Tubular Reabsorption Of Phosphorus Research Articles

Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0–3.5 g are called “large” or “giant” adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm<sup>3</sup> (control group). In both groups, the majority were women (81.5% – study group, 90.5% – control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3–0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>

Cystic Parathyroid Adenomas as a Risk Factor for Severe Hypercalcemia.

(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.

PSAT219 Renal Phosphate Wasting Caused by ENPP-1 mutation.

Abstract Background Increased renal phosphate loss can be Fibroblast Growth Factor-23 (FGF-23) dependent or independent. FGF-23 reduces expression of Sodium-Phosphate co-transporters, responsible for phosphate reabsorption; and by inhibition of 1-alpha hydroxylation of 25-OH-D3. Reduced serum concentration of 1, 25-OH2-D3 results in secondary hyperparathyroidism. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) mutation is one of the rarest causes of hypophosphatemia, which causes FGF-23 dependent hypophosphatemia. Case description 31-year-old female referred to endocrinology for evaluation of recurrent nephrolithiasis despite normalization of PTH and serum Calcium (Ca) after right inferior parathyroid adenoma resection. Repeated renal stone analysis revealed calcium phosphate as the major stone composition. Patient achieved mid parental height, denied history of calcium or phosphate metabolism disorders/ rickets in the family. Physical exam was not suggestive of rickets and skeletal survey showed normal bone mineralization. Initial labs following parathyroid adenoma resection showed normal Ca 9.7 mg/dl, PTH 47 pg/ml, Phosphorus (Ph) 2.3 mg/dl, 25-OH-D3 51 ng/ml, albumin 3.9 g/dl, Mg 1.8 mg/dl. Repeat fasting labs six months later revealed Ca 9 mg/dl, Ph 1.7 mg/dl, 25-OH-D3 52 ng/ml, PTH 67.5 pg/ml and albumin 3.7 g/dl. Persistent low serum phosphate was evaluated further by a 24-hour urine collection which revealed high urine phosphate of 828 mg/day, Ca 181 mg/day, Mg 23 mg/day and creatinine was 1485 mg/day. Tubular reabsorption of phosphorus was 77% (normal: >80%), indicating renal phosphate wasting. Serum FGF-23 on two different days was >180 RU/ml. Next-generation sequencing tested positive for heterozygous ENPP-1 gene mutation variant c1441C>T (p. Arg481Trp). Patient was started on oral Phosphorus supplementation & calcitriol. Repeat labs showed normalization of Ph 2.4 mg/dl. Audiology evaluation suggested mild sensorineural hearing loss. Heart calcium score was zero. Discussion ENPP1 gene mutation's clinical presentations can vary from no symptoms, hypophosphatemic rickets to death in the first six months of life from generalized arterial calcification. ENPP1 is an enzyme, which degrades ATP into adenosine monophosphate (AMP) and pyrophosphate (PPi). PPI is an inhibitor of hydroxyapatite crystallization in vascular tissue and organs, while Ph is a pro-mineralization factor. ENPP1 gene mutation results in a low concentration of PPi, predisposing the patient to pathological calcification. It is speculated that ENPP-1 modulates FGF-23 secretion. FGF-23 elevation in these patients is a protective response, as hypophosphatemia prevents pathological calcification. Treatment target is to keep phosphate at low end of normal. In our patient, ENPP- 1 mutation likely contributed to recurrent renal stones and possible parathyroid adenoma. Evaluation of genetic mutations is necessary to decide for or against FGF-23 antibody/Burosumab treatment. In ENPP-1 mutation. Burosumab should be avoided as it can bind to FGF-23 resulting in pathological calcification. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Proximal tubular dysfunction related to tenofovir in people living with HIV/AIDS: a pharmacogenetic study.

