pyrophosphate and Chronic-Kidney-Disease-Mineral-and-Bone-Disorder

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

Topics: Alkaline Phosphatase; Animals; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Inflammation; Isoenzymes; Parathyroid Glands; Parathyroid Hormone; Phosphates; Phosphorus; Proportional Hazards Models; Treatment Outcome; Vascular Calcification

The usefulness of 99mTc-Pyrophosphate (99mTc-PPi) bone scintigraphy was evaluated in the follow up of 21 haemodialysed patients without clinical or radiological evidence of osteodystrophy. 99mTc-PPi bone scintigraphy was semi-quantitatively analysed using Fogelman's score. Patients were randomised to receive vitamin D analogues (1 alpha hydroxyvitamin D3 or dihydrotachysterol, n = 12) or to serve as controls (n = 9), both groups being given oral calcium supplements. Bone scintigraphy deteriorated in patients only on calcium therapy but not in patients treated by vitamin D-analogues. Vitamin D therapy reduced secondary hyperparathyroidism in all cases but induced rapid intoxication with normal doses in 4 of the 12 treated patients. Since intoxicated patients had significantly lower Fogelman's score than the patients who tolerated the treatment well, 99mTc-PPi bone scintigraphy is proposed as a screening test before vitamin D-analogues trials.

Topics: Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Diphosphates; Humans; Hydroxycholecalciferols; Radionuclide Imaging; Renal Dialysis; Technetium; Technetium Tc 99m Pyrophosphate; Uremia

Hypophosphatemia complicating parathyroidectomy for secondary hyperparathyroidism in renal failure is usually corrected by the oral or intravenous routes. We present a case in which those methods of treatment were not possible, and the phosphate was administered intraperitoneally. Phosphate was added as one molar sodium diphosphate solution to the dialysis fluid. In our case the procedure was well tolerated, phosphate blood levels were rapidly corrected, no alterations in calcium, magnesium or other parameters were detected and the patient was discharged in good condition. In selected cases of hungry bone syndrome after parathyroidectomy, intraperitoneal phosphate can be used safely.

Topics: Adult; Chronic Kidney Disease-Mineral and Bone Disorder; Dialysis Solutions; Diphosphates; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroidectomy; Peritoneal Dialysis; Phosphates

10 patients with chronic renal failure (6 women, 4 men), 19 to 59 years of age, duration of the disease form 3 up to 21 years, treated by hemodialysis from 2 to 5 years, were examined. The scintigraphic examination of the bones with 99mTc pyrophosphate (166.5.10(6) MBq) on the third hour after the i.v. application of the radiocolloid, registered by the scanning device SELO-DS-2, allows the discovery of the initial changes of the so called renal osteodystrophy (bone disease in patients on chronic hemodialysis). The coefficient bones/soft tissues may be used as a quantitative index of the renal osteodystrophy in these patients whereas the coefficient calvaria/sternum has not the same diagnostic value.

Topics: Adolescent; Adult; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Radionuclide Imaging; Renal Dialysis; Technetium; Technetium Tc 99m Pyrophosphate

Fogelman's score (FS) was used to determine the usefulness of 99mTc pyrophosphate (Tc-PP) bone scintigraphy in the evaluation of dialysis osteodystrophy. FS correlated well with bone 47Ca accretion rate. It remained stable after six months in patients treated with 1 alpha (OH)D3 and increased significantly in a randomised group of untreated patients. It decreased after two years of 1 alpha (OH)D3 therapy while serum calcium increased and iPTH and alkaline phosphatases decreased. Patients with low FS, treated by 1 alpha (OH)D3, rapidly developed hypercalcaemia. In cases of spontaneous hypercalcaemia, parathyroidectomy did not normalise serum calcium in patients with low FS despite a significant decrease in serum iPTH. Lower FS were associated with a higher increase in serum aluminium after desferrioxamine (DFO) administration and in two cases of proven aluminium osteomalacia, DFO therapy was followed by a dramatic increase in FS.

