Sunday, January 31, 2010
Saturday, January 30, 2010
This will all likely change in the coming months as the PPS nears finalization. A single lump-sum payment will be charged which will taken into account not only the dialysis procedure but also all medications and laboratories provided during the dialysis procedure. Proponents of the PPS would argue that the ESRD Program already soaks up a large chunk of the Medicare budget (5.8% of the overall budget, despite affecting less than 1% of Medicare beneficiaries), and the "bundling" strategy will encourage nephrologists to use tests and medications (particuarly EPO) more judiciously, resulting in lesser overall costs.
However, there are several controversies with the PPS alluded to in many of these editorials. For instance: in the new plan, all labs ordered during dialysis would be included in the bunding plan. For instance, patients who need to have their INR monitored frequently can have their bloods drawn during dialysis, a practice which is probably both humane and having practical sense from a standpoint of preserving the vasculature for future fistula use. However, many are concerned that dialysis units will be resistant to provide this service for patients, as they will no longer be reimbursed for drawing these labs. Some point out that decreased lab work provided during dialysis will also have a negative effect on completing kidney transplant evaluations in a timely manner. Still others are concerned that many ESRD-specific oral medications (e.g., phosphate binders, cinacalcet) will also fall into the bundled payment: for nephrologists who are responsible not only for the health of their patients but also the health of their dialysis unit, might this not put nephrologists in the unenviable position of having to "ration" expensive oral drugs only to the patients deemed to deserve them the most? Finally, there is also concern that only the largest dialysis corporations will be able to compete with the new regulations, leading to the closure of several smaller and non-profit dialysis centers.
The final PPS is apparently still being tinkered with, so we don't know the exact details quite yet. However in reading these editorials it is clear that there remains some trepidation about how the bundling will change the dialysis landscape.
Friday, January 29, 2010
What’s the evidence for using Rituximab in refractory Lupus Nephritis?
To date, there is published data from over 20 studies, comprising 300 patients, of cases of refractory lupus or lupus nephritis treated with rituximab, with reported response rates of around 75%. However, positive reporting bias is a real concern, and no randomized trials in renal disease exist.
She continues to have very active serology; what does this mean?
Autoantibody levels in lupus and vasculitis do not predict relapse very well in general. The published studies report that responders will typically demonstrate a fall in anti–double-stranded DNA antibodies, and a correction of complement depletion. So, they appear to have more of a role in predicting response to treatment
This patient has now been in remission for over 1 year. However, I’m concerned about the possibility of an impending relapse. Relapses are reported as occurring after an average of 10 to 13 months, although some patients maintain remission for several years. Also, her peripheral B cells (CD19+ or CD20+ lymphocytes) have recently recovered. Patients who fail to achieve depletion tend to have poor or no clinical response, whereas prolonged B cell depletion is associated with a prolonged clinical response. Protocol re-treatment at 4- or 6-mo intervals is under evaluation, so for now there is no good answer to this question.
Thursday, January 28, 2010
Wednesday, January 27, 2010
IgA nephropathy (IgAN) is an unpredictable beast, and identifying patients who will go on to develop progressive disease can be challenging. The classic predictors of progression, namely heavy proteinuria, CKD, glomerular sclerosis and tubulointerstitial fibrosis, are themselves just markers of advanced disease. There is a real need for better early histopathologic predictors of renal prognosis.
One promising prospect is glomerular density (GD), i.e. the number of nonsclerotic glomeruli per mm2, which was the focus of this recent study from Japan. The investigators performed a retrospective analysis of almost 100 IgAN cases with preserved renal function at the time of biopsy (average GFR 90 ml/min). Interestingly, they found that the GD varied hugely between patients, from 1 to 8 glomeruli per mm2. In multivariate analysis, only GD, and the presence of a cellular/fibrocellular crescent, were found to be significant predictors of progression. Patients with a low GD experienced more rapid decline in renal function, and this enhanced risk for progression was increased if a cellular/fibrocellular crescent was also present. Interestingly, the classic predictors of progression listed above did not predict prognosis, presumably due to the early stage of disease.
Of course, these findings will need to be replicated in other ethnic groups. Nonetheless, when a case of IgAN next appears at your biopsy conference, you should pipe up “what’s the GD?”. Just try not to look too smug when you do it.
