Tag: hypertension

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Great cases on call

I’m running the on-call gauntlet.

I was on call Sat and Sun December 6,7

Sat December 13

Sat and Sun December 20,21

Thursday through Sunday December 25-28

four straight week-ends, with Christmas thrown in for the Jew. Ughh.

That said this week-end has had a few great cases:
  • IgM Cold-agglutinin hemolytic anemia in need of plasmapheresis.
  • Fluconazole induced hyperkalemia
  • Urinary obstruction induced electrogenic type 1 RTA (Hyperkalemic variety of type 1 RTA)
  • Primary hyperaldosteronism induced hypertensive emergency
I’ll elaborate on some (all) of these cases in the next few days.

Happy holidays
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Renal Week 2008: CVD and CKD: Case 7

66 yo woman with ESRD due to analgesic nephropathy. Hx of Crohn’s Disease. Extended criteria deceased donor allograft transplant 1.5 yrs ago.

Now SBP of 160.

Next Speaker Ojo. Greatest name in Nephrology.

CVD and CKD in Transplantation

Progressive reduction of acute rejection since 2000 from 17.4 to 10.3% at one year. This should improve outcome of graft and patient; however post-transplant life-span has decreased from 14 in 1995 to 12.7 in ’06.

CVD is the explanation for this conundrum.

After the first year the most common cause of loss of graft is: death with a functioning graft (56%). This is twice as common as number 2, chronic rejection (21%).

43.5% die of CVD.

Hypertension, DM, hypercholesterolemia, obesity, and anemia are all more prevalent in transplant patients than transplant candidates or prevalent dialysis patients.

Focus on immunosupressant drugs

  • In HIV patients with lower cd4 have higher higher CVD death rate
  • Same relationship of CD4 to CVD is seen in patients with radiation exposure (Hiroshima) causing lower cd4 counts
  • also seen in transplant patients.

Rabbit data showing that increased cholesterol plaques with concurrent CSA, without change in lipid profile. Roselaar jci 1995 96 1389.

Steroids are dangerous even at low doses in the normal population.

CSA increase BP.

CSA also causes endothelial dysfunction.

Sirolimus is antiatherogenic, as seen in cardiac stents.
MMF also appears to reduce cholesterol plaque Romero Atherosclerosis 2000: 152:127-133.

Cr alone is a predictor of CVD independent of immunosupression and traditional risk factors.

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Renal Week 2008: CKD and CVD: Antihypertensive therapy

Case report of a patient with HTN
Ray Townsend is the MC (sweet). He presnts a patient with HTN and modest CKD. Cr 1.4 up from 0.9 in 2001.

Ray passes off to Domenic Sica.

Antihypertensive Drug Therapy in patients with HTN and CKD.

Volume expansion

  • Patient was on 25 mg of HCTZ. No need to change to loop if the patient is euvolemic. Chlorathalidone vs hctz
  • Ernst HTN 2006. chlorathalidone reduced 24hr mean bp more (7 vs 12) non-ckd patients. night time bp drop was even more pronounced 6 vs 13 mmHg.
  • Recommends switch within class from hctz to chlorthalidone
  • the increase in calcium may help with PTH. interesting.
  • elison JCI 83: 113; 1989 images of hypertrophy of DCT with loop diuretics
  • He’s pushing torsemide
  • Using FeNa to determine if patient is responding to loops (look for fena>3%)
  • Why is there variability in bioavailability of furosemide: floculation of pills stops some absorption. Use of liquid furosemide doesn’t help because of only a limited area of absorbtion: early duodenum only.
  • He likes the torsemide

Drug accumulation

At gfr 30-50 need to think about dose adjustment.
Renally cleared: atenolol, nadolol, betaxolol

Hepatically cleared
propanolol, metoprolol, carvedilol

Dose response to beta-blockers is flat in CKD.

Don’t titrate atenolol. It is renally cleared and patients are already retaining the drug before you increase the dose. Though the BP effect is not dose dependent, the adverse effects are.

Aldosteronism

  • 20% of patients with CKD.
  • Likely this patient will have aldo level of 14-20 and renin less than 1
  • Aldosterone antagonists (AA) reduce proteinuria
  • Need diuretic on board to get much BP effect
  • Half-life of spironolactone is 24 hours, in liver disease 120 hours, and in CKD multiple days. These figures include active metabolites. He feels eplerenone is safer because you won’t get accumulation.
  • Consider qod dosing of spironolactone. Consider 12.5 mg qd
  • beware of heparin causing hyperkalemia with AA
  • Similar warning for ACEi, ARB, TMP/SMX

Clonidine

  • in CKD clonidine is renally cleared. This decreases rebound htn by extending the half life
  • initially clonidine has a steep dose responce at low doses but then flattens
  • causes dose dependent volume retension. this is worse with TTS
  • at higher doses the peripheral alpha stimulation will overcome the central reduction in alpha activity so patients get increase in BP. This is seen in clonidine OD or with autonomic dysfunction.

CCB

  • Amlodipine has half-life of 40 hours
  • nifedipine’s half-life goes from 2 to 4 hours in renal failure
  • Edema with CCB is worse in patients with CKD because they already have increased volume

ACEi

  • 10 in the US
  • fosinopril and trandolopril have significant hepatic clearance
  • ARB are not renally excreted
  • dialyzable: captopril, enalepril, lisinopril. Use in overdose.

Statin

  • AUC of simva increases 4 fold with diltiazem
  • Cool case report of a patient on 80 of simva who was admitted for A-fib with RVR and gets started on a diltiazem gtt. He developed rhabdo a few days later.

That’s it. Question time.

