Role of Sodium-Glucose Cotransporter 2 Inhibitors for Management of Diabetes Mellitus in Renal Transplant Recipients and Management Strategies for Posttransplant Hypertension.

BACKGROUND: Diabetes mellitus and hypertension are the leading causes of cardiovascular disease in the renal transplant recipients. This review looks at the potential role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and reviews the management strategies for hypertension in this population. SUMMARY: Large-scale clinical trials are needed to study the potential cardiorenal benefits and risks of complications in renal transplant recipients. Future clinical trials are also needed to define optimal blood pressure treatment goals and therapies and how they influence graft and patient survival. KEY MESSAGES: Multiple recent prospective randomized clinical trials have shown the benefits of using SGLT2is to improve the cardiorenal outcomes in patients with chronic kidney disease with or without diabetes mellitus. Renal transplant recipients were not included in these trials due to concerns about genitourinary complications; hence, the role of these agents in this population is unclear. A number of small studies have highlighted the safety of using these agents in renal transplant recipients. Posttransplant hypertension is a complex problem requiring individualized management. Recent guidelines recommend using a calcium channel blocker or angiotensin receptor blocker as the first-line antihypertensive agents in adult renal transplant recipients.

A prospective controlled study of metabolic and physiologic effects of kidney donation suggests that donors retain stable kidney function over the first nine years.

While there have been numerous studies of living kidney donors, most have been retrospective without suitable controls and have yielded conflicting results. To clarify this we studied 205 living donor candidates and 203 controls having no medical conditions precluding donation. Before and at six months, one, two, three, six, and nine years after donation we measured iohexol glomerular filtration rate, clinic blood pressure, urine protein excretion and metabolic parameters reported to be affected by kidney function. We measured 24 hour ambulatory blood pressure at three, six, and nine years and at six and nine years blood pressure after treadmill exercise, carotid-femoral pulse wave velocity and arterial elasticity. Between six months and nine years, the mean (95% confidence interval) change in glomerular filtration rate was significantly different among 133 donors 0·02 (-0·16-0·20) mL/min/1·73m2/year versus -1·26 (-1·52--1·00) mL/min/1·73m2/year in 113 healthy controls. Blood pressure, urine protein, urine albumin, glucose, hemoglobin A1c, insulin, and lipoproteins were not different in controls versus donors; but parathyroid hormone, homocysteine and uric acid remained higher at nine years. At six and nine years carotid-femoral pulse wave velocity was not different, but the mean small artery elasticity was significantly lower in 141 donors 6·1 mL/mmHg x100, versus 113 controls 7·1 mL/mmHg x100, and 6·1 mL/mmHg x100 in 137 donors versus 7·6 mL/mmHg x100 in 112 controls at six and nine years, respectively [significant adjusted difference of 1·1 mL/mmHg x100]. Thus, donors remain healthy with stable kidney function for the first nine years, but differences in metabolic and vascular parameters could be harbingers of adverse outcomes requiring future interventions.

Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States.

Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55 697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N = 48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval [CI] 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9-5.4; N = 89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients.

Impact of Hyperuricemia on Long-term Outcomes of Kidney Transplantation: Analysis of the FAVORIT Study.

BACKGROUND: Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. STUDY DESIGN: Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. SETTING & PARTICIPANTS: Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. PREDICTOR: Uric acid concentration. OUTCOMES: The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. RESULTS: 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models (P=0.5 for CV events; P=0.09 for death, and P=0.1 for transplant failure). LIMITATIONS: Unknown use of uric acid-lowering agents among study participants. CONCLUSIONS: Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation.

Abnormalities in biomarkers of mineral and bone metabolism in kidney donors.

