Tuesday, May 31, 2011

TOPIC DISCUSSION: The return of "Spironolactone"

The mineralocorticoid receptor antagonists have been forgetten the world of ACEI and ARBCS in past decade. Sometimes, when used for hypertension, have done wonders in many pateints and they come of significant number of drugs.  What is the role of aldosterone in CKD and can the antagnosits retard CKD?
Aldosterone has a potential role in progression of CKD via vasoconstriction, oxidative stress, inflammmation, alteration of filtration barrier and perhaps direct glomerulosclerosis based on some initialy proposed mechanisms.  There is some lab data in certain kidney diseases like diabetic nephropathy, cyclosporine nephrotoxicity, proteinuric nephropathies and esrd even that these antagonists might be of some benefit.

There is growing interest in studing combination of RAAS blockade agents and above agents but concern always is hyperkalemia and that has prevented large trials.  More careful studies need to be done and clinical trials to show effect of these old, cheap but powerful agents that might just work.


Match the drugs with the toxicity game!

Match the following 15 drugs with likely injuries noted below:

1. Cleistanthius Collinus
2. Conivaptan
4. Bevacizumab
5. Pamidronate
6. Inteferon alpha
7. Etanecept
8. Hydralazine
9. Star Fruit
10. Zolendronate
11. Sunitinib
12. Omeprezole
13. Melamine
14. Lopinavir
15. Oral Na Phosphate solution

Possible injuries( each drug can have multiple choices)
A. Collapsing FSGS
B. Interstitial Nephritis
D. Distal RTA
E. Diabetes Insipidus
F. Crystalopathy
G. Thrombotic Microangiopathy
H. Acute Tubular Necrosis
I. Oxalate Nephropathy
J. ANCA associted RPGN
K. Phosphate Nephropathy

Monday, May 30, 2011


Microfilariae associated kidney disease has been noted. What would one see on the kidney biopsy?

glomerulus revealing sheathed microfilariae in the capillary lumen micro
  3 (8%)
mesangioproliferative glomerular disease
  2 (5%)
membranoproliferative glomerular disease
  4 (11%)
membranous glomerular disease
  4 (11%)
granulomatous interstitial inflammation and eosinophils in the kidney
  9 (25%)
all of the above can be seen
  13 (37%)

Majority of you got this one right.  Two ways microfilariae can cause glomerular diseases: direct physical invasion and second is via an immune mediated process( would included any form of diseases but mainly MPGN, mesangioproliferative and membranous). AIN with granulomas has also been seen. As a result, all of the above are correct.

Friday, May 27, 2011

TOPIC DISCUSSION: Clinical Pearls for electrolytes!

On a recent reading on Sodium and Water physiology, I realized again and again the following points

1. The best way to identify change in Na balance is to examine the extracellular volume status but there are no good ways to do that clinically( orthostatics, axillary sweat, skin turgor, physical exam??). Perhaps the hemotocrit might be the best marker we have.
2. There are no NORMAL values in electrolyte diseases, there are only what is EXPECTED of the kidney to do or the organ to do for the stimuli.
3. Classic one: " The acute discovery of a chronic condition does not make it an acute disorder"- By ML Halperin
4. Hypernatremia and "no thirst" leads to not a pleasant diagnosis to make requiring a MRI of the brain.

Wednesday, May 25, 2011

TOPIC DISCUSSION: Origins of the 1.73m2 in the GFR formula?

Why is 1.73 m2? and not just m2? and not any other number? Where does this all come from?
Basically, the simple answer is "arbitary".  The 1.73 refers to the standardized body surface area(BSA) used to normalize for all variables for an average 70kg man. Interestingly, this one paper that I reference below taunts the idea of this in a very comical way and shows where this originally came from.  Apparently in 1928, on a basis of just 8 children and 7 adults, the authors found a constant value can be substituted and they said it was 1.73m2- which was the mean of the areas of men and women age 25 from prior medical and acturial tables. So this was based on actuarial data showing the BSA using Dubose formula and then subtracting 1 inch from height in shoes and 5 pounds from weight in clothes and different variables for children and women.  Basically,this was based on american clothing standards and weights in 1920s.
Nothing has changed in using that number in last 80+ years.  The authors of the paper referenced below show that compared to 1920s, current average male weight is 80kg and hence the BSA should be technically corrected by 1.92m2 and not 1.73m2. 
Even if they chose less obese European population, it came to 1.86m2.  Interesting, if we did that, there would be an immediate 9% increase in world GFR per the authors. In general, to get a BSA measurement in the over weight and obese population is a tough task and not easy to measure- for us making GFR a harder thing to measure then as well as almost all measurements of GFR including MDRD correct for BSA and use 1.73m2.

