Editor’s Note: We asked authors of Original Investigations to provide short plain-language summaries that would briefly summarize what inspired their study, the basic approach taken, what was learned, and why it matters. We hope our readers will find this valuable in helping them keep up with the latest research in the field of nephrology. From the October 2019 issue:

Association of Kidney Transplant Center Volume With 3-Year Clinical Outcomes by Elizabeth M Sonnenberg, et al 

From the authors: A strong relationship between the number of surgical procedures and clinical outcomes has been demonstrated across many surgical fields. We examined if a volume-outcome relationship exists in modern kidney transplantation. Transplant centers were categorized as lowest, medium, medium-high, and highest-volume centers. We then examined three-year patient and graft survival by volume quartile using multivariable time-to-event analysis to control for potentially confounding donor, recipient, and graft characteristics. Our study focused on complex patients that plausibly require more difficult judgments and may benefit from referral to a high-volume center. There was no association between center volume and three-year post-transplant outcomes, even among recipients and donors at high risk of adverse outcomes. These findings do not support interpreting transplant center volume as proxy for centers’ quality of care.

DOI: 10.1053/j.ajkd.2019.02.019

Editorial Transplant Center Volume: Is Bigger Better? by John R Montgomery, et al [FREE] 

Associations of Cognitive Function and Education Level With All-Cause Mortality in Adults on Hemodialysis: Findings From the COGNITIVE-HD Study by Anita van Zwieten, et al  

From the authors: Cognitive impairment is common in dialysis patients and is closely intertwined with education level. Associations of cognition and education with mortality in dialysis patients have not been well studied. In this cohort study of 676 adult hemodialysis patients, cognitive impairment was associated with almost a doubling of all-cause mortality over an average of three years follow-up. The number of cognitive domains impaired was associated with mortality risk in a dose-dependent manner, while better global cognitive function was associated with a lower mortality risk. Education level did not appear to be associated with mortality and this did not differ across levels of cognitive function. Future study of the mechanisms that underlie associations between cognitive impairment and mortality may inform the development of targeted interventions.

DOI: 10.1053/j.ajkd.2019.03.424

Editorial Cognitive Impairment and Mortality in Patients Receiving Hemodialysis: Implications and Future Research Avenues by Katharine L Cheung and Michael A LaMantia [FREE] 

Comparative Effectiveness of Medical Therapy, Percutaneous Revascularization, and Surgical Coronary Revascularization in Cardiovascular Risk Subgroups of Patients With CKD: A Retrospective Cohort Study of Medicare Beneficiaries by David M Charytan, et al

From the authors: Prior studies comparing coronary artery bypass surgery (CABG), percutaneous coronary intervention, and medical therapy for coronary disease in chronic kidney disease (CKD) patients are limited by insufficient assessment of both progression to end-stage renal disease (ESRD) and changes to optimize medical therapy. As well, prior research has typically provided limited information regarding underlying cardiovascular risk. We studied patients presenting clinically with evidence of cardiovascular disease and compared outcomes associated with coronary revascularization to medical therapy that included use of new cardiovascular medications. We separately analyzed patients at low, medium, and high underlying cardiovascular risk and assessed the outcomes of mortality and ESRD. CABG was associated with higher rates of ESRD in low-risk patients, but not with patient survival. In contrast, among high-risk patients, CABG was associated with lower mortality despite also being associated with a higher rate of ESRD. Our results suggest that the effects of coronary revascularization on survival and progression to ESRD may differ across levels of underlying cardiovascular disease risk, observations that may inform clinical care.

DOI: 10.1053/j.ajkd.2019.04.018

Editorial Treatment Strategies in CKD Patients With Suspected Coronary Artery Disease by Robert N Foley [FREE] 

Identifying Needs for Self-management Interventions for Adults With CKD and Their Caregivers: A Qualitative Study  by Maoliosa Donald, et al 

From the authors: Patients with chronic kidney disease (CKD) and those who care for them identified a need for strategies to help patients self-manage CKD. Our study identifies and describes the needs of adults with CKD and informal caregivers for CKD self-management support. We held focus groups and individual interviews with 33 patients with CKD (not on dialysis nor having received a kidney transplant) and 15 caregivers. Participants discussed their needs for self-management support encompassing three themes: empowerment through knowledge (awareness and understanding of CKD, diet challenges, medication and alternative treatments, attuning to the body, financial implications, mental and physical health consequences, travel and transportation restrictions, maintaining work and education); activation through information sharing (access, meaningful and relevant, timing, amount); and tangible support for the health journey (family and community, professionals). These identified needs will help guide future efforts to develop innovative patient CKD self-management support interventions.

DOI: 10.1053/j.ajkd.2019.02.006

A Diet Rich in Vegetables and Fruit and Incident CKD: A Community-Based Prospective Cohort Study by Jong Hyun Jhee, et al [FREE] 

From the authors: The association between dietary patterns and incident chronic kidney disease (CKD) in the general population is unknown. Acid content in the diet may promote progression of CKD. We examined the association between foods such as vegetables and fruit that are very low in acid content and the risk of incident CKD in the general population. Our study showed that a diet rich in vegetables and fruit was associated with a lower risk of CKD. These findings may be explained by the reduction of dietary acid and suggest that dietary modification may prevent the development of CKD in healthy adults.

DOI: 10.1053/j.ajkd.2019.02.023

Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study by Dominik Steubel, et al

From the authors: Tubular atrophy and interstitial fibrosis are important predictors of kidney function decline and are highly prevalent in the elderly population. However, non-invasive assessment of tubular atrophy is difficult due to the lack of biomarkers. We assessed serum uromodulin, which is exclusively expressed in tubular cells, and its association with loss of kidney function in a geriatric cohort. We noted that lower levels of serum uromodulin were associated with higher risk of development of ESKD. Future studies should attempt to reproduce these findings and evaluate mechanisms to explain this association.

DOI: 10.1053/j.ajkd.2019.02.024

The P274S Mutation of Lecithin-Cholesterol Acyltransferase (LCAT) and Its Clinical Manifestations in a Large Kindred by Nikolaos Fountoulakis, et al 

From the authors: Two adult men with anemia, splenomegaly, and dyslipidemia for many years were diagnosed with a form of kidney disease associated with deficiency in lecithin cholesterol acyltransferase (LCAT), an enzyme important in lipoprotein metabolism. LCAT deficiency is also associated with corneal opacities, which provided in important clinical clue that led to the diagnosis of familial LCAT deficiency in these two men. Subsequently, 110 of their family members agreed to participate in a study of the identification of disease carriers and the evaluation of the progression of their disease. A new mutation in the LCAT gene, critically affecting enzyme activity, was found in 60% of the family members. Kidney function deteriorated relatively rapidly in affected individuals. Kidney biopsies of the most affected members showed extensive lipid deposition in the kidneys. Five family members developed end-stage kidney failure over a median follow-up of 12 years. Several developed cardiovascular disease as well. Genetic abnormalities that cause abnormal lipid metabolism can cause progressive kidney injury.

DOI: 10.1053/j.ajkd.2019.03.422

On the Cover: This month’s cover depicts a sequence of tomographic images of various fruits and vegetables obtained using spin-echo magnetic resonance imaging (MRI). Color was digitally added to correspond with the MRI signal intensity. These images of passion fruit, pumpkin, cabbage, kiwi, and mandarin orange are evocative of a diet rich in fruits and vegetables thought to reduce incident hypertension and cardiovascular disease risk. However, the effects of such diets on the risk of incident CKD are unknown. In this month’s issue of AJKD, Jhee et al report that a lower dietary acid load resulting from higher consumption of fruits and vegetables is associated with a reduced risk of incident CKD in a community-based cohort. These findings highlight potential public health interventions that may expand our armamentarium for addressing the global burden of CKD.

Graphic assembled from portions of images created by Alexandr Khrapichev, University of Oxford. Component images comprise: Passion fruit, axial view, MRI. Pumpkin, sagittal view, MRI. Cabbage, axial view, MRI. Kiwi, sagittal view, MRI. Mandarin orange, sagittal view, MRI. From the Wellcome Collection, available under CC BY license.

Perspective from the October 2019 Issue:

APOL1 Genetic Testing in Living Kidney Transplant Donors  by Sumit Mohan, et al 

The presence of 2 apolipoprotein L1 gene (APOL1) risk variants is associated with increased risk for chronic kidney disease and end-stage kidney disease. Inferior allograft outcomes following transplantation with kidneys from donors with 2 risk variants have also been reported. These data, coupled with anecdotal case reports and a recent cohort study of living donors, raise important questions about the potential increased kidney disease risk for living donors with APOL1 risk variants and the need for testing as part of the standard living donor evaluation process. In this Perspective, Mohan et al identify a series of questions that are central to the development of clinical policy regarding APOL1 testing of potential living kidney donors given the current uncertainty over the clinical implications of having 2 risk variants. They explore the ethical challenges that arise when determining when and to whom APOL1 testing should be offered, what potential donors should be told about APOL1 testing, how test results should be used to determine suitability for donation, if and when recipients should have access to results, and how clinical policy regarding APOL1 testing should be established.

DOI: 10.1053/j.ajkd.2019.02.007

Image from Pixabay / Thor_Deichmann

Blog Post Ethical Challenges of APOL1 Testing in Living Kidney Donors by Paul Phelan [FREE] 

AJKD Express

Recognizing the efficiency losses to authors and reviewers when a manuscript turned down by a high-profile journal is submitted to a new journal, AJKD is excited to offer a new expedited consideration process for manuscripts that meet the following criteria:

1. The manuscript reports original research within the scope of AJKD and could be reformatted to AJKD style; and
2. The authors supply an unmodified decision letter (including reviews) from a high-impact journal; and
3. The author list excludes any AJKD EIC/Deputy Editor/Education Editor/Associate Editor/International Editor.

In this accelerated manuscript consideration process, the editors aim to provide to authors:

• Notification within 2 business days indicating eligibility for AJKD Express
• Decision letter within a further 5-14 days

Details for AJKD Express are available in this blog post.