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Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.

Mammalian atria possess bioactive peptides that are natriuretic-diuretic and potent relaxants of vascular and nonvascular smooth muscle. Characterization of the biological activity of rat atrial extracts indicates two major peaks, having apparent molecular weight of 20,000-30,000 (atriopeptigen) and less than 10,000 (atriopeptins). The amino acid sequence of atriopeptins I, II and III have been determined, and it has been found that their structures are only slightly different. Atriopeptin I (twenty-one amino acid residues); ser-ser-cys-phe-gly-gly-arg-ile-asp-arg-ile-gly-ala-gln-ser-gly-leu-gly- cys- asn-ser) relaxes intestinal but not vascular smooth muscle strips, and is natriuretic. Atriopeptins II and III (23 and 24 residues; the 21-sequence of I with the addition of phe-arg or phe-arg-tyr at the C-terminus, respectively) relax intestinal and vascular smooth muscle strips and are potent natriuretics. Since atriopeptigen and the atriopeptins exhibit similar biological effects the possibility of a precursor-product relationship was tested. Mild proteolytic digestion (1IU/ml trypsin) of atriopeptigen activates this peptide and reduces its apparent molecular weight. Examination of whether the atria of Krebs perfused isolated hearts released the bioactive atrial peptides revealed the presence in the cardiac effluent of a trypsin-labile substance that was natriuretic-diuretic and a smooth muscle relaxant. To determine which form of the atrial peptide (e.g. atriopeptigen or atriopeptin) is released by the atria the cardiac effluents were concentrated and partially purified. The cardiac effluent contained a substance(s) similar to atriopeptin, but did not appear to possess the less-active high molecular weight peptide, atriopeptigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprague-Dawley rats given bolus intravenous injections of vasoconstrictors, including 1-deamino-Arg8-vasopressin (dAVP), demonstrated remarkable increases in plasma immunoreactivity (APir) to atriopeptin (AP). These elevations were accompanied by increases in systemic blood pressure, right atrial pressure and urinary volume excretion. Fractionated plasma APir peaks obtained by stimulation with dAVP were identified as primarily AP 28, with a smaller amount of AP 24, suggesting that AP 28 is the predominant circulating atrial peptide. Rats with reduced renal mass have increased single-nephron glomerular filtration rates (GFR). Despite these increases, AP 24 stimulated a marked increase in total GFR and promoted a profound natriuresis and diuresis. Atriopeptin 24 may therefore have potential as a therapeutic tool in the management of volume overload in chronic renal failure.

The atriopeptins are potent relaxants of norepinephrine-constricted aortic strips or are dilators of renal blood vessels in isolated perfused rat kidneys that are constricted by norepinephrine. This vasorelaxant property of the atriopeptins requires the presence of phenylalanine arginine (i.e., atriopeptin II, III, or ser-leu-arg-arg atriopeptin III) residues in the carboxy terminus which are considerably more effective than atriopeptin I (the 21 amino acid peptide which lacks the phe-arg C-terminus) or the core peptide (residues 3-19). However, these artificially in vitro precontracted preparations do not accurately predict the vascular effectiveness of the atriopeptins in intact rats. Intravenous administration of the atriopeptins (including atriopeptin I) to anesthetized rats produces concentration-dependent hypotension, a selective decrease in renal resistance in low doses (determined with microspheres), and pronounced diuresis. At higher doses, atriopeptins increase blood flow in other vascular beds. On the other hand, in the anesthetized dog, injection (intraarterially) of the phe-arg-containing peptides produces a concentration-dependent increase in both renal blood flow and sodium excretion, whereas atriopeptin I is inactive. Although there is a species difference in responsiveness to atriopeptin I, these data demonstrate a direct correlation between the renal vasodilation and diuresis produced by this novel family of atrial peptides.