Phosphaturia causes and potential treatments

Increased urine phosphate (>5-10mg/dL, >100mg/day, FEPO4 > 5%) à Renal loses
Decreased urine phosphate (<5-10mg/dL, <100mg/day, FEPO4 < 5%) à GI loses, poor intake

FEPO4 = fractional excretion of phosphate = (urine [PO4] x plasma [Cr] % urine [Cr] x plasma [PO4] ) x 100%


http://emedicine.medscape.com/article/242280-overview
Excessive losses
Phosphate wasting can result from genetic or acquired renal disorders. The genetic disorders generally manifest in infancy, when the children exhibit short stature and bone deformities.
X-linked hypophosphatemic rickets is characterized by short stature, radiographic evidence of rickets, and bone pain. Patients with this condition also may have calcification of tendons, cranial abnormalities, and spinal stenosis. In addition to hypophosphatemia, these patients have relatively low levels of 1,25 dihydroxyvitamin D-3, levels that are inappropriately low for the degree of hypophosphatemia. The defective gene is PHEX, which encodes for a membrane-bound neutral endopeptidase. Present understanding of this disorder is that the inactive neutral endopeptidase is unable to cleave a circulating phosphaturic substance. Data suggest that this circulating substance might be FGF23. This results in impaired phosphate reabsorption by decreasing the sodium-phosphate cotransporter in the kidneys.
Autosomal dominant hypophosphatemic rickets has similar manifestations, with hypophosphatemia, clinical rickets, and inappropriately low levels of 1,25 dihydroxyvitamin D-3. The cause of this disorder is thought to be mutations of FGF23 that result in resistance to degradation, persistently high circulating levels of FGF23, and subsequent phosphaturia.
Hereditary hypophosphatemic rickets with hypercalciuria is a rare disorder characterized by hypophosphatemia, phosphate wasting, hypercalciuria, bone pain, muscle weakness, and high levels of 1,25 dihydroxyvitamin D-3. The cause of this disorder is an inactivating mutation in the type 2c sodium-phosphate cotransporter.
Vitamin D–resistant rickets is an autosomal recessive disorder. In type I, the defect is in renal 1-alpha-hydroxylation. Type II is characterized by end organ resistance to the effects of 1,25 dihydroxyvitamin D-3. These patients present in childhood with hypocalcemia, hypophosphatemia, hyperparathyroidism, rickets, bone pain, muscle weakness, and alopecia. The disease is caused by mutations in the vitamin D receptor that prevent normal responsiveness to circulating vitamin D-3.
Mutations in the type 2a sodium-phosphate cotransporter have been reported in some patients with hypophosphatemia and inappropriate urinary phosphate wasting associated with nephrolithiasis and/or osteoporosis.1,15
Rarely, significant renal phosphate wasting is observed in patients with fibrous dysplasia/McCune-Albright syndrome, disorders that result from mutations in the alpha subunit of the stimulatory G protein. Excess production of FGF23 has been found in some of these patients.16
Acquired phosphate wasting syndromes are of diverse etiologies.
Simple vitamin D deficiency results in hypophosphatemia, at least in part, from renal wasting. Vitamin D deficiency can result from several mechanisms, including poor oral intake, lack of sun exposure, drug-induced hypermetabolism of vitamin D precursors in the liver, or loss of vitamin D binding protein in the urine in persons with nephrotic syndrome. The loss of normal bone mineralization produces rickets in children and osteomalacia in adults.
Primary hyperparathyroidism is another cause of renal phosphate wasting.
Heavy metal intoxication and paraproteinemias can cause global proximal renal tubule dysfunction. These patients have hypophosphatemia along with type II renal tubular acidosis, renal glycosuria, aminoaciduria, and hypouricemia, ie, the condition referred to as Fanconi syndrome. Serum calcitriol concentrations can be either low or inappropriately normal. In children, cystinosis, Wilson disease, and hereditary fructose intolerance are the most common of the syndrome.
Drugs that can produce renal phosphate wasting include loop diuretics; acetazolamide; bisphosphonates, including pamidronate and zoledronate; and multiple chemotherapeutic and biologic agents, including cisplatinum; bevacizumab plus irinotecan17 ; everolimus plus octreotide LAR18 ; imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors19,20 ; sorafenib21 ; carmustine22 ; and ifosfamide.23 In some circumstances, renal phosphate wasting is part of a more generalized, drug-induced Fanconi syndrome.24
Extracellular volume expansion or the administration of bicarbonate can cause loss of phosphate through the kidneys.
Oncogenic osteomalacia is a paraneoplastic syndrome characterized by osteomalacia, hypophosphatemia, renal phosphate wasting, bone pain, and muscle weakness. Several tumors that cause this syndrome have been described, most of which are benign tumors of mesenchymal origin.
Other factors that can increase urinary phosphate excretion are osmotic diuresis (most often due to glucosuria), proximally acting diuretics (acetazolamide and some thiazide diuretics that also have carbonic anhydrase inhibitory activity, such as metolazone), and acute volume expansion (which diminishes proximal sodium reabsorption).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1627603/

