Kidney Injury by Unilateral Ureteral Obstruction in Mice Lacks Sex Differences.

Introduction: Renal fibrosis is a critical event in the development and progression of chronic kidney disease (CKD), and it is considered the final common pathway for all types of CKD. The prevalence of CKD is higher in females; however, males have a greater prevalence of end-stage renal disease. In addition, low birth weight and low nephron number are associated with increased risk for CKD.

Salt-sensitive hypertension after reversal of unilateral ureteral obstruction.

The incidence of ureter obstruction is increasing and patients recovering from this kidney injury often progress to chronic kidney injury. There is evidence that a long-term consequence of recovery from ureter obstruction is an increased risk for salt-sensitive hypertension. A reversal unilateral ureteral obstruction (RUUO) model was used to study long-term kidney injury and salt-sensitive hypertension.

Lack of xanthine dehydrogenase leads to a remarkable renal decline in a novel hypouricemic rat model.

Uric acid (UA) is the final metabolite in purine catabolism in humans. Previous studies have shown that the dysregulation of UA homeostasis is detrimental to cardiovascular and kidney health. The gene encodes for the Xanthine Oxidoreductase enzyme group, responsible for producing UA.

Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension.

Hypertension and kidney disease have been repeatedly associated with genomic variants and alterations of lysine metabolism. Here, we combined stable isotope labeling with untargeted metabolomics to investigate lysine's metabolic fate in vivo. Dietary C labeled lysine was tracked to lysine metabolites across various organs.

Long-term kidney function and survival in recipients of allografts from living kidney donors with hypertension: a national cohort study.

Allografts from living kidney donors with hypertension may carry subclinical kidney disease from the donor to the recipient and, thus, lead to adverse recipient outcomes. We examined eGFR trajectories and all-cause allograft failure in recipients from donors with versus without hypertension, using mixed-linear and Cox regression models stratified by donor age. We studied a US cohort from 1/1/2005 to 6/30/2017; 49 990 recipients of allografts from younger (<50 years old) donors including 597 with donor hypertension and 21 130 recipients of allografts from older (≥50 years old) donors including 1441 with donor hypertension.

p66Shc-mediated hydrogen peroxide production impairs nephrogenesis causing reduction of number of glomeruli.

Aims: Adaptor protein p66Shc, encoded by Shc1 gene, contributes to the pathogenesis of oxidative stress-related diseases. p66Shc ability to promote oxidative stress-related diseases requires phosphorylation of serine 36 residue (Ser36) and depends on translocation of p66Shc to the mitochondria. We tested the hypothesis that abnormal p66Shc-mediated reactive oxygen species (ROS) production could be critically involved in nephrons development during nephrogenesis.

Role of opioid signaling in kidney damage during the development of salt-induced hypertension.

Opioid use is associated with predictors of poor cardiorenal outcomes. However, little is known about the direct impact of opioids on podocytes and renal function, especially in the context of hypertension and CKD. We hypothesize that stimulation of opioid receptors (ORs) contributes to dysregulation of intracellular calcium ([Ca]) homeostasis in podocytes, thus aggravating the development of renal damage in hypertensive conditions.

Upregulated proteoglycan-related signaling pathways in fluid flow shear stress-treated podocytes.

The ultrafiltrate flow over the major processes and cell body generates fluid flow shear stress (FFSS) on podocytes. Hyperfiltration-associated increase in FFSS can lead to podocyte injury and detachment. Previously, we showed that FFSS-induced upregulation of the cyclooxygenase 2 (COX2)-PGE-prostaglandin E receptor 2 (EP2) axis in podocytes activates Akt-glycogen synthase kinase-3β-β-catenin and MAPK/ERK signaling in response to FFSS.

Urinary prostaglandin E is a biomarker of early adaptive hyperfiltration in solitary functioning kidney.

Introduction: Hyperfiltration is a major contributor to progression of chronic kidney disease (CKD) in diabetes, obesity and in individuals with solitary functioning kidney (SFK). We have proposed hyperfiltration-induced injury as a continuum of overlapping glomerular changes caused by increased biomechanical forces namely, fluid flow shear stress (FFSS) and tensile stress. We have shown that FFSS is elevated in animals with SFK and, it upregulates prostaglandin E (PGE), cyclooxygenase-2 and PGE receptor EP2 in cultured podocytes and in uninephrectomized mice.

Vibrodissociation method for isolation of defined nephron segments from human and rodent kidneys.

Our current knowledge of the properties of renal ion channels responsible for electrolytes and cell energy homeostasis mainly relies on rodent studies. However, it has not been established yet to what extent their characteristics can be generalized to those of humans. The present study was designed to develop a standardized protocol for the isolation of well-preserved glomeruli and renal tubules from rodent and human kidneys and to assess the functional suitability of the obtained materials for physiological studies.

