AKI- when do we use CRRT?

Many studies have looked at this question but with no real answer that was put forth.  In a recent 2013 AKI ( European best practice position statement) on KDIGO guidelines on RRT, they mention the following:

##Use of CRRT or IHD as complementary therapies in AKI( Grade 1A)

##Using CRRT or SLED than IHD for hemodynamically unstable patients( no grade given)

##Using CRRT rather than IHD for AKI associated with brain injury or increased intracranial pressure ( grade 2D).  – This is based on limited evidence poor quality studies.  Intermittent modes of renal replacement therapy have been shown to cause an increase in intracranial pressure in susceptible patients, including those with acute liver failure and cerebral edema from trauma or post neurosurgery. Such changes are due to the combination of adverse effects on cerebral oxygen delivery and/or cerebral perfusion pressure and the generation of an osmotic gradient between plasma and cerebral tissues. Compared with standard IHD,  CRRT provides an effective therapy in terms of solute clearance, coupled with improved cardiovascular and intracranial stability. The disadvantage of CRRT is that anticoagulation may be required, and anticoagulants with systemic effects may provoke intracerebral hemorrhage.  CRRT also has been shown to help in case reports to decrease intra cranial HTN.

##The dose of CRRT to be delivered an effluent volume of 20-25ml/kg/h for post dilution CRRT in AKI( Grade 1A)

##Medication adjustment based on clearance needs to be taken into account.

Check out the full set of guidelines here.

IgA Nephropathy and Minimal Change Disease?- a potential association

IgA nephropathy can take many variants. Classically, it can present as the nephritic syndrome but can be just benign hematuria with no other complaints. Sometimes it can be aggressive with crescents and or TMA.  Proteinuria usually suggest a bad prognostic marker in IgA nephropathy.  Sudden onset proteinuria might suggest a dual glomerular process or IgA nephropathy with a minimal change disease variant.  A recent series of cases have been described in CJASN.  A retrospective review of pathology cases in the Columbia Univ path database revealed 17 such cases.  Most had normal creatinine, proteinuria was over 8g for average and biopsy showed co dominant IgA with mesangial deposits and MCD.  14/17 patients got complete remission with steroids and additional agents.

Another case presented in this case report.

IN THE NEWS: Transplantation and risk of death from malignancies

 A recent article in KI looked at death from malignancy after renal transplantation.

Some key findings:

Single center study in England looking from 2001-2012
18% deaths were from malignancy(lymphoma>lung>renal and others)
Age and gender stratified malignancy related mortality risk difference was higher than in transplant compared to general population.
Risk factors: pre transplant history of malignancy, DDRT and age.
Lung cancer was the most common cause of malignancy death in men and lymphoma in women.
There was no significant difference in the rate of cancer-related death or location of cancer with ethnicity in our cohort, although a trend was observed toward less overall malignancy-related death in non-whites versus whites.

Not surprising to find these findings given the nature of immunosuppressive medications and prior hx of malignancies. 

IN THE NEWS: CKD and Renal Cancer Risk?

                A recent study in JASN found that those with stage 3 CKD were 39% to 100% more likely to be diagnosed with renal cell cancer over 5 years than people with Stage 2 CKD.  In addition, urothelial cancer was also more common in this group. Risk was greatest for clear cell renal cancer. No association was found with colon, lung and breast cancer or other cancers. This is the largest outcome study in a single health care system in the US looking at cancer risk and CKD.  As GFR declined, the risk of urothelial and bladder cancer increased.
A recent study in AJKD had also shown similar findings.

One thing to keep in mind in the large data base studies is the variables being adjusted for. It appears that the researchers adjusted for many of the classic cancer associated variables.  Cause was CKD was not well discussed in the manuscript. Cause can make a difference. Glomerular diseases with “ net immunosuppressive” exposure such as SLE patients with CKD are more likely to have exposure to cyclophosphamide, CNIs and other medications making them more prone to malignancies than perhaps diabetic CKDs.  They did adjust for proteinuria and hematuria and perhaps that can serve as a best surrogate as a cause.

Where do we go from here?

Should we be screening for renal cell with yearly ultrasounds on everyone with CKD?  Would it make a big difference? Screening for cancer in CKD has been a black box and perhaps studies like these shed some light on the type of cancers we should be more alerted to than the classic screening done in general population.

In the NEWS: Cancer risk after cyclophosphamide use in membranous GN

A common question has always been in our minds – cancer risk after cyclophosphamide use in renal diseases?

