Dermatologic findings in renal transplant recipients: Possible effects of immunosuppression regimen and p53 mutations.

OBJECTIVE: To analyze the dermatologic lesions and possible effects of immunosuppression treatment and p53 gene mutations on dermatologic findings in renal transplant recipients. MATERIALS AND METHODS: The study included 163 renal transplant recipients. After dermatologic examination, cultures, and histopathologic and genetic analyses were performed. A single-strand conformation polymorphism technique was used to analyze p53 gene mutations. Patients were categorized into 3 groups according to time since the transplantation procedure. Results were analyzed using the χ(2) test, using a software program (SPSS version 13.0; SPSS, Inc, Chicago, Illinois). RESULTS: Mean (SD) age of the 163 transplant recipients (65 women and 98 men) was 40 (11) years, and posttransplantation follow-up was 65 (55) months. The most frequently observed drug-related lesion was hypertrichosis, in 46 of 150 patients. Of 115 lesions, the most commonly observed were verruca vulgaris (n = 34) from viruses, and pityriasis versicolor (n = 21) from superficial fungal infections. Of the total group, 20 patients (12.2%) were mutation carriers. Compared with the entire cohort, the group with premalignant lesions demonstrated more p53 mutations (11% vs 50%; P = .004). Patients given cyclosporine therapy exhibited more premalignant or malignant cutaneous lesions compared with patients who received other agents (P = .03). CONCLUSION: Patients carrying p53 mutations developed a malignant lesion in the late posttransplantation period, which suggests the importance of prediction of risk.

Evaluation of gadolinium pre-treatment with or without splenectomy in the setting of renal ischemia reperfusion injury in rats.

INTRODUCTION: This study aims to investigate gadolinium chloride (Gd) pre-treatment with/without splenectomy (Splx) in the setting of renal ischemia/reperfusion (IR) injury in rats. MATERIALS AND METHODS: Under anesthesia, male Wistar albino rats with or without splenectomized (Splx) were right nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 3 h of reperfusion. Gadolinium chloride (10 mg kg(-1)) or saline was administered 24 hours prior to ischemia via penile vein. Right nephrectomy and intravenous saline administration was performed in the control group. At the end of the reperfusion period, following decapitation, kidney samples were taken for histological examination or determination of renal malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and Na(+)-K(+) ATPase activities. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), TNF-alpha, and IL-1 beta were assayed in the serum samples. RESULTS: Ischemia/reperfusion caused significant increases in the serum TNF-alpha, IL-1 beta, BUN, creatinine, AST, ALT, LDH, and tissue MDA levels and MPO activity, while either Gd pre-treatment or Splx decreased these parameters significantly. On the other hand, IR induced a decrease in the tissue GSH, and Na(+)-K(+) ATPase activity was restored by both gadolinium and Splx. Furthermore, histopathological alterations induced by IR were also reversed. CONCLUSION: The extent of renal IR injury depends on the pro-inflammatory cytokine response. Gd pre-treatment decreases macrophage-derived cytokine secretion and thereby effectively limits the extent of renal IR injury in rats similar to Splx. Further studies needed to define an optimal way of decreasing macrophage-derived cytokine release due to the clinical limitations of Gd.

The clinical significance of parathyroid tissue calcium sensing receptor gene polymorphisms and expression levels in end-stage renal disease patients.

BACKGROUND: The calcium sending receptor (CaSR) allows parathyroid and kidney tubular cells to regulate PTH secretion and tubular calcium reabsorption. In the present report, we examined the relationship between CaSR gene polymorphisms and parathyroid CaSR expression and serum calcium/parathyroid hormone (PTH) levels and clinical progress in ESRD patients in the Turkish population. METHODS: We genotyped the CaSR R990G and Q1011E variants in 192 end-stage renal disease (ESRD) patients by allele-specific PCR. CaSR expression in parathyroid tissues of operated 33 patients was quantified with quantitative reverse transcription-PCR. RESULTS: Compared with other genotypes, the ratio of both codon 990-AA and 1011-CC polymorphisms was found higher in operated patients (p = 0.001). In the total patient group PTH levels were found higher in patients with CC1011 genotype than those with CG1011 (1015.15 +/- 925.41 pg/ml; 523.84 +/- 544.6 pg/ml, respectively, p = 0.002). There were statistically important higher Ca2+ levels in the AA990 allele carrying cases than AG990 positive ones (9.3 +/- 1.0 mg/dl vs. 8.8 +/- 0.9, p = 0.006). On the other hand, the expression of CaSR in parathyroid tissue was found inversely proportional with serum PTH level (r = -0.71). CONCLUSION: Present data suggest that co-presence of CaSR gene AA990 and CC1011 alleles is a possible risk factor for bad prognosis in secondary hyperparathyroidism. Patients carrying this genotype have tendency to require operation early in their medical therapy period and need postoperative close follow up for possible recurrences.