Nephrocalcinosis in the Kidney of the Rat on Atherogenic Diet and the Effect of Calcium Antagonists (Nifedipine)

Self Cite

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.

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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

Lahme

Feil²,

Strohmaier³

et al. 2004

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“…The mean of each collective was called the calcification index. All the histologi cal techniques were performed as previously described in detail [7], Clearance studies (inulin. sodium, calcium, magnesium, phos phate) were performed in 6 rats of each group after 4 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…The concomitant application of the cal cium antagonist nifedipine, however, limited the extent of renal calcifications suggesting the importance of cellular mechanisms in concrement formation [4][5][6]. An intracel lular origin of the deposits was assumed [5,7], The aim of the present study was to obtain further insights into the pathogenesis of stone formation induced by cholesterol and the effects of nifedipine on the process of calcifica tion, urine composition and renal function in this animal model.…”

Section: Introductionmentioning

confidence: 99%

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

Strohmaier

Witte²,

Nelde³

1994

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.

“…A subjective, semiquantitative scoring method, with 4 grades ranging from 0 to 3+ (where 0 = none, 1+ = few, 2+ = several and 3+ = many crystal deposits), was used to score the severity of crystal deposition [11][12][13] .…”

Section: Evaluation Of the Severity Of Renal Crystal Depositionmentioning

confidence: 99%

Prophylaxis of Experimentally Induced Calcium Oxalate Nephrolithiasis in Rats by Zhulingtang, a Traditional Chinese Herbal Formula

Tsai¹,

Pan²,

Lai

et al. 2009

Background: Zhulingtang (ZLT), a traditional Chinese medicine formula, was used to evaluate the antilithic effects of experimentally induced calcium oxalate (CaOx) nephrolithiasis in ethylene glycol (EG)-fed rats. Materials and Methods: A total of 35 male Sprague-Dawley rats were randomly divided into 4 groups. Rats in group 1 (n = 8) served as the normal control. Rats in group 2 (n = 11) were treated with gastric gavages of starch as placebo and 0.75% EG as a stone inducer. Rats in group 3 (n = 8) were given 0.75% EG and a low dose (305 mg/kg) of ZLT. Rats in group 4 (n = 8) were treated with EG and a high dose (915 mg/kg) of ZLT. Twenty-four-hour urine and blood samples were collected at the beginning and at the end of the experiment for biochemical analysis. The histological appearances of the kidneys were observed under a polarized light microscope, and the crystal deposits were evaluated by a semiquantitative scoring method, computer assisted with ImageScoring software. Results: Our results revealed that rats fed with 0.75% EG for 4 weeks successfully produced renal deposition of CaOx. The severities of crystal deposition were significantly reduced in the 2 ZLT-fed groups compared with the placebo group (p = 0.025 and 0.047, respectively). Rats in the low-dose ZLT and placebo groups exhibited significantly lower serum phosphorus in comparison with the control rats (p = 0.005 and 0.03, respectively). Rats of the placebo group (EG + starch) encountered growth retardation, with their body weights slowly increasing, expressed as 160.63 ± 23.06 g, compared with 179.63 ± 13.41 g in normal rats (p < 0.001). Conclusion: ZLT reduced the severity of CaOx crystallization and slowed down the body weight loss effects. Therefore, the traditional Chinese medicine herbal formula ZLT may be an effective reagent for renal stone prophylaxis. Although the mechanism of ZLT in crystal inhibition remains unclear, macromolecules may be involved.