Biochemical and Clinical Effects of Ethane-1-Hydroxy-1,1-Diphosphonate in Calcium Nephrolithiasis

1978 ◽  
Vol 54 (5) ◽  
pp. 509-516 ◽  
Author(s):  
J. M. Baumann ◽  
S. Bisza ◽  
H. Fleisch ◽  
M. Wacker

1. The short- and longer-term effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP), an inhibitor of crystal growth and potential preventive agent against urinary tract stones in man, have been studied. 2. Measurement of urinary excretion of EHDP was used to define the best dosage regimen. When 4·4 mmol of EHDP was given daily in four divided doses the urinary concentration of EHDP achieved was high enough (10−5 mol/l) to inhibit the crystallization of calcium crystals throughout the day. 3. Nine patients with recurrent calcium stones were given this dose of EHDP daily for 12 months and seven were then studied for a further 12 months under placebo. During treatment with EHDP, inhibitory activity in urine towards precipitation of calcium phosphate was restored from low values to greatly above normal. This could be accounted for by the inhibitory effect of EHDP itself, coupled with an increase in urinary inorganic pyrophosphate. After stopping EHDP the excretion of EHDP rapidly fell to undetectable levels but the excretion of pyrophosphate remained elevated throughout the 12 months of placebo treatment. EHDP also induced a rise in plasma phosphate and an increase in the urinary excretion of oxalic acid and uric acid, but these changes were all fully reversible when EHDP was stopped. 4. The average rate of stone formation per patient per year decreased from 2·4 to 0·2 during treatment with EHDP and remained low during the following 24 months. However, the dose needed for this effect is known to affect bone turnover and mineralization.

1960 ◽  
Vol XXXIV (IV) ◽  
pp. 524-530 ◽  
Author(s):  
Per Lingjoerde ◽  
Knut Kirkeby ◽  
Gunnar Hangård

ABSTRACT Plasma 17-OHCS and urinary excretion of 17-KGS and 17-KS have been compared in 24 patients with chronic polyarthritis, who had been treated for years with corticosteroids. All medication was discontinued 3 days before this investigation. To test the adrenal cortical response the patients were given intramuscular injections of 40 IU of a long-acting ACTH preparation twice daily on 6 consecutive days. Plasma 17-OHCS were determined at 8 a. m. before the first ACTH injection and 3 hours after the injection on the first and sixth treatment days. The urinary concentration of 17-KGS and 17-KS were measured in 24 hour samples on the control day, and on the first and sixth days of treatment. The results show a greater variation in the 17-KS groups than in the 17-KGS and 17-OHCS groups, the smallest variation being in the 17-OHCS groups. There is a significant increase in all values after the first ACTH injection and a further significant increase after the sixth injection, but the t-values are much larger in the 17-OHCS groups than in the 17-KS groups, while the 17-KGS groups occupy an intermediate position. The plasma 17-OHCS values correlate better with the urinary 17-KGS than with the 17-KS. The correlation between 17-OHCS and 17-KGS is not very good (P > 0.05). There is a negative correlation between 17-OHCS and 17-KS control values, and the correlation after ACTH is very poor. 17-KGS correlate well with 17-KS (P < 0.01).


2006 ◽  
Vol 134 (1-2) ◽  
pp. 40-43
Author(s):  
Dragica Milenkovic ◽  
Natasa Lalic

The incidence of urinary tract calculosis continuously progresses. The triggering event in the process of stone formation is decreased urinary level of crystallizing inhibitors. The aim of our study was to investigate whether the existing stone or applied therapeutic procedure - extracorporeal shock waves lithotripsy (ESWL) - has effect to urinary levels of Mg, citrate and pyrophosphate. Study included 128 patients with the upper urinary tract stones. ESWL using the Lithostar (Siemens) device was used as a mode of treatment. Out of all patients, 76 (59%) were free of stone particles before 1 month, while 52 (41%) had residual stone fragments even 3 months after ESWL. Mg, citrate and pyrophosphate were measured in 24hurine specimens: before, between days 2 and 3, as well as 1 and 3 months after ESWL. The analysis of the results revealed that stone itself had no effect on urinary crystallizing inhibitors. Detected increased urinary levels of Mg, citrate and pyrophosphate after ESWL, compared with pre-treatment values, could be attributed to applied therapeutic procedure.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247861
Author(s):  
Zhuoran Chen ◽  
Samantha Ognenovska ◽  
Ronald Sluyter ◽  
Kate H. Moore ◽  
Kylie J. Mansfield

