Saturday, December 25, 2010

Chronic renal allograft dysfunction

This month's Kidney International has a special extra edition on Chronic renal allograft dysfunction.
This supplement has >10 articles that highlights latest development in transplantation on pathogenetic mechanisms of T and B cells in Chronic rejection, IF/TA and then few chapters on fibrosis and genomic studies.
Risk factors, infections and immune monitoring are also discussed.

Few of them are linked below:
http://www.ncbi.nlm.nih.gov/pubmed
http://www.ncbi.nlm.nih.gov/pubmed/21116312
http://www.ncbi.nlm.nih.gov/pubmed/21116316

Thursday, December 23, 2010

TOPIC DISCUSSION: Hypokalemic Nephropathy

Yes... Hypokalemia that is chronic can lead to decrease in GFR and nephropathy. How so?
Also known as kaliopenic nephropathy
1. Hypokalemia can lead to a renal concentrating defect leading to polyuria and polydipsia- DI
2. Chronic tubular damage can occur as a result and lead to proximal tubular damage as well
3. Tubular interstitial disease develops
4. Proteinuria can be seen
5. Renal cysts can be noted
6. There is also impairment of  renal angiogenesis, evidenced by progressive capillary loss, reduced endothelial cell proliferation, and loss of VEGF expression in one study.
7. Histologically:- tubular atrophy, interstitial infiltration of macrophages, and fibrosis
Ref:
http://www.ncbi.nlm.nih.gov/pubmed/18178802
http://www.ncbi.nlm.nih.gov/pubmed/17928827
http://www.ncbi.nlm.nih.gov/pubmed/20828906

Tuesday, December 21, 2010

CMV in solid Organ transplantation!

CMV infections are fairly common in solid organ transplantations.  A nice review in Nature Review Nephrology this month highlights prophylaxis treatment, active treatment and serology testing. What I found very useful wa a table on dosage recommendations for ganciclovir and valganciclovir in varied renal function states. 
A nice section on anti viral resistance also reveals some important data on use of foscarnet and when there is UL97 mutations.  These strains usually have ganciclovir resistance.  The UL54 strain mutation can have resistance to even foscarnet and cidofivir.  The advent of commercially available genotyping allows for rapid results of UL97 or 54 and allow for personalized treatment of CMV viremia or disease.  
Resistant CMV guidelines
1. Increase dose of ganciclovir 
2. Change to foscarnet with or without continued ganciclovir
3. Change to Cidofovir only if pol mutations are not present otherwise it cross reacts with ganciclovir resistance.
4. leflunomide has been tried in few cases.
5. CMV immunoglobulin (IVIG) as a last resort and if there is organ damage happening.

Check it out

Monday, December 20, 2010

CLINICAL CASE 30, ANSWERS AND SUMMARY

Tenofovir can cause proximal tubular damage? Recent data show it to damage what part of the cell?

Nucleas 2%

Mitochondria 71%

MRP-2 Channel 17%

NK ATPase pump 7%

The HIV drug Tenofovir, as we all know , can be nephrotoxic. Proximal tubular damage is what we usually see with full blown Fanconi syndrome as well in some cases.  What the organic anion drug do in the proximal tubule cell?  It is delivered to the basolateral membrane of the proximal tubule cell and its transported into the cell by the organic anion transporter OAT-1.  Once it enters the cell, the drug is secreted into the urinary space via MRP-2 and MRP-4 ( multidrug resistance protein transporters).  The damage we see with this drug is via direct mitochondrial DNA depletion and damage done by the drug within the cell.  Disturbances in the secretory pathway ( increased OAT-1 or decreased MRP efflux) can lead to increased drug levels in the cell and ultimate mitochondrial damage.  MRP-2 is a good answer but mitochondria is the best answer as the damage really is via mitrocondria that leads to the final proximal cell tubulopathy. 
This has been shown in EM findings or ultrastructual findings that show eisonophilic intracytoplasmic inclusions within the proximal tubular epithelial cells, that are the giant mitochondria seen usually.  The mitochondria have abnormal cristae and hence don't function.  
This ultimately leads to strange shaped and large shaped mitochondria that are non functional and tenofovir induced toxicity. 
A nice reference from KI is listed below:

Sunday, December 19, 2010

In the NEWS: Angiopoietin like 4 , a glycoprotein that might change the face of glomerular disease.

A recent study published in Nature Medicine reveals some very interesting findings. The researchers in Alabama showed that glomerular expression of angiopoietin-like-4 (Angptl4), a secreted glycoprotein, is glucocorticoid sensitive and is highly upregulated in the serum and in podocytes in experimental models of minimal change disease and in the human disease. Podocyte-specific transgenic overexpression of Angptl4 (NPHS2-Angptl4) in rats induced nephrotic-range, and selective, proteinuria (over 500-fold increase in albuminuria), loss of glomerular basement membrane (GBM) charge and foot process effacement, whereas transgenic expression specifically in the adipose tissue (aP2-Angptl4) resulted in increased circulating Angptl4, but no proteinuria. Mice with no Angptl4 had no proteinuria.  
This is exciting in many ways: This might suggest that this specific protein might be the type of nephrotic syndrome that responds to steroids, so if you have elevations of this protein in your urine or blood you have a certain nephrotic syndrome that will respond to steroids and decrease proteinuria. Lets see what this pans out in human studies.  Great work by the scientists at Alabama on this breakthrough discovery. Check out the link below.

http://www.ncbi.nlm.nih.gov/pubmed/21151138

Saturday, December 18, 2010

Health Care Law Blog: AMA Issues New Policy To Guide Physicians’ Use of ...

Health Care Law Blog: AMA Issues New Policy To Guide Physicians’ Use of ...: "Today the American Medical Association announced that it has adopted and issued a new policy offering guidance to physicians on the use of s..."

