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The molecular variants M235T and T174M of the angiotensinogen gene have been linked to essential hypertension in some populations, but there are discrepancies about this association in other studies. We studied 75 patients with essential hypertension (BP > 160/100 mm Hg) from our outpatient clinic, aged 55+/-1 years, 30 men, systolic BP 182+/-2.5, diastolic BP 109+/-1 mm Hg (mean +/- SEM), and a family history of the disease. Target organ damage was evaluated by measuring urinary albumin excretion rate, left ventricular hypertrophy, and fundoscopy. As a control group, 75 healthy subjects with BP < 130/85 mm Hg and with no family history of cardiovascular disease were selected. M235T and T174M angiotensinogen genotypes were determined by PCR and subsequent digestion of the products with SfaNI and NcoI, respectively. The frequency (q) of genotypes of the variant M235T in the patients with essential hypertension was MM 0.31, MT 0.41, and TT 0.28, not significantly different (P = .93) from that of the controls (MM 0.28, MT 0.44, and TT 0.28). For the variant T174M, the genotype frequencies in hypertensives were TT 0.83, TM 0.15, and MM 0.02, which was not significantly different (P = .89) from that of the controls (TT 0.86, TM 0.12, and MM 0.02). Similarly, there was no evidence for association between angiotensinogen genotypes and hypertension in subjects aged < or = 40 years old (n = 24) or with severe (stage III) hypertension (n = 31). Within the group of patients with essential hypertension, there were no differences in genotype distribution between patients with and without retinopathy (n = 31), left ventricular hypertrophy (n = 37), or microalbuminuria (n = 14). This study shows that M235T and T174M variants are not associated either with essential hypertension or with target organ damage in a Spanish sample.

Linkage analysis was performed on 49 Catalan families with autosomal dominant polycystic kidney disease obtained via the Nephrology Department and related nephrology centers. A total of 336 subjects, 267 at risk for the disease, were investigated using three microsatellites linked to polycystic kidney disease Type 1 (PKD1) and three microsatellites linked to PKD2. All of the subjects underwent physical and sonographic examination. The results demonstrate locus heterogeneity, with 0.85 as the maximum likelihood for the proportion of families linked to PKD1. All of the remaining families were found to be linked to PKD2. Analysis of clinical data in the PKD1 group (N = 146) versus the PKD2 group (N = 20) showed a milder form of the disease in the latter, with a later age at diagnosis (27.4 versus 41.4 yr, P = 0.0002), later age of onset of ESRD (53.4 versus 72.7 yr, P < 0.0001), later age of diagnosis of hypertension (34.8 versus 49.7 yr, P = 0.001) and lower prevalence of hypertension at younger ages. Sonographic findings did not differ significantly between both groups. Although anticipation was observed in both groups, it did not affect the majority of families. No signs of imprinting were found in this study, and the only gender effect was an earlier age of onset of ESRD in men than in women (49.5 versus 53.1 yr in PKD1, P < 0.01 and 70.57 versus 73.6 yr in PKD2, P = 0.1). Molecular analysis of autosomal-dominant polycystic kidney disease allows presymptomatic diagnosis in individuals younger than age 30, and helps in establishing prognosis.

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.

