IN THE NEWS: Remote ischemic preconditioning and prevention of AKI post CABG

Remote ischemic preconditioning(RIPC)  has been used as a protective method from ischemic damage to distant organs.  Application of one or more brief cycles of nonlethal ischemia/reperfusion to an organ or tissue may protect a remote organ or tissue from a sustained episode of lethal ischemia/reperfusion.

In a recent study presented at Europe and published in JAMA,  Zarbock et al examine the effects of RIPC on the rate and severity of AKI in patients undergoing cardiac surgery. In a multicenter trial, 240 patients at high risk for AKI  were randomized to receive either RIPC  or sham control  after induction of anesthesia.

The amazing results showed that AKI was significantly reduced with RIPC (45/120; 37.5%) compared with control (63/120; 52.5%), with an absolute risk reduction (ARR) of 15%. Fewer patients received RRT after RIPC (7 [5.8%] vs 19 control [15.8%]; ARR, 10%) and RIPC reduced intensive care unit stay (3 vs 4 days). RIPC had no significant effect on myocardial infarction, stroke, or mortality.

A recent meta-analysis published in AJKD showed otherwise.  Mostly randomized trials were included ( 13) and total of >1300 patients. There was no differences in levels of post operative AKI and incidence of RRT, in hospital mortality and hospital stay.  A prior meta-analysis had shown similar results as well.

Can we start using this in clinical practice? It is innovative, inexpensive and easily possible.  But long terms risks and harms are not known. Clearly, there is significant risk of AKI post CABG and this might be the only preventive measure that we have that has come close to showing any benefit. 

As suggested by the editorial in JAMA, before RIPC is adopted for clinical use, the potential risks and adverse effects must be considered carefully.  

image source: circres.ahajournals.org

ASN Fellows Survey on Workforce 2015

Nephrology Workforce Annual Fellows report in 2015 is being collected by ASN via a survey. 

This survey, being  performed by colleagues at Geoorge Washington University, will be very useful to understand our workforce related concerns. A prior survey done in 2014 had some alarming results.

See link below at ASN website.
http://asn-online.org/education/training/workforce/home.aspx

The Workforce committee of ASN has spent the last 5 years or more attempting to draw conclusions about fellowship trends and workforce needs from fragmented information. This is one of our few opportunities to gather good data and have it analyzed by those with expertise in healthcare workforce studies.

I think the fellows in the USA should take this opportunity to help out the field of Nephrology. You should try to  must  complete the survey you received from ASN. 

Topic Discussion: Non uremic causes of calciphylaxis

Calciphylaxis, or calcific uremic arteriolopathy(CUA), is a well-described entity in end-stage kidney disease and renal transplant patients; however, little systematic information is available on calciphylaxis from nonuremic causes.

A review I found in CJASN from 2008 discusses non renal causes of CUA.

Besides renal disease, the non uremic( CKD and ESRD) causes are: the top 4 being the most cases of. The remaining were just 1-2 case reports.  Most of these patients listed below had normal renal function, over 50% had normal calcium and >60% had normal phosphorus levels and 50% had low or normal pth levels. One most keep these causes in mind when ESRD or CKD does not explain the cause of CUA.

Primary hyperparathyroidism
Malignancy( Classically breast, melanoma, gall bladder, myeloma)
Alcoholic liver disease
Connective tissue diseases
Chemo induced protein C and S deficiency
Crohn’s disease
Vitamin D deficiency
POEMS syndrome
Diabetes

NK cell leukemia and lymphomas and renal disease

NK cell neoplasms have a wide range of clinical, morphologic, and immunophenotypic characteristics. Aggressive NK cell leukemia usually affects young patients in their 20-30s with equal sex incidence and shows a rapidly progressive clinical course.  Often they don’t respond well to chemotherapy and prognosis is poor.

Kidney involvement in these cancers is rare but here is what I found?

One case report of a collapsing FSGS published in AJKD in 2011. Initially, in this case, the first biopsy was read as FSGS NOS and then a repeat one had collapsing glomerulopathy.

Another recent case series describes cases of renal diseases seen with all types of non-Hodgkin’s lymphoma.  They describe 20 cases. T/NK cell lymphoma was in 4 cases. 2 of the 4 cases had crescentic GN, 1 had minimal change disease and 1 had infiltrative disease. 

A very early description of minimal change disease has been described in a case report in 1980s of a large granular cell lymphoma.

So in summary, NK cell neoplasms likely are related to cause some glomerular involvement-likely podocytopathies such as minimal change to FSGS. Cases of crescentic GN have also been described.

Topic Discussion: Metformin and CKD

The package insert of Metformin says

“Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels 2 I .5 mg/dL [males], 2 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS). “

This is dated back when this drug was introduced decades ago.  Most physicians withhold this very useful agent in most patients with a crt >1.4mg/dl.  But cautious use have been tried by many in advanced CKD and there are not many cases of lactic acidosis. 

This well done study in JAMA by Inzucchi et al reviewed over 800 publications on this topic of CKD and use of metformin from 1950 and 2014 and looked at major studies, case series and retrospective data.

What did they find?

1.       Lactate level was normal in patients with GFR of 60-90ml/min and even in patients with GFR of 30-60ml/min

2.       Most cases of lactic acidosis occurred in setting of a “second hit”- such as volume depletion, sepsis, AKI. Etc

3.       The rate of lactic acidosis in patients taking metformin was same as lactic acidosis in patients not taking metformin

4.       What did they recommend: 

Not to initiate metformin in patients with GFR< 45cc/min
Contraindicated in patients with GFR <30cc/min

5.       They recommended max doses based on GFR:

If GFR >60- max dose 2550mg per day

If GFR 45-59- max dose 2000mg per day

If GFR 30-44- max dose of 1000mg per day

Maybe it’s time we liberalize our guidelines to use metformin in CKD. Look what the Australians and Canadians are doing.  

Detective Nephron Strikes Back

Next venture of Detective Nephron as he takes on a case of hypophosphatemia.
http://www.asn-online.org/publications/kidneynews/archives/2015/KN_2015_05_may.pdf ( check out page 16-17)