Histopathological Changes in the Kidney of the Rat on an Atherogenic Diet

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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“…In der äusseren Markzone, weitgehend einer Lokalisation im distalen Tu bulus entsprechend, kam es zu ausgeprägten Kalzifikationen. Diese Veränderungen können Ergebnis einer Schädi gung des distalen Tubulus sein, wie wir es auch in unseren Voruntersuchungen beschrieben haben [17,19].…”

Section: Diskussionunclassified

Zur Wirkung von Kalziumantagonisten (Nifedipin) auf die Nephrokalzinose und Kalziumausscheidung der Ratte (mit 1 Farbtafel)

Bichler¹,

Strohmaier²,

Schanz³

et al. 1985

Self Cite

An animal model was established to test the effect of a calcium antagonist on nephrocalcinosis, which was induced by an atherogenous diet, and its effect on the excretion of calcium and other parameters relevant for stone formation. With the administration of nifedipine (Adalat®), the grade of nephrocalcinosis could be significantly reduced. Furthermore, with nifedipine the excretion of calcium and sodium in the urine was raised, while phosphate and potassium levels were lowered. The excretion of magnesium and citrate, reduced by an atherogenous diet, could be raised significantly with the administration of nifedipine. The pathophysiological mechanisms underlying the effect of nifedipine on nephrocalcinosis and on the excretion of the urine parameters are discussed. Apparently hypercalciuria is the result of a reduced reabsorption of calcium in the tubulus. The inhibitory effect on the genesis of nephrocalcinosis is possibly due to the lower calcium influx into the tubular cells.

“…This is in accordance Table 3. Means and standard deviations of the urinary excretion of Na, Ca, Mg, P, and citrate (Ci) (mmol/g creatinine, week 4, n = 5 of each group) and the fractional excretion (FE; %) of Na, Ca, Mg and P, as measured by the clearance studies after week 4 (n = 6 of each group) of the cholesterol (CH), cholesterol plus nifedipine (CHpN) and the control group (C) with previous investigations of calcium phosphate stone formation [1,2,[5][6][7], From these studies, however, it was not apparent where the formation of calcifications started, since the histological examinations were only per formed after a long-term application of a cholesterol diet (4 weeks). In the present study, histological investigations were already performed after 1 week demonstrating for the first time that the first small deposits occurred within the renal tubular cells.…”

Section: Discussionmentioning

confidence: 99%

“…Hypercalciuria, possibly caused by increased glucagon secretion, low plasma thyroxine, decreased ex cretion of magnesium and Tamm-Horsfall protein were discussed [1][2][3][4]. 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.