Introduction
Pattern 1: Hypokalaemic, hypochloraemic alkalosis with hypovolaemia
Pattern 1a: Hypokalaemic, hypochloraemic alkalosis with hypovolaemia and hypomagnesaemia
Pattern 2: Hypokalaemic, hypochloraemic alkalosis with hypervolaemia
Pattern 3: Hyperkalaemic hyperchloraemic acidosis with hypovolaemia
Pattern 4: Hyperkalaemic hyperchloraemic acidosis with hypervolaemia
Pattern 5: Hypokalaemic, hyperchloraemic acidosis
Conclusions
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Tubular disorders of renal salt handling primarily affect volume homeostasis: renal salt-wasting disorders are associated with hypovolaemia and salt-retaining disorders with hypervolaemia.
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Plasma sodium concentration is typically normal in disorders of renal tubular sodium handling.
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Tubular disorders of renal salt handling have characteristic biochemical and clinical features that facilitate diagnosis and understanding of its pathophysiology.
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While clinical features and plasma biochemistries are sufficient to identify the general diagnosis, recognition of specific subtypes also requires urine biochemistries.
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Correlation of clinical features/diagnosis with genetic findings is critical for establishment of the correct diagnosis.
Multiple Choice Questions (answers given following the reference list)
Question 1
Biochemistries | Plasma | Urine | Unit | Remarks |
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Sodium | 137 | 25 | mmol/l | FENa: <1% |
Potassium | 3.1 | 17 | mmol/l | FEK: 21% |
Chloride | 113 | 32 | mmol/l | FECl: 1 % |
Bicarbonate | 16 | mmol/l | Urine pH: 5.5 | |
Calcium | 2.45 | 2.3 | mmol/l | UCa/UCr: 1.9 mmol/mmol |
Phosphate | 1.02 | 17.5 | mmol/l | TRP: 35% |
Albumin | 39 | 0.153 | g/l | UA/UCr: 127 mg/mmol |
Urea | 5 | mmol/l | ||
Creatinine | 0.045 | 1.2 | mmol/l | |
Retinol binding protein (RBP) | 48.000 | mcg/l | RBP/UCr: 40.000 mcg/mmol |
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Which of the following statements is correct?a)The pattern of hypokalaemic hypochloraemic acidosis is characteristic for a defect in the distal convoluted tubuleb)The low-normal blood pressure indicates a salt-retaining syndromec)The low plasma phosphate and the low-molecular weight proteinuria (urinary RBP) indicate a defect in the proximal tubuled)The albuminuria indicates a glomerular defect
Question 2
Biochemistries | Plasma | Urine | Unit | Remarks |
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Sodium | 135 | 30 | mmol/l | FENa: 1% |
Potassium | 3.1 | 60 | mmol/l | FEK: 103% TTKG: 17 |
Chloride | 90 | 60 | mmol/l | FECl: 3.6% |
Bicarbonate | 28 | mmol/l | ||
Urea | 17.9 | mmol/l | ||
Creatinine | 0.096 | 1.8 | mmol/l | |
Calcium | 2.75 | 4.1 | mmol/l | UCa/UCr: 2.3 |
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Which of the following statements is wrong:a)The pattern of hypokalaemic hypochloraemic alkalosis is characteristic for a defect in salt reabsorption in TAL or DCTb)The low-normal blood pressure indicates a salt-wasting syndromec)The elevated calcium-creatinine ratio is characteristic for Bartter syndrome types 1 and 2d)The normal fractional excretion of sodium (FENa) excludes a salt-wasting disorder
Question 3
Biochemistries | Plasma | Urine | Unit | Remarks |
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Sodium | 132 | 90 | mmol/l | FENa: 5% |
Potassium | 10.7 | 8 | mmol/l | FEK: 5% TTKG: <1 |
Chloride | 110 | mmol/l | ||
Bicarbonate | 12 | mmol/l | ||
Urea | 17 | mmol/l | ||
Creatinine | 0.086 | 1.2 | mmol/l | |
Renin | 280 | pmol/l/h | (normal <25) | |
Aldosterone | 92000 | pmol/l | (normal <2000) |
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Which of the following statements are correct? (select all that apply)a)The fractional excretion of potassium and the transtubular potassium gradient indicate an appropriate tubular response to hyperkalaemia and the elevated aldosteroneb)The clinical hypovolaemia and the hyperkalaemic hyperchloraemic acidosis with dramatically elevated renin and aldosterone are typical for Pseudohypoaldosteronism type 1c)The constellation of clinical and biochemical findings can be seen in the context of pyelonephritis and/or urinary obstructiond)Uraemia is an intrinsic part of the disordere)Affected children may also suffer from pulmonary and skin manifestations
Question 4
Biochemistries | Plasma | Urine | Unit | Remarks |
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Sodium | 148 | 15 | mmol/l | FENa: 0.5% |
Potassium | 2.7 | 34 | mmol/l | FEK: 60% |
Chloride | 128 | mmol/l | ||
Bicarbonate | 12 | mmol/l | ||
Calcium | 2.48 | 2.3 | mmol/l | UCa/UCr: 2.9 |
Urea | 5 | mmol/l | ||
Creatinine | 0.038 | 0.8 | mmol/l |