"Is it a time to change or is 1.73m2 going to live longer than all of us like it has been!!"

image source: wikipedia.com

Monday, May 23, 2011

Prolia or Xgeva, Denosumab and The Renal world!

Bisphosphonates are established treatment for metastatic bone disease in many cancers.  Recently the RANK ligand inhibitors had come into the picture for treatment of osteoporosis under the name of Prolia. Osteoclasts are activated in part by a signal made by osteoblasts called RANKL (receptor activator of NFkB ligand), which binds to its receptor on osteoclasts( see figure below). Denosumab(Prolia) is a monoclonal antibody against RANKL. It thus prevents activation of osteoclasts and the initiation of resorption. Denosumab is given every six month subcutaneously. A trial called the Freedom trial( listed below in references) enrolled over 7800 women between the ages of 60 and 90 with a T score on their dexa scan between -2.5 and -4.0, denosumab prevented the radiological evidence of vertebral fractures, as well as reduced the risk of hip fractures, non vertebral fractures. It also increased bone mineral density at the lumbar spine and hip.  The side effects were not many. No patients with ESRD were included, but there were a fair amount of CKD stage II, III and IV patients in the trial and in those subgroups, fractures were less as well in the Prolia arm. Following that, three recent randomized trials also showed denosumab under the trade name Xgeva showed non inferior to bisphosphonates in prostate cancer and breast cancer and metastatic cancer to bone and myeloma patients in terms of skeletal related events and preventing bone lesions. And perhaps even preventing hypercalcemia of malignancy???

The studies are interesting and apparently renal monitoring is not needed.  Compared to zoledronic acid(comparison agent), no renal monitoring is required for these agents.  It appears at closer look at the trials that the renal events were similar in both with no significant statistically. 
For us these trials might be important to follow as perhaps this agent might be something that might be used in the near future and we have to monitor for any renal side effects. Besides, it causes significant hypocalcemia in normocalcemic individuals as a common side effect. Hence, it might be an interesting agent to consider in treatment of malignancy associated hypercalcemia. A more recent trial in the US on using this agent that included few myeloma patients as well showed non inferiority to bisphosphonates. Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab.  Osteonecrosis of the jaw occurred at similarly low rates in both groups. Renal adverse events and elevations in serum creatinine were more in the bisphosphonates arm.

Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
Let’s keep a close watch for it. For now, it is expensive and can only be given as an outpatient basis in the oncology clinics.

Check out the references below:
Image sources: medscape.com, cancergrace.org,

Friday, May 20, 2011

Alemtuzumab for Induction- the 2011 update

A recent NEJM May 2011 article has one article that compares use of Alemtuzumab and early steroid removal to Basiliximab and Thymo.  Its a nicely done randomized controlled trial that is multi centered.
On face value:- appears that rate of biopsy confirmed acute rejection was lower in the alemtuzumab group in the low risk patients when compared to basiliximab and similar to thymo when compared in high risk groups.

Few points from the trial:
1. All were steroid sparing making things not standard around all programs
2. The infection events were statistically more higher in the Alemtuzumab group especially in the low risk population
3. WBC count was also <3000 in the treatment arm
4. Cancer, renal injury other complications were similar
5. Rate of late rejection (after 12 months) was higher in both low and high risk groups compared to standard treatment
6. If steroids were withdrawn, and infections were more in the alemtuzumab group, wonder what the rate of infection would have been with steroids!

Till further studies, looking ahead. Awaiting to see what the transplant community thinks


Wednesday, May 18, 2011

TOPIC DISCUSSION: Hibernating Bear's urine?


