Case Study 1
A 6-year-old boy with mild chronic renal failure is started on a low-sodium diet for hypertension. Two weeks later, he notices that he is unable to lift himself out of a chair. On physical examination, slightly decreased skin turgor and marked proximal muscle weakness are found. Blood pressure was 112/68 mmHg. The electrocardiograph (ECG) reveals peaked T waves and some widening of the P wave and QRS complex. The following blood test results are obtained: Sodium 130 mmol/L, potassium 9.8 mmol/L, chloride 98 mmol/L, bicarbonate 17 mmol/L, creatinine 2.7 mg/dL, and arterial pH 7.32.
What are the most likely factors responsible for the hyperkalemia and how would you treat the hyperkalemia?
Increased potassium intake
Hyperkalemic distal renal tubular acidosis (RTA-4)
The correct answer is B
Comment: The underlying renal insufficiency, superimposed volume depletion (due to sodium wasting after the acute institution of a low-sodium diet), and metabolic acidosis may all play a contributory role. However, many patients have these problems without life-threatening hyperkalemia. Therefore, the patient should be questioned about increased potassium intake; this patient gave a history of using large quantities of potassium chloride (KCl)-containing salt substitute.
The patient has both severe muscle weakness and electrocardiographic changes. By definition, pseudohyperkalemia produces no symptoms or signs of potassium intoxication. Therefore, therapy should be initiated with calcium gluconate, followed by glucose, insulin, and sodium bicarbonate to temporarily drive potassium into the cells. For example, 500 mL of 10% dextrose in saline plus 10 units of regular insulin plus 45 mmol of sodium bicarbonate infused over 30 minutes will lower the plasma potassium concentration, raise the plasma sodium concentration, and produce volume expansion. Sodium polystyrene sulfonate should be given orally and repeated as necessary to remove the excess potassium. Dialysis will not be required since the patient does not have severe renal failure.
Case Study 2
A 14-year-old man with no prior medical history complains of chronic fatigue. The positive physical findings include a blood pressure of 100/60 mmHg and increased skin pigmentation. The skin turgor is relatively normal. The laboratory data are as follows: Serum sodium 130 mmol/L, potassium 6.8 mmol/L, Chloride 100 mmol/L, bicarbonate 20 mmol/L, glucose 90 mg/dL, osmolality 275 mOsm/kg, BUN 28 mg/dL, and creatinine 1.2 mg/dL, Urine sodium 50 mmol/L, potassium 34 mmol/L, osmolality 550 mOsm/kg. The electrocardiogram (EEG) shows mild peaking of the T waves in the precordial leads. An infusion of glucose and insulin in appropriate proportions results in an episode of hypoglycemia.
What is the most likely diagnosis and how would you treat this patient?
Chronic kidney disease
Primary adrenal insufficiency
Acute renal failure
The correct answer is B
Comment: By definition, patients with chronic hyperkalemia have a defect in renal potassium excretion, since normal subjects would rapidly excrete the excess potassium in the urine. Thus, the urine potassium concentration of 34 mmol/L is inappropriately low.
The transtubular potassium gradient (TTKG) can be calculated in this patient to assess the degree of aldosterone effect:
The TTKG is low in this patient, a finding that is consistent with some form of mineralocorticoid deficiency or resistance.
The findings of low blood pressure, increased skin pigmentation, a low TTKG, and hypoglycemia after the administration of glucose and insulin all point to the probable diagnosis of primary adrenal insufficiency.
Acutely, sodium polystyrene sulfonate can be given to lower the plasma K + concentration. Chronically, both glucocorticoid and mineralocorticoid replacement will be required because of the persistent adrenal dysfunction.
Case Study 3
A 16-year-old female was admitted for the management of elevated blood pressure. Past medical history was uneventful except for a history of chronic kidney disease secondary to recurrent urinary tract infections diagnosed at 2 years of age. Physical examination on admission revealed a well-nourished and developed adolescent female. She weighed 55 kg and was 157 cm tall. The blood pressure was 148/92 mmHg, pulse 81 beats/min, and respiratory rate 19 breaths/min. Chest was clear to auscultation and percussion. Examination of the eyes, ears, nose, and throat was unremarkable. The remaining physical examination was also normal.
Laboratory investigation on admission showed serum sodium 138 mmol/L, potassium 4.0 mmol/L, chloride 106 mmol/L, bicarbonate 25 mmol/L, BUN 31 mg/dL, and creatinine 1.2 mg/dL. The estimated glomerular filtration rate (eGFR) was 67 mL/min/1.73 m 2 . Urinalysis revealed a pH of 6.0, specific gravity 1.015, 2 + protein and small blood.
Treatment with enalapril (5 mg twice daily) was initiated. After 2 weeks of antihypertensive therapy the blood pressure fell to 128/81 mmHg. A repeat of serum electrolytes at this time showed serum sodium 141 mmol/L, potassium 5.9 mmol/L, chloride 110 mmol/L, total carbon dioxide 26 mmol/L, BUN 38 mg/dL, and serum creatinine concentration 1.5 mg/dL (GFR 54.3 mL/min/1.73 m 2 ).
Which ONE of the following statements is TRUE regarding this patient condition?
She is likely to have bilateral renal artery stenosis and should be evaluated
The angiotensin converting enzyme inhibition (ACEI) should be stopped because of hyperkalemia and the worsening renal function
Stopping ACE inhibitor is a mistake because of long-term benefits on protection against the progression of renal disease
An angiotensin-converting blocker (ARB) should be substituted for ACE inhibitor because it may not affect serum creatinine values
The correct answer is B
Comment: Inhibition of renin-angiotensin system (RAS) by either ACEI or ARB slows the progression of renal disease in patients with preexisting renal insufficiency. The patient’s serum creatinine returned to levels not different from baseline after the 6 weeks of ACEI therapy and remained unchanged during a 2-year follow-up, an observation that supports the notion that the initial rise in serum creatinine is not only reversible but the rate of progression of renal disease can be retarded despite prolonged use of ACEI. Answer A should be considered in individuals when a rise in serum creatinine is 30% or greater above baseline or in patients with decreased effective circulating volume in whom rehydration has not reduced serum creatinine to baseline values within a few weeks. Answer B is incorrect because the initial rise in serum creatinine associated with ACEI use is reversible and stabilizes to baseline values within 2 to 4 weeks of therapy. Withdrawal of an ACEI should occur only when the rise in serum creatinine is greater than 30% above baseline value with the first 8 weeks of ACEI therapy. Answer D is also incorrect. The transient rise in serum creatinine levels has been reported with both ACEI and ARB. Answer E is wrong. Blood pressure reduction clearly slows renal disease progression. Furthermore, many clinical trials demonstrate additional protection against progression of renal disease when ACEI or ARB are used as an antihypertensive medication. The patient’s prognosis for adverse renal outcomes would be better with controlled blood pressure than those whose blood pressure has not been adequately controlled.