Previous studies have suggested that kidney donors may have abnormalities of mineral and bone metabolism typically seen in chronic kidney disease. This may have important implications for the skeletal health of living kidney donors and for our understanding of the pathogenesis of long-term mineral and bone disorders in chronic kidney disease. In this prospective study, 182 of 203 kidney donors and 173 of 201 paired normal controls had markers of mineral and bone metabolism measured before and at 6 and 36 months after donation (ALTOLD Study). Donors had significantly higher serum concentrations of intact parathyroid hormone (24.6% and 19.5%) and fibroblast growth factor-23 (9.5% and 8.4%) at 6 and 36 months, respectively, as compared to healthy controls, and significantly reduced tubular phosphate reabsorption (-7.0% and -5.0%) and serum phosphate concentrations (-6.4% and -2.3%). Serum 1,25-dihydroxyvitamin D3 concentrations were significantly lower (-17.1% and -12.6%), while 25-hydroxyvitamin D (21.4% and 19.4%) concentrations were significantly higher in donors compared to controls. Moreover, significantly higher concentrations of the bone resorption markers, carboxyterminal cross-linking telopeptide of bone collagen (30.1% and 13.8%) and aminoterminal cross-linking telopeptide of bone collagen (14.2% and 13.0%), and the bone formation markers, osteocalcin (26.3% and 2.7%) and procollagen type I N-terminal propeptide (24.3% and 8.9%), were observed in donors. Thus, kidney donation alters serum markers of bone metabolism that could reflect impaired bone health. Additional long-term studies that include assessment of skeletal architecture and integrity are warranted in kidney donors.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative.

BACKGROUND: Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs). PREDICTORS: Categories of eGFR (exposure); race/ethnicity (effect modifier). OUTCOMES: The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death. MEASUREMENTS: We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. RESULTS: During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories. LIMITATIONS: Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. CONCLUSIONS: In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

Association between Renal Function and Bleeding Risk for Dabigatran after Switching from Warfarin.

BACKGROUND: There is a higher risk of gastrointestinal (GI) bleeding in patients treated with dabigatran versus warfarin. We analyzed the impact of renal function on the relative risk of bleeding in patients converted to dabigatran. METHODS: Patients aged ≥65 years who received anticoagulation with warfarin for a minimum of 6 months and subsequently converted to dabigatran or remained on warfarin were studied. Data sources included VA National Patient Care, and VA Decision Support System National Pharmacy and Laboratory. Each patient who converted to dabigatran 150 mg twice daily was matched by propensity score with 2 patients on warfarin who did not convert. Outcomes included rates of hospital admission for GI or other major bleeding and mortality, stratified by estimated glomerular filtration rate (eGFR). RESULTS: Study population included 864 patients who converted and 1,710 patients who did not convert to dabigatran. In patients with eGFR 50-80 ml/min/1.73 m², the hazard of GI bleeding in patients who initiated dabigatran was nearly 3 times higher, (4.1 vs. 1.3 per 100 patient years; hazards ratio 2.94; 95% CI 1.24-7.02; p = 0.015), compared to patients who remained on warfarin. There were relatively few patients with eGFR <50 or >80 ml/min/1.73 m2, and relatively few bleeding events outside the GI tract. CONCLUSIONS: Prescribing healthcare providers should exercise caution and close monitoring for bleeding complications when converting from warfarin to dabigatran, even in patients with renal function in the range considered safe for dabigatran use as per current recommendations.

Effect of extended-release niacin on cardiovascular events and kidney function in chronic kidney disease: a post hoc analysis of the AIM-HIGH trial.

Chronic kidney disease (CKD) in patients is strongly associated with cardiovascular morbidity and mortality, and prevalent abnormal lipid metabolism. The AIM-HIGH trial examined the benefits of adding extended-release niacin (ERN) to simvastatin in patients with established coronary heart disease. Here we conducted a post hoc analysis of the AIM-HIGH trial examining whether participants derived cardiovascular or renal benefits when stratified by renal function. Of 3414 participants, 505 had stage 3 CKD at baseline. Among the CKD subset, demographics and cardiovascular disease (CVD) risk factors were well balanced in the ERN and placebo arms. Compared with placebo, CKD participants receiving ERN had a significant decrease in triglycerides by a median of 59.0 mg/dl, and high-density lipoprotein cholesterol significantly increased by a mean of 11.3 mg/dl over a mean follow-up of 3 years. CVD events were similar between CKD participants in both arms. However, all-cause mortality was significantly higher in the ERN group (hazard ratio of 1.73). Mean change in eGFR among ERN-treated CKD participants was not significantly different between study arms. Thus, among AIM-HIGH participants with CKD, the addition of ERN to simvastatin for secondary prevention of CVD improved triglyceride and high-density lipoprotein-cholesterol concentrations but did not improve cardiovascular outcomes or kidney function, and was associated with higher all-cause mortality.

A prospective controlled study of living kidney donors: three-year follow-up.

