Sunday, January 15, 2017

IN the NEWS: Vancomycin induced CAST nephropathy

Recent literature has linked AKI with vancomycin and zosyn and it was thought that the higher vancomycin levels might have been the culprit.
It was also assumed that the injury was either AIN or ATN. Few biopsies done in these cases were suggestive of ATN in the past( vancomycin mainly). Personal experience, I have seen ATN from vancomycin as well that is biopsy proven.
In JASN,  Luque et al might have discovered what is the mechanism behind vancomycin toxicity. The biopsy of a single case presented showed tubular casts entangled with uromodulin.  EM showed vancomycin particles in the tubular cast when immunogold labeling was used.  Staining with anti-vancomycin antibody revealed the specific accumulation of vancomycin in the tubular lumen mainly. Similar to myeloma casts, this leads to an intratubular obstructive ATN. A CD68+ macrophagic infiltrate was also observed surrounding the casts and within the kidney’s interstitium, suggesting that pathologic casts might induce an inflammatory process. To further confirm the pathogenicity of vancomycin-associated casts, they  retrospectively examined eight additional renal biopsies with ATN that had been performed in the clinical context of high-vancomycin trough levels preceding AKI. Similar findings were noted in the biopsies.  Vancomycin trough levels ranged from 35-106mg/dl in the 8 patients.  50% of the patients required dialysis. To confirm, they did in studies in mice and injected vancomycin and observed effects in the kidney.Kidney injuries have been visible as early as two days after vancomycin injection.
In summary, this article is the first to describe the novel form of injury an antibiotic can give.This can explain the sometimes noticed rapid rises we noted in some cases of acute ATN with vancomycin and perhaps even other antibiotics.
Should we be giving pre and post hydration like we do for acyclovir when giving vancomycin to prevent AKI?
Check out this amazing paper! Kudos on thinking out of the box and finally giving us a potential mechanism!

Thursday, January 12, 2017

IN THE NEWS: Preventing rejection while using immunotherapy in organ transplants

Use of immunotherapy such as CTLA-4 and PD-1 inhibitors have been sparingly used in renal transplant patients due to the concern for rejection.  Several cases and one recently published in NEJM last year showed severe acute cellular and antibody mediated rejection with use of PD-1 inhibitor therapy. In the limited number of patients who have received these agents, it appears that PD-1 inhibitors could be more prone than CTLA-4 antagonists to cause rejection in the transplanted kidney. This is especially true when the patients receive anti–CTLA-4 agents before PD-1 inhibitor treatment

We reported now in NEJM a creative solution of preventing rejection in a patient getting nivolumab (PD-1 inhibitor). By using a prophylactic approach of higher doses of steroids and mTOR inhibitors, we were able to successfully prevent rejection along with successful treatment of the cancer as noted in the supplementary files of the letter. Immune check point inhibitors have revolutionized the treatment of many types of cancers.With this approach, it is possible that these agents can be perhaps safely be used in the organ transplant patient.

We recently reviewed entire literature on the use of immunotherapy in the organ transplant world. As stated above, the rejections were mostly seen in PD-1 inhibitor based therapy compared to CTLA-4 therapy. In addition, the 2 cases of liver transplant where these agent were used and 1 case of heart transplant didn’t lead to a rejection episode.  But in the renal transplant patients, 5 cases have now been reported of leading to acute cellular and antibody mediated rejection when PD-1 inhibitor was administered. The above NEJM case suggests a potential treatment strategy.

Renal effects of immunotherapy are not minor.  AIN, podocytopathy and electrolyte disorders have been reported. It is important for the general nephrologists to know about these effects.Two recent reviews discuss this elegantly.

Sunday, January 8, 2017

NKF Spring Meetings: Pre course on Point of Care Ultrasound for the Nephrologist

04/18/2017     7:30 AM

04/18/2017     12:30 PM

Walt Disney World Swan and Dolphin, Orlando, FL
The renal consultant needs knowledge of lung ultrasound to determine volume status, renal and bladder ultrasound to evaluate for obstruction and knowledge of vascular access guidance to assist in placement of catheters. This course will focus on the above elements in point of care ultrasonography. 

  • Image acquisition will be practiced on human models using high-quality ultrasound machines and supervised by experienced faculty. Training sessions give you practical, hands-on training with a 1:3 teacher-to-learner ratio, so you benefit from personal instruction.
  • Image interpretation during group sessions under the supervision of experienced faculty members offers relevant practice. Numerous ultrasound images demonstrating normal and pathologic findings will give you a comprehensive learning opportunity. As you improve your skills, you will be further challenged with unknowns and case-based image sets.
  • Knowledge base will be enhanced with lectures that focus on important aspects of point of care ultrasonography applicable to the renal consultant. Discussions will have immediate application within your practice.

Learning Objectives:
Upon completion of this course, participants will be able to:
  • Discuss how to perform lung ultrasonography and ultrasonography of the renal system.
  • Identify appropriate uses of ultrasonography in renal practice.
  • Demonstrate appropriate image acquisition techniques required for renal ultrasonography.
  • Interpret image-based clinical cases to help identify abnormalities.