The purpose of this case-control study was to verify the association between single nucleotide polymorphisms (SNPs) in genes encoding drug transporters related to tenofovir disoproxil fumarate (TDF) and proximal renal tubular dysfunction (PRTD), and the association between PRTD and clinical characteristics. The 'cases' met the diagnostic criteria for PRTD, determined by the presence of two or more of the following abnormalities: non-diabetic glycosuria, metabolic acidosis, increased uric acid and phosphorus excretion, decreased tubular phosphorus reabsorption and β2-microglobulinuria. We analyzed eight SNPs in ABCC2, ABCC4, ABCC10 and SLC28A2 genes. Genotyping was performed using real-time PCR. Of the 204 people living with HIV, 38 (18.6%) met the criteria for diagnosis of PRTD and 131 were male (64.2%), with a mean age of 49 years and a history of previous antiretroviral therapy for an average of 5 years. In the multivariate analysis, older individuals, TDF use, protease inhibitor, antihypertensives and anticonvulsants were associated with a risk of developing PRTD. Increased excretion of β2microglobulin was associated with the A/G genotype of rsCC8187710 from ABCC2 ( P = 0.003) and the following genotypes of ABCC4 SNPs: A/G from rs1059751 ( P = 0.023), G/G from rs1059751 ( P = 0.030) and C/C of rs3742106 ( P = 0.041). The increase in the fraction of excreted phosphorus was associated with the C/T genotype of SNCC rsP40037 from ABCC2 ( P = 0.0041). The results indicate an important relationship between SNPs associated with these markers and changes in proximal renal tubule function, and thus support their use as biomarkers for the early detection of PRTD risk.

Abstract 159: Glomus tumour presenting with oncogenic osteomalacia

Introduction: Tumour induced osteomalacia (TIO) is a rare paraneoplastic syndrome of mostly, benign mesenchymal tumours. Glomus tumours causing TIO is a very rare entity. We present a case of unresectable locally invasive glomus tympanicum with hypophosphatemic osteomalacia being misdiagnosed as bone metastases.Case Synopsis: 55 year old man presented with difficulty walking for the 2 years and wheel chair bound for 3 months. Past medical history revealed multiple surgeries for recurrent glomus tympanicum -left ear in 2011, 2013 and 2015. Tumour recurred in 2019-unresectable. Due to his bone pain, a Tc 99 MDP scan done showed increased tracer uptake in multiple ribs bilaterally and iliac bones which was interpreted as metastasis - given radiation therapy and chemotherapy. On examination- Lower limb power was 3/5 bilaterally. Other systemic examination was normal. Investigations showed S. Calcium of 8.5 mg/dl, S. phosphorus – 1.3 mg/dl with ALP- 424 IU/L, 25 (OH) D- 21 ng/ml, S. creatinine -0.9 mg/dl and iPTH-115 pg/ml. His 24 hour urine Calcium, Phosphorus and Creatinine were 107 mg, 588 mg and 1260 mg per day. Tubular reabsorption of phosphorus was 70% with TmP GFR of 1.1 suggesting renal phosphate wasting. MRI spine showed multiple vertebral compression fractures and insufficiency fractures of iliac bones suggestive of metabolic bone disease. FGF 23 was 555.6 RU/ml (0-150). Hence tumour induced osteomalacia was diagnosed. Ga DOTANOC showed only the Left glomus tumour and no other lesion. He was started on oral phosphate and Vitamin D. After 3 months his bone pains have reduced by 40-50%, he is walking independently and his S. Phosphorus levels have increased to 2.5 mg/dl.

Effect of Iron Chelator on Renal Function in Thalassemia Patients who Undergo Regular Transfusion

