eAJKD: smart allocation or bias?

Check out the latest e-letter by Vinay Nair on eAJKD on the new proposal by UNOS on the allocation of DDRT in USA.

http://ajkdblog.org/2012/09/25/proposal-to-change-the-allocation-of-deceased-donor-kidneys-smart-allocation-or-discrimination/

Clinical Case 62: Answers and Summary

A 56 YEAR OLD FEMALE PRESENTS WITH NEPHROTIC SYNDROME AND RENAL VEIN THROMBOSIS. BIOPSY CONFIRMS MEMBRANOUS GN. HOW LONG WOULD YOU CONTINUE ANTI-COAGULATION?

6 months minimum    25%

Lifelong   13%

Till the albumin>2g/dl     21%

Till the remission of syndrome   35%

Not sure    3%

There is very low–quality evidence to suggest the use of 

prophylactic anticoagulation with warfarin in patients with 

idiopathic membranous GN and severe nephrotic syndrome. KDIGO recent glomerular disease recommendations suggests that it might be considered when the serum albumin concentration is <2.0–2.5 g/dl  with one or more of the following: proteinuria over 10g/day; BMI  over 35; prior history of thromboembolism; family history of thromboembolism with documented genetic predisposition; NYHA class III or IV congestive heart failure; recent abdominal or orthopedic surgery; prolonged immobilization.  Per recent KDIGO guidelines, the duration of prophylactic anti-coagulation needed for optimal benefit compared to risk is not known, but it seems reasonable to continue therapy for as long as the patient remains nephrotic with a serum albumin <3.0 g/dl.   Per glomerular disease experts " The treatment of overt thrombotic or embolic events in patients with nephrotic syndrome is relatively straightforward. Anticoagulation with sequential high or low molecular weight heparin and oral warfarin is the recommended. The duration of treatment needed to prevent recurrent events is unknown but is probably equal to the duration of the nephrotic state per se. "  Another article suggests that warfarin therapy is given for a minimum of 6 to 12 months. However, most experts feel that warfarin should be continued for as long as the patient remains nephrotic. So the best answer would be till the remission of the syndrome and following that perhaps 6 months minimum. The remission might be quicker than 6 months in some cases. 

Want to be an attending physician on the ward - or not??

Can Nephrologists be medicine attendings or co-attendings on ward months for residents?

One of the reasons that residents don't get a good flavor of nephrology is because nephrologists have started to back off on serving as medicine attendings at many places and are only focused on subspecialty care consultation services.  Although, studies have shown that replacement of specialists with general-hospitalists in the last 15 years on the wards has had a positive impact on trainees medical education. A recent editorial by Wachter and Verghese in JAMA suggests that specialty attendings might not be ideal in the current health care settings to serve as medicine ward attendings. But they do emphasize that their presence is important. Hence, their exposure to residents can be via conferences or even " short bursts of co-attending."

What does co- attending mean? Do you manage the patient together? What is the second attending's role? Certain academic centers to have two attendings that round with the teams. Perhaps that might work. This might be one of the reasons why many residents don't get exposed to nephrology related education or other specialty related education. A ward "work" attending along with a subspecialty " teaching attending" might be another approach that might work as well.

I wonder how many practicing academic nephrologist do inpatient medicine ward months in 2012?
Would love to hear from many that do and what their experience is compared to 1980s or 1990s?

Check out the full viewpoint in JAMA Sept 2012 issue. 
Check out the podcast that goes along with this topic as well on the main JAMA website

CJASN eJC: September discussion

CJASN's eJC is discussing an important topic regarding nephrology fellows. Please go comment and share your thoughts on the recent article on career choice and satisfaction of nephrology fellows in the Sept issue of CJASN. Use your ASN log in and password to get to the discussion board.

http://ejc.cjasn.org/phpBB3/

eAJKD updates: Medicine 2.0 coverage

Joel Topf, MD from eAJKD advisory board member's team has been live blogging and tweeting from the recent Medicine 2.0 conference in Boston.  Topics have been variable from interactive tools to patient outcomes data using web 2.0 applications.