Tuesday, January 26, 2010
Monday, January 25, 2010
Also included in the figure (not shown here) is the "revenue per treatment"--that is, how much profit each company obtains from the average patient's dialysis run. For example, Fresenius reported a revenue per treatment of $348 for the 3rd quarter of 2009. I'm not sure how they arrive at these numbers, but you can do a quick calculation to figure out how much a single patient dialyzing on the standard 3x/week schedule is worth to the company on a yearly basis: $348/treatment x 3 treatments/week x 52 weeks/year = $54,288.00/year. Like it or not, dialysis is also a business.
Saturday, January 23, 2010
The logo replaces the traditional ASN logo, which is fairly simple:
You can learn more about the new ASN logo on the ASN homepage (just click on Mr. Kidney), but briefly the new logo is intended to go along with the ASN's new tagline, "Leading the Fight Against Kidney Disease," and is supposed to place greater emphasis on ASN's leading role in patient care and important kidney-relevant policies.
Friday, January 22, 2010
A variety of mechanisms of injury have been reported, though most attention has focused on the ability of interferon therapy to cause proteinuria and nephrotic syndrome. This has been noted most commonly with interferon-alpha therapy, though in many of the patients with hepatitis B or C it may be difficult to be certain whether or not the development of nephrotic syndrome comes from the interferon therapy or a direct hepatitis-mediated renal injury such as MPGN. There have also been some recent case reports suggesting that interferon-beta can also cause a minimal change nephrotic syndrome in patients treated for multiple sclerosis and malignant melanoma.
Other mechanisms of renal injury reported with interferon use include acute tubular necrosis, acute interstitial nephritis, and even hemolytic-uremic syndrome. Occasionally, tubuloreticular structures as seen on electron microscopy of a kidney biopsy can be a clue as to the diagnosis of interferon-induced renal injury; these may also be seen in HIV-associated nephropathy.
Thursday, January 21, 2010
Wednesday, January 20, 2010
Bortezomib is a proteosome inhibitor used primarily in the treatment of relapsed myeloma. However, it is increasingly being used in the management of myeloma cast nephropathy (MCN).
Bortezomib binds to, and inhibits the function of, the 26S proteosome in plasma cells. This proteosome ordinarily performs a housekeeping function, degrading ubiquitinylated proteins, and hence clearing the cell of abnormal or misfolded proteins. Inhibition prevents degradation of pro-apoptotic factors and results in programmed cell death. The secretory nature of myeloma cells makes them particularly susceptible to agents which interfere with the ubiquitin pathway. Bortezomib has additional effects on other intracellular signaling systems, such as the NF Kappa B pathway, which may attenuate proximal tubular damage from nephrotoxic monoclonal light chains.
There are now several small case series suggesting bortezomib is efficacious in MCN. One of these reports on 20 patients with relapsed MM and creatinine > 2mg/dL. Renal failure was reversed in 40% in under 3 weeks. Additionally, 50% of patients had a 50% improvement in serum creatinine over the course of one month. Toxicity did not appear to be increased.
Bortezomib is given intravenously and does not require dose reduction in renal impairment. For these reasons, bortezomib is likely to have a particularly important role in the future management of patients with monoclonal Ig-mediated kidney disease.
(Image taken from NEJM June 26 2003 Volume 348; 2597-2598)
Tuesday, January 19, 2010
Although thyrotoxicosis is a predisposing factor to this disease, there was also a clue that genetics was involved: Latin American and Asian populations appeared especially susceptible to TPP. The investigators identified a novel inward-rectifying potassium channel, Kir2.6 (interestingly, a gene which had escaped detection in all versions of the human genome thus far!), and sequenced this gene in affected individuals. In 33% of the unrelated patients in their sample, they identified mutations in Kir2.6 which appear to alter the function of this potassium channel and lead to an altered skeletal muscle excitability. Interestingly, the transcription of Kir2.6 was found to be altered by thyroid hormone, providing an explanation as to why the disease manifests itself most commonly during episodes of thyrotoxicosis.
Monday, January 18, 2010
This is a complex issue, and one which will doubtlessly need to be addressed in a more comprehensive manner in the future.
Friday, January 15, 2010
The situation is even more confusing when you realize that patients with ESRD have an exceptionally high rate of coronary artery disease. This study by Ohtake et al performed screening cardiac caths on 30 patients with ESRD--and found that a full 53% of the sample had "angiographically significant CAD", including an even greater percentage (83%) in the subset of patients with ESRD and diabetes! Although it is controversial whether all of these patients would benefit from revascularization therapy, it makes the case that performing a "screening test" (such as ECHO or stress tests) is ESRD is not really worthwhile--you should just go ahead and cath everybody.
