A novel GLA mutation in a Fabry family with glucose-6-phosphate dehydrogenase deficiency.

Fabry disease is an X-linked lysosomal disease caused by mutations of the alpha-galactosidase A (GLA) gene at chromosome subband Xq22.1. To date, more than 600 genetic mutations have been identified to determine the nature and frequency of the molecular lesions causing the classical and milder variant phenotypes and for precise carrier detection. We report here a Fabry family (mother, son and daughter) where the alpha-galactosidase A defect was associated with a glucose-6-phosphate dehydrogenase (G6PD) deficiency. Mutation analysis revealed for the GLA gene the presence of a new mutation, i.e., a small deletion (c.452delA) on exon 3 and for the G6PD gene the presence of 2 mutations, p.V68M (G6PD Asahi, G6PD A+) and p.N126D (G6PD A+) on exon 3 and exon 4, respectively.

Hyporesponsiveness to erythropoiesis-stimulating agents and renal survival in non-dialysis CKD patients.

BACKGROUND: Lower responsiveness to erythropoiesis-stimulating agents (ESA-R) predicts cardiovascular (CV) events. Whether ESA-R also affects the risk of end-stage renal disease (ESRD) is unknown. METHODS: We evaluated ESA-R in 194 consecutive chronic kidney disease (CKD) patients, regularly seen in outpatient nephrology clinics, who started erythropoiesis-stimulating agent (ESA) therapy between 2002-06. Exclusion criteria were causes of anaemia other than CKD or recent transfusion. ESA-R was calculated as (Hb1-Hb0)/time/ESA dose (g/dL/month/10 µg/week of ESA). Patients were classified, from lower to higher tertile of ESA-R, as poor, intermediate and good responders. Time to ESRD was the primary outcome. RESULTS: Age was 64±16 years, 48% were male, 34% had diabetes and 32% had CV disease, glomerular filtration rate (GFR) 24±13 mL/min/1.73 m2 and proteinuria 0.6 g/dL (interquartile range 0.2-1.9). First ESA dose was 23.7±10.8 µg/week; haemoglobin (Hb) increased from 9.9±0.8 g/dL to 11.0±1.2 g/dL at first control, obtained after 1.4±0.4 months. These changes corresponded to an ESA-R of 0.37±0.38 g/dL/month/10 µg/week of ESA and tertiles limits were 0.17 and 0.47. Poor responders were younger and had lower GFR and higher proteinuria than intermediate and good responders. During the first 6 months of ESA therapy, poor responders showed lower Hb levels and sustained longer periods of Hb level<11 g/dL. During follow-up (median 3.0 years), 99 patients reached ESRD. At multivariable Cox's analysis, poor responsiveness was associated with higher risk of ESRD (hazard ratio 2.49, 95% confidence interval 1.28-4.84). CONCLUSION: ESA-R predicts renal prognosis in CKD patients followed in nephrology practice, where ESRD is the predominant outcome and ESA is commonly used at low dose.

Nephrotic syndrome and autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development and growth of cysts in the kidneys and other organs. In ADPKD patients, nephrotic range proteinuria is unusual and needs to be investigated further to exclude coexisting glomerular disease. Among the anecdotal case reports of ADPKD associated with nephrotic syndrome, focal segmental glomerulosclerosis occurs most frequently. METHODS: We report the case of a 26-year-old male with ADPKD and concomitant nephrotic syndrome, in which an ultrasound (US)-guided renal biopsy showed a mesangioproliferative glomerulonephritis. We treated the patient with prednisone 1 mg/kg/day, because of the failure of treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker association. RESULTS: After 6 months of steroid treatment, we observed a stability of his GFR and a reduction of proteinuria. CONCLUSION: This case report and other cases of the literature underline the importance of a renal biopsy in patients with ADPKD and nephrotic syndrome in order to make an accurate diagnosis and an appropriate treatment/prevention of renal function deterioration.

Simultaneous multicystic kidney and Anderson-Fabry disease: 2 separate entities or same side of the coin.

