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

Tuesday, June 30, 2015

Topic Discussion: What is the incidence of MGRS?


There is a new entity that is now being defined as MGRS ( when MGUS affects the kidney). The incidence of MGUS rises with age and there is lifetime 1% risk of transforming to myeloma or other cancers such as amyloidosis.

What is the incidence of MGRS? So what percentage of MGUS patients develop renal disease? Turns out, no published work has this answer.  An abstract presented at American society of Hematology (ASH) in 2013 might have the closest answer.


The study looked at a large database of lab values and 15 year follow up analyzed.   425 confirmed MGUS patients with no progression to Myeloma were evaluated.  297 patients had MGUS and normal renal function at baseline.  Over median of 852 days , 21/297 developed renal Impairment.  15/21 had monoclonal free light chain production.  Time to renal impairment was shorter with the higher free light chain ratio at baseline. Patients with involved Free light chain >100mg/dl were at the highest risk of renal failure.   So based on this one study, there is about 7% risk of MGRS from MGUS.  Seems high but we really need to wait published data on this topic. If it is truly 7%, screening with UA and protein/crt ratio with a complete metabolic panel might be indicated in patients with rising FLC ratios. 

Saturday, June 27, 2015

ASN and NBPAS

Recent changes to MOC and criticism of ABIM, where does nephrology stand.  Bold move by ASN to interview with founder of the new organization National Board of Physicians and Surgeons(NBPAS).

I think starting this discussion now is so critical. Hats off to Tod Ibrahim and ASN to take this initiative as we need to redefine that is reasonably priced and truly looks at clinical work that we do.

http://asn-online.org/media/podcast.aspx?p=kidneynews&e=2015_06_25_Teirstein.mp3


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