The ratio of maximum rate of renal tubular reabsorption of phosphate to glomerular filtration rate (TmPO4/GFR) was determined in 546 schoolchildren, aged between 6 and 17.9 years, using the nomogram of Walton and Bijvoet.1 TmPO4/GFR correlated with chronological age in girls and boys and in each remained significantly higher than in adults. TmPO4/GFR in the children correlated neither with fasting serum immunoreactive calcitonin and parathyroid hormone levels nor with the urinary cyclic AMP excretion. The study showed a parallel decrease in TmPO4/GFR, excretion of total hydroxyproline and serum alkaline phosphatase activities after puberty, with a significant relationship of both these indices of bone turnover to TmPO4/GFR values. This indicates that the high renal phosphate threshold of children may be an important factor for bone mineralisation by providing high extracellular inorganic phosphate concentrations during normal growth.

http://www.springerlink.com/content/rjbhpwhrjtv1fajy/

Effect of enalapril on proteinuria, phosphaturia, and calciuria in insulin-dependent diabetes

Abstract
Elevated urinary calcium and phosphate excretion have been observed in children with insulin-dependent diabetes mellitus (IDDM). This may be related to a defect in tubular reabsorption. It is well known that converting enzyme inhibition decreases microalbuminuria and may prevent or retard diabetic nephropathy. We investigated whether enalapril also improves the defect in calcium and phosphate reabsorption. We studied 16 children and young adults (age 12–21 years) with IDDM and persistent microalbuminuria before and during 12 weeks of enalapril treatment. Before treatment microalbuminuria, urinary calcium excretion, and fractional tubular phosphorus reabsorption (TPR) were 153±53 μg/min, 5.5±0.9 mg/kg per day, and 71.4±3.6%, respectively. At the end of the 12th week, microalbuminuria had decreased to 20.3±7.9 μg/min and calcium excretion to 3.3±0.4 mg/kg per day (P<0.01), while the TPR increased to 80.1±3.8% (NS). The renal threshold phosphate concentration increased from 1.8±0.15 to 2.92±0.23 mg/dl (P<0.01). The fasting serum glucose and hemoglobin Alc levels did not change significantly during the study. Systolic and diastolic blood pressures were 120.4±2.2/79.3±1.4 mm Hg and 110.5±1.8/ 71.3±0.9 mm Hg before and after 12 weeks, respectively. We conclude that enalapril treatment improves not only microalbuminuria but also abnormal calcium and phosphate excretion in microalbuminuric children with IDDM.
Key words: Angiotensin converting enzyme inhibitors - Hypercalciuria - Hyperphosphaturia - Microalbuminura - Insulin-dependent diabetes
Received February 10, 1997; received in revised form December 29, 1997; accepted January 2, 1998

Blogger comment:
For treamtent of low phosphorus from any cause including the urinary phosphate loss conditions refer to this link:
http://emedicine.medscape.com/article/242280-treatment
Above two intersting article is the importnace of renal threshold of phosphrus which explain when it is normally high at time of growth in puberty it helps bone growth. A drug that increase the renal threshold would also help phospharus loss in urine. Enalpril was effective in particular group of patiens those with type 1 DM had increased tubular renal reabsorption of phosphorus

http://www.gfmer.ch/Clinical_tools/Kidney-diseases/Kidney-diseases_mt.htm