The aim of the present study was to evaluate the regulatory relationship between the cytosolic free calcium concentration ([Ca2+]i and cytosolic pH (pHi). [Ca2+]i and pHi were measured using the fluorescent dyes fura-2 and BCECF [2′,7′-bis-(carboxyethyl)-5,6-carboxyfluorescein] respectively. In a medium with 1 mmol/l extracellular calcium, thrombin (2.5 units/ml) induced an increment in [Ca2+]i of 638 +/- 31 nmol/l (n = 5) and an intracellular alkalinization of 0.14 +/- 0.01 pH units (n = 8). Both responses were dependent on the concentration of thrombin, displaying a sigmoidal dose-response pattern. The intracellular alkalinization was dependent upon extracellular Na+ and was amiloride-sensitive, indicating that it was mediated by activation of the Na+/H+ exchanger. When extracellular calcium was chelated with EGTA prior to the addition of thrombin, the intracellular alkalinization was not affected (0.15 +/- 0.02 at 2.5 units/ml thrombin, n = 8). Under these circumstances, the [Ca2+]i increment represents mobilization from internal stores, reaching 157 +/- 42 nmol/l at 2.5 units/ml thrombin. When platelets were preloaded with the intracellular calcium chelator MAPTAM (1,2-bis-5-methylaminophenoxylethane-NNN'-tetraacetoxymethyl acetate) to block the increase in [Ca2+]i induced by thrombin, no increment in pHi was observed. Moreover, MAPTAM-loaded calcium-depleted platelets had a basal pHi that was more acidic than in the presence of 1 mmol/l extracellular calcium (6.93 +/- 0.09 versus 7.14 +/- 0.01, n = 26, P < 0.001). Ionomycin induced an elevation of [Ca2+]i that was accompanied by a concomitant increase in pHi, which was Na(+)-dependent and amiloride-sensitive. [Ca2+]i and pHi increases induced by ionomycin were both dependent on the concentration of ionomycin. In conclusion, an increase in [Ca2+]i is necessary for the agonist-induced activation of the Na+/H+ exchanger in platelets. Non-agonist-induced increases in [Ca2+]i seems to prompt activation of the exchanger. In addition, Ca(2+)-depleted platelets have a more acidic basal pHi, indicating that the basal level of [Ca2+]i is also important for maintaining the basal pHi.

In this report, we describe 3 patients who had pauci-immune necrotizing alveolar capillaritis-related pulmonary hemorrhage and who never developed other organic involvement, as revealed by clinical and laboratory data and also by autopsy examination in 1 case. Serum samples from these patients disclosed antimyeloperoxidase autoantibodies with initial immunofluorescence titers ranging from 1:1,600 to 1:3,200. Rapid institution of immunosuppressive therapy, as well as plasma exchange, led to prompt clinical improvement in 2 patients who were receiving mechanical ventilation support. We conclude that antimyeloperoxidase autoantibodies become new clues to support an underlying alveolar capillary vasculitis in patients with idiopathic isolated pulmonary hemorrhage, thus facilitating therapeutic decisions in this life-threatening condition.

Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de- endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients.

We examined the incidence and features of liver disease and the presence of serologic markers of hepatitis B virus (HBV) infection in 134 patients on hemodialysis for 2 to 14 years. Twenty-three patients (17%) had had a single episode of acute hepatitis while on dialysis and two patients had had two episodes, which were attributed to infection by hepatitis B virus in 7 instances and by hepatitis non-A, non-B virus in 20. Chronicity supervened in 4 cases of hepatitis B (57%) and in 14 cases of hepatitis non-A, non-B (70%). A prolonged rise of serum aminotransferases, which was not preceded by acute hepatitis, was detected in 23 additional patients (17%). Acute hepatitis and prolonged hypertransaminasemia were more frequent in patients dialyzed at a hospital unit than in patients dialyzed outside the hospital or at home. These observations indicate that development of acute and chronic liver disease, mainly hepatitis non-A, non-B, is frequent in patients on chronic hemodialysis, particularly in those dialyzed in hospital. Serologic evidence of current or past infection by HBV was detected in 57 patients (42%) with sustained positivity of HBV serum markers. Transient positivity for anti-HBc, anti-HBs, or both, possibly related to passive transmission of antibodies by blood transfusion, was observed in 20 patients (15%). These findings indicate that periodic, repeated testing for HBV serum markers is necessary only in a minority of patients on long-term hemodialysis.

In order to evaluate the specificity of tumor markers in chronic renal failure, we have determined serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), carbohydrate antigen 50 (CA 50), alfafetoprotein (AFP), neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), squamous cell carcinoma antigen (SCC), carbohydrate antigen 15.3 (CA 15.3) and carbohydrate antigen 125 (CA 125) in 30 patients with cronic renal failure and in 36 hemodialyzed patients without clinical evidence of neoplasia. CEA, CA 50, NSE and SCC frequently show increased serum levels, suggesting a renal metabolism, while others remain, generally, within the normal levels.