Genetic Nephropathies and Kidney Transplantation

A recent article in Nature Review Nephrology reviews the diseases we always get worried if a living donor can be used.
This review outlines the does and don't of hereditary nephropathies and donor evaluation of kidney transplantation. A table in the articles nicely summarizes the disease entity and if the living related donation would be appropriate.
In Finnish type Congenital Nephrotic syndrome, NPHS2 FSGS, NPHS3 FSGS, Pierson Syndrome, Schimke's immunoosseous dystrophy, nephronophthisis, cystinosis and ARPKD and alport syndrome:- it is ok to use living related donation in transplantation.  In Primary Hyperoxaluria and Atypical HUS, one has to be careful in selecting the donor from a living relative.
In general AR type of diseases, the donor can be a relative and most of the time its not a problem. Autosomal Dominant diseases is always a concern. We come across this most in ADPKD and the donor evaluation in that case is so strict and needs careful screening if its a relative.  Atypical HUS should not receive a kidney transplantation from a living donor because it is a high risk for disease recurrence and graft loss.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20877305

Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura

Friday, December 17, 2010

Medicine for residents: a little step towards cost effectiveness - renal ...

Medicine for residents: a little step towards cost effectiveness - renal ...: "A renal ultrasound is a very good study that gives a lot of useful information for a lot of kidney diseases. Especially...in Acute Kidney in..."

Thursday, December 16, 2010

IN THE NEWS- Article on Online Blogging of Conferences

Check out first of its kind article on "online blogging" of nephrology conferences powered by Nephrology on Demand, Pediatric Nephrology.com and Nephronpower.com.
A treat for all bloggers in Nephrology. Its published in the recent edition of Kidney International.

Ref: http://www.nature.com/ki/journal/v78/n12/abs/ki2010395a.html

Tuesday, December 14, 2010

TOPIC DISCUSSION: Anesthetics and Kidney Disease

Do Anesthetic agents cause Renal Disease?
A recent discussion in a nephrology forum this above question was asked. Evidence on this is scant. On literature review, few cases reports found in 1960-80s and none after that. Perhaps we have not been using these agents anymore.  Some of the older agents might have cause renal disease.  In animal experiments, kidney damage has been reported after low level exposure of halothane.  Few case reports exist of methoxyflurane causing renal dysfunction.  There was a retrospective cohort study and it reported a higher frequency of kidney disease among exposed persons especially women ( in 1968).  Moderate to temporary effect on kidney function has been shown  in patients who got methoxyflurane.  Rats were subjected to chronic exposure to low levels of halothane (10 and 500 ppm for 8 and 4 weeks, respectively). Kidney histology showed proximal tubular changes and mitochondrial injury.
In the 1960s, the widespread use of the inhalational anaesthetic methoxyflurane was associated with a significant occurrence of postoperative renal dysfunction. This was attributed to hepatic biotransformation of methoxyflurane and subsequent release of inorganic fluoride ions into the circulation. It was found that this was more due to the drug containing massive amounts of fluoride and this was all fluoride toxicity. Nowadays, fluoride-related toxicity has been observed neither in animal nor in clinical studies, including prolonged administration and patients with pre-existing renal disease.

Reference:

Friday, December 10, 2010

Concept Map of Hypomagnesemia



A brief overview of Hypomagnesemia using a concept map model
If not complete, help me complete it!

http://www.ncbi.nlm.nih.gov/pubmed/10405219

Quiz 9 Answers

Which drug is paired incorrectly with the target molecule?
Rituximab -- CD20
Alemtuzumab -- CD52
Belatacept -- CD198
Belimumab --- TNFSF13B
Atacicept ---TACI-Ig

The correct answer is Belatacept CD198, that is incorrect pairing. Most of you got it right.
We all are familiar with Rituximab which is a B cell antagonist and since all B cells besides plasma cells are CD20 Positive, its an anti CD20. Alemtuzumab(campath) targets cd52 a protein present on the surface of mature lymphocytes. Atacicept(TACI-Ig) is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B-Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B-cell maturation, function and survival. Atacicept has shown selective effects on cells of the B-cell lineage, acting on mature B cells and blocking plasma cells and late stages of B-cell development while sparing B-cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. The selective inhibitor of T-cell costimulation, belatacept, blocks CD28-mediated T-cell activation by binding CD80 and CD86 on antigen-presenting cells. Understanding the extent to which belatacept binds to its targets in patients may enable correlation of belatacept exposure to receptor saturation as a pharmacodynamic measure of costimulation blockade.
Belimumab (registered name Benlysta previously known as LymphoStat-B), is a fully human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-Lymphocyte stimulator (BLyS), also known as B cell activation factor of the TNF family (BAFF).

Tuesday, December 7, 2010

IN THE NEWS- Meta-analysis in Nephrology

A recent article in Kidney International reviews the role of meta analysis in Nephrology world. Based on the survey this group did in NYC area, most physicians viewed meta analysis in nephrology useful and influenced their patient care.
What are the limitations of meta analyses?( from the article- refer to article for details)
1. Publication bias
2.Mixing apples and oranges
3. Garbage In, Garbage Out
4. Outcome selection bias
5. Patient exclusion bias
6. Truncated study bias
7. data collection errors
What are the strengths  of meta analyses?
1. Power
2. Highlights areas that need work
3. More transparent form of review- and not just a review article
4. Sounder bias offered
Even with all these meta analyses happening in our literature, many of our guidelines are still "opinion" based.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20827259

Monday, December 6, 2010

TOPIC DISCUSSION: Camels and their Kidney!

