A case of distal renal tubular acidosis (type 1) presenting with musculoskeletal pain

A. Negi, C. Rhys-Dillon1 and J. P. Camilleri2

Wrexham Maelor Hospital, Wrexham, 1 Prince Charles Hospital, Merthyr Tydfil and 2 University Hospital of Wales, Cardiff, UK

Correspondence to: A. Negi. Specialist Registrar, Rheumatology, Wrexham Maelor Hospital, Croesnewydd Road, Wrexham, LL13 7TO, UK. E-mail: anuragnegi69{at}hotmail.com

SIR, Musculoskeletal symptoms are often the presenting complaint in patients with renal tubular acidosis (RTA) [1]. The biochemical picture can, however, be incomplete during the early stage of RTA, thus making it difficult to diagnose.

We present a 46-yr-old lady, referred with a 9-month history of widespread myalgia and arthralgia. Past history included hyperthyroidism requiring subsequent thyroidectomy followed by thyroxine replacement. At presentation she was receiving regular lithotripsy, having had recurrent renal stones for 4 yr. Her family history included her grandmother, father and one sister suffering from renal problems, and her brother had recently been diagnosed with nephrolithiasis.

Examination of the cardiovascular, respiratory and abdominal systems was unremarkable. She had generalized muscle weakness but her tendon reflexes, plantar responses and sensory examination were normal. There were no joint abnormalities. She had a wide-based gait and was using one elbow crutch. Investigations showed a normal full blood count, erythrocyte sedimentation rate (ESR), sodium, potassium, urea and creatinine; she was negative for antinuclear antibody (ANA) and rheumatoid factor (RF); alkaline phosphatase was 337 IU/l (normal range 40–140 IU/l), aspartate aminotransferase 13 IU/l (normal range 10–60 IU/l), bilirubin 7 µmol/l (normal range 5–17 µmol/l), parathyroid hormone 3.3 pmol/l (normal range 0.9–5.4 pmol/l) and 25-hydroxyvitamin D3 25.5 IU (normal range 8–50); urinary calcium and creatine kinase were normal. The raised alkaline phosphatase was shown to be bone-derived. The bone scan, requested because of the high alkaline phosphatase, showed symmetrical abnormal uptake in both sacroiliac regions and in both femoral heads, suggestive of avascular necrosis. It also showed an abnormal focus on the left ninth rib that was suggestive of a fracture. The report commented that the overall picture was confusing and an MRI was suggested.

MRI showed abnormal bone texture and marrow and a chronic insufficiency fracture of the sacrum and femoral neck with subchondral bone collapse of the right femoral head. A differential diagnosis between metabolic bone disease and a widespread marrow infiltrative process was suggested.

During this period she also had sudden loss of vision in the left eye due to retinal artery occlusion. The thrombophilia screen, including lupus anticoagulant and anticardiolipin antibodies, was negative.

Repeat investigations showed sodium 140 mmol/l, potassium 2.9 mmol/l, chloride 118 mmol/l, normal urea and creatinine, corrected calcium 2.05 mmol/l, phosphate 0.91 mmol/l, alkaline phosphatase 328 IU/l, parathyroid hormone 3.2 pmol/l, negative urine microscopy and culture, and creatinine clearance 33 ml/min. Urine pH was 7. Arterial blood gases showed pH 7.24, PaO2 106 mmHg, PaCO2 36 mmHg, bicarbonate 16 mmol/l and SaO2 95.8%, confirming a hyperchloraemic metabolic acidosis. The history of recurrent renal stones, a hyperchloraemic metabolic acidosis and alkaline urine was in keeping with a diagnosis of type 1 (distal) RTA.

Her musculoskeletal pain and mobility improved with oral potassium replacement. Oral bicarbonate was added once serum potassium was stable and >4.0 mmol/l. Biochemistry after treatment showed alkaline phosphatase 56 IU/l, corrected calcium 2.31 mmol/l, phosphate 1.19 mmol/l, sodium 139 mmol/l, potassium 5.1 mmol/l, and normal urea and creatinine.

