A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation.

BACKGROUND: Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS: One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS: After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION: Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Cholesterol crystal embolism: A recognizable cause of renal disease.

Cholesterol crystal embolism, sometimes separately designated atheroembolism, is an increasing and still underdiagnosed cause of renal dysfunction antemortem in elderly patients. Renal cholesterol crystal embolization, also known as atheroembolic renal disease, is caused by showers of cholesterol crystals from an atherosclerotic aorta that occlude small renal arteries. Although cholesterol crystal embolization can occur spontaneously, it is increasingly recognized as an iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery, and after anticoagulant and fibrinolytic therapy. Cholesterol crystal embolism may give rise to different degrees of renal impairment. Some patients show only a moderate loss of renal function; in others, severe renal failure requiring dialysis ensues. An acute scenario with abrupt and sudden onset of renal failure may be observed. More frequently, a progressive loss of renal function occurs over weeks. A third clinical form of renal atheroemboli has been described, presenting as chronic, stable, and asymptomatic renal insufficiency. The renal outcome may be variable; some patients deteriorate or remain on dialysis, some improve, and some remain with chronic renal impairment. In addition to the kidneys, atheroembolization may involve the skin, gastrointestinal system, and central nervous system. Renal atheroembolic disease is a difficult and controversial diagnosis for the protean extrarenal manifestations of the disease. In the past, the diagnosis was often made postmortem. However, in the last decade, awareness of atheroembolic renal disease has improved, enabling us to make a correct premortem diagnosis in a number of patients. Correct diagnosis requires the clinician to be alert to the possibility. The typical patient is a white man aged older than 60 years with a baseline history of hypertension, smoking, and arterial disease. The presence of a classic triad characterized by a precipitating event, acute or subacute renal failure, and peripheral cholesterol crystal embolization strongly suggests the diagnosis. The confirmatory diagnosis can be made by means of biopsy of the target organs, including kidneys, skin, and the gastrointestinal system. Thus, Cinderella and her shoe now can be well matched during life. Patients with renal atheroemboli have a dismal outlook. A specific treatment is lacking. However, it is an important diagnosis to make because it may save the patient from inappropriate treatment. Finally, recent data suggest that an aggressive therapeutic approach with patient-tailored supportive measures may be associated with a favorable clinical outcome.

Familial clustering of IgA nephropathy: further evidence in an Italian population.

Several lines of evidence suggest that genetic factors have an important role in the pathogenesis of immunoglobulin A (IgA) nephropathy. We report the prevalence of familial IgA nephropathy in a referral center in northern Italy and present the data on HLA genotypes in the families identified. Twenty-six of 185 patients (14%) with IgA nephropathy investigated in Brescia, Italy, were related to at least one other patient with the disease. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta and HLA-DQ alpha and beta genes, as well as polymerase chain reaction-based oligonucleotide typing, was performed in family members. The 26 patients with IgA nephropathy belonged to 10 families. Familial relationships between the patients varied greatly, ranging from parent-child to sib-pair to more distant familial relationships. No common nephrotoxic factor was identified in the families. The intervals separating the apparent onset of disease in relatives with IgA nephropathy varied from 8 months to 13 years. In patients with a family history of IgA nephropathy, there was an increased incidence of HLA-DRB1*08 compared with those with sporadic IgA nephropathy. The study shows that a significant number of the patients with IgA nephropathy followed up in Brescia had a family history of disease. The fact that the Italian population, an ethnic group not previously examined, also presents an increased familial susceptibility to IgA nephropathy suggests that familial predisposition is a very common finding for IgA nephropathy. Thus, clinicians should become aware that IgA nephropathy may aggregate within families in a substantial number of cases. In addition, this subgroup of patients with IgA nephropathy offers an ideal opportunity to elucidate the molecular genetics of this disease.

Anterior thalamic lesions and neuronal activity in the cingulate and retrosplenial cortices during discriminative avoidance behavior in rabbits.

