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J Zabka

Publications and source records attributed to J Zabka.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Cytokines and adhesion molecules in renal vasculitis and lupus nephritis].

BACKGROUND: Plasma levels and urinary excretion of proinflammatory cytokines and soluble adhesion molecules may be useful parameters of the activity of ANCA-positive renal vasculitis and lupus nephritis. METHODS AND RESULTS: Plasma levels and urinary excretion of TNF alpha, IL-6, IL-8, ICAM-1 and VCAM-1 were measured by ELISA in 14 patients (pts) with ANCA-positive renal vasculitis (8 active-ANCA-A, 6 in remission ANCA-R), 6 pts with active lupus nephritis (L.N), 15 pts with IgA nephropathy (IgAN) 10 pts with autosomal dominant polycystic kidney disease and 9 healthy subjects (Co). Fractional excretion (FE) of selected cytokines and adhesion molecules was also calculated. Pts with LN had in comparison with controls increased plasma levels of ICAM-1, VCAM-1, IL-6, IL-8 and TNF alpha, increased urinary excretion of VCAM-1, IL-8 and TNF alpha and increased fractional excretion of VCAM-1 and IL-8. Patients with ANCA-A had in comparison with controls increased plasma concentrations of ICAM-1 and VCAM-1, increased urinary excretion of VCAM-1, IL-6 and TNF alpha and increased fractional excretion of VCAM-1, IL-6, IL-8 and TNF alpha. Patients with ANCA-R had in comparison with controls higher plasma levels of ICAM-1, VCAM-1, IL-6 and TNF alpha, increased urinary excretion of VCAM-1 and TNF alpha and increased fractional excretion of VCAM-1, IL-6 and TNF alpha. CONCLUSIONS: Patients with ANCA-positive renal vasculitis had in contradistinction to pts with active LN increased fractional excretion of IL-6 and TNF alpha. Both cytokines are probably produced in renal vasculitis locally in the kidney. Increased plasma levels of soluble adhesion molecules and increased plasma levels and fractional excretion of proinflammatory cytokines in patients with ANCA-positive renal vasculitis in clinical remission may explain the strong propensity of these patients to develop relapses of the diseases on withdrawal of immunosuppressive treatment.

Adult↗
PubMed1997

[Clinical spectrum of the antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is characterized by multiple arterial and venous thromboses, repeated spontaneous abortions and thrombocytopenia, together with the presence of antiphospholipid antibodies in serum. We present three patients, two men and a woman, at the age of 43, 24 and 23 years respectively. The younger man and the woman had secondary APS and systemic lupus erythematosus, the older man had primary APS. The symptoms and course of the disease were different. The older man lives 17 years after the onset of first symptoms with multiple neurologic disorders, the younger man is symptomless. The woman died several months after the acute onset of the disease.

Adult↗
PubMed1997

Cytokine profile in autosomal dominant polycystic kidney disease.

To elucidate the pathogenetic mechanism of renal parenchymal injury in autosomal dominant polycystic kidney disease (ADPKD) patients, typically characterized by renal cystic changes paralleled by interstitial inflammation and gradual fibrotic changes, the role of selected inflammatory mediators was evaluated in a group of ADPKD patients with normal glomerular filtration rate. The plasma concentrations of IL-6, IL-8, ICAM-1 and VCAM-1 (which may reflect systemic response to inflammation/infection) were increased in the ADPKD patient group. Coupled with decreased urinary excretion of the IL-1 receptor antagonist (which exerts an anti-inflammatory role), these results suggest that even in overt infection free status, the proinflammatory system is more activated and anti-inflammatory defence system weakened in ADPKD subjects. Our data support the current view that cytokines are candidate contributors to pathogenesis of ADPKD.

Adult↗
PubMed1997

The localisation of TPPS4 in some organs and its possible nephrotoxicity in rats.