Improving sensitivity of amyloid detection by Congo red stain by using polarizing microscope and avoiding pitfalls.

Systemic amyloidosis is a devastating group of disorders for which there is no current cure. The treatment goal is to reduce the burden of amyloidogenic protein precursors. The treatment is only effective if applied early in the disease process before significant and irreversible end organ damage has taken place.

IgM nephropathy - Successful treatment with rituximab.

Immunoglobulin M nephropathy (IgMN) is a primary glomerulonephritis which is characterized by variable degrees of morphological features ranging from minimal glomerular involvement to segmental or global sclerosis. No specific treatment is known to date for this disease because of uncertainties in etiopathogenesis. The mainstay treatment for this disease has been corticosteroids, which has varying degrees of resistance ranging from 0% to 50%.

Hyperfiltration-mediated Injury in the Remaining Kidney of a Transplant Donor.

Kidney donors face a small but definite risk of end-stage renal disease 15 to 30 years postdonation. The development of proteinuria, hypertension with gradual decrease in kidney function in the donor after surgical resection of 1 kidney, has been attributed to hyperfiltration. Genetic variations, physiological adaptations, and comorbidities exacerbate the hyperfiltration-induced loss of kidney function in the years after donation.

Mechanotransduction signaling in podocytes from fluid flow shear stress.

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE-PGE receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes.

Role of biomechanical forces in hyperfiltration-mediated glomerular injury in congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood.

Mechanisms of BK virus infection of renal cells and therapeutic implications.

BK virus (BKV) causes BKV nephritis in renal transplant patients and contributes significantly to the increase of probability of graft loss. BKV, being latent in the urogenital tract, is likely to be transported with the donor kidney to recipients and following reactivation replicates in the nucleus of renal epithelial tubular cells. BKV daughter viruses are released and enter other renal epithelial cells to spread infection.

Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis.

Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding.

Fluid flow shear stress upregulates prostanoid receptor EP2 but not EP4 in murine podocytes.

Podocytes in the glomerular filtration barrier regulate the passage of plasma proteins into urine. Capillary pressure and ultrafiltration impact the structure and function of podocytes. The mechanism of podocyte injury by fluid flow shear stress (FFSS) from hyperfiltration in chronic kidney disease (CKD) is not completely understood.

Identification of nephropathy candidate genes by comparing sclerosis-prone and sclerosis-resistant mouse strain kidney transcriptomes.

Background: The genetic architecture responsible for chronic kidney disease (CKD) remains incompletely described. The Oligosyndactyly (Os) mouse models focal and segmental glomerulosclerosis (FSGS), which is associated with reduced nephron number caused by the Os mutation. The Os mutation leads to FSGS in multiple strains including the ROP-Os/+.

Short-term exposure to tobacco toxins alters expression of multiple proliferation gene markers in primary human bronchial epithelial cell cultures.

The biological effects of only a finite number of tobacco toxins have been studied. Here, we describe exposure of cultures of human bronchial epithelial cells to low concentrations of tobacco carcinogens: nickel sulphate, benzo(b)fluoranthene, N-nitrosodiethylamine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). After a 24-hour exposure, EGFR was expressed in cell membrane and cytoplasm, BCL-2 was expressed only in the irregular nuclei of large atypical cells, MKI67 was expressed in nuclei with no staining in larger cells, cytoplasmic BIRC5 with stronger nuclear staining was seen in large atypical cells, and nuclear TP53 was strongly expressed in all cells.

Recombinant Schistosoma mansoni 3-hydroxymethylglutaryl-coenzyme-A reductase has different inhibitor kinetics compared to the mammalian host enzyme.

Previous publications have clearly demonstrated that hydroxymethylglutaryl coenzyme A [HMG-CoA] reductase activity of Schistosoma mansoni is vital for parasite reproductive activity and that drugs which inhibit this enzyme have been found to be effective antischistosomal agents. In this report we describe the expression and purification of enzymatically active schistosome HMG-CoA reductase enzyme. The recombinant protein was tested, in parallel with the mammalian enzyme, against well-known mammalian HMG-CoA reductase inhibitors obtained from various pharmaceutical companies.

The African American Study of Kidney Disease: do these results indicate that 140/90 mm hg is good enough?

Current national guidelines recommend aggressive lowering of blood pressure (< 130/80 mm Hg) in patients with chronic kidney disease (CKD). In this paper, we summarize recent clinical trial data evaluating the effect of lower blood pressure goals on renal outcomes. The epidemiologic data relating blood pressure to progression of kidney disease, the Modification of Diet in Renal Disease (MDRD) study (in patients with > 1 g proteinuria/d), and meta-analyses of angiotensin-converting enzyme (ACE) inhibitor clinical trials all support lower blood pressure goals in CKD patients, particularly those with proteinuria.