Check out the live blogging posts on eAJKD.
http://ajkdblog.org/tag/medicine2conference/

In the News: The POWER of HERCULES

Renal artery stenosis has taken a story of the classic pendulum swinging.  Studies that were observational in the 1990s suggested benefit in stenting and angioplasty as a treatment of modality. Recent trials such as STAR and ASTRAL ( largest to date) have shown no significant benefit in interventional interventions for atherosclerotic renal artery stenosis(ARAS).

While CORAL is still underway, here comes HERCULES.  This is a large prospective multi-center single arm study of patients with significant RAS and uncontrolled HTN. This is in contrast to prior trails that had less sicker patients. Most were at least on 2 agents and 75% on ACEI or ARBS. The procedure related complications were only 1.5% compared to prior studies suggesting as high as 17%.  The results suggested drop in SBP significantly at 9 months, low in stent restenosis rate and complication rates.

While this is a positive study in terms of intervention- the fact that it is a single arm trial, makes it a major limitation.  HERCULES has limitations too. CORAL is still awaited.

Regardless- check out the full trial at Catheterization and cardiovascular interventions. 

Nephrotic Syndrome: Pathophysiology update

Why does edema happen in nephrotic syndrome?

There has been talk about this topic for decades. There is the underfill and the overfill concepts and both have had their share of evidence for and against it. A recent article in Kidney International describes the journey through the different players in the formation of edema in nephrotic syndrome.

Take home points that the article suggests after review of the basic science and clinical literature.

1. Hypoalbuminemia is not a cause of edema formation in nephrotic syndrome
2. Vascular permeability abnormalities are also less likely the major players
3. Proteinuria leads to increased activation of ENAC channels and leading to Na retention- this might be the major cause of edema. This might be the most active component regardless of the intravascular volume status of the patient.
4. Excess serum ADH levels might also help in water retention.
5. RAS system does not appear to be the primary mechanism of renal Na retention.

This leads us to believe that perhaps a combination of loop diuretic + K sparing diuretics might be a good combination to use in the treatment of the edema( although data is sparse)

Some interesting points from the article regarding edema physiology

1. Extracellular fluid volume expansion excess expands both the intravascular and interstitial space in chronic renal failure compared to nephrotic syndrome- where its largely confined to the interstitial space due to protective effects of interstitial protein washdown and washout.
2. Minimal Change disease or severe hypoalbuminemia might have true decrease in intravascular volume compared to other nephrotic syndromes that are more in the range of normal to expanded blood volume.

In the News: Kidney Transplant Chain- 1 year follow up

A recent publication in AJT describes the largest kidney transplant chain experience. They report the largest series of chain transplantation that were done at 57 centers in USA by pooling incompatible donor/recipient pairs.  Every recipient whose intended donor donated were transplanted. 46% percent included minorities who have hard time getting donors. One year follow up is excellent with mean crt of 1.3mg/dl. This is a remarkable success and a step forward in the field of transplantation. 

Topic Discussion: Music therapy and kidney transplants

Is there any role for music therapy in transplantation? Does a specific type of music or any calming music boost the success of a transplant?

Interactions between the immune response and brain functions such as olfactory, auditory, and visual sensations are likely. A recent study investigated the effect of sounds on alloimmune responses in a murine model of cardiac allograft transplantation. In that study, exposure to opera music, such as La traviata, could affect such aspects of the peripheral immune response as generation of regulatory CD4+CD25+ cells and up-regulation of anti-inflammatory cytokines, resulting in prolonged allograft survival. That is an interesting observation. It is plausible that the environmental or epigenetic changes are playing a role here and leading to a less stressed environment and more regulatory cells and hence better graft survival. A lot of "ifs" and potential relationships. Probably an area worth studying in organ transplantation. 