Case Study 4
A 7-year-old girl with Rett syndrome (RS) was referred to the nephrology service for evaluation of persistent metabolic acidosis. She was the first child of unrelated healthy parents, born at 38 weeks’ gestation, and with a birth weight of 3.0 kg (75th percentile), length 50.2 cm (75th percentile), and head circumference 39 cm (50th percentile). The neonatal period was uneventful. The family history was unremarkable. She grew normally until the age of 9 months, when she was found to have failure to thrive, developmental delay, and hypotonia. She was diagnosed with RS at 2 years of age, following an investigation for seizures complicated by gross motor dysfunction, hand wringing, decelerated head growth, loss of speech, and periodic breathing. She was treated with oxcarbazepine (Trileptal) oral suspension 900 mg daily for seizure control. On examination at 7-years of age, her weight was 18.2 kg, height was 112 cm (both below the 3rd percentile), and head circumference was 47 cm (below the 2nd percentile). Her temperature was 37.0°C, pulse 103 beats/min, respirations 22 breaths/min and blood pressure 94/69 mmHg. There was no clinical evidence of dehydration. Her craniofacial appearance was normal. The lungs were clear to auscultation bilaterally. Her heart had normal sinus rhythm without a murmur. Her abdomen was soft without masses or organomegaly. No rashes or edema were noted. Genital examination findings were normal. On neurological examination, she clearly had significant delay for age. She had limited vocalization. She was unable to sit, creep, or crawl. She exhibited stereotypical hand movements, including alternate opening and closing of the fingers, and twisting of wrists and arms were noted. Her pupils had normal reaction to light. She did not fix or follow. Her facial movements were symmetric, and she did not drool. There was no arching. Her tendon reflexes were 2 + and normal.
Initial laboratory studies revealed serum sodium 139 mmol/L, potassium 5.8 mmol/L, chloride 111 mmol/L, bicarbonate 18 mmol/L, blood urea nitrogen was 7.0 mg/dL, creatinine 0.3 mg/dL, glucose 88 mg/dL, calcium 9.2 mg/dL phosphate 5.3 mg/dL alkaline phosphatase 232 U/L, cortisol 8.8 ng/L, aldosterone 17 ng/dL, and plasma renin activity 1.9 ng/mL/h. White cell count was 4200 with 75% neutrophils. Hemoglobin was 13.1 g/dL hematocrit 40% and platelet count was 275,000. Urinalysis showed a pH of 7.0, specific gravity of 1.014, negative dipstick test result for protein, and blood with unremarkable features on microscopy. The urine culture was sterile. Urine anion gap was positive (Na + + K + ) − (Cl − )=10 mmol/L, fractional excretion of Na + and K + were 0.6% and 4.6%, respectively. Renal ultrasound results were normal. MRI of the brain and spinal canal showed normal findings.
Alkaline therapy with sodium bicarbonate (35 mEq orally, daily for 10 days) failed to lower urine pH below 5.5 or to increase potassium excretion. Therapy with hydrochlorothiazide (HCT), 25 mg orally, daily for 7 days resulted in a fall in urine pH below 5.5, an increase in potassium excretion, and the complete resolution of acidosis. The effect of therapy was remarkable in that the child’s weight and length increased by 1.3 kg and 2.0 cm, respectively, in the following 4 months, exceeding the 3rd percentile weight and height values on the growth chart.
What is the MOST likely diagnosis?
Hyperkalemia distal renal tubular acidosis associated with Rett syndrome
Hyperkalemia related to adrenal insufficiency
Hyperkalemia related to chronic kidney disease
The correct answer is A
Comment: This patient had the classic phenotype of Rett, including normal early development followed by loss of purposeful use of hands, distinctive hand movements, slow head growth, apraxia, seizures, periodic apnea, and mental retardation. The finding of hyperchloremic metabolic acidosis in the presence of normal glomerular function suggests the diagnosis of renal tubular acidosis (RTA). The finding of urinary pH above 5.5 and positive urinary anion gap during acidosis, combined with hyperkalemia, suggests the presence of hyperkalemic distal RTA.
The cause of hyperkalemic distal RTA includes disorders that affect adrenal aldosterone synthesis, the renal response to aldosterone, and a voltage-dependent type of derangement in the distal nephron. The normal values for cortisol, plasma renin activity (PRA) and plasma aldosterone levels in this patient exclude hypoaldosteronism as the cause of impaired urinary acidification. Furthermore, therapy with sodium bicarbonate failed to lower urine pH below 5.5 or increase potassium excretion. Administration of HCT resulted in a fall in urine pH below 5.5 and an increase in urine potassium excretion to normal, suggesting that a voltage-dependent defect, rather than aldosterone deficiency, was responsible for the altered urinary acidification observed in our patient.
Case Study 5
A 4-month-old former term female infant born to a 36-year-old healthy mother was admitted to the hospital for evaluation and management of right neck abscess and cellulitis. Outpatient treatment, including an incision and drainage done in clinic the day prior and two doses of oral antibiotics, resulted in no improvement. Past medical and surgical history was unremarkable. Family history was significant for an unspecified seizure and movement disorder in her older sister. She had appropriate growth for her age, with weight, length, and head circumference all measuring around the 20th percentile. Vitals were unremarkable on presentation, and she remained normotensive during her stay at the hospital. Exam was within normal limits, aside from erythema and induration consistent with her abscess.
Initial blood chemistry panel showed an alarmingly high potassium level of 8.4 mmol/L with slight hemolysis (normal for age is 4.1 to 5.3) with repeat of 7.3 without hemolysis. She had a low bicarbonate level of 10 mmol/L (normal for age is 19 to 24), high chloride level of 116 mmol/L (normal for age is 97 to 108), and elevated creatinine of 0.56 mg/dL (normal for age is 0.2 to 0.4). Anion gap was normal at 10 mmol/L. No electrocardiogram changes were noted. She was promptly transferred to the pediatric intensive care unit for care of her abscess and these incidental findings of hyperkalemia and non-gap metabolic acidosis. Intravenous calcium gluconate, sodium acetate, and Kayexalate (sodium polystyrene sulfonate) were given for hyperkalemia. The following morning, her potassium normalized to 5.8 mEq/L and then further to 4.7 mmol/L. Her bicarbonate level improved to 20 mmol/L, and her serum creatinine improved to 0.19 mg/dL. Renal ultrasound revealed no abnormalities.