Angiotensin converting enzyme gene I/D polymorphism in essential hypertension and nephroangiosclerosis. An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene significantly influences circulating ACE levels and plays a role in the development of target organ damage, that is, left ventricular hypertrophy in essential hypertension (EH), and microalbuminuria in diabetes mellitus. We have examined the role of the I/D polymorphism in essential hypertensive patients with renal involvement. The study was divided in two independent protocols. In protocol 1, we retrospectively analyzed the ACE genotypes in 37 essential hypertensive patients with a clinical and histopathological diagnosis of nephroangiosclerosis. In protocol 2, ACE genotypes as well as microalbuminuria and renal hemodynamic parameters were investigated in 75 patients with EH with normal renal function and a strong family history of hypertension. As control group, 75 healthy subjects with BP < 130/85 mm Hg and no family history of cardiovascular diseases were studied. The ACE variants were determined by PCR and the genotypes were classified as DD, DI and II. In protocol 1, patients with nephroangiosclerosis displayed a significant difference in the genotype distribution (57% DD, 27% DI, 16% II) when compared to the control population (25% DD, 64% DI, 11% II; P < 0.001). There was no significant difference in genotype distribution between hypertensive patients with normal renal function (protocol 2; 33% DD, 59% DI, 8% II) and the control group. There were no differences in age, blood pressure, microalbuminuria and duration of the disease among the three genotypes in the EH group from protocol 2. Taken together, these findings suggest that the DD genotype of ACE is associated with histopathologic-proven kidney involvement in patients with EH and that this polymorphism could be a potential genetic marker in hypertensives at risk of renal complications.

Extremely careful observation of preventive measures seems essential to eradicate HCV transmission in Background. Hepatitis viruses have become one of the main infectious problems in patients on maintenance haemodialysis units. haemodialysis. The aim of this study was to prospect- Key words: blood transfusion; genotypes; HCV; ively investigate the incidence of de novo hepatitis C haemodialysis; nosocomial; transmission virus ( HCV ) infection in a haemodialysis unit and to identify factors currently involved in HCV transmission to haemodialysis patients. Methods. One hundred and fourteen anti-HCV nega- Introduction tive and HCV-RNA negative patients who started long-term haemodialysis were followed for a mean After the introduction of measures aimed to control period of 36 months (range 18‐56 ). Liver tests and the spread of hepatitis B virus infection in dialysis anti-HCV were performed at 6-month intervals. units, it became clear that dialysis patients were at Factors that might be implicated in HCV transmission, increased risk of exposure to the etiologic agent of such as blood transfusions, sexual habits, surgery and parenterally transmitted non-A, non-B (C ) hepatitis. other invasive procedures, were recorded. HCV The prevalence of HCV infection in haemodialysis markers were re-examined in transfused blood and the patients varies markedly from country to country and HCV genotype was investigated in seroconverters to from one center to another and ranges between 5% in anti-HCV and in patients with previous HCV infection North European countries and in the US to more than who were treated in the vicinity of those who 20% in the Mediterranean area [1]. The relevance of seroconverted. HCV infection in patients on haemodialysis is related Results. Eight patients (7%) seroconverted to anti- to the development of serious liver disease, particularly HCV and seven of them became HCV-RNA positive. after renal transplantation [2‐4 ]. HCV markers, including HCV-RNA, were negative in Blood transfusion and the length of time on the blood transfused to seroconverters. No differences haemodialysis were the main factors involved in HCV between seroconverters and non-seroconverters were transmission to haemodialysis patients in the past [5 ]. found in other risk factors not directly related to However, despite screening of blood products for HCV haemodialysis. The investigation of HCV genotype and the wide use of erythropoietin, which reduces suggested that HCV transmission was not restricted to blood transfusion requirements, some patients still patients treated in the vicinity of previously HCV become infected by HCV during haemodialysis. Thus, infected patients. Occasional failure to observe strict mechanisms other than blood transfusion do possibly measures of asepsis was detected in the haemodialysis operate in HCV transmission in this setting. unit and this was the only factor that might be The analysis of genomic sequences of HCV isolates incriminating. from around the world has demonstrated that these Conclusions. HCV acquisition in patients on haemodia- sequences can be classified into distinct genotypes [6 ]. lysis is currently not related to blood transfusion, and The existence of several genetic groups of HCV has nosocomial transmission within the haemodialysis unit clinical relevance and the molecular analysis of HCV seems to be the main mechanism of HCV infection. genomes has been extensively used in epidemiological

