Re: JC at NIH - What's New?

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My understanding of what is said here is limited. Maybe Dr grim can give his inpot in this. Ibelive it is the full text of your abstract. As posted at this link http://content.karger.com/produktedb/produkte.asp?DOI=000337479 & typ=pdf

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In-Depth Topic Review

Am J Nephrol 2012;35:379–386

DOI: 10.1159/000337479

Advances in WNK Signaling of

Salt and Potassium Metabolism:

Clinical Implications

Pablo Arroyo a, b Gerardo Gamba a, b

a Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador

Zubirán, and b Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma

de México, Mexico City , Mexico

The balance of Na + and K + involve the intracellular

and extracellular distribution of these ions. The Na + /K +

ATPase distributes these ions such that Na + is the most

abundant extraceullar ion and K + is the most abundant

intracellular ion. Variations in Na + and water affect volume

status. Low sodium intake activates volume retention

mechanisms necessary to maintain extracellular volume,

while the excess of salt and water in physiological

conditions is excreted by pressure natriuresis, or in pathological

situations results in the formation of edema. In

contrast, distribution of K + is in direct relation to dietary

intake, intracellular handling, and urinary flow rate. Dietary

intake is generally not a cause of alterations in plasma

K + . Occasionally, altered handling of K + by cells (e.g.

rhabdomyolysis) can lead to hyperkalemia and the development

of cardiac arrhythmias and death. Urinary flow

rate, however, is the major determinant of the kidney's

ability to successfully excrete K + , in such a way that high

urinary flow rate favors K + excretion, while low urinary

flow leads to K + retention. How the recently discovered

With No Lysine (K) kinases (WNKs) are involved in the

regulation of the ion transport systems in the distal nephron

has become an area of intense research in the past

years [for extensive reviews, see 1, 2 ].

Key Words

Angiotensin II Electrolytes Hypertension Potassium

Sodium

Abstract

Recent evidence due to the discovery of a family of kinases

implicated in arterial hypertension now points to the underlying

molecular mechanisms that dictate Na + , K + and water

handling in the nephron. These new key players need to be

understood in order to fully comprehend the pathophysiology,

manifestations, and treatment of common clinical entities

such as hypovolemic shock, congestive heart failure, primary

hyperaldosteronism, nephrotic syndrome and hypertension.

It is through the analysis of the volume status and

electrolyte abnormalities that commonly present with these

diseases that we can begin to create a link between the abstract

concept of a kinase regulation and how a patient will

respond to a particular treatment. This review is an attempt

to bridge that gap.

Copyright © 2012 S. Karger AG, Basel

Received: January 19, 2012

Accepted: February 22, 2012

Published online: April 13, 2012

Nephrology American Journal of

Gerardo Gamba

Vasco de Quiroga No. 15

Tlalpan, Mexico City 14000 (Mexico)

Tel. +52 55 5513 38 68

E-Mail gamba @ biomedicas.unam.mx

© 2012 S. Karger AG, Basel

0250–8095/12/0354–0379$38.00/0

Accessible online at:

www.karger.com/ajn

380 Am J Nephrol 2012;35:379–386 Arroyo /Gamba

The WNKs are a group of serine/threonine kinases

which have been associated with the development of hypertension

in humans [3] . Intronic deletions of the WNK1

gene leading to over expression of an otherwise normal

WNK1, or missense mutations of the WNK4 gene in a

highly conserved acidic region, are the cause of an inherited

form of salt sensitive hypertension known as pseudohypoaldosteronism

type II (PHA II; also known as familial

hyperkalemic hypertension or Gordon syndrome) [3] .

This is a rare autosomal dominant disease featuring arterial

hypertension, hyperkalemia, and metabolic acidosis

[4, 5] . The PHA II clinical picture is the exact mirror image

of Gitelman's disease, an autosomal-recessive syndrome

featuring hypokalemic metabolic alkalosis with

arterial hypotension, that is due to inactivating mutations

of the renal thiazide-sensitive Na-Cl cotransporter (NCC)

[6, 7] located in the distal convoluted tubule (DCT) [8–

10] . The fact that these syndromes mirror each other and

the clinical observation that PHA II can be corrected by

low doses of thiazides [4] , led to the proposal that the

modulation of NCC by the WNKs could be underlying

the pathophysiology of PHA II [11] . Observations from

the past few years proved this hypothesis and revealed an

important role for WNKs that not only helps explain

PHA II, but also helps clarify the molecular nature of salt

and/or potassium handling in physiological circumstances

and in common clinical syndromes such as congestive

heart failure, hypovolemia, primary hyperaldosteronism

and hyperkalemia.

The mineralocorticoid hormone aldosterone has been

considered for many years a key player in the modulation

of Na + and K + transport systems in the distal nephron.

Owing to the discovery of WNK kinases, the exact mechanism

through which the kidneys are able to carry out

different responses to hyperkalemia or hypovolemia,

conditions in which aldosterone is elevated, has only recently

begun to be elucidated. Aldosterone is secreted

when salt needs to be retained (low salt diet/hypovolemia)

or when potassium has to be excreted (high potassium

diet/hyperkalemia). During volume depletion, the

reabsorption of salt is increased, but potassium secretion

remains unchanged, allowing for salt retention, without

potassium loss. In contrast, during hyperkalemia, potassium

secretion is favored in the distal nephron, without

greatly modifying the salt reabsorption rate. Thus, potassium

is excreted without retaining salt. How the kidneys

are able to carry out two distinct physiological responses

in two different situations (hypovolemia vs. hyperkalemia)

in which aldosterone is increased is known as the

aldosterone paradox [12] . How does the kidney recognize

the difference between these two states? As we discuss

below, it seems likely that what explains how the kidney

responds to these two states is the presence or absence of

angiotensin II (Ang II), which is elevated in hypovolemia,

but not in hyperkalemia, and its regulatory effects on ion

transport pathways via WNK4 in the distal nephron.

The distal nephron is defined as the portion of the tubule

that is located beyond the macula densa [13] . Changes

in salt transport rate in the distal nephron can no longer

be compensated by the tubuloglomerular feedback

mechanism and thus, have a major effect on salt excretion

in the urine. The distal nephron is composed of the DCT,

the connecting tubule (CNT) and the collecting duct

(CD). The CD receives the fluid from several DCT/CNT

segments. Thus, there are many more DCT/CNTs than

CDs in the kidney. The DCT can be subdivided into early

(DCT1) and late (DCT2) portions based on protein expression

and histological differences [13–15] . Sodium

transport pathways in the distal nephron include NCC,

which is the target of thiazide-type diuretics, exclusively

expressed in the DCT [14, 16] , and the epithelial sodium

channel (ENaC), the target of amiloride, which is expressed

in DCT2 and along the CNT and CD [14, 15, 17] .

The K + transport pathways include the renal outer medullary

potassium channels, ROMK, and the flow-dependent

large Ca 2+ -activated potassium channels (BK channels),

both of which are expressed throughout the distal

nephron [18–20] . WNK1 and WNK4 span the entire distal

nephron. There is, however, a short, kidney specific

isoform of WNK1 (KS-WNK1), which lacks the kinase

domain, that is strategically expressed only in the DCT

(see below) [3, 14, 21, 22] . Additionally, another group of

serine/threonine kinases known as the STE20-related

proline-alanine-rich kinase SPAK and oxidative stress element

1, OSR1 have been shown to lie downstream of

WNKs [23, 24] . SPAK and OSR1 are present in the thick

ascending limb of Henle and also in the DCT [25] and

activation of SPAK/OSR1 by WNKs modulates the interaction/

phosphorylation of these kinases with target

transporters.