1.Mostly TG in adipose tissues are used to generate all ATP needed
2. Some urea is still generated and bear has to get rid of this urea- but not via urine and the bear cannot metabolize urea directly.
3. Urea enters the GI tract and bacteria secrete urease which splits to Nh4+ and HCO3-.  Bacteria then convert that ammonium to non essential and essential amino acids. And then they are re synthesized to bear's needs.
4. Small rate at which the bear catabolizes proteins is matched by the synthesis of new proteins via the bacteria in the GI tract.
For more details read:
Clinical Detective Stories- By Mitch Halperin, MD and below

Tuesday, May 17, 2011

CONSULT ROUNDS: Ethylene Glycol Toxicity

Role of Dialysis in Ethylene Glycol Toxicity
Key Points:
1.     Immediate dialysis should be done if the Anion Gap is significantly increased and there is evidence of acute renal injury
2.      Experts suggested HD in any patient with even suspected toxic alcohol ingestion with unexplained AG and osmolal gap.  Some say ph of 7.3, others ph of 7.1 to initiate dialysis
3.     If non acidemic or not in renal failure, perhaps HD can be put on hold and fomepizole can be tried. But HD can be used to clear the parent alcohol and shorten the course of the other therapies
4.     Long and good HD is needed.  Not real need to start slow. Sometimes two sessions in one day or daily HD might be needed. PD might not be that good for clearance.
5.     Continue HD till Osmolal gap closes or and ph normalizes or other renal parameters permit

Monday, May 16, 2011

Asian Dialysis Modality Survey by Pediatric Nephrology


It is important to understand the preference of the RRT modality
used by various physicians specially in Asia, as it would help to
focus our preventive strategies for the future.
All Asian physicians involved in the care of children with
renal disorders are welcome to fill up this survey.

Saturday, May 14, 2011

Medicine for residents: Elevated pulse pressure and white coat effect

Medicine for residents: Elevated pulse pressure and white coat effect: "Can we differentiate white coat effect from true hypertension in the office? Difficult(we usually need either a 24 hr ambulatory BP monitor..."

TOPIC DISCUSSION: Micro Rnas and Chronic Kidney Disease

CKD has been associated with IF/TA ( interstitial fibrosis and tubular atrophy) and progressive organ function loss. Micro RNAs or miRNAs are endogenous single stranded short RNA molecules that regulate 50% of the gene. So basically tell a gene to turn on or off or regulate the protein expression. miRNAs are deregulated in kidney diseases and in transplantation and perhaps might influence the kidney fibrosis and dysfunction.
Knowledge of these molecules could lead to good treatment options in the near future.

Some interesting points about miRNAs and kidney disease:
1. miRNAs were first mentioned as early as in 1990s, the first one was lin-4.
2. 851 miRNAs have been identified in humans
3. miRNAs in the pheontypic transition of the JG cells were studied in hypertension
4. many miRNAs have been noted in renal biopsy samples of HTN nephrosclerosis
5. miRNA patterns have been noted in transplant allograft rejection as well
6. mir192 is the prototype Diabetic nephropathy mRNA
7. Podocyte biology and especially IgA nephropathy have identified miRNAs as well.
8. miRNAs modulators might be future drug targets for certain renal and non renal diseases.


Friday, May 13, 2011

Nephrology Crosswords- Pediatric Nephrology

Check out the next installment of Crosswords in Kidney International

This time the topic is Pediatric Nephrology, genetic disorders.

Wednesday, May 11, 2011

Donor Risk Scores?

A recent review in Nature Nephrology discuses this important concept.  A large study out of Finland is discussed in this review and how the donor risk score was developed. What they describe is a donor allograft damage index which involves clinical components as well pathology components.
What constitutes the clinical components are: age >50, smoking, unstable blood pressure, HTN, need for CPR, alcohol abuse, untreated HTN, ischemic heart disease, arteriosclerosis, oliguria and the biopsy component is vascular intimal sclerosis, tubular atrophy, interstitial fibrosis, interstitial inflammation, mesangial matrix increase and glomerulosclerosis.  The Biopsies of the donors were graded with a 0-3 point system with each of the six histological criteria and the higher the points- the worse the kidney was.  The authors showed that the presence of >5 risk factors(clinical) and associated with an increase in mean allograft damage score from 0.5 to 1.4 and an increase in percent glomerulosclerosis from 1.5% to 8.1%.  And eventually higher donor risk scores were associated with long term graft outcomes over 5 years as well.
One of the few large studies to look at histological allograft data and comparing that to the clinical data.  Interesting to see what comes next.



