Kidney Week 2013: Fluid, Electrolyte and Acid-Base: The Highlights
Kidney Week 2013: Fluid, Electrolyte and Acid-Base: The Highlights.
This kidney week I attended several sessions in the area of fluid, electrolytes and acid-base physiology and disorders. Here are the highlights:
1. Thursday, November, 10:30 am – 12:30 pm: Urinary Acidification: Mechanisms, Abnormalities and Therapies.
- Dr. Tom Dubose from Wake Forest University talked about the mechanisms of hypokalemia in distal renal tubular acidosis. He mentioned a recent paper in JCI. Inactivating mutations of ATP6V1B1 which encode the Β1 subunit of the proton pump have been described in familial distal RTA. ATP6V1B1 mutations disruption ENaC activity in the cortical collecting duct (CCD) apparently mediated by PGE2 since indomethacin blocks this effect. This ENaC inhibition promotes natriuresis and high tubular flow. ENaC inhibition in the collecting duct also blocks K+ secretion through ROMK. In contrast, Principal cells in the medullary collecting duct (MCD) have an increased ENaC expression. Increased ENaC activity in the MCD is expected to favor K+ secretion through ROMK. Also, high tubular flow activates BK potassium channels and K+ secretion, leading to renal K+ loss.
2. Friday, November 8, 12:45 pm – 1:45pm: Hyponatremia and the Brain
- Dr. David Mount from Brigham’s and Women Hospital/Harvard Medical School showed evidence that chronic hyponatremia is associated with low levels of glutamate in the brain. Glutamate is one of the osmolytes that is extruded from brain cells during adaptation to chronic hyponatremia. Glutamate is essential for neuronal function. Perhaps this glutamate depletion is responsible for gait disturbances and attention deficits encountered in patients with this disorder.
3. Friday, November 8, 4:30 pm – 6:30 pm: ASN/ASH Joint Session – Hypertension Management: “Indecision 2013”.
- Dr. Matthew Weir from University of Maryland reminded us that thiazides probably do not act as antihypertensive by causing volume contraction. This effect is usually transient. On the contrary, Thiazides have been shown to decrease blood pressure in NCC (-/-) knockout animals and in patients with Gitelman syndrome. The main antihypertensive mechanism is still unknown but vasodilation is postulated as a potential mechanism.
4. Saturday, November 9, 2:00 pm – 4:00pm: Rare Inherited Renal Disorders: From Small Numbers to Large Impact.
- Dr. Juliette Hadchouel from INSERM, France presented data in 2 new mutations in a kindred family with Familial Hyperkalemic Hypertension A.K.A. Gordon Syndrome. These mutations are located in Cullin3 and KLHL3. These proteins form an ubiquitin ligase complex that ubiquitinate WNK1 and WNK4.
- Dr. David Ellison from Oregon Health and Science University gave the Robert W. Schrier Endowed lecture about a new paradigm regarding the function of the thiazide-sensitive Na+-Cl- cotransporter (NCC). Patients with Gitelman syndrome are not typically volume depleted and don’t have significant natriuresis. He showed unpublished data from his laboratory, where in conditions of total body K+ depletion NCC was upregulated. NCC cells have a K+ channel in the basolateral membrane called KCNJ10 that might work as a K+ sensor. In situations of total body K+ depletion the difference between ECF and ICF K concentration causes hyperpolarization of the membrane sensed by this KCNJ10 channel which for unknown mechanisms causes NCC upregulation. The idea is that NCC upregulation will maximize Na+ reabsorption in the DCT and minimize Na+ delivery to the collecting duct which could further stimulate K+ wasting and in this way limits further K+ secretion.
5. Saturday, November 9, 4:30-6:30 pm: Hyponatremia and Consequences with and without CKD
- Dr. Juan Carlos Ayus from Renal Consultants of Houston performed an observational study in Argentina where he found that chronic hyponatremia doubles the risk of hip fractures among hospitalized patients. Chronic hyponatremia constitutes a major risk factor for hip fractures even more significant than steroid exposure.
Post written by Dr. Helbert Rondon, eAJKD Contributor.
Check out all of the eAJKD coverage of ASN’s Kidney Week 2013!
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