Owing to these expression patterns, there is a clear and

understandable relationship between sodium reabsorption

and potassium secretion in the distal nephron. Beyond

the DCT, in the CNT/CD, potassium secretion is

favored by increased flow and sodium reabsorption

( fig. 1 ). This is because the entrance of Na + through ENaC,

generates a lumen negative voltage that favors K + secretion

through ROMK [19] . Thus, in order to increase potassium

secretion, the delivery of sodium to CNT/CD

must be increased. This is achieved by inhibiting the upWNKs

Signaling and Salt Metabolism Am J Nephrol 2012;35:379–386 381

stream salt reabsorption transporter NCC in the early

DCT [26] . Additionally, increased fluid delivery to CNT/

CD will also activate BK channels [27] . It is for these reasons

that increased salt and volume delivery to CNT/CD

by loop or thiazide diuretics (K + wasting) increase urinary

potassium excretion, while the K + -sparing diuretics,

such as amiloride that block ENaC, indirectly prevent K +

secretion [6, 28, 29] . This interrelation of sodium and potassium

handling of the distal nephron also explains the

beneficial effect of the Dietary Approaches to Stop Hypertension

(DASH) trial [30, 31] in which the best combination

to prevent or improve hypertension is the low salt/

high potassium diet, because in order to excrete the potassium

excess, salt reabsorption in the DCT must be reduced,

thus increasing the renal salt excretion [32] . This

exact phenomenon was observed by Palmer's group while

studying in rats the effects of low Na + diet with normal

K + versus a low Na + diet with low K + . In the low K + group,

NCC protein expression increased dramatically, thus decreasing

the distal delivery of salt and Na + and inhibiting

K + secretion [33] .

During normovolemia WNK4 purportedly behaves as

an inhibitor of NCC, ENaC, and ROMK [11, 34, 35] . PHA

II mutations alter the way in which WNK4 regulates

these transport systems. NCC and ENaC are no longer

inhibited, and thus, presumably activated, while the inhibition

of ROMK is further increased by mutant WNK4

[11, 34–36] . This increases salt reabsorption while minimizing

K + secretion, which explains the hypertension

and hyperkalemia that characterize the PHA II phenoa

b

Fig. 1. a During hypovolemia, the increase in Ang II modifies

WNK4 activity so that it stimulates NCC and ENaC, while inhibiting

ROMK. The stimulation of NCC in DCT1 significantly reduces

urinary flow along the distal portions of the nephron, thus

minimizing K + secretion. b During hyperkalemia, however, the

presence of aldosterone in the absence of Ang II leads to an inhibited

NCC in the aldosterone insensitive DCT1, and an increase in

ENaC and ROMK from the aldosterone sensitive DCT2 and onward.

The decreased salt reabsorption in DCT1 increases urinary

flow to CNT/CD favoring K + excretion.

Color version available online

382 Am J Nephrol 2012;35:379–386 Arroyo /Gamba

type. This is the extreme, pathophysiological version of

what a regulated response to low blood volume should

entail. In other words, WNK4 harboring PHA II mutations

mimics the neuro-hormonal state required to retain

volume in the face of intravascular volume depletion, in

which the desired response is to retain salt and volume,

without losing K + . Recent evidence supports that Ang II

is an activator of NCC [37–39] and the observation that

Ang II switches WNK4's behavior from an inhibitor to an

activator of NCC [40] , and further enhances the inhibition

of ROMK by WNK4 [41] suggests that PHAII mutations

in WNK4 are of the `gain of function' type, mimicking

the effect that Ang II has on NCC and ROMK. Thus,

according to this model, PHAII with mutations in WNK4

could be viewed as the consequence of a state of `hyperangiotensinism'

localized to the distal nephron, not because

Ang II is elevated, but because the DCT/CNT performs

as if Ang II was permanently elevated.

In PHA II patients, due to overexpression of WNK1,

the explanation of NCC activation and ROMK inhibition

is the following: First, WNK1 directly inhibits ROMK

[42–46] . Therefore, any increase in the expression of

WNK1 leads to a dose dependent decrease in ROMK. Additionally,

WNK1 is an inhibitor of WNK4, but this effect

is in turn prevented by KS-WNK1, the short isoform

which lacks the kinase domain and is expressed only in

DCT ( fig. 2 ). Under physiological conditions KS-WNK1

blunts the WNK1 effect on WNK4 and thus NCC is freely

inhibited by WNK4 [47, 48] . However, in PHA II patients,

the augmented expression of WNK1 increases the

ratio of WNK1/KS-WNK1 overcoming the inhibitory effect

of KS-WNK1, allowing thus WNK1 to inhibit WNK4,

leading to a WNK1-induced activation of NCC ( fig. 2 ).

Thus, hypertension in WNK1 PHAII patients seems to

be also the consequence of increased activity of NCC in

the DCT, similar to what happens in WNK4 PHA II patients

and during hypovolemia.

Another member of the WNK kinase family that by

itself can also mimic this neuro-hormonal state of salt

retention without potassium excretion is WNK3. This kinase,

which is expressed in DCT and CCD, activates NCC

[49] and also inhibits ROMK [50] . The interaction/competition

between WNK3 and WNK4 with regard to NCC

is another potential mechanism for modulation of salt

transport rate in DCT [51] .

These rather complex mechanisms of transport regulation

are starting to explain the complex clinical manifestations

that are observed. In fact, by looking at the

a

b

Color version available online

Fig. 2. a In physiological conditions in the

DCT1, the short KS-WNK1 isoform expression

is severalfold higher than the

long-WNK1 variant. Thus, KS-WNK1

prevents the WNK1-induced inhibition of

WNK4, and thus allowing WNK4 to freely

inhibit NCC and ROMK. b In contrast, in

PHAII due to intronic deletions of the

WNK1, the increased expression of the

long-WNK1 variant overcomes the inhibition

by KS-WNK1 leading to NCC activation,

and ROMK inhibition, as a consequence

of WNK4 inhibition by WNK1. In

addition, the long WNK1 directly inhibits

ROMK.

WNKs Signaling and Salt Metabolism Am J Nephrol 2012;35:379–386 383

common underlying mechanisms, the kidney's response

to various diseases becomes readily apparent ( table 1 ).

Diseases that present with low blood volume, be it by direct

blood loss or extracellular fluid distribution abnormalities

such as chronic heart failure, cirrhosis, nephrotic

syndrome and others, have essentially the same underlying

problem: decreased mean circulatory filling

pressure and decreased urinary flow in the distal nephron.

In these patients, the renin-angiotensin-aldosterone

system is activated (secondary aldosteronism). Through

the mechanisms described above ( fig. 1 ), in secondary aldosteronism

there is decreased flow in the distal nephron

leading to a volume retentive state which attempts to increase

circulating volume, without varying plasma K + .

The decreased urinary flow in this part of the nephron

favors K + retention by inhibiting the BK channels and indirectly

inhibiting the ENaC/ROMK Na + /K + exchange

mechanism. Thus, in untreated patients that present with

conditions where there is activation of both Ang II and

aldosterone, there is an Ang II-WNK4 and aldosterone

induced retention of Na + and volume, due to NCC and

ENaC activation, but no change in plasma K + levels, because

the aldosterone-induced increase in ROMK expression/

activity is overcome by the Ang II-WNK4 and

WNK1 reduction of ROMK activity, plus the reduced

flow and delivery of salt to CNT/CD, due to the increased

salt reabsorption in DCT. Because the increase in circulating

volume comes at the expense of increasing Na + and

water, which is not accompanied by a concomitant increase

in oncotic pressure, this leads to fluid accumulation

throughout the entire extracellular space which will

clinically manifest itself as edema ( table 1 ).

