Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation

Daniel Brennan, Robert J. Stratta, Jeffrey A. Lowell, Suzanne A. Miller, Rodney J. Taylor

Research output: Contribution to journalArticle

Abstract

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient’s renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2,4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean ± SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640±76 ng/ml. SCr increased from 1.2±0.1 mg/dl to 1.6±0.1 mg/dl (33% increase) (P=0.0001). CrCl decreased from 82±9 ml/min to 63±8 ml/min (24% decrease) (P=0.03). GFR decreased from 95±15 ml/min to 70±10 ml/min (26% decrease) (P=0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r=0.77 and 0.98; P=0.3 and 0.7, respectively). Urinary protein decreased from 1.0±0.3 g/day to 0.7±0.3 g/day at both 4 and 6 weeks CP=0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Scrum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6±0.1 vs. 1.7±0.3 mg/dl, P=0.48, and CrCl 68±10 vs. 53 ±3 ml/min, P=0.17, respectively.

Original languageEnglish (US)
Pages (from-to)1606-1611
Number of pages6
JournalTransplantation
Volume57
Issue number11
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Pancreas Transplantation
Cyclosporine
Pancreas
Creatinine
Kidney
Glomerular Filtration Rate
Serum
Diabetic Nephropathies
Kidney Transplantation
Iothalamic Acid
Allografts
Proteins
Transplantation
Transplants

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Brennan, D., Stratta, R. J., Lowell, J. A., Miller, S. A., & Taylor, R. J. (1994). Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation. Transplantation, 57(11), 1606-1611.

Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation. / Brennan, Daniel; Stratta, Robert J.; Lowell, Jeffrey A.; Miller, Suzanne A.; Taylor, Rodney J.

In: Transplantation, Vol. 57, No. 11, 01.01.1994, p. 1606-1611.

Research output: Contribution to journalArticle

Brennan, D, Stratta, RJ, Lowell, JA, Miller, SA & Taylor, RJ 1994, 'Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation', Transplantation, vol. 57, no. 11, pp. 1606-1611.
Brennan, Daniel ; Stratta, Robert J. ; Lowell, Jeffrey A. ; Miller, Suzanne A. ; Taylor, Rodney J. / Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation. In: Transplantation. 1994 ; Vol. 57, No. 11. pp. 1606-1611.
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abstract = "Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient’s renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2,4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean ± SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640±76 ng/ml. SCr increased from 1.2±0.1 mg/dl to 1.6±0.1 mg/dl (33{\%} increase) (P=0.0001). CrCl decreased from 82±9 ml/min to 63±8 ml/min (24{\%} decrease) (P=0.03). GFR decreased from 95±15 ml/min to 70±10 ml/min (26{\%} decrease) (P=0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r=0.77 and 0.98; P=0.3 and 0.7, respectively). Urinary protein decreased from 1.0±0.3 g/day to 0.7±0.3 g/day at both 4 and 6 weeks CP=0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Scrum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6±0.1 vs. 1.7±0.3 mg/dl, P=0.48, and CrCl 68±10 vs. 53 ±3 ml/min, P=0.17, respectively.",
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N2 - Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient’s renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2,4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean ± SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640±76 ng/ml. SCr increased from 1.2±0.1 mg/dl to 1.6±0.1 mg/dl (33% increase) (P=0.0001). CrCl decreased from 82±9 ml/min to 63±8 ml/min (24% decrease) (P=0.03). GFR decreased from 95±15 ml/min to 70±10 ml/min (26% decrease) (P=0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r=0.77 and 0.98; P=0.3 and 0.7, respectively). Urinary protein decreased from 1.0±0.3 g/day to 0.7±0.3 g/day at both 4 and 6 weeks CP=0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Scrum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6±0.1 vs. 1.7±0.3 mg/dl, P=0.48, and CrCl 68±10 vs. 53 ±3 ml/min, P=0.17, respectively.

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