Elevation Of Serum Phosphorus Research Articles

Activation of the Calcium Receptor by Calcimimetic Agents Is Preserved Despite Modest Attenuating Effects of Hyperphosphatemia.

Phosphorus levels in the range seen clinically among patients undergoing dialysis have been reported to attenuate calcium receptor activation and modify parathyroid hormone (PTH) release from isolated parathyroid glands in vitro. Some clinicians and providers of dialysis thus have suggested that calcimimetic agents are ineffective and should not be used to manage secondary hyperparathyroidism among those undergoing dialysis when serum phosphorus concentrations exceed certain threshold levels. To determine whether hyperphosphatemia diminishes the therapeutic response to calcimimetic agents, we used data from large clinical trials to analyze the effects of etelcalcetide and cinacalcet to lower plasma PTH levels in individuals on hemodialysis who had secondary hyperparathyroidism and varying degrees of hyperphosphatemia. Plasma PTH levels declined progressively during 26 weeks of treatment with either etelcalcetide or cinacalcet without regard to the degree of hyperphosphatemia at baseline. However, with each calcimimetic agent, the decreases in PTH from baseline were less at each interval of follow-up during the trials among participants with serum phosphorus levels above one of three prespecified threshold values compared with those with serum phosphorus levels below these thresholds. These in vivo findings are the first in humans to support the idea that hyperphosphatemia attenuates calcium receptor activation by calcium ions and by calcimimetic agents. The effect of hyperphosphatemia on the responsiveness to calcimimetic agents appears relatively modest, however, and unlikely to be significant therapeutically. The efficacy of treatment with calcimimetic agents for lowering plasma PTH levels among those with secondary hyperparathyroidism remains robust despite substantial elevations in serum phosphorus.

Oxidative stress contributes to vascular calcification in patients with chronic kidney disease

Vascular calcification (VC) is a major cause of mortality in patients with chronic kidney disease (CKD). While elevations in serum phosphorus contribute to VC, we provide evidence here for a major role of oxidative stress (OS) in VC pathogenesis without an apparent increase in serum phosphorus in early CKD. In a rat model for stage 5 CKD (CKD5), we observed 1) robust increases of VC and OS, 2) significant reductions of smooth muscle 22 alpha (SM22α) and calponin, and 3) upregulations in Runt-related transcription factor 2 (RUNX2) and collagen I in vascular smooth muscle cells (VSMCs). Inhibition of OS using MnTMPyP dramatically reduced these events without normalization of hyperphosphatemia. In CKD5 patients with VC (n = 11) but not in those without VC (n = 13), OS was significantly elevated. While the serum levels of calcium and phosphate were not altered in the animal model for early stage CKD (ECKD), OS, VC, SM22α, calponin, RUNX2, collagen I and NADPH oxidase 1 (NOX1) in VSMCs were all significantly changed. More importantly, serum (5%) derived from patients with ECKD (n = 30) or CKD5 (n = 30) induced SM22α and calponin downregulation, and RUNX2, collagen I, NOX1 upregulation along with a robust elevation of OS and calcium deposition in primary rat VSMCs. These alterations were all reduced by MnTMPyP, ML171 (a NOX1 inhibitor), and U0126 (an inhibitor of Erk signaling). Collectively, we provide a comprehensive set of evidence supporting an important role of OS in promoting VC development in CKD patients (particularly in those with ECKD); this was at least in part through induction of osteoblastic transition in VSMCs which may involve the Erk singling. Our research thus suggests that reductions in OS may prevent VC in CKD patients.

Elevation of serum phosphorus, an early biomarker of acute kidney injury after cardiac sugery?

Acute kidney injury (AKI) is common after cardiac surgery and is a strong predictor of morbidity and mortality [1]. Hyperphosphatemia following AKI, by renal excretion defect, has never been studied in this context and could be a simple marker of AKI.

Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease

Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease (CKD) in human observational studies. We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease (ESRD) in two population-based prospective cohort studies. Overall, 2269 participants free of CKD [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73(2)] from the Framingham Heart Study (FHS; mean age 42 years; 53% women) and 13,372 participants from the Third National Health and Nutrition Examination Survey (NHANES III; mean age 44.3 years, 52% women) contributed to the present study. In the FHS, we evaluated the relationship between baseline phosphorus category (<2.5 mg/dL, 2.5-3.49 mg/dL, 3.5-3.99 mg/dL and ≥4 mg/dL) and incident CKD (n = 267). In NHANES, we examined the relationship between phosphorus below and above 4 mg/dL in relation to incident ESRD (n = 65). FHS participants in the highest phosphorus category had an increased risk of CKD [odds ratio 2.14; 95% confidence interval (CI), 1.07-4.28; P = 0.03] in multivariable-adjusted models when compared to the referent group (2.5-3.49 mg/dL). Similarly, NHANES III participants with phosphorus levels ≥4 mg/dL demonstrated an increased risk of incident ESRD compared to those <4 mg/dL (relative risk 1.90; 95% CI 1.03-3.53; P = 0.04). In prospective studies of the general population, serum phosphorus levels in the upper-normal range were associated with a doubling in the risk of developing incident CKD and ESRD.

Vitamin D compounds for people with chronic kidney disease requiring dialysis

Clinical guidelines recommend vitamin D compounds to suppress serum parathyroid hormone (PTH) in chronic kidney disease (CKD), however treatment may be associated with increased serum phosphorus and calcium, which are associated with increased mortality in observational studies. Observational data also indicate vitamin D therapy may be independently associated with reduced mortality in CKD. We assessed the effects of vitamin D compounds on clinical, biochemical, and bone outcomes in people with CKD and receiving dialysis. We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and reference lists of retrieved articles. Randomised controlled trials (RCTs) in subjects with CKD and requiring dialysis that assessed treatment with vitamin D compounds. Data was extracted by two authors. Results are summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). Sixty studies (2773 patients) were included. No formulation, route, or schedule of administration was associated with altered risks of death, bone pain, or parathyroidectomy. Marked heterogeneity in reporting of outcomes resulted in few data available for formal meta-analysis. Compared with placebo, vitamin D compounds lowered serum PTH at the expense of increasing serum phosphorus. Trends toward increased hypercalcaemia and serum calcium did not reach statistical significance but may be clinically relevant. Newer vitamin D compounds (paricalcitol, maxacalcitol, doxercalciferol) lowered PTH compared with placebo, with increased risks of hypercalcaemia, although inadequate data were available for serum phosphorus. Intravenous vitamin D may lower PTH compared with oral treatment, and be associated with lower serum phosphorus and calcium levels, although limitations in the available studies precludes a conclusive statement of treatment efficacy. Few studies were available for intermittent versus daily and intraperitoneal versus oral administration or directly comparative studies of newer versus established vitamin D compounds. We confirm that vitamin D compounds suppress PTH in people with CKD and requiring dialysis although treatment is associated with clinical elevations in serum phosphorus and calcium. All studies were inadequately powered to assess the effect of vitamin D on clinical outcomes and until such studies are conducted the relative importance of changes in serum PTH, phosphorus and calcium resulting from vitamin D therapy remain unknown. Observational data showing vitamin D compounds may be associated with improved survival in CKD need to be confirmed or refuted in specifically designed RCTs.

Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients

Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (1,25D(3)) to suppress parathyroid hormone (PTH), but dosing of 1,25D(3) is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)2-vitamin D2 (paricalcitol) and the prohormone 1alpha-OH-vitamin D2 (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca x P, while still suppressing PTH. We performed a prospective study to assess the acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO4, and PTH were measured over 36 h. Serum phosphorus rose faster, and peaked significantly higher at 36 h following doxercalciferol (2.12 +/- 0.11 mmol/l) than paricalcitol (1.85 +/- 0.07 mmol/l; p = 0.025). Ca x P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 +/- 0.26 vs. 4.54 +/- 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca x P.

