Our research broadens the knowledge of kidney disease.

Risk profiles for acute health events after incident atrial fibrillation in patients with end-stage renal disease on hemodialysis

Airy M, Chang TI, Ding VY, Goldstein BA, Bansal N, Niu J, Navaneethan SD, Turakhia MP, Winkelmayer WC

Among 85,000 older incident hemodialysis patients in the U.S., atrial fibrillation was diagnosed in 14% of this population. Atrial fibrillation was associated with up to 9-fold increased risk of mortality, particularly in the first 90 days after diagnosis of atrial fibrillation.

Longitudinal FGF23 Trajectories and Mortality in Patients with CKD

Tamara Isakova, Xuan Cai, Jungwha Lee, Dawei Xie, Xue Wang, Rupal Mehta, Norrina B. Allen, Julia J. Scialla, Michael J. Pencina, Amanda H. Anderson, John Talierco, Jing Chen, Michael J. Fischer, Susan P. Steigerwalt, Mary B. Leonard, Chi-yuan Hsu, Ian H. de Boer, John W. Kusek, Harold I. Feldman, Myles Wolf, Chronic Renal Insufficiency Cohort (CRIC) Study Investigators

FGF-23 is a phosphaturic hormone that may promote cardiovascular disease. People with CKD enrolled in the CRIC study, and those whose blood FGF-23 concentrations rose during follow-up had markedly higher mortality rates than those whose FGF-23 concentrations remained stable or decreased. This provides new evidence that interventions to prevent rising FGF-23 may improve health outcomes in CKD.

Mortality Associated with Metformin Versus Sulfonylurea Initiation: A Cohort Study of Veterans with Diabetes and Chronic Kidney Disease

Marcum ZA, Forsberg CW, Moore KP, de Boer IH, Smith NL, Boyko EJ, Floyd JS

Metformin is the preferred first-line drug used to lower blood glucose for people with diabetes. However, metformin is cleared by the kidneys, and its use has been restricted among patients with CKD. In this observational cohort study of more than 175,000 veterans with diabetes, metformin was associated with better outcomes than a comparator glucose-lowering drug (glipizide) at all evaluated levels of estimated GFR. This supports more widespread use of metformin among people with diabetes and moderate (stage 3) CKD.

The 24,25 to 25-hydroxyvitamin D ratio and fracture risk in older adults: The cardiovascular health study

Ginsberg C, Katz Rde Boer IHKestenbaum BR, Chonchol M, Shlipak MG, Sarnak MJ, Hoofnagle AN, Rifkin DE, Garimella PS, Ix JH

In this cohort study, lower 24,25 to 25-hydroxyvitamin D3 ratio was associated with low bone mineral density and increased risk of fracture, providing evidence that impaired vitamin D metabolism affects bone health and suggesting that this ratio may help guide treatments to improve bone in CKD.

Biomarkers of tubulointerstitial damage and function in type 1 diabetes

de Boer IH, Gao X, Bebu I, Hoofnagle AN, Lachin JM, Paterson A, Perkins BA, Saenger AK, Steffes MW, Zinman B, Molitch ME

This case-control study of people with type 1 diabetes found that 8 urine and plasma biomarkers differed markedly comparing participants with, versus without, albuminuria and low eGFR. The results demonstrate that marked abnormalities in biomarkers accompany reduced eGFR and albuminuria in type 1 diabetes.

Clinical Genetic Testing for APOL1: Are we There Yet?

Young BA, Fullerton SM, Wilson JG, Cavanaugh K, Blacksher E, Spigner C, Himmelfarb J, Burke W

End-stage renal disease (ESRD) disproportionately affects African Americans, who are two to four times more likely than European Americans to develop ESRD. Two independent variants of the apolipoprotein L1 (APOL1) gene, G1 and G2, have been associated with a 7- to 10-fold greater risk of developing nondiabetic ESRD in African Americans.

Is Kidney Donor Profile Index (KDPI) Valid for Hepatitis C Aviremic Kidneys?

Sibulesky L, Kling CE, Limaye AP, Johnson CK

The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) assist clinicians with the selection of deceased donor kidneys. This scoring system is based on 10 donor factors.

Recurrent glomerular disease after kidney transplantation

Blosser CD, Bloom RD

Recurrent glomerular disease is an increasingly recognized and significant cause of chronic allograft failure. Improved understanding of the mechanisms of disease have enabled better biomarkers and therapies and are available for some GNs, including Membranous Nephropathy, Primary FSGS, C3G and atypical HUS. The greater risks and opportunities for treatment of recurrent GN necessitate accurate pretransplant diagnoses.

Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development

Kim YK, Refaeli I, Brooks CR, Jing P, Gulieva RE, Hughes MR, Cruz NM, Liu Y, Churchill AJ, Wang Y, Fu H, Pippin JW, Lin LY, Shankland S, Vogl AW, McNagny KM, Freedman BS

The presence of podocytes - the specialized filtering cells of the kidney - is one of the most exciting aspects of human kidney organoids. However, the maturity of these podocytes has not been clear from previous studies. Here, we show that organoid podocytes mature to a specific stage in kidney development, and that gene-edited podocytes can faithfully recapitulate disease symptoms at this stage, teaching us new lessons about how the podocyte gets its specialized architecture.

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

Cruz NM, Song X, Czerniecki SM, Gulieva RE, Churchill AJ, Kim YK, Winston K, Tran LM, Diaz MA, Fu H, Finn LS, Pei Y, Himmelfarb JFreedman BS

Polycystic kidney disease is a very common disorder in which tiny tubes in the kidneys and other organs swell up to form balloon-like cysts, eventually causing organ failure. The genes that cause PKD are known, but how they work to prevent cysts is not yet understood. Using gene editing, we created human kidney organoids with mutations that cause PKD. These organoids formed massive cysts when liberated from their surrounding attachments, which were not seen in non-PKD organoids. Our findings indicate a critical and understudied role for the extracellular milieu in PKD.