Morphology of Ciclosporin Nephropathy

Mihatsch, Michael J.; Thiel, G; Ryffel, Bernard

doi:10.1159/000318486

Cited by 19 publications

(12 citation statements)

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“…In these studies, cyclosporin increased the prevalence of non-insulin-requiring remission (5,6) and enhanced and preserved p-cell function for as long as the drug was administered in newly diagnosed IDDM patients (6). However, because not all IDDM patients treated with cyclosporin achieved an improved P-cell function resulting in non-insulin-requiring remission and because of the severe adverse effects of current immunosuppressive drugs (7), the identification of immunological selection criteria predicting the clinical outcome of immunotherapy in IDDM is of great importance.…”

mentioning

confidence: 99%

Glutamic Acid Decarboxylase (GAD65) Autoantibodies in Prediction of β-Cell Function and Remission in Recent-Onset IDDM After Cyclosporin Treatment

Petersen¹,

Dyrberg

Karlsen

et al. 1994

Diabetes

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We have investigated whether glutamic acid decarboxylase (GAD) autoantibodies (GAD65 Ab) were affected by cyclosporin therapy and were related to subsequent non-insulin-requiring remission and loss of glucagon-stimulated C-peptide response in 132 recent-onset insulin-dependent diabetes mellitus (IDDM) patients treated with cyclosporin or placebo for 12 months. GAD65 Ab were detected in a quantitative radioligand assay using as tracer recombinant, in vitro translated, human islet [35S]methionine-labeled GAD65. GAD65 Ab were found at onset in 66% (87 of 132) of IDDM patients and in 1% (1 of 100) of healthy control subjects. The prevalence of GAD65 Ab and median GAD65 Ab levels did not change in serum samples taken 3, 6, 9, and 12 months after study entry in either the cyclosporin- or the placebo-treated groups. The presence or absence of GAD65 Ab at study entry did not predict non-insulin-requiring remission in either cyclosporin- or placebo-treated patients. However, the relative (compared with 0 months) glucagon-stimulated C-peptide response was more than 30% lower in GAD65 Ab+ patients receiving placebo at 9 and 12 months compared with the GAD65 Ab- placebo patients (P < 0.035). Islet cell cytoplasmic antibody (ICA) and GAD65 Ab+ placebo-treated patients showed no significant differences in stimulated C-peptide levels compared with those who were ICA- and GAD65 Ab+, suggesting that ICA was not independently associated with loss of beta-cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

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mentioning

confidence: 99%

Glutamic Acid Decarboxylase (GAD65) Autoantibodies in Prediction of β-Cell Function and Remission in Recent-Onset IDDM After Cyclosporin Treatment

Petersen¹,

Dyrberg

Karlsen

et al. 1994

Diabetes

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“…The changes are non-specific and in the chronic, sclerotic phase they are similar to changes observed in other chronic interstitial diseases such as analgesic nephropathy [68], vascular nephrosclerosis [67] cyclosporineinduced nephropathy [69], radiation nephritis [70,71] and aging [70], intoxication with silicate, cadmium, lead, uranium [72], Aristolochia clematitis [45], mycotoxin ochratoxin A [73], and Chinese herbs [46,48].…”

Section: Pathomorphological Changesmentioning

confidence: 79%

“…On the other hand, close similarity of Balkan nephropathy with an-algesic and cyclosporine-induced nephropathy has been recognized [69,70,77]. All this leads to a suggestion that Balkan nephropathy develops following a model of toxic nephropathy, targeting primarily the vascular endothelium where the tubular epithelium is affected either directly or indirectly due to accompanying ischemia.…”

Section: Overview Of Morphological Studiesmentioning

confidence: 94%

Balkan endemic nephropathy

Djukanović

Radovanović

2003

Clinical Nephrotoxins

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“…This side effect is usually reversible when the CsA dose is reduced. [10] Experimental studies in spontaneously hypertensive rats revealed a nephrotoxicity similar to that observed in man. [3] Renal vasoconstriction is attributed to an imbalance in the release of vasoactive substances: on one hand, increased release of vasoconstrictive factors such as thromboxane, [4] endothelin, [5] and angiotensin II; [6] and, on the other, a decrease in vasodilating factors such as prostacyclin [6] and nitric oxide (NO).…”

Section: Introductionmentioning

confidence: 90%

Nifedipine Attenuates Changes in Nitric Oxide Levels, Renal Oxidative Stress, and Nephrotoxicity Induced by Cyclosporine

Chander¹,

Chopra²

2005

LRNF

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Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its action is frequently accompanied by severe renal toxicity. The causes for the nephrotoxicity of CsA have not been fully elucidated. Intrarenal vasoconstriction induced by several different mediators, both in humans and experimental animals, have been proposed. To determine if the renal alterations are mediated directly by cyclosporine or by secondary hemodynamic alterations induced by cyclosporine, we evaluated if nifedipine prevents these alterations. Eight groups of rats were employed in this study, group 1 served as control, group 2 rats were treated with CsA (20 mg/mL, s.c. for 21 days), groups 3, 4, and 5 received CsA along with various doses of nifedipine (5, 10, and 20 mg/kg, p.o.) 24 h before and 21 days concurrently, groups 6, 7, and 8 received L-NAME (10 mg/kg i.p.), propranolol (10 mg/kg i.p.), and aminoguanidine (100 mg/kg p.o.), respectively, along with CsA. Renal function was assessed by measuring serum creatinine, blood urea nitrogen, creatinine, and urea clearance. Tissue and urine nitrite and nitrate levels were measured to estimate the total nitric oxide levels. The renal oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels, and enzymatic activity of catalase and superoxide dismutase. Renal morphological alterations were assessed by histopathological examination. CsA administration for 21 days resulted in a marked renal oxidative stress, and significantly deranged the renal functions as well as renal morphology. Treatment with nifedipine (10, 20 mg/kg) significantly improved the renal dysfunction, tissue and urine total nitric oxide levels, and renal oxidative stress and prevented the alterations in renal morphology. These results clearly demonstrate that nifedipine is beneficial as a protective agent against nephrotoxicity induced by CsA, and the protection afforded by nifedipine appears to be mediated by an increase in endothelial nitric oxide release.

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Morphology of Ciclosporin Nephropathy

Cited by 19 publications

References 0 publications

Glutamic Acid Decarboxylase (GAD65) Autoantibodies in Prediction of β-Cell Function and Remission in Recent-Onset IDDM After Cyclosporin Treatment

Glutamic Acid Decarboxylase (GAD65) Autoantibodies in Prediction of β-Cell Function and Remission in Recent-Onset IDDM After Cyclosporin Treatment

Balkan endemic nephropathy

Nifedipine Attenuates Changes in Nitric Oxide Levels, Renal Oxidative Stress, and Nephrotoxicity Induced by Cyclosporine

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