After transfer to the general pediatrics floor, she again developed hyperkalemia of 7.5 mmol/L and non-gap metabolic acidosis. A subsequent dose of Kayexalate was given. Additional lab work revealed urine potassium of 15 mmol/L, urine sodium of 90 mmol/L, and urine chloride of 65 mmol/L, resulting in a positive urine anion gap of 40 mmol/L. She had a normal serum aldosterone level of 22 ng/L (normal for age is 6 to 89) but low renin activity of 0.2 ng/mL/h (normal for age is 2 to 37). Her hyperkalemia and metabolic acidosis were treated with fludrocortisone, high dose sodium citrate/citric acid, and kayexalate. During the hospital admission, the patient’s abscess significantly improved after repeat incision and drainage and intravenous antibiotics. The family was discharged home with oral antibiotics, fludrocortisone, sodium citrate/citric acid, and Kayexalate with close nephrology follow-up.
What is the MOST likely diagnosis and how would you treat it?
Renal tubular acidosis type 4 (RTA-4)
Primary adrenal insufficiency
The correct answer is C
Comment: This patient had severe recurrent hyperkalemia, hyperchloremic metabolic acidosis, and positive urine anion gap in a setting of low plasma renin and aldosterone levels. RTA-4 was suspected. Differential diagnosis of RTH-4 in children includes sequelae to critical illness, such as obstructive nephropathy, interstitial nephritis, diabetic nephropathy, primary adrenal insufficiency, or medications such as NSAIDs or ACE inhibitors. Our patient had no history of failure to thrive or significant medical history, so likelihood of RTA-4 secondary to chronic conditions or medications was unlikely.
To elucidate whether she may have possible PHA, a genetic analysis was performed and revealed a de novo heterozygous c.1376A greater than T (p. K459M) likely pathogenic variant in the Cullin 3 ( CUL3 ) gene consistent with type PHP (PHA-II). This explained the low renin, hyperchloremia, severe hyperkalemia, and metabolic acidosis.
PHA-I and PHA-II are exceedingly rare genetic disorders that are caused by aldosterone resistance or reduced aldosterone production, respectively. When PHA-I occurs, patients often present with sodium wasting, hypovolemia, metabolic acidosis, and hyperkalemia in the neonatal period. PHA-II presents with hyperkalemia and hypertension in variable ages of patients, though most cases have been reported in adolescence or young adulthood. Severe hypertension tends to develop later in life in the majority of cases.
The mainstay of treatment for PHA type II is thiazide diuretic, which quickly corrects metabolic abnormalities and hypertension within 1 week. In general, dosing is titrated to normalization of blood pressure. Prognosis is good on thiazide treatment. Most patients do not have long-term sequelae as long as vitals are closely monitored over time.
This patient was treated with fludrocortisone, sodium citrate/citric acid, and Kayexalate after hospital discharge. She maintained relatively stable electrolytes on this regimen, but medication dosage adjustments were frequently needed. She was promptly started on hydrochlorothiazide after genetic results confirmed PHA type II. Her other medications were weaned rapidly. To date, her blood pressure measurements have remained within normal range for age, and she is meeting all growth milestones.
Case Study 6
An 8-day-old male baby presented to our emergency unit with lethargy and poor feeding and reduced urine output since 3 days. He was a second born child of a third-degree consanguineous marriage, born at term with a birth weight of 1.8 kg with no history of significant perinatal events. However, a history of sibling death following a similar illness at day 15 of life was reported.
On examination, the child was dehydrated, the skin was mottled, and peripheral pulses were weak. The child was in shock and had a convulsion while in the emergency department. He received saline boluses and supportive management was instituted, while his investigations were awaited. He had severe respiratory distress due to pneumonia for which he required mechanical ventilation and inotropes were started for shock. Intravenous antibiotics were started in view of positive screen for sepsis. His serum potassium was 11.9 mmol/L at admission and serum sodium was 119 mmol/L. Blood urea was 78.42 mg/dL and serum creatinine was 1.41 mg/dL initially, which was subsequently documented normal (23 mg/dL, 0.4 mg/dL respectively). In view of severe hyperkalemia, he was started on peritoneal dialysis (PD) along with supportive management with sodium bicarbonate, salbutamol nebulization and potassium binding resins through nasogastric tube.
The infant improved after supportive management for sepsis and was off inotropes after 48 hours of admission. His potassium improved after 12 hours of PD (K + = 3.7 mEq/L), after which PD was stopped. Forty-eight hours later, the child was weaned off the ventilator, but he again developed hyperkalemia (serum potassium of 9.6 mmol/L) and hyponatremia (serum sodium of 114 mmol/L) and PD had to be instituted again. The child developed a skin rash (miliaria rubra) the following day which improved a week later and during his prolonged course of stay in the hospital he developed pneumonia, which again required him to be ventilated for 7 days. During his hospital stay, the child required a total of eight PD sessions, each time owing to uncontrollable hyperkalemia.
Additional laboratory studies revealed serum cortisol 15.94 μg/dL (reference: 2 to 11 μg/dL); 17–OH progesterone 8.13 ng/dL (reference: 3 to 90 ng/dL); aldosterone 171.1 ng/dL (reference: 2.52 to 39.2 ng/dL); and renin 6.11 ng/mL (reference: 0.15 to 2.33 ng/mL).
What is the cause of hyperkalemia in this neonate?
Sepsis-induced acute kidney injury
Congenital adrenal hyperplasia
Type 4 renal tubular acidosis (RTA-4)
Hereditary pseudohypoaldosteronism type-I (PHA-I)
The correct answer is D
Comment: The first differential considered was late onset sepsis with acute kidney injury (AKI) and electrolyte abnormalities. Since this newborn had hyperkalemia with hyponatremia, out of proportion to his AKI and sepsis, congenital adrenal hyperplasia (CAH-salt wasting type) was also considered. CAH due to 21-hydroxylase deficiency leads to decreased cortisol and aldosterone, which may present clinically like aldosterone resistance. In girls, virilization may be seen while in boys only increased pigmentation may be noted, which was absent in this child. Other inborn errors of metabolism and pseudo-hypoaldosteronism (PHA) (primary or secondary) were also considered as rare differentials. Secondary/transient type 1 PHA occurs in the setting of obstructive urinary tract malformation or a urinary tract infection and usually gets corrected after adequate fluid resuscitation and management of infections, while other types of PHA are genetically mediated disorders of tubular transport of potassium and sodium. Type 4 renal tubular acidosis (RTA) and was also considered in view of deranged renal functions and hyperkalemia, but it occurs in setting of obstructive uropathy or diabetic nephropathy, which were absent in the child.