The therapeutic potential of novel phosphate binders

Hyperphosphatemia and an increased serum calcium-phosphate (CaxP) product are associated with cardiovascular mortality in adult dialysis patients. Target levels for the treatment of elevations in serum phosphorus (P) and the CaxP product have recently been redefined, but are difficult to achieve in clinical practice. This problem may be especially prevalent in children and adolescents who have a higher recommended P intake than adults and also a higher calcium (Ca) load with the intake of comparatively higher doses of Ca-containing phosphate binders. Current treatment practice with Ca-containing P binders carries the risk of hypercalcemic episodes and ectopic calcifications, including vascular calcifications, which are associated with an increased risk of cardiovascular disease. Novel P binders in the development phase include several iron-containing preparations. Clinical experience with lanthanum carbonate is limited to date and further studies are needed to establish its safety. The only available Ca-free P binder with widespread use and large-scale clinical safety data in adults is sevelamer. Preliminary data suggest that this drug can also be safely given to children.

Oral sodium phosphate solution: a review of its use as a colorectal cleanser.

A regimen that administered the first dose of sodium phosphate on the previous evening and a second dose on the morning of the procedure (10-12 hours apart) was significantly more effective than PEG-based regimens for colorectal cleansing in preparation for colonoscopy, sigmoidoscopy or colorectal surgery. A regimen that administered both doses of oral sodium phosphate on the day prior to the procedure offered no colorectal cleansing advantage over PEG-based regimens and was significantly less effective than an oral sodium phosphate solution regimen that administered one dose on the previous evening and a second dose on the morning of the procedure. Oral sodium phosphate solution was generally as effective as other colorectal cleansing solutions (including magnesium citrate-containing regimens with sodium picosulfate). The direct costs of a diagnostic colonic examination with oral sodium phosphate solution were less than those with PEG (US465 dollars vs US503 dollars per patient; 1995 values), according to data from a US study. Oral sodium phosphate solution was significantly more effective than a commercially available tablet formulation as a colorectal cleanser prior to colonoscopy (data from one study only). Oral sodium phosphate solution administered as two 45 mL doses (generally 10-12 hours apart) was well tolerated in well designed trials in which adults with major comorbid conditions were excluded. Sodium phosphate-associated adverse events were mostly gastrointestinal (including abdominal pain/cramping, abdominal fullness and/or bloating, anal or perianal irritation or soreness, nausea, vomiting or hunger pains), although dizziness, weakness/fatigue, thirst, chest pain, chills, headache and sleep loss were also reported. Faecal incontinence was commonly reported in the elderly. Three doses (administered 10 minutes apart) of 15 mL of oral sodium phosphate solution, each diluted in 250 mL of clear fluid was associated with less vomiting than one 45 mL dose of the solution diluted in 250 mL of clear fluid (data from one study). In patients without major comorbid conditions, oral sodium phosphate has been associated with transient and clinically inconsequential changes in intravascular volume and electrolyte disturbances. Serious electrolyte disturbances have been associated with oral sodium phosphate administration in patients in whom sodium phosphate is contraindicated or should be use with caution (the elderly and those with bowel obstructions, small intestinal disorders, poor gut motilderly and those with bowel obstructions, small intestinal disorders, poor gut motility, renal insufficiency, cardiovascular disease or taking concomitant medication) or in patients ingesting more than the recommended dosage. Changes in the colonic mucosa have been reported in patients treated with oral sodium phosphate solution; however, the exact role of this agent in the appearance of these changes has not been fully clarified. The tolerability profile of oral sodium phosphate solution was similar to, or significantly better than, that of PEG or other colorectal cleansing regimens. Oral sodium phosphate solution was generally significantly more acceptable than PEG or other colorectal cleansing regimens. Oral sodium phosphate solution had similar tolerability, but was considered to be more acceptable than commercially available oral sodium phosphate tablets prior to colonoscopy (data from one study).

Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency.