Ever wondered what the camel does differently than us to survive in the hot environment? The camel does have a special kidney and a special GI tract.The camel's kidney actually can concentrate the urine more than sea water but less than a dessert rat.  Since the camel can concentrate the urine more than sea water, salty water intake won't harm the animal. Investigators have studied the  structure of the camelian kidney to discover whether or not the anatomical features necessary for producing a highly concentrated urine were present or not. The relative thickness of the medulla was calculated in the camelian kidney as it has been demonstrated that this thickness has a direct relationship with the ability to produce a highly concentrated urine.  A relative thickness of the medulla is a good measure of the length of the loop of Henle which is an indicator of urine concentration. The thickness reported in camels was 7.89 in comparison to the value of 8.5 in kangaroo rats, much more than humans.
Also, what happens if you haven't drunk water in 5 days and all of a sudden you re hydrate. A dehydrated camel can replace water within minutes of drinking, and some of this water is quickly absorbed into the bloodstream. With water in the bloodstream, ADH declines and the kidney will return to normal renal function within 30 minutes of drinking. Not only does the camel adopt to scarce water but the kidney can also adopt to rapid dehydration and not lead to demylination of the brain.
What are some other features this animal has to store water for long periods of time?
Another interesting part of the camel physiology is that they have 3 stomachs, acting as storage( 1.5 gallons per stomach) for the water and hence when water is not available, they can slowly replenish the system. The camel stores water in its blood stream, an interesting physiological process. Capable of losing forty percent of its body's weight before becoming distressed, it is able to go five to seven days before having to drink. The amount it drinks when water is available would cause severe problems in most animals, up to 21 gallons in about 10 minutes.The camel's mouth, stomach, and teeth have all developed to allow it to eat plants that are not palatable to other desert animals.Contrary to popular myth, the camels don't store water in their humps, its full of fat for food storage.
Some of the rodents in the dessert can actually concentrate up to 7500mOsm.
Fun things you can learn from other animals who adopt better to water problems

http://www.ncbi.nlm.nih.gov/pubmed/511770
http://www.ncbi.nlm.nih.gov/pubmed/407772
http://www.ncbi.nlm.nih.gov/pubmed/475010

Friday, December 3, 2010

Sirolimus- the Positive aspects

The same issue of KI shares another view- the positive aspects of sirolimus
As we mentioned earlier that this agent was discovered as a cancer drug and has antiproliferative properties

Recent animal data and human data have shown it to be beneficial in preventing cancer post transplant
So the benefits of this agents are:

1. Prevention of cancer, as mTOR is responsible for transcription and translation for cell growth.  Definite evidence against Kaposi, Skin cancers and renal cancers.
2. Increase in T regs
3. Anti viral effects - CMV, BK and EBV viral infections ( still not sure- conflicting data)
4. Tolerance inducing potential
5. Control of fibrotic process - conflicting data when compared to CNI alone

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20981120

Thursday, December 2, 2010

Nephsap review: Fluids Electrolytes

Another interesting Nephsap teaching point by a question was an under recognized cause of acquired apparent mineralcoritcoid access.
Liver cirrhotic patients with elevated bilirubins and sickle cell crisis patients who have elevated bilirubins have this happen to them.  When total bilirubin levels are very high, it is hypothesized that worsening cholestasis led to greater bile acid inhibition of 11B - HSDH type II in the distal nephron and this allows for K wasting via cortisol mediation and HTN as well.
Case reports have been reported in liver cirrhosis and sickle cell crisis patients?
Wonder if we see this or its noticed in Post BMT - VOD syndrome?

Tuesday, November 30, 2010

CONSULT ROUNDS: Propofol Infusion Syndrome

Why does a nephrologist care about Propofol infusion syndrome (PRIS)?
Its an important entity for us to know. It is a known cause of Rhabdomyolysis and hence AKI and also causes lactic acidosis. PRIS is a rare but fatal syndrome described in adults and children who get high dose propofol infusion(usually for CNS injury sedation or alcoholics). Usually >48 hours of infusion of 5mg/kg or higher.
Classic features: Rhabdomyolysis, hyperkalemia, hypocalcemia, elevated troponin, severe metabolic lactic acidosis, renal injury, high Triglycerides and features of SIRS without other real findings of Sepsis.  Usually these patients are neurological injuries and getting catecholamines as well or steroids. Tmax could be very high in such cases sometimes in 106-107F range. Cardiac features can include Bradycardia, hypotension, PEA, VT, Atrial Fibrillation and SVTs. Some of the cases described have been with concurrent severe infection as well. What happens at cellular level- this drug impairs free fatty acid utilization and mitochondrial activity leading to these findings?
In summary: Steroids, catecholamines and propofol alter energy production alter the SIRS and MODS syndrome and that leads to worsening rhabdomyolysis and cardiac failure that then leads to metabolic acidosis and acute renal injury. Cerebral Microdialysis can monitor brain energy related metabolites including lactate and pyruvate during head injury.  The cerebral lactate to pyruvate ratio is increased in PRIS. One way to monitor this syndrome.
Some people think that the term PRIS might be misleading and really it is a pathophysiologic state.  Critical illness of any kind is the priming factor and the propofol along with steroids or pressors can be triggering factors.  So really the name critical illness cardiac, renal failure and rhabdomyolysis associated with high dose propofol, steroids or pressors seems more appropriate.
In such cases where this risk is high, best is to use a different agent for sedation and remove propofol from the culprit.
Ref: 

Sirolimus - The negative aspects

A recent article in Kidney International discusses the negative and positive aspects of this interesting drug- sirolimus, mTOr inhibitor.  Initially designed to fight renal cancer, fast caught on to treat rejection and be used as an immunosuppression.
1. Six trials so far have randomized sirolimus vs a calcineurin inhibitor that were mentioned in this article. They all had more acute rejection episodes with sirolimus. So graft survival is a concern.
2. Renal toxicity has been described- from TMA to collapsing FSGS and severe proteinuria making it not as promising as CNI. But CNI have a more chronic toxicity to the kidney
3. Dyslipidemia has been noted as well more with this agent. - close to 60% of the patients getting mTor in clinical trials required lipid lowering agents
4. NODAT was also noted to be higher in this group; 25% more chance than CNI
5. Wound healing:- preventing the surgical wound healing or in future if patients need other surgeries makes it tough.
6. Other- mouth ulcers, myelosuppresion and infertility were more common in this agent as well.
7. Finally, they mention the new findings lately described pulmonary toxicities that are leading to a restrictive disease in the lung.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20703217