Background: The thalassemia family of genetic disorders is characterized by an abnormal synthesis of the hemoglobin chain, resulting in chronic anemia in some people and clinically asymptomatic in others. There have been very few studies conducted on the effects of thalassemia on the kidneys, which typically included patients treated with deferoxamine having both glomerular and tubular dysfunction. Objective: This research aimed to determine whether kidney dysfunction is observed in young thalassemic individuals manipulating both conventional and primitive markers of kidney dysfunction, and to associate the results to the use of iron chelation therapy. Methods: We measured serum cystatin C (Cys C), tubular phosphorus reabsorption (TPRA), fractional sodium excretion (FNE), and 2-microglobulin, urine calcium, protein, and glucose levels in addition to the usual renal biochemistry. Results: A whole of 42 individuals, ranging in age from 4 to 23, were included in this study and were split into two groups for study (group A taking deferoxamine alone, and group B taking deferiprone coupled with deferoxamine). An increased Cys C level (36%) and proteinuria (24%) were seen in a large percentage of patients, as were tubulopathy with hypercalciuria (35.5 %) and point out 2-MG excretion (33.5 %). Conclusion: Patients with -thalassemia seem to suffer from renal dysfunction even when they are young, so it is important to monitor early signs of renal dysfunction. There is a need for further research into the effect of novel chelators on parameters tubular function. Keywords: Deferiporin, iron chelator, thalassemia, Peshawar, dfo

Transient Type 3 Renal Tubular Acidosis during Cyclic Vomiting Syndrome

Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.

Renal manifestations in children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neurocutaneous syndrome affecting various parts of the body, including the renovascular and urinary systems. We evaluated the renovascular, urinary, glomerular, and tubular functions of children with NF1. We compared blood pressures, urinary findings, and renal glomerular and tubular functions in children with NF1 with those of a healthy age- and gender-matched control group. We evaluated 46 NF1 patients and 33 healthy controls. The mean ages of the NF1 group (female/male: 20/26) and the control group (female/male: 15/18) were 10.1 ± 4.6 and 10.6 ± 4.3 years respectively. Six NF1 patients were hypertensive. The mean blood pressures of the NF1 group were significantly higher than those of the control group. Renal artery stenosis was detected in one NF1 patient. Urinary tract anomalies were evident in 21.7% of NF1 but only 9% of control subjects. The mean estimated glomerular filtration rate (eGFR) of the NF1 group was significantly lower than that of the control group. Six NF1 patients evidenced eGFRs < 90 mL/min. In the NF1 group, tubular phosphorus reabsorption was significantly lower and uric acid excretion significantly higher than in the control group.Conclusion: Hypertension, urinary tract anomalies, and impaired renal function were more common in NF1 patients than healthy controls. Regular blood pressure measurements and evaluation of urinary tract and kidney function are essential for NF1 patients. What is Known: • NF1 is most commonly associated with systemic hypertension due to renal artery vasculopathy and the development of a pheochromocytoma. • Hydronephrosis and bladder involvement have been documented in NF1. What is New: • Renal glomerular and tubular functions may be affected in NF1.

Kidney and Urinary Tract Involvement in Epidermolysis Bullosa: Is Routine Follow-Up Necessary?

Several renal and urinary tract complications have been reported in patients with epidermolysis bullosa. This study investigated kidney and urinary tract involvement in patients with epidermolysis bullosa. Patients with epidermolysis bullosa in treatment at the Dermatology Unit were included in the study. Glomerular and tubular functions were investigated. The study included 16 patients (4 females, 12 males) of mean 11.1 years (SD = 8.1 years). Estimated GFR was normal in all patients except one with end-stage renal disease. Excluding this patient, the urinary albumin/creatinine ratio and the fractional excretion of sodium were normal. The mean beta-2 microglobulin/creatinine ratio was 278.8 μg/g, and it was abnormally high in 2 patients. The mean tubular phosphorus reabsorption was 92.6%; it was abnormally low in 1 patient. Severe kidney or urinary tract involvement was present in 2 patients with recessive dystrophic EB-generalized severe (RDEB-GS): one patient had obstructive bullous lesions in the urethra; the other had end-stage renal disease secondary to focal segmental glomerulosclerosis and was on peritoneal dialysis for 3 years. Assessment for renal and urinary tract involvement should become a routine part of the evaluation of patients with any type of EB, but especially of patients with RDEB-GS. Patients with mild tubular dysfunction need long-term follow-up to detect early deterioration of renal function.

