Multiple renal calculi due to hypercalcaemia induced by over-the-counter vitamin D intoxication

Abstract

Renal stone disease is a common and painful condition. Even though it is rarely fatal, patients describe it as the worst pain in their life. While dietary calcium may decrease the risk of stone formation, patients on supplemental calcium are at higher risk. Moreover, patients with diabetes are more prone to develop renal calculi. Hypervitaminosis D is a rare cause of hypercalcaemia. This is a case of an elderly diabetic man who developed multiple calcium oxalate renal stones due to hypercalcaemia following calcium–vitamin D supplementation.

Background

In the present world, people believe that ‘vitamins and minerals’ are extremely important, do not have adverse effects and can be consumed on a daily basis irrespective of the duration. However, fat-soluble vitamins like vitamin D can prove to be toxic at megavitamin levels.¹ Majority of the patients are vitamin D deficient. Hypervitaminosis D is a rare scenario, and patients present with features of hypercalcaemia. Excessive calcium intake in the form of supplements can increase the risk of developing renal calculi. The incidence of renal calculi is also higher in diabetes. The patient being described is an elderly man who was on calcium–vitamin D supplements daily along with weekly bolus vitamin D capsules and developed hypercalcaemia resulting in multiple renal calculi.

Case presentation

A 70-year-old man presented to the Medicine department with a 2-month history of fatigue and loin pain with no radiation. He was a diabetic (on glimipride 1 mg once daily and metformin 500 mg twice daily). Also, he has been taking calcium–vitamin D supplements (1250 mg of calcium carbonate and 250 IU cholecalciferol) daily for the past 2 years, along with cholecalciferol 60000 IU once or twice monthly. Both supplements were started by the patient himself as over-the-counter medications in order to prevent osteoporosis. He used to avoid milk and milk products as he felt they were high on cholesterol. On examination, he was conscious and oriented, with stable vitals and normal systemic examination.

Investigations

He underwent a health check-up package, which showed serum calcium of 11.8 mg/dL (8.7–10.2), vitamin D levels of 206 ng/mL (30–100), fasting and postprandial blood glucose of 256 mg/dL and 304 mg/dL, respectively, and glycated haemoglobin (HbA1c) of 10.2%. Other blood investigations like complete blood counts, renal and liver functions, electrolytes, uric acid, magnesium and TSH were normal. Chest X-ray and ECG were also normal, and ultrasound abdomen showed multiple calculi of 3 to 4 mm size in both kidneys (figure 1). His urine microscopy showed presence of calcium oxalate stones, glucose (3+), pH 6.0 with no proteinuria or haematuria. Twenty-four-hour urinary calcium was 320 mg/day (100–300). His parathyroid hormone levels were normal. CT imaging of pelvis was not done as the patient was not willing for it.

Figure 1.

Ultrasound abdomen showing renal calculus.

Treatment

He was started on syrup pyridoxine with magnesium citrate and potassium citrate (15 mL at night) and oral tamsulosin (0.4 mg at night). Oral diclofenac was given for pain relief. Blood glucose levels were controlled with insulin. He was asked to stop the calcium and vitamin D supplements, avoid foods containing oxalate (spinach and potatoes) along with low-salt diet and increase the water intake to 2 to 3 L/day.

Outcome and follow-up

On follow-up after 4 months, he was asymptomatic with regard to fatigue and loin pain; his calcium and vitamin D levels normalised (9.8 mg/dL and 95 ng/mL, respectively). Repeat ultrasound abdomen showed only a single left renal calculus measuring about 4 mm in size. His blood glucose levels were under control and HbA1c reduced to 7.8%. Urine examination showed pH of 7.4 with no glucose, protein, haematuria or sediments.

Discussion

Vitamin D is required for the absorption of calcium in the body. Most of the people are vitamin D deficient, and its supplementation has helped to decrease the incidence of rickets and osteoporosis. In those with poor dietary intakes, calcium and vitamin D supplements enable to prevent hip fractures, especially in women and elderly. Vitamin D is also essential to decrease the risk of cancers, cardiovascular diseases, inflammatory and other autoimmune conditions.^2–4 Though the human body has the ability to produce vitamin D through sun exposure, our current lifestyle especially white-collar jobs can be an obstacle. In such cases, food alone may be insufficient and vitamin D dietary supplements are required in the form of daily or weekly once doses. The daily recommended dose of vitamin D, according to the Institute of Medicine 2010 report, is 600 IU up to 70 years of age and 800 IU for those above 70 years. The treatment of deficiency states is a weekly dosing of 50000 IU for 3–12 weeks followed by maintenance therapy with 800 IU daily along with calcium.⁵ According to the National Institute of Health, the daily calcium requirements in adults ranges from 1000 to 1200 mg/day.

