Effects of conventional versus biocompatible peritoneal dialysis solutions on peritoneal and systemic inflammation, malnutrition and atherosclerosis in CAPD patients.

BACKGROUND: Chronic inflammation, malnutrition and atherosclerosis (MIA syndrome) are important predictors of high mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. We aimed to evaluate the effects of PD solutions (standard vs. biocompatible) on some parameters of MIA syndrome in patients undergoing CAPD. METHODS: 42 stable patients who were on CAPD at least 2.5 years participated in this cross-sectional study. Patients who had severe anemia (Hb < 10 g/l), immunomodulatory therapy, peritonitis or any inflammatory conditions for at least 3 months before the analysis, malignant disease and acute exacerbation of heart failure, were excluded. 21 (50%) patients were treated with standard PD solutions (CAPDP-1), while the remaining 21 (50% of patients) were treated with biocompatible PD solutions (neutral solutions with lower level of glucose degradation products and lower concentration of calcium, CAPDP-2). All patients underwent echocardiography and B-mode ultrasonography of common carotid arteries together with assessments of nutrition status and parameters of systemic and local inflammation. RESULTS: There were no significant differences between the groups concerning age, gender, underlying disease, residual renal function, peritoneal transport characteristics, comorbidity or therapy applied. Patients from group CAPDP-2 had a significantly lower serum level of hs-CRP (3.7 ± 2.6 mg/l vs. 6.3 ± 4.5 mg/l; p = 0.023) and significantly better nutritional status confirmed by mid-arm circumference (p = 0.015), mid-arm muscle circumference (p = 0.002) and subjective global assessment (14.28% of patients in CAPDP-2 vs. 71% of patients in CAPDP-1 were malnourished; p = 0.000). Group CAPD-2 had less frequent left ventricular hypertrophy (p = 0.039), thinner intima-media thickness (p = 0.005), smaller carotid narrowing (p = 0.000) and fewer calcified plaques of common carotide arteries (p = 0.003). No significant difference between the CAPDP groups was observed in serum and effluent levels of inflammatory cytokines (IL-1, IL-6 and TNF-α) and CA-125 effluent level. Logistic regression analysis did not confirm that biocompatibility of PD solutions was an independent predictor of any parameter of MIA syndrome. CONCLUSIONS: According to the present study and logistic regression analysis, the effect of biocompatible CAPD solutions on parameters of malnutrition, inflammation and atherosclerosis have to be confirmed by well-designed and controlled studies in a higher number of patients.

[Significance of inflammatory cytokines in the pathogenesis of IgA nephropathy]. / Znacaj inflamacijskih citokina u patogenezi IgA nefropatije.

Prospective study was performed on the concentrations of inflammatory cytokines IL-1, TNF and IL-6 in serum and urine (ELISA tests) were determined in the scope of total clinical-laboratory and histologic treatment in 59 patients with primary IgA nephropathy. Control group consisted of 20 healthy subjects. IL-6 was not detected either in serum of patients with IgAN, or in control examinees. TNF alpha and IL-1 beta were detected in control patients' sera and in patients with IgAN, but detected concentrations were not significantly different. IL-1 beta in urine was detected in 82.8%, TNF alpha in 90.0%, and IL-6 in 40% of our patients with IgAN. The concentrations of IL-1 beta were significantly higher compared to IL-1 beta concentrations in urine of healthy subjects and significantly correlated with the severity of glomerular and tubulointerstitial changes, as well as with the degree of proteinuria. Direct and indirect toxicity of TNF alpha on renal structures was confirmed in significantly higher concentrations of that cytokine in urine of patients with mesangial sclerosis of different percentage compared to the patients with isolated mesangial hypercellularity. Also in the patients with index of chronic lesion over 7 significantly higher TNF alpha concentrations in urine were found compared to the patients with lesion index 0-3 and 4-7. Creatinine clearance was in negative correlation with TNF alpha concentrations in urine of our patients with IgAN. Concentrations of IL-6 in urine were in correlation neither with laboratory parameters of renal function, nor with the degree of histologic changes.