Primary Hyperparathyroidism From Ectopic Parathyroid Adenoma in a Patient With Bilateral Slipped Capital Femoral Epiphysis

Background: Primary hyperparathyroidism has been reported in 13 pediatric patients presenting with slipped capital femoral epiphysis (SCFE), but never in patients with ectopic parathyroid adenoma [1]. Case report: A 12-year-old boy with obesity (BMI 99th percentile) and autism spectrum disorder presented with a limp and was found to have bilateral SCFE. Calcium was elevated to 12.3 mg/dL (reference range 8.0–10.5) with phosphorus of 3.2 mg/dL (3.0–5.7), alkaline phosphatase 775 units/L (40–360), tubular reabsorption of phosphorus 89% (> 95%), 25OH-vitamin D 12.1 ng/mL (30–80), 1,25OH-vitamin D 246.6 pg/mL (19.9–79.3), and PTH 1191 pg/mL (10–65). He had significant neuropsychiatric agitation but denied constipation, polyuria, and other symptoms of hypercalcemia. He had in situ pinning of the SCFE bilaterally and was hyperhydrated with minimal improvement in his calcium level. Neck ultrasound revealed no parathyroid adenoma. He was discharged on cholecalciferol 1000 IU daily with plans for outpatient Tc-99m Sestamibi scintigraphy. Following discharge, he developed significant nausea, did not tolerate the cholecalciferol, and was non-weight bearing. Repeat labs and imaging 5 days later demonstrated calcium had risen to 16.7 mg/dL with phosphorus of 2.2 mg/dL. He was admitted and calcium improved transiently to less than 12 mg/dL with intranasal calcitonin therapy. Sestamibi and subsequent CT scan revealed a 2.7x1.6x1.9 cm ectopic parathyroid adenoma in the upper anterior mediastinum. He had thoracoscopic resection of the mass, which was revealed to be intrathymic, and PTH levels fell from 1613 pg/mL pre-operatively to 76 pg/mL 30 minutes post-resection. Post-operatively, he developed hungry bone syndrome with a calcium nadir of 7.6 mg/dL and phosphorus nadir of 1.6 mg/dL, which required oral calcium and calcitriol for 10 days. With normalization of his calcium, his neuropsychiatric symptoms improved. Pathology revealed a parathyroid adenoma. Conclusion: Primary hyperparathyroidism can be associated with SCFE and should be considered even in patients with traditional risk factors for SCFE, especially with bilateral disease. Pediatric patients with primary hyperparathyroidism and negative neck imaging should be further evaluated for ectopic parathyroid adenomas.

MON-353 Tumor-Induced Osteomalacia from a Hypervascular Thoracic Paraspinal Mass: Challenges in Diagnosis and Management

Background: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome driven by ectopic production of fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting, hypophosphatemia, and bone demineralization. Successful therapy requires complete resection of the tumor, which is often challenging to localize. Clinical Case: A bedridden 37-year-old woman presented to Endocrine Clinic after 9 years of progressive pain and weakness in her back, hips, and extremities. She had previously been diagnosed with a neurodegenerative disease, though an MRI from 5 years ago showed bilateral subacute sacral ala fractures. CT scan on presentation showed generalized osteopenia and numerous subacute to chronic atraumatic fractures (involving ribs, scapula, pubic rami, and right femoral shaft) concerning for osteomalacia. On exam, she had profound lower extremity weakness. Laboratory testing was notable for serum phosphorus 0.6 mg/dL (normal (nl) 2.5-4.9), calcium 8.4 mg/dL (nl 8.5-10.5), PTH 216 pg/mL (nl 13-85), 25-OH vitamin D 26 ng/mL (nl 30-100), alkaline phosphatase 345 U/L (nl 45-130), 1,25-(OH)2 vitamin D 28 pg/mL (nl 18-72), renal tubular phosphorus reabsorption TmP/GFR 0.53 mg/dL (nl 2.97-4.45), and inappropriately normal FGF23 level 170 RU/mL (nl<180). Phosphate salts, calcitriol, and cinacalcet were initiated. Octreotide scan was negative, but 18F-FDG PET/CT showed mild hypermetabolic activity in the lower thoracic paraspinal area correlating with a 3.4 cm hypervascular mass near the left 8th rib head and two adjacent nodules on MRI. Due to bleeding risk, biopsy was deferred and further confirmatory studies were pursued. Genetic testing for hereditary forms of hypophosphatemia (FGF23, CLCN5, DMP1, ENPP1, FGFR1, PHEX) was negative. 68Ga-DOTATATE PET/CT was not available, but selective venous sampling for FGF23 revealed a 3:1 ratio between venous drainage of the tumor bed and general circulation. Based on this localization, surgical resection was performed. Pathology was consistent with a phosphaturic mesenchymal tumor, but clear margins could not be confirmed due to intraoperative tumor fragmentation. Three months of medical management with phosphate salts and calcitriol normalized her phosphorus levels (2.5-3.3 mg/dL), and she underwent surgical repair of her femoral fracture. Although MRI revealed only postsurgical changes in the spine, her continued requirement for phosphate supplementation and persistently elevated FGF23 levels (258 RU/mL) are concerning for residual tumor. Conclusion: This case illustrates the challenges of TIO due to a hypervascular mass in a rare paraspinal site localized by selective venous sampling for the first time at our institution. The patient’s continued FGF23 elevation underscores the importance of advancing medical therapies, such as burosumab, in patients with TIO that are not amenable to complete surgical resection.