A completely different situation occurs when aldosterone

is increased in the absence of activation of the

renin-angiotensin-aldosterone system ( fig. 1 . This is

what occurs during a high potassium diet or primary

aldosteronism, in which there is an increased flow rate

in the distal nephron. Aldosterone increases the expression

of the serum glucocorticoid kinase 1 (SGK1), which

in turn phosphorylates and inhibits a protein known as

Nedd4–2 that by ubiquitylating ENaC triggers the internalization

and destruction of the channel. Thus, by inhibiting

Nedd4–2, SGK1 induces and increase of ENaC

expression in the plasma membrane [52] . In addition, by

phosphorylating WNK4 in two critical sites, SGK1 will

also prevent the WNK4-induced inhibition of ENaC

and ROMK, thus releasing the activity of these channels,

a condition that favors K + secretion through the

ENaC/ROMK exchange mechanism (see above) [35, 53] .

Aldosterone is also known to increase NCC protein expression

[54] , through regulation of Nedd4–2, a mechanism

similar to that of ENaC [55] . Aldosterone mediated

increase in NCC, however, would presumably be limited

to DCT2, where the abundance of NCC is relatively minor,

because DCT1 is not considered as part of the aldosterone

sensitive distal nephron due to the absence of

11 -hydroxysteroid dehydrogenase type 2 that precludes

the promiscuous occupation of the mineralocorticoid

receptor by cortisol [22, 56] . Hence, although

NCC expression is increased in DCT2 in a state of isolated

aldosterone secretion, because of the absence of the

Ang II, NCC in DCT1 would remain under WNK4 inhibition.

This results in increased distal delivery of Na +

and volume and activation of ENaC, ROMK and BK

channels leading to an increase in of the Na + /K + exchange

and thus increased K + excretion. This phenomenon

becomes clinically relevant in states of increased

aldosterone secretion with decreased activity of Ang II

and a consequent increased flow in the distal nephron

( table 1 ). The day-to-day scenario that emulates this situation

is the high K + diet where salt reabsorption in

DCT1 is decreased, allowing the Na + /K + exchange in

Table 1. Common clinical entities and the associated changes in aldosterone, Ang II, blood pressure, Na+ balance and K+ balance

Clinical scenario Mineralocorticoid

activity

Ang II Change

in blood pressure

Na+

balance

K+

balance

Edema

Hypovolemia d d f d } no

Secondary hyperaldosteronism

(e.g. CHF, cirrhosis, etc.) d d } d } yes

High potassium diet d f } } f no

Primary hyperaldosteronism d f d } f no

Cushing's syndrome d f d } f no

's syndrome f d f f d no

384 Am J Nephrol 2012;35:379–386 Arroyo /Gamba

CD to secrete the excess K + . A pathophysiological version

is primary aldosteronism, where an autonomous

increase of aldosterone promotes sodium reabsorption

and K + secretion by increasing the activity of ENaC and

ROMK, respectively. Why these patients do not develop

edema, similarly to what happens in patients with secondary

hyperaldosteronism, is due to the presence versus

absence of Ang II in secondary versus primary aldosteronism.

In secondary aldosteronism, as discussed

above, Ang II, presumably via WNK4 activates NCC. In

contrast, in primary aldosteronism, the fact that NCC is

not activated by aldosterone in DCT1 suggests that these

patients are still subject to pressure natriuresis. In fact,

although NCC is considered to be an aldosterone-regulated

protein [54] , during the aldosterone-escape phenomenon,

of all the studied transporters in the kidney,

NCC is the only one whose expression is actually decreased,

despite the continuous administration of aldosterone

[57] . Thus, in primary aldosteronism, the reduced

activity of NCC in DCT1 keeps the salt balance

and because of the increased flow rate provides the salt

and volume delivery to CNT/CD producing hypokalemia.

In other words, the inhibition of NCC in DCT1 is

enough to overcome the ENaC activity, at least to prevent

the edema formation, but at the expense of arterial

hypertension. This mechanism extends to Cushing's

syndrome. When the elevated cortisol in plasma overcomes

the capacity of the 11 -hydroxysteroid dehydrogenase

type 2 to degrade it and thus, occupies and activates

the mineralocorticoid receptor, as if aldosterone

was increased. A similar situation occurs in Liddle's

syndrome in which there is a primary increase in ENaC

activity due to mutations in the or subunits of ENaC

that eliminate the PY motif required for Nedd4–2 and

ENaC interaction, thus precluding the normal regulation

of the channel by Nedd4–2 [58] . The clinical picture

of Liddle's syndrome is similar to primary aldosteronism:

hypertension with hypokalemia. The increased sodium

absorption by ENaC induces hypertension and by

pressure natriuresis mechanisms NCC must be inhibited

to maintain salt balance, preventing edema formation.

In summary, the integration of the renal molecular

mechanisms that are regulated via the WNK kinases has

now shed light on an issue that remained obscure for long

time. The molecular mechanisms of the interaction between

aldosterone and Ang II in the differentiation between

volume retention and K + secretion are beginning

to be elucidated, providing a better molecular understanding

of physiological or pathophysiological processes

associated with classical clinical syndromes of salt and

potassium metabolism.

Acknowledgements

We thank Kimmel, MD, for his critical reading of the

manuscript. This work was supported in part by the Leducq

Foundation Transatlantic Network on Hypertension and El Consejo

Nacional de Ciencia y Tecnología (CONACYT-Mexico) Grant

165815 (to G.G.). J.P.A. was supported by a scholarship from

CONACYT-Mexico and is a graduate student in the Biomedical

Science PhD Program of the Universidad Nacional Autónoma de

México, UNAM.

Disclosure Statement

No conflicts of interest are declared

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31 Sacks FM, Svetkey LP, Vollmer WM, Appel

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32 Huang CL, Kuo E: Mechanisms of disease:

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33 Frindt G, Houde V, Palmer LG: Conservation

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34 Kahle KT, FH, Leng Q, Lalioti MD,

O'Connell AD, Dong K, Rapson AK, Mac-

Gregor GG, Giebisch G, Hebert SC, Lifton

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35 Ring AM, Cheng SX, Leng Q, Kahle KT,

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FH, Hebert SC, Lifton RP: WNK4 regulates

activity of the epithelial Na + channel in

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36 San Cristobal P, De Los HP, Ponce-Coria J,

Moreno E, Gamba G: WNK kinases, renal

ion transport and hypertension. Am J

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37 Sandberg MB, Riquier AD, Pihakaski-

Maunsbach K, McDonough AA, Maunsbach

AB: Angiotensin II provokes acute trafficking

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(NCC) to apical membrane. Am J Physiol Renal

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38 van der LN, Lim CH, Fenton RA, Meima ME,

Jan Danser AH, Zietse R, Hoorn EJ: Angiotensin

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independent of aldosterone. Kidney

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39 Zhao D, Seth DM, Navar LG: Enhanced distal

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40 San Cristobal P, Pacheco-Alvarez D,

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41 Yue P, Sun P, Lin DH, Pan C, Xing W, Wang

W: Angiotensin II diminishes the effect of

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42 Cheng CJ, Huang CL: Activation of PI3-kinase

stimulates endocytosis of ROMK via

Akt1/SGK1-dependent phosphorylation of

WNK1. J Am Soc Nephrol 2011; 22: 460–471.

