Double-blind randomized, crossover trial of calcium supplementation in essential hypertension.

In a double-blind, randomized, placebo-controlled, crossover trial, 23 middle-aged patients with mild to moderate essential hypertension were given an oral calcium supplement (1 g/day) for 8 weeks. At the end of this period, eight patients continued with this treatment for an additional 2 weeks but were also given 0.5 micrograms/day of 1,25-(OH)2 vitamin D3. In the 21 patients who completed the study, arterial pressure during the calcium-supplemented phase was almost identical to that of the placebo phase. In eight patients, mean arterial pressure (MAP) had changed by greater than 5 mmHg at the end of the calcium-supplemented period, compared with the end of the placebo phase (six patients showed an increase in MAP and two a decrease). Changes in arterial pressure were unrelated to age, plasma ionized calcium, parathyroid hormone (PTH), plasma renin activity (PRA), plasma aldosterone, 24-h urinary calcium, sodium and potassium and were only weakly related to body weight. In the eight patients who continued with the treatment of calcium plus 1,25-(OH)2 vitamin D3 after the 8-week study period, arterial pressure changed very little and not significantly. These results do not support the suggestion that calcium supplements lower arterial pressure in middle-aged subjects with mild to moderate essential hypertension.

Characterization of myocardial tissue in patients undergoing maintenance hemodialysis by quantitative echocardiography.

The uremic state affects myocardial structure, bringing about, among other things, interstitial calcium deposition. Abnormalities of myocardial structure can be assessed quantitatively and noninvasively during life by the analysis of the gray-level distribution of conventional two-dimensional echocardiograms. The aim of this study was to evaluate the role of quantitative echocardiography in providing information on myocardial structure in patients under maintenance hemodialysis and to relate the ultrasonic findings with abnormalities in calcium-phosphate metabolism. Forty patients undergoing dialysis without abnormalities in left ventricular regional and global function and 17 hypertensive patients with comparable left ventricular hypertrophy were studied. The distribution of the gray levels within a region of interest in the interventricular septum was analyzed off-line by an array processor-based computer. Compared with hypertensive patients, patients undergoing dialysis showed a greater myocardial echogenicity (mean 92 +/- 20 versus 72 +/- 15; p = 0.004) and a reduced homogeneity of distribution of gray levels (entropy 4.5 +/- 0.2 versus 4.2 +/- 0.2, p < 0.01; uniformity 0.010 +/- 0.003 versus 0.020 +/- 0.004, p < 0.005). In the same patients, a significant negative linear relation was found between entropy and calcium-phosphate product (r = -0.66; p = 0.001). Quantitative analysis of conventional two-dimensional echocardiograms allows the detection of a pathologic myocardial structure in patients under maintenance hemodialysis with normal left ventricular function. These abnormalities are related to disorders of calcium-phosphate metabolism and bear no relationship to the degree of left ventricular hypertrophy.

Postprandial alterations in arterial pressure control during hemodialysis in uremic patients.

To test the hypothesis that eating may adversely affect the hemodynamic response to ultrafiltration-dialysis, we studied the effect of a standard snack (about 400 Kcal) in 13 patients on RDT. Each patient was studied in random order during two standard hemodialysis sessions (snack-HD and control-HD) performed at identical UF rate. Arterial pressure fell significantly (p less than 0.01) during both the Control-HD (from 135 +/- 8/76 +/- 3 to 121 +/- 10/68 +/- 5 mmHg) and the Snack-HD (from 137 +/- 7/77 +/- 3 to 105 +/- 8/59 +/- 4 mmHg). The rate of fall, however, was significantly higher (p less than 0.01) after the snack than during the corresponding period in the control HD. Consequently, there were more hypotensive episodes requiring saline infusion during Snack-HD (23 in 10 patients) than during Control-HD (12 in 6 patients) (p less than 0.025). In spite of the greater number of interventions, the average fall in arterial pressure after a snack (-22 +/- 3/-13 +/- 2 mmHg) was more marked than during the corresponding period in the control-HD (-13 +/- 3/-9 +/- 2 mmHg). The hypotensive effect of snack was more pronounced in the presence of advanced autonomic neuropathy. Food ingestion impairs the arterial pressure response to UF in patients on RDT. Fasting during hemodialysis may in part prevent hypotension.

Cardiothoracic ratio as a guide to ultrafiltration therapy in dialyzed patients.

This study evaluated the cardiothoracic ratio (CTR) and the roentgenologic heart volume (RHV) as indexes of body fluid retention in 37 uremics on maintenance dialysis therapy. Both indexes related to a highly significant degree with the variations of body fluids balance assessed by the changes in body weights. Cardiomegaly (CTR greater than .500) subsided with adequate ultrafiltration therapy in most patients including those having blood pressure values within the normal range. It is concluded that the measurements of CTR provides an useful guide to ultrafiltration therapy especially in those patients whose blood pressure fails to sense the body fluid retention.