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.

Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney.

ABSTRACTIntroduction:Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK.Methods:Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA.Results:The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/ Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/ CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/ Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/ Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively).Conclusions:MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

MON-499 Tumor Induced Osteomalacia: 68Ga-DOTATATE PET/CT Scan For Localization

Introduction: Tumor Induced Osteomalacia (TIO) is a rare condition and a notoriously difficult diagnosis to make due to lack of awareness and nonspecific symptoms. But it is a surgically curable disease, so it should not be missed. We are reporting a case of TIO in a patient with insufficiency fractures who was initially diagnosed as ‘severe osteoporosis’. Clinical Case: A 60-year-old female presented to the Metabolic Bone Disease Clinic at our institution for recurrent stress fractures of hip and femur. A recent DXA scan showed worsening of BMD at the spine and hip with T-scores of -5.0 and -4.3 respectively. She was taking calcium and vitamin D supplementation. She had previously taken Alendronate and stopped for unclear reasons. She was taking Denosumab at the time of her presentation to our clinic. She was found to have very low phosphorus level of 0.8 mg/dl. Osteomalacia was suspected, so we asked her to stop Denosumab. Phosphorus replacement was started and she remained hypophosphatemic with phosphorus levels <1 mg/dl despite increasing doses of phosphorus supplements. A 24-hour urine phosphorus and fractional excretion of phosphorus was inappropriately elevated. A diagnosis of hyperphosphaturic hypophosphatemia causing osteomalacia was made. A hereditary disorder such as X-linked hypophosphatemia was not considered because of lack of family history and onset at an adult age. FGF-23 was elevated and a diagnosis of TIO was made. We used 68Ga-DOTATATE PET/CT scan as our initial, and single test for functional imaging/identification of the culprit tumor. The scan showed uptake in the left proximal medial tibia. Anatomical imaging with MRI confirmed the lesion. She underwent surgery for excision of the tumor and fixation of the tibia. Pathology was consistent with phosphaturic mesenchymal tumor. During follow up, phosphorus levels normalized within one month of surgery. She is currently doing well without any symptoms and no new fractures. We plan to repeat DXA scan and perform periodic monitoring of phosphorus level. Conclusion: TIO is a paraneoplastic disorder caused by FGF-23 secreted by mesenchymal tumors. It results in decreased reabsorption of phosphorus from the proximal tubule of kidneys, causing hyperphosphaturia and subsequently hypophosphatemia leading to defective mineralization of bones. A high index of suspicion is needed to diagnose this rare disorder. Any patient with an insufficiency fracture or a new referral for osteoporosis should have phosphorus level checked. If the phosphorus level is low, renal tubular reabsorption of phosphorus should be evaluated by measuring 24-hour urinary excretion of phosphorus. The culprit tumor should be localized using advanced imaging modalities such as 68Ga-DOTATATE PET/CT scan.

