Search

Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary β-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI. [ABSTRACT FROM AUTHOR]

Multicentric Castleman's disease (MCD) is a benign lymphoproliferative disorder with heterogenous clinical symptoms, and involves systemic organs in addition to lymph nodes. Herein, we present the case of a 55-year-old man with MCD characterized by an extensive infiltration of IgG4+ plasma cells in the kidneys. The patient presented to our hospital with a high fever and diarrhea. On admission, laboratory analysis revealed anemia, renal dysfunction (eGFR 30 mL/min/1.73 m2), polyclonal gammopathy (IgG 7130 mg/dL), elevated serum IgG4 level (2130 mg/dL), and increased C-reactive protein (8.0 mg/dL). An enlargement of lymph nodes in the axillary, mediastinal, para-aortic, and inguinal regions was observed on abdominal computed tomography. Axillary lymph node biopsy revealed interfollicular expansion due to dense plasma cell infiltration. Renal biopsy demonstrated significant plasma cell infiltration into the tubulointerstitium. Immunohistochemical analysis showed a 40% IgG4-positive/IgG-positive plasma cell ratio, meeting the diagnostic criteria for an IgG4-related disease. Amyloid A deposition was observed along vessel walls, and immunofluorescence analysis indicated granular positivity of IgG and C3 along the glomerular capillary wall. Elevated levels of interleukin-6 (21 pg/mL) and vascular endothelial growth factor (VEGF; 1210 pg/mL) were noted. Based on these findings, and the histological finding of the lymph node biopsy, idiopathic MCD was diagnosed. Corticosteroid monotherapy was only partially effective. Subsequently, tocilizumab administration was initiated, leading to sustained remission, even after discontinuation of prednisolone. Due to the diverse responses to steroid therapy and the varying prognoses observed in MCD and IgG4-related disease, it is essential to carefully diagnose MCD by thoroughly assessing the organ distribution of the disease, its response to steroid therapy, and any additional pathological findings. [ABSTRACT FROM AUTHOR]

Introduction: Isolated ultrafiltration (IUF) is an alternative treatment for diuretic-resistant patients with fluid retention. Although hemodialysis (HD) predominantly decreases extracellular water (ECW), the impact of IUF on fluid distribution compared with HD remains unclear. Methods: We compared the effect of HD (n = 22) and IUF (n = 10) sessions on the body fluid status using a bioimpedance analysis device (InBody S10). Results: The total ultrafiltration volume was similar between HD and IUF (HD 2.5 ± 0.3 vs. ICF 2.1 ± 0.3 L/session, p = 0.196). The reduction rate of ECW was significantly higher than that of intracellular water (ICW) after HD (ECW −7.9% ± 0.8% vs. ICW −3.0% ± 0.9%, p < 0.001) and IUF (ECW −5.8% ± 0.9% vs. ICW -3.6% ± 0.8%, p = 0.048). However, the change in the ratio of ECW to total body water in HD was significantly larger than that in IUF (HD −3.2% ± 0.3% vs. ICF −1.1% ± 0.4%, p < 0.001). The reduction rates in serum tonicity (effective osmolality) were higher after HD than after IUF (HD −1.8% ± 0.5% vs. IUF −0.6% ± 0.2%, p = 0.052). Among the components of effective osmolality, the reduction rates of serum K+ and glucose levels after HD were significantly higher than those after IUF (serum K+: HD −30.5% ± 1.6% vs. IUF −0.5% ± 3.8%, p < 0.001; serum glucose: HD −15.4% ± 5.0% vs. IUF 0.7% ± 4.8%, p = 0.026), while the serum Na+ level was slightly and similarly reduced (HD −0.8% ± 0.4% vs. IUF −0.8% ± 0.4%, p = 0.500). The reduction in the osmolal gap value (measured osmolality–calculated osmolarity) was significantly greater after HD sessions than after IUF sessions (HD −12.4 ± 1.4 vs. IUF 2.0 ± 1.0 mOsm/kg, p = 0.001). Conclusion: The extracellular fluid reduction effect of HD is stronger than that of IUF. The different changes in effective osmolality and osmolal gap after HD and IUF sessions may be related to the different effects of HD and IUF on fluid distribution. [ABSTRACT FROM AUTHOR]

