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Hantaviruses belong to the so-called emerging pathogens that are transmitted to humans by infected rodents and their excreta. In Central Europe, hantavirus infections usually occur in a mild to moderate form of hemorrhagic fever with renal syndrome. In contrast to the mostly benign or even asymptomatic course of hantavirus infections in previously healthy individuals, the acute hantavirus infection in kidney transplant recipients represents an exceptional situation regarding diagnosis and therapy. We describe the case of a 44-year-old kidney transplant recipient with acute renal transplant failure associated with acute hantavirus infection. [ABSTRACT FROM AUTHOR]

The article presents the clinical case of a patient who experienced massive bleeding after biopsy of a renal allograft. Digital subtraction angiography using gadolinium was immediately performed. An intragraft active bleeding that also involved the renal pelvis is detected. The patient's condition stabilized after embolization of two small peripheral intrarenal arteries using four endovascular microcoils.

Objective: Early pathophysiological changes like effacement of podocyte footprocesses are importent for the outcome of inflammatory kidney diseases. An increasing number of data provides evidence that genetic factors are involved in inititation and progress of inflammatory kidney diseases. Podocin is one of the structural proteins of the slit membrane, the important filtration barrier of the kidney. Adequate regulation of podocin is essential for stability and regeneration of the filtration barrier. In situ hybridisation studies in several glomerular diseases showed different patterns of glomerular podocin expression. These results lead to the hypothesis that transcriptional regulation might play an important role in the origin of certain kidney diseases. Several mutations in the coding region of the human podocin gene have been described. Whether mutations in the 5′ regulatory region of this gene are also involved in origin and progress of kidney diseases with nephrotic proteinuria is currently unknown. Methods: Genomic DNA of 40 healthy blood donors was screened for polymorphisms in the human podocin promoter. Several polymorphisms were identified and genomic DNA from kidney biopsies of patients with kidney diseases with nephrotic syndrome were screened for these polymorphisms with PCR and restriction digest. The 5′ regulatory region of the human podocin gene was tested for functional changes induced by the polymorphisms and screened for further transcriptional elements with reporter gene constructs and gel shift analyses of HEK293 cells and podocytes. Results: Two C/T transitions were identified at bp-116 and -670. The frequency of the homozygeous T variant in position -670 was equal for healthy blood donors and patients with minimal change nephritis. Patients with membranous glomerulonephritis or FSGS displayed the homozygeous and heterozygous T variant significantly more frequently. Functional studies in podocytes and HEK293 cells showed strong binding of nuclear proteins from differentiated podocytes at position -116 and a loss of protein binding to the T variant in position -670 of nuclear proteins from undifferentiated podocytes. HEK293 cells showed reduced binding of nuclear proteins to the T variant at -116 and decreased luciferase activity. Strong enhancer activity was observed between bp-870 and -800. Within this region the binding of several nuclear proteins was found which displayed different patterns for HEK293 cells and podocytes. Silencing activity was observed between bp-1306 and -1181 which completely knocked out luciferase expression in HEK293 cells. Conclusions: Within the human podocin promoter a strong enhancer and silencer region were characterised which regulate podocin expression in a cell-specific manner. Two functional promoter polymorphisms were identified within the human podocin promoter. They showed significant differences in frequency for several glomerular diseases with nephrotic syndrome. Further investigations will provide information whether these polymorphisms are also correlated with progression of the different diseases. [ABSTRACT FROM AUTHOR]

Membranous nephropathy with nephrotic syndrome occurred in a patient with anterior myocardial infarction 2 months after the start of clopidogrel treatment. Sensitisation by prior treatment with ticlopidine is discussed. [ABSTRACT FROM AUTHOR]

The C57BL/6 mouse strain serves as the genetic background of many transgenic and gene knockout models; however, this strain appears to be resistant to hypertension-induced renal injury. We developed a new model of hypertensive end-organ damage in C57BL/6 mice by combining deoxycorticosterone acetate (DOCA) and salt with angiotensin II infusion. The systolic blood pressure (SBP) was significantly elevated in DOCA salt–angiotensin II mice compared to control mice or mice treated individually with DOCA salt or angiotensin II. Hypertensive glomerular damage, increased expression of profibrotic and inflammatory genes, albuminuria, tubular casts, increased plasma cholesterol, cardiac hypertrophy, and fibrosis were found in mice treated with DOCA salt–angiotensin II. The SBP in the angiotensin II-infused group was further increased by increasing the infusion rate; only mild injury was observed in these mice, suggesting that blood pressure was not a causal factor. Removal of DOCA and the angiotensin pump lowered blood pressure to normal; however, albuminuria along with the glomerular and cardiac damage did not completely resolve. Our study describes a new model of hypertensive end-organ damage and repair in C57BL/6 mice.Kidney International (2008) 73, 643–650; doi:10.1038/sj.ki.5002689; published online 21 November 2007 [ABSTRACT FROM AUTHOR]

