Renal Insufficiency Induced by Parathyroid Hormone: Influence of the Calcium Antagonist Gö 6070

Wl, Strohmaier; Seeger, Drew R.; Oßwald, Hartmut; Kh, Bichler

doi:10.1159/000474865

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…Hormones that affect calcium metabolism are also held responsible for the primary damage to the tubular cell. This has been demonstrated for vitamin D [15] and parathyroid hormone [16][17][18].…”

Section: Introductionmentioning

confidence: 77%

Renal Tubular Alteration by Crystalluria in Stone Disease – An Experimental Study by Means of MDCK Cells

Lahme

Feil²,

Strohmaier³

et al. 2004

Urol Int

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Objectives: Physicochemical properties of urine do not explain the formation of urinary stones. Clinical findings and results of animal experiments suggest that alteration to the renal tubular cell plays a key role in the initiation of urinary stone formation. It is not clear whether this is a primarily intracellular alteration of metabolic origin which, after lysis of the renal tubular cell in the lumen, presents a nucleus for the formation of concretions, or whether in the lumen it is tubular cell damage induced by crystalluria that triggers the formation of urinary stones. Materials and Method: Using Madin-Darby canine kidney cells, the influence of crystalluria on the renal tubular cell was tested in cell cultures. The influence of parathyroid hormone, vitamin D₃, oxalate and calcium concentrations and the extent to which these processes can be inhibited by allopurinol and selenium were investigated. Results: Calcium oxalate monohydrate crystals produced reproducible damage to the renal tubular cell which was independent of parathyroid hormone and vitamin D₃. The crystalluria-induced effects were unrelated to the oxalate and calcium concentration or the pH. Allopurinol and selenium were able to inhibit the processes. Conclusion: The results indicate secondary involvement of the renal tubular cell in lithogenesis as a result of luminal alteration caused by calcium oxalate crystals. Mechanical damage and interaction between crystal and tubular cell lead to the apposition of crystals. The nephroprotective effect of allopurinol and selenium as antioxidants might explain the benefit of allopurinol found clinically in terms of stone metaphylaxis.

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Section: Introductionmentioning

confidence: 77%

Renal Tubular Alteration by Crystalluria in Stone Disease – An Experimental Study by Means of MDCK Cells

Lahme

Feil²,

Strohmaier³

et al. 2004

Urol Int

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“…This confirms our previous studies [5][6][7], Recently it has been shown that this effect is not restricted to nifedipine. Other calcium antagonists such as Go 6070 which is a new 1,4-dihydronaphthyridin current ly under development [8] have similar effects on choles terol-induced nephrolithiasis [13], Since nifedipine did not influence the biochemical parameters in a stone-pro tective way, cellular mechanisms -as already suggested by Bichler et al [5] -seem to be responsible for the stoneprotective effect. Furthermore, this fact suggests that cel lular processes may be even more important in the patho genesis of calcium urolithiasis than abnormalities in urine composition.…”

Section: Discussionmentioning

confidence: 99%

“…sodium, calcium, magnesium, phos phate) were performed in 6 rats of each group after 4 weeks. Techni cal details were recently reported [8]. For the determination o f inulin a colorimetric method was used [9], the other parameters were deter mined as described above.…”

Section: Methodsmentioning

confidence: 99%

Influence of Nifedipine on Stone Formation and Renal Function in Cholesterol-Induced Nephrolithiasis in Rats