Paul Mayo, MD
Mangala Narasimhan, MD,
Daniel Ross, MD
Kenar Jhaveri, MD

Breakfast and Introductions
Lung Ultrasound for the Assessment of Volume Status
Hands on Lung Ultrasound
Image Interpretation Lung Ultrasound
Vascular Access/ IVC Size
Hands on Vascular Access/IVC
Image Interpretation Vascular Access/IVC
Renal Bladder Ultrasound
Hands on Renal Ultrasound
Image Interpretation
Wrap-up and Evaluation
4.25 credits/contact hours

REQUIRED: Separate registration fee of $60 for NKF Members, $75 for Non-Members, $40 for Fellows/Residents. Includes light breakfast, and CME credits. Participation is limited, so register early.  

In the NEWS: US Nephrologists, dialysis and pregnancy

Getty Images/iStockphoto/ThinkStockPregnancy occurs among 1–7% of women on chronic dialysis. Data on how dialysis is provided in ESRD patients who get pregnant in the US is lacking. A recent survey published reveals the latest update on this topic. 

While the response rate is small, the information might be important. Limited providers might have this experience of providing for dialysis for the pregnant patient. Of the respondents, 45% had cared for pregnant females on HD and 78% of pregnancies resulted in live births. In 44% of the pregnancies a diagnosis of preeclampsia was made. There were no maternal deaths. Nephrologists most commonly prescribe 4–4.5 h of HD 6 days/week for pregnant women on dialysis. More dialysis time is associated with better volume and electrolyte control. The frequency of preterm delivery and intrauterine growth restriction tends to correlate with BUN levels. There is an inverse association between BUN level and birthweight and adverse fetal outcome, with more favorable outcomes when the serum urea level is <75 mg/dL. The survey shows that most US nephrologists target a BUN of <50 mg/dL (66%) and 21% aim for a target predialysis BUN of <20 mg/dL. Intensive dialysis is a necessary important finding that is now becoming norm for patients who are pregnant.  Both maternal and fetal outcomes have improved.

What was interesting in the study was "
Women dialyzed cumulatively for >20 h/week were 2.2 times more likely to develop preeclampsia than those who received ≤20 h of HD per week."

Why would that be?.  The authors think that it might be for two reasons: increased hours on HD leading to more vasoconstriction and tighter volume control leading to pre eclampsia. Also since this was a survey, the diagnosis of preeclampsia was dependent on the nephrologist recognizing it and perhaps a "diagnosis" labeling problem. 

Pregnancy on dialysis is becoming frequently encountered, pregnancy care should be part of the health maintenance plan of women of childbearing age on dialysis. OB-Nephrology should be considered a sub field in Nephrology and should become part of academic centers as a career paths for nephrologists and training of fellows. 

Thursday, December 29, 2016

In the NEWS: Fake Nephrology Conferences and Journals: Have you have been getting these emails?

Recently, few of us have noticed we get emails inviting us to submit to " Journal .... nephrology.. and .." The best one I got one was " New England Journal of Nephrology". In addition, there are apparently these emails inviting you to be presenting at conferences that sound so real but for few of us who have been in academia- know that they are a money making scam.  What is gained from these conferences? 
Series of these conferences are run by OMICS. They are apparently for many different fields in medicine.  When I clicked on the Nephrology section for the journals, I got this ( mostly Non nephrology journals)
When clicked on conferences, you get these 

Now take a look at the locations: Las Vegas, Orlando, Dubai!!
It seems that they are happening for many years. Has anyone gone to these? Based on the NYT article that was recently published, The Federal Trade Commission formally has charged OMICS with deceiving academics and researchers on such publications and fees.

The author in the NYT says nicely at the end and I quote "So it’s not surprising that some academics have chosen to give one another permission to accumulate publication credits on their C.V.’s and spend some of the departmental travel budget on short holidays. Nor is it surprising that some canny operators have now realized that when standards are loose to begin with, there are healthy profits to be made in the gray areas of academe."

Perhaps as a community in Nephrology we need to create a page that lists which of these journals and conferences are FAKE and prevent our colleagues on spending money on these ventures.

Wednesday, December 14, 2016

Lupus Nephritis classification: Does it help us?

I recently went to a talk by Stephen Korbet on Lupus Nephritis and it got me wondering on if the current way of classification of lupus nephritis works or not?

MPGN- old way of classification was EM based but the recent updated IF based classification is very clinical and aids the clinician in treating the disease better as a root cause is identified.

In lupus, the story starts back in 1970s and eventually leading to the WHO classification and then the updated ISN classification. A recent review  published in JASN in 2015 summarizes the history and concerns regarding the classifications. The suggestions to improve are more detailed and pathology related and I am not sure if they will help clinically.

What might help a nephrologist help treat the lupus nephritis patient?

1. Is the lesion Proliferative?- segmental or diffuse- most of us will treat. Only context of not treating will be the IFTA present on the biopsy- so does it matter if its segmental or diffuse? as treatment is either MMF or cyclophosphamide anyway.

2. Is the lesion crescentic? - yes this matters to us-- as most crescentic GN( RPGN) and specifically lupus have been excluded in most trials- so treatment might be leaning towards cytotoxic agents and not standard therapy.

3. Is it a podocytopathy ( would like to include membranous GN in this section)- More and more we are seeing MCD, FSGS with this entity and treatment might be slightly different as some of them respond faster with a steroid based regimen.

4. Is there a second entity with it?- ANCA disease or TMA?- as treatment might then entail pheresis and or a different prognosis.

I think the talk by Korbet hinted towards this but not sure which direction the field will go but it's time that we have a less confusing classification but more meaningful one that helps the nephrologists treat the disease better.

What do others think?

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