43 He G, Wang HR, Huang SK, Huang CL: Intersectin

links WNK kinases to endocytosis

of ROMK1. J Clin Invest 2007; 117: 1078–

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44 Huang CL, Yang SS, Lin SH: Mechanism of

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Curr Opin Nephrol Hypertens 2008;

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45 Lazrak A, Liu Z, Huang CL: Antagonistic

regulation of ROMK by long and kidneyspecific

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46 Liu Z, Wang HR, Huang CL: Regulation of

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specific WNK1 kinase. J Biol Chem

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47 Subramanya AR, Yang CL, Zhu X, Ellison

DH: Dominant-negative regulation of

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48 Liu Z, Xie J, Wu T, Truong T, Auchus RJ,

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49 Rinehart J, Kahle KT, De Los HP, Vazquez N,

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50 Leng Q, Kahle KT, Rinehart J, MacGregor

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> > > > > >> > > > > > A K of 3.7 could be a poor blood draw. If they use a > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use > > > a tourniquet except for someone who is very brittle or very > > > dehydrated, and usually only after they have tried the tourniquet > > > first. And many slap the vein/arm and can be a little rough about > > > it, falsely increasing the K. When I ask them now, most act like > > > they knew this about elevating K, but you can tell by their look > > > they didn't know this nor were taught this.> > > > > > Â> > > > > > I had the lab a while back draw my blood and I asked her not > > > to use a tourniquet due to the potassium - she did anyway saying she > > > draws it "fast" and so I let her (because the nurses always know > > > more than anyone).  It came back 4.0, I didn't take my K for a few > > > days and I could tell, absolutely no doubt, that my K was low. So I > > > started taking it again and felt 100 times better. The lab was > > > wrong. My follow up, after taking the K and with no tourniquet was 3.4> > > > > >> > > > >> > > >> > >> > >> >>

[Guest guest]

You missed the point completely. I don't expect any of us to understand it, the best in the world are still trying to figure it out! The point is there is currently a lot of activity in this area and if you are intrested in your QOL I would recommend thorough and complete testing but it is an individual choice! I thought Dr. Grim might like to see some of the current thinking and what current researchers are looking at, especially since it might explain why some may never have a low K issue or may have some other "masked" issue! I guarantee I'm not the only one, there are atleast 3 of us that frequent this site!

Understand that a "trial of Spironolactone" is the absolute WRONG thing to do if you have a "masked cortisol" issue! Cortisol is already high and when Spiro antagonizes androgen at CYP11B2 it allows cortisol (CYP11B1) to increase so you have a double whammy of cortisol. For an intresting exersize you might examine how you get rid of excess cortisol!

> > >> > > > I have recently read that it was okay to use a tourniquet to find> > > > the vien and release it for 5 seconds before the actual draw.> (Makes> > > > sense to me that the "damaged" blood would have moved on before> you> > > > captured your sample.) That's how my friendly vampire at NIH did> it> > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in> > > > from NIH so I can compare to the numbers I get locally. (I do not> > > > expect to find any problems since K was never mentioned and K is> > > > usually not an issue with my style of PA!)> > > >SNIP

[Guest guest]

I belive the question is does your style of PA cause low K. You then point to

this report to show this. I can not see if it does or does not cause low K.

> > > >

> > > > > I have recently read that it was okay to use a tourniquet to

> find

> > > > > the vien and release it for 5 seconds before the actual draw.

> > (Makes

> > > > > sense to me that the " damaged " blood would have moved on before

> > you

> > > > > captured your sample.) That's how my friendly vampire at NIH did

> > it

> > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in

> > > > > from NIH so I can compare to the numbers I get locally. (I do

> not

> > > > > expect to find any problems since K was never mentioned and K is

> > > > > usually not an issue with my style of PA!)

> > > > >

> SNIP

>

[Guest guest]

Due to my QOL I am not sure if I am up to traveling to get thorough and complete

testing.

> > > > >

> > > > > > I have recently read that it was okay to use a tourniquet to

> > find

> > > > > > the vien and release it for 5 seconds before the actual draw.

> > > (Makes

> > > > > > sense to me that the " damaged " blood would have moved on before

> > > you

> > > > > > captured your sample.) That's how my friendly vampire at NIH did

> > > it

> > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in

> > > > > > from NIH so I can compare to the numbers I get locally. (I do

> > not

> > > > > > expect to find any problems since K was never mentioned and K is

> > > > > > usually not an issue with my style of PA!)

> > > > > >

> > SNIP

> >

>

[Guest guest]

I quoted that study to show Dr. Grim some of what is currently being studied and

surfacing. I think I pointed out I didn't even know if WNK applied to me but I

did see " Primary Aldosteronism " mentioned so I presume it is applicble to some

with PA. If I implied I was going back to justify something I said, I didn't

mean to. If I said I read something, you can take it to the bank! I have

verified it to my satisfaction and if I have any question I have verified it

with Dr. Moraitis.

Understand that this is a good (or bad) mystery. There are clues that we (Me

and Dr. Moraitis) are trying to unravel and I am trying to share the ones I

think might be important to others. Take them or leave them but I don't have

time to debate them - I plan to write the final chapter in my lifetime!

> > > > >

> > > > > > I have recently read that it was okay to use a tourniquet to

> > find

> > > > > > the vien and release it for 5 seconds before the actual draw.

> > > (Makes

> > > > > > sense to me that the " damaged " blood would have moved on before

> > > you

> > > > > > captured your sample.) That's how my friendly vampire at NIH did

> > > it

> > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in

> > > > > > from NIH so I can compare to the numbers I get locally. (I do

> > not

> > > > > > expect to find any problems since K was never mentioned and K is

> > > > > > usually not an issue with my style of PA!)

> > > > > >

> > SNIP

> >

>

[Guest guest]

While I certainly can't claim to understand everything from the last 2 articles

posted, it appears to me that current studies are moving toward discovery of the

mechanisms through which PA functions and the mechanisms which lead to the

development of HA. The article regarding roles of Aldo, NA, K and cortisol and

the variety of different results that can be produced illustrates the complexity

of these issues.

> > > > > >

> > > > > > > I have recently read that it was okay to use a tourniquet to

> > > find

> > > > > > > the vien and release it for 5 seconds before the actual draw.

> > > > (Makes

> > > > > > > sense to me that the " damaged " blood would have moved on before

> > > > you

> > > > > > > captured your sample.) That's how my friendly vampire at NIH did

> > > > it

> > > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in

> > > > > > > from NIH so I can compare to the numbers I get locally. (I do

> > > not

> > > > > > > expect to find any problems since K was never mentioned and K is

> > > > > > > usually not an issue with my style of PA!)

> > > > > > >

> > > SNIP

> > >

> >

>

[Guest guest]

Will be interesting as low K and HTN are not as much of a problem in Cushing's as in PA. So will need to study what the NIH is doing in some more detail by reading the papers over the next week or so.Interesting questions. On Apr 28, 2012, at 3:48 PM, wrote: I quoted that study to show Dr. Grim some of what is currently being studied and surfacing. I think I pointed out I didn't even know if WNK applied to me but I did see "Primary Aldosteronism" mentioned so I presume it is applicble to some with PA. If I implied I was going back to justify something I said, I didn't mean to. If I said I read something, you can take it to the bank! I have verified it to my satisfaction and if I have any question I have verified it with Dr. Moraitis. Understand that this is a good (or bad) mystery. There are clues that we (Me and Dr. Moraitis) are trying to unravel and I am trying to share the ones I think might be important to others. Take them or leave them but I don't have time to debate them - I plan to write the final chapter in my lifetime! > > > > > > > > > > > I have recently read that it was okay to use a tourniquet to > > find > > > > > > the vien and release it for 5 seconds before the actual draw. > > > (Makes > > > > > > sense to me that the "damaged" blood would have moved on before > > > you > > > > > > captured your sample.) That's how my friendly vampire at NIH did > > > it > > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to come in > > > > > > from NIH so I can compare to the numbers I get locally. (I do > > not > > > > > > expect to find any problems since K was never mentioned and K is > > > > > > usually not an issue with my style of PA!) > > > > > > > > SNIP > > >

[Guest guest]

Dr. Grim, I don't know if I posted this but I think it is a good summary of what

I think we are looking at:

http://endo.endojournals.org/content/153/4/1575.full.pdf

> > > > > > >

> > > > > > > > I have recently read that it was okay to use a

> > tourniquet to

> > > > find

> > > > > > > > the vien and release it for 5 seconds before the actual

> > draw.

