Serum Phosphate In Patients Research Articles

In-center Nocturnal Hemodialysis Reduced the Circulating FGF23, Left Ventricular Hypertrophy, and All-Cause Mortality: A Retrospective Cohort Study.

Fibroblast growth factor 23(FGF23) is the most important biomarker and pathogenic factor in Chronic Kidney Disease–Mineral and Bone Disorder (CKD–MBD). In the moderate and severe stages of chronic renal failure, abnormally elevated circulating FGF23 can lead to some complications, including myocardial hypertrophy, which is positively correlated with all-cause mortality. However, the circulating FGF23 level of different hemodialysis modalities, the underlying essential regulatory factors, and potential clinical benefits remain to be elucidated. In this retrospective cohort study, 90 in-center nocturnal hemodialysis (INHD) and 90 matched conventional hemodialysis (CHD) patients were enrolled. The complete blood count, intact FGF23(iFGF23), calcium, phosphorus, PTH, and other biochemical and echocardiographic parameters of INHD and CHD patients were collected and analyzed at 1-year follow-up. The all-cause mortality was recorded during the 7-year follow-up. Furthermore, the regulatory factors of iFGF23 and its association with echocardiographic parameters and mortality were investigated by multivariate regression. The levels of iFGF23 and serum phosphate in patients undergoing INHD were significantly lower than those in patients undergoing CHD. The left ventricular volume index (LVMI) in patients with INHD was significantly attenuated and positively correlated with the drop of serum iFGF23. The INHD group had reduced all-cause mortality compared to the CHD group. Multivariate analysis showed that iFGF23 was positively correlated with serum calcium, serum phosphorus, and calcium-phosphate product. The calcium-phosphate product is an independent determining factor of serum iFGF23. Compared with the CHD group, the INHD group presented with a significantly reduced circulating iFGF23 level, which was closely associated with attenuation of left ventricular hypertrophy, but INHD reduced all-cause mortality in an FGF23 independent manner.

A study of serum phosphate levels and its correlation with curb-65 score in community acquired pneumonia

Background: Community acquired pneumonia (CAP) refers to pneumonia contracted by a person with little or no contact with health care system. Phosphorus is an essential molecule in ATP, playing a central role in energy production. A normal range is 2.5 to 4.5 mg/dl. Phosphate disturbance are noted in patients with pneumonia. Hypophosphatemia, plays a role in impairing chemotaxis, phagocytosis and bactericidal activity of macrophages. Hyperphosphatemia in pneumonia result in hypocalcaemia and pulmonary calcification. Hence study of serum phosphate levels in community acquired pneumonia is of clinical significance.
 Aims and Objective: The was aimed to estimate the levels of serum phosphate in patients with community acquired pneumonia and to correlate serum phosphate levels with CURB 65 severity score.
 Materials and Methods: Seventy-five CAP patients admitted as inpatients are included in this study. Chest X ray is obtained in all suspected cases. Serum phosphate levels are determined through blood investigation on Day 1 and Day 3.
 Results: Serum phosphate levels on Day 1 and Day 3 were significantly associated with CURB65 score. Both high and low phosphate levels were associated with high CURB 65 score. The association between phosphate levels and CURB 65 score was significant in patients who got discharged but not in patients who expired.
 Conclusions: Present study of serum phosphate levels as biomarkers in CAP showed that both hypophosphatemia and hyperphosphatemia carried poor prognosis which correlated with high CURB65 score.

Effect of Phosphate-Specific Diet Therapy on Phosphate Levels in Adults Undergoing Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Hyperphosphatemia is a persistent problem in individuals undergoing maintenance hemodialysis, which may contribute to vascular and bone complications. In some dialysis centers, dietitians work with patients to help them manage serum phosphate. Given the regularity of hyperphosphatemia in this population and constraints on kidney dietitian time, the authors aimed to evaluate the evidence for this practice. There was a systematic review and meta-analysis of clinical trials. MEDLINE, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and other databases were searched for controlled trials published from January 2000 until November 2019 in the English language. Included studies were required to examine the effect of phosphate-specific diet therapy provided by a dietitian on serum phosphate in individuals on hemodialysis. Risk of bias and certainty of evidence were assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method. Of the 8054 titles/abstracts identified, 168 articles were reviewed, and 12 clinical trials (11 randomized, one nonrandomized) were included. Diet therapy reduced serum phosphate compared with controls in all studies, reaching statistical significance in eight studies, although overall certainty of evidence was low, primarily due to randomization issues and deviations from protocol. Monthly diet therapy (20-30 minutes) significantly lowered serum phosphate in patients with persistent hyperphosphatemia for 4-6 months, without compromising nutrition status (mean difference, -0.87 mg/dl; 95% confidence interval, -1.40 to -0.33 mg/dl), but appeared unlikely to maintain these effects if discontinued. Unfortunately, trials were too varied in design, setting, and approach to appropriately pool in meta-analysis, and were too limited in number to evaluate the timing, dose, and strategy of phosphate-specific diet therapy. There is low-quality evidence that monthly diet therapy by a dietitian appears to be a safe and efficacious treatment for persistent hyperphosphatemia in patients on HD.

