Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

BACKGROUND AND OBJECTIVES: Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. METHODS: 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. RESULTS: hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. CONCLUSION: hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

Characterization of Mesenchymal Stem Cells Derived from Rat Bone Marrow and Adipose Tissue: A Comparative Study

BACKGROUND AND OBJECTIVES: Stem cell technology offers a new hope for many chronic disorders patients. The types of stem cells are different with many differences existing between each type. Mesenchymal stem cells (MSCs) represent one type of adult stem cells that can be easily isolated, then re-transplanted to the patients. This offers potential for their future application in treating many disorders without fear of rejection possibility. MSCs can be isolated from different sources e.g. bone marrow (BMSCs) and adipose tissue (ADSCs). In the present study we compared BMSCs and ADSCs isolated from Sprague-Dawley rats. METHODS AND RESULTS: For this comparison, immunophenotyping, the analysis of growth rates, proliferation by colony forming unit-fibroblast assay, population doubling time, and trilineage differentiation assays were performed for both BMSCs and ADSCs. The findings revealed that despite no difference in immunphenotypic character between BMSC and ADSC, a better proliferative capacity was observed for ADSCs which would advocate their better use in regenerative applications. On the other hand, BMSCs showed more potential for osteogenic and chondrogenic differentiation. CONCLUSIONS: Our study showed that, despite many similarities between both types of cells, there are differences existing which can offer assistance on choosing type of cell to be used in specific diseases. Although ADSCs seem more promising for regenerative application generally, BMSCs may represent a better choice for treating bone disorders.

Single-center experience with cyclosporine for treatment of idiopathic minimal change nephrotic syndrome in children

Cyclosporine A is used in the treatment of idiopathic nephrotic syndrome. We conducted this study to evaluate the effect of cyclosporine and its combination with ketoconazole in Egyptian nephrotic children with steroid-resistant and steroid-dependant minimal change. Forty-eight children with minimal change lesions who received cyclosporine with or without ketoconazole were studied. Their mean age was 5.17 +/- 1.59 years, and they were 31 boys and 17 girls. The mean duration of the disease was 6.22 +/- 3.16 years. Thirty-one of the children were steroid dependent and 17 were steroid resistant. Cyclosporine treatment was commenced after remission was attained and adjusted to a target trough level of 100 nanogram/mL. The mean cyclosporine therapy at a dose of 2.07 +/- 0.91 mg/kg was administered for a mean of 25.75 +/- 1.95 months. Thirty-three patients received adjunctive ketoconazole therapy. Thirty-eight patients [79.2%] responded well to cyclosporine. Steroid therapy could be discontinued in 43 patients [89.6%], but 9 experienced relapse. Ten patients [20.8%] were resistant to cyclosporine therapy. Fifteen patients received cyclosporine alone, while 33 received concomitant cyclosporine and ketoconazole. The response to cyclosporine was significantly better in those on ketoconazole. The economic effect of ketoconazole therapy was a reduction in the costs of cyclosporine treatment by 47.4% at 1 year of treatment. Cyclosporine treatment in children with minimal change nephrotic syndrome is effective in preventing relapse and decreasing steroid toxicity. Its combination with low-dose ketoconazole is safe, reduces treatment costs, and improves the response to cyclosporine

Steroid and azathioprine versus steroid, cyclosporine, and azathioprine therapies in primary haplo-identical living donor kidney transplantation Twenty-year experience

Achievements in short-term graft survival since the introduction of cyclosporine has not been matched by improvement in long-term graft function, and chronic allograft nephropathy remains the second commonest cause of graft attrition over time. We aimed to evaluate the long-term results of conventional immunosuppression by steroid and azathioprine in comparison with cyclosporine-based triple therapy in living donor kidney transplants. We evaluated the long-term follow-up data of 369 living related kidney transplant recipients that were on prednisolone-azathioprine immunosuppressive therapy [group 1] or triple therapy by prednisolone, cyclosporine, and azathioprine [group 2]. All recipients were followed-up for more than 10 years [mean, 240 +/- 12 months]. Comparative analyses included patient and graft survival rates, condition at last follow-up, graft rejection, and graft function. There were 130 patients in group 1 and 239 in group 2. The overall frequency of acute rejection episodes was not significantly different between the two groups. However, the proportion of patients with chronic allograft nephropathy was significantly higher in group 2 [21% versus 35%, P = .001]. Graft survival rates were 85.3% versus 92.4% at 1 year, 69.9% versus 71.9% at 5 years, and 52.5% versus 50.8% at 10 years in groups 1 and 2, respectively [P = .03]. The two groups were comparable regarding posttransplant malignancies, diabetes mellitus, serious bacterial infections, and hepatic diseases. However, hypertensive patients were significantly more frequent in group 2. Chronic allograft nephropathy was significantly higher in patients receiving cyclosporine, possibly due to the risk of drug-induced nephrotoxicity, glomerular disease recurrence, and hypertension. Nowadays, it is possible to achieve excellent calcineurin inhibitors-free regimen using newer maintenance immunosuppressive agents

Protenuria after kidney transplantation its relation to hepatitis C virus and graft outcome