Photodynamic therapy (PDT) is now being used more frequently in carefully selected cases of malignancies. The drugs used for PDT are mostly derivatives of haematoporphyrine (HPD) and its active component photofrine II. Another compound prepared by total synthesis is meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4) but its application in human medicine was rejected because of its neurotoxicity. Our TPPS4 was prepared by the method of Busby et al. in the modification of Jirsa and Kakac (1987). This product is purer and without neurotoxic effects. In this study, we concentrated our attention on the effect of TPPS4 on nephrotoxicity and its accumulation in some organs. As the parameters of toxic kidney damage we used urine levels of N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine levels, glomerular filtration rate (GFR) and proteinuria. TPPS4 was administered i.v. in a dose of 25 mg/kg b.w. The animals were observed for 21 days after drug application. Urine and blood samples were collected over 24-hour periods on days 0, 5 and 21. The serum creatinine level was significantly higher only on day 5 (65.0+/-1.46 micromol/l vs 56.5+/-2.69 micromol/l on day 0, p<0.05). There were no significant changes in GFR, proteinuria or NAG activity in the urine during the experiment. AST serum activity was increased. We determined the concentration of TPPS4 (pmol/mg w.w.) in rat organs on the 21st day after the injection. The concentration of TPPS4 was high in kidneys (30.8+/-5.5), liver (13.5+/-2.0), lungs (11.7+/-4.6) and spleen (9.7+/-1.5), while the concentration in heart and brain was low. We conclude that TPPS4 has the highest concentration in the kidney 21 days after its administration and does not exert any nephrotoxic effects during this period.

Animals↗
PubMed1996

[Long-term administration of cyclosporine A in patients with IgA nephropathy].

BACKGROUND: IgA nephropathy is the most common glomerulonephritis all over the world and a considerable proportion of the patients reaches end-stage renal failure. Yet the standard treatment for the patients with progressive course and/or great proteinuria is currently lacking. All suggested treatment protocols, including short-term treatment with cyclosporine A had equivocal results. Therefore we decided to try long-term cyclosporine treatment. METHODS AND RESULTS: We treated 6 patients (4 males, 2 females, age 21-31 years) with bioptically proven IgA nephropathy and proteinuria over 3.5 g/24 hrs with or without nephrotic syndrome non responding to corticosteroid therapy administered for at least 3 months. Patients with serum creatinine greater than 200 mumol/l and/or glomerulosclerosis in more than 50% of glomeruli in renal biopsy were excluded. Pts were given cyclosporine A in initial dose 5 mg/kg bw/day then titrated aiming to the serum concentration of 70-150 ng/ml. Prednisone 5-10 mg on alternate days was given with cyclosporine. Proteinuria decreased during first month of therapy from 4.66 +/- 0.43 g/day to 1.38 +/- 0.29 g/day (p < 0.01) and remained low after one year of treatment (0.59 +/- 0.14 g/day, p < 0.001). Glomerular filtration rate (creatinine clearance) did not change during first month of therapy (1.25 +/- 0.21 ml/s vs. 1.38 +/- 0.29 ml/s), but slightly decreased after one year of treatment (1.05 +/- 0.14 ml/s, p < 0.05). We also calculated ratio of proteinuria to glomerular filtration rate (g/l) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80.10(-3) +/- 15.20.10(-3) before cyclosporin therapy, it decreased significantly after one month (11.56.10(-3) +/- 3.24.10(-3), p < 0.05) and achieved the lowest value after one year of therapy (6.78.10(-3) +/- 4.25 .10(-3) +/- 4.25.10(-3), p < 0.01). Serum cholesterol also significantly decreased after 12 months of therapy (6.21 +/- 0.62 vs. 5.41 +/- 0.45 mmol/l, p < 0.05). CONCLUSIONS: CyA significantly lowered moderate to high proteinuria with much less decrease of glomerular filtration rate in 6 patients with IgA. Significant decrease of proteinuria/GFR ratio strongly suggests some non-hemodynamic mechanisms of cyclosporine action in these patients. Therapy was well tolerated and side-effects were not so severe to require cyclosporine withdrawal.

Adult↗
PubMed1996

[Renal vasculitis and glomerulonephritis with anti-neutrophil cytoplasmic antibody positivity].

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) define pathogenetically related group of renal vasculitides and glomerulonephritides mostly with serious prognosis. If unrecognized, these life-threatening diseases may cause loss of independent renal function and other dangerous extrarenal complications (e. g. pulmonary haemorrhage). We concentrated on the diagnosis, treatment and log-term follow-up of these patients. METHODS AND RESULTS: Renal biopsy was performed in 46 ANCA-positive patients. Age and sex distribution, type of ANCA, organ involvement, renal biopsy findings, renal function and effect of therapy were analyzed in these patients. Twenty three patients suffered from renal vasculitis, most commonly Wegener's granulomatosis (14 patients) and microscopic polyarthritis (7 patients). IgA nephropathy (7 patients) and idiopathic necrotizing/crescentic glomerulonephritis (8 patients) prevailed in patients with limited renal involvement. Renal morphology and function was most seriously impaired in patients with Wegener's granulomatosis. Immunosuppressive treatment was able to control the activity of the disease with the negativization of ANCA and improvement or stabilization of renal function in more than 90% of patients.CONCLUSIONS. ANCA-positive renal vasculitis and glomerulonephritis is relatively common. Clinical signs of extrarenal involvement are present in about 50% of patients with ANCA-positive glomerulonephritis. Rapidly introduced immunosuppressive treatment effectively controls renal and extrarenal manifestations of the disease.

