Friday, July 31, 2015

Journal Club: CAPTAIN TRIAL: ACEI /ARB pre cardiac cath: Hold or not to hold

There is unclear evidence on holding ACEi/ ARB prior to coronary angiography reduces contrast induced nephropathy (CIN). The CAPTAIN trail just published in the American Heart Journal was a randomized trial to investigate whether holding ACEi/ ARB prior to cardiac catheterization reduces the incidence of contrast-induced AKI in patients with chronic kidney disease (CKD).

Some key points:
Total of 208 patients underwent randomization over 6 years with CKD as defined - creatinine >1.7mg/dl w/in 3 months before  cardiac catheterization and/or serum creatinine > 1.5 mg/dl w/in 1 week before cardiac catheterization
Primary outcome: incidence of AKI defined as an absolute rise in Scr of >0.5 mg/dl from baseline and/or a relative rise in Scr of > 25% compared with baseline at any time between 48 and 96 hrs post-cardiac catheterization.
Secondary outcome: absolute difference in post-procedure creatinine compared with baseline creatinine
Safety outcome was a composite of CHF or hypertension after the procedure
Results of the study demonstrate that in patients with CKD, holding compared w/ continuing ACEi/ARB prior to cardiac catheterization, with-holding ACEi/ARB resulted in a:
1.       Non-significant reduction in contrast-induced AKI
2.       Significant reduction in post-procedural rise of creatinine.
3.       Study demonstrated a strong trend toward improved clinical outcomes when ACEi/ARB was held before angiography.
4.       No adverse events were reported in the hold ACEi/ARB group
5.       Safety: no rise in CHF or HTN with holding ACEi/ARB therapy

This randomized trial does suggest that in CKD patients, it might be beneficial to hold the ACEI/ARB pre cardiac cath for some potential benefit.  A larger N would have perhaps been important to do to get a better sense of this protective effect. A multi center study would have been useful as well. 

Tuesday, July 28, 2015

Consult Rounds: Ifosfamide Toxicity

Ifosfamide induced renal damage comes in 6 flavors. The toxic agent is metabolite chloroacetaldehyde rather than the parent drug to the tubular cells of the kidney.
1.     Pure hypophosphatemia – this is due to direct proximal damage
2.     Fanconi syndrome
3.     Pure renal potassium wasting syndrome leading to hypokalemia
4.     ATN
5.     Distal RTA
6.     Nephrogenic Diabetes insipidus

Friday, July 17, 2015

In the NEWS: Amyloidosis and potential novel treatment

Systemic amyloidosis contains non fibrillar protein called serum amyloid P ( SAP).   Novel agent that is called CPHPC depletes SAP from the plasma but leaves some SAP in the amyloid deposits.  Following giving CPHPC, if given anti SAP antibodies, it can clear the remainder of the free SAP. A recent study in NEJM did an open label single dose phase 1 trial to look at 15 patients with systemic amyloidosis using the above strategy and there was clearance of amyloid deposits from liver and other tissues.

Few interesting and key points
What type of amylodosis: the patients included had AA, AFib, AL, AApoA1 type of amyloidosis.
What tissues involved: Liver, spleen, kidney, bone marrow, ( no patients with cardiac or severe renal involvement)
Any renal adverse events:- None in liver or kidney

This is a fascinating new pathway of treating patients with fibril based disease like amyloidosis. Wonder if this similar approach might be useful in other renal fibril forming disease such as fibrillary GN or immunotactoid GN. 

Monday, July 13, 2015

Immunosuppresion Medications in Nephrology

Since the 1970s, the transplant literature has been soaring with anti rejection medications. In the last decade, we as nephrologists are starting to learn from Rheumatology and Oncology on novel targets to treat GNs and Rejections in grafts. A recent review in CJASN highlights the different categories of agents in immunosuppression that we have to our disposal.

T cell directed therapy that target signal 1 from TCR and antigen presenting cell such as OKT3 and  and CNIs
T cell directed therapy that target signal 2 that is costimulatory such as Abatecept and belatacept. In addition, there are newer agents being developed for co situmatory blockade by CD154;CD40 targeting.

B cell directed therapy such as Anti CD20 agents such as rituximab, ocrelizumab and veltuzumab
B cell directed therapy such as Anti CD22 agents such as epratuzumab being tried in SLE
B cell targeting agents for B cell differentiation such as belimumab and atacicept.
Plasma cell targeting agents such as bortezomib( carfilzomib hasn't entered the renal world yet)

Complement inhibitors such as eculizumab
Cytokine targeting agents such as steroids
Specific cytokine agents such as anti IL-2 antagonist( basiliximab) and anti TNF alpha
IL-1 antagonists such as anikinra and canakinumab
IL-6 inhibition by tocilizumab being studied in transplant patients
IL-17 inhibition by secukinumab not currently being utilized in renal patients

mTOR inhibitor such as sirolimus and everolimus
Anti CD52 such as campath and alemtuzumab
Inhibition of DNA synthesis by azathioprine, mycophenolate, and leflunomide
Cytotoxic agents such as cyclophosphamide used for many GNs
Finally, pooled polyclonal abs such as IVIG have been used and polyclonal antithymocyte globulins for induction.

Sunday, July 5, 2015

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