BACKGROUND: There have been few prospective controlled studies of kidney donors. Understanding the pathophysiologic effects of kidney donation is important for judging donor safety and improving our understanding of the consequences of reduced kidney function in chronic kidney disease. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: 3-year follow-up of kidney donors and paired controls suitable for donation at their donor's center. PREDICTOR: Kidney donation. OUTCOMES: Medical history, vital signs, glomerular filtration rate, and other measurements at 6, 12, 24, and 36 months after donation. RESULTS: At 36 months, 182 of 203 (89.7%) original donors and 173 of 201 (86.1%) original controls continue to participate in follow-up visits. The linear slope of the glomerular filtration rate measured by plasma iohexol clearance declined 0.36±7.55mL/min per year in 194 controls, but increased 1.47±5.02mL/min per year in 198 donors (P=0.005) between 6 and 36 months. Blood pressure was not different between donors and controls at any visit, and at 36 months, all 24-hour ambulatory blood pressure parameters were similar in 126 controls and 135 donors (mean systolic blood pressure, 120.0±11.2 [SD] vs 120.7±9.7mmHg [P=0.6]; mean diastolic blood pressure, 73.4±7.0 vs 74.5±6.5mmHg [P=0.2]). Mean arterial pressure nocturnal dipping was manifest in 11.2% ± 6.6% of controls and 11.3% ± 6.1% of donors (P=0.9). Urinary protein-creatinine and albumin-creatinine ratios were not increased in donors compared with controls. From 6 to 36 months postdonation, serum parathyroid hormone, uric acid, homocysteine, and potassium levels were higher, whereas hemoglobin levels were lower, in donors compared with controls. LIMITATIONS: Possible bias resulting from an inability to select controls screened to be as healthy as donors, short follow-up duration, and dropouts. CONCLUSIONS: Kidney donors manifest several of the findings of mild chronic kidney disease. However, at 36 months after donation, kidney function continues to improve in donors, whereas controls have expected age-related declines in function.

Risk of cancer in retransplants compared to primary kidney transplants in the United States.

Recipients of kidney transplantation have elevated risk of developing cancer. There are limited data on cancer risk in recipients of kidney retransplantation. We used data from the Transplant Cancer Match Study, which links the U.S. transplant registry with 15 cancer registries. Cancer incidence in recipients of kidney retransplantation and primary kidney transplants was compared utilizing Poisson regression, adjusting for demographic and medical characteristics. We assessed 109 224 primary recipients and 6621 retransplants. Compared to primary recipients, retransplants were younger (median age 40 vs. 46 yr), had higher PRA, and more often received induction with polyclonal antibodies (43% vs. 25%). A total of 5757 cancers were observed in primary recipients and 245 in retransplants. Overall cancer risk was similar in retransplants compared with primary recipients (incidence rate ratio [IRR] 1.06, 95% CI 0.93-1.20, adjusted for age, gender, race/ethnicity, PRA, and use of polyclonal induction). However, renal cell carcinoma (RCC) occurred in excess among retransplants (adjusted IRR 2.03, 95% CI 1.45-2.77), based on 514 cases in primary recipients and 43 cases in retransplants. Overall cancer risk did not differ in retransplants compared to primary recipients. Increased risk of RCC may be explained by the presence of acquired cystic kidney disease, which is more likely to develop with additional time with kidney disease and time spent on dialysis waiting for retransplantation.

A prospective controlled study of kidney donors: baseline and 6-month follow-up.

