Histological and functional characteristics of peritoneal membrane in peritoneal sclerosis of PD patients.

BACKGROUND: Function and structure of peritoneal membrane (PM) are impaired on peritoneal dialysis (PD). Peritoneal sclerosis is a common finding in peritoneal biopsies (PB) of PD patients. The aim of this study was to examine the impact of peritoneal sclerosis on peritoneal function and clinical parameters in PD patients submitted to peritoneal biopsy. METHODS: A PB was performed on 31 PD patients during catheter removal due to malfunction or after drop-out from treatment. For each patient PM transport was evaluated by the last peritoneal equilibration test before PB. Each daily glucose load was calculated. Tissue was formalin-embedded and stained for histological and immunohistochemical studies. RESULTS: Patients with submesothelial sclerosis and those with impairment of submesothelial basement membrane and subendothelial vascular membrane were submitted to a larger daily glucose load. Peritoneal sclerosis > 50 microns was more frequent in high transporters, who were exposed to larger daily glucose load compared to medium-high transporters. Mesothelial loss is correlated to peritoneal sclerosis and vascular injuries. CONCLUSIONS: Peritoneal sclerosis is not constant in PD patients: it is related to the loss of mesothelium integrity, to the daily glucose load of PD treatment and to vascular injuries, but apparently not to the presence of inflammatory infiltrate. It remains a matter of debate how much the peritoneal sclerosis modifies the function of PM and how new more biocompatible PD solutions could reduce PM injury.

[On-line hemodiafiltration with endogenous reinfusion (HFR). Experience of a Centre]. / Emodiafiltrazione con reinfusato on-line di liquido endogeno: esperienza di un Centro.

PURPOSE: Hemodiafiltration reinfusion (HFR) treatment is a dialysis technique that uses the endogenous reinfusion fluid and performs, simultaneously and separately, the three mechanisms of extracorporal depuration: diffusion, convection and adsorption. This study aimed to evaluate clinical and biochemical data of a group of six patients submitted to a dialytic HFR method for >6 months. METHODS: Six patients with a mean age of 53.8 +/- 11 yrs (five males, one female), treated with standard bicarbonate dialysis for a mean of 79.2 months, underwent HFR for a mean period of 14.9 +/- 6 months. Filters used were: a) in all patients polysulfone with 0.7 m2 of surface for the convection; b) polysulfone with 1.7 m2 in one patient, and modified cellulose with 2.0 m2 in five patients for diffusion; c) hydrophobic interaction resin and uncovered mineral carbon 240 mL for the adsorption. For all patients dialysis duration was 240 min and the amount of reinfusion fluid was 2.5 L/h as a mean, calculated according to blood flow and hematocrit (Hct), keeping a filtration fraction <22%. We evaluated, at different times, the following parameters: a) patient weight; b) Hct and erythropoietin (EPO) doses; c) parathyroid hormone (PTH); d) phosphatemia and doses of administered vitamin D; e) homocysteine (Hcy) and Beta2-microglobulin (Beta2-m); f) and albuminemia and transferrinemia as nutritional parameters. RESULTS: We observed an increase in Hct, with a reduction in EPO dosage, and an increase in albumin and transferrin levels, an improvement in nutritional indexes and in patient well-being. The mild increase in Hct with the same EPO dose was present in spite of a switch to intravenous (i.v.) administration from subcutaneous administration. There was low morbidity and only one hospitalization due to an infectious episode. CONCLUSIONS: HFR allows an amino acid saving and pro-inflammatory middle molecule removal, resulting in a better clinical situation for progressively critical uremic patients.

[Morpho-functional study of peritoneum in peritoneal dialysis]. / Studio morfo-funzionale del peritoneo in dialisi peritoneale.

