Long-term outcome of vesicoureteral reflux associated chronic renal failure in children. Data from the ItalKid Project

PURPOSE: The nephropathy associated with vesicoureteral reflux (VUR) is one of the leading causes of chronic renal failure (CRF) in children. We describe the clinical course of the disease based on information available in the ItalKid Project database, and analyze the predictive value of baseline renal function, age at VUR diagnosis and urinary protein excretion in relation to the risk of progressive renal failure. MATERIALS AND METHODS: As of December 31, 2001 the registry included a total of 343 patients (261 males) with a diagnosis of primary VUR, which was the leading single cause of CRF, accounting for 25.4% of all patients with CRF. RESULTS: The estimated risk of end stage renal disease (ESRD) by age 20 years was 56%. The patients with a creatinine clearance (Ccr) of less than 40 ml per minute at baseline had an estimated 4-fold greater risk of ESRD developing in comparison with those whose Ccr was 40 to 75 ml per minute. No significant difference in probability of disease progression to ESRD was found between subjects diagnosed with VUR at age 6 months or less and those diagnosed later (older than 6 months). Furthermore, children with normal urinary protein excretion (a urinary protein [uPr]/urinary creatinine [uCr] ratio of less than 0.2 in 36 patients) and low grade proteinuria (uPr/uCr 0.2 to 0.8 in 34 patients) at baseline showed a significantly slower decrease in mean Ccr than those with moderate proteinuria (uPr/uCr greater than 0.8 in 34 patients). Hypertension and/or antihypertensive treatment (including antiprogressive drugs) were reported in 29.1% of patients. CONCLUSIONS: The results of the present study define the long-term risk of ESRD in a large population of children with CRF and VUR, and provide some critical information for identifying the prognosis.     

Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy

Little is known about the role of proteinuria in the progression of childhood renal diseases. We analyzed the decline in creatinine clearance (C _Cr) and kidney survival in 225 children (185 males) with chronic renal failure (CRF) due to isolated hypodysplasia or hypodysplasia associated with urological abnormalities. The data were based on the information available in the Italian Pediatric Registry of CRF (ItalKid Project), which includes patients from all of Italy aged <20 years with C _Cr levels of <75 ml/min per 1.73 m². Patients aged <2 years and those with C _Cr levels of <20 ml/min per 1.73 m² or a follow-up of <1 year were excluded from the analysis, as were those receiving angiotensin-converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8±4.2 years, a mean C _Cr of 50±16.3 ml/min per 1.73 m², a median urinary protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02–7.21), and a mean duration of follow-up of 3.5±1.1 years. The patients were divided into three groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr <0.2) n=83; group B low (uPr/uCr 0.2–0.9) n=71; and group C mild (uPr/uCr >0.9) n=71. Patients in groups A and B showed a significantly slower decline in C _Cr than those in group C (slope +0.16±3.64 and –0.54±3.67 vs. –3.61±5.47, P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs. 44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio (P<0.01) and age (P<0.0001) correlated with a faster decline in C _Cr irrespective of baseline C _Cr. There was no correlation with mean arterial blood pressure. We conclude that proteinuria is an independent predictor of progression to end-stage renal failure also in children whose renal impairment is due to congenital hypodysplasia.This paper was written on behalf of all the members of the ItalKid Project whose contribution has been essential. Members of the ItalKid Project:G. Aceto (Bari), G. Airoldi (Borgomanero), G. Amici (Ancona), A. Ammenti (Parma), B. Andretta (Padova), G. Ardissino (Milano), F. Ardito (Bologna), B. Assael (Verona), L. Avolio (Pavia), S. Bassi (Montichiari), F. Battaglino (Vicenza), R. Bellantuono (Bari), A. Bettinelli (Merate), C. Bigi (Lecco), S. Binda (Varese), C. Bini (Como), D. Bissi (Gallarate), R. Boero (Torino), R. Bonaudo (Torino), A. Bordugo (Pordenone), M. Borzani (Milano), M. Bosio (Milano), A. Bottelli (Varese), G. Bovio (Pavia), A. Bracone (Bra), G. Capasso (Napoli), M. Capizzi (Milano), D. Caringella (Bari), I. Carnera (Siracusa), M.R. Caruso (Bergamo), D. Cattarelli (Brescia), V. Cecchetti (Milano), M. Cecconi (Ancona), V. Cecinati (Bari), A. Ciofani (Pescara), A. Claris-Appiani (Milano), R. Coppo (Torino), F. Corona (Milano), A. Corsini (Bentivoglio), R. Costanzo (Ragusa), P. Cussino (Savigliano), M. DAgostino (Bergamo), V. Daccò (Milano), G. Daidone (Siracusa), R. DallAmico (Thiene), L. Dardanelli (Cuneo), R. De Castro (Bologna), V. De Cristofaro (Sondrio), M. De Gennaro (Roma), S. De Pascale (Bergamo), N. De Santo (Napoli), D. Delfino (R. Calabria), C.A. DellAgnola (Milano), L. Dello Strologo (Roma), L. Dertenois (Genova), A. Dessanti (Sassari), A. Di Benedetto (Catania), A. Di Leone (Cosenza), F. Di Lorenzo (Bologna), P. Di Turi (Bologna), A. Edefonti (Milano), W. Erckert (Silandro), A. Fabris (Verona), V. Fanos (Verona), C. Fede (Messina), A. Fella (Napoli), R. Ferraro (Scorrano), M.T. Ferrazzano (Anzio), R. Ferré (Breno), A. Ferretti (Napoli), B. Fogazzi (Brescia), P. Formentin (Cittadella), C. Fortini (Ferrara), E. Fossali (Milano), G. Fossati Bellani (Milano), M. Gaido (Torino), R. Galato (Milano), G. Gargano (Modena), V. Georgacopulo (Ferrara), L. Ghio (Milano), R. Giachino (Ivrea), M. Giani (Milano), S. Gianni (Siracusa), B. Gianoglio (Torino), M. Girodano (Bari), V. Goj (Milano), F. Grancini (Milano), G. Grott (Chieri), S. Guez (Milano), R. Gusmano (Genova), A. Iovino (Napoli), C. Isimbaldi (Lecco), A. La Manna (Napoli), G. Lama (Napoli), R. Landoni (Cinisello B.), S. Li Volti (Catania), A. Liardo (Caltagirone), V. Lotti (Cesena), R. Lubrano (Roma), I. Luongo (Napoli), E. Mancini (Bologna), N. Manganaro (Messina), M. Marangella (Torino), C. Marchesoni (Trento), K. Marenzi (Segrate), S. Maringhini (Palermo), G. Marra (Milano), E. Marras (Torino), V. Mei (Bologna), F. Menni (Milano), N. Miglietti (Brescia), R. Mignani (Rimini), P. Minelli (Bologna), R. Moioli (Milano), P. Molinari (Bologna), G. Montini (Padova), M. Montis (Cagliari), G. Mosiello (Roma), L. Murer (Padova), G. Nebbia (Milano), M. Neunhauserer (Brunico), P. Nitsch (Parma), M. Noto (Palermo), C. Oppezzo (Milano), F. Paolillo (Lodi), T. Papalia (Cosenza), R. Parini (Milano), L. Parola (Magenta), F. Passione (Foggia), L. Pavanello (CastelfrancoV.), C. Pecoraro (Napoli), M. Pedron (Bolzano), I. Pela (Firenze), A. Pellegatta (Busto Arsizio), P. Pelliccia (Chieti), M. Pennesi (Trieste), C. Pennetta (Manduria), R. Penza (Bari), L. Peratoner (Pordenone), F. Perfumo (Genova), G. Perino (Torino), C. Pesce (Vicenza), L. Pisanello (Padova), M. Pitter (Mirano), L. Pontesilli (Roma), M. Porcellini (Torino), A. Pota (Napoli), R. Prandini (Bologna), F. Puteo (Bari), I. Ratsch (Ancona), E. Ravaioli (Rimini), G. Remuzzi (Bergamo), G. Riccipetitoni (Cosenza), G. Ripanti (Pesaro), G. Rizzoni (Roma), N. Roberto (Milano), A. Rosini (Ancona), M. Rossi Doria (Bologna), S. Rota (Bergamo), M. Ruzza (Milano), D. Scorrano (Belluno), A. Selicorni (Milano), G. Selvaggio (Milano), F. Sereni (Milano), O. Sernia (Savigliano), C. Setzu (Cagliari), C. Sforzini (Milano), L. Stallone (S. Giovanni Rotondo), M. Tagliaferri (Treviglio), L. Tampieri (Lugo), A. Testagrossa (Messina), A. Turrisi (Trapani), G. Vallini (Cinisello Balsamo), E. Verrina (Genova), S. Viola (Pavia), G. Visconti (Palermo), A. Voghenzi (Ferrara), G. Zacchello (Padova)     