> > > > > (Makes

> > > > > > > > sense to me that the " damaged " blood would have moved on

> > before

> > > > > you

> > > > > > > > captured your sample.) That's how my friendly vampire at

> > NIH did

> > > > > it

> > > > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to

> > come in

> > > > > > > > from NIH so I can compare to the numbers I get locally.

> > (I do

> > > > not

> > > > > > > > expect to find any problems since K was never mentioned

> > and K is

> > > > > > > > usually not an issue with my style of PA!)

> > > > > > > >

> > > > SNIP

> > > >

> > >

> >

> >

>

[Guest guest]

I have been one of those best for about ~40 years but they are making good progress as well. Should know more in another 20 years is my guess. I have seen a number of "advances" come and go. So time will tell.But will follow their work.CE Grim MDOn Apr 27, 2012, at 12:57 PM, wrote: I took the liberty of changing the name of this thread. Hope it better describes what we are talking about. Dr. Grim, I would like to respectfully suggest that there is a lot going on in the advancement of diagnosing and treating hyperaldosteronism. I know from spending 2 weeks at NIH that "the air is electric" and the "best Endocrinologists in the World" are working on it, I even had the privilege of talking with a couple of them. I suspect the following, note it was published 2 weeks ago, may be part of it but my Team is not available this week so I have not verified it. We have talked about the "KCNJ5" gene and I understand they are very interested in dissecting my right adrenal! (I'm still waiting for their complete ideas!) They are also very interested in getting DNA from me and my three children! (Three or III is an interesting number isn't it!) Suggest you pubmed KCNJ5 and pay particular attention to the dates of publiction! You can also see where the work is being done! With that information and the following you might begin to see why I say low K may never be an issue for me, have a look: http://www.ncbi.nlm.nih.gov/pubmed/22508439 "Advances in WNK Signaling of Salt and Potassium Metabolism: Clinical Implications." Abstract Recent evidence due to the discovery of a family of kinases implicated in arterial hypertension now points to the underlying molecular mechanisms that dictate Na(+), K(+) and water handling in the nephron. These new key players need to be understood in order to fully comprehend the pathophysiology, manifestations, and treatment of common clinical entities such as hypovolemic shock, congestive heart failure, primary hyperaldosteronism, nephrotic syndrome and hypertension. It is through the analysis of the volume status and electrolyte abnormalities that commonly present with these diseases that we can begin to create a link between the abstract concept of a kinase regulation and how a patient will respond to a particular treatment. This review is an attempt to bridge that gap. Copyright © 2012 S. Karger AG, Basel. Maybe it will soon be time to update your evolution article! ... > > > > > > > > > > A K of 3.7 could be a poor blood draw. If they use a > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use > > a tourniquet except for someone who is very brittle or very > > dehydrated, and usually only after they have tried the tourniquet > > first. And many slap the vein/arm and can be a little rough about > > it, falsely increasing the K. When I ask them now, most act like > > they knew this about elevating K, but you can tell by their look > > they didn't know this nor were taught this. > > > > >  > > > > > I had the lab a while back draw my blood and I asked her not > > to use a tourniquet due to the potassium - she did anyway saying she > > draws it "fast" and so I let her (because the nurses always know > > more than anyone).  It came back 4.0, I didn't take my K for a few > > days and I could tell, absolutely no doubt, that my K was low. So I > > started taking it again and felt 100 times better. The lab was > > wrong. My follow up, after taking the K and with no tourniquet was 3.4 > > > > > > > > > > > > > > > > >

[Guest guest]

Note these interesting studies were done in cultured adrenal cell carcinoma cells. Will need to await studies in Man before getting too excited. CE Grim MDOn Apr 29, 2012, at 5:12 PM, wrote: Dr. Grim, I don't know if I posted this but I think it is a good summary of what I think we are looking at: http://endo.endojournals.org/content/153/4/1575.full.pdf > > > > > > > > > > > > > > > I have recently read that it was okay to use a > > tourniquet to > > > > find > > > > > > > > the vien and release it for 5 seconds before the actual > > draw. > > > > > (Makes > > > > > > > > sense to me that the "damaged" blood would have moved on > > before > > > > > you > > > > > > > > captured your sample.) That's how my friendly vampire at > > NIH did > > > > > it > > > > > > > > every morning t 5:55 a.m.! I'm waiting for my numbers to > > come in > > > > > > > > from NIH so I can compare to the numbers I get locally. > > (I do > > > > not > > > > > > > > expect to find any problems since K was never mentioned > > and K is > > > > > > > > usually not an issue with my style of PA!) > > > > > > > > > > > > SNIP > > > > > > > > > > > >

[Guest guest]

Hell, we can barely get the corner doc (and throw in the PA's and NP's too) to even consider hyperaldosteronism most of the time or do the tests right to find it. If the air is electric than I compare it to the Chevy VOLT, where, in a teeny tiny circle it is exciting to some, and because you're there it seems bigger than it is, but it certainly isn't the talk of the town in general.

I still say.think one of the biggest reasons is because it, strangely, just isn't "exciting" enough for the average doc and that it just gets perpetuated that way and passed on as rare and not likely - though they all seem to want to find that elusive pheo all the time.

I think I have told the story recently of my two friends, nurse practitioners, who wouldn't even TRY spiro in one of their young hypertensives who was resistant to multiple other meds because his serum aldosterone levels weren't off, even though they didn't stop the other meds AND I gave them Dr G's handout AND tried to educate them on how to do it right. They did put him on a new expensive renin blocker (samples to start with) even though his renin levels were okay too. I don't get it. So freakin what? Try the spiro, if it works, like happened in my case (after a hundred years and a hundred other meds), you have it, or at least now have a great clue. But they don't/won't. I really don't get it - but we argued about it in a freinds way and I tried to advocate for the guy. Sadly I am in no position to do it myself for him right now. But they never gave me a reason why they wouldn't write a script for spiro. I have seen this with a

lot of patients.

I took the liberty of changing the name of this thread. Hope it better describes what we are talking about.Dr. Grim, I would like to respectfully suggest that there is a lot going on in the advancement of diagnosing and treating hyperaldosteronism. I know from spending 2 weeks at NIH that "the air is electric" and the "best Endocrinologists in the World" are working on it, I even had the privilege of talking with a couple of them. I suspect the following, note it was published 2 weeks ago, may be part of it but my Team is not available this week so I have not verified it. We have talked about the "KCNJ5" gene and I understand they are very interested in dissecting my right adrenal! (I'm still waiting for their complete ideas!) They are also very interested in getting DNA from me and my three children! (Three or III is an interesting number isn't it!) Suggest you pubmed KCNJ5 and pay particular attention to the dates of publiction! You can

also see where the work is being done!With that information and the following you might begin to see why I say low K may never be an issue for me, have a look:http://www.ncbi.nlm.nih.gov/pubmed/22508439"Advances in WNK Signaling of Salt and Potassium Metabolism: Clinical Implications."AbstractRecent evidence due to the discovery of a family of kinases implicated in arterial hypertension now points to the underlying molecular mechanisms that dictate Na(+), K(+) and water handling in the nephron. These new key players need to be understood in order to fully comprehend the pathophysiology, manifestations, and treatment of common clinical entities such as hypovolemic shock, congestive heart failure, primary hyperaldosteronism, nephrotic syndrome and hypertension. It is through the analysis of the volume status and electrolyte

abnormalities that commonly present with these diseases that we can begin to create a link between the abstract concept of a kinase regulation and how a patient will respond to a particular treatment. This review is an attempt to bridge that gap.Copyright © 2012 S. Karger AG, Basel.Maybe it will soon be time to update your evolution article!...>