Adult↗
PubMed1996

[Lipid metabolism in the nephrotic syndrome].

BACKGROUNDS: Hyperlipidemia is a common and serious complication in patients with chronic nephrotic syndrome which unremitted may result in accelerated atherosclerosis. Accumulation of lipids in glomeruli may moreover contribute to the progression of renal insufficiency in these patients. METHODS: Total cholesterol, HDL-cholesterol and its HDL2 a HDL3 subfractions, LDL-cholesterol, triglycerides, free fatty acids, apoprotein B, apoprotein A1 and lipoprotein (a) were determined before any immunosuppressive and/or hypolipidemic therapy in 15 patients (pts) with nephrotic syndrome (8 pts with proteinuria higher than 10 g/24 hrs-NS-A, 7 with proteinuria between 5 and 10 g/24 hrs-NS-B), 7 pts with glomerulonephritis with low proteinuria (GN) and 6 pts with autosomal dominant polycystic kidney disease (PKD). All pts had normal glomerular filtration rate. RESULTS: Plasma cholesterol (10.26 +/- 2.22 vs. 4.75 +/- 0.66 mmol/1, p < 0.001), plasma triglycerides (4.03 +/- 1.64 vs. 2.17 +/- 0.12 mmol/1, p < 0.05), LDL-cholesterol (7.16 +/- 1.55 vs. 2.62 +/- 0.67 mmol/1, p < 0.001) and apoprotein B (1.92 +/- 0.47 vs. 1.11 +/- 0.31 g/1, p < 0.01) were significantly higher in NS-A than in PKD. There was no difference in total HDL-cholesterol and the ratio HDL2/HDL3 between investigated groups of pts. Lipoprotein (a) was higher in NS-A than in other investigated groups of pts. The differences between NS-B and PKD were less significant. CONCLUSIONS: Disorder of lipid metabolism is more serious in patients with more severe nephrotic syndrome than in nephrotic patients with milder proteinuria. Hypercholesterolemia is complicated in these subjects by hypertriglyceridemia and by the increase of apoprotein B and A1 and lipoprotein (a). Metabolic and renal consequences of these disorders depend undoubtedly on their duration and probably also on other factors (e.g. age, hypertension, long-term therapy with corticosteroids., etc.).

Female↗
PubMed1996

[Clinical problems in kidney disorders associated with myeloma and other paraproteinemias].

An overview of constantly enlarging spectrum of renal lesions in monoclonal gammapathies and new insights in possible pathogenesis of renal disturbances is given. Between the different types of renal affections a predominant role is played by the "myeloma kidney", induced by the presence of casts, primary amyloidosis with light chains deposition and tubular dysfunctions. Case stories of 3 patients, affected by myeloma kidney (with acute and chronic renal failure) and primary amyloidosis (with pronounced nephrotic syndrome) in context of monoclonal gammapathy are presented. Clinical problems of patients necessitating intensive hematologic and nephrologic care are highlighted, as well as need of early diagnosis and complex care.

Adult↗
PubMed1995

[Renal impairment in monoclonal gammapathies. Clinical study].

BACKGROUND: Renal involvement is an important and frequent complication in patient with monoclonal gammapathy (MG), especially in multiple myeloma (MM). Light chain proteinuria produces many renal manifestations, the most serious form is acute renal failure, which occurs in 5-10% of patients with MM. The frequency and form of renal involvement was determined in a group of patients with MG. The disturbances observed were correlated with the concentration and type of paraprotein in serum and urine. METHODS AND RESULTS: We investigated 82 patients, 37 men and 45 women with an average age of 63.5 years. Apart from standard nephrologic tests the aminoaciduria/24 h and urine acidification capacity was determined. In some patients renal biopsy was performed. Proteinuria was observed in 66 cases (80.5%), in 54 of them of Bence-Jones type. Nephrotic syndrome developed in 4 patients, in all cases the renal amyloidosis was present. Renal insufficiency was diagnosed in 39 patients (47.5%), mostly in MM. In 14 cases was renal insufficiency reversible, in 14 remain stable and in 11 progressed during the course of disease. Irreversible progression developed in terminal phase of disease in most cases. Acute renal failure was observed in 6 patients, only in four of them further course of renal disease could be evaluated. In half of these 4 patients the renal failure was reversible. CONCLUSIONS: Higher frequency of proteinuria and renal insufficiency was detected in patients with light chain paraprotein of lambda type, or biclonal kappa+lambda type. Aminoaciduria was diagnosed in 40% of patients, we did not observe complete Fanconi's syndrome. Incompleted form of renal tubular acidosis we diagnosed in 52% of cases without other signs of renal involvement.

