GI Bleeding in ESRD Patients

While the GI & renal systems are not typically linked together, there are a few aspects to managing a GI Bleed in patients with CKD/ESRD which are somewhat unique.  

For instance, angiodysplasias in the stomach, duodenum and colon (pictured left) tend to occur at a much greater rate in ESRD patients than in the general population and should be included in the differential diagnosis.  Unfortunately, angiodysplasias are notoriously difficult to locate and/or treat.  Bowel ischemia, due to the increased risk of vascular disease in the ESRD population, is also a consideration.  

Uremic platelet dysfunction, particularly in underdialyzed patients or advanced CKD patients who have not yet started dialysis, can contribute to GI bleeding.  Strategies which can be used to improve uremic platelet dysfunction include the administration of ddAVP (given at 0.3 mcg/kg iv up to two times) or, if bleeding is expected to be more long-term, the administration of conjugated estrogens (5-30 mg iv or po daily x 5 days).

  

PPI's are safe in ESRD patients, but H2-blockers (e.g., ranitidine) need to be adjusted for level of renal function.  The drug sucralfate (carafate) should be avoided as it contains aluminum, and therefore if given for prolonged periods of time can accumulate in the CNS and lead to dementia.  Similarly, the use of bismuth (often used in anti-H. pylori therapy) should be minimized due to its accumulation in ESRD patients.  

Since many patients with ESRD are also on the transplant waiting list, it may also be prudent to transfuse these patients with leukocyte-poor pRBCs in order to minimize the risk of generating alloantibodies that might make finding a negative crossmatch that much more difficult.  

FENa False Positives/Negatives

This post is somewhat basic but it's always good to review, right?

The FENa is one of the most commonly used tools by both nephrologists and non-nephrologists to assess the etiology of oliguric renal failure in a patient.  Classically, a FENa less than 1% is consistent with pre-renal etiologies (and means that more than 99% of the Na filtered is being reabsorbed) while a FENa greater than 1% is consistent with acute tubular necrosis or other types of intrinsic renal failure. 

There are however some specific instances in which the FENa fails.  FENa "false positives" (e.g., the FENa is less than 1% but the patient actually has intrinstic renal failure) in the folllowing conditions.  Contrast nephropathy is notorious for causing a FENa less than 1% despite its not being classified as a true pre-renal etiology of renal failure.  Patients with CHF or cirrhosis/hepatorenal syndrome who develop ATN with clear evidence of granular casts may still retain a FENa less than 1%. Acute glomerulonephritis and rhabdomyolysis may also result in FENa's less than 1%. 

Conversely, FENa "false negatives" (e.g., the FENa is greater than 1% but the patient is actually pre-renal) frequently occur due to one very common cause:  diuretics.  In the face of active diuretic use, a FENa greater than 1% is therefore uninterpretable, and one popular alternative is to assess the fractional excretion of urea (FE-urea).  Since urea is reabsorbed less avidly than sodium, the cutoffs for what constitutes pre-renal and renal etiologies are different:  a FE-urea greater than 35% is consistent with intrinstic renal failure while a FE-urea less than 35% is consistent with pre-renal failure. 

On a previous post I noted the problems inherent in using the FENa is patients with significant chronic kidney disease.  

Genetics of Wilms Tumor

Wilms Tumor--named after the German surgeon/pathologist Max Wilms (pictured at left)--is an embryonal tumor that derives from developing kidney tissue. Wilms was the first to postulate that tumors may arise from precursor cells which arise during development, and indeed study of the molecular pathways active in these "nephroblastoma" shed light on normal kidney development.

There are several genes associated with patients with Wilms Tumor. Here are some of the main ones:

1. WT1 is a transcription factor and considered a tumor suppressor gene. Mutations in WT1 account for between 10-15% of sporadic Wilms tumor. It interacts with p53, a classic tumor suppressor involved in a wide variety of cancers. Denys-Drash Syndrome, a familial and severe form of Wilms tumor, is usually caused by congenital WT1 mutations.

2. beta-catenin is a key component of the canonical Wnt signaling pathway, long known to be a key player in kidney development. Interestingly, most patients with WT1 also have gain-of-function point mutations in the beta-catenin gene which result in increased stability of the beta-catenin protein and subsequent unregulated Wnt signaling.