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Which of the following statements is correct?a)The biochemical pattern of hypokalaemic, hyperchloraemic acidosis is typical for a defect in DCTb)The elevated plasma sodium concentration excludes a salt-wasting disorderc)This disorder can be associated with sensorineural deafnessd)Nephrocalcinosis is rarely associated
Question 5
Biochemistries | Plasma | Urine | Unit | Remarks |
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Sodium | 146 | 20 | mmol/l | FENa: 0.8% |
Potassium | 2.6 | 32 | mmol/l | FEK: 74% |
Chloride | 96 | 50 | mmol/l | FECl: 0.3% |
Bicarbonate | 29 | mmol/l | ||
Urea | 2.9 | mmol/l | ||
Creatinine | 0.036 | 0.6 | mmol/l | |
Calcium | 2.45 | 2.1 | mmol/l | UCa/UCr: 3.5 |
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Which of the following statements is correct?a)The history of prematurity and polyuria and the biochemical pattern of hypokalaemic, hypochloraemic alkalosis and the hypercalciuria establish a diagnosis of Bartter’s syndrome in this girlb)The biochemical pattern of hypokalaemic, hypochloraemic alkalosis indicates a problem in the proximal tubulec)The normal fractional excretion of sodium (FENa) excludes a salt-retaining disorderd)The elevated blood pressure suggests a salt-retaining disorder
Answers:
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1 c)The low plasma phosphate and the low molecular weight proteinuria (urinary RBP) indicate a defect in the proximal tubule, as both solutes are exclusively reabsorbed in the proximal tubule. This patient has renal Fanconi syndrome. The pattern of hypokalaemic hypochloraemic acidosis is typical for renal tubular acidosis, which is a defect either in the proximal tubule (as in this case) or in the collecting duct. The low-normal blood pressure indicates hypovolaemia and thus salt wasting. While albumin is often used as an indicator of glomerular dysfunction, some albumin is filtered physiologically and reabsorbed in the proximal tubule. Renal Fanconi syndrome is therefore associated also with albuminuria, yet usually below the nephrotic range and without oedema.2 d)The normal fractional excretion of sodium (FENa) excludes a salt-wasting disorder. This boy has a typical history, as well as clinical and biochemical findings for Bartter syndrome (types 1 or 2), a disorder of the TAL and associated with hypercalciuria. The elevated plasma urea and creatinine reflect hypovolaemia and consequent acute kidney injury. In a steady state, urinary sodium excretion must reflect sodium intake; for this reason, the FENa is usually normal in salt-wasting disorders; however, chloride excretion is typically elevated (> 0.5%) [7].3 b) ,c) and e):Clinical and biochemical features are classic for Pseudohypoaldosteronism type 1 (PHA1), characterised by hyperkalaemic hyperchloraemic acidosis with impaired urinary potassium and proton excretion, indicating a defect in salt reabsorption in the collecting duct. Uraemia is not an intrinsic part of the syndrome, but reflects AKI from hypovolaemia, and the elevated FENa indicates ongoing volume contraction and thus a high risk of hypovolaemic shock. PHA1 can be acquired, typically in association with pyelonephritis and/or urinary obstruction. There are two inherited forms and the autosomal recessive variant (due to defects in the genes encoding the epithelial sodium channel ENaC) can also be associated with extrarenal manifestations, such as elevated sweat sodium and a skin rash called miliaria and cystic fibrosis-like pulmonary problems.4 c)This disorder can be associated with sensorineural deafness. The biochemical pattern of hypokalaemic, hyperchloraemic acidosis is a characteristic for renal tubular acidosis, and the elevated urine pH indicates dRTA. An elevated plasma sodium concentration reflects water loss and does not exclude a salt-wasting disorder. The frequent wet nappies, the low urinary specific gravity and the hypernatraemia suggest a urinary concentrating defect, which is commonly associated with dRTA. The forms of dRTA associated with genes encoding proton pump subunits or the transcription factor FOXI1 are all associated with sensorineural deafness. More than 90% of patients with dRTA have nephrocalcinosis, reflecting the acidosis-mediated high urinary calcium excretion [31].5 d)The elevated blood pressure suggests a salt-retaining disorder. This girl has a diagnosis of apparent mineralocorticoid excess, due to excessive stimulation of the mineralocorticoid receptor by cortisol with consequent salt retention and hypervolaemia. While the history of prematurity and polyuria and the biochemical pattern of hypokalaemic, hypochloraemic alkalosis and the hypercalciuria are also consistent with a diagnosis of Bartter syndrome, the high blood pressure is not. A normal FENa neither excludes a salt-wasting, nor a salt-retaining disorder, as in a steady-state sodium excretion must balance sodium intake. In this case, the salt retention leads to volume expansion until a new steady state is reached, as the volume expansion leads to decreased proximal sodium reabsorption (hence the hypercalciuria).