Bilateral electrolytic lesions of the anteroventral (AV) nucleus of the thalamus given after training impaired retention performance (extinction and reacquisition) of rabbits in a differential avoidance conditioning task. In addition, the lesions abolished the excitatory, discriminative multiple-unit discharges that had developed in the cingulate and retrosplenial cortices to the auditory conditional stimuli (CSs) during the course of behavioral acquisition, prior to the induction of the lesions. The excitatory discharges were supplanted in the subjects with lesions by CS-elicited reduction of neuronal firing to levels below the prestimulus baseline. Lesions given before training did not disrupt behavioral acquisition, but they did eliminate the excitatory tone-elicited neuronal discharges that normally occur in the cortex before and during training. The CS-elicited reduction of neuronal firing did not occur at the beginning of training in the subjects given lesions before training, but it developed during the course of training. The lesions did not eliminate the excitatory and discriminative neuronal activity of the prefrontal cortex. These results demonstrate that excitatory and discriminative neuronal discharges in the cingulate and retrosplenial cortices are critically dependent on the connections of these areas with the anterior thalamic nuclei. Also the lesion-induced disruption of performance during extinction and reacquisition but not during original learning confirms a prediction from past electrophysiological studies, that the AV thalamic nucleus is involved in the mediation of the maintenance and retention of the conditioned avoidance behavior, but not in its original acquisition.

Morbidity and mortality of CAPD and hemodialysis.

We have reappraised studies on morbidity and mortality in continuous ambulatory peritoneal dialysis (CAPD), comparing it with hemodialysis (HD), the standard treatment for end-stage renal disease (ESRD). More hospitalization is required for CAPD, the difference being related to peritonitis, to the more frequent presence of some risk factors (such as diabetes and atherosclerosis) in the patients selected for CAPD, and to the lack of experience in the early years of CAPD practice. CAPD patients have less acute morbidity during treatment that not always requires hospitalization: hypotension, hypertension, arrhythmias, and myocardial ischemia. Cardiac performance is also better in CAPD patients, who develop less myocardial hypertrophy than HD patients. Hospitalization due to infectious disease not referable to technique, beta 2-microglobulin related morbidity, signs of uremic neuropathy, osteodystrophy, and malnutrition are similar in both groups. Method survival is better for HD, the difference being completely accounted for by peritonitis. Patient survival adjusted for pre-treatment differences is similar in CAPD and HD, and this is not an artifact of more drop-outs on CAPD. A high incidence of peritonitis is accompanied by an increased risk of death. Older patients have a lesser risk of death on CAPD than on HD. Diabetics have a worse survival than non-diabetics, with no difference between the two methods. Although patient survivals on CAPD and HD are the same, differences in the mode of blood purification have an interesting impact on particular aspects of morbidity.

Clinical aspects of peritoneal sclerosis.

Peritoneal sclerosis (PS) occurs in various clinical situations in Peritoneal Dialysis (PD) patients. Some degree of PS is often present in long-term PD patients, generally without clinical or functional consequences. At the other end of the spectrum of PS there is Sclerosing encapsulating peritonitis (SEP). Though infrequent, it is very severe. SEP is not a complication exclusive to PD; it is a syndrome related to many diseases of abdominal organs, some drugs and abdominal surgery. Remarkably, in many cases, the first symptoms of SEP appear months or years after the change from PD to HD has occurred. Today there is no full agreement about the microscopical findings of SEP or about the name of this syndrome: SEP or Encapsulating Peritoneal Sclerosis (EPS). The main etiopathogenetic factor for PS is the poor biocompatibility of PD solutions. In the etiopathogenesis of SEP, other factors in addition to the PD fluids have been suggested as possible causes (peritonitis, drugs, disinfectants, etc.). This paper reviews all the clinical aspects of PS and SEP: pathogenesis, clinical signs, diagnosis and therapy.

Diet or dialysis in the elderly? The DODE study: a prospective randomized multicenter trial.

There are no solid data on the real advantage of an early start of dialysis, as suggested by the DOQI guidelines. Uremic patients frequently have a poor nutritional status. However, we cannot distinguish between the detrimental effect on nutrition of too low a residual renal function or too long a period of low protein-diet, per se. However, it appears that a very-low-protein diet (VLPD) supplemented with essential amino acids and keto-analogs of amino acids, and with an adequate quantity of calories, can prevent hypoalbuminemia at the start of dialysis and can slow the progression of chronic renal failure. EDTA and USRDS data suggest that most patients starting dialysis nowadays are elderly, who also have the highest incidence of morbidity and mortality. Moreover, hospitalization rate becomes higher after the start of dialysis compared to the pre-dialysis period. Can an aminoacid-supplemented VLPD, prolonged beyond the GFR limits suggested by DOQI, offer elderly patients better survival and better quality of life than dialysis? The answer can only come from a prospective, randomized trial, in elderly patients, starting at the GFR values suggested by the NKF-DOQI for starting dialysis, comparing outcomes with a vegetarian VLPD supplemented with a mixture of keto-analogs of amino acids and essential amino acids, and with dialysis.

