Administration of Cyclosporine A in Pregnant Rats - the Effect on Blood Pressure and on the Glomerular Number in Their Offspring

Abstract

Background/Aims: Cyclosporine A (CsA) is a commonly used immunosuppressive agent. In some patients treatment with CsA has to be continued during pregnancy. The aim of the study was to assess in an experimental model whether the exposure to CsA during fetal life influences the number and volume of glomeruli, kidney function and blood pressure in the offspring. Methods: Eight pregnant female Sprague-Dawley rats were allocated to 2 treatment regimens: with CsA or solvent. Blood pressure was measured in the offspring at 7 and 11 weeks of age and albuminuria was determined at 11 weeks of age. In the kidney the number and mean volume of glomeruli was assessed using stereological methods. Results: In the offspring of pregnant rats treated with CsA the number of glomeruli was significantly lower and the mean volume of glomeruli was higher when compared to the offspring of pregnant rats receiving solvent. Systolic and diastolic blood pressures as well as albuminuria were significantly higher in the offspring of mothers treated with CsA during gestation compared to the offspring from the control group. Conclusions: Exposure of rats to CsA during fetal life impairs kidney development, thus potentially predisposing to chronic kidney disease and hypertension in the adult life.

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

“…A reduction of nephron number, in the absence of compensatory hypertrophy, would be expected to cause a decreased glomerular filtration rate (GFR). As shown in Table 1, however, variations of GFR observed in different models of renal programming can be reduced [33,34,35,36], unaltered [37,39,40,41,44], or even augmented [42]. These data suggest that there is a differential degree of compensatory hypertrophy in the setting of a low nephron endowment in various models of renal programming.…”

“…As shown in Table 1, a variety of pre-, peri-, and post-natal insults have been reported to cause renal programming and low nephron endowment. These factors include maternal undernutrition, high-salt, low-salt, utero-placental insufficiency, ethanol consumption, maternal inflammation, glucocorticoid exposure, vitamin A deficiency, iron deficiency, drug use, and gestational diabetes [30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. …”

Effects and Interactions of Prenatal Ethanol Exposure, a Post-Weaning High-Fat Diet and Gender on Adult Hypercholesterolemia Occurrence in Offspring Rats

“…In recent years, intrauterine growth retardation (IUGR) and macrosomia have been linked to some adult onset diseases. Specifically, IUGR could be a potential cause of adult hypertension and chronic kidney disease, and the related potential mechanisms have been studied [4-6]; macrosomia can cause the development of childhood obesity and type 2 diabetes and/or cardiovascular diseases in the later stage of life [7]. Traditionally, the incidence of hypercholesterolemia is mainly related to the postnatal environment [8, 9]; however, studies have demonstrated that IUGR is also an independent risk factor for hypercholesterolemia [10, 11].…”

iTRAQ-Based Proteomic Analysis of Neonatal Kidney from Offspring of Protein Restricted Rats Reveals Abnormalities in Intraflagellar Transport Proteins

“…Concern over the fetal programming effects of IUGR on the kidney has gained momentum in recent years, as epidemiological and experimental studies have demonstrated a significant association between birth weight and postnatal kidney function. For example, Gray and colleagues reported that IUGR reduces the volume of the fetal kidney and significantly decreases the number of glomeruli, as compared with the normal fetal kidney [5][6][7]. Based on IUGR models caused by maternal proteinmalnutrition, we previously reported a lower kidney index, glomeruli number, and glomerular filtration rate in IUGR offspring, with an increased incidence of hypertension, as compared with the control group throughout the postnatal follow-up period [8], consistent with other reports [9,10].…”