Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice.

Lipoprotein glomerulopathy (LPG) is a renal disease often accompanied by dyslipidemia and increased serum apoE levels. apoESendai (Arg145Pro), a rare mutant based on the apoE3 sequence carrying an apoE2 charge, causes LPG in humans and transgenic mice, but its effects on the artery wall are unknown. Macrophage expression of apoESendai may also directly influence renal and arterial homeostasis.

Autopsy Renal Pathology.

We provide an overview of assessment of the kidneys at autopsy, with special considerations for pediatric versus adult kidneys. We describe the approach to gross examination, tissue allocation when needed for additional studies of potential medical renal disease, the spectrum of congenital abnormalities of the kidneys and urinary tract, and approach to cystic diseases of the kidney. We also discuss common lesions seen at autopsy, including acute tubular injury, ischemic versus toxic contributions to this injury, interstitial nephritis, and common vascular diseases.

Mechanisms of disease reversal in focal and segmental glomerulosclerosis.

It is well known that progression of chronic kidney disease can be ameliorated or stabilized by different interventions, but more studies indicate that it can even be reversed. Most data suggest that current therapy, especially renin-angiotensin system inhibition alone, is not sufficient to initiate and maintain long-term regression of glomerular structural injury. In this article, we review the potential reversal of glomerulosclerosis and evidence from both human and animal studies.

Kidney regeneration in mammals.

Background: Several organs such as the skin and liver have a great capacity for regeneration. However, many approaches only delay the progression of end-stage kidney disease and do not achieve efficient long-term stabilization, let alone regeneration.

Summary: In mammals, the kidney has an innate but limited capacity for regeneration which can only modify the nephron structure and function but not increase the nephron number.

Expanding the phenotype of proteinuria in Dent disease. A case series.

Background: Dent disease is an X-linked recessive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure (MIM 300009). A recent case series identified four patients with CLCN5 mutations who presented with nephrotic-range proteinuria, histologic evidence of focal segmental and/or global sclerosis, and low molecular weight proteinuria.

Case-diagnosis/treatment: We characterize the clinical, genetic, and histopathological features of seven unrelated adolescent males with nephrotic-range proteinuria and CLCN5 mutations.

Leukocyte chemotactic factor 2 amyloidosis cannot be reliably diagnosed by immunohistochemical staining.

We investigated the role of leukocyte chemotactic factor (LECT2) immunohistochemical staining in the diagnosis of type of renal amyloidosis. Fifty renal amyloidosis cases with available paraffin blocks in our 2002 to 2012 renal biopsy files were reviewed. Patients were designated as a defined amyloid, including amyloid light chain (AL) and amyloid-associated amyloid (AA), or a non-AL/non-AA amyloid group.

Vitronectin-binding PAI-1 protects against the development of cardiac fibrosis through interaction with fibroblasts.

Plasminogen activator inhibitor-1 (PAI-1) promotes or abates fibrotic processes occurring in different organs. Binding of PAI-1 to vitronectin, an extracellular matrix component, may inhibit vitronectin-integrin complex-mediated cellular responses in pathophysiological conditions. To investigate the importance of plasmin suppression vs vitronectin-binding pathways of PAI-1 in cardiac fibrosis, we studied uninephrectomized mice fed a high salt diet and infused with angiotensin II (Ang II) together with different PAI-1 variants, including PAI-1AK (AK) that inhibits plasminogen activators but does not bind vitronectin, PAI-1RR (RR) that binds vitronectin but does not have protease inhibitory effects or control PAI-1 (CPAI), the control mutant that has similar molecular backbone and half-life as AK and RR while retaining all functions of native PAI-1.

Immunopathology of lupus nephritis.

When patients with systemic lupus erythematosus (SLE) present with urinary abnormalities, a renal biopsy is usually needed to rule out or confirm lupus nephritis. Renal biopsy is also needed to define the type of renal manifestation as different entities are associated with different outcomes; hence, renal biopsy results shape lupus management. But why does lupus nephritis come in different shapes? Why do patients with SLE often show change over time in class of lupus nephritis or have mixed forms? How does autoimmunity in SLE evolve? Why does loss of tolerance against nuclear antigens preferentially affect the kidney? Why are immune complex deposits in different glomerular compartments associated with different outcomes? What determines crescent formation in lupus? In this review, we discuss these questions by linking the latest information on lupus pathogenesis into the context of the different classes of lupus nephritis.

C3 glomerulopathy: consensus report.

C3 glomerulopathy is a recently introduced pathological entity whose original definition was glomerular pathology characterized by C3 accumulation with absent or scanty immunoglobulin deposition. In August 2012, an invited group of experts (comprising the authors of this document) in renal pathology, nephrology, complement biology, and complement therapeutics met to discuss C3 glomerulopathy in the first C3 Glomerulopathy Meeting. The objectives were to reach a consensus on: the definition of C3 glomerulopathy, appropriate complement investigations that should be performed in these patients, and how complement therapeutics should be explored in the condition.

AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function.