Monday, November 29, 2010

Nephsap review: Fluids Electrolytes

Interesting thing we learned at our Nephsap about why hypomagnesemia causing hypokalemia
1. Intracellular Mg has inhibitory effects on the K secretion of ROMK channels in the distal nephron.
2. A decrease in Intracellular Mg will release this inhibitory effect and cause Renal K excretion.
3. Also Low Mg can lead to increase distal Na delivery and increased aldo as well and K excretion increases.

Tuesday, November 23, 2010

CLINICAL CASE 29, ANSWERS AND SUMMARY

Which one of these is the most common renal manifestation of the drug "sunitinib"( Tyrosine kinase inhibitor)?

MPGN
  2 (6%)
TMA
  16 (48%)
FSGS
  4 (12%)
AIN
  5 (15%)
ATN
  6 (18%)




Most of you got it right. Dr.Tamim Naber actually gave out the answer in the last post on Onco Nephrology. The Tyrosine Kinase inhibitors have been lately the life saving drugs in kidney cancer. The outcomes with these agents are really good. Since they act downstream of VEGF, there side effects will be similar to the side effects of Anti VEGF agents or " like pre eclampsia".  Hence the most common pathology and clinical finding that we encounter is TMA. Cases of Nephrotic syndrome without biopsy have been described.  AIN has also been shown by biopsy proven cases. Initially, you see HTN, with some non nephrotic proteinuria, slightly low platelets, elevated LDH, lower than usual haptoglobin and slight increase in Crt.  Its not a full blown TTP or HUS but rather a spectrum of TMA as the constellation of findings.

Ref:


Monday, November 22, 2010

ASN 2010 - Live update: "Onco Nephrology"

Onco Nephrology is one of the many interesting fields in nephrology that's growing; as treatment becomes more sophisticated and efficient, so do the renal complications. Key points are: "Dr Larson, R., Glezerman, I"

1- Tumor Lysis Syndrome "TLS":
-Expected within 3 days before and 7 days after starting therapy
-High risk factors to develop TLS: Highly proliferative tumors (ALL, AML, NHL, lymphoblastic or Burkhitt's lymphoma), high tumor load, and those tumors most susceptible to therapy.
-Low risk for TLS: Solid tumors in general, MM, AML, CLL, and Hodgkin's
-Best management is prevention with hydration "Maintain U/O 150-200 ml/hr", Close F/U for complications
-Bicarb shown not much helpful and it carries many potential complications including increase chance for phosphate to precipitate in tubules in the alkaline media. Also, Bicarb can increase total body volume "risk for CHF". Best Hydration fluid is 0.9% NS
-start allopurinol early before therapy.
-If uric acid already high, then Rasburicase is indicated "absolute contra-indicated in G6PD!"
Kayexalate for hyperkalemia "remember: 1gm kayexalate binds 1meq of K+"

2-Tubulo-interstitial disease "2ry to chemotherapy":
a- Cisplatin:
-Dose dependent, highly concentrated in urine
-causes: non-oliguric bland urine, SIADH, HUS, salt wasting, low Mg and high Na in Urine electrolytes analysis!
-Before starting cisplatin, make sure patient is euvolemc and normal GFR

b- I-Phosphamide:
-Dose dependent, and children 3-5 years are more susceptible!
-can develop CKd in up to 50% of cases of AKI
-Causes proximal tubular injury/Fanconi's syndrome

c-Methotrexate:
-95% excreted in urine
-AKI due to crystal deposits/ tubular obstruction, and usually non-oliguric
-treatment: maintain U/O >3 L/day, urine PH >6.5. Leucovorin rescue therapy showed benefit

3- Glomerular toxicity:
a- Gemcitabine:
-can cause Thrombotic Micro Angiopathic syndrome "TMA", as well as worsening HTN
-No evidence for benefit of using plasma exchange therapy for TMA here. Best is withdrawing therapy.

b- Anti VEGF therapy "Sunitinib, Bivacizumab, etc.."
-TMA, proteinurea "some develops nephrotic syndrome", HTN
-AIN; been described by Dr Jhaveri, Kenar in his case series review of a single center experience of 3 cases developed AIN after introducing Sunitinib.

c- Metamycin
-Dose dependent TMA "20% develops TMA for dose >100mg/m2 in contrast to 1% only for dose<50mg/m2!"

Video: The Treatment of Resistant Nephrotic Syndrome with Acthar Gel (ACTH) - Renal and Urology News

Video: The Treatment of Resistant Nephrotic Syndrome with Acthar Gel (ACTH) - Renal and Urology News

ASN 2010 Live Update - Late Breaking Trials

Please refer to Nephrology now for this excellent summary of late breakers!
http://www.nephrologynow.com/publications/asn-2010-late-breaking-clinical-trial-results-sharp-preclot-more

Sunday, November 21, 2010

Dialysis Access Atlas from Fistula First. Check it out!

A nice treat from Dr. Tushar Vachharajani, An Interventional Nephrologist from Wake Forest University Medical Center.