Efficacy and Safety of Tenapanor in Patients with Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial

Guidelines recommend reducing elevated serum phosphate in patients with CKD. Tenapanor, a minimally absorbed inhibitor of gastrointestinal sodium/hydrogen exchanger 3 (NHE3), reduces paracellular phosphate transport. In this phase 3 randomized, double-blind trial, we randomly assigned patients with hyperphosphatemia receiving maintenance hemodialysis to receive twice-daily oral tenapanor (3, 10, or 30 mg [the latter down-titrated, if needed]) for 8 weeks. Patients were then rerandomized 1:1 to receive either their previously assigned dose or placebo for a 4-week 'withdrawal' period. We measured serum phosphate levels over the course of the trial. The primary end point was mean change in serum phosphate over the 4-week withdrawal period for the tenapanor group (using pooled data) versus the placebo group. Of 219 patients randomized, 152 completed both study phases. During the initial 8-week treatment period, all three treatment groups experienced significant decreases in mean serum phosphate (reductions of 1.00, 1.02, and 1.19 mg/dl, corresponding to the 3, 10, and 30 mg [down-titrated] dose groups, respectively). Tenapanor also showed a significant benefit over placebo during the withdrawal period, with a mean increase of 0.85 mg/dl in the placebo group versus a mean increase of 0.02 mg/dl in the pooled tenapanor group. Adverse events were largely limited to softened stool and a modest increase in bowel movement frequency, resulting from increased stool sodium and water content, stemming from tenapanor's mechanism of action. Tenapanor significantly reduced elevated serum phosphate in patients with hyperphosphatemia receiving maintenance hemodialysis. Adverse effects were limited to those induced by its known mechanism of action, which increases stool sodium and water content.

Effect of Tenapanor on Serum Phosphate in Patients Receiving Hemodialysis.

Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis. After a 1- to 3-week washout of phosphate binders, we randomly assigned 162 eligible patients (serum phosphate =6.0 to <10.0 mg/dl and a 1.5-mg/dl increase from before washout) to one of six tenapanor regimens (3 or 30 mg once daily or 1, 3, 10, or 30 mg twice daily) or placebo for 4 weeks. The primary efficacy end point was change in serum phosphate concentration from baseline (randomization) to end of treatment. In total, 115 patients (71%) completed the study. Mean serum phosphate concentrations at baseline (after washout) were 7.32-7.92 mg/dl for tenapanor groups and 7.87 mg/dl for the placebo group. Tenapanor provided dose-dependent reductions in serum phosphate level from baseline (least squares mean change: tenapanor =0.47-1.98 mg/dl; placebo =0.54 mg/dl; P=0.01). Diarrhea was the most common adverse event (tenapanor =18%-68%; placebo =12%) and frequent at the highest tenapanor doses. In conclusion, tenapanor treatment resulted in statistically significant, dose-dependent reductions in serum phosphate concentrations in patients with hyperphosphatemia receiving hemodialysis. Additional studies are required to clarify the optimal dosing of tenapanor in patients with CKD-related hyperphosphatemia.

Bone and Calcium Research Update 2015. Novel treatment for FGF23-related hypophosphatemic diseases

Fibroblast growth factor 23 (FGF23) is a hormone mainly produced by osteocytes and regulates phosphate and vitamin D metabolism by binding to Klotho-FGF receptor complex. Most diseases previously called vitamin D-resistant rickets/osteomalacia or familial hypophosphatemic rickets/osteomalacia have been shown to be caused by excess actions of FGF23. Therefore, several methods to inhibit the actions of FGF23 are now considered as new treatment methods for these FGF23-related hypophosphatemic diseases. It has been reported that anti-FGF23 antibody increases serum phosphate in patients with FGF23-related hypophosphatemic disease.

