Systolic dysfunction portends increased mortality among those waiting for renal transplant.

Individuals waiting for a renal transplant experience excessive cardiovascular mortality, which is not fully explained by the prevalence of ischemic heart disease in this population. Overt heart failure is known to increase the mortality of patients with ESRD, but the impact of lesser degrees of ventricular systolic dysfunction is unknown. For examination of the association between left ventricular ejection fraction(LVEF) and mortality of renal transplant candidates, the records of 2718 patients evaluated for transplantation at one institution were reviewed. During 6355 patient-years (median 27 mo) of follow-up, 681 deaths occurred. Patients with systolic dysfunction (LVEF

Protocol biopsy: today's fine-needle aspiration biopsy?

This counter view of protocol biopsy suggests that the widespread clinical use of this technique may be questionable. It may remain primarily a valuable research tool. Cost and risk remain as major issues. Be it screening by routine computed tomography scan for apparently normal people or routine biopsy of normal functioning kidneys there is always the risk that more harm than good might be done. The proof of benefit should be strong (scientifically strong), which requires confirmation and reproducibility of controlled trials. Patients need to know how protocol biopsy is to be used (research, management or both) and the strength of the scientific evidence concerning benefit in long-term management.

The impact of left ventricular systolic dysfunction on survival after renal transplantation.

BACKGROUND: Gated single photon emission computed tomography (SPECT) provides information on myocardial perfusion and left ventricular ejection fraction (LVEF), which correlates with risk of cardiac events in patients with known or suspected coronary artery disease (CAD). We hypothesize that decreased LVEF at time of renal transplant evaluation is an independent risk factor for cardiac death and nonfatal events after transplant. METHODS AND RESULTS: A total of 653 recipients of renal allografts between 1998 and 2005 had stress SPECT imaging before transplantation. One hundred and nineteen (18%) patients had left ventricular (LV) systolic dysfunction (LVEF

Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation.

BACKGROUND: Patients infected with hepatitis C virus (HCV) frequently develop renal failure after liver transplantation. OBJECTIVE: To describe renal histologic characteristics and concomitant clinical features in HCV-infected patients with end-stage cirrhosis. DESIGN: Case series. SETTING: Single-center liver transplant program in the United States. PATIENTS: 30 patients who received liver transplants for HCV-induced cirrhosis. INTERVENTION: Kidney biopsy during liver engraftment. MEASUREMENTS: Clinical data and laboratory tests of renal function within 6 months before liver transplantation. RESULTS: Twenty-five patients had immune-complex glomerulonephritis: membranoproliferative glomerulonephritis type 1 (n = 12), IgA nephropathy (n = 7), and mesangial glomerulonephritis (n = 6). Of these patients, 10 had normal serum creatinine levels, normal urinalysis results, and normal quantitative proteinuria. For 5 others, the only renal abnormality was an increased serum creatinine level. No patient had cryoglobulins in the blood or kidney. LIMITATIONS: This small observational study did not include patients with nonviral cirrhosis and did not document post-transplantation outcomes. CONCLUSIONS: Immune-complex glomerulonephritis was common in patients with end-stage HCV-induced cirrhosis and was often clinically silent. Its potential to cause renal failure after liver transplantation may be underappreciated.

Large within-day variation in cyclosporine absorption: circadian variation or food effect?

With the recent focus of monitoring cyclosporine (CsA) therapy using measures of CsA absorption, it is important to understand published reports of diurnal variation in CsA exposure. In 10 renal transplant patients, CsA concentrations were measured 0, 1, 2, 3, and 4 h after both the morning and the evening doses and in a repeat session at least 1 wk later. Both area under the curve for the final 4 h after cyclosporine dose and cyclosporine concentrate 2 h after the cyclosporine dose were more than two-fold higher after the morning dose in both sessions. Because the morning levels were collected in a fasted condition and the evening ones in a fed condition, the study was extended to collect evening levels after fasting. The area under the curve for the final 4 h after cyclosporine dose and cyclosporine concentrate 2 h after the cyclosporine dose values observed now were comparable to the morning fasted values. That the large diurnal variation was due to variation in food consumption, as opposed to a biologic circadian rhythm affecting CsA absorption, has significant implications for therapeutic drug monitoring.

Increasing referral for renal transplant evaluation in recipients of nonrenal solid-organ transplants: a single-center experience.

The use of cyclosporine and tacrolimus therapy in nonrenal (heart, heart/lung, lung, and liver) transplantation has resulted in improved patient and graft survival. Nephrotoxicity is one of the major side effects of tacrolimus and cyclosporine therapy and may lead to ESRD. The trend of referral of nonrenal solid-organ transplant recipients for kidney transplant evaluation at a large multiorgan transplant center was examined. Records of all patients who were referred for renal transplantation at the University of Alabama between January 1, 1993, and June 30, 2004, were reviewed. Eighty (0.96%) of 8318 individuals had previously undergone a nonrenal solid-organ transplant and were included in the study. The majority (72%) of patients had their nonrenal transplants performed at the University of Alabama. Twenty-two patients had their nonrenal transplant performed elsewhere and had fewer data available for analysis. From the period 1993-1996 to 2001-2004, an 11-fold increase in the absolute number of referrals of patients with nonrenal transplants was noted. Of patients who were referred for transplant evaluation, 25 became recipients of kidney transplants with a predominance of living-donor transplants. Referral for kidney transplant evaluation among nonrenal solid-organ transplant recipients is increasing and will exacerbate the existing shortage of deceased-donor kidneys that are available for transplantation. There was a trend for liver transplant recipients compared with other solid-organ recipients to develop ESRD at a greater rate.

Hypertensinogenic mechanism of the calcineurin inhibitors.

Kidney transplantation has seen a remarkable improvement in allograft survival rates and patient survival rates, and an equally remarkable reduction in acute rejection rates. Most attribute these changes to the introduction and widespread use of calcineurin inhibitors as part of the standard immunosuppressive regimen. Cyclosporine and tacrolimus are ideal immunosuppressive agents, much more effective and safe than the previous agents used. Especially ironic, however, for those caring for kidney transplant patients has been the finding that these breakthrough agents are toxic to the kidney and can cause hypertension. We can protect the transplanted kidney from rejection, but still damage it paradoxically by the protecting agent. Moreover, the prevalence of hypertension in transplant clinics has increased (from 40%-50% to up to 90%-100%) as these newer agents have gained widespread use. We remain uncertain of the mechanism whereby these agents cause hypertension, and therefore remain uncertain of the ideal treatment; however, the search for a mechanism has taken us from the organ level to intracellular effects of the agents. The fact that both agents cause nephrotoxicity suggests that a renal mechanism is at the heart of the hypertension.