Membranous GN has been the landmark GN where cyclophosphamide has been tried. The regimen with alternating months of this agent with steroids is still the standard of care treatment for Membranous GN.  Other therapies have come and stayed or gone, such as CNIs, MMF and rituximab.  They have varied outcomes.

Cancer risk after use of cyclophosphamide recently waslooked at a single center in Europe in this CJASN manuscript.   Over 250 patients were followed over 6 years and 127 patients were treated with cyclophosphamide (CYP).  Cancer risk was 3 fold higher in this cohort compared to ones not treated with CYP. 

Interesting findings:

1.     As one would think, bladder ca would be the highest risk, it was only 2 of the 20 observed

2.     Hematologic malignancies were highest in this cohort

3.     Could some of their cases be secondary membranous and hence had cases of early malignancies?

4.     Table 3 has malignancies listed as Lung, CLL, lymphoma, prostate Ca, colon, AML, bladder and CML

5.     Majority were men

6.     Varied cancers ( 5) of them had membranous GN that was APLAR2 negative but no time correlations was noted

Full paper at http://cjasn.asnjournals.org/content/early/2014/05/22/CJN.08880813.full

Paging Nephrology Fellows: Does it matter to them?

A recent study appeared as an Article in Press on May 2, 2014 in the American Journal of Kidney Diseases (AJKD) entitled “Prospective Analysis of After-Hour Pages to Nephrology Fellows.” This was an audit of the after hour pages received by 6 nephrology fellows at the University of Rochester, lasting for 61 days and recording 615 after hour pages. This study was prompted by the underwhelming interest in nephrology fellowship, as demonstrated by 44% of nephrology programs that participated in the National Resident Matching Program being unmatched in 2014.

The results demonstrated that fellows had to return to the hospital on 64% of overnight calls, most after hour pages did not require any modification of the current patient care plan, and 50% of the after hour pages occurred after 10pm. Only approximately one third of the nights allowed for the ACGME-recommended 5 hour minimum of uninterrupted sleep. 

This study implies that after hour pages are a major deterrent to those that are considering the field of nephrology. Concern over declining nephrology fellowship applicants has been an area of active interest that has been addressed in several studies as well as an American Society of Nephrology task force.  Shah et.al surveyed 204 US adult nephrology fellows and found that the three top reasons why fellows were somewhat, slightly, or not at all satisfied with their career choice included poor income potential after graduation, poor job opportunities after graduation, and long work hours . Jhaveri et.al performed a survey of 714 internal medicine subspecialty fellows and when asked about what they did not like in nephrology, 35% felt that dialysis and transplant patients were too complicated, and another approximately 30% felt they did not have any role models in the field. The burden of after hour pages did not seem to be a factor in either of these studies.

Most other internal medicine high acuity subspecialties likely receive a similar number of after hour pages.  The overnight consults likely involve the cardiology and gastroenterology services as well, since these fields also have urgent procedures and interventions that may need to be performed emergently overnight.  A survey of these fellows may yield the same results with frustration in after hour pages, although in our institution the cardiology fellowship program utilizes an in-house call model, so the frustration with after hour pages is likely to be different. That being said, only 4.6% of gastroenterology programs and 1.6% of cardiovascular fellowship programs went unfilled, compared with the 44% of nephrology programs cited above. Further studies should be performed in order to determine this disparity. 

Dwindling interest in nephrology needs to continue to be investigated.  As the population continues to age and comorbid diseases such as diabetes mellitus and hypertension become more and more prevalent, there will be a rapidly expanding need for nephrologists. Clearly, the lack of fellowship applicants is a multifaceted problem with far reaching effects. Although the burden of after hour pages may play a part in frustration, there are likely to be a number of other factors that play a role in the increasing dissatisfaction within the field. 

Anonymous Fellow in a US based Nephrology Fellowship

Hyponatremia Guidelines Part 5

What to do for over correction?

1.     Prompt relowering if increased >10mmol/L over 24 hours

2.     Stop ongoing treatment

3.     Nephrology or critical care/ endocrine consultation to see if need for starting electrolyte free water or not and monitoring urine output

4.     Expert opinion re the use of ddavp 2ug

Was interesting to note that the new Stern approach of using 3% and ddavp at the same time was not really entertained. It was mentioned in the rationale discussion but more robust trials are needed in that realm.  

For full review:

http://www.ncbi.nlm.nih.gov/pubmed/24569496