BACKGROUND: Most previous studies of living kidney donors have been retrospective and have lacked suitable healthy controls. Needed are prospective controlled studies to better understand the effects of a mild reduction in kidney function from kidney donation in otherwise healthy individuals. STUDY DESIGN: Prospective, controlled, observational cohort study. SETTING & PARTICIPANTS: Consecutive patients approved for donation at 8 transplant centers in the United States were asked to participate. For every donor enrolled, an equally healthy control with 2 kidneys who theoretically would have been suitable to donate a kidney also was enrolled. PREDICTOR: Kidney donation. MEASUREMENTS: At baseline predonation and at 6 months after donation, medical history, vital signs, measured (iohexol) glomerular filtration rate, and other measurements were collected. There were 201 donors and 198 controls who completed both baseline and 6-month visits and form the basis of this report. RESULTS: Compared with controls, donors had 28% lower glomerular filtration rates at 6 months (94.6 ± 15.1 [SD] vs 67.6 ± 10.1 mL/min/1.73 m(2); P < 0.001), associated with 23% greater parathyroid hormone (42.8 ± 15.6 vs 52.7 ± 20.9 pg/mL; P < 0.001), 5.4% lower serum phosphate (3.5 ± 0.5 vs 3.3 ± 0.5 mg/dL; P < 0.001), 3.7% lower hemoglobin (13.6 ± 1.4 vs 13.1 ± 1.2 g/dL; P < 0.001), 8.2% greater uric acid (4.9 ± 1.2 vs 5.3 ± 1.1 mg/dL; P < 0.001), 24% greater homocysteine (1.2 ± 0.3 vs 1.5 ± 0.4 mg/L; P < 0.001), and 1.5% lower high-density lipoprotein cholesterol (54.9 ± 16.4 vs 54.1 ± 13.9 mg/dL; P = 0.03) levels. There were no differences in albumin-creatinine ratios (5.0 [IQR, 4.0-6.6] vs 5.0 [IQR, 3.3-5.4] mg/g; P = 0.5), office blood pressures, or glucose homeostasis. LIMITATIONS: Short duration of follow-up and possible bias resulting from an inability to screen controls with kidney and vascular imaging performed in donors. CONCLUSIONS: Kidney donors have some, but not all, abnormalities typically associated with mild chronic kidney disease 6 months after donation. Additional follow-up is warranted.

Dissociation between progression of coronary artery calcification and endothelial function in hemodialysis patients: a prospective pilot study.

UNLABELLED: Chronic kidney disease profoundly disturbs calcium-phosphate metabolism and predisposes to premature atherosclerosis. Both coronary artery calcification (CAC) and endothelial dysfunction are common in hemodialysis (HD) patients. We hypothesized that a calcium-free phosphate binder would improve endothelial function and delay progression of vascular calcification in HD patients. METHODS: This was a randomized parallel-group trial in HD patients comparing lanthanum carbonate (LC) with a non-LC phosphorus binders control group (non-LC) at a 1 : 1 randomization. CAC was obtained at baseline, 6, and 12 months, and endothelial function (brachial artery flow-mediated dilation - FMD) at baseline and 6 months. RESULTS: 13 patients were randomized (LC n = 7 and non-LC n = 6). CAC scores (Log ± SE) at baseline were 7.21 ± 0.62 (LC) and 6.07 ± 0.73 (control). CAC increased in the non-LC group (33 ± 17% and 77 ± 22% at 6 and 12 months), but tended to decrease in the LC group (-10 ± 11% and -2 ± 11% at 6 and 12 months). There was statistically less progression in CAC in the LC group compared to control at 6 (p = 0.002) and 12 months (p = 0.003). There was no difference between groups in FMD (p = 0.7). Markers of inflammation did not change significantly. CONCLUSION: A slower rate of progression of CAC occurred in the LC group, independent of changes in FMD. This is the first study showing dissociation between progression of CAC and FMD in HD patients. Larger studies are warranted to elucidate the impact of different phosphate sequestration therapies on atherosclerosis in HD patients.

Impact of Rural Residence on Kidney Transplant Rates Among Waitlisted Candidates in the VA Transplant Programs.

BACKGROUND: Although proportionally more veterans live in rural areas compared to nonveterans, the impact of rurality status on kidney transplantation (KTP) access among veterans is unknown. Our objective was to study KTP rates among veterans listed for KTP and to compare the impact of rurality status on KTP rates among veterans and nonveterans. METHODS: Retrospective cohort study of adult patients waitlisted per the United Network for Organ Sharing from January 2000 to December 2014. Patient characteristics were compared using Chi-square or t tests, as appropriate, by veteran status and patient rurality. Multivariable competing-risks Cox regression was performed. RESULTS: The study sample included 3281 veterans receiving care in Veteran Health Administration transplant programs and 445 177 nonveterans. Veterans, compared to nonveterans, were older (57 versus 50 y; P < 0.001), more likely to be male (96% versus 60%; P < 0.001) or diabetic at waitlisting (51% versus 41%; P < 0.001), and less likely be an urban resident (79% versus 84%; P < 0.001). Among veterans, dialysis duration prior to registration was longer among urban compared to all other rurality types (810 ± 22.1 d versus 632 to 702 ± 41.6 to 77.6 d; P = 0.02). In multivariate competing risks models, there was no evidence that the hazard of transplant among veterans differs by residential rurality. CONCLUSIONS: Among waitlisted veterans served by Veteran Health Administration transplant programs, residential rurality status does not portend longer waiting time for KTP.