That being said, the more common approach to a cardiac workup in a patient being evaluated for kidney transplant is to use such a screening test. The two most popular are probably dobutamine stress echocardiography (which according to this recent AJKD review by Lentine et al has sensititives and specificities ranging from 37% - 95% and 71% - 95%, respectively) and myocardial perfusion studies (sensititives and specificities from 37% - 90% and 40% - 90%, respectively). As you can tell from the wide range of values reported above, the positive and negative predictive values of these tests are worse in the ESRD population than in the general population, making interpretation somewhat tricky. Electron beam CT scan, which determines a "calcium score" within coronary arteries to provide a risk assessment for CAD, has not been rigorously evaluated in the ESRD population.
The KDOQI Guidelines state that dialysis patients on the kidney transplant waiting list should undergo annual performance of non-invasive stress tests, such as those above, if they are considered "high risk"--which they define as having diabetes, known CAD, or having more than 2 traditional risk factors.
Thursday, January 14, 2010
New poll starts tonight.
Wednesday, January 13, 2010
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the gradual enlargement of multiple fluid filled cysts in both kidneys, which compress and destroy normal adjacent nephrons, typically resulting in ESRD by the fifth decade of life. Management has traditionally been limited to the treatment of the complications of hypertension and renal failure; however, several promising new therapies are on the horizon, such as nonpeptide vasopressin 2 receptor antagonists, inhibitors of the receptors for EGF and vascular endothelial growth factor (VEGF), and inhibitors of cmyc expression. All of which have been shown to inhibit disease progression in experimental models of PKD.
The mTOR inhibitor Sirolimus (Rapamycin) is another promising potential therapy, having also been shown to slow cyst development in rat models. Interestingly, it also slows the increase in size of native polycystic kidneys in human renal transplant recipients. It is currently the subject of three clinical trails underway in the US and Europe. Mechanistically, the cytoplasmic tail of wild-type Polycystin 1 normally interacts with, and inhibits, mTOR; loss of function of Polycystin 1, as seen in ADPKD, results in marked activation of mTOR within the epithelial cells of renal cysts. Sirolimus is believed to exert its effect via this mechanism. As mutations in PKD1, which encodes PC1, account for 85% of cases of ADPKD, Sirolimus has the potential to ameriorate the condition of the vast majority of APCKD patients.
Tuesday, January 12, 2010
Monday, January 11, 2010
In patients without CKD or ESRD, either carotid endarterectomy or carotid stenting are commonly used strategies; however, many surgeons are reluctant to advise such procedures in patients with kidney problems. For one, definitive diagnosis often relies on imaging that involves injection of either iv contrast dye or gadolinium, which have well-documented complications in patients with CKD. Furthermore, patients with CKD/ESRD are more likely to suffer surgical complications than those without.
Interestingly, however, a new paper in this month's JASN by Mathew et al (with an accompanying editorial) describes a subgroup analysis of CKD patients within the North American Symptomatic Carotid Endarterectomy Trial (NASCET), a large randomized trial of carotid endarterectomy versus medical management in which creatinine levels were routinely available. They found that individuals with a GFR less than 30 ml/min and symptomatic high-grade carotid stenosis (defined as greater than or equal to 70% stenosis) who do NOT undergo carotid stenosis have exceedingly poor outcomes. Although the study requires the usual caveats associated with subgroup analysis such as the presence of unforeseen confounders, these data will likely provide a stimulus to consider carotid endarterectomy more routinely in individuals with kidney disease.
Sunday, January 10, 2010
Patients diagnosed with a hydrothorax should be advised to temporarily cease PD. If necessary, patients can be transiently converted to hemodialysis while waiting for resolution of the hydrothorax. A trial of re-introducing low pressure PD (e.g. small volume) can then be attempted. If this strategy fails, switching to hemodialysis is a viable option. Video-assisted talc pleurodesis or operative repair are other alternatives available to patients who wish to continue PD.
Saturday, January 9, 2010
1. PTHrP (PTH-related peptide): this is the most common cause of hypercalcemia of malignancy, and is sometimes referred to as "humoral hypercalcemia of malignancy." The PTHrP essentially mimics the effects of PTH by virtue of its interaction with the PTH receptor, though since PTHrP is not detected by standard PTH assays the measured PTH level is typically very low. Sending a PTHrP level may be helpful, though in my experience it often takes several days to come back. PTHrP is most commonly secreted by solid tumors, such as breast cancer.