Effect of filgrastim on serum lactate dehydrogenase and alkaline phosphatase values in early breast cancer patients

To improve chemotherapy dose intensity and to optimize the use of granulocyte-colony stimulating factor, 506 patients with early breast cancer were randomly assigned to high dose epirubicin and cyclophospamide (EC) with or without prophylactic subcutaneously filgrastim, according to 5 different schedules: 480 µg or 300 µg daily or every other day, on day 8 through day 14, and 300 µg daily on days 8 and 12 of each chemotherapy course, Serum levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) were significantly higher in patients given EC plus filgrastim than EC alone (P + 0.0001), the rate of G1-3 toxicity being 33.4% and 13.1% vs. 1.6% and 1%, respectively. No clinical evidence of filgrastim-related hepatic damage or significant difference in transaminase and γ-GT elevation was seen between the two groups. LDH and AP closely resembled peripheral blood leukocytes count and increased with increasing leucocytosis, throughout the 5 schedules. Although no patient continued treatment for filgrastim-related side effects, and LDH and AP rises resolved spontaneously within 3 weeks following the chemotherapy course, physicians should be aware of the transient and innocuous change in serum chemistry associated to leucocytosis, since it could be misinterpreted as expression of disease activity.     

Prion deposition in olfactory biopsy of sporadic Creutzfeldt-Jakob disease

Currently, definite peripheral markers for the in vivo diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) are not available. Here, we report the presence of pathological prion protein in the olfactory mucosa of a case with sporadic Creutzfeldt-Jakob disease. Prion protein immunoreactivity was detected in an olfactory biopsy performed 45 days after the disease onset, suggesting that the involvement of olfactory epithelium is an early event in sporadic Creutzfeldt-Jakob disease.     

Non-invasive diagnostic and functional evaluation of cardiac and pulmonary involvement in systemic sclerosis

BACKGROUND: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value. PATIENTS AND METHODS: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated. RESULTS: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis. CONCLUSION: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.     

Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients

A longitudinal study of Ig V gene segments utilized by B cells from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS) was carried out using RT-PCR methodologies. One patient with a relapsing-remitting (RR)-MS was investigated at onset and at relapse, 1 year later. A patient with secondary-progressive (SP)-MS was tested 9 and 13 years after disease onset. Sequence analyses of V(H)DJ(H) segments bearing V(H)3 and V(H)4 that were obtained from Cgamma cDNA genes demonstrated a substantial proportion of shared clones in the samples taken at different times; these clones were identical or closely related, i.e. had the same third complementary determining region (CDR) of the H chain variable region gene (HCDR3) with different mutations in the V(H) segment. Collectively, these data demonstrate that in MS patients there is a strong selective pressure, which could be exerted by antigen (or autoantigen) stimulation, for the maintenance and partial diversification of certain V(H)DJ(H) Cgamma sequences.     

Vulvar carcinoma associated with lichen sclerosus. Experience at the Florence,Italy, Vulvar Clinic

