C-KIN( Cancer and Kidney International Network)

The first ever international society specifically for onconephrology has been created.
It's called the C-KIN( Caner and Kidney International Network).
Check out the their twitter feed at https://twitter.com/CKINnews and their annual conference schedule and abstract details as well. C-KIN aims at improving patient care through better knowledge, education and awareness on cancer and the kidney related issues and research.

Clinical Case 85: Answers and Summary ( iron use in ESRD)

ESRD patient with anemia, Fe sats of 12%, Ferritin 450 needs IV iron. Patient has bacteremia.

A. Proceed to give IV iron as anemia and low Fe sats demands it.  (2%)

B. Given active infection, do not give IV iron till 2 weeks after infection resolved (73%)

C. Given active infection, do not give IV iron till 4 weeks after infection resolves. (24%)

There have been no clinical trials of adequate sample size and duration to provide us sufficient understanding of the safety of intravenous iron. Is bolus iron better or continuous form? Is iron infusion pose an infection risk?

Brookhart et al. retrospectively studied patients on dialysis treated at Davita Inc. dialysis facilities and found that patients receiving 200mg intravenous iron per month had an increased risk for hospitalization or death because of infection. They also found that bolus dosing was more associated with infection. More recently, A CJASN study by Miskulin et al. found a increased risk for infection-related mortality when cumulative iron dose exceeded 1050 mg over 3 months or 2100 mg over 6 months( not statistical but a trend). In an accompanying editorial to the Miskulin study, Fishbane et al (must read) discuss what the USRDS data suggests. As the mean serum ferritin of United States patients on dialysis approximately doubled from 1993 to 2001, the rate of bacteremia/sepsis increased approximately by 40%. From 2001 to 2010, serum ferritin stabilized, and soon enough the bacteremia/sepsis rate also stabilized. In light of these above findings, it is advisable to hold iron infusions in setting of active bacteremia.  

What about other active infections such as cellulitis or pneumonias? No data exists for those at this point. How long do we wait is a good question. Most likely choice is 2 weeks but data for that is not clear. Some of you chose 4 weeks: might also be a reasonable choice.  Another concern might be catheter use.  Infection risk as stated by the Brookhart study that risks are largest among patients with a catheter and the ones with a recent infection. 

Topic Discussion: Ebola and the Kidney

Ebola is a RNA virus that has a high rate of transmission.  As we have now noted the world’s largest outbreak of this virus to date, the cure for this entity remains a mystery.  Ebola hemorrhagic fever is a severe infection. It can have a mortality rate of up to 70-90%. The infection can occur in humans and animals. The virus family is Filoviridae and genus Ebolavirus. It was first discovered in 1970s near Ebola river in Congo.  Since then most of the outbreaks have been in Africa.  While the natural reservoir host of Ebola remains unknown, some believe it might be bats.

How does the kidney get involved? Severe volume depletion from this hemorrhagic disease leads to acute kidney injury.  Electrolyte abnormalities such as hyponatremia, hypokalemia and so forth can be noted as well.  Renal failure was described in this entity in early 1980s. DIC ensues and a shock state leads to AKI. Prior animal studies have shown that there is some necrosis and calcification in tubules and glomerular tufts of kidney. The first victim in the US in Texas was on dialysis as well.

While some treatments and preventions are being considered, there is only supportive therapy that can be offered at this time. However, survival is improved by early supportive care with rehydration and symptomatic treatment. Early intensive care therapy might be necessary.

What might be of interest to us as nephrologists is the use of dialysis modalities to help clear the virus. Hemopurifier, a device from  Aethlon Medical (San Diego, CA) that’s capable of filtering blood of impurities like viruses is available. Apparently it is being used currently ( per their report) for filtering the blood of an infected doctor with the virus in Germany. The device can be used with standard dialysis and continuous renal replacement therapy (CRRT) machines and doesn’t require any special hardware upgrades.