Treatment of IgA nephropathy with nephrotic syndrome using pulse doses of IgG.

This paper presents the preliminary results of the treatment of nephrotic syndrome in IgA nephropathy (IgAN) using pulse doses of IgG. Diagnosis was established only by percutaneous ultrasonically-guided renal biopsy, as well as on the basis of typical immunofluorescence and light microscopy findings. Histopathologic changes were classified according to the World Health Organization classification for IgAN, by determination of average glomerular, vascular and interstitial fibrosis indices and the degree of tubular atrophy. IgG therapy was administered in three patients with nephrotic syndrome associated with IgAN characterized by minimal histological changes, i.e., by diffuse mesangioproliferative glomerulonephritis. Initial IgG pulse dose was 0.4 g/kg, given as slow intravenous infusion during three consecutive days in the course of the three-month period. Maintenance therapy consisted of intramuscular IgG in the doses of 2.5 g twice a month, for the next three months. After a six-month treatment, clinical and biochemical remission was achieved in patients with minimal histologic changes, but in other two patients with diffuse mesangioproliferative glomerulonephritis, the effect of the therapy consisted of reduced proteinuria by more than 50%, with the renal function restored to the level before therapy. Transient increase in the serum creatinine level was found in two patients. These preliminary results with IgG pulse therapy, although obtained on a small number of patients, suggest the drug's potent immunomodulatory properties, but its complexity and levels of actions should be further investigated.

[Treatment of nephrotic syndrome in IgA nephropathy with IgG pulsed doses]. / Lecenje nefrotskog sindroma u IgA nefropatiji pulsnim dozama IgG.

The preliminary results of nephrotic syndrome treatment in IgA nephropathy (IgAN) with pulse IgG doses have been presented. The diagnosis of IgAN has been made exclusively by percutaneous ultrasonically guided biopsy of kidneys, on the basis of characteristic finding of immunofluorescent and light microscopy. Histopathological changes were classified upon the Classification of World Health Organization for IgAN with the calculation of average glomerular, vascular and indices of interstitial fibrosis and tubular athrophy. The therapy with IgG was applied in 3 patients with nephrotic syndrome in complex of IgAN with minimal histologic changes, i.e. diffuse mesangioproliferative glomerulonephritis. Initial pulse dose of IgG was 0.4 g/kg and it was administered in slow intravenous infusion for three days running during three months. The therapy of maintenance consisted of intramuscular administration of IgG in the dose of 2.5 g, twice a month, for the next three months. After the six-month treatment, clinical and biochemical remission was achieved in the patient with minimal histologic changes, and in the other two patients with diffuse mesangioproliferative glomerulonephritis the effect of therapy was revealed in proteinuria decrease for over 50% and the preserved renal function on the level before the therapy has started. Temporary increase of creatinine serum concentration was registered in two our patients. Preliminary results of pulse therapy with immunoglobulin G, although obtained on the small patient number, imply its powerful immunomodulatory features, which complexity and action levels should be more investigated.

[IgA nephropathy--IgA1 disease]. / IgA nefropatija--bolest IgA1.

The aim of this study was to prove the increased IgA1 production in patients with IgA nephropathy compared to the control group of healthy subjects, by determination of serum subclasses IgA, IgA1 and IgA2 levels. That with the exclusive presence of IgA1 in kidney tissue, justified the assertion that IgAN was IgA1 disease. Eighteen patients with IgA nephropathy, 15 male and 3 female, average age 17-54 (mean +/- SD = 34.1 +/- 5.18) were included in the prospective study. The diagnosis was proved by immunofluorescent assay of bioptic kidney material obtained by ultrasonically guided biopsy. The total serum IgA and IgA1 and IgA2 subclasses levels were determined in the patients and healthy conscripts from the control group. The methods of immunonephelometry and radial immunodiffusion were used. Increased IgA values were found in 22.75% and of IgA1 subclass in 38.85% patients. Patients with IgA nephropathy had significantly higher IgA1 values (p < 0.01), compared to the control group. There was no significant difference in IgA2 subclass levels. Renal function did not significantly affect IgA1 and IgA2 subclasses values.

