Diabetic Kidney Disease: Old and New View

A recent article by Dr Sally Marshall in ACKD reviews the natural history of CKD in diabetic patients and reviews the old and the new view of looking at Diabetic Nephropathy. Highly recommend this article for everyone to review.  Here is a short summary of the review.

Old view:

Microalbuminuria is permanent and progresses to proteinuria in most cases.
The peak incidence of DN is 16 years and few after 35 years>
Classically, the microalbumuria progresses to proteinuria and then GFR declines
Usually, this was an older individual disease.

New view:

Low levels of albuminuria( rather than microalbuminuria) is a reversible phenomenon in majority( likely representing more of a hemodynamic change, inflammatory change or endothelial injury rather than structural damage in the kidney)

Higher levels of albuminuria are more likely to progress to proteinuria.
Peak incidence of diseases now ranging from 16-30 years
Atypical forms of presentations are becoming common where GFR decline can be seen without any prior proteinuric variant.  A vigilant watch is needed to notice this “non classical” DN
Finally, young adults are being effected with this entity and CKD become more of a common disease in Type 2 DM at an earlier age.

Frequent Hemodialysis Trials: ASN 2011 update

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. This trial was launched because it was noticed from small studies that more frequent nocturnal dialysis may help improve outcomes in dialysis patients. A multicenter study headed by Dr. Rocco et al where 87  patients randomized to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea).  NO significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) was found. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Sample size was small which could have been a reason of these negative result.

A sister of this trial was conducted: this time it was morning dialysis ( not nocturnal) but daily vs conventional hd on 245 patients. Compared two groups 6times weekly vs 3times weekly. This was an in-center trial. Average delivered 5.2 days vs 2.9 days in the two arms respectively. The time was shorter in the daily so the total hours were only 20% more in the daily arm overall. However patients in the daily arm still did better compared with the conventional group. Both primary outcomes and secondary outcomes were the same as for the nocturnal trial but they were significantly better for the latter(during the day). The reason for the discordance is being investigated.( of note the nightly dialysis received much more time on dialysis than either daily frequent or conventional)

Final note :

"FHN participants were younger and the racial composition for each study was different from the racial composition of the aggregate US dialysis population. Catheters for vascular access were more common in FHN Nocturnal Trial participants."

Post by

Dr. Azzour Hazzan

Hofstra NSLIJ Nephrology

ASN2011: Dialysis Mortality

SOME TEACHING POINTS FROM ASN 2011 Pre course on Dialysis Care

We all know that mortality is very high for incident hemodialysis and could reach as high as 50%. 

Hakim et all showed in a retrospective study in looking at Fersenius data. They looked 10 years back and found out that those with the highest mortality had catheters. One conclusion could be that these deaths could be  infectious complications. It behooves us therefore to prevent these kind of deaths. 

Unfortunately people had these catheters and died despite the fact that thery were followed by nephrologists for more than six months.

Bradbury et al, AJKD, 2009 showed that mortality decreased by 36% and 29% when catheter was changed to AVF, and AVG respectively; and mortality increased by 80% when permanent access was changed to a catheter.

What are some reasons to this suboptimal care: 

Late referal to nephrology, priamary avf failure, patient-induced delays and in-decisions, etc. (NDT)

Patients were reluctant bc of fear of needels and fear of surgery and prior failures of fistulas.

Our job as nephrologists is to prevent these deaths and spend the time and energy to convince patients get AVF or AVG.

Post from

Dr.Azzour Hazzan

Hofstra NSLIJ Nephrology

 

Topic Discussion: Nano Medicine ( ASN 2011)

Nano medicine  was one of the topics presented at ASN 2011. What is that?

Dr.Chan described it very well for us at the ASN meet.

It is the science of application of nano techology principles in biology principals. If one thinks of a single atom, that is called the atomic state.  If we have 26 atoms, that is the bulk state. Anywhere in-between 6-19 atoms, is the tunability state.  Hence in this part of the molecule's structure of growth, it can be used to tube physical and biological properties. That is the nano state of the particle(sub micron size).  The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery.

These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs.

Nano is actually the same size as DNA and protein. Hence one advantage of such technology is to introduce relevant size particles to specific body parts and have effect( chemo, biology. etc)

Example. Make a particle that is 60 nm and get to the target site of the tumor.  Then can be used for imaging purposes or delivering chemotherapy.  It is in clinical phase trials for invivo cancer, diagnostics as well, and in research phase in cardiovascular diseases, diabetes and pathology.

The limitations are:  delivery is poor- 5percent and the particle can stay in body for MONTHS. 

So toxicity in unclear. 

Nevertheless, nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. Technically,  nano carries can do drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. But not sure if this is clinically able to happen. The leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB).  Finally, direct in vivo imaging of nanomaterials is possible leading to provide real-time tracking of those nanocarriers. 

But this can open up a whole area of research in Renal diseases in terms of podocyte biology and perhaps even renal imaging of certain smaller structures.  