A 12-Week, Double-Blind, Placebo-Controlled Trial of Ferric Citrate for the Treatment of Iron Deficiency Anemia and Reduction of Serum Phosphate in Patients With CKD Stages 3-5

Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. Double-blind, placebo-controlled, randomized trial. 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2), iron deficiency anemia (hemoglobin, 9.0-12.0 g/dL; transferrin saturation [TSAT]≤ 30%, serum ferritin ≤ 300 ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate. Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7 ± 0.6 to 4.4 ± 0.8 mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms. The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes. Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

Anti-fibroblast growth factor 23 antibody therapy.

The review is intended to provide an update on the expanding knowledge regarding diseases caused by the excess actions of fibroblast growth factor 23 (FGF23) and also on the new therapeutic measures for these diseases, with an emphasis on the anti-FGF23 antibody. FGF23 decreases serum phosphate and 1,25-dihydroxyvitamin D levels. After the cloning of FGF23, several hypophosphatemic diseases, including tumor-induced osteomalacia and X-linked hypophosphatemic rickets (XLHR), were shown to be caused by excess actions of FGF23. In addition, recent studies indicated that mutations in the family with sequence similarity 20, member C (FAM20C), HRAS and NRAS genes, also caused FGF23-related hypophosphatemic diseases. The inhibition of FGF23 production or activity is, theoretically, an ideal treatment for these hypophosphatemic diseases. The C-terminal fragment of FGF23, inhibitors of FGF receptor and extracellular signal-regulated kinase, and anti-FGF23 antibody were shown to inhibit FGF23 actions both in vitro and in vivo. A phase I clinical trial of anti-FGF23 antibody has shown that this antibody increases serum phosphate in patients with XLHR. These recent findings confirm that FGF23 has a pivotal role in phosphate metabolism. The inhibition of FGF23 production or activity is promising as a new therapy for FGF23-related hypophosphatemic diseases. Further studies are clearly necessary to establish the clinical utility and long-term safety of these measures.

The Slo-Niacin Trial: A Randomized Double-Blind Placebo-Controlled Cross-Over Trial of Extended Release Niacin for Phosphate Lowering in Haemodialysis Patients

Aim: Is once daily low dose extended release niacin effective at lowering phosphate? Background: Serum phosphate levels correlate with mortality in dialysis patients. Current phosphate binders often cause side-effects leading to poor compliance. Niacin has previously been shown to lower serum phosphate in patients with kidney disease. However, at doses previously used (≥ 1 g daily), it is poorly tolerated. Slo-niacin® is a extended release formulation taken once daily.

Benefits and harm of niacin and its analog for renal dialysis patients: a systematic review and meta-analysis

Clinical trials have shown that niacin and its analog, niacinamide, significantly reduce serum phosphate in patients undergoing dialysis. This review aimed to assess the benefits and harm of niacin and niacinamide in renal dialysis patients. PubMed, EMBASE, and Cochrane Library were searched, without language limitation, randomized controlled trials (RCTs). Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, version 5.2, was used for meta-analysis. Five RCTs with a sample size of 230 patients were included. The meta-analysis showed that niacin and niacinamide significantly decreased serum phosphorus levels [weight mean difference (WMD) -0.88; 95 % confidence interval (CI) -1.19 to -0.57] as well as the calcium × phosphorus product (Ca × P) (WMD -9.15; 95 % CI -13.23 to -5.08), and increased high-density lipoprotein (HDL) levels (WMD 9.30; 95 % CI 5.86-12.74) in renal dialysis patients. Niacin significantly increased the risk of flushing [relative risk (RR) 33; 95 % CI 4.71-232.12] in these patients, while the risk of thrombocytopenia was significantly increased in the niacinamide group (RR 2.82; 95 % CI 1.14-6.94). However, sensitivity analysis showed that our finding regarding thrombocytopenia should be regarded with a low degree of certainty. Niacin and its analog effectively improved phosphorus metabolism in renal dialysis patients. However, niacin can cause flushing and niacinamide probably cause thrombocytopenia. Further larger sample size and well-designed RCTs are needed.

