HyperPP is an autosomal dominant disorder, characterized by episodic muscle weakness

It is caused by mutations in the skeletal muscle Na⁺ channel (α-subunit)

It is generally precipitated by exposure to cold, rest following exercise, high K⁺ intake, or glucocorticoids

Treatment includes β₂-agonists (salbutamol) and acetazolamide (250–750 mg/day)

CKD patients are able to maintain serum [K⁺] near normal until glomerular filtration rate (GFR) is < 20 mL/min. Under certain conditions such as metabolic acidosis or severe tubulointerstitial disease, hyperkalemia develops even under moderate GFR

Some of the causes of hyperkalemia in patients with GFR < 20 mL/min include decreased nephron mass, low lumen-negative voltage in the distal tubule because of low Na⁺ reabsorption via epithelial sodium channel (ENaC), metabolic acidosis, defective renin–aldosterone axis, and concomitant intake of medications that interfere with K⁺ secretion

Treatment includes diuretics, correction of acidosis, and underlying cause of CKD

Autoimmune adrenalitis is the most common cause of Addison disease

Lack of aldosterone is the primary cause of hyperkalemia due to low ENaC activity and lack of lumen-negative voltage

Electrolyte abnormalities besides hyperkalemia include hyponatremia, hyperchloremia, hypobicarbonatemia, and at times hypercalcemia

Patients are hypovolemic because of Na⁺ loss in urine

Plasma renin is high. Aldosterone and cortisol levels are high

Adrenal crisis is a medical emergency

Normal saline and hydrocortisone restore volume and other electrolytes toward normal

Rare disorders of aldosterone deficiency. Glucocorticoid deficiency also occurs

One of the most common disorders of adrenal hyperplasia is caused by the deficiency of 21α-hydroxylase. This enzyme converts progesterone to 11-deoxycorticosterone in the biosynthetic pathway of aldosterone

Affected patients present with salt-wasting, hyponatremia, hyperkalemia, volume depletion, and high renin levels

Treatment in children includes supplementation of fludrocortisones and a glucocorticoid

SHH is a common disorder, which is associated with many disease conditions (Table 16.1)

It is characterized by low renin and aldosterone levels, adequate GFR (CKD stages 2–3), hyperchloremic metabolic acidosis, and hyperkalemia

Volume expansion and associated increase in atrial natriuretic peptide seem to be responsible for low renin and aldosterone levels

Fludrocortisone therapy and discontinuation of the causative agent normalize plasma [K⁺]

PHA I occurs during infancy. It is characterized by salt-wasting, hypovolemia, hyponatremia, hyperkalemia, metabolic acidosis, and normal blood pressure (BP)

Plasma renin and aldosterone levels are elevated

PHA I is inherited as autosomal dominant or autosomal recessive forms

Autosomal Dominant Form: Caused by mutations in the mineralocorticoid receptor. The disease is limited to the kidney. Salt supplementation for 1–3 years and carbenoxolone are recommended to improve electrolyte abnormalities

Autosomal Recessive Form: Caused by mutations in α, β, or γ-subunit of ENaC

Affects multiorgans, including the skin

Treatment includes life-long salt supplementation and K⁺-restricted diet. Carbenoxolone is not helpful

It is an autosomal dominant disease; usually called familial hyperkalemia and hypertension or Gordon syndrome

It is considered a “mirror image” of Gitelman syndrome

It is caused by mutations in the genes that encode WNK family of serine–threonine kinases, WNK1, and WNK4. Both kinases are expressed in the distal nephron

WNK4 downregulates the expression of Na/Cl cotransporter as well as renal outer medullary potassium (ROMK) channel

WNK1 inhibits WNK4 as well as ROMK

When mutations occur in WNK4 or its activity is suppressed by WNK1, NaCl reabsorption is increased in the distal tubule, leading to fluid overload and hypertension. WNK4 mutations further inhibit ROMK channel, causing hyperkalemia

Plasma renin and aldosterone levels are reduced to a variable degree

Thiazide diuretic is the treatment of choice

Check electrocardiogram (EKG), as hyperkalemia is an emergency. If no EKG abnormalities, proceed to step 2

Obtain serum chemistry, osmolality, and complete blood count (CBC)

Establish true hyperkalemia after excluding pseudohyperkalemia and transcellular shift of K⁺

Obtain urine pH, osmolality, urine Na⁺, K⁺, and creatinine

Calculate transtubular potassium concentration gradient (TTKG) (Chap. 3)

Obtain plasma renin and aldosterone levels, as indicated

Use 0.05 mg fludrocortisones orally to differentiate between aldosterone deficiency and aldosterone resistance (Fig. 16.1).