Access Educational Tool

Listening to the right sound in AVF and AVG can get your ear trained. Just like a cardiologist. The Fistula First Has a nice tool on the page listed below. Towards the bottom of the page, listen to the bruits!
The link for this tool:

 

Saturday, November 20, 2010

ASN 2010 Live Update- Nephrology Education

 Nephrology education Oral Free communication presentations.
1. Michael Choi presented the data on the NKF KDOQI web based survey on how useful are the KDOQI guidelines and how many times does one access them and if the website is useful in getting these easily.
The survey showed that the guidelines have right amount of details but few felt that a summary page might be helpful, most people felt that the NKF website needed to be rewamped to get more information faster.
2. The physicians at East Carolina university did an interesting project with primary care setting and education of CKD. The nephrologist went to PMD clinic and spent half a day there for period of time and saw patients that were potential CKD as well with the PCPs.  They also gave lectures in the noon on key CKD topics. Over time, this led to more better CKD care, more ckd labs ordering, more pick up of Vitamin D deficiency and better understanding of CKD in Primary care setting.
3. John Hopkins group showed that a web based internet CKD teaching tool was significantly improving resident understanding of CKD based on their large database statistical analysis.
4. Fellow peer review done at Mayo Clinic on CKD care by fellows for co fellows and to see if pth was checked, anemia was checked and so forth showed excellent promise, The program director did have some overview of this process but the fellows were blinded.
5. One of my favorites was a Harvard undergraduate student who presented about a project undergraduates are helping out along with high school students with Harvard Nephrology Faculty and medical students called KDSAP, using KEEP screening and allowing undergraduates and high schools to be part of it. This helps two fold, helps community screening but also allows excellent early mentorship in probably choosing nephrology or if not medicine as a career choice, This will very likely increase nephrology workforce! Kudos to this group
6. Finally, Dr Calvin Chau talked about an interesting way of giving feedback in medical education.
KEEP, STOP, START.
What you learned and are doing you shall keep doing?
What you will STOP doing?
What you shall START doing?

ASN 2010 Live Update - hyponatremia

Hyponatremia  Updates
By Richard Sterns and Biff Palmer
Take home points
1. Make sure you rule out pseudohyponatremia( glycemia, mannitol use, sucrose use)
2. A commonly used agent in our transplant patients that might be sucrose based is IVIG and that can lead to pseudohyponatremia.
3. TURP syndrome leading to hyponatremia is another entity that is missed and non electrolyte water is used so that it doesn’t conduct electricity in these procedure.
4. Treatment of acute hyponatremia is very important, treating promptly is key. There is data that 12meq/day is safe to prevent Osmotic Demylination Syndrome. But going 0.5meq/hour is not required and there is no data.  You might need to correct much faster.
5. Rule of 6 to treat acute symptomatic  hyponatremia is very important.  Correct up to 6meq over first 6 hours and then stop and re assess.  Use 3%normal saline.
6. Use of vaptans in acute hyponatremia is still in early stages.  Few cases reported of using it.
7. Risk factors for ODS are age, alcohol, low solute intake and chronic hyponatremia and correcting too fast is as we all know very dangerous.
8. Using 3%NS and starting simultaneous DDAVP as well in high risk patients who present with acute symptomatic hyponatremia might be a good way to prevent overcorrection.

ASN 2010 Live Update - Transplantation in the Elderly

TRANSPLATATION IN THE ELDERLY - TOO OLD TO TRANSPLANT??

This was a nice discussion by Dr. Gabriel Danovitch, MD from UCLA during the Medically High-Risk Kidney transplant candidates lecture series.

Take home points:
1.  Decreased relative risk of death after kidney transplant as compared to dialysis leads to increased survival, but Quality of life seems to be worse.
2.  Pre transplant work up is the same Standard w/u for elderly as in the general population.
3.  Overall, lower incident of rejection in elderly (? Weaker immune system)
4.  But Increased donor age seems to be associated with increased risk of Acute rejection and AR treatment in elderly is associated with worse morbidity/mortality than AR treatments in younger patients
5.  Older patients statistically get older patients’ Kidneys and more likely to be listed for ECD kidney.
6.  Dilemma – should living donation be encouraged in Elderly?….. Studies have shown that older patients usually receive suboptimal kidney (read ECD) and have high waiting list time….. But given lower life expectancy is this perhaps a “wasted” younger living kidney??
7.  Elderly patients have higher risk of infectious complication leading to death post transplant.  Also increased risk of lymphoma at this extreme of life
8.  Also have to worry about Polypharmacy in elderly while on immunosuppression.  There are great transplant research drug protocols that are targeted to elderly patients.

Overall, Dr. Danovitch recommends  --  choose patients carefully
Use biological age vs chronological age to help decide?
Make sure patients know what they are getting into – (i.e risk/benefits pertaining to Quality of life issues, other complications, death)
Do not take their immune systems for granted
Older patients do better with younger kidneys
Higher risk of DGF in ECD kidneys
Do not take their immune systems for granted
? Risk of thymo in elderly?  But there is no good data
watch out for infections

By Stanley Crittenden, MD

ASN 2010 Live Update- KDIGO guidelines for HTN

KDIGO Upcoming guidelines:
This was a special reports lecture from the KDIGO (Kidney disease: improving global outcomes) group on their upcoming guidelines for AKI:
These guidelines should be published probably in early 2011.
Dr. Norbert Lameire from Belgium presented and chairs the AKI committee.

AKI guidelines:
The known RIFLE and AKIN definitions of AKI  -->  should be changed to one single definition of AKI.

KDIGO defines AKI defined as any one of the following
A.  Increase in SCre by 0.3 mg/dL with in 48 hour
B.  Or increase SCr by 1.5 fold above known baseline which occurred in past 7 days
C.  Or Urine volume of less 0.5 ml/kg/h for 6 hour

KDIGO also recommending a new concept – called AKD (acute kidney disease)
If patients recovery back to normal serum creatinine, This “presumed” recovered AKI should be be called AKD.
Patients with AKI often go on to develop CKD (due to ultra-structural renal pathologic changes) despite “normalized” Serum Creatinine à hence that patient’s diagnosis is AKD.

