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Ten Berge I.J.M.,Nephrology Unit
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell-Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed. © 2010 The Author(s).


Shroff R.C.,Nephrology Unit | Shroff R.C.,University College London | Shroff R.C.,King's College London | McNair R.,Addenbrookes Hospital | And 6 more authors.
Journal of the American Society of Nephrology | Year: 2010

In chronic kidney disease (CKD) vascular calcification occurs in response to deranged calcium and phosphate metabolism and is characterized by vascular smooth muscle cell (VSMC) damage and attrition. To gain mechanistic insights into how calcium and phosphate mediate calcification, we used an ex vivo model of human vessel culture. Vessel rings from healthy control subjects did not accumulate calcium with long-term exposure to elevated calcium and/or phosphate. In contrast, vessel rings from patients with CKD accumulated calcium; calcium induced calcification more potently than phosphate (at equivalent calcium-phosphate product). Elevated phosphate increased alkaline phosphatase activity in CKD vessels, but inhibition of alkaline phosphatase with levamisole did not block calcification. Instead, calcification in CKD vessels most strongly associated with VSMC death resulting from calcium- and phosphate-induced apoptosis; treatment with a pan-caspase inhibitor ZVAD ameliorated calcification. Calcification in CKD vessels was also associated with increased deposition of VSMC-derived vesicles. Electron microscopy confirmed increased deposition of vesicles containing crystalline calcium and phosphate in the extracellular matrix of dialysis vessel rings. In contrast, vesicle deposition and calcification did not occur in normal vessel rings, but we observed extensive intracellular mitochondrial damage. Taken together, these data provide evidence that VSMCs undergo adaptive changes, including vesicle release, in response to dysregulated mineral metabolism. These adaptations may initially promote survival but ultimately culminate in VSMC apoptosis and overt calcification, especially with continued exposure to elevated calcium. Copyright © 2010 by the American Society of Nephrology.


Moroni G.,Nephrology Unit Fondazione IRCCS Ca Granda Ospedale Maggiore | Ponticelli C.,Nephrology Unit
European Journal of Internal Medicine | Year: 2016

For many years pregnancy has been contraindicated in patients with SLE, particularly when kidney involvement was present. Today, pregnancy is no longer considered impossible in women with lupus. Yet, lupus pregnancies are still considered high-risk. The prognosis has considerably improved for pregnant women but the fetal risk, although progressively reduced, is still higher in pregnancies of patients with SLE than in pregnancies of healthy women. Miscarriage, premature delivery, and preeclampsia, as well as heart problems in the baby are the major complications that can occur. In this paper we will review the outcome of pregnant women with SLE, the influence of lupus on fetal outcome, the effects of pregnancy on lupus, and the management of pregnant lupus patients based on our personal experience and the revision of the most recent and significant papers on the subject. © 2016 European Federation of Internal Medicine.


Menni F.,University of Milan | Testa S.,Nephrology Unit | Guez S.,University of Milan | Chiarelli G.,University of Milan | And 2 more authors.
Pediatric Nephrology | Year: 2012

Background Inborn errors of cobalamin (Cbl) absorption and metabolism form a large group of rare diseases that include Cbl-C disorder. Among the renal complications of Cbl-C disorder, atypical hemolytic uremic syndrome (HUS) is the least common and has been described only in a small number of cases. Case-diagnosis/Treatment Four patients were admitted to our clinic after 15-30 days of life with vomiting associated with poor sucking, failure to thrive, lethargy and hypotonia. Examinations showed thrombocytopenia and microangio-pathic hemolytic anemia associated with renal damage. The neonates had high blood homocysteine levels, increased urinary levels of both homocystine and methylmalonic acid, increased propionylcarnitine (C3) levels and an increased C3/ acetylcarnitine ratio. Homozygosity for c.271-272dupA (p.Arg91LysfsX14) of the MMACHC gene was detected in three patients, and heterozygosity for c.271-272dupA and c.666C > A(p.Tyr222X) in one patient, which confirmed the diagnosis of Cbl-C disorder. Treatment with parenteral hydroxycobalamin in combination with folic acid and betaine gradually normalized the metabolic test findings and hematological and renal parameters after about 1 week. Conclusions Atypical HUS in neonates with Cbl-C disorder may be associated with mild to moderate renal involvement also in early-onset disease, and early adequate therapy can reverse renal damage. © 2011 IPNA.


