Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation.
OBJECTIVE
Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant.


METHODS
The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 +/- 0.3 years from kidney transplant).


RESULTS
The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P < 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 +/- 0.08 to 2.78 +/- 0.44 mg/dl, P < 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 +/- 0.01 to 0.68 +/- 0.01%, P < 0.01; KI-s at baseline: 0.72 +/- 0.02 to 0.69 +/- 0.02%, P < 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 +/- 9.0 to 82.9 +/- 33.6 mg/l, P < 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown).


CONCLUSIONS
In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function.
Fiorina
Paolo
P
Department of Medicine, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
Venturini
Massimo
M
Folli
Franco
F
Losio
Claudio
C
Maffi
Paola
P
Placidi
Claudia
C
La Rosa
Stefano
S
Orsenigo
Elena
E
Socci
Carlo
C
Capella
Carlo
C
Del Maschio
Alessandro
A
Secchi
Antonio
A
D000328:Adult; D001706:Biopsy; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery*; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D006984:Hypertrophy; D007165:Immunosuppression Therapy / Q000379:methods; D016381:Islets of Langerhans Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000401:mortality / Q000473:pathology / Q000502:physiology*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D002096:C-Peptide; D006442:Glycated Hemoglobin