Over 50% of women with detrusor overactivity (DO), who do not respond to therapy have been shown to have bacteriuria, which may stimulate the release of inflammatory cytokines than can enhance nerve signalling, leading to symptoms of urgency. This study made use of a consecutive series of urine samples collected from women with refractory DO, who participated in a clinical trial of rotating antibiotic therapy. The aim was to determine the effect of bacteriuria and antibiotic treatment on the levels of urinary cytokines, and to correlate the cytokine concentration with patient outcome measures relating to urgency or urge incontinence. The urinary cytokines chosen were IL-1α, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, CXCL10 (IP-10), MCP-1 and TNF-α. The presence of bacteriuria stimulated a significant increase in the concentrations of IL-1α (P 0.0216), IL-1 receptor antagonist (P 0.0264), IL-6 (P 0.0003), IL-8 (P 0.0043) and CXCL-10 (P 0.009). Antibiotic treatment significantly attenuated the release of IL-1α (P 0.005), IL-6 (P 0.0027), IL-8 (P 0.0001), IL-10 (P 0.049), and CXCL-10 (P 0.042), i.e. the response to the presence of bacteria was less in the antibiotic treated patients. Across the 26 weeks of the trial, antibiotic treatment reduced the concentration of five of the nine cytokines measured (IL-1α, IL-6, IL-8, IL-10 and CXCL-10); this did not reach significance at every time point. In antibiotic treated patients, the urinary concentration of CXCL-10 correlated positively with four of the six measures of urgency. This study has shown that cytokines associated with activation of the innate immune system (e.g. cytokines chemotactic for or activators of macrophages and neutrophils) are reduced by antibiotic therapy in women with refractory DO. Antibiotic therapy is also associated with symptom improvement in these women, therefore the inflammatory response may have a role in the aetiology of refractory DO.


1972 ◽  
Vol 50 (10) ◽  
pp. 1082-1093 ◽  
Author(s):  
Sailen Mookerjea

The stimulatory effect of CDP-choline on N-acetylglucosaminyltransferase activity is marked in rough microsomes but is almost absent in Golgi-rich membranes or in serum. The marked CDP-choline effect on the enzyme is evident even when the nucleotide–sugar substrate concentration is raised to near saturation. Diglyceride has an inhibitory action on the enzyme which is effectively reversed by further addition of CDP-choline. Of the other different lipid factors tested only CDP-ethanolamine has a stimulatory effect similar to CDP-choline. CDP-choline alone activates the enzyme better than Triton. CDP-choline and Triton, in different combinations of doses, show a marked synergistic effect. Cationic detergents do not activate the enzyme and inorganic pyrophosphate almost completely inhibits the enzyme activity. Phospholipase A has an inhibitory effect in the presence of CDP-choline. Phospholipase C, by itself, stimulates the enzyme activity. In the presence of CDP-choline, a higher concentration of phospholipase C partially abolishes the CDP-choline effect on the enzyme. Phosphorylcholine from labeled CDP-choline is rapidly incorporated into lecithin in the assay system used for measuring N-acetylglucosaminyltransferase activity. Capacity for lecithin synthesis is poor in Golgi membranes. However, lecithin synthesis is stimulated by adding exogenous diglyceride, but CDP-choline plus diglyceride failed to activate N-acetylglucosaminyltransferase in Golgi membranes. Finally, various possibilities have been discussed to explain the mechanism of action of CDP-choline on the enzyme.