Female↗
PubMed1995

[The spectrum of diseases associated with antineutrophil cytoplasmic antibodies].

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are considered as a diagnostic marker of systemic vasculitis and rapidly progressing glomerulonephritis. They are frequently associated with other pathological conditions. The author's objective was to analyze a group of patients examined at the Department of Clinical Immunology of the First Medical Faculty Charles University in the course of one year and evaluation of the diagnostic asset of the ANCA examination. METHODS AND RESULTS: ANCA was assessed in serum using the method of indirect immunofluorescence. In cases of p-ANCA the ELISA test was used to assess antimyeloperoxidase antibodies. Clinical data were evaluated on the basis of analysis of a questionnaire sent to doctors of patients where ANCA was detected. In 1992 1010 specimens were examined and in 115 ANCA was detected. This was the case in a group of 65 patients with the following diagnoses: systemic vasculitis 26x, systemic immunopathological diseases 12x, renal diseases 9x, inflammatory bowel diseases 7x, inflammatory eye diseases 6x, monoclonal paraproteinaemia 2x, other 4x. The patients had renal affections (45%), affections of the joints (20%), skin (18%), eyes (14%), lungs (12%), GIT (11%), ENT (9%), and nerves (9%). Type c in titres above 1:160 was always associated with the diagnosis of Wegener's granulomotosis, in other instances c- or x-types titres of 1:20 were involved. Antibodies against myeloperoxidase were detected in four instances. CONCLUSIONS: The authors confirmed that c-ANCA in high concentrations are specific for the predominantly active form of Wegener's granulomatosis. The group of patients with p-ANCA is too small to generalize the diagnostic impact. Low ANCA concentrations are found in many other diseases. The importance of ANCA can be evaluated only in a clinical context and the importance of their presence must not be overestimated.

Adolescent↗
PubMed1995

[Diagnostic and pathogenic significance of antineutrophil cytoplasmic antibodies in vasculitides].

OBJECTIVES: The study represents a complex report on diagnostic and pathogenic significance of antineutrophil cytoplasmic autoantibodies (ANCA). Our report is founded on the results of our clinical and experimental studies. METHODS: ANCA was examined by indirect immunofluorescence, or ELISA-anti MPO. The data for evaluation of diagnostic ANCA associations were gained by means of questionnaires. The experimental part involved examination of the impact of sera containing ANCA and monoclonal antibodies (MoAb) against proteinase 3 and control MoaB specific for neutrophils. RESULTS: Within the course of 1 year we have examined 1010 samples, ANCA was found in 65 patients: 26 cases of systemic vasculitis, 12 cases of other autoimmune diseases, 9 cases of isolated glomerulonephritis, 7 cases of inflammatory intestinal diseases, 6 cases of ophthalmic inflammatory diseases, and 6 cases of other diseases. Vasculitis of small vessels found in our group of patients are concomitted by ANCA positivity in 90% (Wegener's granulomatosis 15/16, Churg--Strauss's syndrome 3/5, MPA 9/9), vasculitis of medium vessels 12% (classical polyarteritis nodosa 1/2, Kawasaki disease 0/2, Henoch--Schönlein's purpura 0/4, Takayasu's arteritis 1/4). The ANCA-containing sera inhibit the candidacidal activity by 65% in average. THe inhibitory impact is yielded by anti-proteinase MoAb, in contrast to the control MoAb. CONCLUSION: c-ANCA in high concentration is specific for active form of Wegener's granulomatosis, other types of ANCA in low titres are not of diagnostic value for vasculitis. ANCA is concomitted especially by small vessels vasculitis. The proved inhibition of microbicidal PMN activity by ANCA can participate in some clinical signs of immunodeficiencies in vasculitis. (Tab. 5, Ref. 18.).