[Ultrasound guided percutaneous biopsy of the kidney]. / Perkutana biopsija bubrega vodena ultrazvukom.

In the course of 5 years, 582 ultrasound guided percutaneous renal biopsies were performed in 558 patients. Kidney tissue was obtained in 507 patients (90.9%), and in 485 (86.9%) the obtained sample was sufficient to establish the diagnosis. Complications following renal biopsies were observed in 221 patients, or 38% of total biopsies. There were 212 (36.4%) clinically moderate complications. The most frequent ones were asymptomatic hematomae (32.6%), and infrequently lumbar pain (2.4%) and hematuriae lasting less than 12 hours (1.4%). In 9 patients 10 (1.7%) serious clinical complications in the form of hematuria lasting more than 12 h (1%), large perirenal hematomae (0.5%) and urinary infections (0.2%). In the older age group and in patients with pronounced renal failure no significant difference in the incidence of complications was observed. Ultrasound guided percutaneous renal biopsy is a safe diagnostic method, and the associated complications do not seriously curb its use. The therapy of complications is primarily conservative, and only rarely surgical.

[Correlation of inflammatory cytokines in the urine and serum with clinico-laboratory and pathohistologic features in patients with IgA nephropathy]. / Korelacija koncentracije inflamacionih citokina u urinu i serumu s klinicko-laboratorijskim i patohistoloskim odlikama kod bolesnika s IgA nefropatijom.

Complete examination of 21 patients with IgA nephropathy included determination urine and serum IL-6, TNF alpha and INF gamma levels by ELISA (Luzernachen, Luzern Switzerland). Control group included 15 healthy volunteers. Urine IL-6 levels ranging 37-274.1 pg/ml were detected in 15 (71.2%) patients with IgA nephropathy. IL-6 serum levels were undetectable. In the control group serum and urine levels were also undetectable. Correlation between the IL-6 level and proteinuria degree and endogenous creatinine clearance rate has not revealed statistically significant relationship. In relation to histologic groups (minimal changes, focal glomerulonephritis, mesangial proliferative, diffuse sclerosing) patients with minimal changes had (statistically) significantly higher IL-6 urine levels than the third and fourth group. Average the urine levels were 145.8 +/- 166.6 pg/ml and the serum ones were 148 +/- 101 pg/ml. In relation to the control group (statistically) significant difference was not found. Correlation between TNF alpha level and proteinuria degree and creatinine clearance rate has revealed (statistically) significant relationship (p < 0.05). Average interferon gamma serum levels in lgA nephropathy patients were 312.0 +/- 111.8 and in comparison with the control group (statistically) significant difference was found (p < 0.01). The obtained results suggest the important role of cytokine production disregulation associated with the pathogenesis of IgA nephropathy.

[Clinical and morphologic characteristics of adult IgA nephropathy]. / Klinicke i morfoloske karakteristike adultne IgA nefropatije.

Within the period 1987-1992 IgA nephropathy was diagnosed at the Nephrology Clinic of the Military Medical Academy in 61 patients aged from 17 to 41 years (mean +/- SD = 24.31 +/- 6.39). The aim of the study was to evaluate their importance as markers of progressive forms of IgA nephropathy by analysis of mutual relationship of clinical-laboratory and histopathological characteristics. Clinical form of the disease with recurrent macroscopic hematurias existed in 30 (49.2%) patients, and oligosymptomatic form in 31 (50.8%) patients. Acute renal failure of reversible oliguric character had 5 (8.2%) patients. Patients with recurrent macroscopic hematurias had more progressive course of IgA nephropathy which could be indirectly seen from the parameters of the global renal function. The most frequent histological form of IgA nephropathy was diffuse mesangioproliferative glomerulonephritis registered in 30 (49.2%) patients.