Reduced renal function is associated with a variety of biochemical abnormalities. However, the extent of these changes and their magnitude in relation to renal function is not well defined, especially among individuals with mild to moderate chronic renal insufficiency (CRI). We analysed the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) data for 14722 adults aged >/=17 years with measurements of serum creatinine and all electrolytes including ionized calcium. General linear models were used to determine the relationship between mean concentrations of electrolytes and different levels of Cockcroft-Gault creatinine clearance (CrCl). Sample weights were used to produce weighted regression parameters. Changes in mean serum phosphorus and potassium concentration were evident at relatively modest reductions in CrCl (around 50 to 60 ml/min). Changes in the anion gap and mean levels of ionized calcium and bicarbonate were not apparent until CRI was advanced (CrCl </=20 ml/min). For example, compared with women with CrCl >80 ml/min, those with CrCl 60-50, 50-40, 40-30, 30-20 and </=20 ml/min had mean serum phosphorus concentrations that were higher by 0.1, 0.1, 0.2, 0.3 and 0.8 mg/dl (all P<0.05), and mean serum potassium concentrations that were higher by 0.1, 0.1, 0.1, 0.2 and 0.4 mmol/l (all P<0.05), respectively. These changes were independent of dietary intake and the use of angiotensin converting enzyme (ACE) inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs). Increases in serum phosphorus and potassium levels are apparent even among people with mild to moderate CRI. These findings should be broadly generalizable to the larger CRI population in the United States. Subtle elevations in serum phosphorus might contribute to the initiation and maintenance of secondary hyperparathyroidism, which is known to occur in mild to moderate CRI.

1 alpha-Hydroxyvitamin D2 is less toxic than 1 alpha-hydroxyvitamin D3 in the rat.

An LD50 of 0.2 mg/kg body wt has been determined for 1 alpha-hydroxyvitamin D3 in the rat. In comparison, the LD50 for 1 alpha-hydroxyvitamin D2 is between 3.5 and 6.5 mg/kg. In terms of chronic toxicity, 1 alpha-hydroxyvitamin D3 at a dose of 5 micrograms/kg/day causes death of one-half the animals in a 4-week period. On the other hand, 20 micrograms/kg/day of 1 alpha-hydroxyvitamin D2 is required to induce similar toxicity. The body weight record and renal calcium accumulation during chronic treatment support the above conclusion. It therefore appears that 1 alpha-hydroxyvitamin D2 is between 5 and 15 times less toxic than 1 alpha-hydroxyvitamin D3. This surprising result prompted a reexamination of the relative biological activity of 1 alpha-hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3. Both compounds are equally potent in the stimulation of intestinal calcium transport, bone calcium mobilization, in the elevation of serum phosphorus, and in the healing of rickets in the rat. The reason for lower toxicity of 1 alpha-hydroxyvitamin D2 is unknown. The results suggest that 1 alpha-hydroxyvitamin D2 might represent a therapeutically superior compound.

26,26,26,27,27,27-Hexafluoro-1,25-dihydroxyvitamin D 3: A highly potent, long-lasting analog of 1,25-dihydroxyvitamin D 3

A new fluoro analog of 1,25-dihydroxyvitamin D 3, i.e., 26,26,26,27,27,27-hexafluoro-1, 25-dihydroxyvitamin D 3, has been compared with the native hormone, 1,25-dihydroxyvitamin D 3, in its biological potency, duration of action, and binding to the vitamin D transport protein and intestinal receptor protein. The fluoro analog is about 5 times more active than the native hormone in healing rickets and elevating serum inorganic phosphorus levels of rachitic rats. It is about 10 times more active than 1,25-dihydroxyvitamin D 3 in increasing intestinal calcium transport and bone calcium mobilization of vitamin D-deficient rats fed a low-calcium diet. Furthermore, the higher biopotency is manifested in animals after oral dosing. Of great importance is that the action of the fluoro analog is longer lasting than that of 1,25-dihydroxyvitamin D 3. This is especially apparent in the elevation of serum phosphorus and bone mineralization responses. The fluoro analog is only slightly less competent than 1,25-dihydroxyvitamin D 3 in binding to the vitamin D transport protein in rat blood, and is one-third as competent as 1,25-dihydroxyvitamin D 3 in binding to the chick intestinal cytosol receptor for 1,25-dihydroxyvitamin D 3. These results suggest that the basis for increased potency of this analog is likely the result of less rapid metabolism.