Other recommendations in their upcoming guidelines includes:
Contrast AKI – use only iso-osmolar or low osmolar contrast at lowest volume
Use isotonic Saline or NaHCO3 isotonic in at risk patients
Recommend N-Acetyl Cysteine (Mucomyst) together with IV Isotonic fluids, but There is NO role for N-Acetyl Cysteine ALONE.

And a couple of recommendations on dialysis in AKI from the guidelines:
Suggest CRRT only for patients with Acute brain injury versus Intermittant  HD (Grade 2B recommendation)

Dialysis Dosing recommendations:
Weekly Kt/V of 3.9/week in intermittent HD
Or CRRT dose of 20 – 25 cc/min effluent volume as optimal dosing

Remember, guidelines are not the “Gospel” and nor should they be considered the Gold “standard if care”. 

Stay tuned for full published guidelines on AKI in early 2011. 
Also, there will be upcoming KDIGO guidelines on Blood pressure control in CKD coming in late 2011 or 2012.  It will be interesting to see now these differ from the JNC and KDOQI guidelines!

By Stanley Crittenden, MD

ASN Live Update 2010: Drugs in Osteoporosis and CKD

Drugs in Osteoporosis in CKD: Orson Moe, MD
1. Anti reabsorptive agents: Kill osteoclasts
        Bisphosphanates: work fast, blasts slow down and increase bone quantity but turnover is reduced ( so not a good option for someone with Adynamic bone disease). Usually contraindicated in GFR<30. If you have CKD stage 3 and you have a low DEXA and aydnamic bone disease and get a bisphosphanate, now hyou have zero turnover more fractures.
        HRT/SERM: inhibit osteoclast proliferation and function, again leading to low turnover
        Calcitonin: doesn’t completely kill osteoclast, the balance of blasts is maintained. Not widely used though.
        Anti RANKL M ab: data on CKD lacking and transplant no experience
        
2. Osteo anabolic agents
        Pth: pulse pth, data on CKD not very strong
        Strontium, IGF-1 and other s in pipeline
Best agents in CKD: Calcicum, Vitamin D, Exercise and dietary acid lowering.

ASN Live Update 2010; CKD -BMD or Osteoporosis

Is it Osteoporosis or CKD-BMD?  Miller Brent,MD
1. Fractures in CKD can be caused by CKD-BMD and osteoporosis
2. Clinical risk factors in CKD: chronic heparin use, hypoganadism, steroid exposure, increase prolactin, poor nutrition, Vitamin D def, secondary pth
3. KDIQO guidelines for osteoporosis in CKD-BMD
Stage 1-3  low bone mass or fracture noticed, more likely osteoporosis related than CKD-BMD
Stage IV-V bone biopsy might be necessary to differentiate
4. If bone specific Alk Phos is elevated, you can rule out osteoporosis, and adynamic bone disease as long Paget and malignancy has been ruled out
5. An elevated Pth ( 6 normal) excludes adynamic bone disease
6. A normal alkaline phosphatase, and normal to low pth cannot rule out adynamic bone disease
7. Gold standard would be Bone biopsy 
8. Is osteoporosis and CKD-BMD overalap, or is osteoporosis a part of CKD-BMD or is CKD-BMD a type of osteoporosis is not clear?

ASN Live Update 2010: Osteoporosis, steroid induced and CKD

Bones and Nephrologists
Steroid related Osteoporosis , Mary Leonard , MD
Take Home Points
1. Steroid induced osteoporosis is 2nd most common cause of osteoporosis
2. Steroids uncouple bone formation and reabsorption
3. They increase osteoclast apoptosis
4. Besides other known risk factors, kidney associated risk factors are microalbuminuria and proteinuria, medications like CNI.
5. Vitamin D is albumin bound and in nephritic syndrome, there is Vitamin D loss.  Usually in NS, the 250H levels are low, this is temporary as pth levels don’t really rise as much based on studies compared to true Vitamin D deficiency.  
6. FRAX program online is a good tool to assess risk for fractures.  Age, gender, BMI, prior fracture, smoking and other factors are all entertained.
7. Recent ACR 2010 guidelines say that Steroid induced osteoporosis can be divided into three categories based on FRAX scores, <10% low risk, 10-20% is mod risk and rest high risk.
8. Bisphosphanates work best for steroid induced osteoporosis. Data on Forteo is new and can be better than bisphosphanates.

ASN Live Update 2010; Is fibrosis harmful? in the intact nephron?

At the plenary session at ASN 2010, Dr. Kriz discussed about fibrosis and is that really harmful to the intact nephron? studies showed that it is not! at least in the early stages.
The key points are
1. Progressive renal failure is based on the progressive loss of nephrons and they all loose nephrons independently.
2. Fibrosis is an advanced stage that has an autonomous drestruction of so far unaffected nephron remains an open question

ASN Live Update 2010: Glomerular Damage leading to IFTA? How?

A nice plenary session at ASN 2010 by Dr. William Kriz discussed the ways glomerular damage leads to Tubular interstitial damage?
Two theories exist: Leak theory and loss of albumin and other proteins can be damaging to the tubules
Data on this theory not that great.
second theory: As glomruli get damaged, eventually the damage gets closer to glomuler tubular juunction and that leads to spreading of misdirected filtrate and cell proliferation and that leads to intra tubular obstruction and degeneration of tubules.
Leads to IFTA in glomerular disease...
Interesting concepts and worth exploring more on this...