Conditional transgenic mice that express one of the human immunodeficiency virus (HIV)-I accessory genes, vpr, selectively in podocytes using a podocin promoter and a tetracycline-inducible system develop renal injuries similar to those of patients with HIV-associated nephropathy (HIVAN). We have shown that a heminephrectomy accelerates podocyte injury, which is alleviated by angiotensin II (ANG II) type 1 receptor blocker (ARB). The current study further explores the role of ANG II in the genesis of HIVAN in this murine model. With ANG II infusion, heavy proteinuria was observed at 1 wk after the initiation of doxycycline administration to induce vpr expression in podocytes. Severe morphological and phenotypical changes in the podocytes were observed at 2 wk, together with extensive glomerulosclerosis. Norepinephrine infusion, instead of ANG II, increased the systemic blood pressure to the same level as that achieved using ANG II. However, albuminuria and glomerular injury were modest in norepinephrine-infused mice. Treatment with an ARB, olmesartan, almost completely inhibited glomerular injury. In contrast, lowering the blood pressure with a vasodilator, hydralazine, partially decreased albuminuria but did not produce any histological changes. ANG II infusion alone without doxycycline resulted in a lower level of albuminuria and minimal histological changes. These data demonstrate that excessive ANG II accelerates vpr-induced podocyte injury in a mouse model of HIVAN. human immunodeficiency virus-associated nephropathy; proteinuria; glomerulosclerosis; angiotensin II type 1 receptor blocker; conditional transgenic mice

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.03.011 Byline: Akito Maeshima, Duke A. Vaughn, Yohan Choi, Sanjay K. Nigam Keywords: Wolffian duct; Activin; Ureteric bud outgrowth; Smad; BMP4; Mesonephros; Ectopic bud; Nephrogenesis; Autocrine Abstract: Development of metanephric kidney begins with ureteric bud outgrowth from the Wolffian duct (WD). GDNF is believed to be a crucial positive signal in the budding process, but the negative regulation of this process remains unclear. Here, we examined the role of activin A, a member of TGF-[beta] family, in bud formation using an in vitro WD culture system. When cultured with the surrounding mesonephros, WDs formed many ectopic buds in response to GDNF. While the activin signaling pathway is normally active along the non-budding WD (as measured by expression of activin A and phospho-Smad2/3), activin A was absent and phospho-Smad2/3 was undetectable in the ectopic buds induced by GDNF. To examine the role of activin A in bud formation, we attempted to inactivate activin action. Interestingly, the addition of neutralizing anti-activin A antibody potentiated GDNF action. To further clarify the role of activin A, we also tested the effect of activin blockade on the WD cultured in the absence of mesonephros. WDs without mesonephros did not form ectopic buds even in the presence of GDNF. In contrast, blockade of activin action with a variety of agents acting through different mechanisms (natural antagonist, neutralizing antibodies, siRNA) enabled GDNF to induce ectopic buds. Inhibition of GDNF-induced bud formation by activin A was accompanied by inhibition of cell proliferation, reduced expression of Pax-2, and decreased phosphorylation of PI3-kinase and MAP kinase in the WD. Our data suggest that activin A is an endogenous inhibitor of bud formation and that cancellation of activin A autocrine action may be critical for the initiation of this process. Author Affiliation: Departments of Pediatrics, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, USA Article History: Received 8 November 2005; Revised 7 March 2006; Accepted 10 March 2006

We assessed the function of the [[beta].sub.c]-subunit of activin in hepatocytes. We studied the effect of conditioned medium of Chinese hamster ovary (CHO) cell line stably expressing the [[beta].sub.c] gene (CHO-[[beta].sub.c]) on growth of AML12 hepatocytes. We also examined the effect of recombinant activin C and transfection of the [[beta].sub.c] gene by using adenovirus vector. CHO-[[beta].sub.c] secreted activin C, a homodimer of the [[beta].sub.c], as well as precursors of the [[beta].sub.c]. The conditioned medium of CHO-[[beta].sub.c] increased both [[sub.3.H]]thymidine incorporation and the cell number in AMLI2 cells. It also supported survival of AML12 cells in a serum-free condition. Recombinant human activin C also increased both [[sub.3.H]]thymidine incorporation and the number of AML 12 cells. Transfection of AML12 cells with the [[beta].sub.c]-subunit led to the stimulation of [[sub.3.H]]thymidine incorporation. Analysis of the conditioned medium revealed that the [[beta].sub.c]-subunit formed a heterodimer with the endogenous [[beta].sub.A], the formation of which was dependent on the amount of [[beta].sub.c] expressed. Recombinant activin C did not affect the binding of [sup.125]I-activin A to its receptor or follistatin. These results indicate that activin C stimulates growth of AML12 cells. The [[beta].sub.c]-subunit modifies the function of the [[beta].sub.A]-subunit by multiple mechanisms. activin C; growth; apoptosis