2. osteolytic metastases: this is the 2nd most common mechanism of hypercalcemia of malignancy, and is due to osteoclast-mediated bone breakdown. It occurs in characteristic tumor types, which can be recalled by this nifty mnemonic, "BLT with a Kosher Pickle, Mustard & Mayo":
B = breast cancer
L = lymphoma, lung cancer
T = thyroid cancer
K = kidney cancer
P = prostate cancer
M & M = multiple myeloma
3. tumor production of calcitrol: the mechanism is here is similar to that of granulomatous disease: tumor cells provide enzymatic synthesis of 1,25 OH-vitamin D, the active form of vitamin D, leading to unregulated GI uptake of calcium. It is most commonly seen in Hodgkin's lymphoma and some cases of NHL as well. It can be diagnosed by finding an elevated 1,25 OH vitamin D level in the presence of malignancy.
Very, very rarely one can observe ectopic PTH secretion as a mechanism for hypercalcemia of malignancy.
Thursday, January 7, 2010
Check out the new poll question in the right margin.
Wednesday, January 6, 2010
Tuesday, January 5, 2010
Monday, January 4, 2010
Originally described by Duncan and Dixon in 1960, FJHN is an autosomal dominant disease characterized by hyperuricemia, gout, and progressive renal failure. It was only recently discovered that FJHN was caused by mutations in the UMOD gene encoding the protein uromodulin, an 85 kDa glycoprotein involved in renal stone formation, the modulation of immune responses, and urothelial cytoprotection. These mutations lead to reduced renal excretion of urate. In vitro animal models of the disease suggest that the mutant forms of uromodulin cause the protein to be retained in endoplasmic reticulum, which inhibits normal trafficking to and expression at the cell surface. Patients often present in early adulthood with hyperuricemia or gout and normal blood pressure. The fractional excretion of urate is generally low. Renal dysfunction in these patients develops between ages 15-40 and is progressive, usually leading to ESRD in 10-20 years. On biopsy, patients are found to have chronic interstitial nephritis as well as thickening and splitting of the tubular basement membrane.
The optimal treatment strategy for FJHN is not clear at this time. Treatment with allopurinol to prevent gout has been recommended, though it remains uncertain as to whether or not allopurinol offers any significant benefit to preventing progression of renal disease.
Saturday, January 2, 2010
1. What kind of PD does the patient use: for the most part, we distinguish between CAPD (continuous ambulatory peritoneal dialysis, in which the individual manually performs fluid exchanges, often several times throughout the course of a day) versus CCPD (continuous cycling peritoneal dialysis, in which a PD "cycler" machine is used to perform automated exchanges, usually at night), though often components of both are part of the prescription.
2. How much fluid volume per bag? Usually either 2 Liter or 2.5 Liter bags are used.
3. What percentage of dextrose solution is used? I've included in a previous post the common color-coding scheme PD patients use to specify which solution they use; this is often invaluable because patients often know only what color bag they use, not the numerical value of how much dextrose is in their PD fluid. The higher the % of dextrose, the greater the amount of UF is generally achieved.
4. How many exchanges per day? For CAPD, this may be as simple as saying that a patient gets 4 exchanges a day. However, the answer may be more complicated for patients who use a cycler.
For example: a typical CAPD script might look like this: 2 Liters x 2.5% x 4 exchanges per day.
Another common dilemma encountered by renal fellows is what to do with CCPD patients who are admitted to the hospital, since cyclers are rarely available for inpatient use and patients do not always bring their own into the hospital. Generally, cycler regimens can be converted to CAPD regimens by calculating their total daily infusion volume and then dividing this by 4 exchanges per day.
Other details of the PD prescription worth mentioning: often one needs to distinguish between "low calcium" and "regular calcium" dialysates; some patients will regularly use heparin with each fill; and icodextrin is being increasingly used for individuals who fall into the "high transporter" category of PD patients.
Any questions? Your best bet is usually just to call the PD nurse on call--in my experience, they tend to know their individual patients extremely well, and can troubleshoot most technical issues relatively rapidly.
Friday, January 1, 2010
A free article on the Development of the Modern Cystoscope via Medscape can be found here. The French instrument described above was not the first attempt at endoscopy, but was apparently one of the earliest. It is described as a "long metal channel through which a mirror reflected light from a petroleum-fueled lamp," and could be used to demonstrate the presence of gallstones and kidney stones in some situations. However, one of its major limitations was that the metal heated up pretty quickly and caused significant patient discomfort. I can't imagine being one of the first patient subjects trying out the new, experimental cystoscope...