calcitriol and Nephrolithiasis

Hypercalcemia, hypercalciuria, and recurrent nephrolithiasis are all common clinical problems. This case report illustrates a newly described but possibly not uncommon cause of this presenting complex.. We report on a patient studied for over 30 years, with the diagnosis finally made with modern biochemical and genetic tools.. This study consists of a case report and review of literature conducted in a University Referral Center.. A single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis was treated with low-calcium diet, low vitamin D intake, prednisone, and ketoconazole.. We measured the patient's clinical and biochemical response to interventions above.. Calcium absorption measured by dual isotope absorptiometry was elevated at 37.4%. Serum levels of 24,25-dihydroxyvitamin D were very low, as measured in two laboratories (0.62 ng/mL [normal, 3.49 ± 1.57], and 0.18 mg/mL). Genetic analysis of CYP24A1 revealed homozygous mutation E143del previously described. The patient's serum calcium and renal function improved markedly on treatment with ketoconazole but not with prednisone.. Chronic hypercalcemia, hypercalciuria, and/or nephrolithiasis may be caused by mutations in CYP24A1 causing failure to metabolize 1,25-dihydroxyvitamin D.

Topics: Aged; Confusion; Delayed Diagnosis; Fatigue; Humans; Hypercalcemia; Hypercalciuria; Hypertension; Male; Nephrolithiasis; Recurrence; Steroid Hydroxylases; Vitamin D; Vitamin D3 24-Hydroxylase

Loss-of-function mutations of CYP24A1, the enzyme that converts the major circulating and active forms of vitamin D to inactive metabolites, recently have been implicated in idiopathic infantile hypercalcemia. Patients with biallelic mutations in CYP24A1 present with severe hypercalcemia and nephrocalcinosis in infancy or hypercalciuria, kidney stones, and nephrocalcinosis in adulthood. We describe a cohort of 7 patients (2 adults, 5 children) presenting with severe hypercalcemia who had homozygous or compound heterozygous mutations in CYP24A1. Acute episodes of hypercalcemia in infancy were the first symptom in 6 of 7 patients; in all patients, symptoms included nephrocalcinosis, hypercalciuria, low parathyroid hormone (PTH) levels, and higher than expected 1,25-dihydroxyvitamin D levels. Longitudinal data suggested that in most patients, periods of increased sunlight exposure tended to correlate with decreases in PTH levels and increases in calcemia and calciuria. Follow-up of the 2 adult patients showed reduced glomerular filtration rate and extrarenal manifestations, including calcic corneal deposits and osteoporosis. Cases of severe PTH-independent hypercalcemia associated with hypercalciuria in infants should prompt genetic analysis of CYP24A1. These patients should be monitored carefully throughout life because they may be at increased risk for developing chronic kidney disease.

Topics: Bone Density Conservation Agents; Calcium; Child; Child, Preschool; Diphosphonates; Female; Fluid Therapy; Humans; Hypercalcemia; Hypercalciuria; Infant; Kidney Function Tests; Male; Middle Aged; Monitoring, Physiologic; Mutation; Nephrocalcinosis; Nephrolithiasis; Parathyroid Hormone; Renal Insufficiency, Chronic; Seasons; Sunlight; Treatment Outcome; Vitamin D; Vitamin D3 24-Hydroxylase

Calcium metabolism changes in pregnancy and lactation to meet fetal needs, with increases in 1,25-dihydroxyvitamin D [1,25-(OH)2D] during pregnancy playing an important role. However, these changes rarely cause maternal hypercalcemia. When maternal hypercalcemia occurs, further investigation is essential, and disorders of 1,25-(OH)2D catabolism should be carefully considered in the differential diagnosis.. A patient with a childhood history of recurrent renal stone disease and hypercalciuria presented with recurrent hypercalcemia and elevated 1,25-(OH)2D levels during pregnancy. Laboratory tests in the fourth pregnancy showed suppressed PTH, elevated 1,25-(OH)2D, and high-normal 25-hydroxyvitamin D levels, suggesting disordered vitamin D metabolism. Analysis revealed low 24,25-dihydroxyvitamin D3 and high 25-hydroxyvitamin D3 levels, suggesting loss of function of CYP24A1 (25-hydroxyvitamin-D3-24-hydroxylase). Gene sequencing confirmed that she was a compound heterozygote with the E143del and R396W mutations in CYP24A1.. This case broadens presentations of CYP24A1 mutations and hypercalcemia in pregnancy. Furthermore, it illustrates that patients with CYP24A1 mutations can maintain normal calcium levels during the steady state but can develop hypercalcemia when challenged, such as in pregnancy when 1,25-(OH)2D levels are physiologically elevated.

Topics: Adult; Female; Humans; Hypercalcemia; Metabolic Networks and Pathways; Mutation; Nephrolithiasis; Pregnancy; Pregnancy Complications; Vitamin D; Vitamin D3 24-Hydroxylase

We report two patients with medullary nephrocalcinosis and nephrolithiasis. The first patients had unspecific symptoms of a systemic inflammatory disease, the second patient was asymptomatic.. Both patients had normocalcemia and normal parathyroid hormone levels, very high 1,25(OH)(2)-vitamin D and normal to low 25-OH-vitamin D levels. On renal ultrasound, both patients displayed nephrocalcinosis and nephrolithiasis.. Both patients showed dysregulation of the 1α-hydroxylase activity. The first patient suffered from a systemic inflammatory disease with consecutive activation of macrophages with extrarenal α-hydroxylase activity. The second patient had a "loss of function" mutation of the calcium sensing receptor with - for the situation - inadequatly high parathyroid hormone levels and consequently a renal dysregulation of the 1α-hydroxylase.. After immunosuppressive treatment with prednisolone and hydroxychloroquin there was complete remission of the systemic inflammatory disease in the first patient. In consequence the 1,25-(OH)(2)-vitamin D levels regressed and renal function stabilized. The second patient was completely asymptomatic with normal renal function, so far we did not initiate any treatment.. Nephrocalcinosis and nephrolithiasis can result from hypercalciuria due to dysregulated hydroxylation of vitamin D. For both renal and extrarenal sources causal treatment is available.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Calcium; Diagnosis, Differential; DNA Mutational Analysis; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Kidney Function Tests; Kidney Medulla; Nephrocalcinosis; Nephrolithiasis; Parathyroid Hormone; Prednisolone; Receptors, Calcium-Sensing; Ultrasonography; Vitamin D