[The hemodialysed patient and his/her family caregiver. Comparison of perceptions of the chronic illness]. / Il paziente emodializzato e il caregiver familiare. Percezioni a confronto sulla malattia cronica.

BACKGROUND: According to health psychology, the family caregiver (fc), i.e. the person who takes care of a hemodialysed patient, plays a pivotal role in coping with dialysis. This study explored and compared the lifestyle and the main needs of a cohort of hemodialysis patients, with reduced personal autonomy, to their fc, evaluating some psychological functional parameters, such as the perception of familial and social support, the psychological quality of life, the disability due to chronic illness, and the communication style. METHODS: An anonymous multiple versions questionnaire, administered according to the caregiver's family relationship, was given for self assessment to 54 couples of patients and related fc (spouse, son/daughter and brother/sister), mean age 66 and 60, respectively; mean dialytic patients' age: 8 years and 6 months. The questionnaire consisted of three different sections, demographics, renal disease and psychological evaluation, with 4 standard scales (Social Support Satisfaction, Marital Communication, Psychological General Well-Being Index and Evaluation of Needs). A multivariate variance analysis (MANOVA) was subsequently performed. RESULTS: Women have a higher perception of their lifestyle change after dialysis, and, in general, patients communicate more easily with their fc than vice versa. Communication problems are more common in patients with a recent diagnosis. Patients and fc mostly need a better dialogue with their nephrologists and urge some psychological help. CONCLUSIONS: The quality of the relationship between physicians, patients and their families is a key element in the process of healing.

The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis.

Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients.

Medical prevention and treatment of urinary stones.

Despite revolutionary developments in minimally invasive methods for the removal of stones in the last 15 years, the medical prevention of urinary stones remains very rewarding, due to the continual increase in the prevalence of nephrolithiasis in western countries, the high recurrence rate of the disease, its complications, discomfort and the costs of lithotripsy. Medical prevention is highly effective (50-95% efficacy in different series) and cost-convenient; its basic elements are appropriate metabolic evaluation, adequate hydration, "common sense" diet, and, in selected cases, drugs of proven efficacy. Clinical-metabolic evaluation should aim at the recognition of specific types of nephrolithiasis, and sort out secondary and/or remediable cases, define urinary risk factors, assess patients' compliance and the side effects of any therapy during follow-up. Hydration has proved effective in clinical trials and population-based observational studies; "fluids" may consist of water (any kind), coffee (caffeinated or decaffeinated), tea, beer and wine; grapefruit juice appears to have an unexplained ill effect. Despite the lack of clinical demonstration that dietary manipulations reduce the recurrences of stones, biochemical and epidemiological data suggest that high sodium, animal protein and sucrose intake increase the risk. Undue reductions in Ca intake also appear to be detrimental both for stone recurrences and bone mineralisation: "adequate" Ca intake (800-1000 mg/day) should be encouraged, but only in food since supplemental Ca, as drugs, appears to increase the risk of stones. Effective drugs are available for cystine, uric acid, infected stones and several secondary causes of Ca nephrolithiasis; in "idiopathic" Ca nephrolithiasis, thiazides, allopurinol, K and K-Mg citrate and possibly neutral K phosphate have been shown to be effective, at least in specific metabolic contexts.

Immunophenotyping of mononuclear cell infiltrates associated with renal disease.

Twenty-eight frozen renal biopsy specimens with a marked mononuclear cell interstitial infiltrate (MCI) were analyzed with monoclonal antibodies and a biotin-avidin peroxidase technique to define the surface phenotype distribution of the infiltrating cells. Twelve cases were diagnosed as tubulointerstitial nephritis of acute and chronic presentation, of unknown cause in 5 cases or secondary to multiple myeloma or drug reactions. Sixteen cases occurred in primary and secondary glomerulonephritis, 3 cases being associated with lymphoproliferative disorders. The results showed a remarkable heterogeneity of the MCI composition, even in cases with similar clinical and pathological findings. Namely, the T cells accounted for the majority of the infiltrating cells in most cases but a variable predominance of the T cell subsets Leu3 and Leu2 was observed. B cells and monocytes were also prominent in some cases. Such differences in the MCI composition may indicate the activation of different mechanisms of tissue damage, or a different phase of the renal disease. In the three cases of glomerulonephritis associated with lymphoproliferative disorders, the malignant origin of the MCI was demonstrated in one case, while in the remaining cases it was excluded.