Henoch Schönlein Purpura in children: Clinical features and risk factors for renal involvement

Objective: This study aimed to evaluate the clinical and laboratory features of children diagnosed with Henoch Schonlein purpura (HSP), risk factors of renal involvement and their effect on prognosis. Methods: A total of 80 pediatric HSP patients (44 males and 36 females) between ages 2 to 13 (average age 7.68±3.09) admitted to the Pediatrics Clinic and follow-up cases from the Pediatric Rheumatology and Nephrology Clinic of the Istanbul Medeniyet University, Goztepe Training and Research Hospital, between April 1998 and June 2003 were enrolled for the study. In order to precisely evaluate glomerular and tubular function, urinary β 2 microglobulin, microalbumin and tubular reabsorption of phosphorus (TRP) were determined. Results: A retrospective evaluation of the HSP patients showed that 26 (32.5%) had symptoms of renal impairment. In terms of renal function, 20 (25%) out of the 54 asymptomatic children initially subjected to routine renal tests had renal involvement. In terms of age, there was a significant difference (p < 0.016) in developing renal involvement between patients above 5 years old and those younger than 5 years. Conclusion: It was therefore suggested that long-term follow-ups in addition to examinations such as routine kidney function tests, tubular reabsorption of phosphate (TRP) and microalbumin levels should be conducted in order to detect the early phase of renal damage.

Degree of functional capacity, bone mineral density and phosphocalcic metabolism alterations in paediatric patients with reduced mobility

Mobility is essential for adequate bone mineralisation. Neuromuscular diseases can cause pathological fractures, bone pain, and a decrease in bone mineral density (BMD). Establish the association between BMD, phosphocalcic metabolism parameters, and degree of functional capacity. Observational, cross-sectional and prospective study in children under 18 with reduced mobility. The selection is performed by consecutive, non-randomised sampling. Variables analysed: age, gender, functional capacity according to the Functional Mobility Scale (FMS), which evaluates the ability to walk in 3 distances (5 metres, 50 metres and 500 metres) from 0 to 6, BMD (L2-L4) by DXA expressed in Z-scores according to bone age and gender, calcium, phosphorus, parathormone, 25-hydroxy-vitamin D3, alkaline phosphatase and osteocalcin in blood and calcium/creatinine ratio, tubular reabsorption of phosphorus and cross-linked N-terminal telopeptides of type I collagen in urine (NTX-I). Alkaline phosphatase, osteocalcin and NTX-I values are expressed in standard deviations according to reference values for age/gender. The results are analysed with the SPSS programme. Thirty-six patients (53% children), average age of 8.6 ± 4.7 years. Mean FMS value was 5.3 out of 18 (36% obtained a value of 0). Mean BMD was −1.99 ± 1.7, average alkaline phosphatase was −2.64 ± 1.08 SD, mean osteocalcin was −2.15 ± 1.39 SD, and mean NTX-I was +3 ± 1.72 SD. A significant association was observed between BMD and the FMS for the 5-metre distance ( P = 0.017) and for the total score ( P = 0.029), and between parathormone and the FMS at 5 ( P = 0.041), 50 ( P = 0.033) and 500 metres ( P = 0.046). There is a decrease in BMD and in bone neoformation markers such as alkaline phosphatase and osteocalcin in our population, and elevation of bone resorption markers such as NTX-I. Patients with a lower degree of mobility have a lower BMD.

