Tyson Rogers

Long-term consequences of kidney donation.

BACKGROUND The long-term renal consequences of kidney donation by a living donor are attracting increased appropriate interest. The overall evidence suggests that living kidney donors have survival similar to that of nondonors and that their risk of end-stage renal disease (ESRD) is not increased. Previous studies have included relatively small numbers of donors and a brief follow-up period. METHODS We ascertained the vital status and lifetime risk of ESRD in 3698 kidney donors who donated kidneys during the period from 1963 through 2007; from 2003 through 2007, we also measured the glomerular filtration rate (GFR) and urinary albumin excretion and assessed the prevalence of hypertension, general health status, and quality of life in 255 donors. RESULTS The survival of kidney donors was similar to that of controls who were matched for age, sex, and race or ethnic group. ESRD developed in 11 donors, a rate of 180 cases per million persons per year, as compared with a rate of 268 per million per year in the general population. At a mean (+/-SD) of 12.2+/-9.2 years after donation, 85.5% of the subgroup of 255 donors had a GFR of 60 ml per minute per 1.73 m(2) of body-surface area or higher, 32.1% had hypertension, and 12.7% had albuminuria. Older age and higher body-mass index, but not a longer time since donation, were associated with both a GFR that was lower than 60 ml per minute per 1.73 m(2) and hypertension. A longer time since donation, however, was independently associated with albuminuria. Most donors had quality-of-life scores that were better than population norms, and the prevalence of coexisting conditions was similar to that among controls from the National Health and Nutrition Examination Survey (NHANES) who were matched for age, sex, race or ethnic group, and body-mass index. CONCLUSIONS Survival and the risk of ESRD in carefully screened kidney donors appear to be similar to those in the general population. Most donors who were studied had a preserved GFR, normal albumin excretion, and an excellent quality of life.

Cryptogenic stroke and underlying atrial fibrillation

BACKGROUND Current guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out atrial fibrillation. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of atrial fibrillation after cryptogenic stroke has therapeutic implications. METHODS We conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional follow-up (control) for detecting atrial fibrillation in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of atrial fibrillation (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of atrial fibrillation within 12 months. Data were analyzed according to the intention-to-treat principle. RESULTS By 6 months, atrial fibrillation had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, atrial fibrillation had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001). CONCLUSIONS ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT00924638.).

Pregnancy Outcomes After Kidney Donation

The outcome of pregnancy in kidney donors has generally been viewed to be favorable. We determined fetal and maternal outcomes in a large cohort of kidney donors. A total of 2102 women have donated a kidney at our institution; 1589 donors responded to our pregnancy surveys; 1085 reported 3213 pregnancies and 504 reported none. Fetal and maternal outcomes in postdonation pregnancies were comparable to published rates in the general population. Postdonation (vs. predonation) pregnancies were associated with a lower likelihood of full‐term deliveries (73.7% vs. 84.6%, p = 0.0004) and a higher likelihood of fetal loss (19.2% vs. 11.3%, p < 0.0001). Postdonation pregnancies were also associated with a higher risk of gestational diabetes (2.7% vs. 0.7%, p = 0.0001), gestational hypertension (5.7% vs. 0.6%, p < 0.0001), proteinuria (4.3% vs. 1.1%, p < 0.0001) and preeclampsia (5.5% vs. 0.8%, p < 0.0001). Women who had both pre‐ and post‐donation pregnancies were also more likely to have these adverse maternal outcomes in their postdonation pregnancies. In this large survey of previous living donors in a single center, fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population, but inferior to predonation pregnancy outcomes.

Prevalence, severity, and predictors of fatigue in subjects with primary Sjögren's syndrome

OBJECTIVE To investigate the relationship of fatigue severity to other clinical features in primary Sjögrens syndrome (SS) and to identify factors contributing to the physical and mental aspects of fatigue. METHODS We identified 94 subjects who met the American-European Consensus Group criteria for the classification of primary SS. Fatigue was assessed with a visual analog scale, the Fatigue Severity Scale (FSS), and the Profile of Fatigue (ProF). Associations with fatigue were compared using multivariate regression. RESULTS Abnormal fatigue, defined as an FSS score >or=4, was present in 67% of the subjects. Pain, helplessness, and depression were the strongest predictors of fatigue according to the FSS and the somatic fatigue domain of the ProF (ProF-S), both with and without adjustment for physiologic and serologic characteristics. Depression was associated with higher levels of fatigue; however, the majority of subjects with abnormal fatigue were not depressed. Anti-Ro/SSA-positive subjects were no more likely to report fatigue than seronegative subjects. The regression models explained 62% of the variance in FSS and 78% of the variance in ProF-S scores. Mental fatigue was correlated with depression and helplessness, but the model predicted only 54% of the variance in mental fatigue scores. CONCLUSION Psychosocial variables are determinants of fatigue, but only partially account for it. Although fatigue is associated with depression, depression is not the primary cause of fatigue in primary SS. Investigation of the pathophysiologic correlates of physical and mental aspects of fatigue is needed to guide the development of more effective interventions.

Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics.

Introduction Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000–2003. The last population-based assessment of TSS was 1986. Methods Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000–2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases. Results Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32–0.77), 0.69 (0.39–1.16), and 0.32 (0.12–0.67), respectively. Women 13–24 years had the highest incidence at 1.41 (0.63–2.61). No increase in incidence was observed from 2000–2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively]. Discussion TSS incidence remained stable across our surveillance period of 2000–2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden.

The performance of three serum creatinine-based formulas in estimating GFR in former kidney donors.

Studies addressing long‐term consequences of living with one kidney have used serum creatinine‐based formulas that have not been validated in former kidney donors. Therefore, we evaluated the performance of Cockcroft–Gault (CG), Modification of Diet in Renal Disease (MDRD) and Mayo Clinic formulas in predicting iohexol glomerular filtration rate (iGFR) after donation in 112 randomly selected former kidney donors. Mean time from donation was 12.2 ± 8.5 years. Serum creatinine was 1.1 ± 0.2 mg/dL and iohexol GFR was 72 ± 12 mL/min/1.73 m2. The majority, 83.9%, of donors had a GFR >60 mL/min. CG formula overestimated GFR by 3.35 ± 13.6 mL/min and was within 10% of iohexol GFR in only 43.7% of cases. MDRD formula underestimated iohexol GFR by 6.45 ± 9.5 mL/min and was within 10% of actual GFR in half of the cases. In contrast, the Mayo Clinic equation was the most biased at 14.71 ± 12.3 mL/min and was within 10% of measured GFR in only a fifth of the cases. Only MDRD and CG formulas provide estimates of GFR in former kidney donors that are within a clinically acceptable range of actual GFR. In conclusion, the majority of former kidney donors have excellent kidney function and the MDRD formula should be the recommended GFR estimating model in this population.

Predictors for atrial fibrillation detection after cryptogenic stroke Results from CRYSTAL AF

Objective: We assessed predictors of atrial fibrillation (AF) in cryptogenic stroke (CS) or transient ischemic attack (TIA) patients who received an insertable cardiac monitor (ICM). Methods: We studied patients with CS/TIA who were randomized to ICM within the CRYSTAL AF study. We assessed whether age, sex, race, body mass index, type and severity of index ischemic event, CHADS2 score, PR interval, and presence of diabetes, hypertension, congestive heart failure, or patent foramen ovale and premature atrial contractions predicted AF development within the initial 12 and 36 months of follow-up using Cox proportional hazards models. Results: Among 221 patients randomized to ICM (age 61.6 ± 11.4 years, 64% male), AF episodes were detected in 29 patients within 12 months and 42 patients at 36 months. Significant univariate predictors of AF at 12 months included age (hazard ratio [HR] per decade 2.0 [95% confidence interval 1.4–2.8], p = 0.002), CHADS2 score (HR 1.9 per one point [1.3–2.8], p = 0.008), PR interval (HR 1.3 per 10 milliseconds [1.2–1.4], p < 0.0001), premature atrial contractions (HR 3.9 for >123 vs 0 [1.3–12.0], p = 0.009 across quartiles), and diabetes (HR 2.3 [1.0–5.2], p < 0.05). In multivariate analysis, age (HR per decade 1.9 [1.3–2.8], p = 0.0009) and PR interval (HR 1.3 [1.2–1.4], p < 0.0001) remained significant and together yielded an area under the receiver operating characteristic curve of 0.78 (0.70–0.85). The same predictors were found at 36 months. Conclusion: Increasing age and a prolonged PR interval at enrollment were independently associated with an increased AF incidence in CS patients. However, they offered only moderate predictive ability in determining which CS patients had AF detected by the ICM.

Immunoglobulin M-to-Immunoglobulin G Anti-Human Leukocyte Antigen Class II Antibody Switching in Cardiac Transplant Recipients Is Associated With an Increased Risk of Cellular Rejection and Coronary Artery Disease