Sepsis induced AKI as a primary cause for his illness was ruled out as the child continued to have severe hyperkalemia despite improvement in sepsis and initial resuscitation. CAH was ruled out as serum cortisol level was elevated and 17–OH progesterone was suppressed. Serum ammonia, lactate, and blood sugar were normal, which ruled against inborn errors of metabolism.
RTA type 4 and secondary or transient PHA was also ruled out as renal dysfunction improved after correcting the initial shock and fluid bolus, and ultrasound of kidneys and urinary tract did not reveal any obstructive pathology.
Serum aldosterone and renin activity were normal. When both elevated, favoring a diagnosis of PHA, likely of genetic etiology as secondary and transient forms were ruled out.
Among the various types of PHA that are described, the PHA type 1 may be (a) systemic/multiple site form or (b) renal limited. The former occurs due to defects in epithelial sodium channel (ENaC) or defective mineralocorticoid receptor at multiple sites. Since the ENaC is expressed in all epithelial tissues, it is associated with widespread systemic manifestations such as pulmonary infections. One may find a high sweat or salivary sodium level, which provides a clue to multisystem involvement. This helps to differentiate it from the renal limited form, which occurs due to defects in receptors for mineralocorticoid on tubular epithelial cells.
Since our patient had skin as well as respiratory system infections, the possibility of type 1 autosomal recessive variant of PHA was considered, which could be confirmed further by performing a genetic analysis.
PHA occurs due to renal tubular unresponsiveness to the action of aldosterone. Aldosterone acts on the aldosterone receptor and then through nuclear transcription pathways and increases the activity of basolateral Na + /K + adenosine triphosphate (ATP)ase, luminal expression of epithelial sodium channel (ENaC) and the activity of luminal renal outer medullary potassium (ROMK) channels. A defective mineralocorticoid receptor function or a failure of ENaC would lead to sodium wasting and failure of potassium excretion.
Multiple site type 1 PHA (ar-PHA1) is inherited as an autosomal recessive trait due to mutations in SCNN1A located in 12p13.31, SCNN1B , and SCNN1G , both situated in the locus 16p12.2. Each of these three genes is responsible for making one of the subunits of the ENaC protein complex. When homologous mutations are introduced into alpha, beta, or gamma subunits of ENaC, they all bring about a change in sodium channel gating, causing a reduction in sodium channel opening probability.
Renal form (ad-PHA1) shows autosomal dominant inheritance and is due to heterozygous mutation of NR3C2 located at 4q31.1, which is responsible for making the mineralocorticoid receptor protein. Various mutations have been described worldwide in coding regions of ENaC subunit genes. Most of these cases are attributed to mutations in the alpha subunit gene ( SCNN1A ). In the present case, a known homozygous mutation in the SCNN1B gene was identified, which is relatively uncommon, as well as a new variant.
In the acute phase of illness, the child may require adequate fluid resuscitation, supportive measures for hyperkalemia and even transient dialysis for management of refractory hyperkalemia. For AD-PHA, only sodium supplementation may be required that generally becomes unnecessary by 3 years of age, which may be due to maturation of renal salt conserving ability. In children with AR-PHA, management entails lifelong salt supplementation and intensive monitoring for management of systemic features like respiratory complications. The requirement of sodium may sometimes be very high, reaching up to 15 to 20 g a day. A diet low in potassium or measures to reduce potassium content of foods should be instituted for every child. The use of potassium binding resins, like sodium polystyrene, helps to excrete large amounts of potassium. In refractory cases, indomethacin may be used to reduce loss of sodium in urine, as it helps inhibit prostaglandin synthesis. Though fludrocortisone is effective in congenital adrenal hyperplasia, the same is not true for PHA as the defective ENaC channel causes resistance to both aldosterone and fludrocortisone.
Case Study 7
A 13-year-old girl was admitted with a history of periorbital edema for 10 days and intermittent fever and arthralgia of 6 months duration. She had been diagnosed with urinary tract infection several times before her admission based on the presence of leukocytes in her urine. There was no history of drug intake, facial rash, or joint pains. Her weight and height were within normal ranges. Vital signs, including blood pressure (BP), were normal. Physical examination was remarkable for periorbital edema. There were no signs of oral ulcer, rash, lymphadenopathy, or joint swelling.
The laboratory results on admission were as follows: hemoglobin, 10.7 g/dL, total white blood cell count 4500/mm 3 , lymphocyte count 1000/mm 3 , platelet count 127,000/mm 3 , erythrocyte sedimentation rate 102 mm/h, sodium 130 mmol/L, potassium 6.7 mmol/L, chloride 111 mmol/L, bicarbonate, 16.8 mEq/L, blood urea nitrogen 25 mg/dL, creatinine 1.42 mg/dL, total protein 6 g/dL, albumin, 2.6 g/dL. Venous pH was 7.31, pCO 2 34.5 mmHg, base excess −8 mEq/L. The anion gap was calculated to be 13. Urinalysis revealed a pH of 5.5, protein of 250 mg/dL, and 10 to 15 red blood cells. The 24-hour urinary protein excretion was 113 mg/m 2 /h, and creatinine clearance was positive. The antinuclear antibody (ANA) titer was 1:320, and the antinative DNA antibody titer was negative. Serum complement levels were low; with a C3 of 0.18 (normal 0.8 to 2) g/L and a C4 of 0.06 (normal 0.15 to 0.5) g/L. Anti-cardiolipin immunoglobulin G (IgG) and IgM were 92 (normal 0 to 10) and 300 (normal 0 to 18) g/L, respectively.
She was diagnosed with systemic lupus erythematous (SLE) according to the American College of Rheumatology criteria, based on Coombs test-positive anemia, thrombocytopenia, nephrotic syndrome, positive ANA, and positive anticardiolipin antibody. Renal biopsy revealed severe diffuse proliferative glomerulonephritis (Renal Pathology Society/International Society of Nephrology World Health Organization class IV). There was also severe interstitial mononuclear cell infiltration and widespread tubulitis. While she was being investigated for hyperkalemia and metabolic acidosis, intravenous methylprednisolone therapy (1 g daily) was given for 3 days, along with sodium bicarbonate and calcium polystyrene sulfonate. This was followed by treatment with prednisone and oral cyclophosphamide 2 mg/kg for 3 months. Her condition improved remarkably, and her renal function and proteinuria remained normal at the 1-month follow-up clinic visit. Admission laboratory values were sodium 130 mEq/L, potassium 6.7 mEq/L, chloride 111 mEq/L, creatinine 1.4 mg/dL, blood pH 7.31, bicarbonate 16.8 mEq/L, urine pH 5.5, urine sodium 88 mEq/L, urine potassium 43 mEq/L, urine osmolality 360 mOsm/kg, and plasma osmolality 280 mOsm/kg.
