Friday, May 29, 2009
Primary hyperparathyroidism, as we are all aware, usually results from either a parathyroid gland adenoma or 4-gland parathyroid hyperplasia. The PTH level is either high or inappropriately normal, and as a result there is constant high urinary calcium reabsorption, constantly high Ca reabsorption from bone, and increased 1,25-OH vitamin D synthesis leading to increased Ca uptake in the gut. The urine calcium concentration is high; hence, the increased risk of nephrolithiasis in these patients. Also, the urine concentrating ability may be diminished in primary hyperparathyroidism.
In contrast, the defect in familial hypocalciuric hypercalcemia is genetic--an autosomal-dominant-inherited mutation in the calcium-sensing receptor gene. Despite hypercalcemia, PTH levels are normal to only mildly elevated. The urine calcium concentration is low (often measured as the urine calcium:creatinine ratio, which in FHH should be <0.01). The urine concentration ability is usually intact in FHH. It is important to make the distinction between primary hyperparathyroidism and FHH because parathyroidectomy surgery is usually highly effective in the former but not the latter.
Thursday, May 28, 2009
Tuesday, May 26, 2009
Monday, May 25, 2009
Sunday, May 24, 2009
The link is here.
Saturday, May 23, 2009
Why would these professional football players be taking bumetanide? Did they have refractory anasarca with a history of congestive heart failure? Of course not. Diuretics are frequently used as a masking agent for illicit anabolic steroid use, as they may dilute the urine enough to reduce the concentration of substances in the urine.
Actually, it's somewhat controversial as to why these players (not just the Williamses) actually took bumetanide, as no steroids were detected in these urine samples. The use of diuretics as a masking agent for steroids is less effective now that more sensitive techniques such as HPLC are used. And as this informative article on "The Steroid Report" blog points out, several non-FDA-approved dietary supplements marketed for weight loss have trace amounts of bumetanide in them.
One thing is for sure: with the Vikes' heading into the pre-season with two terrible choices for their starting QB (Tarvaris Jackson & Sage Rosenfels), Minnesota will need much more than a strong loop diuretic to compete this season...
Friday, May 22, 2009
Wednesday, May 20, 2009
The milk-alkali syndrome first rose to prominence when Bertram Sippy in 1915 developed a regimen for the treatment of peptic ulcer disease that involved drinking large volume of milk on an hourly basis along with "Sippy powders" that contained significant amounts of sodium bicarbonate. This provides really an ideal setup of a situation in which hypercalcemia, metabolic alkalosis, and acute renal failure can occur simultaneously, the hallmark of the milk-alkali syndrome.
It was not until 1936 that the toxicities associated with the Sippy protocol were tied to hypercalcemia by a Dr. Cope, who determined that in patients with milk-alkali syndrome the hypercalcemia and metabolic alkalosis could be relatively rapidly reversed by stopping calcium/base input and giving fluids. Although it is seldom used, the moniker "Cope's Syndrome" is occasionally used to refer to the acute- or subacute- forms of milk-alkali syndrome.
In 1949, Burnett et al described a chronic form of milk-alkali syndrome which involved the long-term toxicities of these metabolic derangements, including manifestations such as renal failure secondary to nephrocalcinosis and band keratopathy, in which calcium deposition on the cornea occurs. Fittingly the chronic form of milk-alkali syndrome is sometimes called "Burnett's Syndrome."
With the advent of H2-blockers to more effectively deal with peptic ulcer disease, the milk-alkali syndrome became quite rare for several decades as the general population's intake of popular antacids such as TUMS was greatly reduced. However, there has been a more recent increase in milk-alkali syndrome, particularly in women, with the increased attention to osteoporosis prophylaxis with calcium supplements. Several recent reviews cite milk-alkali syndrome as the third-most-common reason for hypercalcemia requiring hospitalization, after malignancy and primary hyperparathyroidism.
Tuesday, May 19, 2009
Monday, May 18, 2009
A recent article just published in Nature Genetics by Kottgen et al identifies several loci which appear to confer susceptibility to the development of CKD. How did researchers identify these genes? By a genome-wide association study. Briefly, researchers obtained genetic samples from some of the largest existing public health databases--such as the Framingham Heart Study, just to name one--and performed a genome-wide associated study in order to identify single-nucleotide polymorphisms (SNPs) that are associated with a low estimated GFR (using either creatinine or cystatin as the measurement of GFR). They identified significant SNP associations with low GFR in the genes UMOD, SHROOM3, GATM-SPATA5L1, CST, and STC1.