Interesting concept.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/22059114

http://www.ncbi.nlm.nih.gov/pubmed/20199661

ASN2011: Complement related disorders

This ASN, there was a series of talks regarding complement glomerulopathy and the use of certain newer agents for treatment. Dr Licht discussed this in detail in one of the talks.

Bottom line

1. MPGN pattern of injury is seen in complement related glomerular diseases.
2. DDD is now part of C3 glomerulopathies
3. Complement factor H antibodies, complement factor B antibodies have been associated with C3 glomerular disease since they will enhance c3 conversion and eventually affect the alternate pathway.
4. Genetic forms such as mutations in Factor H, CFHR5, C3 polymorphisms were also noted in that case.
5. It is possible that what we used to call perhaps C3 only post infectious GN or resolving post infectious GN was really C3 glomerulopathy.
6. Treatment is plasma exchange as there might be antibody that exists ( if you think there is)
7. Complement inhibition is the key- and the only drug we have is eculizumab ( 4 doses 900mg IV per week and 1200mg per week following that for 4 doses):- but expensive
8. Overall, there is a paradigm shift happening in introduction of these disorders.

ASN2011: Pearls on Peritoneal Dialysis

From the pre course on ASN 2011, on Dialysis Modalities

The following are different strategies to decrease risk of peritonitis; they are unrelated concepts.

 

1-Russo et al in KI did a multi center Italian study. 353 pts answered a questionnaire. 191 pts had home visits with a score card.  23% were non-compliant with exchange procedure. This was associated with increased peritonitis rates.  So it maybe worthwile retraining Pd patients for 4days yearly to decrease the risk.

 

2-Diverticulitis may be associated with increased peritonitis rates. 

 

3-Hypokalemia and constipation can cause peritonitis; Bacteria in the colon migrate across the visceral peritoneum and enter the peritoneal cavity which is filled with dialysis fluid which inhibits immune function.

 

4-We should use prophylaxis medications for GI procedures to decrease risk of infections.

 

5-Fix all hernias before starting PD. On exam, one needs to have patients stand to uncover hernias and leaks. Umbilical hernias may be the smallest but have the biggest risk of incarciration.

 

And one more interesting tit bit of information was a new way of reporting Peritonitis instead of N of months between episodes;  is to use the number of infections per year and this will help compare centers to each other and also get a sepecific bug rates internally and within centers. 

Post by 

Dr.Azzour Hazzan

Hofstra NSLIJ Nephrology

ASN2011: CPC- Adenovirus Nephropathy

One of the highlights of ASN is always the CPC conference. This year the case was a transplant case with viral nephropathy and the nephropathy was Adenoviral origin.

Adenovirus nephropathy

Adenovirus is an important virus to consider in the differential of post kidney and BMT transplant nephropathies.  The urinary subgroup is 34 or 35 and the incidence is < 1% causing nephropathy.

Can see hematuria, testicular tenderness, and subjective complaints.

The kidney biopsy usually has ATN or AIN or abscess.  The viral particles are mostly in the epithelial cells unlike CMV which can infect endothelium and epithelium.  In the EM, there are 70nm non enveloped bodies noted.

Treatment is decreasing immunosuppresion or cidofivir ( nephrotoxic) but may have to be used.

A diagnosis that we should keep in mind when thinking of viral etiologies of nephropathies post transplant. 

Take a look at this recent JASN article.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21436288

ASN2011: Late Breaking Oral Presentation: FISH Trial

Dr Lok from Canada presented the findings of the FISH trial that looked at use of 4gm of fish oil as a primary preventive for AVG stenosis.  The primary outcome was native potency and they did a randomized controlled placebo based trial.  It was a large group of patients and it was a well designed trial.

Unfortunately, the primary outcome was negative and there was no statistical significance of native potency prevention. But the secondary outcomes such as rate to thrombosis, number of interventional procedures, and cardiac events( MI and CHF) were statistically significant in the fish oil group.  

Also, the rate of corrective interventions was more in the placebo arm. Interestingly, there was no difference in cholesterol, TG and LDL in both groups. But HTN mean SBP was less in the fish oil group post intervention.  

A nice trial, but negative results. But there is some suggestion here that fish oil might be helpful in preventing cardiac events. This is the largest cause of death in ESRD patients. Something to follow up on as the research gets published

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/17848497

ASN Kidney News 3 day podcast from ASN

History of Nephrology: First ASN

It was 1967 ( first ASN ever)
Some words of wisdom and pride from Dr. Grantham, John Peters Award Recipient
"Nephrology is the best kept secret of internal medicine"

ASN 2011: West Nile Nephropathy

An oral abstract presented at the ASN 2011 session talked about an interesting new entity that we should now consider in our diagnosis - West Nile associated Nephropathy presented by Dr. Podoll.
West nile is a zoonotic infection that infects horses and humans and bird as the vector. WN is an arbovirus, sRNA and there are 3.8 million infected cases in the USA.
There are many neurological sequelae that we have read about that can come from WN. Apparently, many also develop chronic neurological damage. Bird autopsies have shown that the virus can also live in the kidney and usually in the tubules. The Hampster model has shown that it can have peri tubular damage.
Of 208 patients with chronic WN neuropathy, 70 were found to have been shedding WN RNA in their urine.  Most of them were male and 47% had proteinuria.  28% had GFR < 60 and the urine sediment showed predominant monocytes, epithelial cells.  6 biopsies found chronic tubular interstitial disease with predominantly monocytes. Glomeruli were normal.  EM showed virion particles within the tubules. Immuno was negative in all cases.  There was chronic interstitial fibrosis and tubular atrophy.  


