Reversal of Lesions of Diabetic Nephropathy after Pancreas Transplantation

Fioretto P, Steffes MW, Sutherland D, Goetz F, Mauer M. New England Journal of Medicine. 1998;339(2):69-75.

ABSTRACT RESULTS:-All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (±SD) creatinine clearance rate declined from 108±20 ml per minute per 1.73 m2 of body-surface area at base line to 74±16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74±14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570±64 and 928±173 nm, respectively) and at base line (594±81 and 911±133 nm, respectively) but had decreased by 10 years (to 404±38 and 690±111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33±0.07) to 5 years (0.39±0.10, P=0.02) but had decreased at 10 years (0.27±0.02, P=0.05 for the comparison with the base-line value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix.

This article reports on patients with Type 1 diabetes mellitus who received a pancreas transplant and were followed for a period of 10 years.

Table A: Renal function and metabolic indices.

  Mean Standard Deviation
Age (yrs) at baseline: 33 3
Duration of diabetes (yrs) at baseline: 22 5
Urinary albumin excretion rate (mg/24hrs)
at baseline: 103  
5 years: 30  
10 years: 20  
Creatinine clearance (mL/min/1.7m2)
at baseline: 108 20
1 year: 65 12
5 years: 74 16
10 years: 74 14
Mean HbA1c (%)
at baseline: 8.7 1.5
avg. over 10 years: 5.3 0.4

Thirteen patients underwent pancreas transplantation, all of whom had insulin-dependent diabetes prior to transplantation. Of the original cohort, 2 patients subsequently received kidney transplants (at 6 and 8 years after pancreas transplantation), 2 patients lost pancreatic graft function and required insulin therapy and 1 patient declined to participate in the 10-year follow-up studies. This left 8 patients who completed the protocol (2 males and 6 females remained for the entire study). Four patients had received cadavaric pancreas grafts and the other 4 patients had received segmental pancreas grafts from living related donors (3 from HLA identical siblings). All patients received immunosuppressive treatment with Prednisone, Cyclosporine, and Azathioprind Azathioprine throughout the study. Renal function tests and metabolic indices were studied before pancreas transplantation and at 1, 2, 3.5, 5, 7.5 and 10 years afterwards. Renal biopsies were performed before transplantation and at 2, 5 and 10 years thereafter.

The patients' mean glycosylated hemoglobin values significantly improved (p<0.001) compared with baseline values at 5 and 10 years. Interestingly, the mean creatinine clearance rate did diminish 1 year after baseline (p<0.001) but remained stable and did not statistically change thereafter. Urinary albumin excretion rate diminished but results did not reach statistical significance. Mean blood pressures did not change significantly from baseline. Two patients were receiving antihypertensive therapy at baseline, 4 patients were receiving antihypertensive therapy at 5 and 10 years.

Percutaneous renal biopsies were performed before pancreas transplantation and 5 and 10 years thereafter. A single investigator measured morphometric analysis on all biopsy samples. Photomicrographs were used to measure the fraction of glomeruli occupied by mesangial matrix mesangial cells and the thickness of tubular basement membrane. These morphometric measurements showed a decrease in glomerular basement membrane most evident at 10 years after biopsy as well as a decrease in tubular basement membrane, again, more evident at 10 years after transplantation.

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