Pathomorphological sequence of nephron loss in diabetic nephropathy.

Following our previous reports on mesangial sclerosis and vascular proliferation in diabetic nephropathy (DN) (Kriz W, Löwen J, Federico G, van den Born J, Gröne E, Gröne HJ. 312: F1101-F1111, 2017; Löwen J, Gröne E, Gröne HJ, Kriz W. 317: F399-F410, 2019), we now describe the advanced stages of DN terminating in glomerular obsolescence and tubulointerstitial fibrosis based on a total of 918 biopsies.

Coding Microsatellite Frameshift Mutations Accumulate in Atherosclerotic Carotid Artery Lesions: Evaluation of 26 Cases and Literature Review.

Somatic DNA alterations are known to occur in atherosclerotic carotid artery lesions; however, their significance is unknown. The accumulation of microsatellite mutations in coding DNA regions may reflect a deficiency of the DNA mismatch repair (MMR) system. Alternatively, accumulation of these coding microsatellite mutations may indicate that they contribute to the pathology.

Evolution of allograft fibrosis and function in kidney transplant recipients: a retrospective analysis of stable patients under CNI and mTORi.

Histological evaluations of renal allograft biopsies are essential for diagnosis, but still show a low predictive value for long-term allograft function. One limitation relies on the fact that the analysis is usually based on a single biopsy sample, and therefore, no dynamic changes are considered. Using two distinct approaches, we evaluated the evolution of fibrosis and related markers in 36 stable kidney transplant patients under calcineurin inhibitor therapy with two indication biopsies each, prior and at least 6 months after substitution by mTORi (N = 18), or maintenance on CNI (N = 18).

Erythropoietin combined with ACE inhibitor prevents heart remodeling in 5/6 nephrectomized rats independently of blood pressure and kidney function.

Background: Cardiovascular disease is the primary cause of mortality in patients with chronic kidney disease (CKD). Heart remodeling in CKD comprises mainly interstitial fibrosis and capillary loss. Beyond correcting renal anemia, erythropoietin (Epo) has potentially beneficial pleiotropic effects on heart remodeling.

The calcimimetic R-568 prevents podocyte loss in uninephrectomized ApoE-/- mice.

Calcimimetics are indicated for secondary hyperparathyroidism in chronic kidney disease, and some data have suggested their protective role for progression of renal damage. We aimed to evaluate whether a calcimimetic can slow the progression of kidney damage in uninephrectomized apolipoprotein E (ApoE)-deficient (ApoE-/-) mice. To this end, we compared its effect with that of calcitriol.

Cellular infiltrates and NFκB subunit c-Rel signaling in kidney allografts of patients with clinical operational tolerance.

Background: Nuclear factor kappa B (NFκB) plays a potential role in tolerance by orchestrating onset and resolution of inflammation and regulatory T cell differentiation through subunit c-Rel. We characterized cellular infiltrates and expression of NFκB1, c-Rel and its upstream regulators phosphatidylinositol 3-kinase/RAC-alpha serine/threonine kinase, in allograft biopsies from patients with spontaneous clinical operational tolerance (COT).

Methods: Paraffin-fixed kidney allograft biopsies from 40 patients with COT (n=4), interstitial rejection (IR; n=12), borderline changes (BC; n=12), and long-term allograft function without rejection (NR; n=12) were used in the study.

High salt intake causes adverse fetal programming--vascular effects beyond blood pressure.

Background: High salt intake causes hypertension, adverse cardiovascular outcomes and potentially also blood pressure (BP)-independent target organ damage. Excess salt intake in pregnancy is known to affect BP in the offspring. The present study was designed to assess whether high salt intake in pregnancy affects BP and vascular morphology in the offspring.

Estrogen receptor alpha expression in podocytes mediates protection against apoptosis in-vitro and in-vivo.

Context/objective: Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes.

Both high and low maternal salt intake in pregnancy alter kidney development in the offspring.

In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.

Spontaneous arterial dissection: phenotype and molecular pathogenesis.

Arterial dissection (AD) is defined as the longitudinal splitting up of the arterial wall caused by intramural bleeding. It can occur as a spontaneous event in all large and medium sized arteries. The histological hallmark of AD is medial degeneration.