RTA is a disorder of renal acidification out of proportion to the reduction in glomerular filtration rate. It is characterized by hyperchloraemic metabolic acidosis [2]. Type 1 RTA is a disorder of the distal nephron resulting in failure to lower urinary pH, due either to excessive back-diffusion of hydrogen ions from the lumen to the blood or to inadequate transport of hydrogen ions [2], and can be familial or acquired. Type 1 RTA may be associated with hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, hypokalaemia, progressive renal failure, growth retardation and metabolic bone disease [3]. Secondary causes include Sjögren's syndrome, hypergammaglobulinaemia, chronic active hepatitis and systemic lupus erythematosus. Familial cases are mostly autosomal dominant and likely to be a consequence of an inherited defect in the AE1 gene [4, 7]. Our patient's family history suggests a familial cause. The renal conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 is impaired causing osteomalacia and rickets [2]. The muscle and joint manifestations in RTA can partly be explained by hypokalaemia and metabolic bone disease [1]. The nephrolithiasis/nephrocalcinosis result from a combination of alkaline urine, hypercalciuria and decreased urinary citrate.

Treatment includes correction of hypokalaemia and alkali replacement [2, 6]. The hypokalaemia should be corrected first, as alkali replacement can worsen the hypokalaemia with dangerous consequences. Correcting hypokalaemia improves the musculoskeletal symptoms. Early treatment also improves the nephrocalcinosis and prevents recurrence of renal stones and progression to chronic renal failure.

In retrospect, our case highlights some important learning points. (i) Musculoskeletal symptoms are a common clinical manifestation of RTA. Harrington et al. report 48 patients with RTA of whom 25 presented with rheumatic complaints [1]. (ii) Patients with renal stones must be screened for RTA. Osther et al. recommend using morning fasting urine pH followed by a short ammonium chloride loading test if urinary pH is above 6.0 [5]. (iii) Although uncommon, RTA must be included in the differential diagnoses in patients presenting with musculoskeletal symptoms and nephrolithiasis.

The investigations for RTA are simple and will obviate more expensive radiological investigations, thus avoiding a delay in diagnosis. It is important to make an early diagnosis, as many musculoskeletal manifestations resolve with treatment. Also, nephrocalcinosis/nephrolithiasis causes substantial morbidity and can be prevented by timely treatment.

We could not find any reports of retinal artery occlusion in association with RTA.

The patient has given consent for this material to appear in Rheumatology.

The authors have declared no conflicts of interest.

References

  1. Harrington TM, Bunch TW, Van den Berg CJ. Renal tubular acidosis. A new look at treatment of musculoskeletal and renal disease. Mayo Clin Proc 1983;58:354–60.[ISI][Medline]
  2. Paillard M. Renal tubular acidosis. In: Davison AM, Cameron JS, Grunfeld J, Kerr DNS, Ritz E, Winearls CG, eds. Oxford Textbook of Clinical Nephrology, Vol. 2, 2nd edn, Oxford: Oxford University Press, 1998:1063–84.
  3. Caruana RJ, Buckalew VM. The syndrome of Distal (type1) renal tubular acidosis. Clinical and laboratory findings in 58 cases. Medicine 1998;67:84–99.
  4. Chaabani H, Hadj-Khlil A, Ben-Dhia N, Braham H. The primary hereditary form of distal renal tubular acidosis: clinical and genetic studies in 60-member kindred. Clin Genet 1994;45:194–99.[ISI][Medline]
  5. Osther PJ, Hansen AB, Rohl HF. Screening renal stone formers for distal renal tubular acidosis. Br J Urol 1989;63:581–3.[ISI][Medline]
  6. Richards P, Chamberlain MJ, Wrong OM. Treatment of osteomalacia of renal tubular acidosis by sodium bicarbonate alone. Lancet 1972; Nov. 11:994–7.[CrossRef]
  7. DuBose TD. Autosomal dominant distal renal tubular acidosis and the AE1 gene. Am J Kid Dis 1999;33:1190–7.[ISI][Medline]
Accepted 14 January 2004





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