Pneumoperitoneum in peritoneal dialysis patients.

The prevalence and clinical significance of pneumoperitoneum in peritoneal dialysis (PD) patients is not fully defined in current literature and some reports suggest that unlike in non-PD patients, it is rarely caused by gastrointestinal perforation. We reviewed 403 chest X-ray films of the 118 PD patients following our PD program in 1995-96, in order to define the prevalence of pneumoperitoneum. We found pneumoperitoneum in 3.7% of the X-rays (15/403) from five patients (4.2%). Its causes might have been: faulty bag exchange technique in two cases and extension tube exchange in three. One patient suffered from a simultaneous episode of peritonitis. Our data and the literature review suggest that 0-11% of pneumoperitoneum episodes in PD patients are due to gastrointestinal perforation; the main causes generally are abdominal operations and catheter manipulation. The amount of air is not useful in assessing the cause of pneumoperitoneum, which takes some weeks to disappear. Computed tomography is more sensitive than standard X-ray in diagnosis.

Familial membranous nephropathy.

Numerous HLA studies suggest that genetic factors play an important role in the development of membranous nephropathy (MN). We studied seven patients with idiopathic MN, from three unrelated families of Italian ancestry. Complement phenotype analysis and restriction fragment length polymorphism (RFLP) typing of HLA class II and of the switch region genes were done in family members. In the first family, the father, one son, and one daughter had MN; another daughter had clinical glomerulonephritis. The three members with MN shared one HLA haplotype carrying DR beta 11; in the two siblings with the disease, the second HLA haplotype carried the DR beta 3.2 allele. In families 2 and 3, two brothers had MN: in family 2, they differed in at least one haplotype; in family 3, they differed in both haplotypes. Only family 3 was informative with regard to the RFLP of the switch region genes: the two siblings were identical for both Ig heavy chain haplotypes. No clinical, laboratory or morphologic features consistent with a secondary form of the disease were found. Familial clustering of MN suggests a genetically transmitted mechanism.

Molecular analysis of uromodulin and SAH genes, positional candidates for autosomal dominant medullary cystic kidney disease linked to 16p12.

BACKGROUND: The location of a second genetic locus for autosomal dominant medullary cystic kidney disease (ADMCKD) at chromosome 16p12 led us to further investigate the molecular analysis of the critical region where two genes coding for uromodulin and SA proteins with renal specific functions, UMOD and SAH, are localized. METHODS: We characterized the intron-exon boundary sequences by screening phage and BAC DNA genomic clones for the development of new molecular tools functional to the mutation analysis of UMOD and SAH genes. RESULTS: No consistent mutations for ADMCKD2 were found in the UMOD and SAH genes. We identified a silent polymorphism in the UMOD gene at codon C174 which co-segregates with the disease in the ADMCKD2 family. CONCLUSIONS: This study excludes the involvement of uromodulin and SAH genes in ADMCKD2, and provides new tools for their molecular analysis in other diseases.

CAPD is a first class treatment: results of an eight-year experience with a comparison of patient and method survival in CAPD and hemodialysis.

An 8-year experience on CAPD, in a single center with all treatments of ESRF (end-stage renal failure) available, is presented. Method choice was left to the patient, after extensive counselling. However, CAPD selection was very negative, and CAPD patients were older, with a much larger percentage of diabetics and loaded by more risk factors, suggesting an influence of the staff preferences on patient choice. After a first period with unsatisfactory results, we obtained an important improvement of patient and method survival coinciding with the introduction of a new connector with disinfectant (Y-system) which allowed a reduction of peritonitis rate to 1 episode for 36 patient/months. For the period 1.1.81 to 31.12.86 a comparison was made (life table analysis) between new ESRF patients placed initially on CAPD or on HD. The 5-year survival was not statistically different in spite of the very negative CAPD selection of patients, who were 10 years older, on the average. Excluding diabetics, survival curves were identical in the two methods. Age at death and causes of death were not different. Method survival was better on HD (98% vs. 71% on CAPD, at 5 years, p less than 0.01): significance and limits of this evaluation are discussed. Drop-out figures were definitely lower than in the literature and this was attributed to the sharp reduction in peritonitis rate. Only 1.7% of CAPD patients discontinued the method due to inadequate ultrafiltration. In 29 CAPD and 28 HD patients with more than 4 years treatment some biochemical and clinical data were compared. Serum cholesterol was significantly higher and serum proteins lower in CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Body composition and nutritional status in patients on continuous ambulatory peritoneal dialysis (CAPD).

