Five hundred years of glomerulonephritis
Genealogical studies are one way to establish the role of genes in the etiology of any disease. Scolari et al. have approached this age-old problem with remarkable perseverance and originality. They studied the prevalence of primary glomerulonephritis in an isolated population from the Valtrompia valley in northern Italy. They identified 42 patients with different types of glomerular diseases, half of whom had renal biopsies. Scolari et al. constructed genealogies of the affected individuals by studying church records of births, deaths, and marriages in three villages dating back to 1570. It turned out that many of the pedigrees previously thought to be independent were related. With the use of molecular markers, this relationship was statistically demonstrated. All individuals could be traced back to common ancestors and fell into three large pedigrees. This study suggests that these patients share a common genetic susceptibility to develop primary glomerulonephritis. But the fact that the related individuals showed different types of glomerulonephritis raises the question of whether they had inherited a component of a pathway that allowed glomerular injury of diverse causes. See page 1033.
Payment for kidneys
It is a truism that the waiting list for kidney transplantation around the world is growing longer, and that the field is at a loss to significantly improve this situation. Expansion of the donor pool to include spouses and even friends has helped lessen the burden a little, but it is certainly not sufficient to overcome the growing demand. Increasingly, kidneys from donors that even a few years ago would have been considered too marginal are now being used with reasonable success. Meanwhile, in some regions of the world, kidneys are being sold, leading to ethical and humanitarian problems attendant on the commodification of what is, ideally, a 'gift of life.' As a solution, should one regulate the sale of kidneys? Or provide a benefit to the families of potential donors to encourage donation, or to cover the expenses of transplantation? Transplantation experts E. and A. Friedman make an impassioned argument supporting these views. We asked two transplant surgeons and a nephrologist to discuss their views on the topic. Frank Delmonico thinks that ethical concerns prevent us from paying money to encourage donations, whereas Tony Monaco supports the idea of payment for kidney donations but argues that it should be regulated by the government. Donald Landry proposes alternatives to monetary encouragement, including the argument that organ donation can be driven by our inherent altruistic sense. Have you looked at your driver's license lately? Did you check the box that indicates you are willing to donate your organs if you are in a fatal car accident? The issues surrounding kidney donation need to be debated and resolved with informed judgment by society as a whole. See pages 954, 955, 957 and 960.
Aldosterone and plasminogen activator inhibitor
After it was found that aldosterone antagonists had a significantly protective effect on the outcome of congestive heart failure, the search began for a mechanism to link the known effects of aldosterone to its supposedly injurious effect. In a study reported in this issue, Ma et al. gave mice a high-salt diet with or without aldosterone and compared the results with those of the same treatments performed in mice deficient in plasminogen activator inhibitor-1 (PAI-1). They found that blood pressure was higher in wild-type than in knockout mice after a long period of aldosterone and salt loading. Aldosterone-infused wild-type mice had more proteinuria than those with deleted PAI-1, and the glomeruli were larger with greater mesangial expansion. Expression of several extracellular matrix proteins was also enhanced by aldosterone in both wild-type and mutant mice, as was cardiac hypertrophy. However, there were some small differences in the expression of collagen subtypes between the wild-type and knockout mice. Hence, it appears that PAI-1 was involved in the mechanism of action of aldosterone on glomerular structure and function. This action was probably due to greater systolic hypertension in the wild-type animals, but it raises the question of how PAI-1 protects the animals from elevated blood pressure. See page 1064.
Acute renal failure during liver transplantation
Liver transplantation is a long and often traumatic procedure that can result in acute renal failure. When it does, it carries a poor prognosis. Cabezuelo et al. studied the rate of acute renal failure in a large number of consecutive liver transplants. They found that almost one-third of the patients developed acute renal failure in the early phase of transplantation, and almost one-fifth had late appearance of the syndrome. As expected, most of the patients had ischemic acute tubular necrosis. Early acute renal failure was more likely to occur in patients who had had the condition before the transplantation, in patients whose albumin was below 3.2 g/dl, and in those with a long history of treatment with dopamine, which presumably reflected cardiovascular instability. Patients who developed acute renal failure in the late phase of transplantation developed it, for the most part, in association with graft failure or a bacterial infection. See page 1073.