We present the case of a 54-year-old man with multicystic kidney and concomitant Anderson-Fabry disease. He was referred to our hospital with multiple renal and hepatic cysts, without apparent family history of autosomal dominant polycystic kidney disease. His clinical history suggested Anderson-Fabry disease, so an extensive work-up for Anderson-Fabry disease was subsequently undertaken. The alpha-galactosidase activity in his serum was low, and a final diagnosis of Anderson-Fabry disease with concomitant multicystic kidney was confirmed by genetic analysis.

Fabry disease: perspectives of urinary proteomics.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the gene encoding the lysosomal enzyme a-galactosidase A (a-GalA). The resulting deficiency in a-GalA activity leads to intra-lysosomal accumulation of neutral glycosphingolipids, mainly globotriaosylceramide (Gb3), in various organ systems. As a consequence, a multisystem disorder develops, culminating in strokes and progressive renal and cardiac dysfunction. Enzyme replacement therapy (ERT) offers a specific treatment for patients affected by FD, though monitoring treatment is hampered by a lack of surrogate markers of response. Furthermore, even if signs and symptoms of the disease become manifest in childhood, its diagnosis is often delayed. Biomarkers that predict disease progression and respond relatively quickly to effective therapy may be useful to follow individual patients or groups of patients. Here we report the use of 2 different mass spectrometry-based proteomic techniques to identify disease-associated compositional changes that can be used as early biomarkers of the pathology, as well as for monitoring the effectiveness of ERT. To this purpose, we compared the renal Fabry urinary proteome with normal (control) urine using, respectively, 2-dimensional gel electrophoresis and label-free quantification. Our preliminary results show that the urinary protein pattern of affected patients can be easily distinguished from that of healthy subjects both qualitatively and quantitatively, thus encouraging further studies in the search for FD-specific biomarkers using this proteomic approach.

Prognostic indicators of renal disease progression in adults with Fabry disease: natural history data from the Fabry Registry.

BACKGROUND AND OBJECTIVES: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (eGFR) values over a span of ≥12 months before starting enzyme replacement therapy were included. RESULTS: Most men (86 of 121, 71%) had more rapid loss of kidney function than the normal adult population (loss of eGFR > -1 ml/min per 1.73 m(2) per year), whereas fewer women (133 of 341, 39%) had rapid loss of kidney function. Patients with rapid progression had significantly higher mean averaged urinary protein to urinary creatinine ratios (UP/Cr) than patients with slower progression (1.5 versus 0.2 for men; 1.4 versus 0.5 for women; P < 0.0001). Patients were grouped into quartiles based on averaged UP/Cr; renal function in men declined more rapidly with higher UP/Cr, with the steepest declines observed in men with UP/Cr > 1.5 (mean eGFR slope, -5.6 ml/min per 1.73 m(2) per year; n = 30). eGFR slope declined more slowly in women, with the steepest declines observed in women with UP/Cr > 1.2 (mean eGFR slope, -1.3 ml/min per 1.73 m(2) per year; n = 85). Regression models of eGFR slope indicated that UP/Cr is the most important indicator of renal disease progression in adult Fabry patients. In women, lower baseline eGFR and age were also associated with renal disease progression. Women who had clinical events had more rapid loss of kidney function. CONCLUSIONS: Urinary protein excretion is strongly associated with renal disease progression in men and women with Fabry disease.

End-stage renal disease in patients with Fabry disease: natural history data from the Fabry Registry.

BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase activity, is associated with progressive loss of kidney function. This study was undertaken to characterize Fabry disease among patients who reached end-stage renal disease. METHODS: Data from 2,712 patients in the Fabry Registry were analysed to identify clinical characteristics of patients who received renal replacement therapy (RRT) during the natural history period (i.e. prior to any enzyme replacement therapy). RESULTS: A total of 213 patients [186 of 1,359 males (14%) and 27 of 1,353 females (2%)] received RRT at a median age of 38 years in both males and females. Males who received RRT were diagnosed at a median age of 35 years, compared to 23 years for non-RRT males. Sixty-one males and 10 females were not diagnosed with Fabry disease until after they had received RRT. Compared to other Fabry Registry patients, a higher percentage of RRT patients also experienced either a serious cardiovascular event or a stroke. Ninety-two of 186 males who had RRT (50%) experienced a cardiac event or stroke, compared to 230 of 1,173 non-RRT males (20%). Ten of 27 RRT females (37%) had experienced a cardiac event or stroke, compared to 226 of 1,326 non-RRT females (17%). Patients who had RRT experienced cardiovascular events and strokes at earlier ages than did patients who had not received RRT, and most received RRT before having a cardiac event or stroke. CONCLUSIONS: While all Fabry patients are at risk of cardiovascular events and strokes, patients with Fabry nephropathy who develop kidney failure appear to have concurrent involvement of other major organ systems. It is important that Fabry patients are diagnosed early and that their renal function is monitored carefully.