Friday, November 19, 2010

ASN Live Update 2010: VEGF and Diabetic Nephropathy

The VEGF and Diabetic Nephropathy
Take home points from Fuad Ziyadeh lecture

1.  Glucose, glycosalation, ROS, TGF B and Ang II all increase VEGF –A ( in podocyte) and lead to proteinuria.
2.  Two new players that might be interesting are Notch 1 and Mir 93 in this concept
3. Two mechanisms of albuminuria are paracrine and autocrine effects.  Paracrine meaning effecting the receptor of the VEGF ad autocrine meaning affect the VEGF directly
4. Paracrine: increase glucose, ROS and ang II lead to endothelial NOS and VEGF expression and then vascular injury
5. Autocrine effects: a decrease in nephrin and nephrin is in the podocytes hence leading to an autocrine effects
6. A recent paper referenced below showed that VEGF was activated in many human GNs
7. Early in DM – you get increase VEGF, later on there is loss of podocytes and hence a decrease in VEGF. So using VEGF inhibitors can lead to bad outcomes as well and sclerosis.
reference:
http://www.ncbi.nlm.nih.gov/pubmed/20395257

ASN Live Update 2010: VEGF and the podocyte

Podocyte and VEGF
Few take home points from Dr. Susan Quaggin Lecture
1. Local VEGF is important for glomerular development
2.VEGF and VEGF R-2 signal against the flow of urine
3. Modulation of VEGF is important.
4. When you remove VEGF in mice, you get TMA , but when you remove the VEGF-R , no TMA
5. If all VEGF-R2 receptors are removed from entire body endothelial cells, showed TMA in all of the kidney.  The liver  showed endothelial damage and nodular liver as well

ASN Live Update 2010: Cirrhosis and the Kidney

Th The Kidney in Liver Disease
Garcia-Tsao, MD
Take home points
1.      Pre liver transplant creatinine affects even post transplant survival of patient( based on data)
2.      Patients with Crt >1.0 pretransplant do worse post transplant
3.      Why is the serum crt low in cirrhosis( falsely): Decreased synthesis, malnutrition, less muscle mass, hyperbilirubenemia, and dilutational
4.      AKI can be divided in pre renal, renal and post renal causes in cirrhosis
5.      Pre renal causes are GI bleed, diarrhea usually due to lactulose, and hepatorenal syndrome(HRS)
6.      HRS is not volume responsive
7.      Intre renal causes  are ATN and GNs
8.      Post renal are rare
9.      20% of patients with cirrhosis in hospital have kidney injury( 19% is AKI and 1% is CKD). 68% of all are pre renal.  Of all pre renal most are volume responsive.
10.     In a study comparing pre renal ( diarrhea and GI bleed) causes and HRS, HRS has the lowest Na, lowest Mean arterial pressure and highest mortality
11.     Two things that make HRS worse worse splanchnic vasodilation and worse decrease in effective blood volume
12.     HRS-1 is aki, HRS2 is usually a chronic renal injury.  HRS -1 is a diagnosis of exclusion.  20% of AKI in cirrhosis, usually followed by infection and kidney is really not injured. 
13.     Diagnosis includes stopping all volume depleting agents first , looking for infection, giving IV Albumin 1g/kg qd or bid and if still no response in 48 hours, then check a cvp to see ifvolume replete and renal us, if all normal, then HRS Is diagnosed
14.     There is no data or studies on using bladder pressure in cirrhotics to date to discuss intra abdominal HTN


ASN Live updates from nephrology on demand

Check out the link for live updates from NOD at
http://blog.ecu.edu/sites/nephrologyondemand/?p=5161

ASN Live Update 2010:when do to combined liver-kidney transplants?


When to do a combined Liver and Kidney Transplant?
Take home points from Dr.Aklin's talk1.      After the introduction of MELD scoring system, the crt was in that and that led to increase number of combined liver and kidney transplants from 2% to 6%
2.      Who gets combined: ESRD with Cirrhosis, ESLD with GFR<30, ESLD +AKI+>8 weeks on HD, ESLD + biopsy proven >30% IFTA and >30% glomerulosclerosis
3.      After Introduction of MELD, the outcomes of Liver and kidney combined were worse , not donor related, perhaps recipient related as they were sicker. Now if MELD>23, they do worse and surgeons think twice before a combined liver kidney
4.      A biopsy proven way of deciding if you want to do a kidney and liver was suggested.  Interestingly they found that the most common biopsy finding was GN and DM being top, followed by MPGN, FSGS and IgA nephropathy
5.      >30% had biopsy complications, especially inr>1.5
6.      Interesting GN found after liver transplant alone( some sort of nodular GN, as it looks like DM nephropathy but they don’t have DM and never develop it)

Thursday, November 18, 2010

Diet and CKD - Historical Interest

http://www.ncbi.nlm.nih.gov/pubmed/5939526
Check out the above article.It has one of the oldest classifications of CKD and use of protein diet breakdown for a diet used in CKD.

The Kidney Transplant in HIV patients- the NEJM study

Kidney Transplantation was rare in HIV+ cases few years ago and now many centers have developed protocols that have allowed this to happen with relatively good outcomes.
No prospective studies were ever done in this matter for rejection rates, outcome measures and so forth,
This month in NEJM 2010, a nice multi center study takes a look at this particular question. The investigators evaluated 150 patients for close to 2 years, multicenter fashion, non randomized prospective fashion.
The mean graft survival was 90% at one year and 3 years was 73.7%.  The ones that didn't do well were the ones with rejection episodes, use of thymoglobulin, and non living donors.  The rejection rate was higher than expected, close to 31% at 1 year and 41% in 3 years.