What is the MOST likely diagnosis?
Hyperkalemic renal tubular acidosis (RTA-4)
Congenital adrenal hyperplasia
The correct answer is B
Comment: Our patient initially presented with lupus nephritis and hyperkalemia, with a normal anion gap and hyperchloremic metabolic acidosis. A wide range of conditions has to be taken into account in the differential diagnosis for hyperkalemia. Based on our patient’s laboratory findings, acute renal failure, drugs, blood transfusion and hemolysis were ruled out. Persistent hyperkalemia and normal anion gap metabolic acidosis led us to suspect the presence of type 4 RTA. This is included in the general classification of RTA as its cardinal feature is hyperkalemia with a mild (normal anion gap) metabolic acidosis and normal measured urinary acidification.
Unlike distal RTA, in which proton secretion is defective, causing high urine pH, the main defect in type 4 RTA is transport abnormality of the distal tubule, which is secondary to aldosterone deficiency, resistance, or inhibition. The primary effect of aldosterone on the collecting duct is to stimulate sodium reabsorption and potassium secretion in principle cells, which results in an increase in the negative electrical potential of the lumen, promoting proton secretion. Aldosterone also directly affects the alpha intercalated cells to promote proton secretion by upregulating the expression of the proton ATPase as well as carbonic anhydrase. Thus, patients who are aldosterone deficient or resistant to aldosterone have increased sodium excretion. Our patient also had mildly increased of sodium excretion.
The preferred method to estimate potassium excretion by the distal tubule is the TTKG. Our patient’s TTKG was 5 in the presence of hyperkalemia (normal > 10), which indicates a defect in potassium secretion. A low TTKG is associated with aldosterone deficiency or resistance. The renin activity was 2.3 (5 to 27.8) pg/mL and the aldosterone level was 10 (reference: 13 to 34 pg/L) in the presence of high plasma levels of potassium. She appeared to have two distinct disorders, namely, renin–aldosterone deficiency or hyperkalemic distal RTA. Her urine pH was 5.5 when the blood pH was 7.3, and the HCO 3 − was 16.8 mEq/L, which are suggestive of hyporeninemic hypoaldosteronism (type 4 RTA).
Type 4 RTA is the most common form of renal tubular acidosis and occurs in various disorders. The most common causes of hyporeninemic hypoaldosteronism include diabetic nephropathy, tubulointerstitial disease and, in particular, interstitial nephritis associated with non-steroidal anti-inflammatory drugs (NSAIDs). Other causes in which hypoaldosteronism is present but not matched by hyporeninism include adrenal destruction (whether surgical, malignant, or hemorrhagic), Addison disease, angiotensin converting enzyme inhibitor therapy or angiotensin receptor blockade, and the inhibition of aldosterone synthesis by heparin. Our patient was investigated for the other causes of hyperkalemic RTA (diabetes, monoclonal gammopathies, NSAIDs), which were all ruled out.
Since our patient had a low renin level, other causes, which are characterized by hypoaldosteronism, such as primary hypoaldosteronism, congenital adrenal hyperplasia, and Addison disease, were ruled out. Within 3 days our patient showed a dramatic response to steroid treatment, with a normal potassium level. After treatment of lupus nephritis with prednisolone, plasma renin activity and plasma aldosterone concentration were elevated.
Case Study 8
A male infant presented with recurrent episodes of hyperkalemia and acidosis since birth. He was born by normal vaginal delivery at term weighing 2.7 kg (9th percentile) with a head circumference of 33 cm (9th percentile) to a mother with a known history of alcohol abuse. There were no perinatal problems. Mother’s antenatal ultrasound scan at 20 weeks’ gestation did not identify any fetal abnormalities.
At 1 month of age, the boy was admitted to the local hospital with a week’s history of “funny spells,” where he had extensor posturing of his trunk and limbs and cried out. These lasted for 2 to 3 minutes at a time. There was no apparent relationship to feeding or passing bowel motions. On examination, the child was noted to be thriving, with a weight of 3.29 kg (2nd percentile), a head circumference of 36 cm (9th percentile), and a length of 52 cm (9th percentile). Blood pressure was 78/52 mmHg. Clinical examination was unremarkable. He was not dehydrated on clinical assessment. The external genitalia appeared normal.
Initial blood investigations (performed by venipuncture) showed serum potassium 7 mmol/L, sodium 135 mmol/L, chloride 112 mmol/L, bicarbonate 19 mmol/L, urea 2.1 mmol/L, and creatinine 0.3 mg/dL. The complete blood count showed normal hemoglobin, white blood cell and platelet values. Liver function tests were within normal limits. Calcium, phosphate, and magnesium were within the normal range. Serum ammonia, lactate and creatinine kinase were normal. Capillary blood gas showed a mild metabolic acidosis with a base deficit of 5.2 mmol/L.
A working diagnosis of sepsis was originally considered, and he was treated with antibiotics intravenously. A complete septic screen was negative. Cerebrospinal fluid (CSF) lactate, plasma, and CSF amino acids; random cortisol; thyroid function tests; and 17-hydroxyprogesterone were all within the normal range. Serum aldosterone was entirely normal for age at 454 pmol/L (reference: 300 to 1500 pmol/L). Plasma renin activity was low at less than 0.2 mmol/L/h (reference: 1.1 to 2.7 nmol/L/h). Urinary potassium was 10 mmol/L; urine osmolality 151 mOsm/kg and plasma osmolality 290 mOsm/kg Urinary screen for drugs and toxins was negative. An ultrasound scan of the renal tract demonstrated two normal kidneys with no evidence of hydronephrosis or hydroureter.
The child had a trial of sodium bicarbonate, fludrocortisone, and calcium at 2 months of age. However, these were not sufficient to correct the hyperkalemia, which at this stage was associated with poor weight gain (3.7 kg). He was then commenced on low-potassium-containing milk. This corrected the hyperkalemia. He was discharged home with serum potassium 3.8 mmol/L, sodium 139 mmol/L, chloride 100 mmol/L, urea 12 mg/dL, and creatinine 0.3 mg/dL.
What is the MOST likely cause of hyperkalemia in this infant?
Acute renal failure
Congenital adrenal hyperplasia
The correct answer is A
Comment: The child has presented in infancy with hyperkalemia associated with a hyperchloremic metabolic acidosis and a normal anion gap of 11 (normal 10 to 14). His estimated glomerular filtration rate (eGFR) is normal. Hyperkalemia in the presence of eGFR greater than 15 mL/min/1.73 m 2 is generally due to aldosterone deficiency or aldosterone resistance in the distal nephron.