Effect of a low- versus moderate-protein diet on progression of CKD: follow-up of a randomized controlled trial.

BACKGROUND: Whether low-protein-diet (LPD) as opposed to moderate-protein-diet (MPD) regimens improve the long-term survival of patients with chronic kidney disease (CKD) or induce protein-caloric malnutrition is unknown. STUDY DESIGN: Intention-to-treat analysis of follow-up data from a randomized controlled trial. SETTING & PARTICIPANTS: 423 patients with CKD (stages 4-5) were randomly assigned between January 1999 and January 2003 and followed up until December 2006 or death. The first phase of follow up was from January 1999 to June 2004; additional follow-up was from July 2004 to December 2006. INTERVENTION: LPD versus MPD (protein intake, 0.55 vs 0.80 g/kg/d). OUTCOMES: Protein-caloric malnutrition (defined as the occurrence of 1 of the following: loss of body weight > 5% in 1 month or 7.5% in 3 months or body mass index < 20 kg/m(2) with serum albumin level < 3.2 g/dL and normal C-reactive protein level [<0.5 mg/dL]), dialysis, death, or the composite outcome of dialysis and death. RESULTS: Baseline mean age was 61 years, estimated glomerular filtration rate was 16 mL/min/1.73 m(2), proteinuria had protein excretion of 1.67 g/d, body mass index was 27.1 kg/m(2), protein intake was 0.95 g/kg/d, and there were 57% men. Duration of follow-up was 32 months (median, 30 months; 25th-75th percentiles, 21-39). Average protein intakes were 0.73 +/- 0.04 g/kg/d for the LPD and 0.9 +/- 0.06 g/kg/d for the MPD. 3 patients (0.7%) met criteria for protein-caloric malnutrition. 48 patients died (11%), 83 initiated dialysis therapy (20%), and 113 (27%) reached the composite outcome. In unadjusted Cox survival analyses, effects of the LPD on these outcomes were 1.01 (95% CI, 0.57-1.79), 0.96 (95% CI, 0.62-1.48), and 0.98 (95% CI, 0.68-1.42), respectively. LIMITATIONS: Low event rates for dialysis therapy initiation and death. CONCLUSIONS: Most patients, who were regularly followed up in CKD clinics, were acceptably adherent to the prescribed dietary protein intake restrictions; the LPD and MPD did not lead to protein wasting; and the LPD did not decrease the risk of death or dialysis therapy initiation compared with the MPD.

Epoetin therapy and hemoglobin level variability in nondialysis patients with chronic kidney disease.

BACKGROUND AND OBJECTIVES: Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb variability and renal survival in nondialysis CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy). RESULTS: Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P = 0.002). The area under the curve for Hb (11.56 +/- 0.87, 11.46 +/- 1.20, and 10.95 +/- 1.48 g/dl per yr; P = 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 +/- 2.0 to 3.0 +/- 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P = 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio [95% confidence interval]), risk for renal death was increased in the middle and higher tertiles (2.79 [1.36 to 5.73] and 2.94 [1.40 to 6.20]) and reduced by longer time in target (0.90 [0.83 to 0.98]). CONCLUSIONS: Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship.

Italian randomized trial of hemoglobin maintenance to prevent or delay left ventricular hypertrophy in chronic kidney disease.