Total body water (TBW), extracellular water (ECW), exchangeable potassium pool (EKP), and alkali-soluble nitrogen in skeletal muscle tissue (N) were determined in 9 CAPD patients on treatment from 5 to 14 months (mean 8.6 months). The parameters were reevaluated in 6 of these patients 5 to 13 months later (mean 8.6 months). The mean value of TBW was normal and directly correlated to body weight (BW), but TBW was abnormally distributed between extracellular and intracellular space. ECW volume was significantly lower than the predicted value (12.1 +/- 1.4 versus 16.8 +/- 1.9 l) and out of proportion to TBW (34.8 +/- 3.9% versus 47.8 +/- 1.5%). The calculated intracellular water, therefore, appeared clearly hyperexpanded. The mean value of EKP was slightly reduced, but in three patients there was a 25% reduction. N content was low in 5 out of 9 patients. When the parameters were re-evaluated BW and TBW were unchanged in two subjects. A third patient showed a simultaneous increase in both BW (12.7%) and TBW (19%). TBW variations (+19%, -23%, -24%) without changes in BW were seen in three patients. The mean value of EKP was unchanged, but there was a 25% reduction in one patient. N content improved in two and worsened in one of the three patients in whom it was determined. The data suggest that cell overhydration was the distinctive feature in our CAPD patients, and that the evolution of the nutritional status was variable, since the patients could remain stable, gain or loose body fat, and probably change their lean body mass.

Renormalization of high cardiac output and of left ventricular size following long-term recombinant human erythropoietin treatment of anemic dialyzed uremic patients.

To obtain information on the effects of the correction of uremic anemia on cardiac function and size, nine normotensive dialyzed patients were studied before, during and six months after the start of i.v. treatment with recombinant human erythropoietin (rHuEPO). Pulsed-doppler echocardiographic determinations of the cardiac index (CI) and M-Mode echocardiographic estimations of the indexed left ventricular end diastolic diameter (LVEDDi), interventricular septum (IVSi), left ventricular posterior wall (LVPWi), with calculations of the left ventricular mass index (LVMi), were made on every occasion. Mean (+/- SD) hemoglobin (Hb) concentration before rHuEPO was 5.9 +/- 1.3 g/dl and rose significantly (p less than 0.0001) up to the third month, then remained constant. Baseline CI (3.4 +/- 0.6 l/min/m2bsa) was significantly higher (p less than 0.0001) than in healthy subjects (2.5 +/- 0.5 l), and decreased after the third month to a value (2.8 +/- 0.5 l) no longer different from that of controls. From pooled baseline and third month data, an inverse relationship between Hb and CI was found (p less than 0.0001). Baseline LVEDDi (32.7 +/- 4.3 mm/m2bsa), IVSi (6 +/- 1.1 mm/m2bsa) and LVPWi (5 +/- 0.8 mm/m2bsa) were all significantly higher than in controls. After three months of therapy, the only change was a decrease in LVPWi while after six months all indices, including the LVMi, decreased to values no longer higher than in controls. From pooled baseline and six months data, an inverse relationship between Hb and LVMi was found (p less than 0.0001). We conclude that treatment of uremic patients by rHuEPO is able to renormalize their already increased cardiac output soon after correction of the anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of changes in intravascular volume on atrial size and plasma levels of immunoreactive atrial natriuretic peptide in uremic man.

To study the trigger for the release of atrial natriuretic peptide (ANP) in man, we measured the atrial areas (AA) by 2-D echocardiography, the total blood volume (TBV) by 131I-serum albumin and plasma immunoreactive ANP (i-ANP) concentrations by radioimmunoassay, after prior plasma extraction, for 10 dialyzed uremic patients. Measurements were made when the patients were volume-loaded or volume-depleted by isoosmotic ultrafiltration and again 48 h later, when they were again volume-loaded. Analysis of plasma extracts by high-performance gel permeation chromatography revealed that the greatest amount of the i-ANP fraction was a peptide eluting like human synthetic alpha-ANP. Ultrafiltration consistently decreased the TBV, while spontaneous regain of body-fluids caused TBV to rise to pre-ultrafiltration levels. Changes in TBV were closely related in time to changes in both right (RAA) and left (LAA) atrial area and in plasma i-ANP concentrations. Significant direct relationships were found between TBV and RAA, TBV and i-ANP and between both LAA and RAA and i-ANP. Furthermore, the decreases and the increases in TBV, RAA and LAA were closely correlated with changes in i-ANP. Multiple regression analysis, however, revealed that the changes in plasma i-ANP were mainly related to the changes in RAA, with little or no relationship to the changes in TBV or LAA. These findings are evidence for a positive feed-back between the level of intravascular filing volume, extent of atrial distention and amount of i-ANP released into the blood stream.