Ponticelli C.,Nephrology Unit | Moroni G.,Nephrology Unit
Expert Review of Clinical Immunology | Year: 2015

Most pregnancies are successful in women with systemic lupus erythematosus, particularly if the disease is quiescent and there are no signs of active nephritis. There is no major impact of immunosuppression on maternal outcome. However, high doses of cyclosporine and glucocorticoids are used which may favor development of hypertension or preeclampsia. Some immunosuppressive drugs may exert toxic effects on the fetus. Glucocorticoids may cause small birth weight, and azathioprine and calcineurin inhibitors may be associated with lower birth weight, gestational age and prematurity. Cyclophosphamide may cause fetal malformation when given in the first trimester. Mycophenolate and leflunomide are teratogenic drugs and should be withdrawn before conception in case of programmed pregnancy or should be rapidly discontinued in case of unexpected pregnancy. Option counseling for pregnancy and correct use of immunosuppressive drugs are prerequisites for a successful pregnancy in women with lupus. © Informa Uk, Ltd.


Shavit L.,Nephrology Unit | Reinus C.,Shaare Zedek Medical Center | Slotki I.,Nephrology Unit
Clinical Nephrology | Year: 2010

Malignant nephrosclerosis is acute renal failure in the setting of malignant hypertension and may be associated with thrombotic microangiopathy. Although the prognosis has improved considerably over the past decades, renal dysfunction remains an important cause of morbidity and mortality. Adequate control of blood pressure is crucial, allows gradual healing of the necrotizing vascular lesions and may induce stabilization and improvement of renal function in about 50 - 80% of involved patients. In addition, recent investigations have provided a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. We report 3 patients who developed severe acute renal failure requiring dialysis initiation in the setting of malignant hypertension. All patients had kidney biopsy proven malignant nephrosclerosis and presented with symptoms of thrombotic microangiopathy. Despite adequate blood pressure control the prognosis of our patients varied. ©2010 Dustri-Verlag Dr. K. Feistle.


Shavit L.,Nephrology Unit | Lifschitz M.,Nephrology Unit | Galperin I.,Shaare Zedek Medical Center
Archives of Gerontology and Geriatrics | Year: 2012

The purpose was to check the influence of enteric nutrition on BUN in very elderly patients. Clinical data on patients in whom enteral feeding was initiated after a period of poor oral intake are presented. Patients with evidence of volume depletion, signs of gastrointestinal bleeding or medicines that might increase BUN were excluded. We evaluated 5 patients (mean age 90.6±3 years) who were admitted to geriatric department. Mean plasma creatinine concentration was 1.17±0.34mg/dl, but mean estimated glomerular filtration rate (eGFR) was 41.6±17ml/min/1.73m 2. Enteral nutrition was administered at a dose of mean 1580±53ml/day at mean duration of 9±4 days. Mean BUN was 52±30mg/dl at baseline, increases to 109±9.4mg/dl after initiation of feeding and decreased to 82±1.1mg/dl with reduction of dose of enteral nutrition. Our conclusion was that initiation of enteral feeding may induce a large accumulation of nitrogen waste products in elderly patients in whom serum creatinine is an unreliable indicator of kidney function. High protein intake should be considered in differential diagnosis of disproportionate high increment of BUN. © 2011 Elsevier Ireland Ltd.