Adolescent↗
PubMed1994

[Rapidly progressive glomerulonephritis in a solitary kidney positive for anti-glomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies].

The authors describe the case-report of a 72-year-old female patient with acute failure of a solitary kidney with complete functional breakdown which developed within several days and was due to rapidly progressive glomerulonephritis (RPGN) with concurrent positivity of antineutrophil cytoplasmatic autoantibodies (ANCA) and anti-glomerular basement antibodies (AGBMA). Intensive combined immunosuppressive therapy with methyl prednisolone, cyclophosphamide and azathioprine and concurrent plasmaphereses led to negativity of both types of antibodies but were not able to restore sufficient renal function and regular dialysis treatment to be started. Subsequently AGBMA remained negative, while ANCA became again positive. Despite this partial restoration of renal function was manifested by an increased diuresis and the frequency of dialyses could be reduced. The case-report has several remarkable features. An uncommon RPGN of the antirenal type is involved, moreover in a solitary kidney with concurrent C-ANCA positivity. The concurrent presence of ANCA and AGBMA autoantibodies in RPGN has been described in the literature only in several tens of cases. So far it was not described in our country. Based on their experience the authors conclude: 1. a solitary kidney cannot be considered in case of suspected RPGN as a strict contraindicatio of renal biopsy, 2. RPGN with concurrent positivity of ANCA and AGBMA is indicated for long-term immunosuppressive therapy on account of a more favourable prognosis than simple antirenal RPGN, and also with regard to a possible suspected systematic vasculitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Renal resistance to atrial natriuretic factor as a cause of the escape failure phenomenon in patients with non-ascitic liver cirrhosis].

BACKGROUND: Chronic administration of synthetic mineralocorticoids leads in healthy subjects only to temporary fluid retention with subsequent restoration of sodium balance, i.e. the so-called mineralocorticoid escape phenomenon. There is a failure of mineralocorticoid escape in patients with ascitic liver cirrhosis with progressive fluid retention. The aim of this study was to contribute to the elucidation of the mechanisms of the escape phenomenon in patients with preascitic liver cirrhosis. METHODS AND RESULTS: Synthetic mineralocorticoid, fludrocortisone, was administered for 7 days to 8 patients with non-ascitic liver cirrhosis (LC) and 6 controls (CO) on a high sodium diet. CI seemed to have some central volume expansion before fludrocortisone administration, as assessed from a higher left atrial diameter and lower plasma aldosterone. Fludrocortisone administration in CI led to a comparable increase of ANF and suppression of plasma aldosterone as in CO with a higher diameter of the left atrium and lower PRA than in controls. Despite a comparable increase of ANF after fludrocortisone administration cGMP excretion was significantly higher in CO than in CI (434.5 + 247.1 vs. 824.6 + 317.3 pmol/min, p < 0.05). Natriuresis of CI seemed to depend on urinary cGMP excretion before fludrocortisone administration. The natriuretic response of these CI to a high sodium diet was exaggerated (290.0 + 53.9 vs. 160.0 + 18.3, p < 0.05), but they were unable to escape completely from the retaining effect of fludrocortisone. CONCLUSIONS: Failure of mineralocorticoid escape in patients with preascitic liver cirrhosis may be due to the renal resistance to ANF with insufficient increase of urinary cGMP excretion.

Adult↗
PubMed1994

[Plasma volume in polycystic kidney disease].

Hypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), occurring early in the course of the disease. Disorders of tubular transport of sodium and increased plasma and blood volume (PV and BV), as a consequence, are thought to be involved in the pathogenesis of hypertension in ADPKD. In order to evaluate PV and BV in early stage of ADPKD, PV and BV were measured with radioactive serum albumin dilution technique. Three groups of subjects with normal glomerular filtration rate were studied: ADPKD hypertensive (ADPKD H, n = 10, age: 36.2 +/- 8.7 y), ADPKD normotensive (ADPKD N, n = 15, age: 33.4 +/- 7.4 y), and healthy volunteers (C, m = 8, age: 32.6 +/- 6.8 y). PV and BV expressed per kilogram of body weight did not differ among the 3 groups. When PV and BV were expressed per meter square of body surface area, diminished BV in the group ADPKD H in comparison to ADPKD N and group c (p < 0.05) was found, other parameters did not differ between the 3 groups. In conclusion--our results do not support the hypothesis of a significantly increased PV and BV of patients with ADPKD prior to the onset of hypertension.

Adult↗