The effect of niacin on serum phosphorus levels in dialysis patients

Hyperphosphatemia is common in patients with end-stage renal disease. Recent studies have shown that niacinamide and niacin achieve clinically significant reductions in serum phosphate in patients undergoing dialysis. The aim of the present study was to evaluate the serum phosphorus lowering effect of niacin in long-term hemodialysis patients. In this 8-week randomized, double-blind clinical trial, 37 patients were assigned to niacin or placebo with titration from 400 to 1000 mg daily. A 2-week washout preceded the switch from niacin to placebo or vice versa. The mean dose of niacin at the end of the 8-week treatment period was 750±200 mg/day. Serum phosphorus decreased from 6.66±1.40 to 5.96±0.87 mg/dL (P = 0.006) in the niacin-treated group after 8-weeks. However, the main reduction occurred at the beginning of study and seems not to be related to the phosphate-lowering effect of drug. In spite of a sharp increase in phosphorus level between w6 and w8 in patients on placebo, phosphorus values in drug-treated group showed nearly steady trend, presumably due to the inhibitory effect of niacin on phosphate absorption from gut. Niacin also increased the high density lipoprotein (HDL) cholesterol (P = 0.018). Our study suggests that niacin should be considered as adjunctive therapy for patients with hyperphosphatemia despite management with phosphate binders. The modest increase in HDL values may be another beneficial effect of this treatment.

Development and validation of an ion chromatography method for the determination of phosphate-binding of lanthanum carbonate

Lanthanum carbonate is indicated to reduce serum phosphate in patients with end stage renal disease (ESRD). When given orally, lanthanum carbonate dissociates in the acid environment of the upper gastrointestinal tract to release lanthanum ions. The free lanthanum ions bind with dietary phosphate released from food during digestion to form highly insoluble lanthanum–phosphate complexes which prevent the absorption of phosphate, consequently reduce the serum phosphate. In order to evaluate the in vitro binding capacity of lanthanum carbonate, a simple and efficient ion chromatography (IC) method was developed and validated for determination of phosphate across the pH range encountered in the gastrointestinal tract. Chromatographic separation was achieved on a Dionex ICS-2000 IC system using a Dionex AS16, IonPac (4 mm × 250 mm) analytical column and Dionex AG16, IonPac (4 mm × 50 mm) guard column. Column temperature was maintained at 30 °C. Injection volume was 10 μL. The compounds were eluted isocratically at a flow rate of 1 mL/min and detected by suppressed conductivity. The analytical method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, quantification limit, linearity, and stability. The intra-day accuracy ranged from 89% to 103% for the solutions of pH 1.2–6.8. The intra-day precision (RSD) ranged from 0.6% to 3.7% for the solutions of pH 1.2–6.8. The analytical range was linear from 2 to 200 ppm (mg/L). The R 2 ranged from 0.9998 to 1.0. This method was found to be simple, robust, sensitive, specific, and accurate. It has been successfully applied for determination of phosphate binding to lanthanum carbonate over the human gastrointestinal pH range at different time-points (from 0.5 to 24 h).

Dietitian-Led Education Program to Improve Phosphate Control in a Single-Center Hemodialysis Population

We sought to analyze the effect of a structured, dietitian-led education program on patients' general knowledge of phosphate and phosphate binders, and its impact on serum phosphate concentrations in a single-center hemodialysis population. We compared subjects before and after intervention. This study involved two dialysis units operated by a single center. One hundred and fifteen hemodialysis patients consented to participate in this study (54% male; mean age, 61.1 years; 32% Asian). Patients acted as their own controls. One hundred and eight patients completed the study. All patients completed a questionnaire to assess their knowledge of phosphate and phosphate-binder therapy. Small group teaching sessions were then delivered to patients by a single dietitian, with the aid of a hospital interpreter as required. Patients also received information booklets or audio cassettes translated into Urdu. A second identical questionnaire was completed a month later. Outcome measures involved pre-education and posteducation knowledge scores, monthly measurements of serum phosphate, calcium, and mean Kt/V, and parathyroid hormone concentrations every 3 months during the 5 month run-in period and subsequent 5-month study period. The education program significantly improved patients' general knowledge of phosphate and of phosphate-binders (P < .001), especially in patients with a low pretest score and those of South Asian origin. This result was associated with a significant reduction in serum phosphate in patients with hyperphosphatemia (P = .032). These findings suggest that a combination of educational initiatives is effective in enhancing patients' knowledge of phosphate and phosphate-binders, and consequently in improving serum phosphate levels in patients with hyperphosphatemia.

