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Cyclosporine nephrotoxicity in type 1 diabetic patients. A 7-year follow-up study
H H Parving1, L Tarnow, F S Nielsen
1Steno Diabetes Center, Gentofte, Denmark.
Objective:
To evaluate kidney function 7 years after the end of treatment with cyclosporine A (CsA) (initial dosage of 9.3 tapered off to 7.0 mg.kg-1.day-1) in young patients (mean age 20 years) with newly diagnosed type 1 diabetes participating in a randomized, double-blind, placebo-controlled CsA trial.
Research Design And Methods:
In this study, 21 patients received CsA for 12.5 +/- 4.0 months (mean +/- SD) and 19 patients received placebo for 14.4 +/- 3.8 months. The two groups were similar with regard to mean arterial blood pressure (BP), urinary albumin excretion rate (UAER), serum creatinine, and estimated glomerular filtration rate (GFR [Cockcroft and Gault]) at initiation of CsA treatment (baseline). HbA1c (mean +/- SEM) during 7 years of follow-up was also the same: 8.7 +/- 0.4 vs. 8.3 +/- 0.4% in the CsA and placebo groups, respectively.
Results:
During the 7 years after cessation of study medication, two CsA group patients and one control patient were lost to follow-up. One placebo-treated patient developed IgA nephropathy (biopsy proven) and was excluded. Four CsA-treated patients developed persistently elevated UAER > 30 mg/24 h (n = 3 with microalbuminuria), whereas all the 17 placebo-treated patients had normal UAER (< 30 mg/24 h) after 7 years of follow-up. At the end of follow-up, the CsA group had a more pronounced rise in UAER: 2.5-fold (95% CI 1.4-4.5) higher than baseline value vs. 1.1-fold (0.7-1.7) in the placebo-treated group (P < 0.05). Estimated GFR (ml.min-1.1.73 m-2) declined from baseline to end of follow-up (1994) by 6.3 +/- 6.0 in the former CsA group, whereas it rose by 7.4 +/- 5.0 in the placebo group (P = 0.05). In 1994, 24-h blood pressure was nearly the same: 131/77 +/- 4/2 vs. 127/75 +/- 2/2 mmHg (NS) in the CsA and placebo groups, respectively. Five randomly selected CsA-treated patients had a kidney biopsy performed shortly after the CsA treatment was stopped. Interstitial fibrosis/tubular atrophy and/or arteriolopathy were present in two subjects who both subsequently developed persistent microalbuminuria.
Conclusions:
The results of our 7-year follow-up study suggested that short-lasting CsA treatment in young, newly diagnosed type 1 diabetic patients accelerated the rate of progression in UAER and tended to induce a loss in kidney function. Longer term follow-up is mandatory to clarify whether CsA-treated patients are at increased risk of developing clinical nephropathy.
Insights
Short-term cyclosporine A (CsA) treatment in young type 1 diabetes patients accelerated urinary albumin excretion rate and tended to reduce kidney function over 7 years. Further follow-up is needed to assess long-term nephropathy risk.
Area of Science:
- Nephrology
- Endocrinology
- Immunosuppression
Background:
- Cyclosporine A (CsA) is an immunosuppressant used in various conditions.
- Its long-term effects on kidney function in young type 1 diabetes patients are not fully understood.
Purpose of the Study:
- To evaluate kidney function 7 years after short-term cyclosporine A treatment in young patients with newly diagnosed type 1 diabetes.
- To assess the long-term impact of CsA on urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (GFR).
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving young type 1 diabetes patients.
- Patients received CsA or placebo for approximately 12-14 months.
- Kidney function markers including UAER and GFR were monitored for 7 years post-treatment.
Main Results:
- CsA-treated patients showed a 2.5-fold increase in UAER compared to baseline, while placebo patients had a 1.1-fold increase (P < 0.05).
- Estimated GFR declined in the CsA group, whereas it increased in the placebo group (P = 0.05).
- Kidney biopsies in some CsA patients revealed interstitial fibrosis/tubular atrophy and arteriolopathy, associated with subsequent microalbuminuria.
Conclusions:
- Short-term CsA treatment in young type 1 diabetes patients appears to accelerate UAER progression and may impair kidney function.
- Longer-term studies are necessary to determine if CsA-treated patients face an increased risk of clinical nephropathy.