Not to long ago, a study from the Kansas looked at some aspect of this. The investigators evaluated the impact of music therapy with and without a specific emphasis on emotional-approach coping. This randomized, controlled trial aimed to use Active Music Engagement with Emotional-Approach Coping to improve well-being in post-operative liver and kidney transplant recipients (N = 29). Results indicated that music therapy led to significant increases in positive affect, music therapy using led to significant decreases in pain, and both conditions led to significant decreases in negative affect, an indicator of perceived stress/anxiety. Another study that had evaluated this in Minnesota: Results indicated there were significant improvements in self-reported levels of relaxation, anxiety , pain, and nausea. Although there was no reliability measure, there were significant increases in positive verbalizations and positive affect in liver and kidney transplant recipients. It appears that in both the above transplant related studies, music was a good way to relieve nausea.  It appears that music as an anti emetic therapy is an old concept. Does classical music have the same effect as opera versus rap versus techno versus listening in your own language is another question?

CLINICAL CASE 61: Answers and Summary

PREGNANCY STATE CAN LEAD TO THROMBOTIC MICROANGIOPATHY. WHICH OF THE FOLLOWING ARE MECHANISMS VIA WHICH TMA HAPPENS DURING PREGNANCY?( MULTIPLE ANSWERS POSSIBLE)

HELLP syndrome associated 35%

ADAMTS 13 deficiency associated 10%

Complement alternative pathway associated 13%

VEGF deficiency associated 35%

Unknown mechanism associated 5%

Obstetric nephrology is a field with significantly complex patients who have high risk of maternal and fetal complications. Thrombotic microangiopathy(TMA) during pregnancy can have a vast differential. There is a new way of thinking of TMA after the advent of the atypical HUS diseases. Pregnancy associated TMA accounts for 8-18% of all cases of TMA. Its a secondary form of TMA.

Acquired causes of TMA from ADAMTS13 is a cause that is definitely one form that can be see in pregnancy and non pregnancy states that clinically would present as TTP more than HUS.

Dysregulation of the complement cascade especially the alternative pathway would lead to the newly discovered forms of atypical HUS and this can also be noted in pregnancy. Unknown mechanisms would be the other big category in the this as well.

HELLP syndrome: is this really a TMA or not a TMA? AKI is associated with fair amount of cases of HELLP syndrome. The pathology in the liver suggestive of TMA and some forms of HELLP syndrome share same genetic features as some atypical HUS syndromes. Kidney biopsies have rarely been done and those have shown TMA.

VEGF deficiency: Pre eclampsia has now been associated with antiangiogenic factors that might lead to anti VEGF state just like what we might see in cases of avastin toxicity. The biopsy in such cases might be also suggestive of  TMA. 

A recent review in CJASN reviews this nicely. Figure 1 has a nice timeline of when these syndromes might best fit during the three trimesters. 

Publication trends by speciality among Internal Medicine residents

A recent study done published in the American J of Medicine suggests that internal medicine residents publish their research during residency and continue to publish up to 5-7 years thereafter.  There is an exponential rise in number of publications compared to many years ago.  Interestingly, what caught my attention was the subspecialty breakdown in Figure 5 of the manuscript.  Gastroenterology had the highest number of publications ( 2 publications per person-year) 5-7 years after fellowship training. Interestingly, hematology was next at 1.59 and nephrology quickly followed at 1.56. Cardiology was at 1.0.  Rest all were < 1.0.
This is a positive trend at least in our field to be in the top 3 publications trends of specialty as moving the field forward is important part of nephrology as well.

NEPHSAP review: Glomerular Disease: Hematuria Risk long term?

At Nephsap review, we discussed a question re asymptomatic isolated hematuria in an young adult and the discussion was regarding the long term risk to ESRD? Is it truly measurable risk?
Young adults often present with asymptomatic hematuria. This was elegantly studied by the researchers in Israel looking at close to a million sample size.  It was a retrospective cohort study using medical data from ages 16-25 (60% males and 40% females) who had been examined for fitness to the military.