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Two Ell

This month I’m attending on the renal ward at Saint John Hospital and Medical Center. I have a huge team: one fellow, one second year resident, three interns (2 categorical and one ER resident) and two medical students. I have been having a blast teaching them.

I am going to track all of the teaching I do this month here.

So far this is the formal (as opposed to bedside) teaching we have done:

Monday June 2: Introduction to Two-Ell
Tuesday June 3: Nephrotic Syndrome
Wednesday June 4: Dialysis basics and Anti-hypertensive agents saves lives
Thursday June 5: Renal Adventures in Imaging (the nephrologic implications of Gadolinium and NFD, phosphate nephropathy as a complication of colonoscopy prep, and contrast nephropathy)

Adventures in Renal Imaging

More to come.

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Patient with a Liddle problem

The Set Up

42 year old African American woman presents with muscle weakness and palpitations. Her blood pressure is 180/110. Her hypertension has been documented since age 16.

Her sister has a history of hypokalemia and hypertension. Three of her six kids, all of which are younger than 20 have hypertension.

Na 144
Cl 96
BUN 14

Photo: Creative Commons/Paleontour

K 2.7
Bicarb 42
Cr 0.8

ABG
pH 7.54
pCO2 51
paO2 97

Step one


What is the primary acid-base disturbance.
pH is elevated, so its an alkalosis. The pH, pCO2 and HCO3 are all going up (same direction) so it is a metabolic condition. Metabolic alkalosis.

Step two


Is compensation appropriate.
To find the target pCO2 add two thirds of the delta bicarb to a normal pCO2 of 40 mmHg.

Her bicarb is 42, and the delta (42 – normal bicarb of 24) = 18.
Two thirds of 18 is 12.
40 + 12 = 52 mmHg.

Actual pCO2 is 51, so we are in the house, pCO2 is appropriate for a serum bicarbonate of 42, no second primary disorder affecting compensation.

Step three


What is the differential of hypokalemia, metabolic alkalosis and abnormal blood pressures?

Hypokalemnia and metabolic alkalosis is an important pattern. The first concept that medical students invariably want to lean on is the intracellular exchange of hydrogen and potassium. When there is hypokalemia, potassium flows from the cells. To maintain electroneutrality hydrogen goes into the cells. The certainly is operating in these cases, however a model that looks at changes in total body potassium is much richer.

The reason that metabolic alkalosis and hypokalemia can walk together is that they both are responces to hyperaldosteronism. The increased aldosteronism can be primary, secondary or unusual.

  • Secondary hyperaldosteronism. Patients with GI losses, diuretics or other causes of volume depletion will upregulate their aldosterone. Aldosterone will fight the volume depletion by reabsorbing sodium in the principle cells, flowing down its concentration gradient through the eNAC. Aldosterone increases the number and activity of the eNAC channels (it also increases the number and activity of the potassium channels and the Na-K-ATPase).
    • Volume deficiency
    • Renal artery stenosis decreases renal blood flow and induces a secondary hyperaldosteronism
  • Primary hyperaldosteronism. This is major cause of hypertension. Patients can have metabolic alkalosis and hypokalemia. If your patient has hypokalemia and alkalosis, definatly pursue primary hyperaldo, but do not rule out primary hyperaldo if you don’t have the electrolyte abnormality. Most patients with pimary hyperaldo do not have the typical electrolytes.
  • Unusual: one conditions to remember that cause metabolic alkalosis and hypokalemia:
    • Liddle syndrome. Patients have a mutation at 16p12 that encode the beta and gamma subunits of the eNAC. The eNAC is no longer sodium selective and is always open. The sodium reabsorption causes hypertension. The eNAC channel also increases potassium and hydrogen secretion.
    • The functional opposite of Liddle syndrome is Pseudohypoaldosteronism type 1. Here mutations to the alpha, beta or gamma subunits results in resistance to the effects of aldosterone. Patient have sodium wasting and hyperkalemia. There is an autosomal recessive and autosomal dominant form.
    • Licorice and SAME (Syndrome of Apparent Mineralocorticoid Excess) The structure of cortisol and aldosterone are almost identical and the mineralocorticoid receptors in the principle cells are unable to differentiate between these molecules. This means that cortisol can activate the mineralocorticoid receptors. This is made worse by the fact that cortisol typically is found at concentrations a 1000-fold higher than aldosterone. To prevent cortisol from acivating the mineralocorticoid receptors, cortisol is rapidly metabolised by 11-beta-hydoxysteroid dehydrogenase. If this enzyme is absent (SAME) or inhibited (licorice ingestion) you can get wildly up-regulated mineralocorticoid activity with simultaneous suppression of aldosterone.
  1. Sodium is reabsorbed through the ENaC. Sodium moves
    down its concentration gradient.
  2. The movement of sodium is electrogenic and results in
    a negative charge in the tubule.
  3. Chloride in the tubule can be reabsorbed paracellularly.
    The more chloride that is reabsorbed the less potassium
    is secreted.
  4. Potassium flows down an electrical and chemical gradient into the tubule.

Step four


The family history shows first degree relatives with a similar condition. This suggestes autosomal dominant transmission. This is consistant with Liddle syndrome.

Step five

Next steps in the diagnosis. Though the genetics are suggestive of autosomal dominant transmission, Liddle Syndrome is very uncommon while primary hyperaldosteronism is relatively common. A serum aldosterone level will separate these patients neatly. In Liddle Syndrome the aldosterone is suppressed, while in primary hyperaldosteronism it is up regulated. Genetic testing is available to confirm the diagnosis.

See these posts at the Renal Fellow Network for additional information.