An Unexplained Hyperphosphatemia in an Hispanic Woman , a Diagnosis Challenge

Introduction Hyperphosphatemia could be a finding in renal failure, tumor lysis syndrome, hypoparathyroidism, and ingestion of exogenous phosphate. We present the case of a woman with hyperphosphatemia in which we finally diagnosed multiple myeloma, serum phosphate level achieved normal range after chemotherapy started. Although hyperphosphatemia in multiple myeloma is a very rare finding, there are some reports. The proposed mechanisms include a large amount of paraproteins that interferes with phosphorus level determination showing a false increased level. When samples have been deproteinated before analysis, serum phosphorus level can decrease obtaining a true level. This case reminds clinicians the importance of seeking additional causes for abnormal phosphorus levels before starting treatments that could lead to hypophosphatemia. Case report An hispanic woman at the 7th decade of life that only suffered from controlled hypothyroidism, who assisted with complaints of axial pain mainly in thoracic and lumbar segments. She denied neurological and B symptoms. She had a CT scan performed and was referred to the hematology service.On clinical examination we didn't find any neurological signs, no megalies and no palpable nodes. The patient brought a CT spine scan showing thoracic images suggestive of mets with collapse of 50% in T12-L1 and a mass in S2.With these findings we decided to start intrahospitalary studies for excluding malignancy.Her relevant laboratories were: creatinine 0,7, BUN 25, Hemoglobin 9 gr/dl VCM 102 WBC 3330 Granulocytes 55% Platelet 222.000, UN 10,7, albumin 2.8, Lactate dehydrogenase 425. A series of labs seeking secondary causes of malignancy was made including plasmatic cell neoplasie.The hepatic function was normal but an unusually high Phosphorus level was detected (19,6) with normal calcemia (8.98), the tumoral biomarkers were in normal range (CEA, CA 19-9, Ca 125, AFP) and an elevated B2 microglobulin (8) was found. Additional labs included bence jones protein and PTH, both in normal range. A new Thoracic CT described mosaic infiltrates and an extensive bone involvement suggestive of lytic metastatic changes. The abdomen CT showed multiple lytic lesions in lumbo-sacral spine and pelvis, The skull radiography had lytic lesions too. The nephrology service was required by the Hyperphosphatemia and they asked about external intake of phosphorus finding that she was taking "hydrolyzed collagen", so they started iv fluid and chelators (aluminium hydroxide and no calcium chelators).Because of unresponsive hyperphosphatemia, nephrology started hemodialysis.Hematology found high IgG levels (5500) concluding the need for bone marrow studies . Finally a the bone marrow study was performed and prescribed steroids on suspicion of Multiple myeloma. Until this day the Phosphorus level still remained in high levels (17,7) despite hemodialysis sessions. The bone marrow study revealed a plasmatic cell population of 28,9% with big and abundant cytoplasm, some of them with binucleations suggestive of infiltration by plasmatic cell neoplasie. The seric electrophoresis revealed a paraprotein (seric protein of 9,3 with a monoclonal peak of gamma region of 3,4 gr/dl), the seric immunofixation was positive for a monoclonal IgG lambda component. With this report we began chemotherapy treatment for Myeloma with CyBorD regimen (Cyclophosphamide, Bortezomib, dexamethasone). After treatment was initiated, phosphorus level began to lower and achieved normal range (4.28) in the first two weeks. Then she was discharged to continue outpatient management. Nowadays she is receiving her 3rd chemotherapy cycle without complications, her phosphorus level still remains within normality. Conclusions Spurious hyperphosphatemia in patients with paraproteinemias like multiple myeloma can occur. The IgG monoclonal can interfere with the phosphomolybdate principle used in the assay of serum phosphate on most automated chemistry analysers. For labs which do not have a multilayered film technology based system, a serial dilution analysis of the suspected analyte could be performed. Disclosures No relevant conflicts of interest to declare.