24,24-Difluoro-25-hydroxyvitamin D 3-enhanced bone mineralization in rats comparison with 25-hydroxyvitamin 3 and vitamin D 3

The biological activity of 24,24-difluoro-25-hydroxyvitamin D 3 was assessed using elevation of serum phosphorus and healing of rickets of vitamin D-deficient rats. Various levels of 24,24-difluoro-25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 3 were administered daily for 2 weeks in the dose range of 6.5 to 3250 pmol after feeding rats a low phosphorus, vitamin D-deficient diet for 3 weeks. Vitamin D 3 was concurrently tested at dose levels of 650 and 3250 pmol. 24,24-Difluoro-25-hydroxyvitamin D 3 is approximately equipotent with 25-hydroxyvitamin D 3 in stimulation of growth, mineralization of rachitic bone, and elevation of serum inorganic phosphorus. Radiological manifestations of rickets were also equally improved by 24,24-difluoro-25-hydroxyvitamin D 3 and 25-hydroxyvitamin D 3. Compared with vitamin D 3, these compounds were approximately 5 to 10 times more active in mineralization using rats on a low phosphorus, vitamin D-deficient diet. The functional role, if any, for 24-hydroxylated vitamin D compounds, such as 24,25-dihydroxyvitamin D 3, therefore remains obscure. It appears that vitamin D compounds that cannot be 24-hydroxylated evoke no disorder in bone mineralization.

Effect of hydrochlorothiazide on phosphorus during treatment with diphosphonate.

The effects of probenecid and hydrochlorothiazide on renal handling of phosphorus during hyperphosphatemia induced by diphosphonate (ethane-1-hydroxy-1, 1-diphosphonate, EHDP) was studied. Measurements of calcium, phosphorus, and creatinine clearance were performed in 2 sessions on each of 3 consecutive days in 10 normal fasting volunteers during the morning hours from 8 A.M. to 12 noon. During 2 to 3 wk thereafter, each subject was treated with EHDP, 30 mg/kg/day. The second group of studies were performed in the same manner as the first except the EHDP administration was continued throughout. EHDP caused elevation of serum phosphorus in all cases. Probenecid did not affect urine phosphorus. Hydrochlorothiazide caused a transient phosphaturia of similar magnitude in the EHDP treated and untreated states. Creatinine clearance was not affected by any of the treatments and urine calcium was decreased by EHDP. It was concluded that hydrochlorothiazide inhibits tubular reabsorption of phosphorus but that it does not affect the mechanism whereby EHDP causes increased tubular reabsorption of phosphorus. Chronic administration of hydrochlorothiazide along with EHDP may inhibit hyperphosphatemia and may change the bone effects of EHDP.

Biological activity of 1,25-dihydroxyvitamin D3 in the rat.

The biological activities of vitamin D3, 25–hydroxyvitamin D3, and 1,2 5–dihydroxyvitamin D3 given each day ip to rats have been compared. Under these conditions, 1,25–dihydroxyvitamin D3 is about 10 times more active than vitamin D3 in the elevation of serum phosphorus and calcification of bone of rats on a low phosphorus diet. It is also about 5 times more active than vitamin D3 in the maintenance of serum calcium and stimulation of growth of rats on a low calcium diet. The 25–hydroxyvitamin D3 equals 1,25–dihydroxyvitamin D3 in its effect on serum calcium and growth of rats on the low calcium diet, but is 1/5 as active in antirachitic activity in rats on the low phosphorus diet. In addition, 1,25–dihydroxyvitamin D3, but not vitamin D3 or 25–hydroxyvitamin D3, tends to produce a hypercalcemia even at low doses in rats on a high calcium diet. (Endocrinology 92: 417, 1973)