> > > >> > > > > A K of 3.7 could be a poor blood draw. If they use a > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use > > a tourniquet except for someone who is very brittle or very > > dehydrated, and usually only after they have tried the tourniquet > > first. And many slap the vein/arm and can be a little rough about > > it, falsely increasing the K. When I ask them now, most act like > > they knew this about elevating K, but you can tell by their look > > they didn't know this nor were taught this.> > > > > Â> > > > > I had the lab a while back draw my blood and I asked her not > > to use a tourniquet due to the potassium - she did anyway saying she > > draws it "fast" and so I let her (because the nurses always know > > more than anyone).  It came back

4.0, I didn't take my K for a few > > days and I could tell, absolutely no doubt, that my K was low. So I > > started taking it again and felt 100 times better. The lab was > > wrong. My follow up, after taking the K and with no tourniquet was 3.4> > > > >> > > >> > >> >> >>

[Guest guest]

Maybe Arizona is too far away from Bethesda to feel the electricity! Actually,

I might suggest it would be a good experience for you to spend 10 days a little

closer to that electricity! (Food is good!)

Of course it is not the " talk of the town " it is still in RESEARCH! Hopefully

when/if there are conclusions it will become better published and more

recognized.

I suggest doctors may choose to consider it rare because the preparation for

testing may make that their easiest choice! If you are going to continue

advocating " a trial of Spironalactone " I recommend you do a late-night salivary

cortisol test and check their testosterone level blood test. Remember tht

" first do no harm " clause! (At least 3 of the 750 on this site would have

benefitted!)

> > > > > >

> > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > a tourniquet except for someone who is very brittle or very

> > > dehydrated, and usually only after they have tried the tourniquet

> > > first. And many slap the vein/arm and can be a little rough about

> > > it, falsely increasing the K. When I ask them now, most act like

> > > they knew this about elevating K, but you can tell by their look

> > > they didn't know this nor were taught this.

> > > > > > Â

> > > > > > I had the lab a while back draw my blood and I asked her not

> > > to use a tourniquet due to the potassium - she did anyway saying she

> > > draws it " fast " and so I let her (because the nurses always know

> > > more than anyone). Â It came back 4.0, I didn't take my K for a few

> > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > started taking it again and felt 100 times better. The lab was

> > > wrong. My follow up, after taking the K and with no tourniquet was 3.4

> > > > > >

> > > > >

> > > >

> > >

> > >

> >

>

[Guest guest]

Maybe it is more exciting when you are being considered to be that man (or one

of them!)

> > > > > > > > >

> > > > > > > > > > I have recently read that it was okay to use a

> > > > tourniquet to

> > > > > > find

> > > > > > > > > > the vien and release it for 5 seconds before the

> > actual

> > > > draw.

> > > > > > > (Makes

> > > > > > > > > > sense to me that the " damaged " blood would have

> > moved on

> > > > before

> > > > > > > you

> > > > > > > > > > captured your sample.) That's how my friendly

> > vampire at

> > > > NIH did

> > > > > > > it

> > > > > > > > > > every morning t 5:55 a.m.! I'm waiting for my

> > numbers to

> > > > come in

> > > > > > > > > > from NIH so I can compare to the numbers I get

> > locally.

> > > > (I do

> > > > > > not

> > > > > > > > > > expect to find any problems since K was never

> > mentioned

> > > > and K is

> > > > > > > > > > usually not an issue with my style of PA!)

> > > > > > > > > >

> > > > > > SNIP

> > > > > >

> > > > >

> > > >

> > > >

> > >

> >

> >

>

[Guest guest]

Well dont know about benifited. So let's see the testing for test and cort ( they rCommend 2 x each would be about $200 x 750 is talking about real $. Would like more data on use of cort and test testing to select out those that might not benefit from Spiro. May your pressure be low!CE Grim MS, MDSpecializing in DifficultHypertensionOn Apr 30, 2012, at 7:48, <jclark24p@...> wrote:

Maybe Arizona is too far away from Bethesda to feel the electricity! Actually, I might suggest it would be a good experience for you to spend 10 days a little closer to that electricity! (Food is good!)

Of course it is not the "talk of the town" it is still in RESEARCH! Hopefully when/if there are conclusions it will become better published and more recognized.

I suggest doctors may choose to consider it rare because the preparation for testing may make that their easiest choice! If you are going to continue advocating "a trial of Spironalactone" I recommend you do a late-night salivary cortisol test and check their testosterone level blood test. Remember tht "first do no harm" clause! (At least 3 of the 750 on this site would have benefitted!)

> > > > > >

> > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > a tourniquet except for someone who is very brittle or very

> > > dehydrated, and usually only after they have tried the tourniquet

> > > first. And many slap the vein/arm and can be a little rough about

> > > it, falsely increasing the K. When I ask them now, most act like

> > > they knew this about elevating K, but you can tell by their look

> > > they didn't know this nor were taught this.

> > > > > > Â

> > > > > > I had the lab a while back draw my blood and I asked her not

> > > to use a tourniquet due to the potassium - she did anyway saying she

> > > draws it "fast" and so I let her (because the nurses always know

> > > more than anyone). Â It came back 4.0, I didn't take my K for a few

> > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > started taking it again and felt 100 times better. The lab was

> > > wrong. My follow up, after taking the K and with no tourniquet was 3.4

> > > > > >

> > > > >

> > > >

> > >

> > >

> >

>

[Guest guest]

I guess it depends on whether you are one of the ones adversely affected (nobody

ever explained why God sends us with so much testosterone, is it so you can take

it away?)

Let's examine a sample of one (you replace the ???'s)

Annual Mammogram: ???/yr X 25 yrs = ??? (QOL & travel risks)

Psychiatrist: (???/trip which costs me $100 per out of pocket) X say 5 since I

will only charge half of the 10/yr until I see the effects of reduced cortisol!

(QOL & travel risks) (Run that out 25 years or so.)

General reduction in QOL just dealing with these two issues and what did it cost

the VA?

Now I'm talking REAL MONEY! (But happy I saved $200!) (BTW, $200 is 4 trips for

treatment for me just in travel expenses!)

> > > > > > > >

> > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > > > a tourniquet except for someone who is very brittle or very

> > > > > dehydrated, and usually only after they have tried the tourniquet

> > > > > first. And many slap the vein/arm and can be a little rough about

> > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > they knew this about elevating K, but you can tell by their look

> > > > > they didn't know this nor were taught this.

> > > > > > > > Â

> > > > > > > > I had the lab a while back draw my blood and I asked her not

> > > > > to use a tourniquet due to the potassium - she did anyway saying she

> > > > > draws it " fast " and so I let her (because the nurses always know

> > > > > more than anyone). Â It came back 4.0, I didn't take my K for a

few

> > > > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > > > started taking it again and felt 100 times better. The lab was

> > > > > wrong. My follow up, after taking the K and with no tourniquet was 3.4

> > > > > > > >

> > > > > > >

> > > > > >

> > > > >

> > > > >

> > > >

> > >

> >

> >

>

[Guest guest]

But need data that the testing selects hose hat will not benefit or maybe gynecomastia is the best indicator and as soon as it develops switch to elere or even start with eplereMay your pressure be low!CE Grim MS, MDSpecializing in DifficultHypertensionOn Apr 30, 2012, at 11:50, <jclark24p@...> wrote:

I guess it depends on whether you are one of the ones adversely affected (nobody ever explained why God sends us with so much testosterone, is it so you can take it away?)

