Addition of ET(A) receptor blockade increases renoprotection provided by renin-angiotensin system blockade in 5/6 nephrectomized Ren-2 transgenic rats.

Aims: There is evidence that in addition to hypertension and hyperactivity of the renin-angiotensin system (RAS), enhanced intrarenal activity of endothelin (ET) system contributes to the pathophysiology and progression of chronic kidney disease (CKD). This prompted us to examine if this progression would be alleviated by addition of type A ET receptor (ETA) blockade to the standard blockade of RAS.

Main Methods: Ren-2 transgenic rats (TGR) after 5/6 renal ablation (5/6 NX) served as a model of CKD.

Cell-free nucleic acids as biomarkers in dialyzed patients.

In this review, we discuss the origin, possible biological meaning, quantitative and qualitative changes in the concentrations of cell-free nucleic acids in human circulation with regard to renal failure and the process of dialysis. We focus on the inflammatory response and apoptosis known to be in close relationship not only with hemodialysis but also with different comorbidities frequently detected in hemodialyzed patients. 
Hemodialysis itself is able to promote the changes in the quantity and quality of circulating nucleic acid pool, but large spectrum of comorbidities in hemodialyzed subjects can further complicate the interpretations of results of cell-free nucleic acid analysis.

Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.

Placental growth factor, pregnancy-associated plasma protein-A, soluble receptor for advanced glycation end products, extracellular newly identified receptor for receptor for advanced glycation end products binding protein and high mobility group box 1 levels in patients with acute kidney injury: a cross sectional study.

Background: Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). However, their clinical significance in acute kidney injury (AKI) is unknown. The aim of this cross-sectional study was to determine whether selected biomarkers are changed in AKI patients.

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer.

Endothelial activation and dysfunction may play a significant role in the progression of breast cancer. In our study we examined markers of endothelial activation (soluble ICAM-1, P-selectin, E-selectin) in 98 young patients with breast cancer (< 40 years). In 50 of them (and 20 age-matched controls) we also measured flow mediated vasodilation.

Mutational analysis of ACTN4, encoding α-actinin 4, in patients with focal segmental glomerulosclerosis using HRM method.

α-Actinin 4, encoded by ACTN4, is an F-actin crosslinking protein which belongs to the spectrin gene superfamily. It has a head-to-tail homodimer structure with three main domains. Mutations in ACTN4 are associated with idiopathic nephrotic syndrome (NS).

Placental growth factor may predict increased left ventricular mass index in patients with mild to moderate chronic kidney disease--a prospective observational study.

Background: Placental growth factor [PlGF) is a cardiovascular (CV) risk marker, which is related to left ventricle hypertrophy (LVH) in animal models. Currently there are no data available regarding the possible relationship of PlGF and the development of LVH or diastolic dysfunction in patients with chronic kidney disease (CKD) and the relationship of PlGF to other CV risk factors in CKD patients. The aim of our study was to determine the possible association of PlGF and several other CV risk markers to echocardiographic parameters in CKD population.

[Hypertension in patients with polycystic kidney disease - incidence, pathogenesis, prognosis, therapy].

Hypertension is common in patients with autosomal dominant polycystic kidney disease (ADPKD) very early usually already in adolescence and its occurrence precedes the decrease of glomerular filtration rate. Expansion of renal cysts causing local renal ischemia and activation of the reninangiotensin system is believed to play a decisive role in its pathogenesis. Hypertension in ADPKD leads to early development of left ventricle hypertrophy and definitely contributes to the progression of chronic renal insufficiency.

Recent insights into the pathogenesis of nephrotic syndrome.

Nephrotic syndrome is characterized by heavy proteinuria followed by hypoproteinemia, hypercholestrolemia, lipiduria, and edema. The glomerular filtration barrier (GFB) consists of glomerular endothelial cells covered with glycocalyx, the basement membrane, subpodocyte space and podocytes with foot processes and slit membranes between them. The coordinated function of GFB has been considered to be the major barrier against filtration of plasma proteins to urine.

ANCA-associated renal vasculitis - an update.

ANCA-associated vasculitis (AAV) is a potentially life-threatening disease with frequent and often severe kidney involvement which may result in end-stage renal disease. Anti-PR3 and anti-MPO disease are genetically distinct diseases and may have a different pathogenesis. Recent discovery of new autoantibodies (anti-LAMP-2) and the role of complement activation in the pathogenesis of AAV could result in better monitoring of the activity of the disease and identification of new treatment targets.

Proteinuria and hypertension in patients treated with inhibitors of the VEGF signalling pathway--incidence, mechanisms and management.

Anti-VEGF therapy dramatically improved the outcome of patients with renal cancer and other advanced malignancies, but may be complicated by proteinuria and hypertension. VEGF is indispensable for the normal development of glomerulus and preservation of glomerular filtration barrier. Interference with its action may result in damage to glomerular endothelial cells and (in severe cases) in renal thrombotic microangiopathy.

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations.