Circulating phosphorus level and risk of prostate cancer: a Mendelian randomization study

Background Recent observational studies have suggested that circulating phosphorus levels are positively associated with risk of prostate cancer. However, little is known about the causal direction of the association. Objective To explore the potential causal relationship between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. Design Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) consisting of 79,148 cases and 61,106 controls. Single nucleotide polymorphisms (SNP) associated with serum phosphorus level were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse-variance weighted (IVW) method, supplemented with simple-median, weighted-median, maximum likelihood-based, MR-Egger regression and MR-PRESSO test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus level with risk of prostate cancer. Results In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus levels were used as instrumental variables. Genetically predicted serum phosphorus levels were associated with a 19% increased risk of prostate cancer (95% confidence interval (CI): 9%, 31%) per one SD increment of serum phosphorus by IVW (P = 1.82 × 10–4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.422). For meta-analysis, eight studies for dietary phosphorus intake and four for serum phosphorus levels were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus levels were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively. Conclusions Our study suggested a potential causal relationship between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer.

Hypophosphatemia and weaning of Mechanically Ventilated patients with Chronic Obstructive Pulmonary Disease during acute exacerbations

Background Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease. It is currently the third leading cause of death in the United State and is predicted to be the third leading cause of death worldwide by 2020 Objectives The aim of this study is to evaluate the predictive value of serum phosphorus level on weaning of mechanically ventilated chronic obstructive pulmonary disease (COPD) patients with acute exacerbation (AECOPD). Patients and Methods After approval of the medical ethics committee of Faculty of medicine, Ain Shams University, informed consents were taken from the patient’s next of kin to include their data in this study. Results In this prospective cohort study, 116 patients were assessed for enrollment. 26 patients were excluded due to very early mortality at day 1, administration of total parentral nutrition containing phosphorous and very low phosphorus level (less than 1.5 mg/dL or who needs correction). Conclusion In the light of the previous results Hypophosphatemia (1.5 - 2.5 mg/dL) was associated with poor prognosis in terms of longer durations of mechanical ventilations and higher ICU mortality rates in mechanically ventilated patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), Hypophosphatemia should be included in initial assessment of such patients to stratify them.

Therapeutic Effects of Add-On Tenapanor for Hemodialysis Patients with Refractory Hyperphosphatemia

<b><i>Introduction:</i></b> Phosphate binders are used to treat hyperphosphatemia. Some patients have inappropriately controlled serum phosphorus levels, which may occur for many reasons, including a high pill burden and adverse events (AEs). Tenapanor selectively inhibits the passive paracellular transfer of phosphate in the gastrointestinal tract, thereby reducing serum phosphorus levels. This novel mechanism of action may contribute to improved phosphate management. The efficacy and safety of tenapanor have not been evaluated in Japanese patients with high serum phosphorus levels despite treatment with phosphate binders. This study aimed to assess the efficacy and safety of add-on tenapanor therapy for reducing serum phosphorus levels in this population. <b><i>Methods:</i></b> This multicenter, double-blind, randomized, placebo-controlled trial enrolled patients with refractory hyperphosphatemia undergoing hemodialysis. Patients were randomly assigned in a 1:1 ratio to receive tenapanor or placebo as an add-on to their phosphate binder regimen for 6 weeks. Change in serum phosphorus levels at week 6 (day 43) compared with the baseline value (day 1, week 0) (primary endpoint), achievement of target serum phosphorus levels (serum phosphorus level ≤6.0 or ≤5.5 mg/dL), and safety, based on all AEs and drug-related AEs, were among the outcomes evaluated. <b><i>Results:</i></b> In total, 24 patients were randomly assigned to the placebo group and 23 to the tenapanor group. The mean serum phosphorus level decreased from 7.01 mg/dL on day 1 to 6.69 mg/dL on day 43 in the placebo group and from 6.77 mg/dL on day 1 to 4.67 mg/dL on day 43 in the tenapanor group. In the placebo and tenapanor groups (modified intent-to-treat population), the mean (standard deviation) change in the serum phosphorus level at day 43 (last observation carried forward [LOCF]) was 0.08 (1.52) mg/dL and −1.99 (1.24) mg/dL, respectively, with a between-group difference of −2.07 (95% confidence interval: −2.89, −1.26; <i>p</i> &#x3c; 0.001). The target achievement rate (serum phosphorus level ≤6.0 mg/dL at week 6 [LOCF]) was 37.5 and 87.0% in the placebo and tenapanor groups, respectively. Diarrhea was the most common drug-related AE, and it occurred in 8.3 and 65.2% of patients in the placebo and tenapanor groups, respectively. No specific AEs were observed with add-on tenapanor or with phosphate binders. <b><i>Discussion/Conclusion:</i></b> Therapy with existing phosphate binders and add-on tenapanor resulted in a significant decrease in serum phosphorus level compared with the placebo group in patients with refractory hyperphosphatemia despite treatment with phosphate binders. No new safety signals were raised, and add-on tenapanor was generally well tolerated.