Topics: Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Radionuclide Imaging; Renal Dialysis; Technetium; Technetium Tc 99m Pyrophosphate

In order to determine the place of Technetium-99m-pyrophosphate bone scintigraphy in the assessment of renal osteodystrophy, 17 patients with chronic renal failure requiring hemodialysis underwent bone scans and these were compared to results of biochemical, radiological and histologic studies. Bone histology was abnormal in all patients with most having evidence of osteomalacia and hyperparathyroid bone disease. Using semi-quantitative scan scores and regional bone-standard ratios, isotope uptake was increased in 16 patients, while 15 had elevated alkaline phosphatase levels and 7 had X-ray changes. An osteoid-osteoclast index combining histological osteomalacia and hyperparathyroid disease was derived and was found to correlate more closely with alkaline phosphatase and parathyroid hormone levels than with scan parameters. It was concluded that bone scans did not provide therapeutically useful information that could not be obtained from biochemical and radiological studies. It appeared that only bone histology could differentiate osteomalacia and hyperparathyroid bone disease.

Topics: Adult; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Adult; Calcinosis; Cardiomyopathies; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Kidney Transplantation; Lung Diseases; Male; Parathyroid Glands; Radionuclide Imaging; Technetium; Transplantation, Homologous

Topics: Adult; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Prednisone; Renal Dialysis; Whole-Body Counting

This communication describes a series of clinical and animal in vivo and in vitro investigations designed to elucidate the mechanism of 99mTc-Sn-phosphate complex concentration in metabolic bone disease. Rachitic and lathyritic animals were used as experimental models. Based on these studies it is concluded that 99mTc alters the pharmacology of the phosphate complexes, in particular pyrophosphate, which was the test agent most extensively employed, so that the usual affinity for mineral is for the greater part replaced by organic matrix binding. There is also evidence to suggest the immature collagen moiety of the organic matrix is the prime target of 99mTc-Sn-phosphate complex binding. Specifically, the aldehyde groups of the collagen molecule are suspected as being the major site of interaction.

Topics: Aminopropionitrile; Animals; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Humans; Hydroxyproline; Hyperparathyroidism; In Vitro Techniques; Lathyrism; Organophosphorus Compounds; Osteitis Deformans; Osteomalacia; Radionuclide Imaging; Rats; Renal Dialysis; Rickets; Technetium

25 Patients with chronic renal disease are investigated. In 16 cases with conservative treatment the bone scintigram showed pathological uptake according to the creatinine level, mainly in the joints of iliosacrum, hip, knee and ankles. In three patients increased uptake in the skull was found. The bone uptake found by scintigraphy was highly pronounced in the patients treated by dialysis. The most frequently involved regions were the joints of iliosacrum and hip, facial cranium, skull, pelvis and metatarsus. The count-rate ratio of cranium to chest was significantly increased in 6 patients. The investigations 6 months later showed in 4 cases a further increase compared with the first values. Count-rates of the skull were found to be comparable to the highly increased uptake in Paget's disease. Bone scintigraphy is a suitable method to estimate semiquantitatively the bone turnover in renal disease.

Topics: Alkaline Phosphatase; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Female; Humans; Male; Radionuclide Imaging; Renal Dialysis; Technetium

A high incidence of abnormal 99mTechnetium-tin-pyrophosphate (99mTcPPi) is reported in a population of chronic renal failure patients. Using the 5 hour bone to soft tissue ratio as a quantitative index of increased uptake, 78% of 45 long-term dialysis patients and a similar proportion of non-dialyzed chronic renal failure patients were found to have increased uptakes. In animal studies using a uremic model, similar increased uptakes of 99mTcPPi was found with evidence of increased vascularity as reflected by red cell or plasma volumes in the bone or by the uptake of concomitantly administered 45Ca. The evidence suggests that the abnormal bone scans reflect abnormalities in collagen metabolism that occurs in the uremic state and that 99mTcPPi scans are useful in the diagnosis and management of renal osteodystrophy.

Topics: Animals; Bone and Bones; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Female; Femur; Humans; Kidney Failure, Chronic; Radionuclide Imaging; Rats; Renal Dialysis; Technetium; Time Factors; Tin; Uremia

Topics: Adolescent; Adult; Aged; Alkaline Phosphatase; Calcium; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Diphosphates; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Parathyroid Glands; Phosphates; Phosphorus Isotopes; Radiography; Renal Dialysis; Transplantation, Homologous