BACKGROUND: This study is part of a 3-country study testing whether normal levels of hemoglobin (Hgb) delay the progression of left ventricular (LV) growth in chronic kidney disease (CKD) patients not on dialysis. METHODS: This was an open-label, randomized, multicenter, controlled trial conducted in 27 tertiary-care hospitals in Italy. Treated subjects (n=46) received epoetin-alpha (EPO-alpha) to maintain Hgb levels in the range 12-14 g/dL. Control subjects (n=49) were not treated unless their Hgb decreased to 9.0 g/dL. Primary outcome was LV mass index (MI) change after 24 months. Subcutaneous EPO-alpha was withdrawn in Europe and the study prematurely terminated; therefore, a 12-month analysis was carried out. RESULTS: Mean age was 57 years (38% were women, 18% with diabetes, 76% taking ACEI or ARB and 22% statins). EPO-alpha median final dose was 2,000 IU/week. Hgb significantly increased (12.4 -/+ 1.1 g/L) for the treatment group and decreased for controls (11.3 -/+ 1.3 g/L; p<0.001). The intention-to-treat analysis was conducted in 78 patients. Mean baseline LVMI for treated patients and controls was 109.5 -/+ 23 g/m2 and 108.7 -/+ 29 g/m2, respectively. LVMI did not change among controls, whereas it decreased slightly, though not significantly, among treated patients. CONCLUSIONS: The current Italian trial was negative, maybe due to its limitations: lack of power, 1-year follow-up and normal LVMI in some patients at start; however, it was consistent with other published studies. Thus, it is unlikely that targeting hemoglobin in the normal range for CKD patients is of benefit.

Renal transplantation and sleep: a new life is not enough.

Renal transplantation is associated with better survival and improved quality of life compared to maintenance dialysis. Although many sleep disorders improve or even disappear after a successful transplantation, sleep quality remains low, and the prevalence of sleep complaints, although lower than in dialysis patients, is much higher than in the general population. Few studies have dealt with sleep problems of renal transplant patients: despite reporting obvious differences in the prevalence of the single sleep disorders, all underline the importance of psychological problems in conditioning sleep. In the diagnosis of sleep disorders, the nephrologist must learn to distinguish medical risk factors (pain, pruritus, tremors, drugs) and psychological aspects (depression, anxiety, fear), since they are potentially modifiable with the appropriate treatment.

Nephropathy in males and females with Fabry disease: cross-sectional description of patients before treatment with enzyme replacement therapy.

BACKGROUND: Fabry disease, an X-linked genetic disorder with deficient alpha-galactosidase A activity, is characterized by kidney disease and kidney failure. The spectrum of kidney disease has not been well defined, especially in female patients. METHODS: We did a cross-sectional retrospective analysis of natural history of glomerular filtration rate (estimated- eGFR), albuminuria and proteinuria in 1262 adult patients (585 males, 677 females) from the Fabry Registry. RESULTS: Twenty-eight percent of males (age 20-79 years) and 13% of females (age 20-82 years) had chronic kidney disease (CKD) with eGFR < 60 ml/min/1.73 m(2). Overt proteinuria (>300 mg/24 h) was demonstrated in 43 and 26% of males and females with CKD stage 1, respectively, and the proportions were higher with more severe kidney involvement. However, 11% of males and 28% of females with eGFR < 60 ml/min/1.73 m(2) had proteinuria <300 mg/ 24 h. Of eGFR >/= 60 ml/min/1.73 m(2) patients without overt proteinuria (n = 93), 55% of the males and 35% of the females had albuminuria >30 mg/24 h. Systemic blood pressure was >/=130/80 mmHg in 48% and 67% of patients with eGFR >/= and <60 ml/min/1.73 m(2), respectively, with no significant differences between males and females. Proteinuria values were significantly correlated with systolic blood pressure in both sexes. CONCLUSIONS: Kidney involvement in Fabry disease is more prevalent and heterogeneous than previously reported. Proteinuria is an early complication, but may not be overt in patients with advanced kidney disease. This analysis, which includes more females than males, confirms that a significant proportion of females suffer moderate to severe kidney involvement in Fabry disease.

Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy.

BACKGROUND: In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). METHODS: This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. RESULTS: The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. CONCLUSIONS: Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

MRI characterization of myocardial tissue in patients with Fabry's disease.