3. WTX is mutated in a different subset of patients than those with WT1 mutations, and is found on the X-chromosome.

4. BDNF (brain-derived neurotrophic factor): mutations in this growth factor are postulated to result in the WAGR Syndrome--a constellation of symptoms that includes Wilms Tumor along with aniridia, GU abnormalities, and mental retardation.

5. BRCA2: interestingly, mutations in the well-known breast cancer-susceptibility gene can also lead to Wilms tumor.

Location of Culprit Lesion in Acute MI's in CKD Patients

The presence of chronic kidney disease (CKD) portends a much higher mortality in patients who suffer an acute myocardial infarction. There are several potential reasons as to why this might be the case--for instance, the treatment of resultant heart failure may be much more challenging in patients with advanced CKD--but another potential reason is that at the time of presentation their CAD is fundamentally more severe.

A relevant study by Charytan et al in a 2009 Kidney International edition speaks to this issue: they analyzed a cohort of patients who underwent acute myocardial infarction with either the presence or absence of Stage 3 CKD or worse, and examined where the culprit lesion was located with respect to the cardiac vascular anatomy. Interestingly, they found that patients with CKD are much more likely to have lesions which are more proximal than those without CKD. In general, more proximal lesions are generally more severe, as ischemia may occur to a larger region of the myocardium. These results highlight the current thinking that cardiovascular disease in CKD patients may be more aggressive and severe than in the general population, and may even operate by slightly different pathophysiologic mechanisms.

Doing My Part for Kidney Awareness

So it was my Dad's 65th birthday this past weekend, and the kids & grandkids all flew in to Indianapolis to help him celebrate. As my father is also a nephrologist, I wanted there to be a kidney theme to the festivities. As luck would have it, the Indiana branch of the National Kidney Foundation possesses a sweet, human-sized kidney mascot costume named "Billy the Kidney" (a play on the Western hero "Billy the Kid") which the folks at NKF were nice enough to lend. I donned the suit right during the traditional singing of Happy Birthday, and was quite popular for both the nephrologists and non-nephrologists in attendance. Billy the Kidney: rasing CKD awareness one birthday at a time. Happy Birthday, Dad.

The CKD-Epi Equation: An Improved MDRD?

Currently, the most widely-utilized method for routine estimation of GFR (eGFR) is the 4-variable MDRD Equation, in which serum creatinine, age, gender and race are the variables entered into a mathematical formula. eGFR as determined by the MDRD Equation also serves as the basis for CKD Staging. Despite the fact that MDRD appears to be relatively successful as estimating an accurate GFR for patients with CKD Stage 3 and above, there are some increasingly recognized limitations to its use. Most notably, the MDRD Equation is not as accurate for higher degrees of GFR (e.g., GFR > 60 cc/min), and overall tends to overestimate the prevelance of CKD stage 1 & 2 in the general population. In addition, the original MDRD cohort did not contain any patients with diabetic kidney disease or those > 70 years of age, both of which represent a sizeable (and growing) portion of today's CKD population.

To help deal with these limitations, researchers have developed a modified version of the MDRD called the CKD-EPI Equation, recently published by Levey et al in a 2009 issue of Annals of Internal Medicine. Briefly, researchers took a larger and more diverse patient population and measured their GFR using isothalamate clearance as a "gold standard." They then performed a series of statistical manipulations to generate a slightly different mathematical equation than the MDRD in order to arrive at an estimated GFR using the 4 standard values. In particular, they used a mathematical function termed a "spline-knot function" (way beyond my field of expertise) which apparently reduces bias at higher levels of kidney function. Perhaps this equation, with the appropriate follow-up tests & validations, could one day replace the MDRD Equation in routine clinical use, and be more useful at estimating kidney function in individuals with less severe disease.

The Power of Pee

Often, my ideas for blog postings come from reputable journals such as JASN, CJASN, AJKD, Kidney International, NEJM, etc...

But today's topic derives from my regular reading a website I simply can't recommend highly enough...Geekologie. From the July 8th posting, there comes a report that chemists from Ohio University led by Geraldine Botte have succeeded in harnessing the power of urine to drive a hydrogen fuel cell, as recently described in an issue of the Chemical Communications.

Briefly, the authors describe the development of a nickel-based electrode that is able to oxidize ammonia into both nitrogen gas and hydrogen gas, the latter of which could be used to power hydrogen cells. The ammonia is easily derived from urea, the major component of urine. The urine-powered hydrogen car? Don't lose hope.