Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells.

Scattered tubular cells (STCs) are a phenotypically distinct cell population in the proximal tubule that increase in number after acute kidney injury. We aimed to characterize the human STC population. Three-dimensional human tissue analysis revealed that STCs are preferentially located within inner bends of the tubule and are barely present in young kidney tissue (<2 years), and their number increases with age. Increased STC numbers were associated with acute tubular injury (kidney injury molecule 1) and interstitial fibrosis (alpha smooth muscle actin). Isolated CD13+ CD24- CD133- proximal tubule epithelial cells (PTECs) and CD13+ CD24+ and CD13+ CD133+ STCs were analyzed using RNA sequencing. Transcriptome analysis revealed an upregulation of nuclear factor κB, tumor necrosis factor alpha, and inflammatory pathways in STCs, whereas metabolism, especially the tricarboxylic acid cycle and oxidative phosphorylation, was downregulated, without showing signs of cellular senescence. Using immunostaining and a publicly available single-cell sequencing database of human kidneys, we demonstrate that STCs represent a heterogeneous population in a transient state. In conclusion, STCs are dedifferentiated PTECs showing a metabolic shift toward glycolysis, which could facilitate cellular survival after kidney injury. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Abdominal aortic calcification in patients with CKD.

BACKGROUND: Abdominal aortic calcification (AAC) is independently associated with cardiovascular events in dialysis patients and in the general population. However, data in non-dialysis chronic kidney disease (CKD) patients are limited. We analyzed determinants and prognostic value of AAC in non-dialysis CKD patients. METHODS: We included patients with CKD not receiving renal replacement therapy from the MASTERPLAN study, a randomized controlled trial that started in 2004. In the period 2008-2009, an X-ray to evaluate AAC was performed in a subgroup of patients. We studied AAC using a semi-quantitative scoring system by lateral lumbar X-ray. We used baseline and 2-year data to find determinants of AAC. We used a composite cardiovascular endpoint and propensity score matching to evaluate the prognostic value of AAC. RESULTS: In 280 patients an X-ray was performed. In 79 patients (28 %) the X-ray showed no calcification, in 62 patients (22 %) calcification was minor (<4), while 139 patients (50 %) had moderate or heavy calcification (≥4). Older age, prior cardiovascular disease, higher triglyceride levels, and higher phosphate levels were independent determinants of a calcification score ≥4. AAC score ≥4 was independently associated with cardiovascular events, with a hazard ratio of 5.5 (95 % confidence interval 1.2-24.8). CONCLUSIONS: Assessment of AAC can identify CKD patients at higher cardiovascular risk, and may provide important information for personalized treatment. Whether this approach will ultimately translate into better outcomes remains to be answered.

Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy.

BACKGROUND: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. METHODS: We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria <3.5 g/day and >50% reduction from baseline. RESULTS: Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome. CONCLUSION: Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value compared to measurement of either alpha-1-microglobulin or beta-2-microglobulin.