A variety of conditions can be associated with aldosterone deficiency or aldosterone resistance in the distal nephron including pseudohypoaldosteronism type 1 and type 2, systemic lupus erythematous, amyloidosis, obstructive uropathy, sickle cell nephropathy and drugs such as potassium sparing diuretics and pentamidine.
Our patient had a reduced transtubular potassium gradient (TTKG) [Urine K + × Plasma osm]/Urine osm × Plasma K + ] of 2.7 in the presence of hyperkalemia (normal range in infants 4.9 to 15.5), suggesting aldosterone deficiency or end organ resistance. The differential diagnosis would thus include congenital adrenal hyperplasia or hypoplasia, hypoaldosteronism or insensitivity to aldosterone.
In view of the early presentation and the fact the infant was not on any medication and in the presence of a normal serum aldosterone makes end-organ resistance to this mineralocorticoid the most likely cause.
Type I PHA reflects the apparent lack of aldosterone effect on sodium reabsorption and potassium secretion and thus features hypotension and hyperkalemia. These children have renal salt wasting and often have hyponatremia. Plasma renin levels are elevated, as are plasma levels of aldosterone. The latter finding, as well as the lack of response to mineralocorticoid replacement therapy, differentiates them from infants with selective aldosterone deficiency that otherwise have a similar constellation of clinical findings. There are autosomal dominant and autosomal recessive forms of this disease, caused by mutations of the mineralocorticoid receptor and epithelial Na + channel (ENaC), respectively. Therapy with salt supplementation is effective in treating both the salt depletion and the hyperkalemia. As in other instances of mineralocorticoid deficiency, volume contraction with decreased distal delivery of salt and water appears necessary for overt hyperkalemia to develop. Spontaneous recovery usually occurs by the age of 2 years, although episodic hyperkalemia may still occur during episodes of acute illness.
PHA type II (Gordon’s syndrome or familial hypertension with hyperkalemia) exhibits an autosomal dominant mode of transmission and is usually seen in late childhood or adulthood. These patients also have hyperkalemia and hyperchloremic metabolic acidosis, but do not exhibit renal salt wasting, have low plasma renin levels and are usually hypertensive. Aldosterone levels are normal or high and most of these patients have a normal eGFR. This syndrome is also characterized by short stature, intellectual impairment, dental abnormalities, and muscle weakness. Recent positional cloning has linked mutations of WNK1 (on chromosome 12p) and WNK4 (on chromosome 17q21) to type II PHA. With-no-lysine [K] (WNK) kinases are a new family of large serine–threonine protein kinases with an atypical placement of the catalytic lysine. Wild type WNK1 and WNK4 inhibit the thiazide-sensitive sodium chloride co-transporter in the distal tubule. Mutations of these proteins are associated with gain of function and increased co-transporter activity, excessive chloride and sodium reabsorption and volume expansion. Hyperkalemia, another hallmark of this syndrome, might be a function of diminished sodium delivery to the cortical collecting tubule. Sodium reabsorption provides the driving force for potassium excretion, which is mediated by the renal outer medullary potassium channel (ROMK). Alternatively, the same mutations in WNK4 that result in gain of function of the Na–Cl co-transporter (NCC) might inhibit ROMK activity, resulting in hyperkalemia. Treatment consists of either a low salt diet or thiazide diuretics, aimed at decreasing chloride intake and blocking Na + –Cl − co-transporter activity (NCC), respectively.
The presence of hyperkalemia in association with hyperchloremic metabolic acidosis, a low serum renin, a normal serum aldosterone and an adequate GFR in this child makes PHA type II the most likely diagnosis. In this syndrome, hypertension tends to develop in the third decade, so its absence in our patient does not exclude the diagnosis. As the condition is inherited in an autosomal dominant pattern, we proceeded to screen the child’s father, who was 28 years old and asymptomatic. He was hypertensive with a blood pressure reading of 160/90 mmHg. His serum potassium was elevated at 6.4 mmol/L. His renal function and acid base status was normal. The father and the infant were commenced on chlorothiazide, which led to normalization of the serum potassium (and blood pressure in the father) and eliminated the need for dietary restriction of potassium. Initial genetic screening for WNK1 and WNK4 gene mutations in our patient was negative. However, further mutation studies are ongoing.
Case Study 9
A 5-month-old male infant was referred to our medical center with a possible diagnosis of Bartter syndrome. The patient had been admitted, 2 days before referral, to a local hospital with gastroenteritis and abdominal distension. Repeated investigations there had shown hypokalemia (K + 2.0 to 2.6 mEq/L), (Cl − 92 to 95 mEq/L) metabolic alkalosis (pH 7.5 to 7.58, HCO 3 – 38 to 42 mEq/L, and base excess + 8 to + 14 mEq/L). The patient had been treated with IV fluids and potassium replacement. Results from other investigations were: urea 10.0 mg d/L, creatinine 0.3 mg/dL, Hb 10.1 g/dL WBC 9700/mL, and platelets 3.12 × 10 6 mL; abdomen ultrasound revealed normal-sized kidneys and no abnormality.
The patient had been born at term with a birth weight of 2.8 kg and had an uneventful perinatal period. The patient thrived well on breast feeds and formula milk feeds until approximately 7 weeks of age. The patient then started to suffer from repeated episodes of watery diarrhea and was diagnosed as milk protein/lactose intolerant and switched to soya-based formula. The patient was thriving well on this formula until 15 days before this illness when his parents switched to ordinary formula milk feeds. Development was normal for his age.
Examination revealed an active, 5.5-kg male (growth 25th centile), length 61.5 cm (25th centile), and head circumference 40 cm (25th centile) with stable hemodynamics, mild dehydration, abdominal distension, and reduced bowel sounds. Investigations revealed K + 2.0 mEq/L with pH 7.59, PCO 2 52 mmHg, PO 2 73 mmHg, HCO 3 – 48 mEq/L, BE + 28 mEq/L, Na + 129 mEq/L, Cl − 95 mEq/L Hb 9.2 g/dL, WBC 6400/mL platelets 2.1 × 10 6 /mL, urea 16.0 mg/dL, creatinine 0.3 mg/dL. Plain X-ray abdomen was suggestive of adynamic ileus. Simultaneous urine electrolytes were K + 3 mEq/L and Na + 40 mEq/L. A provisional diagnosis of pseudo-Bartter syndrome was made, and the patient was started on intravenous hydration and potassium supplementation K + 30 mEq (deficit) plus maintenance, over 24 hours. Sixteen hours after starting the treatment potassium was 3.8 mEq/L with blood pH 7.36, HCO 3 – 32 mEq/L, and BE + 2 mEq/L, diarrhea and abdominal distension improved, and the patient was started on soya-based formula.