A 2-year-old boy who developed hypophosphatemic rickets without signs of muscular weakness or neurological disturbances is presented. Biochemical findings included hypophosphatemia, metabolic acidosis, hypouricemia, hyperphosphaturia, severe glucosuria, generalized hyperaminoaciduria, hypercalciuria, proteinuria with elevated excretion of IgG, transferrin, albumin and high levels of α-1-microglobulin. Urine concentration capacity and creatinine clearance were normal. Lactaturia without elevated levels of plasma lactate and a high urinary excretion of β-hydroxybutyrate were suggestive for mitochondriopathy. Partial deficiency of cytochrome c oxidase (complex IV of the respiratory chain) was found in skeletal muscle. A renal biopsy specimen demonstrated enlarged mitochondria with abnormal arborization and disorientation of the cristae in the proximal tubular cells. Reduced activity of mitochondrial cytochrome c oxidase in tubular cells could be demonstrated by ultracytochemistry. In conclusion, rickets due to the renal Fanconi syndrome can be the first clinical sign of mitochondrial cytopathies without extrarenal symptoms. Elevated excretion of lactate and ketone bodies in urine may serve as a diagnostic marker. [ABSTRACT FROM AUTHOR]

Objective: The infiltration of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases affecting the endothelium such as glomerulonephritis, thrombotic angiopathies, allogaft rejection and vasculitis. Chemokines are the chemotactic cytokines considered to be the main regulators of leukocyte trafficking under inflammatory conditions. The aim of our study was to analyze the expression and function of the chemokine IP-10/CXCL10 (acting via CXCR3 on activated T cells) in a rat model of renal microvascular endothelial injury. Methods: Renal microvascular endothelial injury was induced in rats by selective renal artery perfusion with anti-endothelial-antibody (Kidney Int 97, Johnson et al). Chemokine expression (Real time-PCR and in situ hybridization), T cell and monocyte infiltration (immunohistochemistry and FACS analysis) and serum creatinine/urea levels were assessed 24 h and 4 days after disease induction. To analyze the functional role of IP-10/CXCL10, rats were treated with a characterized neutralizing anti IP-10 antibody following induction of the endothelial injury. Results: Induction of microvascular endothelial injury increased renal IP-10/CXCL10 expression at 24 h (117-fold) and 4 days (5-fold). In situ hybridization revealed that IP-10/CXCL10 RNA is selectively expressed in the tubulointerstitial area (mainly by endothelial cells), co-localizing with infiltrating T cells. Treatment with a neutralizing anti IP-10/CXCL10 antibody significantly reduced the number of infiltrating tubulointerstitial T cells, serum creatinine and urea level. No significant glomerular IP-10/CXCL10 expression and T cell infiltration was detectable. Monocyte recruitment was not affected by anti IP-10/CXCL10 treatment, demonstrating a predominant role of this chemokine in tubulointerstitial T cell recruitment. Conclusions: Our findings demonstrate that microvascular renal injury leads to the tubulointerstitial expression of IP-10/CXCL10. The data provide strong evidence that a IP-10/CXCL10 mediated T cell recruitment is of functional importance in this model of microvascular injury. [ABSTRACT FROM AUTHOR]

Objective: Recent studies showed a crucial role for B cells in acute renal allograft rejection. It remains largely unknown, however, which mechanisms lead to the B cell recruitment into the allograft. The chemokine BCA-1/CXCL13 and its corresponding receptor CXCR5 play a central role in B cell trafficking to secondary lymphatic tissue. We therefore investigated the potential role of BCA-1/ CXCL13 and CXCR5 in formation of B cell clusters in renal transplant rejection. Methods: Serial immunohistochemical staining for BCA-1/ CXCL13, CXCR5 and CD20 was carried out in biopsies of 23 patients obtained between day 4 and day 9 after renal transplantation. Intragraft mRNA expression of BCA-1/CXCL13 was assessed by real time PCR analysis. Results: Of 23 kidney biopsies routinely obtained between days 4 and 9 after renal transplantation, 13 revealed an acute rejection. Four of these patients showed a substantial infiltration of the transplant with cluster forming B cells. By immunohistochemistry BCA-1/ CXCL13 and the corresponding receptor CXCR5 were exclusively detected in areas of B cell clusters. Intrarenal BCA-1/CXCL13 mRNA expression was 27-fold higher in transplants with B cell clusters compared to rejecting allografts without B cell accumulation (p = 0.011). Conclusions: We describe a striking co-localization of BCA-1/ CXCL13 expression with CXCR5 and CD20 positive B cells in renal transplants undergoing rejection. This is the first study demonstrating a potential role of BCA-1/CXCL13 and its specific receptor CXCR5 in recruitment of B cells in renal allograft rejection. [ABSTRACT FROM AUTHOR]