Dendritic Cells(DC) are important players in transplant immunology. Which one of these syndromes is associated with loss of IL-12 producing myeloid dendritic cells?
IPEX syndrome 16%IRF8 syndrome 41%BCG syndrome 33%OPES syndrome 8%

Nice work but slightly tough question. Not many responders. No such syndromes as BCG and OPES( made it up).  IPEX syndrome is a T reg FOXP3 deficiency syndrome. Hence, the right answer is IRF8 syndrome.  A recent article in NEJM May 2011 talks about description of this syndrome in few cases.  Infants were evaluated and looked at genetic analysis.  Disseminated infection caused by BCG vaccines is the early manifestation of primary immunodeficiencies - such as SCID.  Two distinct disease causing mutations were noted.  Both effecting Interferon regulatory factor 8 or IRF8 and leading to the disorder.  IRF8 is critical for development of monocytes and dendritic cells and anti mycobacterial immunity.  This is an interesting finding.
As we discover more and more of such associations ( FOXP3 deficiency and T regs) and this one now- we can use this information for better understanding immunology and hence transplant medicine benefits. Dendritic cells are antigen presenting cells and knowing that IRF8 is crucial in their functioning, perhaps an inhibitory molecule to IRF8 might be a target for future drug development in transplantation.  Lets see where this new disease entity takes us: as everyone knows- its not that simple.

take a look:

Tuesday, May 10, 2011

"Brain Drain" in nephrology

A series of articles in ASN Kidney News and CJASN recently have highlighted the fact that Nephrology is having a brain drain and loss of interest in application to this field. As a results ASN has created a task force to create more people going into Nephrology.  To me - don't know why people choose what they choose but to all those undecided medical students out there and residents:- 
Renal Medicine is the BEST!! 
It has everything you want in it:

1. Excitement:- acute issues to combat like Hyperkalemia, acid base, HTN crisis and Acute Rejection and saving the graft.
2. Novelty:- Transplant Immunology is growing rapidly and new agents are coming to the surface to make the field more and more exciting. The fact that dialysis will soon be a device that can be carried around - future might be here. Organs being developed and created via stem cells- can't get better than that! 
3. Variety:- From Glomerular diseases that remain mysteries to all to the facets of dialysis. From acid base to hypertension management. From a simple Acute renal injury to a complex rapidly progressing vasculitis
4. Future:- Interventional Nephrology, Geriatric Nephrology, Onco-Nephrology and upcoming special fields one can master in this exciting field
5. Mind boggling:- Always makes you think! The "thinkers" as the other docs call us. Even "Dr.House MD" is marketed as a Nephrologist!!!  We make cool diagnosis all the time!!!
6. Empathy:- Dealing with ESRD and transplant, nephrologists are kind hearted and compassionate individuals.  

Medical students and residents:- go for the field of medicine, at least take a rotation and try it out. It will be worth your time. Give The kidney a chance! and it will make a difference in your education and career!

Take a look at recent article from CJASN 2011 May
Image source: Iheartguts.com

Monday, May 9, 2011

TOPIC DISCUSSION: The Distal Hypoperfusion Ischemic Syndrome-NKF 2011 recap

Hand ischemia: Often we encounter patients who complains of numbness and pain during dialysis in the ipsilateral side of the access; and often diagnose it as steal syndrome; well not entirley true all the time.(70-% of patient have a steal on angiograms without symptoms)

We should all do a detailed history and exam and then think of other common differential before we reach the steal syndrome diagnosis because the steal syndrome indicates a specific management such as ligation of the access.

What is a better term to use is DHIS; distal hypoperfusion ischemia syndrome. important differential diagnosis list below:
CTS, carpal tunnel syndrome; DA, destructive arthropathy; DHIS, distal hypoperfusion ischemic syndrome; IMN, ischemic monomelic neuropathy.

DHIS has multiple causes: Arterial stenosis, vascular steal, and distal arteriopathy as well as combinations of these three; so it is important to visulize the whole access with angiogram including the central vessels to diagnose an arterial stenosis which usally improves after angioplasty and does not need ligation. now important clues are cold extremities on exam and lack of distal pulse. high risk patients are DM, smokers.

