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Renal function after kidney transplantation in children. A comparison of conventional immunosuppression with
Insights
Cyclosporine (CsA) treatment in transplanted children significantly reduced kidney allograft function compared to azathioprine (CIS). This impairment was global, appearing early post-transplant, and not linked to CsA levels but rejection episodes.
Area of Science:
- Pediatric Nephrology
- Transplantation Immunology
- Pharmacology
Background:
- Cyclosporine (CsA) is a key immunosuppressant in organ transplantation.
- Assessing long-term renal allograft function in pediatric recipients is crucial.
- Comparing CsA-based regimens with older immunosuppressants like azathioprine (CIS) is important for optimizing treatment.
Purpose of the Study:
- To compare renal allograft function in pediatric transplant recipients treated with CsA versus azathioprine (CIS).
- To evaluate the impact of CsA on specific kidney functions, including filtration and tubular reabsorption.
- To determine the relationship between CsA blood levels, rejection episodes, and graft function.
Main Methods:
- Clearance studies were conducted in 32 children on CsA and 29 children on CIS.
- Serum creatinine and urea levels were measured at 6 weeks and 1 year post-transplant.
- Creatinine clearance (Ccr), inulin clearance (Cin), and PAH clearance (CPAH) were assessed.
Main Results:
- CsA group showed significantly higher serum creatinine and urea levels.
- Lower Cin and CPAH rates were observed in the CsA group at 6 weeks post-transplant (P < 0.001).
- Creatinine clearance declined in both groups, inversely correlated with rejection episodes (r = -0.72, P = 0.001), not CsA levels.
Conclusions:
- Renal allografts in CsA-treated children exhibit significantly lower function than in CIS-treated children.
- The observed reduction in kidney function is global, appears early, and is not due to specific tubular toxicity.
- Graft function decline post-CsA is related to overall kidney function and rejection episodes, not CsA blood levels.
Abstract:
Clearance studies were performed in 32 transplanted children treated with CsA in combination with low-dose prednisolone (CsA group), and the results were compared with those of 29 children transplanted earlier and treated with azathioprine and prednisolone (CIS group). Serum creatinine and urea levels 6 weeks and 1 year after transplantation (Tx) were significantly higher in the CsA than in the CIS group. Clearance studies 6 weeks after Tx exhibited significantly lower rates in the CsA group: Cin = 47 +/- 16.5 versus 83 +/- 25 ml/min/1.73 sqm, CPAH = 271 +/- 110 versus 503 +/- 181 ml/min/1.73 sqm (P less than 0.001). The filtration fractions were not different (19.1 versus 17.1%). The tubular phosphate reabsorption per ml GFR (Tp/Cin) was only slightly lower in the CsA group (0.76 +/- 0.23 mumol/ml versus 0.93 +/- 0.29; P = 0.09). The endogenous glucose clearance rates were equally elevated in both groups and returned to normal after 1 year. The creatinine clearance (Ccr) had dropped in both groups by a mean for 13 ml/min/1.73 sqm between 6 weeks and 1 year after Tx. No correlation was found between the Ccr and the CsA blood levels, but Ccr was inversely correlated with the number of rejection episodes (r = -0.72, P = 0.001). In conclusion, renal allografts in CsA-treated children exhibited a significantly lower function than in CIS-treated children. The effect was related to the global kidney function without any signs of additional tubular toxicity and was apparent within the first weeks after Tx. Thereafter, the decline in graft function was comparable in both groups and could not be related to CsA treatment.