Coxsackie B viruses and the kidney—a neglected topic

Coxsackie B viruses types 1-6 (CVB1-6) occur worldwide and cause a broad spectrum of diseases, including myocarditis and aseptic meningitis. Although renal damage due to CVB has been suspected since the 1950s, these agents are only rarely searched for in today's clinical nephrological practice. Nevertheless, CVB can infect mesangial cells. Furthermore, infections with these viruses lead to a histological picture resembling mesangioproliferative glomerulonephritis and IgA-nephropathy in mice. In the present article, we provide an overview of this largely neglected topic, and of the slowly and steadily increasing evidence suggesting a link between coxsackieviral infections and kidney disease

Low prevalence of nonconservative mutations of serum and glucocorticoid-regulated kinase (SGK1) gene in hypertensive and renal patients

Background. The serum- and glucocorticoid-regulated kinase (SGK1) gene is an important mediator of aldosterone action, regulating the expression of the renal epithelial Na+ channel. In renal failure, blood pressure (BP) is markedly salt-dependent and increases with decreasing renal function. Mutations of the SGK1 gene affecting phosphorylation could be responsible for salt-mediated increases in BP and hypertension-related progression to end-stage renal disease (ESRD). Methods. The SGK1 gene was analysed for mutations in the exons 4, 5, 8 and 10-12, because of potential phosphorylation sites, in 591 subjects, including 311 ESRD patients (either dialysis or transplanted). In addition, an intron 6 single-nucleotide polymorphism (SNP) described previously was also investigated in this study. Genotyping was performed either by using a strategy based on single strand conformation polymorphism analysis of polymerase chain reaction (PCR) products and subsequent direct sequencing of identified gel shift variants or by using high throughput 5′ nuclease allelic discrimination assay. Results. Two SNPs in coding regions of SGK1 potentially influencing the phosphorylation of Sgk1 were identified. Both SNPs were synonymous. The prevalence of the first variant, a previously reported SNP at codon 240 in exon 8, did not differ between ESRD patients (16.3%) and controls (15.7%). There was no association between the SNP in exon 8 and either BP within the control population or progression of renal disease in the ESRD population. The second SNP at codon 398 in exon 12 was identified in one patient only. Intron 6 and exon 8 SNPs were in strong linkage disequilibrium, but did not show any association with either BP or renal diseases. Conclusions. Based on statistical analysis homozygosity for nonconservative mutations in the coding region of the SGK1 gene is estimated at < 1/300 000 when a white Caucasian population is considered, arguing against an important role of mutations of this coding region in hypertension and hypertension-associated progression of renal diseas

Risk of Infectious Complications in Patients Taking Glucocorticosteroids

The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3-1.9; P 1; P = .03) diseases. The rate was not increased in patients given a daily dose of <10 mg or a cumulative dose of <700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practic

Statics and Dynamics of the Wormlike Bundle Model

Bundles of filamentous polymers are primary structural components of a broad range of cytoskeletal structures, and their mechanical properties play key roles in cellular functions ranging from locomotion to mechanotransduction and fertilization. We give a detailed derivation of a wormlike bundle model as a generic description for the statics and dynamics of polymer bundles consisting of semiflexible polymers interconnected by crosslinking agents. The elastic degrees of freedom include bending as well as twist deformations of the filaments and shear deformation of the crosslinks. We show that a competition between the elastic properties of the filaments and those of the crosslinks leads to renormalized effective bend and twist rigidities that become mode-number dependent. The strength and character of this dependence is found to vary with bundle architecture, such as the arrangement of filaments in the cross section and pretwist. We discuss two paradigmatic cases of bundle architecture, a uniform arrangement of filaments as found in F-actin bundles and a shell-like architecture as characteristic for microtubules. Each architecture is found to have its own universal ratio of maximal to minimal bending rigidity, independent of the specific type of crosslink induced filament coupling; our predictions are in reasonable agreement with available experimental data for microtubules. Moreover, we analyze the predictions of the wormlike bundle model for experimental observables such as the tangent-tangent correlation function and dynamic response and correlation functions. Finally, we analyze the effect of pretwist (helicity) on the mechanical properties of bundles. We predict that microtubules with different number of protofilaments should have distinct variations in their effective bending rigidity

The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism

Background. Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroidectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. Methods. A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 µmol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. Results. On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72±0.03 mmol/l; 1 month 2.42±0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. Conclusion. Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculo-skeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patient