From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival1 year mean hospitalization days was 9.6 (P0.001). The median survival was 20 months and six patients survived for3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long-term survivors.

Isolated mesangial C3 proliferative glomerulonephritis is a nephropathy poorly defined among glomerular diseases. Clinical picture is characterized by episodes of gross hematuria and/or persistent or recurrent microhematuria and/or proteinuria. Short-term prognosis (less than 3 years) is considered to be benign, although not much information is available in reference to long-term follow-up. We reviewed all renal biopsies performed in our center between 1978 and 1992 (n = 2,200) in order to study clinical course of these patients. Isolated mesangial C3 deposition was found in 11 cases (0.5%). Isolated proteinuria (0.5 g/d) was present in 3 patients and nephrotic syndrome in 2. Hematuria with proteinuria was detected in 5 patients. In one patient hematuria was the only clinical finding. Arterial hypertension was observed in 4 cases. At the time of renal biopsy, renal function was accurately normal in all but one patient. In our series, renal function showed no changes during the first 3 years, accordingly to data referred to in the literature. After 7 years of follow-up, however, renal function was declining in 4 of 5 patients who developed terminal renal failure up to requiring hemodialysis. Therefore, initial benign prognosis ascribed to this glomerulonephritis would not be confirmed in a long-term follow-up.

To investigate the possible relationships between blood pressure, parathyroid hormone (PTH) and platelet cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in patients with essential hypertension, we studied 17 patients with this disease aged 48±2 years and 17 normotensive controls aged 44±3 years. Platelet [Ca 2+ ] i was measured by spectrofluorimetry using the dye Fura-2 acetoxymethylester. Patients with essential hypertension displayed lower levels of serum ionized Ca 2+ (0.99±0.03 versus 1.1±0.01 mmol/l, P

Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension. To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 ± 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 ± 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 ± 3 vs. 48 ± 1 nmol/liter, P < 0.005), but there were no differences in resting pHi between both groups (7.16 ± 0.01 vs. 7.16 ± 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 ± 21 vs. 206 ± 19; P < 0.05) as was the pHi increment (EH: 0.137 ± 0.01; NT: 0.095 ± 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pHi were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01). At higher doses of thrombin (2.5 U/ml), the enhanced increment in both platelet [Ca2+]i (EH: 732 ± 20; NT: 619 ± 15 nmol/liter, P < 0.05, N = 6) and in pHi (EH: 0.193 ± 0.001; NT: 0.150 ± 0.004 P < 0.005, N = 6) was also observed in patients with EH. In the absence of Ca2+○ (chelated with EGTA), there were no significant differences between patients with EH and NT in thrombin-induced increases neither in [Ca2+]i (EH: 140 ± 18; NT: 121 ± 22 nmol/liter) nor in pHi (EH: 0.098 ± 0.01; NT: 0.079 ± 0.01). When the agonist-induced increase in [Ca2+]i was prevented with the Ca2+i chelator MAPTAM, no rise in pHi was observed in either group. In conclusion, in platelets challenged with thrombin, the agonist-induced activation of the Na+/H+ exchanger occurs in correlation with the increment in [Ca2+]i, and both are significantly increased in patients with EH only in the presence of Ca2+○. Furthermore, the magnitude of the agonist-induced changes in [Ca2+]i and in pHi showed a direct relationship with MAP in the EH group. The agonist-induced activation of the Na+/H+ exchanger requires a rise in [Ca2+]i both in patients with EH and in NT subjects.