BACKGROUND: Peritoneal dialysis (PD) impairs both structure and function of the peritoneal membrane (PM). Aim of the study is to examine the relationship among dialytic, histological and functional parameters in PD patients. METHODS: Thirty-one PD patients were submitted to peritoneal biopsy (PB) during catheter removal for malfunction or after dropping out of the treatment. For each patient PM transport was evaluated by the last peritoneal equilibration test (PET) prior to PB. Each daily glucose load was calculated. PB was performed at a distance of at least 5 cm from the catheter insertion point. The tissues were promptly embedded in formalin and stained for histological and immunohistochemical studies. RESULTS: 1) Patients with mesothelial impairment had longer treatment time. 2) Patients presenting submesothelial sclerosis (SS) and those with impairment of submesothelial basement membrane and subendothelial vascular membrane (SVM) were submitted to larger daily glucose loads. 3) High transporters were exposed to larger daily glucose loads and presented an SS thickness greater than 50 micron more frequently than medium-high transporters. 4) Mesothelial loss was correlated with SS and vascular alterations. 5) SS and vascular injuries were related to each other and not to inflammatory infiltrate. CONCLUSION: Our study suggests that PD length seems to be mainly involved in mesothelial impairment; glucose load appears to damage mainly the submesothelial layer; SS is not a constant event in PD patients and in itself does not seem to be a decisive factor in PD drop out.

Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uraemic patients.

BACKGROUND: Myocardial disorders are a remarkable cause of morbidity and mortality in chronic haemodialysed patients (HD). They could be favoured by alteration of cell Ca(2+) handling. In previous studies we characterized an erythrocyte Ca(2+) influx, sensitive to membrane potential and inhibited by Ca(2+) antagonists. Since its maximal influx rate was decreased in HD patients, this study investigates if Ca(2+) influx alterations are related to myocardial disorders in HD patients. METHODS: Voltage-sensitive erythrocyte Ca(2+) influx was measured in 30 healthy controls and in 53 patients (47 HD patients and six patients with left ventricular hypertrophy and normal kidney function), using fura 2. In 29 HD patients and in six healthy subjects Ca(2+) influx was also determined in the presence of parathyroid hormone (PTH) in vitro. Patients were classified according to Lown's ventricular arrhythmias classification after 24-h Holter electrocardiograph (ECG) monitoring. Forty-six patients underwent echocardiography. RESULTS: Voltage-sensitive erythrocyte Ca(2+) influx was significantly reduced in HD patients. Maximal influx rate was significantly higher in HD patients of Lown's classes 3 and 4 (0.789 +/- 0.156 nmol/s, n = 8; P < 0.01) than in patients of classes 1 and 2 (0.499 +/- 0.055 nmol/s, n=15), or without ventricular arrhythmias (0.400 +/- 0.041 nmol/s, n = 24). Maximal influx rate was directly correlated to left ventricular mass index (LVM) (r = 0.353, P < 0.05). Subjects with left ventricular hypertrophy and normal kidney function displayed erythrocyte Ca(2+) influx similar to that of normal subjects. Multiple regression indicates that LVM and Ca(2+) influx were independently related to severity of arrhythmias. When added to the influx assay, PTH increased the maximal influx rate only in patients with ventricular arrhythmias. CONCLUSION: Myocardial dysfunction and altered ventricular excitability could be related in uraemic HD patients to alterations of calcium transport, as found in the erythrocyte model. Reduced resistance to PTH could contribute to this phenomenon.

Left ventricular mass, stroke volume, and ouabain-like factor in essential hypertension.

Many patients with essential hypertension (EH) exhibit increased left ventricular mass. Similarly, elevated circulating levels of an endogenous ouabainlike factor (OLF) have been described in some but not all patients with EH. Moreover, ouabain has a hypertrophic influence on isolated cardiac myocytes. Accordingly, we investigated relationships among plasma OLF, left ventricular mass, and cardiac function in patients with EH. Plasma OLF was determined in 110 normotensive subjects and 128 patients with EH. Echocardiographic parameters and humoral determinants were measured in EH. Plasma OLF levels were increased (P<0.0001) in patients with EH (377+/-19 pmol/L) versus normotensive (253+/-53 pmol/L) subjects. The distribution of plasma OLF was unimodal in normotensives, whereas it was bimodal in EH. Twenty-four-hour diastolic ambulatory blood pressure was slighter higher in EH with high OLF compared with EH with normal OLF (93.2+/-1.14 versus 89.4+/-1.33 mm Hg, P=0.03). Left ventricular mass index and stroke volume in EH with high OLF were greater than in EH with normal OLF (101.9+/-3.3 versus 86.1+/-2.5 g/m(2), P=0.0003, and 57.10+/-1.48 versus 52.30+/-1.14 mL/m(2), P=0. 02, respectively), although heart rate was slower (74.2+/-1.3 versus 80.5+/-1.3 bpm, P=0.005). Multiple regression analysis that tested the influence of body mass index, age, gender, 24-hour blood pressure, and OLF on left ventricular mass revealed independent contributions of systolic (13.2%) and diastolic (12.4%) blood pressure and plasma OLF (11.6%) to left ventricular mass. We conclude that approximately 50% of patients with uncomplicated EH have elevated-high circulating OLF levels, higher diastolic blood pressure, greater left ventricular mass and stroke volume, and reduced heart rate. We propose that the OLF affects cardiovascular function and structure and should be considered as a factor that contributes to the risk of morbid events.

