Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease ...and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.
Clusterin is a heterodimeric glycoprotein that has been associated with such diverse biologic functions as reproduction, cell regression, cell aggregation, and regulation of the cytolytic activity of ...the membrane attack complex of complement. Clusterin is a component of glomerular immune deposits in the kidney, and increased clusterin expression occurs in a number of renal injury states. To further explore the interaction between clusterin and complement, the requirement for an intact complement system for renal clusterin induction in an acute (folic acid nephropathy) and a chronic (subtotal renal ablation) model of renal injury was examined. After it was first demonstrated that folic acid increased renal clusterin mRNA in the rat, a species in which renal clusterin was highly inducible by other stimuli, the effects of folic acid (250 mg/kg ip) on clusterin mRNA and immunoreactivity were examined in mice sufficient and deficient for the fifth component of complement. Similar increases in clusterin mRNA and immunoreactivity were seen in both the C5-sufficient and C5-deficient mice compared with their respective vehicle-injected control groups. Renal clusterin mRNA was also increased to a similar extent in the remaining kidney of both C5-sufficient and C5-deficient mice 10 days after subtotal nephrectomy. In conclusion, the induction of clusterin after folic acid administration or subtotal nephrectomy was independent of the presence of an intact complement system, because similar increases in clusterin expression were observed in C5-sufficient and C5-deficient mice.
The human nephrotic syndrome is accompanied by important alterations of the coagulation system related proteins. The purpose of the present study was to examine the activity of coagulation- and ...fibrinolysis-related proteins in plasma and urine of control and puromycin aminonucleoside injected rats on days 2 (prenephrotic stage) and 10 (nephrotic stage). We measured the prothrombin time (PT), the activated partial thromboplastin time (aPTT), and the activities of (1) the coagulation factors (CFs) I, II, V, and VII-XII; (2) the inhibitor of coagulation antithrombin III (ATIII), and (3) the component of the fibrinolytic system alpha 2-antiplasmin (alpha 2-APL). PT and aPTT and the activities of CF, ATIII, and alpha 2-APL were not measurable in the urine of control and puromycin amino-nucleoside injected rats on day 2. On this same day, plasma ATIII and CF VIII decreased. On day 10 (1) PT and aPTT decreased in plasma and were not measurable in urine; (2), plasma CFs I, II, V, VII, VIII, X, and XI increased; (3), plasma ATIII decreased; (4), plasma CFs IX and XII and alpha 2-APL did not change, and (5) ATIII and CFs II, VII, VIII, IX, X, XI, and XII, but not CFs I and V and alpha 2-APL, appeared in urine on day 10. ATIII deficiency was secondary probably to the urinary losses; however, the plasma activity of CFs II, VII, VIII, X, and XI increased and that of CFs IX and XII remained unchanged in spite of their urinary losses which suggests that other mechanisms such as deranged catabolism and altered hepatic synthesis may be involved.
Plasma concentration and urine excretion of the renin-angiotensin system proteins are altered in rats with nephrotic syndrome (NS). In this work the messenger ribonucleic acid (mRNA) levels of ...angiotensinogen (Ao) were analyzed with the slot-blot hybridization technique in liver and other extrahepatic tissues: kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed (PF) rats. NS was induced by a single injection of puromycin aminonucleoside (PAN). Although a great urinary excretion and half-normal plasma levels of Ao were observed on day 6 after PAN injection, when NS was clearly established, hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not change in any of the extrahepatic tissues studied on day 6, nor did its hepatic levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the hepatic and extrahepatic Ao mRNA levels are unaltered during the development of the acute NS induced by PAN.
Postnatal nephrogenesis and growth of the rat kidney is greatest during the first 10 days of life. The renin-angiotensin system has important growth-promoting effects. To explore the relationship ...between postnatal renal development and the renin-angiotensin system, we examined the steady-state levels of messenger ribonucleic acid (mRNA) for renin, angiotensinogen, histone H2b (a marker of DNA synthesis) and the structural protein actin. The pattern of expression for renin and histone H2b were similar, with maximal levels of both mRNAs occurring during the first 10 days of life, the time of most marked postnatal nephrogenesis and kidney growth. A different pattern was seen for angiotensinogen mRNA, with low to undetectable levels during the first 15 days of life, and for actin mRNA, with fairly stable expression at the time points examined, providing evidence that the increase in renin and histone H2b mRNA was not due to a nonspecific increase in mRNA in the newborn kidney. In conclusion, the increase in renal histone H2b mRNA during the early postnatal period is consistent with this being a time of increased DNA synthesis. The similar time course for renin mRNA, histone H2b mRNA and previously defined changes in postnatal nephrogenesis suggests a role for the renin-angiotensin system in postnatal nephron formation.
We investigated the presence of HIV antigen in dialysis fluid of patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD), previously known to be ...infected with this virus. Sixteen adult patients and 6 adult volunteers were included in the study in 4 groups as follows: Group A: 3 patients on CAPD, previously known to be positive for serum HIV antibodies; Group B: 7 patients on CAPD, serum HIV negative; Group C: 6 AIDS patients without renal disease; and Group D: 6 healthy volunteers. Of the 3 patients of Group A, the HIV-1 Ag was positive in dialysis fluid in only 2. In 1, serum Ab and Ag were present, while in the others only serum Ab was detected. The samples from Group B were all negative for the viral antigen in dialysis fluid. We conclude that dialysis fluid of HIV-infected patients may contain the Ag and is therefore potentially infective. The presence of the HIV antigen was not constant, and was not related to antigenemia. It is possible that the presence of the Ag depends on local factors that influence viral replication or to alterations in the permeability of the peritoneal membrane. We discuss other possible factors that could influence the presence of viral Ag in peritoneal dialysis fluid.
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