QUESTION:: Hyporeninemia with hypokalemia.   I have a 73 year old gentleman who was found to have elevated potassium on few occasions. He was referred from nephrologist who is managing his hyperkalemia with kayexelate.  He has hypertension 160/90 was on ramipril 10 mg that was stopped by his nephrologist
Feb 2017: eGFR: 80, Na: 144, K: 4.8, Cl: 105, Bicarb: 26, Random cortisol: 339, ACTH: 8.2,  Renin: 1   (5-60 ng/L) Aldosterone: 519 (83-979) pmol/l , renin/aldo ratio: 472.( < 53)
November 2016: HbA1c: 5.9, eGFR: 83, Bicarbonate: 27, Alb/Cr: 0.7, Renin - Upright: <1.0, Aldosterone - Upright: 486 (83-979)pmol/l.
I am not sure what is the cause for these findings. I added amlodipine 5 mg to manage his HTN. Please advise .  Muhammad Z. Shrayyef, MD., ECNU., FACP., FACE, Toronto

RESPONSE:-Aging leads to a decline in kidney structure and function including a reduced GFR and altered renotubular function. If the GFR of 80 in this is accurate, I doubt that there is a major kidney issue. Also, hyperkalemia often is associated with acidosis but here the Bicarb is rather high normal. A thorough medication intake analysis should be performed (Trimethoprim, any prostate meds, etc.), also including over the counter supplements. Apparently, stopping ramipril may have helped given the K of 4.8 which is normal or almost within normal range. Urinary lytes including K and Na would be helpful.

K is a stimulator of aldosterone secretion and the aldosterone measured (in pmol or nmmol?) is not low and perhaps equivalent to 15 ng/dl while renin ?activity is low at 1, providing an Aldo/Renin ratio of 15 (which is considered "normal"). Random cortisol (339 nmol?) appears to be within normal range. Adrenal insufficiency could be excluded if cortisol were exceeding 500 nmol. Secondary adrenal insufficiency usually is not causative of hyperkalemia (as opposed to primary adrenal insufficiency with a lack of mineralocorticoid aldosterone). At this point, I recommend rechecking K in plasma and urine (without hemolysis), thorough analysis of supplement and medication intake, and BP control considering symptoms and cognition/cerebral blood flow. Amlodipine may be fine. Pseudohypoaldosteronism type 2 (familial hyperkalemic hypertension) is unlikely (no acidosis although variable etc).


Kovesdy CP. Updates in hyperkalemia: outcomes and therapeutic strategies. Rev Endocr Metab Disord. 2016 Sep 6. [Epub ahead of print]

Patiromer, which was recently approved for use in the United States, has been shown to be well tolerated and effective for decreasing serum potassium in patients with CKD when taken for up to a year. Sodium zirconium cyclosilicate for which approval is pending has also shown promise in treating both acute and chronic hyperkalemia in patients with CKD. Both medications have been well tolerated with minimal adverse events in relatively short-term follow-up.

Sterns RH, Grieff M, Berstein PL. Treatment of hyperkalemia, something old, something new. Kidney Int 2016;89:546

Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin, sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals, Cary, NC), over 50 years ago. Although clinicians of that era did not have ready access to hemodialysis or loop diuretics, the other tools that we use today-calcium, insulin, and bicarbonate-were well known to them. Currently recommended insulin regimens provide too little insulin to achieve blood levels with a maximal kalemic effect and too little glucose to avoid hypoglycemia. Short-acting insulins have theoretical advantages over regular insulin in patients with severe kidney disease. Although bicarbonate is no longer recommended for acute management, it may be useful in patients with metabolic acidosis or intact kidney function. Kayexalate is not effective as acute therapy, but a new randomized controlled trial suggests that it is effective when given more chronically. Gastrointestinal side effects and safety concerns about Kayexalate remain. New investigational potassium binders are likely to be approved in the coming year. Although there are some concerns about hypomagnesemia and positive calcium balance from patiromer, and sodium overload from ZS-9 (ZS Pharma, Coppell, TX), both agents have been shown to be effective and well tolerated when taken chronically. ZS-9 shows promise in the acute treatment of hyperkalemia and may make it possible to avoid or postpone the most effective therapy, emergency hemodialysis.

Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia despite normal glomerular filtration rate (GFR) and frequently by hypertension. Other associated findings in both children and adults include hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. Aldosterone levels are variable, but are relatively low given the degree of hyperkalemia (elevated serum potassium is a potent stimulus for aldosterone secretion). Hypercalciuria is well described. Treatment: Thiazides

Hope this is useful.  Christian Koch, MD



QUESTION--I am Endotext reader and really like your site which has helped me and thousands for best management of thyroid disorders. I have attached a blood test of a young lady with Type1 DM and Coeliac disease with recent thyrotoxic symptoms and persistently suppressed TSH despite normal FT4 and FT3.She has positive TSH stimulating Ab's and taking 10 mg Carbimazole since Nov till she was referred to me. She feels better but still clinically not euthyroid.
Do you think she might have antibodies direcetd against T3/T4 as well ?I have not asked for uptake scan yet but it might be helpful as ultrasound showed heterogenous echogenecity and lidly increased flow and was not very helpful.I am grateful of your input. Dr Ali Sharafi

RESPONSE- Dear Dr Sharafi--This lady has Graves disease (+ve TRAb) and almost certainly Hashimoto's disease as well as judged by her TPO antibody status.It is not unusual for Patients on carbimazole to retain a supressed TSH for up to 2 years or so while the T4 and T3 are normal.
She needs to stay on the Carbimazole for up to 18 months. I do not think she will have T4 or T3 antibodies.An uptake scan will not be very helpful at this stage. Kind regards, John Lazarus, MD