Improvement of glucose/insulin metabolism reduces hypertension in insulin-dependent diabetes mellitus recipients of kidney-pancreas transplantation.

There is increasing evidence that metabolic disorders are common in patients with hypertension. To evaluate the relationship between glucose/insulin metabolism and hypertension in diabetes, 61 hypertensive uremic insulin-dependent diabetes mellitus patients who were recipients of kidney or pancreas/kidney transplants were studied through a 1-year follow-up. Twenty of them received a kidney (K) transplant alone, 13 received a kidney and segmental pancreas (KSP), and 28 received a kidney and whole pancreas (KWP) with duodenocystostomy. All subjects received the same immunosuppressive treatment including steroids, azathioprine, and cyclosporine. The three groups of patients were comparable for biochemical parameters, clinical characteristic, cyclosporine levels, and renal function (creatinine < 2 mg/dl). The association between hypertension and type of transplant was evaluated according a global chi-square test, then the results were broken down into two components to test for differences in hypertension between KP versus K and KWP versus KSP groups. The improvement of hypertension rate was statistically associated with KP transplant the first week after surgery, at discharge, and 1 year after transplantation (hypertension% at 1 week: KWP = 75, KSP = 23 vs. K = 70, P = 0.004; at discharge: KWP = 39, KSP = 31 vs. K = 75, P = 0.017; at 1 yr: KWP = 44, KSP = 54 vs. K = 85, P = 0.02). One year after graft fasting, free immunoreactive insulin as well as glycosylated hemoglobin and glucose levels were statistically lower in the KP groups than in the K-alone recipients. The improvement of hypertension observed in KP recipients suggests a key role of glucose and insulin metabolism on pathogenesis of diabetic hypertension.

Erythrocyte calpain activity and left ventricular mass in essential hypertension.

BACKGROUND: Calpains are cytoplasmic proteases widely distributed among eucaryotic cells. Low levels of calpain activity were found in hypertrophic hearts from hypertensive rats, but its role in hypertrophic hearts from human hypertensives is unknown. Therefore, calpain activity was investigated in erythrocytes from essential hypertensive patients in relation to their left ventricular mass. OBJECTIVE: To study the role of calpain activity in the development of left ventricular hypertrophy (LVH) in human essential hypertension. METHODS: A total of 115 hypertensives (72 untreated and 43 with treatment interrupted for at least 4 months) were included in the study. Calpain I activity was measured in human erythrocytes and LVH was measured as left ventricular mass index (LVMI) by M-mode echocardiography. RESULTS: Values are given as mean+/-SEM. The hypertensives (97 men and 18 women) were 43.5+/-0.9 years old with mild to moderate levels of hypertension (systolic/diastolic blood pressure of 147.9+/-1.4/98.7+/-0.9 mmHg) and relatively recent LVH onset (3.5+/-0.5 years). An inverse relation between LVMI and erythrocytic calpain activity was present in all (P = 0.0023, R2 = 7.9%). This relation was still present considering only untreated hypertensives (P = 0.008; R2 = 9.7%), but was lost in the 43 previously treated hypertensives. Moreover, in the untreated hypertensives, after excluding the possible confounding effects of sex, age, body mass index, blood pressure and duration of hypertension, a stepwise regression showed that only two variables remained significantly related to LVMI: calpain (F = 6.23) and mean arterial pressure (F = 4.689). No relations were found between LVMI and calpastatin activity either in the whole population, or in treated or untreated hypertensives. CONCLUSIONS: If we assume that the level of erythrocyte calpain activity mirrors the level in cardiomyocytes, these data seem to suggest that increased protein degradation by calpain may prevent the development of LVH in hypertensive patients. This effect is independent of the duration and severity of hypertension.