
A recent study in Am J of Physiology Renal Physiology is showing a novel concept. The investigators did a basic science study on role of epithelial mesanchymal transdifferentiation (EMT) in the development of HIVAN phenotype. Their data showed that in mice, it appears that myofibroblasts are migrating from either glomerular or tubular sites and then proliferating. Series of stainings confirmed that EMT was happening and was contributing to the proliferative phenotype in HIVAN mice.
So its likely that in collapsing FSGS there is proliferation, but not of podocytes as once thought. So it still might be a podocytopenic process due to proliferation of other types of cells and leading to EMT causing this change. Its a start of an out of box thinking of this process.
Hopefully this might shed some light and perhaps help in treatment of HIVAN in addition to HAART when it occurs.
CONSULT ROUNDS
TMA in Lupus. This is a controversial topic and evidence is not really present on what to do. The topic was about using plasmapheresis for such patients.
Key Points
1. Lupus Nephritis and plasmapheresis --> the evidence is negative for use of it.
2. TMA in Lupus( evidence of schistocytes, LDH , low haptoglobin, thrombocytopenia, renal failure, proteinuria, hemolytic anemia) ---> plasmapheresis has shown some benefit if given early to reverse the TMA process and or renal function improvement( its all based on case series and case reports)
3. In prior cases, acute renal failure and MAHA resolved with use of pheresis, steroids or heparin. The cases reported provided further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases. ADAMTS-13 Antibodies might play a role in lupus TMA or possible role of anti endothelial antibodies. Removal of these antibodies with pheresis is the goal.
Anti CD20 agents might be helpful as well given their role in decreasing production of those antibodies!
Key Points
1. Lupus Nephritis and plasmapheresis --> the evidence is negative for use of it.
2. TMA in Lupus( evidence of schistocytes, LDH , low haptoglobin, thrombocytopenia, renal failure, proteinuria, hemolytic anemia) ---> plasmapheresis has shown some benefit if given early to reverse the TMA process and or renal function improvement( its all based on case series and case reports)
3. In prior cases, acute renal failure and MAHA resolved with use of pheresis, steroids or heparin. The cases reported provided further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases. ADAMTS-13 Antibodies might play a role in lupus TMA or possible role of anti endothelial antibodies. Removal of these antibodies with pheresis is the goal.
Anti CD20 agents might be helpful as well given their role in decreasing production of those antibodies!
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