135glucosuria, and phosphaturia support the diagnosis of proximal RTA. Further,
proximal RTA can be confirmed by bicarbonate loading test. Nephrocalcinosis/
nephrolithiasis is usually a feature of distal RTA due to hypercalciuria and hypoci-
traturia. High urinary calcium in the presence of low urinary citrate allows the
calcium to precipitate in the renal interstitium, thereby resulting in nephrocalcino-
sis. The index patient had concurrent stage 3 CKD (eGFR 40 ml/min and bilateral
shrunken kidneys) which itself may be contributing to the metabolic acidosis.
However, normal anion gap metabolic acidosis even in presence of mild to moder-
ate CKD suggests the possibility of associated RTA. Metabolic acidosis leads to
increased bone resorption and impaired bone mineralization. Activation of RANK
ligand by systemic acidosis results in increased bone resorption. Further, the aci-
dosis also inhibits bone mineralization due to its effect on osteoblast, thereby
resulting in decreased bone collagen production and reduced alkaline phosphatase
activity. The common cause of distal RTA in majority of patients is idiopathic;
however, some patients may have concurrent autoimmune disorders or use of
drugs associated with distal RTA. These include Sjogren’s syndrome, systemic
lupus erythematosus, PHPT, Wilson’s disease, sarcoidosis, and use of certain
drugs like amphotericin B, ifosfamide, and lithium carbonate. As the patient had
history suggestive of dry mouth and dry eyes, a possibility of Sjogren’s syndrome
as the etiology of distal RTA was considered. Antinuclear antibody and lip biopsy
confirmed the same in the index patient. The presence of primary hypothyroidism
in the index patient is another component of autoimmunity. The primary aim of
treatment is effective correction of metabolic acidosis. The other concurrent bio-
chemical abnormalities like hypokalemia and hypercalciuria get spontaneously
normalized with correction of metabolic acidosis. However, potassium and cal-
cium supplementation may be required initially. Short-term use of calcitriol may
be required for rapid healing of osteomalacia; however, it is associated with
increased risk of nephrocalcinosis. Therefore, periodic monitoring of urinary cal-
cium excretion and renal ultrasonography should be performed.
5.3 Clinical Rounds
- What are the constituents of bone?
Bone is made up of cells and matrix. The cellular component contributes to
only 2 % of the dry weight of bone, while the rest is by matrix. The cellular
component includes osteoblasts, osteoclasts, bone-lining cells, and osteocytes;
the latter accounts for approximately 95 % of cellular compartment. The bone
matrix comprises of inorganic (60–70 %) and organic constituents (30–40 %).
The inorganic components include calcium hydroxyapatite and magnesium.
Approximately 90 % of the organic component is constituted by type 1 collagen
and the rest by non-collagenous proteins like bone sialoprotein, osteopontin,
osteonectin, and osteocalcin. The constituents of bone are shown in the figure
given below (Fig. 5.2).
5 Rickets–Osteomalacia