Shavit L.,Nephrology Unit | Grenader T.,Shaare Zedek Medical Center
Clinical and Experimental Rheumatology | Year: 2014

Objectives: Pauci-immune ANCA-related glomerulonephritis (GN) is extremely uncommon in patients with underlying Sjögren's syndrome (SS) and its clinical and laboratory characteristics have not been previously explored. Methods: We carried out a thorough literature review in order to establish predisposing factors, clinical and laboratory manifestations, kidney biopsy features, treatment modalities and response to treatment of biopsy proven ANCA-related pauci-immune GN in patients with SS. Results: From 1967 to 2011, seven patients with a mean age of 63±14.7 years were identified. The average duration of SS prior to development of pauci-immune GN was 50±62 months. A high incidence of extraglandular manifestations was identified: 50% had interstitial lung disease and/or peripheral neuropathy. All patients suffered from proteinuria (average 1397±905 mg per 24 hours) and haematuria at presentation. Almost 70% of patients suffered from severe anaemia (average haemoglobin 6.6±1.9 gr%). ANCA MPO was positive in all six patients, while ANCA PR3 was negative in all. All patients received corticosteroids and 70% received cyclophosphamide. One patient died and one patient developed end stage kidney disease. The rest of the study patients had improved renal function over time. Conclusions: Our study emphasises that patients with SS can present with atypical kidney pathology as ANCA-related GN. Thus, high clinical awareness is warranted to establish correct diagnoses. Given the powerful impact of kidney pathology on management of these patients and responsiveness to treatment demonstrated in our case series, the significance of timely diagnosis can not be overestimated. © Clinic Cal and Expe Erime Ental Rrhe Eumatology 2014.


Guella A.,Nephrology Unit | Mohamed E.,Nephrology Unit
Transplantation Proceedings | Year: 2011

Worldwide reports from national renal registries show a donor gender imbalance in living renal transplantation. In these studies women represent on the one hand about 65% of living donors and on the other hand, receive fewer kidneys than men. Because of scarcity of reports on this matter from the Eastern world, we undertook this study to assess the gender demographics of recipients and living donors in our transplant center in the eastern region of Saudi Arabia. We retrospectively reviewed our living related transplantations performed from 1992 to 2008 (n = 135). Ninety-one males (67.4%) versus 44 females (32.6%) donated a kidney (P = .0000.) The male predominance (n = 80; 59.3%) was also noticed among recipients with 80 versus 55 females (40.7%; P = .001). When splitting the results into two periods, 1992 to 1999 versus 2000 to 2008, we noticed a trend to an improved donation rate from females, rising from 29% to 38.7% (P = NS). Further analysis showed that brothers were giving more frequently to brothers than to sisters (38 vs 11; P < .001) and that sisters donated equally to brothers and sisters (12 vs 11; P = NS). Interspousal donation showed no significant difference between husband to wife and vice versa (4 vs 5). Unlike the international experience, our study showed men to be donating more kidneys than women. Sociocultural reasons may have a role in such findings. © 2011 by Elsevier Inc. All rights reserved.


Marenzi G.,Intensive Cardiac Care Unit | Cosentino N.,Intensive Cardiac Care Unit | Guastoni C.,Nephrology Unit
Journal of Nephrology | Year: 2015

Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease (CAD), which remains the most common cause of morbidity and mortality in CKD patients. Although the management of CAD is more challenging in patients with CKD than in the general population, and coupled with concerns about further deterioration of renal function and therapy-related toxic effects, CKD patients and those receiving dialysis have not traditionally been included in randomized trials evaluating either medical or revascularization therapies. Thus, only scant data from small prospective studies or retrospective analyses of controlled trials and registries are available, and to date no optimal treatment approach has been defined for this subgroup of patients. However, they potentially have much to gain from the pharmacological, interventional, and surgical strategies used in the general population. Thus, the objective of this review is to summarize the current evidence regarding the management of CAD in CKD patients, in particular with respect to uncertainties regarding coronary revascularization options, and their risk–benefit relationship in such a high-risk population. © 2015, Italian Society of Nephrology.

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