1988 ◽  
Vol 34 (9) ◽  
pp. 1937-1941 ◽  
Author(s):  
J D Macfarlane ◽  
B J Poorthuis ◽  
J J van de Kamp ◽  
R G Russell ◽  
A M Caswell

Abstract Hypophosphatasia is an inherited disease in which a deficiency of the bone/liver/kidney or tissue nonspecific isoenzyme of alkaline phosphatase (AP; EC 3.1.3.1) occurs. All forms of the disease are characterized clinically by defective mineralization. Several biochemical abnormalities are associated with the deficiency of AP activity, e.g., increased urinary excretion of inorganic pyrophosphate (PPi) and phosphoethanolamine (PEA). Measurement of these analytes in kindreds of patients with hypophosphatasia may be useful in identifying carriers, and in understanding the inheritance of the disease. We studied biochemically 22 members of the kindred of a 24-year-old woman with hypophosphatasia. We measured activity of AP in serum and leukocytes, and the urinary excretion of PPi and PEA. Within this kindred, urinary excretion of PPi appeared to indicate carrier status, and among the clinically normal adults, values for this analyte were inversely correlated with the activity of AP in serum. These results suggest that urinary excretion of PPi is sensitive to subtle changes in the activity of AP.


2015 ◽  
Vol 87 (2) ◽  
pp. 105 ◽  
Author(s):  
Domenico Prezioso ◽  
Pasquale Strazzullo ◽  
Tullio Lotti ◽  
Giampaolo Bianchi ◽  
Loris Borghi ◽  
...  

Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Results: Evidence from the selected studies were used to form evidencebased guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. Hypercalciuria: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. Hyperoxaluria: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. Hyperuricosuria: In patients with renal calcium stones the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not clearly demonstrated. Hypocitraturia: The administration of alkaline-citrates salts is recommended for the medical treatment of renal stone-formers with hypocitraturia, although compliance to this treatment is limited by gastrointestinal side effects and costs. Increased intake of fruit and vegetables (excluding those with high oxalate content) increases citrate excretion and involves a significant protection against the risk of stone formation. Citrus (lemons, oranges, grapefruit, and lime) and non citrus fruits (melon) are natural sources of dietary citrate, and several studies have shown the potential of these fruits and/or their juices in raising urine citrate levels. Children: There are enought basis to advice an adequate fluid intake also in children. Moderate dietary salt restriction and implementation of potassium intake are useful in limiting urinary calcium excretion whereas dietary calcium restriction is not recommended for children with nephrolithiasis. It seems reasonable to advice a balanced consumption of fruit and vegetables and a low consumption of chocolate and cola according to general nutritional guidelines, although no studies have assessed in pediatric stone formers the effect of fruit and vegetables supplementation on urinary citrate and the effects of chocolate and cola restriction on urinary oxalate in pediatric stone formers. Despite the low level of scientific evidence, a low-protein (&lt; 20 g/day) low-salt (&lt; 2 g/day) diet with high hydration (&gt; 3 liters/day) is strongly advised in children with cystinuria. Elderly: In older patients dietary counseling for renal stone prevention has to consider some particular aspects of aging. A restriction of sodium intake in association with a higher intake of potassium, magnesium and citrate is advisable in order to reduce urinary risk factors for stone formation but also to prevent the loss of bone mass and the incidence of hypertension, although more hemodynamic sensitivity to sodium intake and decreased renal function of the elderly have to be considered. A diet rich in calcium (1200 mg/day) is useful to maintain skeletal wellness and to prevent kidney stones although an higher supplementation could involve an increase of risk for both the formation of kidney stones and cardiovascular diseases. A lower content of animal protein in association to an higher intake of plant products decrease the acid load and the excretion of uric acid has no particular contraindications in the elderly patients, although overall nutritional status has to be preserved.


2008 ◽  
Vol 36 (6) ◽  
pp. 303-307 ◽  
Author(s):  
Armando Luis Negri ◽  
Francisco Rodolfo Spivacow ◽  
Elisa Elena Del Valle ◽  
Mariano Forrester ◽  
Gabriela Rosende ◽  
...  

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