This is interesting - chronic TI disease from West Nile Nephropathy- keep this in your differential in the endemic areas of USA and the world


Ref
http://www.ncbi.nlm.nih.gov/pubmed/16102323
http://www.ncbi.nlm.nih.gov/pubmed/15772329
http://www.sochinf.cl/sitio/templates/sochinf2008/documentos/persistenciavirusdelnilo.pdf

ASN 2011: MPGN revisted

MPGN classically has been associated with Type 1, II and III variant and divided based on electron microscopic(EM) findings.
This ASN, a paradigm shift of thinking was mentioned.

The thinking now is to think of it more like a pattern of injury and classify based on immunofluorescence (IF) rather than EM.

The four major categories are:

Immune complex :  chronic infection related or auto immune 

Complement dysregultion : familial and acquired, the c3 glomerulopathies

Chronic tma:  atypical hus, other TMAs, APLAS

Paraprotein.  Any variant can come here, that is monoclonal

Old classification:  Based on extent of deposits on EM and where they are

New classification: Based on pathophysiology and IF findings more

So If you have IgG and C3 on IF:- then think more immune complex based

If you have Ig G monoclonal:- think monoclonal disease 

If you have C3 only:- think C3 glomerulopathies  or Dense Deposit Disease

If you have No C3 or IgG:- then think TMA

Idiopathic MPGN in an adult is a diagnosis of exclusion, more common in children and its usually polyclonal and C3 positive. 

So think differently when thinking about MPGN from now on. Always a tough disease to battle

take a look at a prior concept map on this

http://www.nephronpower.com/2011/08/concept-map-of-mpgn-pattern-of-injury.html

E Journal Club:- CJASN feature

CJASN is doing live journal clubs or e journal clubs of the articles published in CJASN.

Take a look at this new and innovative feaure

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

eAJKD, the official blog of AJKD

I would like to introduce to the blogsphere:- eAJKD: the official blog of American Journal of Kidney Diseases.
http://ajkdblog.org/

The American Journal of Kidney Diseases (AJKD) is the official journal of the National Kidney Foundation and is recognized worldwide as a leading clinical kidney journal. AJKD is pleased to now offer eAJKD, the official blog of the journal. A central goal ofeAJKD is to highlight selected journal content in an engaging, timely format.  The blog will have interviews with authors, educational material, as well as podcasts and video. We are looking forward to bringing AJKD into the future and offering engaging new means for authors and readers alike to interact with the journal!

It's also a landmark as this is the first time all prominent Nephrology bloggers or e-nephrologists are uniting for a single mission:- Education and sharing of knowledge. Please welcome: Matt Sparks, Tejas Desai, Vinay Nair, Joel Topf, Sidharth Sethi, Kellie Calderon and Jordan Weinstein to this. 

Come visit us all at the eAJKD and we shall show you many new things in the coming months.

ASN Abstracts 2011 online

ASN 2011 abstracts are now online live at
http://www.asn-online.org/education_and_meetings/kidneyweek/archives/KW11Abstracts.pdf

Check out the google page of ASN as well

http://www.google.com/reader/shared/06308306117959986613?c=CM_W4__Z9KsC

ANIO event at ASN 2011

American Nephrologists of Indian Origin (ANIO) is having its annual dinner at ASN Nov 2011 this year.
The overall purpose of ANIO is to bring together like-minded nephrologists, nephrology trainees and health care professionals in the field of nephrology who have their origins in the Indian subcontinent and/or those who have worked in areas related to the Indian subcontinent. While the group is principally drawn from the United States, ANIO seeks to have a broader reach and would aim to draw membership from other parts of the world.


The event details can be found at www.an-io.com

The American Nephrologists of Indian Origin (ANIO) invite you to join
us for a reception and dinner at the American Society of Nephrology
Meeting 2011

We will be recognizing two outstanding colleagues for their
contributions to nephrology:

Dr. Karl Nath, Mayo Clinic
Dr. Ravi Thadhani, Massachusetts General Hospital

6:45 pm
Thursday, November 10, 2011
Marriott Hotel
1201 Market Street
Philadelphia Downtown
Philadelphia, PA 19107
(215) 625-2900Venue: Marriott Downtown, Philadelphia, PA

Special talk:
Understanding Hyponatremia: Treating Beyond the Primary Diagnosis

Ekambaram Ilamathi, MD
Medical Director,
Suffolk Nephrology Consultants, NY