Fluorocytometric analysis of anti-HLA class 2 autoantibodies in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) patients are known to produce a variety of autoantibodies (AAb), some of which may be directed against immunocompetent cells. Anti-B cell autoimmunity may encompass reactivity against HLA-class 2 molecules, which are also expressed on kidney tissue. We studied 15 patients with moderate to severe renal involvement and 5 lupus patients with no clinical renal disease, in order to detect the presence of anti-HLA class 2 AAb. Flow cytometry was employed in an inhibitory assay using patient sera, autologous cells and two anti-class 2 monoclonals, to establish the specificity of anti-B cell AAb. Seven out of 15 nephritis patients had detectable anti-class 2 AAb with an epitopic heterogeneity, as demonstrated by different degrees of inhibition on the binding of non-overlapping monoclonals. The specificity of the reaction was confirmed by the lack of inhibition of non-class 2 antibody binding. The presence of such AAb was not correlated with disease activity but with the presence of a diffuse proliferative glomerulonephritis on renal biopsy. Anti-class 2 AAb may be a marker of SLE diffuse proliferative nephritis.

Inhibitors of myo-inositol monophosphatase, ATCC 20928 factors A and C. Isolation, physico-chemical characterization and biological properties.

During the course of a screening program for inhibitors of myo-inositol monophosphatase we fermented the strain ATCC 20928, a known producer of L-671,776. We now show that this strain produces a complex of at least three sesquiterpenic compounds, L-671,776 (termed factor B) and two structurally related substances, termed factors A and C. Both factors A and C, like L-671,776, exhibited inhibitory activity against myo-inositol monophosphatase. Six other fungi producing the above mentioned compounds were also isolated and taxonomically characterized.

Clinical relevance of fractionation characteristics in cascade filtration.

Plasmapheresis performance is improved in the treatment of hyperviscosity syndromes with one of the several cascade filtration techniques (CF), intended for plasma fractionation and reinfusion of albumin-enriched plasma filtrate to the patients, avoiding the need for exogenous reinfusion solutions. A retrospective open analysis of 103 CF, performed by dead-end mode, in 14 patients with macroglobulinemia, cryoglobulinemia, multiple myeloma and other diseases, has been performed. Protein fractions removals have been calculated, normalized to the treatment of one plasma volume, compared in different macromolecular diseases and according to the different plasma fractionators employed. [table: see text] Protein removal is partially dependent of the surface area of the fractionator, but a wide variability has been reported, mainly depending on the underlying macromolecular disease.

Different cascade filtration operating modalities in clinical use.

Cascade filtration (CF) can be performed in either the single-pass or dead-end configuration. The distinction, as predicted by experimental models, is that solute removal is lower but constant in the former, and higher but variable with the quantity of filtrate in the latter. Moreover, unpredictable plugging reduces permeability during operation. It is therefore unclear which configuration is preferable in clinical use. In four cryo- and three macroglobulinemic patients, the data of 10 dead-end CF (QP) and 11 modified single-pass CF with high flow rate recycling plasma (QD) were compared. Both groups had similar starting values. Centrifugal primary plasma separation was performed. No exogenous reinfusions were used. Either 0.8 and 1.2 sq.m. surface secondary filters were employed. The ratio of plasma processed to patients' plasma volume was 1.1 +/- 0.3 in QP, and 0.94 +/- 0.09 in QD. The mean percentage removals of albumin, IgG and IgM respectively were 25.8 +/- 9, 32 +/- 17 and 47.5 +/- 26% in QP, 30.5 +/- 12, 40.5 +/- 19 and 48 +/- 17.5% in QD: albumin vs IgM p less than 0.025 in QP and p less than 0.02 in QD. A/G ratio increased from 1.6 +/- 0.5 to 2.06 +/- 0.6 in QP, and from 1.5 +/- 0.3 to 1.7 +/- 0.3 in QD. Plugging occurred in both groups, requiring 2.3 +/- 1.8 washouts/run in QP vs 1.5 +/- 1.2 in QD. IgM removal was comparable. Removal of albumin and IgG was slightly higher in QD. Similar performances can be obtained with either technique in clinical use, provided an adequate fractionation surface is available.

Performance evaluation of cascade filtration with high flow rate recirculating plasma on the secondary filter.

Cascade filtration (CF) has been performed in 67 on-line procedures in 9 normolipidemic patients with paraproteinemic disorders. A modified dead-end technique has been employed, with high flow rate recirculating plasma on the plasma fractionation filter (QD recycled CF), and an albumin-rich, globulin-poor filtrate was reinfused into the patient. Postprocedure recoveries were 81 +/- 15% for albumin, 55 +/- 23% for IgM and 48% for cryocrit, with an increase in A/G ratio from 1.8 to 2.1. An improvement was observed also in antiatherogenic/atherogenic lipoproteins ratio, suggesting a possible use of this technique in the treatment of familial hypercholesterolemia. Plasma primary separation was obtained by centrifugation or by filtration, and no significant differences were observed on subsequent protein fractionation process. An albumin priming of the plasmafractionation circuit accounted for an additional 13% saving in postprocedure level. Different surface area secondary filters have been employed: with larger surfaces, larger volumes were processed without any increase in the waste volume and with reduced need for washouts, but with an additional loss of small molecules possibly due to entrapping onto the membrane.

Calcium metabolism and calciotropic hormone levels in Gitelman's syndrome.

