Our research broadens the knowledge of kidney disease.

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.

Circulating levels of soluble Fas (sCD95) are associated with risk for development of a nonresolving acute kidney injury subphenotype

Bhatraju PK, Robinson-Cohen C, Mikacenic C, Harju-Baker S, Dmyterko V, Slivinski NSJ, Liles WC, Himmelfarb J, Heckbert SR, Wurfel MM

Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different.

Non-GFR Determinants of Low-Molecular-Weight Serum Protein Filtration Markers in the Elderly: AGES-Kidney and MESA-Kidney

Foster MC, Levey AS, Inker LA, Shafi T, Fan L, Gudnason V, Katz R, Mitchell GF, Okparavero A, Palsson R, Post WS, Shlipak MG

In this current study we showed that, in two elderly community based cohorts, cystatin C, β2-microglobulin (B2M), and beta-trace protein (BTP) were less affected by age and gender and unaffected by ethnicity than those of creatinine. These findings are important for the development of GFR estimating equations.

Development of a microphysiological model of human kidney proximal tubule function

Weber EJ, Chapron A, Chapron BD, Voellinger JL, Lidberg KA, Yeung CK, Wang Z, Yamaura Y, Hailey DW, Neumann T, Shen DD, Thummel KE, Muczynski KAHimmelfarb J, Kelly EJ