Comment on Chan et al. FGF23 Concentration and APOL1 Genotype Are Novel Predictors of Mortality in African Americans With Type 2 Diabetes. Diabetes Care 2018;41:178–186

We read with great interest the article by Chan et al. (1) demonstrating that fibroblast growth factor 23 (FGF23) concentration is a novel predictor of mortality in African Americans with type 2 diabetes. FGF23 is the main hormone mediating serum phosphorus concentration through inhibiting tubular reabsorption of phosphorus from the urine (2). Meanwhile, serum phosphorus is the main stimulus for FGF23 secretion. In progressive chronic kidney disease …

Changes With Lanthanum Carbonate, Calcium Acetate, and Phosphorus Restriction in CKD: A Randomized Controlled Trial

IntroductionAbnormal phosphorus homeostasis develops early in chronic kidney disease (CKD). It is unclear if its correction results in improved clinical outcomes in non–dialysis dependent CKD.MethodsWe conducted a randomized controlled, parallel design clinical trial in 120 patients with estimated glomerular filtration rate 15 to 59 ml/min per 1.73 m2 and abnormal phosphorus homeostasis (serum phosphorus >4.6 mg/dl, parathyroid hormone [PTH] >70 pg/ml or tubular reabsorption of phosphorus [TRP] <80%). Patients were randomized to open-label lanthanum carbonate versus calcium acetate versus dietary intervention over 1 year. The co-primary outcomes were month 12 (vs. baseline) biochemical (serum phosphorus, TRP, PTH, calcium, bone-specific alkaline phosphatase [bALP], and fibroblast growth factor 23 [FGF23]) and vascular parameters (coronary artery calcium score, pulse wave velocity, and endothelial dysfunction) in all patients. Secondary outcomes were between-treatment differences in change for each parameter between month 12 and baseline. All analyses were intention to treat.ResultsBaseline characteristics were similar in the 3 groups. A total of 107 patients (89%) completed 12 months of follow-up. Differences were not significant at month 12 (vs. baseline) for any of the outcomes except bALP (median [25th, 75th] percentile at month 12 versus baseline: 13.8 [10.6, 17.6] vs. 15.8 [12.1, 21.1], P < .001) and FGF23 (132 [99, 216] vs. 133 [86, 189], P = .002). Changes for all outcomes were similar in the 3 arms except for PTH, which was suppressed more effectively by calcium acetate (P < .001).ConclusionA 1-year intervention to limit phosphorus absorption using dietary restriction or 2 different phosphorus binders resulted in decreased bALP suggesting improved bone turnover, but no other significant changes in biochemical or vascular parameters in patients with CKD stage 3/4. (ClinicalTrials.gov: NCT01357317)

Association of brucellosis with renal tubular and glomerular damage in children in Turkey.

Brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations. Until now, no studies have been performed on renal tubular disorders in patients with brucellosis. The present study aims to investigate renal tubular disorders in patients with brucellosis. This prospective case-control study includes a total of 31 brucellosis patients (Group 1) and 30 healthy controls (Group 2) matched for age and sex. Renal tubular functions of children who were diagnosed as having brucellosis in outpatient pediatric clinics were evaluated. First-morning urine samples were collected from Group 1 and Group 2 at the same time. Urea, creatinine, potassium, sodium, and phosphorus were determined in serum and urine by an autoanalyzer. Tubular reabsorption and excretion of urine electrolytes were calculated using the related formulas. Patients with brucellosis had significantly lower levels of tubular reabsorption of phosphorus and serum phosphorus than those of the control group. Furthermore, urine sodium and serum potassium levels and fractionated sodium excretion of brucellosis patients were significantly higher than healthy control group. Estimated glomerular filtration rate was remarkably higher in the patient group (P < 0.001).We concluded that tubular and glomerular functional parameters demonstrate deterioration in patients with brucellosis compared to those in healthy participants.

Renal Function in Transfusion-Dependent β-Thalassemia Patients: A Decade of Follow-up and Comparison between Chelation Regimes