Background— Activation of T cells induces immunoglobulin (Ig)M-to-IgG B-cell isotype switching via costimulatory regulatory pathways. Because rejection of transplanted organs is preceded by alloantigen-dependent T-cell activation, we investigated whether B-cell isotype switching could predict acute cellular rejection and the subsequent development of transplantation-related coronary artery disease (TCAD) in cardiac transplant recipients. Methods and Results— Among 267 nonsensitized heart transplant recipients, switching from IgM to IgG anti-human leukocyte antigens (HLA) antibodies directed against class II but not against class I antigens was associated with a shorter duration to high-grade rejection, defined as International Society for Heart and Lung Transplantation grade 3A or higher (P<0.001), a higher cumulative rejection frequency (P=0.002), accelerated development of TCAD (P=0.04), and decreased late survival (P=0.03). Conversely, the persistence of IgM anti-HLA antibodies against class II but not against class I antigens for >30 days and the lack of IgG isotype switching were associated with protection against both acute rejection (P=0.02) and TCAD (P=0.05). Alloisotype switching coincided with T-cell activation, as evidenced by increased serum levels of soluble CD40 ligand costimulatory molecules. Finally, a case-control study showed that reduction of cardiac allograft rejection by mycophenolic acid was accompanied by reduced CD40 ligand serum levels and the prevention of IgM-to-IgG anti-HLA class II antibody switching. Conclusions— T-cell-dependent B-cell isotype switching and the consequent production of IgG anti-HLA class II antibodies are strongly correlated with acute cellular rejection, a high incidence of recurrent rejections, TCAD, and poor long-term survival. Detecting this isotype switch is a clinically useful surrogate marker for in vivo T-cell activation and may provide a noninvasive approach for monitoring the efficacy of T-cell targeted immunosuppressive therapy in heart transplant recipients.

Graft loss from recurrent glomerulonephritis is not increased with a rapid steroid discontinuation protocol.

Background. The risk of recurrence of glomerulonephritis in kidney transplant recipients on a steroid-free maintenance immunosuppression protocol is unknown. Methods. We studied the 4-year graft and patient survival in 105 adult kidney transplant recipients who received their transplant for glomerulonephritis (GN) and were treated with a protocol incorporating rapid discontinuation of prednisone for 5 days (group 1). We compared these outcomes to two control groups; 439 concurrent recipients who received a transplant for causes other than GN (group 2) and to 260 kidney transplant recipients who received an allograft for GN between 1994 and 1999 and were maintained on a steroid-based immunosuppressive protocol (group 3). Results. The 4-year graft and patient survival were similar in the three groups. Acute rejection-free survival was also similar. Serial annual serum creatinine and estimated GFR were also comparable amongst the three groups. Two grafts were lost in group 1 from biopsy-proven recurrent GN and eight other subjects had evidence of histological recurrence at 11.2±11.9 months. Seven grafts were lost for recurrent disease in group 3 and 15 others had evidence of histological recurrence at 29.1±32.6 months. The mean time to graft loss from recurrence was 52±22 months. Conclusion. A regimen that utilizes rapid discontinuation of steroids conveys no added risk of graft loss from recurrent GN in the short term but longer follow-up is needed. A consideration should be made to discontinue corticosteroids in the potential recipients who are on them at the time of transplantation.

Infarct Topography and Detection of Atrial Fibrillation in Cryptogenic Stroke: Results from CRYSTAL AF.

Background: Insertable cardiac monitors (ICM) have been shown to detect atrial fibrillation (AF) at a higher rate than routine monitoring methods in patients with cryptogenic stroke (CS). However, it is unknown whether there are topographic patterns of brain infarction in patients with CS that are particularly associated with underlying AF. If such patterns exist, these could be used to help decide whether or not CS patients would benefit from long-term monitoring with an ICM. Methods: In this retrospective analysis, a neuro-radiologist blinded to clinical details reviewed brain images from 212 patients with CS who were enrolled in the ICM arm of the CRYptogenic STroke And underLying AF (CRYSTAL AF) trial. Kaplan-Meier estimates were used to describe rates of AF detection at 12 months in patients with and without pre-specified imaging characteristics. Hazard ratios (HRs), 95% confidence intervals (CIs), and p values were calculated using Cox regression. Results: We did not find any pattern of acute brain infarction that was significantly associated with AF detection after CS. However, the presence of chronic brain infarctions (15.8 vs. 7.0%, HR 2.84, 95% CI 1.13-7.15, p = 0.02) or leukoaraiosis (18.2 vs. 7.9%, HR 2.94, 95% CI 1.28-6.71, p < 0.01) was associated with AF detection. There was a borderline significant association of AF detection with the presence of chronic territorial (defined as within the territory of a first or second degree branch of the circle of Willis) infarcts (20.9 vs. 10.0%, HR 2.37, 95% CI 0.98-5.72, p = 0.05). Conclusions: We found no evidence for an association between brain infarction pattern and AF detection using an ICM in patients with CS, although patients with coexisting chronic, as well as acute, brain infarcts had a higher rate of AF detection. Acute brain infarction topography does not reliably predict or exclude detection of underlying AF in patients with CS and should not be used to select patients for ICM after cryptogenic stroke.