Effect of famotidine and lansoprazole on serum phosphorus levels in hemodialysis patients on calcium carbonate therapy

Histamine H2 receptor antagonists (HRA) or proton pump inhibitors (PPI) are frequently administered to patients on hemodialysis, because their intestinal mucosa is fragile. Although three studies have indicated that concomitant HRA administration causes a decrease in the binding of phosphate by calcium carbonate, the HRA doses tested in these studies were 2-4 times higher than the recommended dose for hemodialysis patients. In addition, it remains unclear whether PPI therapy affects serum phosphate levels in hemodialysis patients taking calcium carbonate. Accordingly, the aim of this study was to evaluate the influence of lansoprazole and the recommended dose of famotidine on serum phosphate and calcium levels in hemodialysis patients. The study included 115 hemodialysis patients who were taking calcium carbonate and who were also treated with either famotidine (10 mg/day) or lansoprazole (30 mg/day). Changes of the mean serum phosphate and calcium levels over 2 months before and after the start of famotidine or lansoprazole therapy were compared. The same parameters were also compared when famotidine was switched to lansoprazole. The mean serum phosphate level increased significantly after administration of either famotidine or lansoprazole (by 6.6 +/- 21.9% or 13.0 +/- 26.3%, p = 0.032 and p = 0.029, respectively). The mean serum calcium level was unchanged after administration of famotidine, but showed a significant decrease after administration of lansoprazole (by 3.44 +/- 7.73%, p = 0.013). Therefore, the calcium x phosphorus product was significantly increased by administration of famotidine, but not by administration of lansoprazole (6.68 +/- 23.37% and 8.73 +/- 27.41%, p = 0.046 and p = 0.251, respectively). When famotidine was switched to lansoprazole, the serum phosophate level did not change, but serum calcium decreased significantly by 3.8 +/- 13.0% (p = 0.0006). Not only administration of 20 mg/ day of famotidine as previously reported, but also 10 mg/day of this drug (the recommended dose for hemodialysis patients) caused a significant increase of serum phosphate in patients taking calcium carbonate. PPIs have been reported to show no effect on the serum phosphate level, but 30 mg/day of lansoprazole also caused a significant increase of serum phosphate in patients taking calcium carbonate.

PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: Lanthanum Carbonate—A First Line Phosphate Binder?

AbstractHyperphosphatemia is associated with increased morbidity and mortality in dialysis patients. Oral phosphate binders are necessary to control serum phosphate in patients eating a normal diet and undergoing peritoneal dialysis or thrice weekly hemodialysis. Until recently, none of the available drugs came close to the model of an ideal oral binder, which would demonstrate high affinity, rapid binding regardless of pH, low solubility and absorption, lack of toxicity, palatability, and reasonable cost. Lanthanum carbonate is a safe and effective binder with data demonstrating no toxic effects after continuous exposure up to 6 years. Suggestions that absorption and accumulation of lanthanum is significant and of clinical importance do not stand up to close scrutiny and recommended it as a first line treatment for dialysis patients, particularly if they have evidence of vascular calcification.

Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospectively, serial measurements of serum phosphate were performed in 125 patients with severe acetaminophen poisoning. The optimum threshold value of serum phosphate to discriminate nonsurvivors was identified. Prognostic value and speed of identification were compared with those of the King's College Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 ± 1.18 mmol/L vs. 0.68 ± 0.22 mmol/L, P < .001) as well as 72 to 96 hours after overdose (2.12 ± 0.22 mmol/L vs. 0.59 ± 0.23 mmol/L, P < .001). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than the KCH criteria, and it identified patients significantly earlier after transferal [median 1 hour (range 1-38 hours) vs. 12 hours (2-192 hours), P < .05, respectively]. In nonsurvivors, the degree of hyperphosphatemia correlated with renal dysfunction ( R = .55; P = .02). In conclusion, hyperphosphatemia after acetaminophen overdose is seen exclusively in nonsurvivors, which makes it a highly specific as well as sensitive predictor of nonsurvival. We propose that hyperphosphatemia is caused by renal dysfunction in the absence of hepatic regeneration, as the latter appears to be associated with lowering of serum phosphate. (H EPATOLOGY 2002;36:659-665.)

High prevalence of hypophosphataemia amongst patients with infectious diseases. A retrospective study.