Let's examine a sample of one (you replace the ???'s)

Annual Mammogram: ???/yr X 25 yrs = ??? (QOL & travel risks)

Psychiatrist: (???/trip which costs me $100 per out of pocket) X say 5 since I will only charge half of the 10/yr until I see the effects of reduced cortisol! (QOL & travel risks) (Run that out 25 years or so.)

General reduction in QOL just dealing with these two issues and what did it cost the VA?

Now I'm talking REAL MONEY! (But happy I saved $200!) (BTW, $200 is 4 trips for treatment for me just in travel expenses!)

> > > > > > > >

> > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > > > a tourniquet except for someone who is very brittle or very

> > > > > dehydrated, and usually only after they have tried the tourniquet

> > > > > first. And many slap the vein/arm and can be a little rough about

> > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > they knew this about elevating K, but you can tell by their look

> > > > > they didn't know this nor were taught this.

> > > > > > > > Â

> > > > > > > > I had the lab a while back draw my blood and I asked her not

> > > > > to use a tourniquet due to the potassium - she did anyway saying she

> > > > > draws it "fast" and so I let her (because the nurses always know

> > > > > more than anyone). Â It came back 4.0, I didn't take my K for a few

> > > > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > > > started taking it again and felt 100 times better. The lab was

> > > > > wrong. My follow up, after taking the K and with no tourniquet was 3.4

> > > > > > > >

> > > > > > >

> > > > > >

> > > > >

> > > > >

> > > >

> > >

> >

> >

>

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Reply to group |

Reply via web post |

Start a New Topic

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[Guest guest]

Well, I think we may be making some headway! Did you really just say start with

Epelerenone? I've been advocating that for a year and a half! Never could

understand why you wanted to mess with androgen now that you don't have to! And

did you remove the word " painful " from gynecomastia? At least we won't make a

cortisol situation for most or a cortisol sitution worse for a few if we don't

use Spironolactone!

> > > > > > > > > >

> > > > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT

use

> > > > > > > a tourniquet except for someone who is very brittle or very

> > > > > > > dehydrated, and usually only after they have tried the tourniquet

> > > > > > > first.ÃÆ'‚ And many slap the vein/arm and can be a little

rough about

> > > > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > > > they knew this about elevating K, but you can tell by their look

> > > > > > > they didn't know this nor were taught this.

> > > > > > > > > > ÃÆ'‚

> > > > > > > > > > I had the lab a while back draw my blood and I asked her not

> > > > > > > to use a tourniquet due to the potassium - she did anyway saying

she

> > > > > > > draws it " fast " and so I let her (because the nurses always know

> > > > > > > more than anyone). ÃÆ'‚ It came back 4.0, I didn't take my

K for a few

> > > > > > > days and I could tell, absolutely no doubt, that my K was low. So

I

> > > > > > > started taking it again and felt 100 times better. The lab was

> > > > > > > wrong. My follow up, after taking the K and with no tourniquet was

3.4

> > > > > > > > > >

> > > > > > > > >

> > > > > > > >

> > > > > > >

> > > > > > >

> > > > > >

> > > > >

> > > >

> > > >

> > >

> >

> >

> > Reply to sender | Reply to group | Reply via web post | Start a New Topic

> > Messages in this topic (84)

> > RECENT ACTIVITY: New Members 5</

>

[Guest guest]

, I did very poorly on spiro. Ended up needing a D & C. I'm doing fine on Inspra. BP averages 132/71. Maybe my cortisol, aldo, renin, PTH, calcium, osteoporosis are all related? Val From: hyperaldosteronism [mailto:hyperaldosteronism ] On Behalf Of Well, I think we may be making some headway! Did you really just say start with Epelerenone? I've been advocating that for a year and a half! Never could understand why you wanted to mess with androgen now that you don't have to! And did you remove the word " painful " from gynecomastia? At least we won't make a cortisol situation for most or a cortisol sitution worse for a few if we don't use Spironolactone!

[Guest guest]

Thank God I got off Spiro before I needed a D & C! Did you have an adenoma? If

not, you might want to keep track of maggieKat, she's back there for more

testing either this week or next. I know they started her on Inspra and it will

be intresting to hear what else they suggest. Glad to hear you are doing well.

.....

>

> , I did very poorly on spiro. Ended up needing a D & C. I'm doing fine

> on Inspra. BP averages 132/71. Maybe my cortisol, aldo, renin, PTH,

> calcium, osteoporosis are all related?

>

>

>

> Val

>

>

>

> From: hyperaldosteronism

> [mailto:hyperaldosteronism ] On Behalf Of

>

>

>

> Well, I think we may be making some headway! Did you really just say start

> with Epelerenone? I've been advocating that for a year and a half! Never

> could understand why you wanted to mess with androgen now that you don't

> have to! And did you remove the word " painful " from gynecomastia? At least

> we won't make a cortisol situation for most or a cortisol sitution worse for

> a few if we don't use Spironolactone!

>

[Guest guest]

Yes, thank God you didn't need a D & C. Oh … neva' mind. I had a parathyroid adenoma, visible on a Sestimibi scan and removed. No adenoma has been found on CT and I had an extremely small slice CT at National Jewish (one of three machines in the U.S. at that time). Of course, there are adenomas smaller than small slice. I read all the emails, sometimes more slowly than others. Val From: hyperaldosteronism [mailto:hyperaldosteronism ] On Behalf Of Sent: Monday, April 30, 2012 7:53 PMhyperaldosteronism Subject: Re: JC at NIH - What's New? Thank God I got off Spiro before I needed a D & C! Did you have an adenoma? If not, you might want to keep track of maggieKat, she's back there for more testing either this week or next. I know they started her on Inspra and it will be intresting to hear what else they suggest. Glad to hear you are doing well..... >> , I did very poorly on spiro. Ended up needing a D & C. I'm doing fine> on Inspra. BP averages 132/71. Maybe my cortisol, aldo, renin, PTH,> calcium, osteoporosis are all related?> > > > Val> > > > From: hyperaldosteronism > [mailto:hyperaldosteronism ] On Behalf Of > > > > Well, I think we may be making some headway! Did you really just say start> with Epelerenone? I've been advocating that for a year and a half! Never> could understand why you wanted to mess with androgen now that you don't> have to! And did you remove the word " painful " from gynecomastia? At least> we won't make a cortisol situation for most or a cortisol sitution worse for> a few if we don't use Spironolactone!>

[Guest guest]

y'know what's bugging me? This group is supposed to be supportive and helpful

to those of us suffering and searching for answers. There are several here who

offer up good links to research and some of us give our opinions based on

experience, but I would think that if there is concrete evidence out there based

on research, that we would want to embrace those data and learn and share

current knowledge in this area. When I first was dealing with all of this, a

while ago, there were numerous studies that clearly stated that a " trial " of

meds is simply not the way to deal with HA. Why is this being told to people

over and over again who are new and don't know any better? They deserve better,

don't they? We have a poster child, , who shouldn't have been trialed on

Spiro. We have me, who should not have been trialed. We have research that

says not to. We have docs at NIH that say not to. Looks to me like starting

someone with HA labs, hypertension or whatever on a trial med to diagnose HA is

a no no.

BTW, there's been a tragic death in my family (google katie death malibu) and I

will be absent for a while due to that and an upcoming NIH stint. See y'all

after things get better.

> > > > > > > > >

> > > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > > > > a tourniquet except for someone who is very brittle or very

> > > > > > dehydrated, and usually only after they have tried the tourniquet

> > > > > > first. And many slap the vein/arm and can be a little rough

about

> > > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > > they knew this about elevating K, but you can tell by their look

> > > > > > they didn't know this nor were taught this.