Influence of blood temperature on vascular stability during hemodialysis and isolated ultrafiltration.

We tested the hypothesis that differing temperature (T) changes in extracorporeal blood circuit might partly account for the difference in vascular stability (VS) between isolated ultrafiltration (UF) and simultaneous UF-hemodialysis (HD). The study was carried out in 6 patients who presented frequent episodes of symptomatic hypotension during the routine dialytic sessions. During simultaneous UF-HD with dialysate T set at 37.5 degrees C (standard HD), blood reentered the patients with a T of about 2 degrees C higher, whereas during isolated UF (standard UF) 2 degrees C lower, than at its exit. These extracorporeal blood T changes were reciprocated by warming the venous line in isolated UF (warm UF) and by setting the dialysate at 34.5 degrees C in simultaneous UF-HD (cold HD). During warm UF mean arterial pressure (MAP) fell and heart rate (HR) increased nearly as much as during standard HD. Vice versa, during cold HD MAP and HR remained nearly as stable as during standard UF. It is concluded that the T changes in blood flowing through the extracorporeal circuit largely account for the differing VS between isolated UF and simultaneous UF-HD.

Suppression of post-apheresis autoantibody rebound in cryoglobulinemia and cold agglutinin hemolytic anemia.

We studied the effect of immunosuppressive treatment on the autoantibody rebound that follows autoantibody withdrawal accomplished by extracorporeal plasma treatment. The study was carried out on 9 patients, 8 having essential mixed cryoglobulinemia and 1 cold agglutinin hemolytic anemia. As immunosuppressive drugs we used either cyclophosphamide and prednisolone or arabinoside C and cyclophosphamide. The effect of immunosuppressive treatment on autoantibody rebound (Igm anti-IgG; IgM cold agglutinins) varied widely, a suppressive effect of varying degree having been observed in about half the cases treated with either drug regimen.

Complement activated leucopenia during hemodialysis: effect of pulse methyl-prednisolone.

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was withheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97-27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 micrograms/ml +/- SEM 33) and in patients off dialysis (177 micrograms/ml +/- 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.

Blood temperature and cardiovascular stability in hemofiltration.

Temperature (T) changes in the blood flowing through the extracorporeal circuit markedly affect cardiovascular tolerance to fluid removal during either hemodialysis (HD) and isolated ultrafiltration. In this study we investigated the effect of blood T changes during postdilutional hemofiltration (HF). To this purpose we compared the changes in mean arterial pressure (MAP) and heart rate (HR) during HF and HD carried out at equivalent T of blood in the venous segment of the extracorporeal circuit. Results show that HF entails some heat loss from blood flowing in the extracorporeal circuit; if heat loss is made similar, HD affords nearly as much blood pressure protection as HF does. On the other hand at equivalent heat gain, HF causes nearly as much hypotension as HD does. We conclude that blood T changes in the extracorporeal circuit affect vascular stability (VS) even in HF. The marginal benefit of HF over HD, still observed at equalized T changes, remains to be elucidated.

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypothensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Thermal balance and dialysis hypotension.

Many studies have confirmed our original observation that dialysate T set at about 35 degrees C affords a better hemodynamic protection than the standard dialysate T of 37-38 degrees C. In this review we present some new data on the hemodynamic mechanism of the protective effect of cold dialysis on blood pressure. The study was based on serial assessment of the percent changes occurring during dialysis treatment in estimated stroke volume (aortic blood flow determined by Doppler echocardiography), blood volume (hemoglobinometry), arterial pressure (Dynamap), and heart rate (ECG), from which cardiac output (CO) indexes and total peripheral vascular resistances (TPVR) were derived. Of the 14 pts studied, 7 showed a drop in mean arterial pressure (MAP) of 25% or greater during standard dialysis (unstable patients). Compared with the 7 patients having more stable intradialysis MAP, unstable pts showed greater reduction in CO which was disproportionately greater than the reduction in blood volume, and a paradoxical decrease in TPVR, the difference being highly significant (p < 0.01 for both changes). When crossed-over to cold dialysis, along with a significantly lower reduction in MAP (p < 0.01) the unstable pts showed a lower decrease in CO which paralleled the reduction in blood volume, and an increase in TPVR. These changes were highly significant (p < 0.01). Data suggest that dialysis hypotension is characterized by an impaired venous return, probably due to the peripheral blood pooling (increased ratio between the 'unstressed' and 'stressed' blood volume) associated with the decrease in TPVR. Exposure of extracorporeal blood to cold dialysate favours the venous return to the heart by increasing TPVR and the 'stressed' blood volume.

Long term effects of cryoapheresis and cytostatic treatment in essential mixed cryoglobulinemia.