CAPD viability: a long-term comparison with hemodialysis.

OBJECTIVE: To compare the long-term viability of continuous ambulatory peritoneal dialysis (CAPD) to that of hemodialysis (HD). DESIGN: Retrospective study of patients of our institution starting dialysis between January 1, 1981, and December 31, 1993, and surviving for at least 2 months. PATIENTS: Five hundred and seventy-eight new patients (51.3% on CAPD and 48.6% on HD). MAIN OUTCOMES STUDIED: Cox-adjusted assessment of patient and technique survival, and of technique success. Differences in results for two successive periods of time. RESULTS: Patient survival did not differ between CAPD and HD after adjusting for age and comorbidity, and significantly improved in the second part of the follow-up (1987-1993). Technique failure was significantly higher on CAPD, in which it was inversely related to age. The probability of a patient continuing on the first method of dialysis ("technique success") was significantly lower on CAPD than on HD, but the difference decreased progressively with age and disappeared in patients > or = 75 years. CONCLUSION: CAPD is as effective as HD in preserving life in uremic patients in the long-term, and gives better results in the older elderly. In adults, the lower technique success rate may not be a problem for patients with access to a good transplantation program; for others, this drawback must be weighed against the advantages of home treatment.

Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

A multicenter, selection-adjusted comparison of patient and technique survivals on CAPD and hemodialysis.

Four hundred and eighty CAPD and 373 HD patients started regular dialysis treatment between 1981 and 1987 in 6 dialysis centers. The CAPD patients were 6 years older, on average, than the HD patients and had more complicating conditions (43.3% with 3 or more coexisting risk factors versus 28.9% with coexisting complications). The 7-year patient survival rate was not significantly different. Cox's proportional hazards regression showed that age, cardiovascular disease, cerebrovascular disease, peripheral vascular disease, diabetes, malignancy and multisystem disease had significant adverse effects on patient survival. After correcting for the influence of these factors, no significant differences in patient survival were seen. However, after 53.5 years of age, the increase in the risk of death was significantly higher in HD than in CAPD patients. Technique survival was significantly different in the 6 centers and was better for HD than for CAPD. There was no statistically significant difference between CAPD and HD technique survival when peritonitis was eliminated as a cause of failure. Based on this 7 year analysis, CAPD would appear to be an excellent alternative to HD.

A randomized controlled trial of a bicarbonate- and a bicarbonate/lactate-containing dialysis solution in CAPD.

OBJECTIVE: To evaluate the safety and efficacy of bicarbonate- and bicarbonate/lactate-based PD fluids. DESIGN: A randomly allocated prospective controlled trial lasting eight weeks. SETTING: Five renal units in Europe. PATIENTS: Individuals who have been treated by CAPD for at least three months and who have had at least one month's therapy with 40 mmol/L lactate PD fluid. Those with recent infection, diabetes or other serious illness are excluded. Forty-seven individuals have entered the study so far. INTERVENTIONS: Patients are randomly allocated to three groups. Group 1 receive 40 mmol/L lactate dialysate, Group 2 are given 38 mmol/L bicarbonate fluid and Group 3 are tested with a 25 mmol/L bicarbonate and 15 mmol/L lactate dialysate. OUTCOME MEASURES: The primary outcome measure is the plasma bicarbonate level. Adverse events and ease of use of the two-chambered bags used by Groups 2 and 3 are also being assessed. RESULTS: To date, plasma bicarbonate levels have been the same in all treatment groups up to the end of the trial period. There are no differences in serum lactate levels. No side effects are attributable to the test fluids. The patients have managed the two-chambered bags successfully. CONCLUSION: This trial is still ongoing, but to date, neutral bicarbonate based fluids have been as effective as lactate dialysate in treating uremic acidosis.

Association between silica exposure and necrotizing crescentic glomerulonephritis with p-ANCA and anti-MPO antibodies: a hospital-based case-control study.

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

Clinical manifestations in patients on chronic dialysis with high titres of ANCA.

Eight untreated patients with an apparent renal-limited disease continued to maintain high titres of ANCA long after the onset of the disease and the start of dialysis. In spite of the high ANCA titres, three of them remained for a long time free of symptoms related to the disease. Three pts developed, at various times from the beginning of the disease, fatal pulmonary hemorrhages.