> > > > > > > > > Â

> > > > > > > > > I had the lab a while back draw my blood and I asked her not

> > > > > > to use a tourniquet due to the potassium - she did anyway saying she

> > > > > > draws it " fast " and so I let her (because the nurses always know

> > > > > > more than anyone). Â It came back 4.0, I didn't take my K for a

few

> > > > > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > > > > started taking it again and felt 100 times better. The lab was

> > > > > > wrong. My follow up, after taking the K and with no tourniquet was

3.4

> > > > > > > > >

> > > > > > > >

> > > > > > >

> > > > > >

> > > > > >

> > > > >

> > > >

> > >

> > >

> >

>

[Guest guest]

Ah I forgot to ask the NIH TEAM if folks with PTSD might have higher cortisol. Prob has been looked at.May your pressure be low!CE Grim MS, MDSpecializing in DifficultHypertensionOn Apr 30, 2012, at 19:24, Valarie <val@...> wrote:

, I did very poorly on spiro. Ended up needing a D & C. I'm doing fine on Inspra. BP averages 132/71. Maybe my cortisol, aldo, renin, PTH, calcium, osteoporosis are all related? Val From: hyperaldosteronism [mailto:hyperaldosteronism ] On Behalf Of Well, I think we may be making some headway! Did you really just say start with Epelerenone? I've been advocating that for a year and a

half! Never could understand why you wanted to mess with androgen now that you don't have to! And did you remove the word "painful" from gynecomastia? At least we won't make a cortisol situation for most or a cortisol sitution worse for a few if we don't use Spironolactone!

[Guest guest]

The reason I recommend a trail is the low long term cure rate with surgery. When I was young like the NIH team perhaps I recommended surgery for every one. Many came back with recurrent HTN BUT usually K was much better. My guess is that after 20 or so years they will move more the same way. And of course at that time DASH was not around. The striking responses we have seen here with adding DASH has strengthened my recommendation that a medical trial is indicated first. If BP and or K dont get to goal and one is feeling normal then why do surgery? Also a failure to improve with Spiro suggests that surgery will not help. May your pressure be low!CE Grim MS, MDSpecializing in DifficultHypertensionOn Apr 30, 2012, at 22:56, maggiekat7 <ljurkovic@...> wrote:

y'know what's bugging me? This group is supposed to be supportive and helpful to those of us suffering and searching for answers. There are several here who offer up good links to research and some of us give our opinions based on experience, but I would think that if there is concrete evidence out there based on research, that we would want to embrace those data and learn and share current knowledge in this area. When I first was dealing with all of this, a while ago, there were numerous studies that clearly stated that a "trial" of meds is simply not the way to deal with HA. Why is this being told to people over and over again who are new and don't know any better? They deserve better, don't they? We have a poster child, , who shouldn't have been trialed on Spiro. We have me, who should not have been trialed. We have research that says not to. We have docs at NIH that say not to. Looks to me like starting someone with HA labs, hypertension or whatever on a trial med to diagnose HA is a no no.

BTW, there's been a tragic death in my family (google katie death malibu) and I will be absent for a while due to that and an upcoming NIH stint. See y'all after things get better.

> > > > > > > > >

> > > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT use

> > > > > > a tourniquet except for someone who is very brittle or very

> > > > > > dehydrated, and usually only after they have tried the tourniquet

> > > > > > first. And many slap the vein/arm and can be a little rough about

> > > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > > they knew this about elevating K, but you can tell by their look

> > > > > > they didn't know this nor were taught this.

> > > > > > > > > Â

> > > > > > > > > I had the lab a while back draw my blood and I asked her not

> > > > > > to use a tourniquet due to the potassium - she did anyway saying she

> > > > > > draws it "fast" and so I let her (because the nurses always know

> > > > > > more than anyone). Â It came back 4.0, I didn't take my K for a few

> > > > > > days and I could tell, absolutely no doubt, that my K was low. So I

> > > > > > started taking it again and felt 100 times better. The lab was

> > > > > > wrong. My follow up, after taking the K and with no tourniquet was 3.4

> > > > > > > > >

> > > > > > > >

> > > > > > >

> > > > > >

> > > > > >

> > > > >

> > > >

> > >

> > >

> >

>

[Guest guest]

Certainly not a question for what this protocol is investigating, IMHO! If you

are referring to my PTSD episode, I doubt it has much effect if any. My PTSD is

very well controlled except for one very specific time of year. The episode I

experienced while at NIH is very rare now, it was the first I had experienced in

3-5 years so I think we can close that issue for me.

Now, if you want to investigate cortisol effect on MDD you probably have a very

real issue, IMHO!

>

> > , I did very poorly on spiro. Ended up needing a D & C. I'm doing fine

on Inspra. BP averages 132/71. Maybe my cortisol, aldo, renin, PTH, calcium,

osteoporosis are all related?

> >

> >

> >

> > Val

> >

> >

> >

> > From: hyperaldosteronism

[mailto:hyperaldosteronism ] On Behalf Of

> >

> >

> > Well, I think we may be making some headway! Did you really just say start

with Epelerenone? I've been advocating that for a year and a half! Never could

understand why you wanted to mess with androgen now that you don't have to! And

did you remove the word " painful " from gynecomastia? At least we won't make a

cortisol situation for most or a cortisol sitution worse for a few if we don't

use Spironolactone!

> >

> >

> >

> >

>

[Guest guest]

And wht happens if you hve this type?(Read the last sentence twice!)

" FH 3 — this represents a new type, characterized by severe hypertension in

early childhood. The genetic basis of this disorder is unclear with no

abnormality in the aldosterone synthase or 11-[beta] hydroxylase genes

identified in the affected subjects.[30] It is associated with marked

hyperaldosteronism, hypokalemia, and significant end-organ damage with a

markedly increased production of several adrenal corticosteroids (greater than

or equal to 1,000 times the normal), three to four times more than sporadic PA

or FH II and 10 times more than FH I. The adrenal gland is strikingly enlarged

(three to six times the normal weight) and demonstrates a diffuse hyperplasia of

the zona fasciculata and atrophy of the zona glomerulosa. FH 3 responds

differently to the dexamethasone suppression test with a paradoxical increase in

aldosterone and a lack of suppression of cortisol. They are resistant to

aggressive antihypertensive therapy including spironolactone and amiloride, and

frequently require bilateral adrenalectomy. "

source:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3230101/?report=printable

> > > > > > > > > > >

> > > > > > > > > > > A K of 3.7 could be a poor blood draw. If they use a

> > > > > > > > tourniquet,, and I have never seen a nurse in an ER or floor NOT

use

> > > > > > > > a tourniquet except for someone who is very brittle or very

> > > > > > > > dehydrated, and usually only after they have tried the

tourniquet

> > > > > > > > first.ÃÆ'‚ And many slap the vein/arm and can be a little

rough about

> > > > > > > > it, falsely increasing the K. When I ask them now, most act like

> > > > > > > > they knew this about elevating K, but you can tell by their look

> > > > > > > > they didn't know this nor were taught this.

> > > > > > > > > > > ÃÆ'‚

> > > > > > > > > > > I had the lab a while back draw my blood and I asked her

not

> > > > > > > > to use a tourniquet due to the potassium - she did anyway saying

she

> > > > > > > > draws it " fast " and so I let her (because the nurses always know

> > > > > > > > more than anyone). ÃÆ'‚ It came back 4.0, I didn't take

my K for a few

> > > > > > > > days and I could tell, absolutely no doubt, that my K was low.

So I

> > > > > > > > started taking it again and felt 100 times better. The lab was

> > > > > > > > wrong. My follow up, after taking the K and with no tourniquet

was 3.4

> > > > > > > > > > >

> > > > > > > > > >

> > > > > > > > >

> > > > > > > >

> > > > > > > >

> > > > > > >

> > > > > >

> > > > >

> > > > >

> > > >

> > >

> >

> >

>