This study shows that graft survival is good but the rejection rates are high still and needs some work. Perhaps the drug interaction with HAART therapy play a role in the fluctuation of perhaps CNI levels and higher rejection risk or the immunosuppresive agents we have now are not the ideal ones for an immunodeficiency diseases model?


ref:
http://www.nejm.org/doi/full/10.1056/NEJMoa1001197
http://www.ncbi.nlm.nih.gov/pubmed/19776780

Wednesday, November 17, 2010

ASN 2010 Live Update - Careers in nephrology

CAREERS IN NEPHROLOGY
Academic Nephrology: Job Security, Diversity, lifestyle advantages (Division of labor), opportunities for multidisciplinary interventional studies (e.g. CKD-CVD) ,opportunity to be part of translational research team, reward of teaching endeavors
Clinical Nephrology: Integration of care of CKD patients with PCP’s through the PCMH (Patient centered medical health) concept, need for outcomes research related to new reimbursement strategies, addition to workforce
New Concepts  PCMH (Patient centered medical health) CKD to be one of the major chronic disease to model  for the PCMH and the Nephrologist as a PCMH-N( Neighbor) This being an attempt to lay ground work for coordinated care of CKD patients by attempting to do the following : Better collaboration for consultation , information exchange and evidence based decision making , PCP’s to continue to manage CKD due to HTN and DM and nephrologists to adhere to diagnosis and management of specific Glomerular diseases , Nephrologists developing systems for PCP’s to ensure  early detection of CKD
GUIDELINES FOR JOB IN ACADEMIC NEPHROLOGY 

Have a plan at least for next five years; Negotiate Contract;Ask About promotion guidelines; Apply for Grants ( Sure shot way to secure dedicated research  time!);Have more than one Mentor;Don’t move too quickly into leadership roles; Don’t take up assignments that others will not !

Reported by ITI YADAV, MD

What Dialysis Modality you would want? Survey

As physicians and nurses, we take care of dialysis patients and we assume that this was their choice of dialysis.
What would you want if you were in need of dialysis? Does evidence matter to you? What modality gives better outcomes -- does it matter? or is it just lifestyle?
Take 2 minutes for this survey and let us know your thoughts
http://www.surveymonkey.com/s/R83LJPK

Monday, November 15, 2010

Presentations from the Prevention in Renal Disease conference by Ukidney.com

Check out a 2 page presentations on http://ukidney.com/prevention-in-renal-disease-meeting-2010
about the recent prevention in renal disease meeting in Toronto 2010.

Medicine for residents: urinalysis in rhabdomyolysis

Medicine for residents: urinalysis in rhabdomyolysis: "Urinalysis is an important part of the evaluation of any renal disorder.It is very simple, easy to perform and gives quick and valuable info..."

Saturday, November 13, 2010

CKD videos from The Visual MD

http://www.thevisualmd.com/health_centers/urological_health/chronic_kidney_disease

This is an interesting 15 videos on CKD using lifestyle changes and epigenetic ( way you think) change your body.

Friday, November 12, 2010

IN THE NEWS- DENSE DEPOSIT DISEASE AND MGUS?

The connection of Dense Deposit Disease and MGUS is unique and recently investigators explored this in a series of patients at the Mayo Clinic.
All 10 patients had a serum monoclonal spike of IgG k or lambda and then had a biopsy proven dense deposit disease.
A presumptive pathophysiology is mentioned: Perhaps the MGUS leads to activation of formation of Antibodies of Factor H or regulators of complement activators.  This can be compounded by H402 Allele of Factor H that is making it second hit for DDD.  This leads to dysregulated complement activation and a full blown C3 glomerulopathy and dense deposit disease.
Most of these 10 patients either had a low alternative pathway , autoantibody to factor H or heterozygosity to H402 allele of Factor H.  MGUS is associated with this phenomenon or just another bystander and nothing to do with DDD, is not clear.  4 of their 10 patients became ESRD, 2 are CKD and remaining are a recent diagnosis. So its unclear if this DDD is behaving like the classic DDD with quick progression to ESRD.

Interesting observation and something to keep in mind.
Image source: Imperial College, London, UK
References:

http://www.ncbi.nlm.nih.gov/pubmed/20832153
http://www.ncbi.nlm.nih.gov/pubmed/20185597
http://www.ncbi.nlm.nih.gov/pubmed/20852386

New Website

Check out this excellent blog on Fixing the current system of dialysis

http://www.fixdialysis.com/

Thursday, November 11, 2010

JOURNAL CLUB: FGF 23 and UREMIC parathyroid glands

Medicine for residents: Hyperkalemia with beta blockers!

Medicine for residents: Hyperkalemia with beta blockers!: "I recently had a Chronic kidney diesease patient on low dose Ramipril with a stable potassium level for many months, got admitted to the hos..."

CONSULT ROUNDS: Risk Factors of Contrast Induced Nephropathy

1. What are the risk factors for contrast nephropathy?
Some we came up with and I confirmed with literature are: Pre existing renal disease, CKD with DM, reduced intravascular volume are the three classic ones.
Other risk factors that people can consider as risk factors are: Load of contrast, presence of CHF, Use of IABP, age, anemia and being on nephrotoxic agents.
2. There have been developed few point systems based on Literature in the cardiology world and can give a better risk assessment of chance of having CIN.
Risk Factors:
Systolic blood pressure <80 mm Hg - 5 points
Intraarterial balloon pump - 5 points
Congestive heart failure (Class III-IV or history of pulmonary edema) - 5 points
Age >75 y - 4 points
Hematocrit level <39% for men and <35% for women - 3 points
Diabetes - 3 points
Contrast media volume - 1 point for each 100 mL
Renal insufficiency: Serum creatinine level >1.5 g/dL - 4 points
or GFR 40–60 mL/min/1.73 m2 -2 points
 20–40 mL/min/1.73 m2- 4 points
 < 20 mL/min/1.73 m2 - 6 points
And how does the scoring work:
5 or less point :Risk of CIN - 7.5% and Risk of Dialysis - 0.04%
6–10 points Risk of CIN - 14.0% and Risk of Dialysis - 0.12%
11–16 points Risk of CIN - 26.1% and Risk of Dialysis - 1.09%
>16 points Risk of CIN - 57.3% and Risk of Dialysis - 12.8%
Here is the website where you can calculate the risk

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