Persistent asymptomatic isolated microscopic hematuria was diagnosed in 3690 of 1,203,626 eligible individuals (0.3%). After over 21 years, ESRD developed in 26( 0.7%) of the hematuria group and 529( 0.045%) without the hematuria group. This was a hazard ratio of 19.5.  A substantially increased risk for treated ESRD attributed to primary glomerular disease was found for individuals with persistent asymptomatic isolated microscopic hematuria compared with those without the condition. The authors concluded that the "presence of persistent asymptomatic isolated microscopic hematuria in persons aged 16 through 25 years was associated with significantly increased risk of treated ESRD for a period of 22 years, although the incidence and absolute risk remain quite low."

Hypercalcemia and hypokalemia- is there a link?

Interestingly, we do encounter this combination sometimes and likely has no connection.  This was indeed studied in a 1977 paper in Annals of Internal Medicine. They studied 103 patients with hypercalcemia in a cancer hospital with normal renal function and no history of taking potassium depleting agents. Interestingly, 32% were hypokalemic.  The cause of hypercalcemia is most cases was malignancy followed by primary hyperparathyroidism. Also, as the calcium levels were higher, the frequency of hypokalemia was greatest.

Why does hypercalcemia cause hypokalemia?

Perhaps the calcium delivery increases the na delivery to the distal tubule which in turn results in na-k exchange with loss of potassium. This is what might be postulated based on animal studies and prior human trials.  This above study was only done in the cancer ward and hence might have many other confounders that were not accounted for such as chemotherapy agents that cause low K, diarrhea in setting of infections, chemotherapy and so forth.  While the pathophysiology is plausible, the more likely explanation might be true-true and unrelated.

NEPHRONPOWER 1000th post: A tribute to a Nate Hellman

The 1000^th post on Nephronpower is dedicated to the pioneer in the use of Web 2.0 and blogging in nephrology- Dr. Nathan Hellman (Nate). 

       

Nate was the creator and founder of renal fellow network, the most influential blogging site in nephrology and in many ways- medicine. It’s his dedication and passion that inspired the creation of nephronpower.

Nate was a fellow in the Division of Nephrology at MGH-BWH Harvard University, died in 2010 at the MGH following a short illness. He was 36 years old. Hellman completed his residency training in Internal Medicine at the Hospital of the University of Pennsylvania in 2006 and spent the following year as a Fulbright research scholar at the Hôpital Necker-Enfants Malades in Paris, France. He joined the MGH in August 2007 as a clinical fellow in the Division of Nephrology. He was to be appointed a faculty member in the Division of Nephrology in July. A recent award has been created under his name. 

I asked one of his colleagues Dr. Anna Greka to comment and she said, "Nathan touched all of our lives with his warm heart and spirit, great sense of humor and remarkable intellect." 

       Blogging in nephrology was non existence before him. He made this possible. The nephrology community has embraced what he had been doing for many years prior to its prime time. It’s due to his passion and commitment, many physician based blogs exist in nephrology. A recent publication by a prior renal fellow network writer summarizes that.  It’s due to his commitment, now journal based Web 2.0 websites have come to exist in nephrology namely CJASN and AJKD.  Divisions around the world also have blogging sites now with ECU and Univ of Toronto leading the way.

       None of this would have been possible without Nate. Thank you, Nate for making a positive dent in nephrology education. Today, he deserves a standing ovation from the medical education world of nephrology. 

Special: Top 10 posts of all time on Nephronpower

10. KDIGO GLOMERULAR DISEASE GUIDELINES IgA nephropathy (2012)
9. CONCEPT MAP: Chemotherapy nephrotoxicity review (2012)
8. CONCEPT MAP: Types of Hypertension (2010)
7. CONCEPT MAP: Hyponatremia(2011)
6. TOPIC DISCUSSION: Wunderlich syndrome (2011)
5. Top Ten reasons to Love your kidneys (2011)
4. TOPIC DISCUSSION: Warfarin related nephropathy (2011)
3. TOPIC DISCUSSION: Lactic acidosis and dialysis (2011)
2. TOPIC DISCUSSION: DEXA SCAN in transplant patients (2010)
1. CONCEPT MAP: Hypercalcemia (2010)

Concepts maps in medical education are a common way to tie many concepts together. Best use of them are during rounds, or at a lecture to summarize or open a discussion. The best use is to "learn about the learner" and how they are thinking.