More information regarding this can be found at the website

http://www.medgadget.com/2014/10/aethlon-hemopurifier-now-filtering-blood-of-ebola-patient.html

New York Society of Nephrology 2014-2015 Lecture series

New York Society of Nephrology  2014-2015 lecture series for this upcoming academic calender.
If you are around, come join this amazing group of speakers( basic science and clinical).  This happens at the Faculty Club at Weill Cornell Medical Center

http://nysn-online.org/lecture.html

October 22, 2014

2014 Gibbs Awardee Lecture **NYAM

Fred Coe on Renal Stones

December 3, 2014 ( Hypertension and kidney disease)

1. JNC VIII update.  Ray Townsend 
2. Update on APOL1-associated nephropathy; The search for modifiable “second hits”    Barry Freedman

January 7, 2015 

1. IgA nephropathy: Beyond KDIGO. Dan Cattran
2.  The Burton Rose Neprhology Lecture: Orsen Moe

February 4, 2015( GN/Onco-nephrology)

1. Glomerular cell regeneration in disease-what we should be doing for patients.  Stuart Shankland
2. Paraproteinemic renal diseases: an update   Nelson Leung

March 4, 2015 ( Acute Kidney Injury)

1. New Insights Into Tubule Cell Injury and Death During Acute Kidney Injury". Joel Weinberg
2. Acute Kidney Injury Associated with Cardiac Surgery. Mitch  Rosner. 

April 22, 2015( Transplantation)

1. Update in Antibody Mediated Rejection. MillieSamaneigo.  
2. Regulatory B cells in Transplant Tolerance. David Rothstein.

May 20, 2015 

Fellows’ Night NYAM

TOPIC DISCUSSION: IgA nephropathy and FSGS

What is the significance of findings of FSGS in biopsies that are predominately IgA nephropathy?

Two studies have looked into this matter in 2009 and 2011.

The NDT study in 2009 looked at 75 patients ( split into IGA with FSGS, IGA without FSGS).  In the multivariate model, the FSGS+ group showed a worse GFR decline.  It is no surprise that when there is sclerotic lesions, the prognosis is going to be worse. The question arises if this is part of IGA progression or it is two processes happening independently? Would steroids be indicated in such settings?

The KI study from 2011 looked at over 100 patients and used the Oxford classification for IgA and Columbia classification for FSGS to evaluate the two seen in the same biopsy.  Collapsing FSGS with IgA had worse outcomes.  Overall, worse outcomes were noted with any form of FSGS was present when compared to IgA alone.  In addition, when FSGS was present with any other glomerular findings( mesangial hypercellularity, necrosis, deposits), outcomes were worse compared to “pure” FSGS.
Staining studies they performed showed that the changes related to the podocytopathy were present even with mild IgA disease suggesting that the two processes might be independent and not just an end pathway for any glomerular disease. 

IgA can present with preserved renal function and MCD like podocytopathy.  Presenting with FSGS is more challenging and treatment may be difficult to decide upon.  If there is good preservation of IFTA on biopsy and if there is >1gm of proteinuria, perhaps it’s worth treating with steroids or at least a trial of steroids.  

In the NEWS: FSGS and CD40- a potential new finding

A new potential culprit might have been found for the recurrence of FSGS post transplant. A recent article evaluated pathogenic antibodies in 141 serum samples over 64 patients and looked at many potential culprits such as CD40, PTPRO, CGB5.etc and pre transplant elevation of anti CD40 alone was the best predictor of FSGS recurrence after transplantation.  Another study highlight is the observation that patient-derived antibodies against CD40 functionally cooperate with a previously identified culprit of FSGS called soluble urokinase plasminogen activator receptor (suPAR). Co-injection of patient-derived CD40 anti-autobodies and suPAR caused enhanced kidney filter failure more than each component did by itself.

This is fascinating as can anti CD40 therapies then lead to preventing FSGS in kidney transplantation?

Abatacept or belatacept may have some role in FSGS treatment. A recent study showed the success of using such agents in minimal change disease. It is interesting to note that in presence of cd40 auto antibody, the wild type suPAR becomes pathogenic to the podocyte.  There seems to be an on/off switch for suPAR perhaps with Cd40 and a trial of belatacept in FSGS might be warranted.  

Would co stimulating blockade agents be sufficient as their interaction as an anti CD40 is possible?- as we use those in transplant anyway? Perhaps, looking at the recurrence of FSGS in patients on belatacept might be a good start.  Or are we specifically going to look at ant CD40 agents( some of which are being studied as anti cancer agents in colon cancer and others)

There is some data of use of this agent in panc transplantation as well.

http://www.jimmunol.org/content/166/1/89.abstract

http://www.bloodjournal.org/content/102/4/1449?sso-checked=true

http://cancerimmunolres.aacrjournals.org/content/early/2013/10/19/2326-6066.CIR-13-0067

For full paper look here

http://stm.sciencemag.org/content/6/256/256ra136