OBJECTIVE: Fabry's disease is a multisystem X-linked disorder of lysosomal metabolism frequently associated with left ventricular (LV) hypertrophy. In this study, we aimed to assess whether myocardial T2 relaxation time determined by a black blood multiecho multishot MRI sequence could be used to evaluate cardiac involvement in patients with Fabry's disease. CONCLUSION: Myocardial T2 relaxation time is prolonged in patients with Fabry's disease compared with that of hypertrophic patients and healthy control subjects. MRI may be useful for the characterization of myocardial tissue in patients with Fabry's disease.

Inhibition of Ras/ERK1/2 signaling protects against postischemic renal injury.

The small GTPase p21 Ras and its downstream effectors play a central role in the control of cell survival and apoptosis. We studied the effects of Ras/ERK1/2 signaling inhibition on oxidative damage in cultured renal and endothelial cells and on renal ischemia-reperfusion injury in the rat. Primary human renal tubular and human endothelial ECV304 cells underwent significant cell death when subjected to oxidative stress. This type of stress induced robustly ERK1/2 and phosphoinositide 3-kinase (PI3-kinase) signaling. Inhibition of Ras/ERK1/2 with a farnesyl transferase inhibitor, chaetomellic acid A (S-FTI), or with PD-98059, an inhibitor of MEK, a kinase upstream ERK1/2, significantly reduced the fraction of dead cells. The inhibitor of the PI3-kinase/Akt pathway, LY-294002, failed to exert a protective effect. We have translated these data in a rat model of renal ischemic injury in vivo. In uninephrectomized animals, anesthetized with pentobarbital sodium (Nembutal, 50 mg/kg i.p.), 24 h after an acute ischemic renal insult (45-min occlusion of left renal artery) a significant fraction of kidney cells succumbed to cell death resulting in renal failure [glomerular filtration rate (GFR) 0.17 +/- 0.1 vs. 0.90 +/- 0.4 ml x min(-1) x 100 g body wt(-1) in normal rats]. Rats treated with S-FTI maintained the renal function (GFR 0.50 +/- 0.1 ml x min(-1) x 100 g body wt(-1)), and the kidneys showed a significant reduction of tubular necrosis. Reduction of ischemic damage in kidney and tubular cells paralleled Ha-Ras inhibition, assayed by cytosolic translocation of the protein. These data demonstrate that inhibition of farnesylation and consequently of Ras/ERK1/2 signaling significantly reduces acute postischemic renal injury.

Enzyme replacement therapy in Fabry disease patients undergoing dialysis: effects on quality of life and organ involvement.

BACKGROUND: Fabry disease is a lysosomal storage disease resulting from deficient alpha-galactosidase A (alpha-Gal A) activity. End-stage renal disease generally occurs around the fourth decade of age, and dialysis therapy is a life-saving procedure. For patients with Fabry disease undergoing dialysis, death usually occurs from cardiac or cerebrovascular complications. Recently, enzyme replacement therapy was introduced for treatment of the disease. METHODS: We report results of several clinical outcomes after 2 years of treatment with alpha-Gal A in patients with Fabry disease undergoing dialysis. Nine dialysis patients underwent a complete clinical, cardiac, and cerebrovascular evaluation at baseline and after 24 months of treatment. Two patients reported a recurrent pain crisis, and 6 patients reported gastrointestinal symptoms. In all patients, enzyme replacement therapy was undertaken because of the presence of Fabry cardiomyopathy. A complete echocardiographic study was performed in 6 patients 12 and 24 months before and 12 and 24 months during enzyme replacement therapy. RESULTS: Enzyme replacement therapy was well tolerated. Pain crises disappeared completely after approximately 6 months of treatment, and patients with gastrointestinal involvement reported improvement in symptoms after 6 to 8 months. At baseline, all patients had left ventricular concentric hypertrophy. Enzyme replacement therapy did not affect heart rate or mean arterial pressure. The mean slope of left ventricular mass index progression decreased from 0.98 +/- 0.01 in the pretreatment period (24 months) to 0.46 +/- 0.960 in the enzyme-replacement-therapy period (P = 0.06). CONCLUSION: Our observation indicates that in dialysis patients, enzyme replacement therapy is safe and effective, improving global quality of life and possibly ameliorating the progression of typical Fabry cardiomyopathy.

Gastroduodenal lesions and Helicobacter pylori infection in dyspeptic patients with and without chronic renal failure.

