isotretinoin and Kidney-Diseases

Isotretinoin has been reported to elevate creatine kinase, which may lead to fatal rhabdomyolysis.. To review the literature and propose practice guidelines for management of elevated creatine kinase during isotretinoin therapy.. Patients have intrinsic and extrinsic qualities that may synergistically work with isotretinoin to elevate serum creatine kinase. Darker skin types and males on isotretinoin are more likely to have elevated creatine kinase. Isotretinoin may induce oxidative stress within muscle tissue, thereby leading to elevations in serum creatine kinase.. Evidence supports a tenuous correlation between isotretinoin, elevated creatine kinase, and exercise. Physicians should consider obtaining baseline creatine kinase on elite athletes and counseling patients on risk factors that may elevate creatine kinase. However, the potential for elevated CK is not a contraindication for isotretinoin therapy.

Topics: Acne Vulgaris; Creatine Kinase; Dermatologic Agents; Exercise; Humans; Isotretinoin; Kidney Diseases; Muscle, Skeletal; Oxidative Stress; Rhabdomyolysis; Risk Factors; Sex Factors; Skin Pigmentation

Retinoids are anti-proliferative and anti-inflammatory compounds. We had previously shown that retinoids alleviate kidney damage in acute models of renal disease. We now examined whether retinoids are also effective in a chronic renal ablation model. Subtotally nephrectomized rats (SNx; two-third ablation) were compared to sham-operated controls (sham). SNx rats were administered either 10 mg/kg b.w. (low dose, LD) or 40 mg/kg b.w. (high dose, HD) isotretinoin or vehicle (n = 10 per group). The experiment was terminated after 16 weeks. Systolic blood pressure was significantly higher after SNx compared to sham but lower in SNx with LD isotretinoin (vs. SNx + vehicle). Compared to SNx + vehicle, SNx + LD isotretinoin had lower glomerular cell numbers, less glomerular hypertrophy and sclerosis, and less interstitial expansion. Morphological improvement in SNx + LD isotretinoin was accompanied by improvement in creatinine clearance and reduced urinary albumin excretion. In contrast, HD isotretinoin caused aggravation of renal damage with fibrinoid necroses of vessels and elevated urinary albumin excretion despite lower blood pressure. The dichotomous effects of isotretinoin are at least in part due to time- and dose-dependent alterations of transforming growth factor beta1 and collagen IV gene expression as also suggested by cell-culture studies in vascular smooth muscle cells. In addition, isotretinoin affected the systemic and the renal renin-angiotensin system (which was further analyzed in a model of angiotensin II infusion of the rat). Isotretinoin failed to cumulate at LD but cumulated at HD in SNx. We conclude that LD isotretinoin attenuates progressive renal damage, whereas HD isotretinoin cumulates and aggravates renal damage independent of blood pressure reduction.

Topics: Albuminuria; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Cells, Cultured; Chronic Disease; Collagen Type V; Dermatologic Agents; Dose-Response Relationship, Drug; Gene Expression Regulation; Isotretinoin; Kidney Diseases; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nephrectomy; Rats; Rats, Sprague-Dawley; Time Factors; Transforming Growth Factor beta1

Topics: Adult; Humans; Isotretinoin; Keratolytic Agents; Kidney Diseases; Male