On the third day after admission the patient became irritable and was sweating more than his usual. He was otherwise sucking well, had infrequent loose motions, passed urine freely, and was afebrile. Repeat investigations revealed Hb 9.0 g/dL, WBC 5700/mL, platelets 2.56 × 10 6 /mL, K + 9.3 mEq/L, Na + 129 mEq/L, urea 18 mg/dL, creatinine 0.4 mg/dL, and normal blood gas (pH 7.34, PCO 2 40 mmHg, PO 2 86 mmHg, HCO 3 – 23 mEq/L, BE 1.5 mEq/L), blood sugar 102 mg/dL. Repeat sample ruled out any hemolysis. Electrocardiogram (ECG) showed tall-tented T waves with broad QRS complex (0.12 second) and increased QT c (0.5). The patient was given one bolus of calcium gluconate (2 mmol/kg) intravenously over 15 minutes, which resulted in normalization of ECG. The patient was started on treatment for hyperkalemia with continuous intravenous calcium infusion (1 mEq/k/h), intravenous hydration (120 mL/kg/day) and salbutamol nebulization (1 mg per dose every 2 hours).
Other investigations revealed urea 18 mg/ dL, creatinine 0.3 mg/dL, CPK 790 IU/L (normal reference range: 25 to 175 IU/L), SGOT 81 IU/L, SGPT 71 IU/L; calcium 8.2 mg/dL, bilirubin 0.3 mg/dL pH 7.38, PCO 2 36 mmHg, PO 2 123 mmHg, HCO 3 – 21 mEq/L, and BE 1.5 mEq/L.
What is the MOST likely cause of hyperkalemia in this infant?
Inborn error of metabolism
The correct answer is A
Comment: In our patient rhabdomyolysis was the cause of hyperkalemia. Evidence that rhabdomyolysis was present were extremely high CPK levels and results from urine examination suggestive of myoglobinuria. There was no evidence of renal failure.
The patient was managed for hyperkalemia. Potassium levels gradually decreased to normal by the end of 24-hour treatment, maximum being 10.4 and 3.8 mEq/L at the end of 24-hour. The total potassium intake in the 24-hour preceding hyperkalemia was 4 mEq/kg/day. CPK decreased to 490 IU/L after 24-hour. The urine was positive for hemoglobin and there were no red blood cells (RBCs) in the urine, indicating likely presence of myoglobin in the given clinical setting. A week later, the patient on follow-up was normal, abdominal distension had decreased and serum potassium, CPK, and renal function tests were normal.
Rhabdomyolysis is defined as an acute increase in serum creatinine phosphokinase to more than five times the normal with/without associated acute renal failure and hyperkalemia. Various causes of rhabdomyolysis have been identified and may be subdivided into traumatic, exercise-induced, toxicological, environmental, metabolic, infectious, immunological, and inherited causes. The occurrence of rhabdomyolysis in hypokalemia is found to be independent of the etiology and degree of hypokalemia. It has been reported that sub-clinical rhabdomyolysis is a common complication of hypokalemia, which is detected only as elevated muscle enzymes and, as a result, hypokalemia as a cause of rhabdomyolysis goes unnoticed because of the counteracting response of rhabdomyolysis on serum potassium concentration.
Clinical presentation of rhabdomyolysis varies between patients. Muscle pain and myoglobinuria are not always found on presentation. The usual laboratory features of rhabdomyolysis are acute renal failure with or without hyperkalemia, hyperkalemia without renal failure, and myoglobinuria. Other uncommon features are hyperphosphatemia, hypocalcemia, hyperuricemia, and disseminated intravascular coagulopathy (DIC).
Case Study 10
A 2-month-old female infant was admitted with 2 days history of poor feeding and lethargy. She was born to a 28-year-old primary gravid at 38 weeks gestation via normal vaginal delivery with a birth weight of 2.9 kg. The neonatal period was uneventful.
On admission to the hospital, her weight was 3.7 kg, blood pressure 92/55 mmHg, pulse 139 beats/min, and temperature 90.1°C. Examinations of lung, heart, and abdomen were normal. Laboratory data: white blood cell counts 17 × 10 3 /μL with a shift to the left, platelets 107 × 10 3 /μL, hematocrit 33.2%, serum sodium 129 mmol/L, chloride 111 mmol/L, potassium 9.2 mmol/L, bicarbonate 9.1 mmol/L (anion gap 8.9 mmol/L), creatinine 0.8 mg/dL, BUN 32 mg/dL, calcium 8.1 mg/dL phosphate 4.4 mg/dL, and urate 6.1 mg/dL. Estimated glomerular filtration rate (eGFR) using the original Schwartz equation was 32.1 mL/min/1.73 m 2 . Repeated measurements of serum potassium confirmed the initial value. Urinalysis revealed pH 6.5, specific gravity 1.009, without proteinuria or hematuria. Urine culture was positive for Escherichia coli . Arterial blood gas determinations on room air showed pH 7.24, PCO 2 18 mmHg, bicarbonate 11.4 mmol/L, base excess −8.2. A renal ultrasound showed bilateral obstructive hydronephrosis. The diagnosis of ureteropelvic junction obstruction (UPJO) was suspected and confirmed by diuretic 99 mTc diethylenetriamine pentaacetic acid (DTPA) renography. Serum renin activity was 18.8 ng/mL/h (normal range 0.1 to 3.1), aldosterone l98 ng/dL (normal range 3 to 16) and cortisol 36.1 ug/dL (normal range 2.3 to 11.9). The admission electrocardiogram (EEG) showed normal sinus rhythm, normal PR, QRS, and T waves morphology.
After therapy with intravenous 0.9% saline, antibiotic, sodium bicarbonate, glucose and insulin, nebulized salbutamol (β 2 agonist), and sodium-potassium ion exchange resins and insertion of nephrostomy tubes, the serum potassium concentrations returned to normal; her BUN and serum creatinine concentrations also returned to normal values of 12 mg/dL, and 0.4 mg/dL, respectively. A repeat EEG when the serum potassium concentration was 4.4 mEq/L, was unchanged compared to that taken on admission.
Which of the following statements is correct? (Select all that apply)
Pseudo hyperkalemia without ECG manifestations
True hyperkalemia without ECG manifestations
Both of the above
None of the above
The correct answer is B
Comment: The finding of normal ECG in our patient with severe hyperkalemia suggests the ECG findings may not be a reliable indicator in patients with chronic kidney disease or a useful observation to monitor therapy aimed to lower the serum K + concentration.