The nephrologist should be very involved in the diagnosis phase as well as the management and our role should NOT be just a referral to the vascular suergon.

Friday, May 6, 2011

Nephrology Fellow Career Choice Satisfaction Survey

Dear Nephrology Fellows,

We are conducting the Nephrology Fellow Career Choice Satisfaction Survey.  We are conducting this survey to determine your satisfaction with nephrology as a career choice. This brief survey will take approximately 5-10 minutes. Your help is greatly appreciated. We will share the results of the survey with all of you. Thanks for your time and participation.

Hitesh H. Shah, MD
Prasanth Krish, MD 
Matthew Sparks, MD
Kenar D. Jhaveri, MD

Dual Live Transplants performed

Check out the latest on dual liver and kidney( live donor) combined transplants done recently.


Thursday, May 5, 2011

Interesting Urine Lytes

1. Oliguric/anuric individual
Urine lytes obtained after foley inserted:- Una 27, UK 24, UCl 27 and U Crt 9

2. Hyponatremic individual Na 107, conivaptan stated
Urine lytes obtained after 4 hours:- Una <10, UK<10 U Cl <10 and U Osm 150

Any thoughts? on what is going on?

Wednesday, May 4, 2011

NKF 2011 Live: First Clinical Guidelines on Acute Kidney Injury Issued

This is a summery of one of the talks at The NKF meeting ; MEdscape nephrology conducted an interview with Dr. Kellum who co-chaired the KDIGO initiative.

Go to the link above for the full interview: here are some points of the talk

RIFLE and AKIN should be used by frontline practitioners to diagnose AKI, and this should serve to increase awareness about the prevention, recognition, and management of acute kidney injury.

Up to 33% of ICU patients and as many as 20% of all hospitalized patients develop acute kidney injury. even mild injury, resulting in small changes in renal function acutely, can have significant short-term and long-term consequences.

Replacement fluid should be crystolloids and colloids(avoid albumin, hetastarch and alike).

CIN prophylaxis: Normal saline or bicarbonate are both of equally effective with no preference.

Citracate bath and US-guided catheter insertion were strongly recommended. this maybe controversial the committee admitted.

More in the full interview.

Ezra Hazzan MD

Tuesday, May 3, 2011


Which of the following regarding Anti GBM disease in elderly is true?

This entity is non existent in the age> 65   0%
Anti GBM disease in the elderly is more of a female predominance
Anti GBM disease in the elderly is more severe than in the younger patients
Anti GBM disease has more severe lung hemorrhage than younger patients
Anti GBM disease has a significantly higher proportion of positive ANCA results in this age group

Good work all. Majority got this one right. Recently in AJKD this topic was reviewed looking especially at cases in the elderly.  This entity does exist in the elderly and fairly common. It has more of a male predominance and it is actually LESS severe than when it happens in younger patients.  The lung disease is also LESS severe. The correct answer hence is the last one- it does occur a lot of time concurrently with a positive ANCA blood test in this age group. This group also has lower proteinuria at presentation and higher GFR on presentation. 


Monday, May 2, 2011

IN THE NEWS- Hyponatremia and Mortality( its the underlying cause that is more important)

Severe hyponatremia (<120 mEq/L) in hospitalized patients has a high mortality rate. This new study in CJASN 2011 issue online reviews this in a retrospective fashion. Medical records of 53 patients who died after developing Na <120 mEq/L before or after admission and of 32 patients who survived after developing Na <110 mEq/L were reviewed. Mortality rates tended to increase as the Na fell from 134 to 120 mEq/L.
Interestingly, Less than Na of 120 mEq/L, the trend reversed, such that the mortality rate progressively decreased as Na fell. More than two thirds of patients who died after Na <120mEq/L had at least two additional acute severe progressive illnesses, most commonly sepsis and multiorgan failure.  Most patients who survived with Na <110 mEq/L had medication-induced hyponatremia. The authors conclude that the nature of underlying illness rather than the severity of hyponatremia best explains mortality associated with hyponatremia. Neurologic complications from hyponatremia are uncommon among patients who die with hyponatremia.

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