Saturday, May 16, 2009
Friday, May 15, 2009
Thursday, May 14, 2009
Wednesday, May 13, 2009
We all know that if you are stranded on a lifeboat in the middle of the ocean, you are not supposed to drink the salt water. Why is this the case--shouldn't the kidney be smart enough to retain the water and excrete the salt?
It turns out that the high osmolarity of seawater (usually >1000mosm/L) either approaches or exceeds the concentrating capacity of the kidney--and therefore you can't expect to retain any free water. In addition, seawater contains high concentration of magnesium and sulfate-containing minerals which can result in an osmotic diarrhea when large quantities are ingested; this can exacerbate free water loss which may likely already be high due to high insensible losses from wind and sun.
Some animals have impressive adaptive mechanisms to maintain homeostasis of osmolarity in a high salt environment;for instance, the albatross' nasal gland excretes a highly-concentrated salt solution, and the shark rectal gland has the same ability as detailed in another post.
Tuesday, May 12, 2009
Monday, May 11, 2009
Saturday, May 9, 2009
There are many potential reasons for ADPKD patients to get pain syndromes:
1. Cyst Growth: Obviously the growing cysts themselves can cause pain by compressing on other structures or stretching out the renal capsule.
2. Cyst hemorrhage: Hemorrhage into a cyst can also occur, causing acute pain. Sometimes this is associated with gross hematuria, though only if the cyst is in communication with the rest of the nephron.
3. UTI's/recurrent pyelonephritis: not surprisingly, this is more common in women than in men. Again, because not all cysts communicate with the urine, it’s possible that you can have a cyst infection even with a sterile urine. If there is an infection, it’s also important what antibiotic you chose, since not all antibiotics have good penetration into the cysts. Penicillins, for example, are not very good at penetrating cysts; fortunately, both quinolones or Bactrim are quite good at cyst penetration.
4. Nephrolithiasis: up to 25% of ADPKD patients have nephrolithiasis; the most common type of stone in ADPKD is uric acid stones.
5. Chronic back pain: enlarging cysts can cause increased abdominal girth, leading to increased lumbar lordosis.
6. Polycystic liver disease: the same process which causes cyst formation in nephrons commonly causes cyst formation in bile ductules, though this is usually asymptomatic. Occasionally, severe liver cyst growth can cause severe abdominal distension and pain.
Friday, May 8, 2009
But why are only 1% of nephrons involved? What's different about the affected nephrons compared to the unaffected ones? One current thought (though this remains controversial) is the "two-hit hypothesis." As described in this excellent 1996 Cell paper, researchers managed to isolate epithelial cells from individual cysts in ADPKD individuals. First, they demonstrated that individual cysts are monoclonal, and therefore derive from a single renal tubular epithelial cell. Then, they demonstrated that within the majority of each monoclonal population, there was loss of heterozygosity at the PKD1 locus. In other words, cysts arise from cells in which a "2nd hit" of the remaining good copy of PKD1 suffers a somatic mutation. This mechanism is much like how tumor suppressor genes (such as APC in colon cancer). The fact that the PKD1 gene is so large (46 exons) makes it especially susceptible to the possibility of mutation. Thus, although the disease is inherited in an autosomal dominant fashion, at a molecular level the cysts themselves are autosomal recessive. This "two-hit hypothesis" is one possible explanation as to why only a small fraction of nephrons ultimately form cysts.
Thursday, May 7, 2009
Wednesday, May 6, 2009
An interesting paper in this month's JASN by Hallan et al suggests an alternative staging system: instead of using only eGFR, the authors define a strategy whereby eGFR is combined with the degree of albuminuria to arrive at a new classification system. They arrived at this strategy by looking at over 65,000 adults from an older large-scale health screening study (HUNT2) and determining what factors best predicted the development of ESRD. The authors argue that their newer CKD staging system is much more efficient at identifying patients truly at risk for developing ESRD compared to the traditional KDOQI system.
- They calculate that referring all patients with CKD Stage 3 or above to a nephrologist would lead to working up 4.7% of the general population
- Which would identify 69% of all patients who progress to ESRD.
Tuesday, May 5, 2009
As we all know, erythropoietin is secreted predominantly by the kidney (85% from the kidney, 15% from the liver) in response to hypoxia and its function is to stimulate erythropoiesis in the bone marrow. What is the receptor on which erythropoietin works?
Monday, May 4, 2009
There is some suggestion that FMD has a genetic component to it, though no gene has yet been identified. The diagnosis is usually made by angiography showing a "beads on a string" pattern in the affected artery. FMD can affect arteries other than just the renal arteries (e.g. the carotid arteries), but the disease is most famous for its effect on the renal arteries where it may cause secondary hypertension due to activation of the renin-angiotensin system.