Chronic Hepatitis C Virus [HCV] infection has been associated with glomerular disease in native and transplanted kidneys. We evaluated the presence of HCV infection at the time of transplantation and occurrence of proteinuria in Egyptian kidney transplant patients and their link with graft survival. This retrospective study was done on 273 patients with end-stage renal disease transplanted in Mansoura Urology and Nephrology Center Between 1993 and 1996. Their sera were routinely assayed for anti-HCV antibodies at the time of transplantation. The relationship between the HCV and the development of posttransplantation proteinuria was evaluated, along with the possible effects of proteinuria on long-term graft survival. A total of 169 kidney recipients [61.9%] were positive for anti-HCV antibodies. The mean durations of post-transplant follow-ups were 87.73 +/- 26.79 months [range, 19 to 123 months] and 84.29 +/- 28.55 months [range, 11 to 123 months] for the patients with and without anti-HCV antibodies, respectively. The patients in these groups were comparable regarding the incidence of proteinuria [33% and 32%, respectively] and its quantity [median, 0.6 g/d and 0.4 g/d, respectively]. Irrespective of the HCV infection, patients with nephrotic-range proteinuria showed a worse graft survival [P < .001] and a higher frequency of chronic allograft nephropathy [P = .03] compared with nonproteinuric patients. There is a high prevalence of HCV infection in our patients with end-stage renal disease awaiting kidney transplantation. The incidence and quantity of proteinuria do not increase by HCV infection, and nephrotic-range proteinuria is independently associated with chronic allograft nephropathy and a poorer graft outcome

Transfer of serum suppressive activity, which inhibit lymphocyte proliferative response to Schistosoma mansoni antigens, from Schistosoma mansoni infected mothers to their offspring

The study objective was to find if serum specific suppressive activities on Lymphocyte transformation in response to Schistosoma mansoni [S. mansoni] antigens, usually present in serum of chronic S. mansoni infected patients, are permeable through the placenta from S. mansoni infected mothers to their newborns. Also, to find if such transferred activities are maintained during breast feeding and after weaning. Control group of 8 normal mothers and their offspring and 3 study groups of 13, 11, 11 S. mansoni infected mothers and their newborns, breast-fed infants and weaned children were included in the study. Proliferative response of Lymphocytes, from S. mansoni donors, to S. mansoni soluble egg antigen [SEA] and adult worm antigen [AWA], in presence of serum from each infected mothers groups, showed significantly higher suppressive activity than when the same lymphocytes were incubated with the same antigens in presence of serum from normal mothers group. This suppressive activity was transferred from S. mansoni infected mothers to their newborns' serum and maintained in their barest-fed infants' serum as donors' lymphocytes showed significantly higher suppressive activity in presence of serum from these two groups than in presence of serum from offspring of normal mothers. Serum from weaned children of S. mansoni infected mothers still showed suppressive activity significantly higher than serum from offspring of normal mothers but significantly lower than suppressive activity of serum from newborns and breast-fed infants of S. mansoni infected mothers. No significant difference in suppressive activity in presence of serum from different groups when donors' lymphocytes were stimulated by PHA indicating that this transferred suppressive activity is specific to S. mansoni antigens. Interleukin-10 [IL-10] production by donors' lymphocytes when stimulated by different stimulants showed results parallel to suppressive activity. Also, IL-10 production by donors' lymphocytes when stimulated by SEA and AWA in presence of serum from offspring of S. mansoni infected mothers showed highly significant positive correlation with suppressive activity of donors' lymphocytes when stimulated by the same antigens in presence of the same serum [P = 0.001 and < 0.001 respectively]. The parallelism and correlation between effect of serum on suppressive activity and IL-10 production suggest that IL-10 production is one of the main mechanisms by which serum affect lymphocytes transformation. These results suggest that the antischistosomal immunological status of S. mansoni infected mothers affects the future of their offspring when infected with S. mansoni and encourage studying the use of effective pathology modulating vaccines with mothers during pregnancy and lactation

role of parenteral iron therapy in treating the chronic hemodialysis associated anemia, a comparative study between iron saccharate and gluconate

Anemia in hemodialysis patients is a complex syndrome and many factors other than absolute or relative erythropoietin [EPO] deficiency may contribute to it. The most important factor is the presence of iron depletion. The impetus of this study was to assess the safety and efficacy of iron saccharate complex [ISC] and sodium ferric gluconate complex [SFGC] as relatively new parenteral iron preparations in treating anemia in hemodialysis patients. Forty-eight adult anemic patients of both genders [33 males and 15 females] who had an adequate level of both hemodialysis and nutrition status and received neither EPO nor parenteral iron therapy during the preceding 6 months were randomized into two groups. The first group, comprised 22 patients who were treated with parenteral ISC, 100 mg twice weekly for two months and once weekly thereafter. The second group included 26 patients who received SFGC, 62.5 mg twice weekly for two months and once weekly thereafter. The patients were followed up for 6 months. Our results showed that iron stores had been adequately repleted by the use of both parenteral iron formulas. Repletion of iron stores was associated with a significant rise of both hemoglobin and hematocrit% in both groups at the end of follow up period in comparison to their initial values at the start of the study [P < 0.001]. Both parenteral iron therapy preparations were tolerated and comparable with no statistical difference between both groups. Parenteral iron saccharate and gluconate are effective and sale treatment of anemia associated with chronic hemodialysis patients provided that they had an adequate level of both dialysis and nutrition

Hepatitis B and hepatitis C viral infections among Egyptian hemodialysis patients: study on some of the contributing factors

In this work we studied the incidence of hepatitis B virus [HBV] and hepatitis C virus [HCV] infections among 150 Egyptian hemodilaysis patients, 70% of them had hepatitis viral infections, 73% were HBV infected, 8% were HCV infected and 25% had combined HBV and HCV infection. When investigating the possible contributing factors, blood transfusion and prolonged hemodialysis were found significantly associated with HCV infection [P<0.05]. Two serum liver function tests were studied as possible non invasive predictors for these viral infections in such patients; the elevated s. bilirubin level was found non significantly associated with HCV infection while elevated sGPT was found significantly associated with HCV infections. These viral infections could be easily predicted by serum biochemical tests, should be screened periodically and precautionary steps have to be set up to reduce the high incidence of infection