The etiology of hyperkalemia in our patients was the impaired K + excretion as a result of acute or chronic kidney disease. Hyperkalemia is usually not seen until the glomerular filtration rate falls below 30 mL/min/1.73 m 2 . One possible explanation for the absence of typical ECG changes may be the slow rises in serum K + concentrations and the presence of chronic kidney disease in five of our patients. It is known that patients with CKD tolerate higher levels of serum K + concentration than patients without chronic kidney disease. It is not known if the present observation can be applied to patients with other hyperkalemic syndromes
The rate of increase in serum K + can also potentiate the cardiotoxic effect of hyperkalemia and influence the development of ECG abnormalities.
Hyperkalemia is defined as a serum K + level greater than 5.5 mmol/L. Clinical symptoms including cardiac arrhythmias, muscle weakness and paralysis usually develops at levels higher than 7.0 mmol/L, but the rate of change is more important than the level of K + concentration.
Mild to moderate hyperkalemia (serum K + concentrations between 6 and 7 mmol/L) is associated with the appearance of tall, peaked T waves, known as tenting T wave. As potassium levels rise further, the PR interval increases, and p wave amplitude decreases followed by widening QRS complex and disappearance of p waves.
Calcium gluconate is the first line of therapy in patients with evidence of cardiac toxicity. Insulin and glucose will lower serum K concentration by allowing the K + back into the cells. A common practice is 10 units of regular insulin given with 50 mL of 50% dextrose solution. Beta-2adrenergic agents such as albuterol will also shift K + intracellular. Sodium bicarbonate is given in patients with metabolic acidosis. Loop diuretics may be helpful in non-oliguric and volume overload patients by enhancing the urinary K + excretion. Gastrointestinal cation exchangers such as patiromer or sodium polystyrene sulfonate may be administered in patients with renal insufficiency. Hemodialysis should be considered in patients with severe renal injury (GFR ≤ 30 mL/min/1.73 m 2 ).
Case Study 11
A 2.5-month-old girl was admitted to our emergency department with a 1-day history of fever and vomiting. She was born at the 35th week of gestation by cesarean section and admitted to the neonatal intensive care unit. Her past medical history was significant for urinary tract infection in the neonatal period and congenital anomalies of the kidney and urinary tract (CAKUT), which was completely identified at 4 weeks of age. She had antenatal hydronephrosis and was diagnosed with right multicystic dysplastic kidney and severe left ureterovesical junction (UVJ) obstruction with imaging tests including 99m Tc-mercaptoacetyltriglycine (MAG3) scintigraphy and voiding cystourethrography (VCUG). When she was 3 weeks old, a double J catheter was inserted due to severe left UVJ obstruction. VCUG did not demonstrate any vesicoureteral reflux (VUR). She was on prophylactic antibiotics. Her weight was 4210 g (3rd to 10th percentile), height 56 cm (10th percentile), head circumference 37 cm (3rd to 10th percentile), and blood pressure 110/70 mmHg (95th percentile 98/65 mmHg). She had signs of mild–moderate dehydration with dry mucosal membranes and normal female external genitalia on physical examination. While there was no abnormality in the previous biochemical parameters of the patient, the results of the laboratory examination at the time of admission were blood urea nitrogen (BUN), 25 mg/dL (5 to 20 mg/dL); serum creatinine, 0.34 mg/dL (0.3 to 1 mg/dL); sodium, 111 mmol/L (135 to 145 mmol/L); potassium, 7.4 mmol/L (3.5 to 5 mmol/L); chloride, 98 mmol/L (98 to 115 mmol/L); glucose, 88 mg/dL (50 to 90 mg/dL); hemoglobin, 13 g/dL; leukocytes, 16,870/mm 3 (7000 to 15,000/mm 3 ); and platelets, 656,000/mm 3 (150,000 to 450,000/mm 3 ). Hormonal analysis showed elevated plasma renin greater than 500 pg/mL (reference: 2.77 to 61.8 pg/mL) and serum aldosterone greater than 1500 pg/mL (reference: 50 to 900 pg/mL). Random adrenocorticotrophic hormone (ACTH) was 30.8 pg/mL (reference: 8.6 to 46.3 pg/mL) and cortisol was 7.2 μg/dL (reference: 1 to 24 μg/dL). Venous blood gas analysis was pH 7.20, pCO 2 38 mmHg, bicarbonate 11 mmol/L, and base excess −13 mmol/L. Her urine analysis results were pH 5, density 1025, leukocyte esterase (3 +) positive, nitrite positive, and leukocyturia with bacteriuria in microscopic examination. She was hospitalized with a diagnosis of acute pyelonephritis.
What is your diagnostic approach to hyperkalemia and hyponatremia?
Congenital adrenal hyperplasia
The correct answer is C
Comment: Diagnosis of pseudohypoaldosteronism (PHA) was confirmed with hyponatremia, hyperkalemia, metabolic acidosis, and elevated levels of renin (> 500 pg/mL) and aldosterone (> 1500 pg/mL). After pyelonephritis treatment, biochemical parameters were completely normal, and renin and aldosterone levels decreased to normal limits. Based on clinical and laboratory results, she was diagnosed with secondary (transient) PHA type 1. Congenital adrenal hyperplasia (CAH) and other aldosterone synthesis defects were excluded by clinical course as well as female genitalia with normal pigmentation, and the hormonal profile of the patient.
This patient was treated with appropriate antibiotic therapy for urinary tract infection (UTI), and appropriate fluid and electrolyte therapy for hyponatremia and hyperkalemia. After initiation of UTI treatment, serum sodium, potassium, bicarbonate, renin, and aldosterone levels normalized within a few days, which confirmed the diagnosis of secondary PHA1. Infants with secondary PHA1 require long-term follow-up of serum electrolytes after surgical treatment of obstruction.
Pseudohypoaldosteronism is a rare heterogeneous syndrome of mineralocorticoid resistance that is characterized by systemic or renal tubular unresponsiveness to aldosterone. Two different forms of PHA have been described, type 1 (PHA1) and type 2 (PHA2). PHA1 has been sub classified into primary and secondary (transient) PHA1. Primary PHA1 is caused by mutations in the epithelial sodium channel (ENaC) genes or mineralocorticoid receptor (MR) gene. The secondary (transient) form of PHA1 is associated with urinary tract malformations and/or infections during infancy. Therefore, a urinary ultrasound examination should be performed in infants with salt loss and hyperkalemia. Other causes of secondary PHA1 are systemic lupus erythematous, acute renal allograft rejection, chronic allograft nephropathy, and sickle cell nephropathy. The common presenting symptoms in children with PHA are poor feeding, failure to thrive, polyuria, dehydration, and vomiting. Clinical features of PHA are hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels. Our patient presented with vomiting and dehydration. Severe hyponatremia, hyperkalemia, and metabolic acidosis were detected.