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Bioimpedance spectroscopy (BIS) is suitable for continuous monitoring of body water content. The combination of body posture and time is a well-known source of error, which limits the accuracy and therapeutic validity of BIS measurements. This study evaluates a model-based correction as a possible solution. For this purpose, an 11-cylinder model representing body impedance distribution is used. Each cylinder contains a nonlinear two-pool model to describe fluid redistribution due to changing body position and its influence on segmental and hand-to-foot (HF) bioimpedance measurements. A model-based correction of segmental (thigh) and HF measurements (Xitron Hydra 4200) in nine healthy human subjects (following a sequence of 7 min supine, 20 min standing, 40 min supine) has been evaluated. The model-based compensation algorithm represents a compromise between accuracy and simplicity, and reduces the influence of changes in body position on the measured extracellular resistance and extracellular fluid by up to 75 and 70%, respectively.

In addition to lymphomas, vascular tumors represent the most common neoplasms of the spleen. Littoral cell angiomas are benign vascular tumors originating from the littoral cells lining the splenic sinuses. In this report, we describe the case of a 63-year-old patient who developed night sweats 16 months after renal transplantation. Diagnostic workup showed multiple splenic masses believed to represent lymphoma infiltration to the spleen. Lymph nodes and bone marrow were unaffected, and diagnostic splenectomy was performed. Histological examination of the pathological specimen from the splenectomy specimen showed multiple littoral cell angiomas of the spleen. We recommend that physicians involved in the area of organ transplantation, especially kidneys, remain alert for other rarer splenic lesions in transplant recipients than posttransplantation lymphoma. More specific tools need to be developed to aid in the differential diagnosis of splenic masses to avoid splenectomy in patients with littoral cell angiomas.

Our current understanding of the initial pathogenetic steps in IgA nephropathy (IgAN) provides relatively limited rationale for immunosuppressive therapy. However, it is conceivable that immunosuppressive drugs might affect secondary inflammatory events triggered by glomerular immune deposits or even proteinuria per se. Some, but not all, randomized clinical trials on either corticosteroid monotherapy, mycophenolate mofetil monotherapy, or immunosuppressive combination therapy have provided evidence for a benefit on either surrogate parameters such as proteinuria or hard end points such as renal failure. The central problem of these studies is that most were designed in the 1980s or 1990s, when recommendations for supportive therapy were strikingly different from those of today. In the meantime an equal number of randomized clinical studies reporting a benefit of supportive therapy has been published only regarding patients with IgAN and, unfortunately, no head-to-head comparisons of these 2 approaches currently are available. Several ongoing clinical trials may help to resolve this dilemma. Until the data of such studies become available, a pragmatic approach is to first optimize supportive therapy and reserve immunosuppressive medication for those patients failing a supportive approach and remaining at risk for progressive loss of renal function.

Renal fibrosis complicates most chronic renal diseases, leading to a progressive loss of function and ultimately resulting in terminal renal failure. Molecular mechanisms underlying the development and progression of renal fibrosis have been increasingly identified, and much progress has been made towards a better understanding of the roles of different growth factors/cytokines and regulators of matrix turnover, as well as of the interactions between renal inflammation and fibrosis. This review focuses on recent advances in the identification of novel targets, as well as the development of new therapeutic tools for use in the treatment of progressive fibrosing renal diseases. Using our growing knowledge, treatment strategies need to be identified that prevent progression more effectively, as well as inducing regression of developed renal fibrosis. This is likely by combining compounds that interfere with a variety of targets simultaneously.

Heat shock proteins (Hsp) are ubiquitous intracellular proteins that can be released in various forms of cellular stress. Some Hsp, such as Hsp60, have been shown to stimulate directly T cell-mediated immune responses in vitro. Here, it is demonstrated that Hsp60 is released from the kidneys and excreted into the urine of mice with nephrotoxic nephritis (NTN), a model of rapidly progressive glomerulonephritis. For examining the functional relevance of Hsp60 release, this protein was injected into mice with subnephritogenic NTN, in which only transient proteinuria and minimal organ damage occur that do not progress to terminal kidney failure. Injection of Hsp60 strikingly aggravated disease, as evidenced by global glomerular necrosis, tubulointerstitial damage, and complete anuria after 10 to 12 d. This effect was mediated neither by endotoxin contaminations of Hsp60 nor by autologous antibodies. It was strictly T cell dependent but not associated with a systemic Th1/Th2 shift. Thus, Hsp60 is an endogenous mediator stimulating immune effector mechanisms that contribute to the progression of NTN. These findings demonstrate in vivo that Hsp60 fulfills criteria of immunologic danger signals and suggest that such signals may be involved in immune-mediated kidney disease.

Platelet-derived growth factor B-chain (PDGF-B)- and transforming growth factor beta (TGF-beta)-mediated accumulation of extracellular matrix proteins contributes to many progressive renal diseases. In vivo, specific antagonism of either PDGF-B or TGF-beta in experimental mesangioproliferative glomerulonephritis resulted in an almost complete inhibition of matrix protein accumulation, which suggests an interaction between signaling pathways of these two growth factors. Because nothing is known on the nature of this possible interaction, PDGF-B was antagonized in the rat anti-Thy 1.1 model of glomerulonephritis by use of specific aptamers and its effects on the TGF-beta system were investigated. Antagonism of PDGF-B led to a significant reduction of glomerular matrix accumulation compared with scrambled aptamer-treated nephritic controls. PDGF-B antagonism had no effect on the overexpression of glomerular TGF-beta mRNA, TGF-beta protein, or the expression of TGF-beta receptor type I and II mRNA. By immunohistology, it was possible to detect overexpression of the cytoplasmic TGF-beta signaling molecules Smad2 (agonistic) and Smad7 (antagonistic) in glomeruli of nephritic control rats which peaked on day 7 after disease induction, i.e., the peak of mesangial cell proliferation in this model. However, immunohistology and Western blot analysis again revealed no difference in the glomerular expression of both Smad proteins between PDGF-B antagonized and nonantagonized nephritic animals. In addition, no difference in the glomerular expression of phosphorylated Smad2 (P-Smad2) was detected between the differently treated nephritic groups. These observations suggest that the effects of PDGF-B antagonism are independent of TGF-beta in mesangioproliferative glomerulonephritides.