This meta-analysis-of seven randomized control trials on CsA for nephrotoxicity risk-do not deny the absence of a degree of harm, however, it demonstrated the absence of a significant harmful effect for incidence of permanent nephrotoxicity. Nephrotoxicity was insignificant and transient, compared to the benefit of CsA in remission of newly onset juvenile diabetes, with preservation of beta cell function through the first year followed the diagnosis [17]. In general the conclusion was hearty and no publication bias was sensed. However, forward-looking progressive analyses by status adjustments and study designs showed no significant correlations, also, showed absence of intolerable, significant or permanent side effects. And this was clear in the effect of CsA on GFR, serum potassium, renal plasma flow, lithium clearance, serum albumin and bicarbonate, 6 months after withdrawal and even during the course of treatment. Not to mention the sub-group analysis by study sites, GFR, serum potassium, follow up after withdrawal and blood pressure. Prolonged treatment of high dose CsA, which was a major participator in treatment of many autoimmune diseases and in the field of transplantation, was reported to be associated with development of many side effects [18].
CsA, the aforementioned, was used in treatment of new onset type 1 juvenile diabetes. It Causes remission and autoimmune suppression of antibodies. Therefore, restoration of beta cell function and patients protection from final adverse undesirable outcome, reducing by that morbidity and mortality. However, it may lead to transitional outcomes as a drawback of CsA itself. These adverse effects were proved by researches, to be minor and transient, where the creatinine level did not exceed 160 umol/L. The clinical and biochemical side effects of cyclosporine came across this meta-analysis were not greater than expected.
The level of serum creatinine in all studies selected was established by six months and lingered stable through the first year. When we compared the estimation of Glomerular Filtration Rate (GFR) made in the same subjects, in the selected studies used in subgroup analysis, we accepted our alternative hypothesis. As shown in a study done on 49 subjects on cyclosporine and 45 subjects on placebo, which indicated alike equivalent reductions of both renal functions in cyclosporine-treated subjects (serum creatinine 18%, GFR 20%) [19].
Feldt and his colleagues did not use the creatinine as indicator for renal function evaluation, however, the renal function in terms of creatinine clearance was returned to normal following withdrawal of CsA. It was noticed that reduction in GFR, renal plasma flow and lithium clearance, had disappeared, six months after withdrawal of CsA. The net result of our analysis demonstrated absence of serious nephrotoxicity that could be observed. In all studies reviewed, the rise in plasma creatinine above normal in cyclosporine treated subjects was transient and insignificant.
The difference noticed between the uppermost levels in serum creatinine level when we come to compare it with the placebo group was insignificant. However in most of studies when the dose of CsA was remodeled, all the parameters used to evaluate the kidney functions was normalized and improved within less than six months. No one could deny the presence of minor adverse effects in order to obtain the desired effect of the drug, among the subjects of the study population treated with CsA. However, none of the researchers was obliged to suspend the treatment. Additionally, the double-blind nature of the trials might have a trivial effect, if any, which testifies the occurrence of such similar side effects in the placebo group. The reversible increase in serum creatinine was the gravest side effect noticed in most of the included and excluded trials, even the one which disturb the balance of our meta-analysis. Secondary side effects and drawbacks of CsA administration at low to moderate doses were infrequent and negligible. Serum level of creatinine did not change considerably in the study group treated with cyclosporine [20].
Trials conducted on cyclosporine have demarcated a structure of cause and effect that passes from augmentation of endogenous insulin release by immunotherapy to glycemic control to decrease in peripheral neuropathy diabetic retinopathy and microvascular pathology. We imagine that further clinical trials will keep an eye on these visions and we hope that this hard work will lead to a foremost bargain in the disease’s burden of grief. The limitation of the study was, some of the available data was abundant but descriptive and confined to; numbers, means, SEs and p values, with no further statistical analysis. This put a heavy load over us and pushed us for more digging and in-depth searching and analysis. For example the author mentioned in the last paragraph that p value was considered to be <0.05, we extract the rest of data by ourselves like mean differences, differences between groups, upper level and lower level CIs.