BACKGROUND: Patients with chronic renal failure (CRF) often have dyspeptic symptoms and may develop peptic disease or digestive disorders leading to severe gastrointestinal complications. The primary aim of this study was to evaluate the prevalence of peptic lesions and Helicobacter pylori infection, and the severity of dyspeptic symptoms, in dyspeptic patients with and without CRF. Our secondary aim was to investigate whether uremic status may affect the diagnostic efficiency of the [13]C-urea breath test ([13]C-UBT). PATIENTS AND METHODS: We consecutively enrolled in the study 50 dyspeptic patients with chronic kidney failure (mean age 52 +/- 5 years), of whom 11 were on hemodialysis treatment (HD), and 93 subjects (mean age 54 +/- 7 years) with chronic dyspepsia and normal renal function (NRF). All patients completed an oriented and validated questionnaire scoring the severity of nine dyspeptic symptoms (i.e. epigastric pain, epigastric burning, postprandial fullness, early satiety, bloating, belching, nausea and vomiting) and underwent upper endoscopy with multiple bioptic sampling for rapid urease test and histological examination, [13]C-UBT and HpSA test. RESULTS: The prevalences of peptic lesions and H. pylori infection and mean symptom score were 74%, 52% and 3.5 +/- 3, respectively, in dyspeptic patients with CRF and 18%, 36% and 8 +/- 5, respectively, in dyspeptic patients with NRF. The diagnostic accuracy of [13]C-UBT with respect to histological diagnosis was 94% and 97% for dyspeptic patients with and without renal failure, respectively. CONCLUSIONS: 1, A high frequency of peptic lesions and low symptom scores were observed in uremic patients in spite of H. pylori infection; 2, uremic status did not affect the diagnostic accuracy of [13]C-UBT.

Insomnia in maintenance haemodialysis patients.

BACKGROUND: Studies in the last 15 years have shown a high prevalence of sleep disorders in maintenance haemodialysis (HD) patients. METHODS: To investigate whether the new technical and therapeutic advances of the last decade have had a positive impact on sleep disturbances in HD patients: 694 patients (384 males, 310 females) were surveyed using a specific questionnaire; their clinical, lifestyle and dialysis data were also recorded. RESULTS: Forty-five per cent of patients (n=311; 156 males, 155 females) complained of insomnia, defined either by delayed sleep onset and/or night-time waking, and were included in the insomnia group; the remainder were used as controls (control group). There was a significantly higher risk of insomnia in patients with >12 months on dialysis, in patients dialysed in the morning (P<0.003), and in patients with higher parathyroid hormone (PTH) levels (P<0.05). Body mass index, body weight gain and blood pressure did not differ between the groups, and neither did the dialysis parameters. Creatinine and urea plasma levels were higher in the control group vs the insomnia group (P<0.001), but there was no difference in haemoglobin concentrations or use of erythropoietin, calcitriol and antihypertensive drugs. Cigarette smoking, caffeine or alcohol intake were comparable in the two groups. The most frequently recorded sleep disorders were night-time waking (92%), trouble falling asleep (67%) and early morning waking (62%). Restless leg symptoms were described in 52% of patients with insomnia. CONCLUSIONS: The prevalence of insomnia in HD patients is still very high; elderly patients, and those with longer time on dialysis and high levels of PTH are at major risk of insomnia, whereas type of dialysis, haemoglobin levels and behavioural factors do not seem to play a critical role in determining this sleep disorder.

Visceral Leishmaniasis in renal transplant recipients: is it still a challenge to the nephrologist?

A case of visceral Leishmaniasis in a renal transplant recipient is reported because of its peculiar clinical presentation: the presence of most clinical signs of the disease, such as high-grade fever, marked leucopenia, and splenomegaly, but persistent negativity of serology and of bone marrow smear. Forty days after the first bone marrow biopsy, the diagnosis was made possible by a second biopsy, and the treatment was started with antimonial compounds, which led to complete remission of symptoms. A relapse was observed 1 month after discontinuation of therapy, successfully treated with a new cycle of the same drug and allopurinol. The diagnosis of Leishmaniasis must always be considered in immunosuppressed transplant recipients with fever and leucopenia of unknown origin, even when serology and bone marrow smear are negative.