Diabetic microvascular complications have been considered to be mediated by a glucose-driven increase in mitochondrial superoxide anion production. Here, we report that superoxide production was reduced in the kidneys of a steptozotocin-induced mouse model of type 1 diabetes, as assessed by in vivo real-time transcutaneous fluorescence, confocal microscopy, and electron paramagnetic resonance analysis. Reduction of mitochondrial biogenesis and phosphorylation of pyruvate dehydrogenase (PDH) were observed in kidneys from diabetic mice.

Low nitric oxide bioavailability upregulates renal heparin binding EGF-like growth factor expression.

Decreased nitric oxide bioavailability has an important role in the initiation and progression of diabetic nephropathy, but the underlying mechanisms remain unclear. Here, we found that heparin-binding epidermal growth factor-like growth factor (HB-EGF) expression levels increased in the kidneys of both endothelial nitric oxide synthase (eNOS)-knockout and eNOS-knockout diabetic (Lepr(db/db)) mice as early as at 8 weeks of age. Further increases in expression were only seen in eNOS-knockout diabetic mice and paralleled the progression of glomerulopathy.

Thymosin β4 and its degradation product, Ac-SDKP, are novel reparative factors in renal fibrosis.

Previously, we found thymosin β4 (Tβ4) is upregulated in glomerulosclerosis and required for angiotensin II-induced expression of plasminogen activator inhibitor-1 (PAI-1) in glomerular endothelial cells. Tβ4 has beneficial effects in dermal and corneal wound healing and heart disease, yet its effects in kidney disease are unknown. Here we studied renal fibrosis in wild-type and PAI-1 knockout mice following unilateral ureteral obstruction to explore the impact of Tβ4 and its prolyl oligopeptidase tetrapeptide degradation product, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), in renal fibrosis.

AKI in an HIV patient.

The renal manifestations of patients infected with HIV are diverse. Patients may have podocytopathies ranging from a minimal-change-type lesions to FSGS or collapsing glomerulopathy. Furthermore, such patients produce a variety of autoantibodies without clinical signs of the disease.

Immune complex disease with a lupus-like pattern of deposition in an antinuclear antibody-negative patient.

Immune complex-mediated glomerulonephritis can be caused by a multitude of disease processes and may manifest in a variety of histologic patterns. Lupus nephritis is an immune complex disease, the diagnosis of which requires that the affected patient have systemic lupus erythematosus (SLE). In the absence of SLE, the finding of glomerulonephritis with certain patterns of immune complex deposition characteristic of lupus nephritis has been referred to as lupus-like glomerulonephritis.

mVps34 deletion in podocytes causes glomerulosclerosis by disrupting intracellular vesicle trafficking.

Recent studies have suggested that autophagy is a key mechanism in maintaining the integrity of podocytes. The mammalian homologue of yeast vacuolar protein sorting defective 34 (mVps34) has been implicated in the regulation of autophagy, but its role in podocytes is unknown. We generated a line of podocyte-specific mVps34-knockout (mVps34(pdKO)) mice, which were born at Mendelian ratios.

Association of histologic variants in FSGS clinical trial with presenting features and outcomes.

Background And Objectives: FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS.

Design, Setting, Participants, & Measurements: Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists.

Validation of the Oxford classification of IgA nephropathy for pediatric patients from China.

Background: The Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations.

Methods: A total of 218 children with IgAN from 7 renal centers in China were enrolled.

Dysfunctional high-density lipoprotein in patients on chronic hemodialysis.

Objectives: This study examined the functionality of high-density lipoprotein (HDL) in individuals with end-stage renal disease on dialysis (ESRD-HD).

Background: The high rate of cardiovascular disease (CVD) in chronic kidney disease is not explained by standard risk factors, especially in patients with ESRD-HD who appear resistant to benefits of statin therapy. HDL is antiatherogenic because it extracts tissue cholesterol and reduces inflammation.

Lupus nephritis: is the kidney biopsy currently necessary in the management of lupus nephritis?

Most patients with SLE develop kidney disease related to this systemic underlying disease process. Lupus nephritis is an important cause of morbidity and even mortality in patients with systemic lupus erythematosus. Lupus nephritis has diverse morphologic manifestations with varying clinical presentations and consequences.

Renal biopsy findings among Indigenous Australians: a nationwide review.

Australia's Indigenous people have high rates of chronic kidney disease and kidney failure. To define renal disease among these people, we reviewed 643 renal biopsies on Indigenous people across Australia, and compared them with 249 biopsies of non-Indigenous patients. The intent was to reach a consensus on pathological findings and terminology, quantify glomerular size, and establish and compare regional biopsy profiles.

Parietal epithelial cell activation marker in early recurrence of FSGS in the transplant.

Background And Objectives: Podocyte loss is key in glomerulosclerosis. Activated parietal epithelial cells are proposed to contribute to pathogenesis of glomerulosclerosis and may serve as stem cells that can transition to podocytes. CD44 is a marker for activated parietal epithelial cells.

A canine autosomal recessive model of collagen type III glomerulopathy.

Collagen type III glomerulopathy (Col3GP) is a rare renal disease characterized by massive glomerular accumulations of collagen type III. The disease occurs in both humans and animals, and has been presumed to be heritable with an autosomal recessive inheritance pattern. The pathogenesis is unknown.