Nephmadness 2014:

March madness fever has begun. This month is National Kidney month. In spirit of nephrology education and kidney centric month, eAJKD and nephrology blogsphere presents Nephmadness 2014 to all of you.
This year, its more sophisticated with newer brackets, more interactive online platform and moderators that are experts in the field.

Check out the official website of Nephmadness at www.nephmadness.com
Select your brackets starting this sunday March 16th 11:00AM onwards.
eAJKD will also host the discussions and bracket details on the blog site as well.

Let the educational game begin!!

Detective Nephron: Next venture

Take a look at the March 2014 ASN Kidney News for the next Detective Nephron venture as the detective tackles an AKI case.
http://onlinedigeditions.com/publication/?i=200100

Clinical case and answers 81

What leads to hyponatremia in adrenal crisis?

Pre renal state due to low cortisol	5 (26%)
CRH release leads to hyponatremia	2 (10%)
Cortisol normally suppresses ADH and in adrenal insuff, this doesn't happen	11 (57%)
The mechanism is not known	6 (31%)

The hypersecretion of ADH seen in low cortisol states may be due in part to the reductions in blood pressure and cardiac output. However, a more important mechanism may be that cortisol deficiency lead to increase CRH production leading to increase ADH state.  Cortisol feeds back negatively on CRH and ACTH, an inhibitory effect that is removed with adrenal insufficiency. In addition, cortisol appears to directly suppress ADH secretion. Thus, ADH levels increase when plasma cortisol levels are low.  Alternatively, the hypersecretion of ADH induced by aldosterone deficiency is caused by renal salt wasting with resultant volume depletion. Many studies support the concept that hyponatremia in patients with hypopituitarism is mainly caused by failing inhibition of ADH secretion because of hypocortisolism.

http://jasn.asnjournals.org/content/17/7/1820.long is an amazing reference from JASN that looks at water homeostasis in adrenal disorders. 

IN the NEWS: Is this the end of suPAR?

Clinical and experimental evidence suggests the pathogenic role of circulating permeability factors, including soluble urokinase plasminogen activating receptor (suPAR). Serum suPAR levels were found to be elevated in Caucasian adults with primary FSGS and in two cohorts of children with FSGS from Europe and the United States. 

          This new study in KI March 2014 issue from India looked at the role of suPAR in all children with nephrotic syndrome. Compared to controls, suPAR levels were highest in FSGS and then other nephrotic syndromes from MCD and other congenital diseases. Interestingly, the study failed to show that this circulating factor that was really hallmark of FSGS diagnosis was specific for FSGS. Rather, it might be a biomarker for nephrotic syndrome in general.  Interestingly, levels of suPAR significantly correlated inversely with eGFR and CRP.

          So what this study is telling us is that suPAR gets elevated with downtrending GFR- perhaps it’s just a renal clearance marker. In addition, suPAR has been found to be elevated in sepsis, malaria and chronic infections such as Hepatitis and HIV. So it’s unclear if suPAR really is a marker of podocyte injury but rather a marker of generalized inflammation. 

          So, suPAR doesn’t answer our question for FSGS permeability factor anymore.  This study really highlighted the non specificity of suPAR for FSGS and even perhaps podocyte injury.

          

eJC: Provider and Care Characteristics With Timing on Dialysis

CJASN's eJC feature is doing a hosting the journal club article at different institutions and sharing their thoughts on the manuscript on their eJC website.  Jan 2014 topic is a study that looked at provider and care characteristics with timing on dialysis. This is an interesting topic is discussed in a retrospective cohort manner and showed that provider factors are associated with timing of dialysis in the US.
The renal fellow network has commented on this article along with a discussion that took place at Duke Nephrology Journal club. Visit and log in via your ASN membership to eJC website of CJASN and provide your thoughts. If your institution does this for journal club, then post a summary statement of thoughts you all had regarding this study.

Complement system in ANCA vasculitis

          Classically associated with a pauci immune RPGN, ANCA disease has traditionally been not associated with complement activation. Recent data in JASN 2014 from the UNC group suggests otherwise.  Passive transfer of anti MPO in mice induced ANCA associated necrotizing crescentic GN with activation of alternate complement system.  The researcher highlighted the role of C5a receptor in the mediation of this disease. As we know, C5 has a role more downstream close to the MAC system in the complement cascade.  Hence blocking C5a receptor will halt alternate pathway.  The researchers then showed that C5a receptor/CD88 engagement enhances the inflammation and C5L2 ( C5 a like receptor) suppresses inflammation.  Given an oral agent that blocks C5a receptor/CD88 ameliorated the GN in the mouse model. No human trials have been suggested yet but pharmaceuticals are already on the go for this proof of concept.

          http://ir.chemocentryx.com/releasedetail.cfm?ReleaseID=811237

          In a different study, the elevated plasma and urinary C5a levels indicated complement activation in human ANCA disease. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.

          The role of complement in ANCA disease is not completely novel. If C5A receptor can be of help, why not block C5 directly with an agent we already have for C3GN, DDD, PNH and aHUS: eculizumab.
Looking at clinicaltrials.gov, we find a withdrawn study.( thanks to anonymous for pointing this out)

Clinical Case 80: Answers and Summary

Which statement best describes the relationship of microalbuminuria and cardiovascular disease?

Microalbuminuria causes cardiovascular disease Atherothrombosis causes microalbuminuria A common risk factor causes both microalbuminuria and cardiovascular disease A common pathophysiological process such as endothelial dysfunction might lead to  both microalbuminuria and cardiac disease

Most of you got this one correct. The age old question is " is microalbuminuria cardio toxic?" This is tough. Is it a surrogate marker of inflammation as some believe it is the ESR for the kidney or is it truly a risk factor for cardiac disease?  A paper in JASN many years ago looked at 4 potential mechanism of how these two might be related. The 4 mechanisms are listed above as your 4 choices. 

There is no direct evidence that supports statement " microalbuminuria causes cardiovascular disease".  The second statement may be partially true based on the authors argument but not many times hence atherothrombosis causing microalbuminuria might not be the problem either. Clearly common risk factors do exist with these two condition such as insulin resistance and or metabolic syndrome, and no one has looked at whether the association of the two conditions disappears when adjusted for insulin resistance and or other variables that are common risk factors. 

Hence, the most likely statement that makes sense is a common process that leads to endothelial damage leads to both microalbuminuria and cardiac disease.  Endothelial damage makes most sense as we as nephrologist see this all the time:- both diabetics get proteinuria and then the SLE patients with endothelial damage and then the pre eclamptics with endothelial damage.