Background-Uremia is proposed to increase sympathetic nerve activity (SNA) in hemodialysis patients. The aims of the present study were to determine whether reversal of uremia by successful kidney transplantation (RTX) eliminates the increased SNA and whether signals arising in the diseased kidneys contribute to the increased SNA in renal failure. Methods and Results-We compared muscle sympathetic nerve activity (MSNA) in 13 hemodialysis patients wait-listed for RTX and in renal transplantation patients with excellent graft function treated with cyclosporine (RTX-CSA, nϭ13), tacrolimus (RTX-FK, nϭ13), or without calcineurin inhibitors (RTX-Ø, nϭ6), as well as in healthy volunteers (CON, nϭ15). In addition to the above patients with present diseased native kidneys, we studied 16 RTX patients who had undergone bilateral nephrectomy (RTX-NE). Data are meanϮSEM. MSNA was significantly elevated in hemodialysis patients (43Ϯ4 bursts/min), RTX-CSA (44Ϯ5 bursts/min), RTX-FK (34Ϯ3 bursts/min), and RTX-Ø (44Ϯ5 bursts/min) as compared with CON (21Ϯ3 bursts/min), despite excellent graft function after RTX. RTX-NE had significantly reduced MSNA (20Ϯ3 bursts/min) when compared with RTX patients. MSNA did not change significantly with RTX in 4 hemodialysis patients studied before and after RTX (44Ϯ6 versus 43Ϯ5 bursts/min, PϭNS). In contrast, nephrectomy resulted in reduced MSNA in all 6 RTX patients studied before and after removal of the second native kidney. Conclusions-Despite correction of uremia, increased SNA is observed in renal transplant recipients with diseased native kidneys at a level not significantly different from chronic hemodialysis patients. The increased SNA seems to be mediated by signals arising in the native kidneys that are independent of circulating uremia related toxins. (Circulation.

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term prognosis in kidney transplant recipients depends on multiple factors. To investigate whether mild proteinuria within the first 6 months following transplantation is a determinant of the long-term function and survival of kidney transplants, 357 patients transplanted between 1980 and 1990 were retrospectively examined over a period of 5 years. 25.5% of the patients developed an early proteinuria between 0.25 and 1.0 g/day over 6 or more months. This group was well matched concerning gender, age of recipient, underlying disease, time on hemodialysis, donor age, cold ischemia time and HLA mismatches with the group without proteinuria (n = 266). Five-year transplant survival in the group with proteinuria was 58.9% in contrast to 85.6% in recipients without proteinuria. Intermittent proteinuria did not worsen long-term prognosis. Proteinuria of 12 months or longer further reduced 5-year transplant survival to 42.6%. Over the whole observation period, serum creatinine in recipients with proteinuria was about 0.5 mg/dl higher as compared with patients without proteinuria. No correlation between proteinuria and gender, age of recipient, duration of hemodialysis, age of donor, cold ischemia time and mismatches could be detected. In conclusion, early proteinuria apparently is not due to established donor or recipient factors. However, there is a strong correlation of proteinuria with worse transplant function and survival.

Long-term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so-called 'syndrome X', i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p < or = 0.05), while a statistically significant correlation between hyperglycemia and graft survival could not be detected in the present study. The transplant survival rates 2, 4, and 5 yr post-kidney-transplantation were 96.7, 80.7, and 78.7 in normogylcemic patients vs. 96.9, 85, and 82.7% in hyperglycemic ( > 100 mg,dL) kidney transplant recipients (p > 0.05). Transplant survival in hyperuricemic patients (male, > 8 mg dL; female, > 6.2 mg/dL) 2, 4, and 5 yr post-transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post-kidney-transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p < or = 0.01) and between serum uric acid concentrations and diuretic therapy (p < or = 0.05) and gender (p < or = 0.(5). In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.

Abstract-Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the ␤-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, Ͻ220 mol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96Ϯ1 to 84Ϯ1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96Ϯ1 to 83Ϯ1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129Ϯ8 mol/L at entry and 148Ϯ19 mol/L after 24 months in the quinapril group and 131Ϯ6 mol/L at entry and 152Ϯ15 mol/L after 24 months in the atenolol group; PϭNS for both groups). After 24 months, the change in urinary albumin excretion from baseline was Ϫ10Ϯ15 mg/d in the quinapril group and 52Ϯ32 mg/d in the atenolol group (Pϭ0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function. (Hypertension. 1999;33:862-868.)