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.

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.

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.

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.

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.

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.

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.

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.

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).

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 ).

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.