Persistent Calciphylaxis and Secondary Hyperparathyroidism in End Stage Renal Disease Patient Due to Ectopic Mediastinal Parathyroid Adenoma- A Case Report

Intruducion: Secondary hyperparathyroidism (SHPT) is prevalent in patients with end-stage renal disease (ESRD) with reported prevalence of 90%. SHPT treatment is usually medical. Although 5% ends up with parathyroidectomy. Indications of parathyroidectomy in ESRD patients include persistent elevation of PTH more than 800, Calcyphylaxis, Osteitis Fibrosa Cystica, and persistent anemia. Among these patients who require surgery, 5–20% present with persistent or recurrent disease and require further re-exploration and excision of parathyroid tissue. We present a case of persistent Calciphylaxis and SHPT in ESRD patient despite Parathyroidectomy which prompted diagnosing an ectopic mediastinal parathyroid adenoma. Case Presentation: 49 year-old male with ESRD for 15 years complicated with SHPT, presented due to worsening Caciphylaxis of bilateral lower extremities despite Cinacalcet, IV sodium thiosulfate, and Phosphate binder. Serum Calcium level was 9.0 mg/dl with corrected levels of 10.2 mg/dl, Phosphorus level of 9.3 with Intact PTH level 1,369 pg/ml. Ultrasound of parathyroid glands was normal. Due to failure of medical treatment, He underwent Total parathyridectomy and left arm parathyroid autograft. Intraoperative PTH level went down to 300 (less than 50%). Calciphylaxis never improved. 5 months later, Parathyroid hormone was elevated 1338 pg/ml, Calcium level 6.9 mg/dl and Phosphorus level 10.0 mg/dl. 99mTc-sestamibi parathyroid scan didn’t show any activity in thyroid gland area and no increased uptake at the autograft area. Although it showed a small focus of persistent activity in substernal area suggestive of ectopic parathyroid tissue. Patient was referred for removal of ectopic adenoma. Discussion: Persistent SHPT is identified as the persistence or recurrence of symptoms, lab abnormalities and radiologic findings within 6 months after parathyroidectomy. Pathophysiology of recurrence is not well studied but one theory suggests that in SHPT, altered Calcium-phosphate hemostasis leads to hyperplasia of parathyroid tissue including ectopic and supernumerary tissue. This aforementioned altered hemostasis continues even after parathyroidectomy and cause hyperplasia and hyperfunction of the residual parathyroid tissue left accidentally by seeding within surgical site or implanted autograft or It can present with ectopic adenoma, even if they were undetected prior to or in the first intervention. Ectopic parathyroid tissue is an uncommon etiology of persistent or recurrent secondary hyperparathyroidism, it is reported in many cases where it was missed at initial workup. Prevalence reported up to 14% in patients with persistent SHPT. It is warranted further investigations to look for ectopic parathyroid tissue in patients with ESRD who present with recurrent or persistent secondary hyperparathyroidism after total parathyroidectomy with reimplantation.

MO456DOES PHOSPHORUS EXCRETION PER NEPHRON AFFECT THE PROGNOSIS OF CHRONIC KIDNEY DISEASE?