Long-term outcome of severe alveolar haemorrhage in ANCA-associated vasculitis: a retrospective cohort study.

Objectives: Alveolar haemorrhage (AH) is a major cause of early death in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There is a paucity of information regarding the outcomes of AAV patients presenting with severe AH.

Method: A retrospective cohort study.

The coincidence of IgA nephropathy and Fabry disease.

Background: IgA nephropathy (IgAN) is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD).

Case Presentation: A 26 year-old man underwent a renal biopsy in February 2001.

The protective effects of erythropoietin on rat glomerular podocytes in culture are modulated by extracellular matrix proteins.

Background/aims: Podocytes are typically cultured on collagen I; however, collagen I is absent from healthy glomerular basement membranes. Erythropoietin (EPO) is thought to protect podocytes in vivo. Here, we studied how various types of extracellular matrix (ECM) proteins and EPO affect podocytes in culture.

Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy.

Background: Antibodies against M-type phospholipase A2 receptor (PLA2R) are serological markers of disease activity in patients with idiopathic membranous nephropathy (iMN). To determine the most sensitive test for the diagnosis of PLA2R-related membranous nephropathy (MN) irrespective of sampling time, we investigated the presence of PLA2R in glomerular immune deposits and assessed circulating anti-PLA2R antibodies in a retrospective cohort of Czech patients with idiopathic, lupus and other few secondary MN.

Methods: We tested archival paraffin-embedded kidney biopsies of 84 consecutive patients with biopsy-proven MN, for the presence of PLA2R in glomerular immune deposits and we measured circulating anti-PLA2R antibodies using the indirect immunofluorescence test, all reagents being commercially available.

TRPC6 gene variants in Czech adult patients with focal segmental glomerulosclerosis and minimal change disease.

Blood filtration and formation of primary urine in the kidney glomerulus is provided by a specialized membrane called slit diaphragm located between well-branched pedicels of podocytes. Actually, the slit diaphragm is a protein supercomplex, whose disruption can cause failure of renal filtration, and patients usually manifest nephrotic syndrome. Recently, familial forms of nephrotic syndrome have been described which arise from malfunction of mutated proteins making up the slit diaphragm.

Renalase, hypertension, and kidney - the discussion continues.

Hypertension and cardiovascular complications are very common in chronic kidney disease (CKD). Overactivation of sympathetic nervous system is also widely recognized in CKD. Renalase may play an important role in the control of blood pressure (BP) by its regulatory function of catecholamine metabolism.

Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis.

Objectives: To develop recommendations for the management of adult and paediatric lupus nephritis (LN).

Methods: The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus.

Serum cytokine profile in patients with active lupus nephritis.

Purpose: Determination of disease activity of lupus nephritis remains challenging. Since cytokines play a role as inflammatory mediators extending renal injury, measuring serum cytokine levels might help in the clinical assessment of patients with lupus nephritis. Therefore, the aim of this study was to determine the diagnostic value of a panel of serum cytokines in patients with active lupus nephritis.

Genetically distinct subsets within ANCA-associated vasculitis.

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis.

Recent news in the treatment of lupus nephritis.

Patient survival and renal survival of patients with lupus nephritis improved, but still in a significant proportion of patients the disease progresses to end-stage renal failure, possibly at least partly due to slow and incomplete response to induction treatment and high relapse rate on the maintenance treatment. Mycophenolate mofetil was recently demonstrated to be a comparably effective and safe induction treatment of lupus nephritis as high-dose cyclophosphamide pulses, in Caucasian patients it has become a reasonable alternative to low-dose cyclophosphamide pulses according to the EUROLUPUS protocol. Mycophenolate was shown to be more effective than azathioprine in the maintenance treatment and is currently the treatment of choice for this phase of the disease.

Determinants of circulating matrix metalloproteinase-2 and pregnancy-associated plasma protein-A in patients with chronic kidney disease.

Background: Matrix metalloproteinase-2 (MMP-2) and pregnancy-associated plasma protein-A (PAPP-A) have been implicated in chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the serum determinants of MMP-2 and PAPP-A in CKD are unknown. The aim of the present study is to evaluate the clinical significance of MMP-2 and PAPP-A and their determinants in patients with CKD.

Changes in levels of matrix metalloproteinase-2 and -9, pregnancy-associated plasma protein-A in patients with various nephropathies.

Background: Specific changes and imbalanced concentrations of matrix metalloproteinases (MMPs) and pregnancy-associated plasma protein-A (PAPP-A) may reflect the pathophysiology of various nephropathies (GN). We compared MMP-2, MMP-9 and PAPP-A levels in patients with GN, with those found in healthy controls.

Methods: We studied 45 controls and 128 patients with GN, defined by kidney biopsy: IgA nephropathy (IgAN, n=33), membranous glomerulonephritis (MN, n=23), minimal change nephrotic syndrome (MCNS, n=7), focal segmental glomerular sclerosis (FSGS, n=11), lupus nephritis (LN, n=22) and ANCA-associated glomerulonephritis (AAV, n=32).