Francesca Bosio

Mesenchymal stromal cells improve renal injury in anti-Thy 1 nephritis by modulating inflammatory cytokines and scatter factors

MSC (mesenchymal stromal cells) can differentiate into renal adult cells, and have anti-inflammatory and immune-modulating activity. In the present study, we investigated whether MSC have protective/reparative effects in anti-Thy1 disease, an Ab (antibody)-induced mesangiolysis resulting in mesangioproliferative nephritis. We studied five groups of rats: (i) rats injected with anti-Thy1.1 Ab on day 0 (group A); (ii) rats injected with anti-Thy1.1 Ab on day 0+MSC on day 3 (group B); (iii) rats injected with anti-Thy1.1 Ab on day 0+mesangial cells on day 3 (group C); (iv) rats injected with saline on day 0+MSC on day 3 (group D); and (v) rats injected with saline on day 0 (group E). Rats were killed on days 1, 3, 7 and 14. MSC prevented the increase in serum creatinine, proteinuria, glomerular monocyte influx and glomerular histopathological injury. Furthermore, MSC suppressed the release of IL-6 (interleukin-6) and TGF-β (transforming growth factor-β), modulated glomerular PDGF-β (platelet-derived growth factor-β), and reset the scatter factors and their receptors, potentiating HGF (hepatocyte growth factor)/Met and inactivating MSP (macrophage-stimulating protein)/Ron (receptor origin nantaise). Few MSC were found in the kidney. These results indicate that MSC improve anti-Thy 1 disease not by replacing injured cells, but by preventing cytokine-driven inflammation and modulating PDGF-β and the scatter factors, i.e. systems that regulate movement and proliferation of monocytes and mesangial cells.

The role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation

Cytomegalovirus (CMV) infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Ganciclovir (GCV) and its prodrug valganciclovir are successfully used to prevent and treat CMV infection; however, in a small percentage of patients, CMV gene mutations may lead to drug resistance. GCV resistance is defined as increasing CMV viremia or progressive clinical disease during prolonged antiviral therapy, due to CMV gene mutation. This has emerged as a new challenge, especially because alternative drugs such as cidofovir and foscarnet have a number of important side effects. Here we report the case of a kidney transplanted patient who experienced life-threatening CMV disease, which initially appeared to be GCV-resistant, but was instead found to be associated with inadequate antiviral drug levels. The patient was then successfully treated by monitoring plasma GCV levels. We suggest using plasma GCV monitoring in the management of all cases of critical CMV disease, in which GCV resistance is suspected.

Mesenchymal stromal cells reset the scatter factor system and cytokine network in experimental kidney transplantation

BackgroundIn former studies we showed in a rat model of renal transplantation that Mesenchymal Stromal Cells (MSC) prevent acute rejection in an independent way of their endowing in the graft. In this study we investigated whether MSC operate by resetting cytokine network and Scatter Factor systems, i.e. Hepatocyte Growth Factor (HGF), Macrophage Stimulating Protein (MSP) and their receptors Met and RON, respectively.MethodsMSC were injected into the renal artery soon after reperfusion. Controls were grafted untreated and normal rats. Rats were sacrificed 7 days after grafting. Serum and renal tissue levels of IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10, MSP/RON, HGF/Met systems, Treg lymphocytes were investigated.ResultsIn grafted untreated rats IFN-γ increased in serum and renal tissue and IL-6 rose in serum. MSC prevented both the phenomena, increased IL-10 serum levels and Treg number in the graft. Furthermore MSC increased serum and tissue HGF levels, Met tubular expression and prevented the suppression of tubular MSP/RON expression.ConclusionsOur results demonstrate that MSC modify cytokine network to a tolerogenic setting, they suppress Th1 cells, inactivate monocytes/macrophage, recruit Tregs. In addition, MSC sustain the expression of the Scatter Factor systems expression, i.e. systems that are committed to defend survival and stimulate regeneration of tubular cells.

GM-CSF contributes to prompt healing of ecthyma gangrenosum lesions in kidney transplant recipient

BACKGROUND Ecthyma gangrenosum (EG) is an unusual, potentially fatal cutaneous disease, commonly associated with Pseudomonas aeruginosa septicemia. CASE REPORT We report the case of a 61-year-old man admitted to the Nephrology Department for fever, leukopenia and inguinal and scrotal painful lesions. Physical examination revealed inguinal and scrotal macules, nodules, blisters and ulcers with central necrosis. P. aeruginosa was isolated from an ulcer. EG was diagnosed. Because of the severe leukopenia, granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered until the white blood cell count significantly increased. Based on antibiogram, intravenous ceftazidime and teicoplanin were given for 11 days. Cutaneous manifestations were completely healed in about 2 months. CONCLUSION We suggest that the combination of GM-CSF with appropriate antibiotics can resolve EG and avoid or minimize the risk of septicemia in immunosuppressed patients.

Atraumatic Spleen Rupture in Dialyzed Patients: Clinical Report and Review of the Literature

Atraumatic spleen rupture (ASR) is a rare but lifethreatening event. It can present either with a dull and unspecific abdominal pain or with severe shock because of intraperitoneal hemorrhage. It requires prompt intensive medical support while preparations are made for emergency splenectomy. The term “atraumatic” should be used only in the absence of abdominal trauma, and thus 3 categories have been identified (1):

Multiple electrolyte disorders in a neurosurgical patient: solving the rebus

BackgroundIt is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury.Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized.Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus.Case presentationHere we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria.We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance.ConclusionThe comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.

Massive liver polycystic disease in a kidney transplanted patient.

A 57-year-old woman was admitted for nausea, vomiting and bdominal pain. She had an adult dominant polycystic kidney isease (ADPKD), associated with multiple liver cysts with normal epatic function. The kidneys had been removed ten years earier, when she underwent kidney transplantation. At admission enal function was normal, but severe liver injury was proven by ew-onset ascites, increased bilirubin level (2.1 mg/dl), reduced lbumin concentration (2.6 g/dl) and prolonged prothrombin nternational normalised ratio (INR 1.7). The patient reported she ad been involved in a road accident two weeks earlier. Magnetic esonance imaging (MRI) showed massive polycystic liver disease PCLD) (Fig. 1, Panel A, star indicates the transplanted kidney) with aemorrhagic cysts, probably due to the recent trauma (Fig. 1, anel B, arrows).