Background and Aims Serum phosphorus is an important factor associated with mortality and cardiovascular disease in dialysis patients as well as in non-dialysis patients with chronic kidney disease (CKD) and healthy individuals. One observational study reported that elevated phosphorus is a risk factor for end-stage renal disease and is linked to reduced renal function, even within the normal range. Although the mechanism is unknown, an excessive load of phosphorus to the kidney is presumed to cause renal damage via phosphorus-containing nanoparticles. In this study, we examined the association between phosphorus excretion per nephron and the prognosis of CKD. Method A single-center, retrospective cohort study was conducted in 276 patients with CKD category G3 to G5 who were admitted to our hospital and received an inpatient educational program on CKD between June 2016 and November 2019 and who could be followed up for at least 1 year or started on dialysis within 1 year after hospitalization. Phosphorus excretion per nephron was defined as daily phosphorus excretion divided by creatinine clearance (Ccr), and its association with the annual rate of decline in estimated glomerular filtration rate (eGFR) was investigated for each CKD category. For statistical analysis, multiple regression analysis was performed using the following covariates: age, sex, presence/absence of diabetes mellitus, mean arterial blood pressure, amount of daily urine protein, serum phosphorus level, and use of a renin-angiotensin system inhibitor. Results There were 108 patients with CKD G3, 106 patients with CKD G4, and 62 patients with CKD G5. Daily phosphorus excretion was 442 mg in G3, 350 mg in G4, and 350 mg in G5 patients. Phosphorus excretion per nephron was 8.4 mg/Ccr in G3, 14.0 mg/Ccr in G4, and 24.2 mg/Ccr in G5 patients. It increased with the progression of renal damage. In G4 patients, phosphorus excretion per nephron was significantly negatively correlated with the rate of decline in eGFR (p = 0.004); however, no correlation was found between the two in G3 and G5 patients (p = 0.09 and p = 0.16, respectively). Multiple regression analysis showed that phosphorus excretion per nephron was not a significant worsening factor for renal function in G3, G4, and G5 patients (p = 0.09, p = 0.36, and p = 0.41, respectively). On the other hand, serum phosphorus level was a significant worsening factor for renal function in G3 and G5 patients (p = 0.03 and p = 0.01, respectively). Conclusion No association was found between phosphorus excretion per nephron and the rate of the subsequent decline in renal function.

MO582LONGITUDINAL STUDY TO FIND THE ASSOCIATION OF SERUM PHOSPHORUS LEVEL WITH FGF 23 IN THREE DIFFERENT HYPERPHOSPHATEMIA MANAGEMENTS GROUPS OF STAGE 3 AND 4 CHRONIC KIDNEY DISEASE (CKD) PATIENTS

Background and Aims There were paucity of clinical evidence on target serum phosphorus levelsin early CKD. Present longitudinal study finds target phosphorus level and its association with FGF 23 in three different hyperphosphatemia managements groups. Method This one year, prospective, randomised controlled, open labelled study was conducted among three equally allocated treatment groups in 120 screened early CKD patients.Group1 Dietary phosphorus modificationn40; Group2 calcium-based phosphate bindersn40 and Group3 non calcium-based phosphate bindersn40.Three monthly dietary assessment, MDRD e-GFR, phosphorus, calcium, iPTH, Alkaline phosphatise and six monthly FGF23, 2D Echocardiography, X ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9 mg/dl, 4 to 5mg/dl and &gt;5mg/dl, rate of progression of all parameters and correlation with FGF 23among all three groups were studied. Results At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 in all the three categories of phosphorus level among all groups. Association of serum phosphorus at the level of 5 mg/dl was there with iPTH and e-GFR at one year. Over one year there were significant decline in serum phosphorus levels in Group1 p 0.02, Group2 p 0.00,Group3p 0.05;FGF23 was declined significantly only in group3p 0.00.Correlation of FGF23 was positive and negative with iPTH r 0.19,p 0.03 and e-GFR r-0.30, p 0.00respectively but not with phosphorus p0.13 Conclusion Serum phosphorus levels up to 5mg/dl has no effect on FGF 23 at early CKD stages. Although different treatment groups have significant phosphorus reduction, non-calcium phosphate binder has major impact on FGF23 reduction.