Luigi Gastaldi

IMMUNE DEFICIENCY IN UREMIA : INTERLEUKIN-2 PRODUCTION AND RESPONSIVENESS AND INTERLEUKIN-2 RECEPTOR EXPRESSION AND RELEASE

We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.

Controlled Trial of Thymopentin in Hemodialysis Patients Who Fail to Respond to Hepatitis B Vaccination

Uremic patients are at high risk of hepatitis B virus (HBV) infection and, despite the availability and efficacy of hepatitis B vaccine, a high rate of non responders has been reported. Forty uremic patients undergoing maintenance hemodialysis who failed to produce any measurable anti-HBs antibody response after 4 administrations of 5 micrograms of Hevac B Pasteur vaccine were admitted to a randomized controlled clinical trial. Group A (14 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals and 12 doses of 50 mg s.c. of thymopentin on alternate days between the first and the second vaccination. Group B (11 patients) received 3 doses of 5 micrograms s.c. each of vaccine at monthly intervals. Group C (15 patients) received 3 doses of 10 micrograms s.c. each of vaccine at monthly intervals. Immunization rates were 86% in group A (on both 1-month and 6-month checks), 36% on the 1-month and 27% on the 6-month check in group B, 53% on the 1-month and 47% on the 6-month check in group C. Anti-HBs antibody titers were similar in group A and C but notably lower in group B. Thymopentin seems as useful therapeutical tool for non responder patients. As it promotes T cell maturation and responsiveness, which are impaired in uremia, it could play a major part in the management of uremic immunodeficiency.

Hemodialysis-Associated Cardiac Arrhythmias: A Lower Risk with Bicarbonate?

The role of hemodialysis (HD) as an arrhythmogenic event has recently been emphasized. We studied 18 patients by Holter monitoring, comparing the arrhythmogenic effect of acetate dialysis (AHD) and bicarbonate dialysis (BHD). The frequency of ventricular arrhythmias was 93 +/- 66/h in AHD and 32 +/- 26/h in BHD (p less than 0.005). According to the classification of Lown and Graboys, classes III and IV were more often to be found in AHD than in BHD and no patient on BHD was in class IVB and class V. Five patients affected with ischemic heart disease had more frequent and dangerous ventricular arrhythmias than the others; a significant difference between buffers was recorded in all cases but 1. Intradialytic changes in body weight, hematocrit, osmolarity, ionized calcium and potassium during AHD and BHD were similar. The two methods only differed in the quickness and degree of correction of acidosis, and this was related to a significant difference in intraerythrocytic potassium at the end of the session. The quicker and more regular correction of acidosis with BHD and the consequent difference in ionic flows between the intra- and extracellular spaces, as demonstrated by changes in intraerythrocytic potassium at the end of the session, could account for the seemingly less arrhythmogenic effect of BHD.

Does Lead Overload Develop in Hemodialysis Patients

Marco Martegani, MD, Divisione di Nefrologia, Ospedale Multizonale di Varese, USSL no 3, v. le Borri 57, I-21100 Varese (Italy) Dear Sir, Lead has been variously associated with gout, hypertension, and renal failure. Thomson et al. [1] described a significant but slight increase in concentrations of red blood cell lead in patients with chronic renal failure (CRF) and on hemodialysis. After EDTA chelation test, Batuman et al. [2] found higher levels of urinary lead in gouty patients with CRF than in gouty patients with normal renal function. The same author measured larger amounts of mobilizable lead in hypertensive patients with reduced renal function than in patients who had hypertension without renal impairment but suggested that this increase could not be due to the renal disease since normotensive CRF patients did not excrete such large amounts [3]. Among CRF patients, Colleoni and D’Amico [4] found a linear correlation between serum creatinine and mobilizable lead only in gouty patients. On the other hand, Behringer et al. [5] and Ritz et al. [6] observed elevated chelatable lead in patients with impaired renal function and lead exposure. Environmental pollution leads to an increasing body lead content in healthy subjects [7], which means that, as lead is mainly removed by urinary excretion [8], a lead overload could occur in patients affected by CRF even without a known or suspected exposure. In a preliminary study, the erythrocyte zinc protopor-phyrin IX (Zn PP IX) level (the increase of which may reflect a lead overload) was determined in 3 groups of patients: healthy subjects, mild to moderate chronic renal failure patients and hemodialysis patients. The results are shown in table I. The differences among the three groups were highly significant; moreover, a linear correlation between serum creatinine and Zn PP IX levels was observed (p < 0.001). Fifteen dialysis patients without lead exposure and high Zn PP IX levels were tested for serum lead. The Table I. Erythrocyte Zn PP IX levels in healthy subjects, CRF and hemodialysis patients determined by direct hematoñuorimetric method (Model 4000; Experimental Sciences Associated) Healthy subjects CRF patients Hemodialysis patients

Acute Renal Failure and Mediterranean Spotted Fever

Dr. Donato Donati, MD, Divisione di Nefrologia, Ospedale Multizonale – USSL n.3, Via le Borri, 57, I-21100 Varese (Italy) Sir, Herein we report a rather unusual case of acute renal failure associated with Mediterranean spotted fever. The patient was a 58-year-old male living in the countryside of Central Italy. He was a heavy drinker (about 250 g of ethanol/day) but he had always been in perfect health. He presented with fever (40 °C), chills and diffuse maculo-papular exantema which had appeared 5 days before admission to the hospital. On admission, he was in good general condition, well oriented in space and time and the only subjective complaint was a moderate headache. Blood pressure was 150/90, heart rate ranged around 96/min, no sign of dehydration was clinically evident in spite of the high body temperature. Pulmonary auscultation revealed rales in the basal right side where X-ray examination showed a pneumonitis focus. Serum creatinine was 3.2 mg/dl, urea 112 mg/dl, acute phase proteins were elevated, hematocrit was 40%, hemoglobin 14 g/dl, blood leukocytes were 9,210/mm3 (84% of neutrophiles), serum hepatic cytolysis enzymes were elevated, fibrinogen/fibrin degradation products were normal and the research of pathologic seric and urinary myoglobin was negative. The patient was oliguric and the few urine contained hemoglobin and 1.5 g/l of protein. Urinary sodium was 38 mEq/1, urinary potassium was 11 mEq/1. Urinary sediment showed 15–20 erythrocytes pmf, 20–25 leukocytes pmf and a number of casts, mainly hemoglobinic ones. On ultrasound, both kidneys were normal in shape and size. Acute renal failure rapidly developed, the patient became absolutely anuric and hemodialysis was started 8 days after admission. Table 1. Skin biopsy Endothelial hyperplasia Perivascular lymphocytic infiltrates Renal biopsy Tubules: segmental necrosis and proximal tubule epithelium, hemoglobin casts, intact membranes Glomeruli: intact Interstitium: edema and inflammation Vasa: no lesions Immunofluorescent staining, negative: IgG, IgA, IgM, C3, fibrinogen

The immune system and the kidney

The kidney has traditionally been viewed as a target for the immune system. It is recognized that the immune system may participate directly in the induction of acute and chronic renal injury. However, only in few clinical conditions, such as in systemic or renal-limited vasculitis, acute glomerulonephritis or acute interstitial nephritis, the immune system may directly induce acute renal failure (ARF). An increased body of evidence indicates that the kidney not only acts as a passive target for immune injury, but actively participates both in the induction of the immune response and in the activation of effector branches of natural immunity.