Introduction: Glomerular and tubular dysfunctions in β-thalassemia major (β-TM) patients (pts) have been attributed to iron overload, chronic anemia and iron-chelation therapy (ICT) toxicity. We studied glomerular and tubular function in β-TM pts treated with 2 different ICT regimes.Patients and methods: We studied 36 β-TM pts (18 females and 18 males). Mean age was 20.92 ± 9.7 (range 5-45) years. Pts were treated at Emek Medical Center under standard protocols for regular blood transfusions and ICT: 26 pts received deferasirox (DFX) for a mean period of 59 months; this was the first ICT for 6 of them; 10 pts were treated with deferoxamine (DFO) or DFO + deferiprone (DFP) (4 and 6 pts, respectively; hereafter DFO+/-DFP group). Clinical data were collected from pts' files.We evaluated serum urea, creatinine (sCr) and electrolytes, and estimated glomerular filtration rate (eGFR) according to the Schwartz formula for pediatric pts and the Chronic Kidney Disease Epidemiology Collaboration formula for adults; fractional excretion of sodium (feNa), fractional excretion of potassium (feK), calcium-to-creatinine ratio (Ca/Cr), uric acid excretion (UAE), and tubular phosphorus reabsorption were calculated. Urinary N-acetyl-β-D-glucosaminidase (uNAG) was also measured as a marker of tubular injury.Results: No significant differences were found in age, gender or mean hemoglobin (Hb) level between the groups. Levels of sCr, K, Na and feNa were in the normal range for all pts, as was eGFR (mean 104.6 ± 19 mL/min per 1.73 m2); in the DFX group, eGFR was slightly lower than in the DFO+/-DFP group (100.9 ± 17.09 vs. 114.0 ± 22.31 mL/min per 1.73 m2; p= 0.0676). Hypercalciuria (Ca/Cr > 0.25) was found in 28% of pts, increased feK (>15%) in 33%, high UAE (>0.56 mg/dL) in 64%, and high levels of TmP /GFR (>5mg/dL) in 25%. There were no differences in these parameters between the DFX and DFO+/-DFP groups.Increased uNAG was found in 9 pts (25%)-30% in the DFX group vs. 10% in the DFO+/-DFP group, and was significantly higher in the DFX group (mean 10.4 ± 6.1 vs. 5.3 ± 2.7 IU/L, p= 0.012). A moderate negative correlation was found between uNAG levels and mean serum ferritin for the prior 10 years (r= -0.35, p= 0.03). In the DFO+/-DFP group, a strong positive correlation was found between uNAG levels and the amount of iron transfused over the prior 10 years (r= 0.7647, p= 0.021); this correlation was not found in DFX pts. A moderate negative correlation was found for urinary Ca/Cr ratio with 10-year mean serum ferritin level and with 10-year amount of transfused iron (r= -0.35, p= 0.34; r= -0.4, p= 0.014, respectively). These correlations were stronger in the DFO+/-DFP group. A positive correlation was found between urinary Ca/Cr ratio and Hb levels, strongest in the DFO+/-DFP group than the DFX group (r= 0.41, p= 0.001, r= 0.7, p= 0.018), respectively.Renal function had been previously evaluated in 20 pts treated with DFO (Smolkin et al, 2008) and those results were compared with the current values. The eGFR significantly declined in pts switched to DFX (mean eGFR in first study 113.5 ± 26 vs. 100.1 ± 17 mL/min per 1.73 m2, p= 0.0093) but not in pts who continued DFO+/-DFP. A significant increase in sCr compared to the previous study was found in pts who switched to DFX (mean 0.51 ± 0.9 vs. 0.67 ± 0.1 mg/dl, p= 0.0008), but not in pts who continued treatment with DFO+/-DFP. The same observation was made regarding urine Ca/Cr (mean 0.08 ± 0.11 vs. 0.176 ± 0.12, p= 0.001).Conclusion: Ahigh prevalence of renal tubular abnormalities was observed in our pediatric and adult β-TM pts, particularly in the DFX group. The marker of tubular injury-uNAG-was negatively associated with mean 10-year serum ferritin, suggesting ICT's involvement in tubular injury. Moreover, uNAG was associated with transfusional iron burden in the DFO+/-DFP group, but not in the DFX group, proposing a mechanism other than iron overload for the pathogenesis of tubular injury in DFX-treated pts. Finally, glomerular function remained within the normal range in all pts; however a significant decline in glomerular function compared to a decade earlier was observed only in the pts currently treated with DFX. Strict follow-up of renal function in β-TM pts, especially children, is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.