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 September 2020 issue:

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants by Justin Ashley et al 

From the authors: Which type of oral anticoagulant (vitamin K antagonists, VKAs, or direct oral anticoagulants, DOACs) is optimal in patients with chronic kidney disease to prevent cardiovascular (CV) disease is uncertain. We examined all patients of advanced age who received a new prescription for a DOAC or a VKA and compared their risks of CV disease or mortality, CV disease alone, and major hemorrhage. Furthermore, we examined whether the risk of adverse outcomes differed by eGFR level. Using a matched study design of over 27,000 pairs, we found a lower risk of CV events or mortality with DOACs compared to VKAs and the effect was greater the lower the eGFR. The therapeutic implications of these findings await further study.

DOI: 10.1053/j.ajkd.2020.02.446

Editorial: Do Direct Oral Anticoagulants Have Cardiovascular Benefits in CKD? We Need More Evidence by Jung-Im Shin and Morgan E Grams [FREE] 

Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis by Suetonia C Palmer et al 

From the authors: Calcimimetic agents prevent problems related to calcium and phosphate metabolism in people with chronic kidney disease. Treatment options include cinacalcet, etelcalcetide and evocalcet. It is unclear whether any of these three specific treatments is more effective or safer than the others. By combining information from 36 clinical trials, this study shows that all three calcimimetic treatments lower serum parathyroid hormone better than placebo. These 3 calcimimetic agents have different side effects and methods of administration that should be considered when selecting one agent as a treatment. Whether these treatments improve patient-level outcomes such as heart or blood vessel complications or bone pain has yet to be studied in clinical trials.

DOI: 10.1053/j.ajkd.2020.02.439

Editorial: Calcimimetics: A Promise Unfulfilled by James B Wetmore [FREE] 

Incidence of ESKD Among Native Hawaiians and Pacific Islanders Living in the 50 US States and Pacific Island Territories by Jie Xiang et al

From the authors: In this study, we sought to estimate the incidence rates of kidney failure requiring chronic dialysis or transplantation (ESKD) in the US among Native Hawaiians and Pacific Islanders (NHPI) living in the 50 states and Pacific Island Territories when including NHPI who reported multiple races in both numerators and denominators of the calculation. NHPI living in both the 50 states and Pacific Island Territories were found to have higher ESKD incidence rates than had other race groups. Diabetes was most frequently listed as the primary cause of ESKD for NHPI and American Indians/Alaska Natives. Patients with ESKD among NHPI living in the Pacific Island Territories received much less pre-ESKD nephrology care than did those living in the 50 states. The high incidence rate of ESKD among NHPI requires urgent attention by both the clinical and public health communities.

DOI: 10.1053/j.ajkd.2020.01.008

Kidney Histopathology and Prediction of Kidney Failure: A Retrospective Cohort Study by Michael T Eadon et al 

From the authors: Patients with a wide variety of kidney diseases undergo kidney biopsies to help diagnose the cause of or provide the prognosis for their kidney disease. A number of prior studies have examined the demographic, co-morbid conditions, or laboratory tests that inform our estimation of a patient’s likelihood of progressing to end-stage kidney disease. This study seeks to understand how features of kidney disease interpreted from a kidney biopsy specimen may aid in the prognosis of end-stage kidney disease. To accomplish this, 2720 biopsy records with associated clinical features were extracted from a database. The study concluded that there was improvement in the prediction of progression to end-stage kidney disease when biopsy information was added to standard clinical and demographic information.

DOI: 10.1053/j.ajkd.2019.12.014

Immunoglobulin A nephropathy with endocapillary proliferation and cellular crescent formation (Jones silver stain). Figure 2 from Fogo et al, AJKD © National Kidney Foundation

Blog Post Can Histopathology Assist in Predicting the Time of Kidney Failure?! What’s New! by Sai Sudha Mannemuddhu [FREE] 

Association of HLA Typing and Alloimmunity With Posttransplantation Membranous Nephropathy: A Multicenter Case Series by Ibrahim Batal et al

From the authors: Post-kidney transplant (post-KTx) membranous nephropathy (MN) can be encountered as recurrent or de novo disease. Data on genetic predisposition and pathogenesis of post-KTx MN are scarce and mostly limited to small studies. The current case series represents the largest clinical and pathological assessment of post-KTx MN. Our data confirm the association of de novo MN with antibody-mediated rejection, and provide a rationale to investigate novel therapeutic approaches, such as blocking antibody formation against donor antigens. For recurrent MN, we demonstrate that recipient features, donor factors, and immunosuppressive regimens are potential predictors of recurrent disease. These findings open new avenues of investigation into genetic assessment of donor-recipient pairs and identification of potential immune triggers to reduce the incidence of recurrent MN.

DOI: 10.1053/j.ajkd.2020.01.009

Blog Post Association of HLA Typing With Posttransplantation Membranous Nephropathy by Andrew Malone [FREE] 

Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients by Lara Meyer et al 

From the authors: Fibrinogen A alpha-chain amyloidosis (Afib-amyloidosis) is a rare disease caused by a mutation in the fibrinogen gene, which is solely synthesized by the liver. Afib-amyloidosis leads progressively to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear when it is best to pursue these approaches. We studied a French case series of 32 patients with Afib-amyloidosis) and described their clinical course . Clinical presentation was characterized by late and less aggressive disease in the setting of the most common genetic variant, E526V, compared either to the R554L or frameshift variants. Recurrence after KT may be less common, with less graft loss, in patients with E526V and R554L mutations compared to those carrying a frameshift mutation. No amyloid recurrence was reported in a small number of patients who underwent LKT. KT appears to be a valid treatment option in patients with the most common E526V variant, while LKT may be preferred in patients with frameshift variants.

DOI: 10.1053/j.ajkd.2020.02.445

This month’s Case Report:

Kidney Infarction in Patients With COVID-19 by Adrian Post et al [Open Access] 

From the authors: Recent findings indicate an increased risk for acute kidney injury during COVID-19 infection. The pathophysiologic mechanisms leading to acute kidney injury in COVID-19 infection are unclear but may include direct cytopathic effects of the virus on kidney tubular and endothelial cells, indirect damage caused by virus-induced cytokine release, and kidney hypoperfusion due to a restrictive fluid strategy. In this report of 2 cases, we propose an additional pathophysiologic mechanism. Our findings implicate that the differential diagnosis of acute kidney injury in COVID-19–infected patients should include kidney infarction, which may have important preventive and therapeutic implications.

DOI: 10.1053/j.ajkd.2020.05.004

On the Cover: This month’s cover shows the noni plant, which has been used for centuries by kahuna lapa’au (traditional Hawaiian medicine healers) to alleviate symptoms or treat illnesses including kidney stones and high blood pressure. In 1778, the arrival of Captain Cook brought profound changes to the Hawaiian Islands, including the introduction of infectious diseases that devastated the population. The subsequent history of colonization, oppression, and marginalization is evident today in the excess burden of social and health disparities experienced by Native Hawaiians and Pacific Islanders (NHPI). In this issue of AJKD, Xiang et al demonstrate that NHPI living in both the 50 states and Pacific Island Territories have ESKD incidence rates higher than those experienced by other race groups.

The photograph “starr-060422-7896-Morinda_citrifolia-flowers_and_fruit-Waianapanapa-Maui” is by Forest and Kim Starr on Flickr, released under the CC BY 3.0 license.

Special Collection: Patient-Centered Research

This collection of recent AJKD articles highlights patient-centered research that can help elucidate outcomes of importance to patients with kidney disease. All articles in the collection are freely available until October 1, 2020.