Strohmaier

Witte²,

Nelde³

1994

Urol Int

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Previous investigations showed that nifedipine limited calcium phosphate stone formation induced by a high-cholesterol diet in rats. This study was performed to obtain further insights into the effects of nifedipine on stone prevention, renal function and urine composition. Male Wistar rats were assigned to one of the following groups: (1) cholesterol diet (n = 22), (2) cholesterol diet plus nifedipine (n = 22) and (3) control (n = 6). A high-cholesterol diet was given for 4 weeks, nifedipine was administered by gavage to group 2 for 4 weeks (50 mg/kg/24 h). During weeks 1 and 4, 5 rats of each group were housed in metabolic cages for urine collection. Sodium (Na), calcium (Ca), magnesium (Mg), phosphate (P_i), citrate and creatinine were determined in the urine. The kidneys of 4 animals of group 1 and 2 were perfused and removed for histology after 1,2,3 and 4 weeks, respectively. Clearance studies (inulin, Na, Ca, Mg, P_i) were performed (n = 6/group) after 4 weeks. The cholesterol diet induced a marked renal stone formation which was significantly limited by nifedipine [calcification index (week 4) 1.75 ± 0.5 vs. 0.75 ± 0.5]. The sequential histological examinations showed that concrement formation started intracellularly after only 1 week in group 1 whereas in group 2 the first concretions were observed only after 3 weeks. The cholesterol diet induced an increased excretion of Ca and P_i, citrate and Mg were reduced. The concomitant application of nifedipine resulted in a higher excretion of Ca, Mg and citrate when compared to the cholesterol group. The inulin clearance was decreased in the latter group. Nifedipine limited this decrease. The fractional excretion (FE) of Ca, P_i and Mg was increased with the cholesterol diet. Nifedipine further increased the FE of Ca and Mg; FE of P_i was decreased when compared to group 1. Our results show that nifedipine limits nephrolithiasis and the deterioration of renal function in rats fed a cholesterol diet. Tubular cells obviously play a key role in the process of cholesterol-induced stone formation, probably being more important than changes in urine composition.

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Reduction of vitamin D induced stone formation by calcium

Strohmaier¹,

Seeger²,

Oßwald³

et al. 1994

Urol. Res.

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Investigations were carried out as to whether cytoprotective agents such as calcium antagonists can influence vitamin D induced nephrolithiasis. Increased vitamin D levels are found in 10-30% of all calcium oxalate stone formers. Male rats were assigned to one of the following groups: (1) 1,25-dihydroxycholecalciferol (DHCC) (n = 8), (2) 1,25-DHCC + calcium antagonist Goe 6070 (a new 1,4-dihydronaphthyridine, Goedecke, Berlin) (n = 8), or (3) control (n = 8). 1,25-DHCC was administered for 6 days (120 pmol/24 h s.c.), Goe 6070 (1 mg/kg/24 h) by gavage. Clearance studies were performed on day 6. Kidneys were taken for histological examination and determination of calcium tissue content. 1,25-DHCC induced substantial concrement formation, which could be significantly limited by Goe 6070. The calcium tissue content was also reduced (0.17 vs. 0.04 mg/100 mg dry weight). 1,25-DHCC induced a dramatic fall in the glomerular filtration rate (GFR) (3.84 ml/min per kilogram). This reduction could be almost completely inhibited by the concomitant application of Goe 6070 (9.4 ml/min per kilogram; control 10.7 ml/min per kilogram). Goe 6070 did not influence the calcium handling. The results demonstrate a protective effect of Goe 6070 on vitamin D induced nephrolithias. The histological pattern (intracellular and membrane-bound concretions) and the fact that biochemical parameters were not influenced significantly by Goe 6070 indicate that cellular proceses are important for 1,25-DHCC-induced nephrolithiasis.

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Renal Insufficiency Induced by Parathyroid Hormone: Influence of the Calcium Antagonist Gö 6070

Cited by 5 publications

References 16 publications

Renal Tubular Alteration by Crystalluria in Stone Disease – An Experimental Study by Means of MDCK Cells

Renal Tubular Alteration by Crystalluria in Stone Disease – An Experimental Study by Means of MDCK Cells

Influence of Nifedipine on Stone Formation and Renal Function in Cholesterol-Induced Nephrolithiasis in Rats

Reduction of vitamin D induced stone formation by calcium

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