The upper limit of vitamin D required to cause toxicity is unclear, but doses up to 10000 IU/day has been considered safe in healthy adults.² Toxicity has been reported in individuals taking 40000 IU/day.⁵ Vitamin D at a dose of 100000 IU/day of vitamin D for at least 1 month can result in toxicity.⁶ A complete cessation of these supplements along with adequate hydration forms the mainstay of treatment. Steroids, either oral prednisolone or intravenous hydrocortisone, are useful in vitamin D intoxication as they inhibit the conversion of vitamin D to calcitriol.

The incidence of renal calculi has increased these days. Urine may be considered as a complex solution, and the formation of crystals is due to supersaturation. Among the different types of renal stones, calcium oxalate is the most common (75%), followed by calcium phosphate (15%), uric acid (8%), struvite (1%) and cystine (<1%). Dietary intake of calcium has been associated with lower risk of renal stones. This may be due to low intestinal absorption of dietary oxalate resulting in low urinary oxalate. However, decreased calcium intake can lead to increased bone resorption, thereby posing a risk of developing renal stones and low bone density. Excessive calcium supplementation can also result in renal stones. Helical CT without contrast is the gold standard diagnostic test. Laboratory tests include renal functions, calcium, vitamin D, electrolytes, parathyroid hormone levels and urine analysis. Adequate hydration with a diluted urine volume of at least 2 liters/day is essential for stone prevention. Calcium intake of more than 1200 mg/day should be avoided. Thiazide diuretics along with dietary sodium restriction can reduce the recurrence of calcium oxalate stones by about 50%. Avoidance of high doses of vitamin C and reduced intake of oxalate-rich foods like spinach, rhubarb and potatoes is advisable. High potassium intake decreases urinary calcium excretion. Magnesium may also decrease the risk of calculi. Citrate is a natural inhibitor of calcium oxalate stones and supplemental alkali with magnesium and potassium citrate can be useful as it increases the urinary citrate excretion. The role of supplemental vitamin B6 is uncertain. Urological interventions like extracorporeal shockwave lithotripsy, laser fragmentation, percutaneous nephrostolithotomy, ureterolithotomy and pyelolithotomy are indicated in cases with urinary tract infection, low probability of spontaneous passage and extreme pain.⁷

A significant association has been noticed between diabetes and renal stones, with high HbA1c values showing strongest relation.^{8 9} Insulin resistance in diabetes mellitus is associated with defects in the production of renal ammonium, thereby leading to low urinary pH.^{10 11} Acidic urine can predispose to formation of uric acid stones.^{12 13} Moreover, a defect in renal acid excretion causes hypocitraturia, which in turn can lead to formation of calcium stones.^{14 15} The hyperinsulinaemia of insulin resistance may also increase the urinary excretion of calcium.^{16 17} Family history of renal stones, male gender and alcohol consumption are risk factors for development of nephrolithiasis in diabetes.¹⁸ A cross-sectional prospective study of three large cohorts concluded that the risk of renal stones in diabetics was independent of age, Body Mass Index, thiazide diuretic use and diet.¹⁹ The incidence of renal stones is as high as 13% in dialysis patients, and this is similar in non-dialysis population.^{20 21} About 80% of dialysis patients with renal stones develop recurrence of nephrolithiasis.²² These patients are prone to mineralised protein stones comprising a mixture of lysozyme, β2-microglobulin, serum amyloid P protein, albumin and Tamm-Horsfall protein.^{23 24}

The incidence of hypercalcaemia due to vitamin D toxicity is uncommon, with only a handful of cases being reported.^25–27 Our patient was a diabetic with uncontrolled blood glucose levels and was on self-medication with supplements containing 250 IU cholecalciferol with 1250 mg calcium daily along with 60000 IU cholecalciferol once or twice monthly. His dietary intake of milk and milk products were low. All these factors lead to hypervitaminosis D and hypercalcaemia, thereby resulting in multiple calculi involving both kidneys.

Learning points.

• Dietary intake of calcium decreases the risk of renal stones, while supplemental calcium increases it.

• Calcium and vitamin D supplementation should be started only after an estimation of their serum levels.

• Diabetes is strongly associated with incidence of renal stones.