We studied the effects of cryoapheresis combined with different immunosuppressive treatments on the course of the glomerulonephritis of essential mixed cryoglobulinemia. The study was carried out on 11 patients. The effects of immunosuppressive treatments on cryoglobulin rebound after cryoapheresis varied widely. In those responding with sustained reduction in serum cryoglobulin levels, creatinine clearance increased, an effect that lasted several years in 4 patients. In one patient cryoglobulin disappeared, with almost fully recovery of renal function and normalization of blood pressure. One patient died of acute liver failure shortly after the first observation and another entered regular dialysis treatment. All the other patients are still alive after follow-up of 2-9 years. These results compare favourably with those reported by other investigators and suggest that cryoapheresis and cytostatic drugs are beneficial for glomerulonephritis associated with essential mixed cryoglobulinemia.

[Prevalence of insulin-dependent and non-insulin-dependent diabetes among Italian patients on replacement therapy. Preliminary survey at 3 dialysis centers]. / Prevalenza del diabete insulino e non insulino-dipendente nei pazienti Italiani in terapia sostitutiva. Indagine preliminare su tre Centri Dialisi.

We carried out a retrospective survey to assess prevalence and type of diabetes in three Italian Renal Units located respectively in the North (Tradate, Varese), in the Middle (Latina) and in the South (Reggio Calabria) of Italy. The prevalence of diabetes among patients accepted for RRT was 10.5% (60/659). 40 patients (66.7%) were non-insulin dependent and only 6 patients were insulin-dependent. A similar pattern was observed among the 289 patients referred to the Renal Unit of Reggio Calabria during 1972-1987 for evaluation of Chronic Renal Failure. Our data suggest that among the Italian diabetic patients treated by dialysis and transplantation insulin-dependent diabetes is uncommon. This finding could be explained by the low incidence of insulin-dependent diabetes in Italy.

[Oxolinic acid treatment of urinary sepsis in patients with renal insufficiency]. / Trattamento con l'acido ossolinico delle sepsi urinarie nei pazienti con insufficienza renale.

The effect of oxolinic acid, administered at the rate of 750 mg twice/day, has been studied on 31 patients with urinary tract infections. Many of them had a marked impairment of renal function due to nephropathies of various origin. Favourable results, with sterile urine and complete remission of symptoms, were obtained in 73.3%. Patients who were resistant to previous different therapies, were successfully treated. Oxolinic acid was on the whole well tolerated and proved to be effective also in patients with impaired renal function. In some of the latter an improvement in renal function occurred as a result of the effective urinary infection care. The tolerability of oxolinic acid was good: only one patient interrupted the treatment because of insomnia; other 4 had transient and mild side-effects.

[Early diagnosis of rapidly progressive glomerulonephritis]. / Diagnosi precoce delle glomerulonefriti rapidamente progressive.

The term rapidly progressive glomerulonephritis (RPGN) designates a group of glomerular diseases with different pathogenetic and clinical features, rapidly leading to renal or patient death in about 90% of the untreated cases. Histopathologically, it is characterized by glomerular crescents in at least 50-75% of the glomeruli (necrotizing crescentic glomerulonephritis), and very often, glomerular necrosis. The situation is, however, potentially reversible if adequately treated, and a favourable outcome depends largely on early diagnosis and treatment. Early diagnosis can be achieved if due importance is given to even seemingly unspecific manifestations such as "flu like syndrome" associated with "glomerular" hematuria. These manifestations are detectable before the down-hill course of renal functional derangement becomes evident and should lead the physician to consider RPGN among the diagnostic possibilities. Final diagnosis rests on serological tests and kidney biopsy. The battery of diagnostic serological tests (anti-GBM, anti-DNA antibodies, cryoglobulins, etc.) has recently been enriched by the assay of anti-neutrophil cytoplasmic antibodies (ANCA). These antibodies are detectable in over 90% of cases of Wegener's granulomatosis and primary necrotizing crescentic glomerulonephritis with or without lung involvement. ANCA-associated glomerulonephritis is the commonest form of RPGN, and the new serological assay provides an important tool for its early recognition. Renal biopsy is necessary to evaluate the severity of the nephritic process and modulate treatment accordingly. Timely diagnosis is one of the most important factors contributing to successful treatment outcome over both the short and the long term.

[Deposits with anti-globulin activity in dermatitis herpetiformis]. / Depositi con attività antiglobulinica nella dermatite erpetiforme.

Skin biopsy specimens from 2 patients with dermatitis herpetiformis were examined by means of direct immunofluorescence with fluoresceinated aggregated human IgG (FAIgG) for the presence of tissue antiglobulin activity. Positive FAIgG staining was seen in both skin biopsy specimens yielding a fluorescence pattern similar to that of immunoglobulin and complement deposits. Tissue antiglobulin activity was no more detectable in a second skin biopsy obtained from one patient whose rash was controlled by Dapsone. These findings suggest an involvement of tissue antiglobulin activity in the pathogenesis of dermatitis herpetiformis. In fact, tissue antiglobulin activity is capable of acting as an immunoabsorbent and binding immunocomplexes from the circulation.