To describe the prevalence of hypophosphataemia amongst all patients treated during 1993 for infectious diseases. The associations between serum C-reactive protein, serum albumin and white blood cells in blood were studied amongst hypophosphataemic patients. Comparisons were made according to the severity of infection. A retrospective study of the prevalence of hypophosphataemia, and a case-control study amongst a subgroup of patients. The Department of Infectious Diseases, University Hospital, Umeå, Sweden. For the prevalence study all 967 patients (449 women and 518 men) treated during 1993 were included. In the case-control study, 108 cases, with serum phosphate < or =0.64 mmol L(-1), 216 age-and sex-matched controls with serum phosphate >0.82 mmol L(-1) (men) and >0.86 mmol L(-1) (women), respectively, were included. In 402 of 967 patients (42%) at least one serum phosphate value was below the reference level. Hypophosphataemia was found in 573 of 1966 blood samples (29%). Severe hypophosphataemia (<0.30 mmol L(-1)) was seen in 1.2% of the patients (0.9% of blood samples). The prevalence of hypophosphataemia was higher amongst women than amongst men. In the case-control study, the serum C-reactive protein and the number of white blood cells was higher amongst the cases compared with the controls (124 vs. 94 mg L(-1) and 11.4 vs. 9.3 cells/L x10(9), respectively). The multiple logistic regression showed a 4-fold higher risk of having low serum phosphate in patients with severe infection, compared with mild infections. None of the other variables (albumin, days of hospital stay or white blood cells in blood) increased the risk for hypophosphataemia. The high prevalence of low serum phosphate levels and the increased risk of having low levels in severe infections shown in this study needs further attention.

Verapamil increases serum ionized calcium and serum phosphate in patients with post-surgical hypoparathyroidism.

The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean +/- SD of 1.10 +/- 0.06 to 1.24 +/- 0.38 mmol l-1; P less than 0.05), as well as total serum calcium corrected for protein (from 2.11 +/- 0.13 to 2.18 +/- 0.13 mmol l-1; P less than 0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 +/- 0.15 to 1.19 +/- 0.20 mmol l-1 P less than or equal to 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22 +/- 0.69 to 1.83 +/- 0.97; P less than or equal to 0.05). The serum 1,25-dihydroxyvitamin-D3 and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 +/- 0.70 before treatment and 1.25 +/- 0.71 micrograms l-1 after treatment). Thus in patients with post-surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil affects bone mineral metabolism.

Elevated ATP levels in the red cells of patients with renal failure.

Red cell ATP levels were measured in 65 patients with renal failure and in 50 controls using the firefly luciferin luciferase assay. The average ATP levels were increased in patients with renal failure (4.88 µmol/g Hb,p < 0.01) as compared to the controls (3.64 µmol/g Hb). A correlation was obtained between red cell ATP levels and inorganic serum phosphate (r=0.6186,p<0.001). ATP levels and correlation to inorganic serum phosphate were further analysed in respect to treatment of renal insufficiency by hemodialysis, peritoneal dialysis (CAPD), kidney transplantation or duration of renal disease. No significant differences were observed except that red cell ATP did not correlate with inorganic serum phosphate in patients treated by CAPD. The severity of renal disease as judged by clinical findings was not related to red cell ATP levels. The mechanisms leading to elevated red cell ATP levels in uremic subjects are not completely understood. A stimulated red cell glycolysis due to hyperphosphatemia, a reduced ATP hydrolysis due to inhibition of membrane bound Na/K ATPase and a younger red cell population in patients with renal insufficiency were put forward. There is some evidence that an altered adenosine metabolism is also involved.

Serum phosphate abnormalities in sickle cell anemia.

AbstractPersistent or intermittent elevation of serum phosphate levels was observed in five adults with sickle cell anemia. Since this may be clinically relevant, possible causes for the high phosphate levels were examined and the association with painful crises was evaluated. Increased serum phosphate levels were regularly associated with increased renal tubular reabsorption of phosphate. Normal parathormone levels and normal renal responses to parathormone were observed in this group and no change in the serum phosphate level or in the renal tubular defect was noted after transfusion to a normal hemoglobin level. Increased renal clearance of sodium was also observed in this group. The findings show that increased levels of serum phosphate in patients with sickle cell anemia are related to altered renal handling of phosphate which is associated with increased clearance of sodium. The frequency of crises was markedly increased in the patients with high levels of serum phosphate.