OBJECTIVE: To compare demographic and clinical characteristics of patients with lichen sclerosus (LS)-associated squamous cell carcinoma (SCC) of the vulva with those of patients with tumors not histologically associated with LS in a series of patients with vulvar SCC not HPV correlated. STUDY DESIGN: We retrospectively reviewed histologic specimens and clinical files of all vulvar SCCs referred to the Vulvar Clinic, University of Florence, Florence, Italy, since 1990. RESULTS: Twenty-five out of the 72 cases in this study (34.7%) were LS associated. Among these cases, 8 (32%) were diagnosed with LS before occurrence of the cancer and received treatment for the disease. In 17 cases the diagnosis of LS was simultaneous with that of SCC; in 13 cases the diagnosis was achieved by clinical examination and confirmed afterwards histologically. In 4 cases this was confirmed only by means of histologic examination. The shared profile of patients with LS-associated vulvar SCC was a subject (mean age, 72 years) seldom with a past medical history of vitiligo (16% of cases), with invasive cancer (92% of cases), clinically characterized by an exophitic tumor (73%), seldom ulcerated (18%) or showing hyperkeratosis (9%). Labia majora (32%), labia minora (27%) and vestibule (23%) were the most frequently involved sites. In most cases (80%) the cancer was limited to 1/3 of the vulvar region. An itch was the most frequent symptom. However, for all of these variables, no overall statistically significant difference was found with patients who had SCCs not associated with LS. CONCLUSION: The experience of the Vulvar Clinic, University of Florence, confirms the suggested role of LS as a possible precursor of vulvar carcinoma since 32% of our cases not HPV related were LS associated. We demonstrated that the profile of patients with LS-associated cancer does not differ from that of patients with cancer not associated with LS, excluding HPV-related cases. The existence of accessory conditions, probably needed to promote the progression from LS to cancer in a minority of subjects remains to be established.     

Risk factors for poor renal prognosis in children with hemolytic uremic syndrome

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D^–STEC^– recovered normal renal function compared with 65%–76% of D⁺STEC⁺, D⁺STEC^– and D^–STEC⁺ patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D^– but STEC⁺ patients have a significantly better prognosis.     

MRI lung perfusion 2D dynamic breath-hold technique in patients with severe emphysema

BACKGROUND: Our aim was to prospectively evaluate a semi-quantitative pulmonary perfusion MR technique using a breath-hold 2D dynamic sequence in patients with severe pulmonary emphysema. MATERIALS AND METHODS: Thirty patients with severe emphysema were studied with pulmonary perfusion MRI. Results were compared with those obtained through lung scintigraphy, considered as the gold standard technique. We used Fast Field Echo (FFE) pulse sequences in the coronal and sagittal planes, with paramagnetic contrast agent administration. Ten healthy volunteers were studied as the control group. Three thoracic radiologists independently reviewed all the subjects, evaluating the site and entity of perfusional defects. Peak intensity and apparent mean transit time were calculated. RESULTS: MRI showed high sensitivity (86.7%) and good specifity (80.0%) in detecting perfusional defects. We observed lower peak signal intensities in emphysematous regions. CONCLUSION: Lung perfusion MR is a potential alternative to Nuclear Medicine in the evaluation of severe pulmonary emphysema.     

Prolonged donor ischemic time does not adversely affect long-term survival in adult patients undergoing cardiac transplantation

OBJECTIVE: With liberalization of donor eligibility criteria, organs are being harvested from remote locations, increasing donor ischemic times. Although several studies have evaluated the effects of prolonged donor ischemic times on short-term survival and graft function, few have addressed concerns regarding long-term survival. METHODS: Over the last 11 years, 819 consecutive adults underwent cardiac transplantation at Columbia Presbyterian Medical Center. Recipients were separated into the following 4 groups based on donor ischemic time: <150 minutes, 150 to 200 minutes, 200 to 250 minutes, and >250 minutes. Statistical analysis included Kaplan-Meier survival and Cox proportional hazard models to identify predictors of long-term survival. RESULTS: Donor ischemic time was 120.1 +/- 21.1 minutes for group 1 (n = 321), 174.1 +/- 14.7 minutes for group 2 (n = 264), 221.7 +/- 14.6 minutes for group 3 (n = 154), and 295.5 +/- 37.1 minutes for group 4 (n = 80) (P <.001). There were no significant differences in recipient age, donor age, etiology of heart failure, United Network for Organ Sharing status, or history of previous cardiac surgery among the groups (P = NS). Prolonged donor ischemic time did not adversely affect long-term survival, with actuarial survival at 1, 5, and 10 years of 86.9%, 75.2%, and 56.4% for group 1; 86.2%, 76.9%, and 50.9% for group 2; 86.4%, 71.0%, and 43.7% for group 3; and 86.7%, 70.1%, and 50.9% for group 4 (P =.867). There was no significant difference in freedom from transplant coronary artery disease among the 4 groups (P =.474). CONCLUSIONS: Prolonged donor ischemic time is not a risk factor for decreased long-term survival. Procurement of hearts with prolonged donor ischemic time is justified in the setting of an increasing recipient pool with a fixed donor population.