Renal Function Profile in White Kidney Donors: The First 4 Decades.

Previous studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean±SD follow-up of 16.6±11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m(2), and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m(2) or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m(2) or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77-1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors.

The renin-aldosterone axis in kidney transplant recipients and its association with allograft function and structure.

The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney transplant recipients has not been extensively studied or serially profiled. To describe this axis and to determine its association with glomerular filtration rate (GFR) change, interstitial expansion, and end-stage renal disease (ESRD), we measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5 years in 153 kidney transplant recipients randomly assigned to losartan or placebo. PRA and plasma aldosterone levels were in the normal range at all times and did not vary by immunosuppression regimen. Those on losartan exhibited higher PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or plasma aldosterone levels were associated with GFR decline, proteinuria, or interstitial expansion. Losartan use (hazard ratio (HR) 0.48 (95% confidence interval (CI) 0.21-1.0), insignificant) and Caucasian donor (HR 0.18 (95% CI 0.07-0.4) significant) were associated with less doubling of serum creatinine, death, or ESRD. Hypertension, <3 human leukocyte antigen matches, the combination of tacrolimus-rapamycin, and acute rejection were associated with more events. Neither PRA nor plasma aldosterone levels were independently associated with this outcome. Higher serial plasma aldosterone levels were associated, however, with a significantly higher risk of ESRD (HR 1.01 (95% CI 1.00-1.02)). Thus, systemic RAAS is not overly activated in kidney transplant recipients, but this may not reflect the intrarenal system. Importantly, plasma aldosterone levels may be associated with more ESRD.

Cognitive impairment, perceived medication adherence, and high-risk medication use in patients with reduced kidney function: A cross-sectional analysis.

Background and Aims: Reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) is a risk factor for cognitive impairment (CI) and medication nonadherence. However, the association between CI and medication adherence in adults with reduced eGFR has not been adequately examined. Our pragmatic objectives were to assess the cross-sectional relationship between CI and self-reported medication adherence, medication number, and use of potentially high-risk medications among adults with reduced eGFR. Methods: An observational cohort study of the epidemiology of CI in community-dwelling adults aged 45 years or older with reduced eGFR. Results: Our analytic cohort consisted of 420 participants (202 with CI; mean age: 69.7 years) with reduced eGFR, at least one prescription medication, and nonmissing medication adherence data. Participants with CI had four times greater unadjusted odds of reporting good medication adherence than participants without CI (self-report of missing medications <4 days/month; odds ratio [OR]: 4.04, 95% confidence interval [CI]:​​​​​ 1.62-10.10). This difference persisted following adjustment for demographic factors and comorbidities (OR: 5.50, 95% CI: 1.86-16.28). Participants with CI were no more likely than participants without CI to report forgetfulness as a reason for missing medication doses. Participants with CI were, on average, taking more total (mean: 13.3 vs. 11.5, median: 12 vs. 11) and more high-risk (mean: 5.0 vs. 4.2, median: 5 vs. 4) medications than those without CI; these differences were attenuated and no longer significant following adjustment for demographics and comorbidities. Conclusion: Given the well-documented association between CI and medication nonadherence, better self-reported medication adherence among those with CI may represent perceptions of adherence rather than actual adherence. Participants with CI were, on average, taking more total and more high-risk medications than those without CI, suggesting a possible increased risk for adverse drug events. Our results highlight the potential risks of relying on self-reported medication adherence in reduced eGFR patients with CI.