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Biomedical subjects

R A K Stahl

Publications and source records attributed to R A K Stahl.

6 recordsLinked to original sources
PubMed2006

Antihypertensive therapy induces compartment-specific chemokine expression and a Th1 immune response in the clipped kidney of Goldblatt hypertensive rats.

The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 wk. The vasopeptidase inhibitor dose dependently lowered blood pressure. The tubulointerstitial damage was accompanied by a diffuse infiltration of mononuclear cells and circumscript mononuclear inflammatory cell cluster formation consisting mainly of T cells and to a lesser degree of macrophages and B cells. Real-time PCR analyses showed a dose-dependent induction of MCP-1 and the Th1-type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN-gamma. In situ hybridization and laser microdissection revealed a strong expression of these Th1-associated transcripts in the clusters and, in the case of MCP-1, also diffusely in the interstitium. The inflammation was accompanied by the appearance of myofibroblasts and synthesis of the fibrogenic factor plasminogen activator inhibitor-1 as well as the collagenase matrix metalloproteinase-2, leading to collagen I upregulation and interstitial scarring. No inflammation or fibrosis was found in normotensive rats treated with the vasopeptidase inhibitor. The renal injury in the clipped kidney is accompanied by compartment-specific chemokine expression and cell cluster formation of Th1 specificity associated with upregulation of fibrogenic proteins and matrix metalloproteinases. These findings suggest that the Th1 chemokines IP10 and Mig as well as their receptor CXCR3 are potential targets for therapeutic interventions in ischemic nephropathy.

Actins↗
PubMed2006

Statin therapy in patients with chronic kidney disease: to use or not to use.

Dyslipdemia is a common complication of chronic kidney disease (CKD) and contributes to high cardiovascular morbidity and mortality of CKD patients. Experimental studies have demonstrated that lipids induce glomerular and tubulointerstitial injury and that lipid-lowering treatments ameliorate renal injury. Therapy with statins not only has the potential to lower cardiovascular morbidity and mortality in patients with CKD but also to slow progression of renal disease. Whereas the guidelines for treatment of hyperlipidaemia in nonrenal patients are based on prospective, randomized, placebo-controlled mega-trials, such data are not available for CKD patients. This review outlines the limited information currently available on the effect of statins among patients with CKD and summarizes the ongoing randomized trials designed to address this question.

Cholesterol↗
PubMed2004

[Dysfunction of a kidney allograft with life-threatening results].

Post-transplant lymphoproliferative disease (PTLD) is a serious complication after organ transplantation. We describe the case of a 45-year old patient who developed an EBV associated B-cell lymphoma in a cadaveric renal allograft. This case underscores the importance of considering PTLD as possible differential diagnosis for allograft dysfunction. Careful diagnostic evaluation should be undertaken in patients who present with risk factors for development of PTLD such as high doses of immunosuppression for rejection therapy, suspicious EBV serologies or negative EBV serologies before transplantation. PTLD can be of donor or recipient origin. Independent of its origin PTLD needs an immediate therapy which depends on the histology of the lymphoma and on the clinical conditions of the patient. Therapeutic options are reduction of the immunosuppression, chemotherapy or radiation, administration of lymphocyte-specific antibodies or removal of the kidney allograft.

Diagnosis, Differential↗
PubMed2003

Erk 1,2 phosphorylates p27(Kip1): Functional evidence for a role in high glucose-induced hypertrophy of mesangial cells.

AIMS/HYPOTHESIS: Mesangial cell hypertrophy is one of the earliest morphological abnormalities of diabetic nephropathy. We have previously shown that high glucose induces p27(Kip1) by a post-transcriptional mechanism and that mesangial cell hypertrophy depends on G(1)-phase arrest mediated by this CDK-inhibitor. However, it remains poorly understood how high glucose stimulates p27(Kip1) expression in mesangial cells. METHODS: Mesangial cells were isolated from p27(Kip1) +/+ and -/- mice and characterized by light microscopy and immunohistochemistry. It was tested by Western blotting and autoradiography whether high glucose medium activates Erk 1,2 and whether this activation phosphorylates p27(Kip1). The three consensus phosphorylation sites of p27(Kip1) were mutated and these constructs were expressed in p27(Kip1) -/- mesangial cells. Hypertrophy was assessed by different methods. RESULTS: High glucose stimulates phosphorylation of MAP kinases Erk 1,2 in p27(Kip1 )+/+ and -/- mesangial cells. Activation of Erk 1,2 leads to phosphorylation of p27(Kip1 )in vitro and in vivo. Mutations of serine(10) or threonine(187) still supported high glucose-induced hypertrophy. In contrast, a mutation of serine(178) converted the hypertrophic response into a proliferative phenotype. Mutation of serine(178) leads to the attenuated expression of p27(Kip1) protein in the presence of high glucose. CONCLUSIONS/INTERPRETATION: Our study shows that high glucose stimulates Erk 1,2 that phosphorylate p27(Kip1) at serine(178) increasing its expression. This is an important molecular mechanism of high glucose-induced hypertrophy of mesangial cells.

Animals↗
PubMed2003

[Membranous glomerulonephritis].

Membranous nephropathy remains the most common cause of nephrotic syndrome in adults. The common variant is idiopathic membranous nephropathy with no evidence of any known precipitating factors. Membranous nephropathy also occurs as a secondary form in association with inflammatory or neoplastic diseases. Prognosis is mostly favorable as shown by the frequency of spontaneous remissions which averages 30%, although about one-third of patients progress to end-stage renal failure. Risk factors for a poor prognosis include severe proteinuria, hypertension, older age, male gender and impaired renal function. Therapy should include an ACE-Inhibitor and/or angiotensin-II receptor blocker to lower proteinuria (blood pressure < or =130/80 mmHg). The majority of patients should be observed for six months whilst receiving conservative treatment before deciding about an immunosuppressive approach. The debate over its management continues today. Steroids alone are ineffective. Evidence-based medicine supports the use of cyclosporine or the Ponticelli regimen (monthly cycling routine of chlorambucil or cyclophosphamide alternating with prednisone).

Age Factors↗