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Although 4000 pancreas transplants have now been done, alone or in combination with a kidney transplant, the risk/benefit profile of the procedure has not been established by controlled studies. A solo pancreas transplant abolishes the need for daily insulin but requires chronic immunosuppression, has high failure rates, and is not proved to lessen the chronic complications of diabetes. Thus, it is probably justified only in those diabetic patients with incapacitating disease. For uraemic diabetic patients, combined pancreas and kidney transplantation often removes dependence on both insulin and dialysis, and has lower rejection rates than pancreas transplant alone. However, it needs more immunosuppression than kidney transplant alone, has no proven benefit on chronic complications of diabetes, and carries an increased risk of rejection, infection, and cancer. Living-related-donor kidney transplantation followed by cadaver pancreas transplantation is a possible alternative. Transplantation of pancreatic islets could offer the advantages of strict metabolic control without the drawbacks of immunosuppressive therapy. Thus, research efforts should concentrate on immune-protected islet transplantation. An alternative approach to avoiding long-term immunosuppression is the promotion of allograft tolerance.

The kidneys as a target organ for secondary microvascular complications of diabetes mellitus represents a health problem of enormous social cost. Recent studies in man and animals strongly support the concept that the primary responsibility for diabetic nephropathy rests with the metabolic derangements of the diabetic state. However, these metabolic derangements have complex biological effects; it is unlikely that hyperglycemia, per se, produces all of the nephropathic influences of diabetes. Alterations in microvascular hemodynamics in diabetes probably contribute to glomerular pathology. These alterations may be based upon disturbed vasoactive control mechanisms regulating angiotensin and prostaglandin secretion and metabolism. Although much remains to be learned about the pathogenesis of glomerular basement membrane and mesangial thickening in diabetes, these central structural abnormalities appear separable. Mesangial thickening is reversible by cure of the diabetic state in rats whereas glomerular basement membrane thickening is not. Treatment for the diabetic patient with end-stage renal failure has recently improved markedly. Although presently, kidney transplants from living related donors appear best, cadaver transplants and long-term hemodialysis are reasonable options.

A clinicopathologic study of forty-eight infants with nephrotic syndrome. The clinical and histopathologic features of 48 children presenting with the nephrotic syndrome during the first year of life were analyzed. Proteinuria was discovered soon after birth to 3 months of age in 39 infants (congenital nephrotic syndrome), and nine infants had an infantile onset presenting between 4 and 12 months of age. Neither histologic parameters—microglomeruli, epithelial, or mesangial proliferation, focal segmental or global sclerosis, fibrinoid necrosis, or tubular microcysts—nor histologic classification—microcystic disease, mesangial proliferative glomerulonephritis, focal segmental glomerular sclerosis/hyalinosis–predicted the outcome. Rather, age at presentation was found to predict outcome: One of 39 infants with a congenital onset and seven of nine infants with an infantile onset underwent a complete remission (P < 0.0001).Une étude anatomo-clinique de quarante-huit nourrissons avec syndrome néphrotique. Les caractéristiques cliniques et histopathologiques de 48 enfants atteints de syndrome néphrotique au cours de la première année de vie ont été analysées. La protéinurie avait été découverte peu après la naissance, jusqu'à l'âge de 3 mois chez 39 nourrissons (syndrome néphrotique congénital) et neuf nourrissons avaient eu un début infantile, entre les âges de 4 et 12 mois. Ni les paramètres histologiques—microglomérules, prolifération épithéliale ou mésan-giale, sclérose segmentaire et focale ou globale, nécrose fibrinoïde ou microkystes tubulaires—ni la classification histologique—maladie microkystique, glomérulonéphrite proliferative mésangiale, sclérose/ hyalinose glomérulaire segmentaire et focale n'étaient prédictifs du devenir. A l'opposé, l'âge à la découverte était prédictif du devenir: L'un des 39 nourrissons ayant un début congénital et sept des neuf nourrissons ayant un début infantile ont eu une rémission complète (P < 0,0001).

Observations of glomerular epithelial cell structure in patients with type I diabetes mellitus. Overt proteinuria is a hallmark of diabetic nephropathy while microalbuminuria is thought to be a predictor of later onset of diabetic nephropathy. Yet the mechanisms for abnormal urinary protein leak in diabetes have not been defined. We studied 28 patients with type I diabetes for 7 to 33 years. Creatinine clearance, urinary albumin excretion rate (UAE), and multiple blood pressures were obtained in each patient. A renal biopsy was performed in each patient and in 28 normal subjects. Quantitative stereology was used to determine foot process (FP) width, filtration slit length density (FSLV) and filtration slit length/glomerulus (FSLG). FP width was slightly wider than normal in diabetic patients with UAE < 250 mg/24 hr while FP was significantly wider than both of these groups in diabetics with UAE > 250 mg/24 hr. FSLV and FSLG were similar in normals and diabetics with UAE < 250 mg/24 hr but both were reduced in diabetics with UAE > 250 mg/24 hr. UAE correlated with FP width (P < 0.05), FSLG (P < 0.01) and most precisely and FSLV (P < 0.001). Diabetics with microalbuminuria had values for all the structural parameters measured here not different from diabetics with UAE in the normal range. Perturbations of epithelial cell structure are present in diabetes mellitus especially in patients with nephropathy. The exact relationships between albuminuria and epithelial cell structure remains to be elucidated.

The one million or so glomeruli present in each of our kidneys are remarkably constructed. It is here that the ultrafiltrate of plasma is formed to be economically reabsorbed by tubules, leaving behind substances of no further use to the body. It is also here that the movement of macromolecules across the peripheral glomerular capillary is impeded by the basement membrane and by fixed polyanions in the capillary wall. Also within the glomerulus is an anatomically distinct region—the mesangium. The traffic of macromolecules through this zone appears to be significantly influenced by changes in the peripheral glomerular capillary as well as by other experimental manipulations. In human glomerulonephritis, immune deposits are found here, often exclusively. Morphologic abnormalities have ranged from the mesangial matrix expansion and the characteristic intercapillary nodule formation of diabetic nephropathy to the prominent proliferation of membranoproliferative glomerulonephritis and the segmental changes seen in a host of different diseases.