RENAL FUNCTION IN HYPERPARATHYROIDISM

ABSTRACT Clearances of inulin and para-aminohippurate (PAH) were studied before as well as three to nine years (average 5½) after surgery in 35 cases of primary hyperparathyroidism. The preoperative inulin clearance ranged from 18 to 105 (average 67) and the PAH clearance from 61 to 666 (349) ml/min/1.73 m2 BSA. In the follow-up studies clearances of inulin and PAH were, on the whole, well maintained both in subjects with normal as well as in cases showing depressed clearance values before surgery. In fact, a slight but statistically significant increase of inulin clearance was demonstrated in the material as a whole, whereas no significant change occurred in PAH clearance. The renal concentrating capacity was estimated before and after operation in 22 of the patients. An increase was almost regularly observed postoperatively but the concentrating capacity remained subnormal in almost half of the subjects studied. The changes in the concentrating capacity and clearances of inulin and PAH did not always run parallel. The renal clearance of phosphate was studied simultaneously with inulin and PAH clearances. Phosphate clearance decreased after surgery concomitantly with an elevation of serum phosphorus. However, restoration to the normal was not always obtained. Arterial hypertension was present in 40 per cent of the patients before and/or after surgery. Only grade I-II eye ground changes were found. Blood pressure was easily controlled by hypotensive drugs. A spontaneous disappearance or a decrease in the number of kidney stones was demonstrated radiologically at the follow-up studies in almost half of the patients. In only two subjects were additional kidney stones found. It is concluded that, following surgical treatment of hyperparathyroidism, the long-term outcome regarding renal function may be more favourable than has hitherto been thought.

Acromegaly—Hot or cold?: Some clinical and metabolic observations

Subjects suffering from acromegaly may present with complaints related to (1) an expanding intracranial mass, (2) the anabolic and/or diabetogenic actions of HGH, and (3) irritation or compression of neighboring pituitary cells. In ‘fugitive’ acromegaly, peripheral nerve, joint, skeletal and cardiac muscle lesions may antedate florid evidence of acromegaly. Even when the anatomical diagnosis has been established, it may be difficult to distinguish active from burnt out acromegaly. Elevation of serum phosphorus and evidence of continuing acral enlargement are satisfactory but insensitive tests. These tests can be supplemented by (1) direct assay of growth hormone levels in plasma, and (2) measurement of basal forearm metabolism and the response of forearm to intra-arterial insulin.

Atherosclerosis in pigeons—Its spontaneous occurrence and resemblance to atherosclerosis in man

Following parathyroidectomy, serum calcium decreases to tetanic levels prior to increase of serum phosphorus, thus supporting the concept that parathyroid hormone has a direct skeletal effect and indicating an indirect or delayed action on phosphorus. This problem was evaluated by parallel measurements of serum and urinary calcium and phosphorus in four patients in whom hypoparathyroidism developed following thyroid surgery. In all cases tetanic manifestations preceded elevation of serum phosphorus. A profound fall in phosphorus excretion-demonstrated by a low phosphate clearance (Cp)-occurred soon after surgery. In two subjects with transient tetany, Cp decreased prior to elevation of serum phosphorus and returned to normal before regression of the hyperphosphatemia. In the instances of permanent parathyroid deficiency changes were even more marked; one patient with severe hypocalcemic tetany demonstrated no elevation of serum phosphorus until the third postoperative day; however, Cp was only 0.3 ml/minute on the day after surgery. These studies offer further evidence for a dual action of parathyroid hormone but indicate that changes in phosphorus excretion occur with equal or greater rapidity than those of serum calcium. The delayed elevation of serum phosphorus in hypoparathyroidism can be attributed to the magnitude of the phosphate compartment.

AbstractRenal Osteitis. By SussmannM. L. and PoppelM. H..Amer. Journ. Roentgen., Vol. xlviii, pp. 726–731, 1942.

In patients with chronic renal insufficiency in whom there is retention of non-protein nitrogen, there is almost always phosphate retention, elevation of serum-phosphorus, lowering of serum-calcium and hyperplasia of parathyroid glands to meet this tendency.