Mitomycin C (MMC) is an alkylating agent that has been recently associated with the hemolytic-uremic syndrome (HUS). Pulmonary impairment in the HUS is rarely reported in the literature, and no reports of pulmonary hemorrhage, as a clinical feature of the HUS, have been documented. We describe two women who developed HUS after MMC therapy and presented massive pulmonary bleeding. Pulmonary hemorrhage is an uncommon feature in the HUS, and seems to appear especially in the HUS associated with MMC therapy. It is extremely resistant to standard treatment, and confers a poor prognosis for this disease.

Cytomegalovirus (CMV) is an ubiquitous agent and is recognized as a pathogen in all age groups. Although symptomatic infection by CMV (CMV disease) in normal adults is generally mild, the virus is known to produce severe symptoms, mostly in immunocompromised patients. In this group of patients, the primary involvement of the colon by CMV is reported to be rare. However, chronic renal failure patients are prone to CMV infection. Nevertheless, despite the high incidence of infection in these patients and the recognition of a defective immune response in some of them, clinical manifestations are an exception. Two chronic renal failure patients who developed acute colitis due to CMV infection are presented. Of interest are the rarity of the association, the favorable clinical course and the differential diagnosis with other gastrointestinal disorders which are more common in these patients.

We have conducted a prospective study of 372 patients with well-defined forms of systemic vasculitis and connective tissue diseases to determine the prevalence, the antigenic specificities and the clinical associations of ANCA in such cases. These antibodies were detected by indirect immunofluorescence on ethanol-fixed neutrophils and also by enzyme-linked immunosorbent assay using myeloperoxidase (MPO) as a substrate. In our study, ANCA with a cytoplasmic immunostaining pattern were mainly found in patients with biopsy-proven Wegener’s granulomatosis with or without renal involvement and pulmonary hemorrhage. Furthermore, MPO-ANCA strongly correlated with necrotizing glomerular and alveolar capillaritis, mostly in patients having a well-established diagnosis of polyarteritis nodosa.

In order to study the development of acquired renal cystic disease (ARCD) and its potential complications, we studied, macro- and microscopically, 82 surgical specimens of nephrectomy carried out on young patients with chronic renal failure previous to renal transplantation. Statistical correlation of pathological findings with age, sex and time on hemodialysis (HD) have been done. There were 72 cases of ARCD (87.8%). It was statistically correlated with male sex (p less than 0.02) and prolonged time on HD (p less than 0.001) as has been previously reported. Hyperplasia of the cystic epithelium was found in 42 cases (52%), with 18 (22%) showing marked papillary proliferation. Also, there were 22 cases (27%) with renal adenomas. This incidence of hyperplastic and neoplastic proliferations, more than would be common in such a young population (males: 33.5 +/- 9.3 years; females: 35.4 +/- 11.7 years), suggests the potential of patients affected by ARCD to develop neoplasms. Thus, we consider that these patients must be checked periodically to detect possible malignant neoplasms.

A case is presented of a patient affected of chronic renal failure caused by multiple myeloma who was under a chelating treatment with Depreroxamine as a consequence of iron intoxication and suffered a disseminated mucormycosis. We performed a literature search of previous cases and discuss the probable relation between this opportunistic infection and depheroxamine treatment.

We report a patient with NHL=NON-HODGKIN LYMPHOMA who developed synchronously acute renal failure due to focal necrotising glomerulonephritis. A review of similar cases reported in the literature and a discussion about its pathogenetic relationship are presented

Hemolytic uremic syndrome (HUS) is a severe complication that has been associated with mitomycin C(MMC) therapy and is referred to be mostly unresponsive to treatment. In the last 2 years we have observed 3 patients affected by HUS associated with MMC therapy which were treated with plasmapheresis