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C.

BACKGROUND: In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. METHODS: A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. RESULTS: By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P< or =0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. CONCLUSIONS: Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.

Positive serum cryoglobulin is associated with worse outcome after liver transplantation for chronic hepatitis C.

BACKGROUND: Recurrent hepatitis C virus (HCV) infection in patients after liver transplantation is an important clinical problem. Because serum cryoglobulins (CG) are known to be associated with an increased incidence of cirrhosis in nontransplant patients, the authors tested the hypothesis that CG would also predict aggressive recurrent HCV in patients after liver transplantation. METHODS: Using a longitudinal database, the outcomes of 105 allografts transplanted into 97 HCV-positive patients from 1991 through 2002 were analyzed on the basis of CG status using a retrospective cohort design. Fifty-nine CG-negative and 38 CG-positive patients were identified. Histologic outcomes and graft survival were analyzed using Kaplan-Meier estimates and Cox univariate and multivariate analyses. Both overall survival and HCV-specific survival (non-HVC-related deaths and graft losses censored) were analyzed. RESULTS: By Kaplan-Meier estimates, CG-positive patients showed earlier graft failure with decreased time to severe histologic activity and fibrosis as compared with CG-negative patients (P<0.05 for all outcomes). By univariate analysis, CG-positive patients had significantly higher risk ratios for shortened HCV-specific graft survival, severe activity-free survival, and severe fibrosis-free survival as compared with CG-negative patients (P<0.05 for all outcomes). In the multivariate model, CG was an independent predictor for severe activity-free, severe fibrosis-free, and HCV-specific graft survival (P<0.05 for all outcomes). CONCLUSIONS: CG-positivity is associated with severe recurrent HCV disease in liver transplant recipients.

Long-term outcome of deceased donor renal transplants correlates with the 30-day creatinine reduction ratio.

A simplified model to correlate early allograft function with long-term allograft survival in recipients of deceased donor renal transplants (DDRT) remains challenging. We propose here a novel approach, using the change from the pretransplant creatinine to the 30-day posttransplant creatinine. The outcomes of 153 consecutive DDRT performed at our center between January 1998 and March 2001 were reviewed. The percentage change in creatinine from the pretransplant to 1 month posttransplant, termed here, the creatinine reduction ratio (CRR), was calculated as follows: (pretransplant creatinine-creatinine at 1 month)/pretransplant creatinine *100%. Patients were divided as follows: group 1 CRR>or=67% and group 2<67%. Group 1 had a graft survival at 1 and 5 years of 100% and 89.1% versus 88% and 69.1% for group 2 (log-rank p=0.0008). The risk ratio for graft loss during the follow-up period was four times lower for the patients on group 1. Using the Cox hazards model to compare CRR>or=67% with determinants of long-term outcome, the risk ratio of graft loss during the observational period was 0.26 (p=0.001). The creatinine reduction ratio, when stratified by a level of >or=67% has a strong correlation with superior long-term allograft survival in recipients of DDRT.

Determinants of cardiovascular mortality after renal transplantation: a role for cytomegalovirus?

Death with a functioning graft (DWF) is now the most common cause of late renal transplant failure, with cardiovascular disease its most frequent etiology. In some populations, infection with cytomegalovirus (CMV) increases risk of coronary disease. Few data exist regarding CMV and cardiovascular mortality after renal transplantation. We reviewed charts of 158 adult patients who died more than 90 days after receiving renal allografts and a matched cohort of 143 (of 2398) surviving patients transplanted at the University of Alabama at Birmingham between 1990 and 1998. Only advancing donor and recipient age increased risk of DWF; CMV infection did not. However, of 50 patients who died of cardiovascular causes, 94% were seropositive for CMV, while only 74% of the other 108 deaths occurred in CMV-seropositive patients (p < 0.05). Risk of cardiovascular death was greatest (p < 0.05) in patients with diabetes, advancing age, and CMV seropositivity. In renal transplant recipients, infection with CMV increases risk of death as a result of cardiovascular causes.