In 10 adult patients (5 females and 5 males, aged 13-57 years) with Gitelman's syndrome (GS, or hypocalciuric variant of Bartter's syndrome, characterized by chronic renal hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria), parameters of Ca metabolism and calciotropic hormone levels were evaluated. Hypocalciuria was associated with a marked reduction of fractional excretion of ionized Ca (as compared with 16 sex- and age-matched controls) and normal filtered Ca load, as indicated by serum ionized Ca; hypocalciuria was thus the result of increased tubular reapsorption of filtered Ca. Plasma levels of total Ca were increased in GS (p < 0.02) but ionized Ca was not different from controls; percent fraction of ionized to total Ca was reduced, indicating increased Ca complexation and/or protein binding, possibly related to a metabolic alkalosis-induced increase of plasma albumin affinity for Ca. Levels of plasma total protein and albumin were similar in GS and controls. Despite similar ionized Ca levels, PTH1-84 was lower in GS than in controls, indicating abnormal ionized Ca-PTH relationship, possibly related to hypomagnesemia. Plasma 1,25(OH)2D levels were not different in GS and in controls, and intestinal fractional Ca absorption (evaluated with a simplified method using stable Sr as a tracer) was not reduced in 4 patients. However, in 5 patients bone mineral density in the forearm (3 patients) or lumbar spine (2 patient) was normal. Thus, despite chronic hypocalciuria and normal 1,25(OH)2D levels, Ca 'thesaurosis' does not occur in bones of GS patients; a likely explanation is that, despite normal 'fractional' intestinal Ca absorption, 'net' intestinal absorption is reduced, due to increased intestinal Ca secretion.

Polymorphonuclear cell phagocytosis and surface receptor modulation after extracorporeal circulation.

Polymorphonuclear cells (PMN) from patients treated with hemodialysis (HD) or plasma exchange (PE) were analyzed by flow cytometry to determine modulation in phagocytic capacity and Fc-gamma and C3bi receptor expression following extracorporeal circulation (EC). Fluorescent microbeads (phi 2.02 m) were used in the evaluation of phagocytosis, and phycoerythrin conjugated Leu11c and Leu15 monoclonals identified Fc-gamma and C3bi receptors respectively. The percentage of positive cells and mean receptor density on PMN surfaces were calculated for each antibody before and after the procedures. Fc-gamma receptor expression was reduced overall in HD and PE cases, but unaffected after EC even with specific paraprotein removal. C3bi receptor was normally expressed on PMNs before and after EC, but receptor density on the cell surface increased, and phagocytosis was qualitatively and quantitatively depressed after EC. The resulting effect of EC on PMNs was therefore a temporary increase in C3bi receptor density after the procedure, which was independent of HD or PE technique, of the primary disease, and of the quality of the PE reinfusion solutions, suggesting a procedure-related effect, and a down-regulation of PMN phagocytic activity. Both effects may be related to membrane biocompatibility.

Abnormal reabsorption of Na+/CI- by the thiazide-inhibitable transporter of the distal convoluted tubule in Gitelman's syndrome.

Eleven patients with Gitelman's syndrome and 23 controls underwent acute administration of the thiazide diuretic hydrochlorothiazide and/or the loop diuretic furosemide (FUR) in order to indirectly evaluate the activity of the two electroneutral Na+/Cl(-)-reabsorptive systems of the distal nephron, namely the thiazide-sensitive Na+-Cl- symporter of the distal convoluted tubule and the FUR-sensitive Na+-K+-2Cl- symporter of the loop of Henle. The patients were characterized by hypokalemia, mild metabolic alkalosis, hypomagnesemia, hypocalciuria, and reduced free water generation during maximally diluted diuresis which indicated reduced distal nephron NaCl reabsorption. The plasma Na and Cl levels were similar in patients and controls. Hydrochlorothiazide induced a significantly lower increase of urinary Na and Cl excretions in 6 patients with Gitelman's syndrome than in 6 controls, indicating reduced NaCl reabsorption by the thiazide-sensitive Na+/Cl- symporter of the distal convoluted tubule in Gitelman's syndrome. FUR induced a slightly higher increase of urinary Na and Cl excretions in 11 patients with Gitelman's syndrome than in 17 controls, in keeping with reduced NaCl reabsorption in tubular sites past the loop of Henle during FUR effect or increased NaCl reabsorption in the loop itself (as a compensatory mechanism for NaCl-reabsorptive defect in the distal convoluted tubule) or both. Our results confirm that the functional activity of the renal thiazide-sensitive Na+-Cl- cotransporter (but not of the FUR-sensitive carrier) is deficient in patients with Gitelman's syndrome, in keeping with the recently described genetic link between the syndrome and a wide variety of nonconservative mutations of the gene encoding the protein; it is suggested that dynamic studies with diuretic administration may be of diagnostic help in this condition.

Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment.

The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU-E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84-parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo.