Friday, July 31, 2009
Thursday, July 30, 2009
Wednesday, July 29, 2009
According to this article, Rosenbaum was initially suspected to be dealing in human organ trafficking by a UC-Berkeley anthropologist. The actual sting operation involved an FBI agent posing as an individual seeking a kidney for a fictitious uncle who had been on dialysis for two years and was tired of waiting on the transplant list. During a series of meetings Rosenbaum described himself as a "matchmaker", asked for a total of $160,000 for the kidney, and implied that he had brokered many such deals in the past, even providing as references past individuals who had successfully used his kidney matchmaking service. Allegedly, he would obtain his kidneys from impoverished donors from Israel and Eastern Europe, often for a sum of only about $10,000. There are even tales of his threatening reluctant donors at gunpoint when they attempted to back out of a planned donation.
The story suggests that transplant programs may need to be more vigilant in their screening of potential donor/recipient pairs. It's been long suspected that "transplant tourism" takes place elsewhere. The discovery that it is being controlled from within the U.S. is even more chilling.
Tuesday, July 28, 2009
The article describes children with an autosomal recessive inherited condition termed "EAST Syndrome", which stands for epilepsy, ataxia, sensorineural deafness, and tubulopathy. Specifically, patients had evidence of renal salt wasting with low-normal blood pressure, resulting in activation of the renin-angiotensin system and a resultant hypokalemic metabolic alkalosis. Individuals also demonstrated significant hypomagnesemia and hypocalciuria. Genetic studies identified the cause of EAST Syndrome: mutations in the gene KCNJ10, a potassium channel which is expressed in all of the affected tissues (brain, inner ear, and kidney) in this disorder. They go on to demonstrate that mice made deficient for KCNJ10 show a similar salt wasting phenotype as in affected humans.
What does KCNJ10 do? The authors propose that this potassium channel sits at the basolateral membrane of tubular epithelial cells where it recycles potassium, which is necessary for maintaining the activity of the Na/K-ATPase. Although rare, EAST Syndrome helps provide greater molecular detail of how the kidney absorbs salt, and suggests that researchers look for polymorphisms in this gene which may explain some of the genetic predisposition towards hypertension and salt handling by the kidney.
Monday, July 27, 2009
Sunday, July 26, 2009
Saturday, July 25, 2009
Friday, July 24, 2009
CRT/DDKT: CRT = cadaveric renal transplant, which is starting to be replaced by DDKT (deceased donor kidney transplant)--I guess some people find using the term "cadaveric" too grisly.
ECD: expanded criteria donor: ECD kidneys are "suboptimal" kidneys defined as coming from a deceased donor more than 60 years of age, or more than 50 years of age with the following risk factors:
DCD: donor after cardiac death. These are kidneys donated from deceased individuals who have severe, irreversible brain damage but do not actually meet the criteria for brain death. Typically, the donor patient's family will agree to withdraw life support, the patient will experience cardiac arrest, and the donor kidneys are then harvested for use.
LURT: living unrelated renal transplant
SPK: simultaneous pancreas-kidney transplant
PAK: pancreas after kidney transplant
"Status 7": when a potential kidney transplant already on the waiting list is deemed temporarily unsuitable for transplant--e.g., if they have an active infection. Patients who are made "status 7" will still accrue time on the waiting list.
Thursday, July 23, 2009
Wednesday, July 22, 2009
Tuesday, July 21, 2009
Monday, July 20, 2009
The logic is as follows: The growth of cysts in PKD is thought to be driven by low intracellular calcium levels and elevated cAMP levels. The calcium sensing receptor (upon which cinacalcet acts) is activated by binding to serum ionized calcium, and results in a G-protein-mediated decrease in cAMP levels & increase in intracellular calcium concentration. The investigators therefore suggested that cinacalcet might be an effective way to reduce cyst growth in late PKD.
Sunday, July 19, 2009
Saturday, July 18, 2009
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.
Friday, July 17, 2009
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.
Thursday, July 16, 2009
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.
Tuesday, July 14, 2009
Monday, July 13, 2009
Thursday, July 9, 2009
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.
Wednesday, July 8, 2009
The molecular mechanism of rapamycin is already known: it inhibits a cell signaling pathway known as the mTOR pathway (mTor = "mammalian target of rapamycin"). In support of its usefulness in ADPKD, the epithelium lining cysts (arrow) shows intense staining with an antibody against phosphorylated (active) mTOR, while non-cystic tubules (depicted by the arrowhead) do not show mTOR activity, as shown in this 2006 PNAS paper by Shillingford et al.
We will obviously have to see how rapamycin does in clinical trials. One of the obvious caveats is that this is not a wholly benign medication as observed by many transplant nephrologists, and bear in mind that it would likely be a chronic medication taken to prevent the growth of cysts and resultant ESRD. In the meantime, an article in this month's Kidney International by Gattone et al successfully uses rapamycin to decrease cyst growth in a mouse model of nephronophthisis (the pcy mouse), providing further rationale for this approach.
Tuesday, July 7, 2009
Monday, July 6, 2009
The MRI above depicts a classic example of posterior reversible encephalopathy syndrome (PRES), sometimes also called reversible posterior leukoencephalopathy, an increasingly-recognized consequence of malignant hypertension. The whitish areas ("hyper-intense signal") in the bilateral occipital and parietal lobes represent edema in these regions. PRES has also been reported in other disorders such as eclampsia and lupus. The lesion is allegedly reversible if the hypertension is appropriately treated.
Sunday, July 5, 2009
Saturday, July 4, 2009
A 2006 cross-sectional study by Yoshino et al using an international WHO mortality database helps to get at this question by noting a close correlation between all-cause mortality rates and cardiovascular mortality in the general population and showed that this correlation is even stronger within dialysis patients. This, it appears that at least some of the reason that U.S. ESRD patients do poorly is because of the relatively high rate of cardiovascular disease in the general population here.
There remain, however, other variables between countries which could also potentially explain the difference in mortality. U.S. patients tend to spend less overall time on dialysis than in Japan, for instance, and the U.S. also performs poorly in terms of having a low percentage of patients who begin dialysis with catheters as opposed to AV fistulas. Dialysis units in the U.S. are often staffed by a high percentage of dialysis technicians who have less formal training than dialysis nurses, which are required in greater numbers in Europe. I have also suspected that in the U.S. we may tend to dialyze the very elderly or the very ill with greater frequency than in other countries, which would obviously tend to make our numbers look worse. Explaining the mortality discrepancy likely has a complex answer, but it makes sense to try and figure out what aspects of our dialysis care might be improved to help lessen the mortality difference.
Friday, July 3, 2009
Thursday, July 2, 2009
There has long been strong evidence in support of a circulating factor which causes podocyte injury and resultant nephrotic syndrome. Additional evidence from the neutral endopeptidase story further suggested that an autoantibody directed again some podocyte antigen might be the culprit. In this issue, the researchers demonstrate that in 70% of patients with idiopathic membranous nephropathy (but 0% of patients with secondary membranous nephropathy or other forms of proteinuric kidney disease such as FSGS or diabetic nephropathy) contain an autoantibody against the podocyte antigen phospholipase A2 receptor. Furthermore, the autoantibody's presence appears to correlate with disease activity, suggesting a possible pathogenic role.
The work has a number of implications. First, it suggests that membranous nephropathy is indeed a separate disease than FSGS and other distinct forms of nephrotic syndrome. The common final pathway for proteinuria is the same (podocyte injury), but the ways in which to get there is likely different. Second, it suggests that detection of serum antibodies against phospholipase A2 receptor may be a useful part of the diagnostic workup for nephrotic syndrome--perhaps even making biopsies unnecessary--and perhaps could be used to follow disease activity in response to various therapeutic maneuvers. That is, this test may well become the "ANCA" of membranous nephropathy.