[Gastrointestinal stromal tumors]. / Gastrointestinální stromální tumory.

Gastrointestinal stromal tumours (GISTs) are the most common group of mesenchymal tumours affecting the gastrointestinal tract. Despite this, GISTs are relatively rare, since all mesenchymal tumours constitute just 1 percent of all primary GI cancers. Most often, GISTs affect the stomach and proximal small intestine but can be found in any section of the alimentary tract, including, occasionally, the omentum, mesentery and peritoneum. Virtually all GISTs (especially those larger than 1 cm) have malignant potential. Malignant potential of a tumour increases with its size and its mitotic rate, and it also depends on its anatomic location: intestinal GISTs are more aggressive than gastric tumours. Treatment of GISTs was revolutionized when it was discovered that mutational activation of KIT or PDGFRA stimulates the growth of these cancer cells. Mutational activation of KIT or PDGFRA led to abnormal activation of receptor tyrosine kinase and uncontrolled oncogenic signalling. This uncontrolled oncogenic signalling can be specifically targeted therapeutically with small molecule inhibitors of the receptor tyrosine kinase (imatinib, sunitinib). All GISTs > or = 2 cm in size should be resected. To reduce disease recurrence, adjuvant imatinib therapy is recommended for all high-risk patients after resection. Neoadjuvant therapy is recommended for primarily unresectable tumours or a limited amount of potentially resectable metastatic disease. The goal of treatment is to reduce tumour size, thus facilitating complete surgical resection and increasing the likelihood of organ preservation.

Long-term outcome of patients with idiopathic membranous nephropathy.

Although idiopathic membranous nephropathy (iMN) is a common glomerular disease, its therapy still remains controversial. The aim of our study was to analyse the outcome of patients with iMN diagnosed and treated in our center. We retrospectively studied 82 patients with iMN that were diagnosed between January 1991 and June 2002. The group consisted of 57 males (69.5%) and 25 females (30.5%) with a mean age of 53 years. The mean follow-up was 56 +/- 38 months. Remission was achieved in 59.2% of patients treated with chlorambucil, 71.4% treated with cyclophosphamide, 85.7% treated with cyclosporine and in 71.4% of those who were left untreated intentionally. However, the proportion of patients in the different treatment subgroups differed significantly (60% vs. 8.5% vs. 8.5% vs. 23%, respectively). The relapse rate was 31.3%. The second-line treatment was effective in a majority of the patients. At the end of follow-up, almost 70% of the patients were in remission with the parameters of nephrotic syndrome significantly improved and renal function unchanged. The renal survival was 100%. Immunosuppressive therapy is effective in iMN, but spontaneous remissions occur as well. Although relapses are frequent, almost 70% of the patients were in remission at the end of follow-up. The renal survival in our group of iMN patients was very good, probably due to preserved renal function at diagnosis.

Daily oral versus pulse intravenous cyclophosphamide in the therapy of ANCA-associated vasculitis--preliminary single center experience.

The aim of the multicentric randomized trial CYCLOPS is to optimize the treatment of induction of remission in patients with generalized, but not immediately life-threatening ANCA (antineutrophil cytoplasmic antibodies) -associated vasculitis. This will be achieved by reducing the dose of cyclophosphamide by administering it as intermittent pulses. The lower cumulative dose will be very probably accompanied with lower toxicity, whereas the effectivity should be comparable. We have enrolled 28 patients to the study. At present, 18 of them are suitable for evaluation. Our preliminary results show that pulse intermittent administration of cyclophosphamide is safer from the point of morbidity and mortality due to infectious complications. In our hands, this treatment modality does not seem to be less effective than the conventional daily oral cyclophosphamide. However, unambiguous results and treatment recommendations will not be available until the final evaluation of all patients enrolled in the trial.

[An unusual cause of acute anuric renal failure]. / Neobvyklá prícina akutního anurického renálního selhání.

We present a case of a 79-years old woman with acute anuric renal failure due to biopsy confirmed immunotactoid glomerulonephritis. Despite biclonal gammopathy IgG lambda, no hematologic or any other underlying malignancy was found. A possible association with viral hepatitis, cryoglobulinemia or autoimmune disease was also excluded. The patient was treated with pulse i.v. dexamethasone with very good results. Diuresis resumed and renal function gradually normalized. Our patient is one of the oldest patients with immunotactoid glomerulonephritis described. The presentation by acute renal failure with an improvement of renal function after therapy has not been previously published.

[Fibrillary glomerulonephritis]. / Fibrilární glomerulonefritis.

An overview of fibrillary glomerulonephritis (GN) is given as well as the description of clinical course in four patients diagnosed and treated in our department. Fibrillary GN and immunotactoid glomerulopathy are entities, characterized by fibrillar and microtubular deposits in mesangium and the glomerular capillary loops. Decisive for diagnosis of fibrillary GN (resp. immunotactoid GN) remains the electron microscopy (EM) of the renal biopsy (RB) specimen. At the nephrologic division of 1st Internal Department of 1st Medical School of Charles University four cases of patients with fibrillary GN were diagnosed from the mid seventies (when both entities were newly described) by the end of the year 2001. In all patients the diagnosis was proven by EM. RB was indicated mainly for proteinuria, hematuria and decrease of renal function. On conclusion: though fibrillary GN/immunotactoid GN are relatively rare disorders, they represent entities, which should not be omitted in the differential diagnosis of nephrotic syndrome/renal insufficiency and which deserve further study.

[Bartter syndrome or renal tubular acidosis?]. / Bartteruv syndrom ci renální tubulární acidóza?

In normotensive patients (pts) with apparently inherited electrolyte disorder characterized by hypokalemia and with metabolic alkalosis the suspicion is usually pronounced on the diagnosis of Bartter syndrome or Gitelman syndrome. During the last two years three pts were admitted to our nephrologic unit of the 1st Internal Department of the 1st Medical School who presented with hypokalemia, metabolic alkalosis and alkalic urine and were followed previously under working diagnosis of (incomplete) renal tubular acidosis. In the article we give the description of the clinical picture in the three pts diagnosed as Bartter/Gitelman syndrome. In conclusion--the problems of differential diagnosis in pts with such a complex disorder of acidobase balance are discussed and new diagnostic approach with mutational studies is suggested.

[Kidney involvement in light-chain deposition disease]. / Postizení ledvin na podklade nemoci z ukládání lehkých retezcu.

An overview concerning different types of kidney involvement associated with monoclonal gammapathy (MG) is given, focused on light-chain deposition disease (LCDD). Pathophysiologic basis of LCDD remains in the light-chain tissue deposition (resp. in tissue deposition of immunoglobulin's stable domain). This mechanism is typical for monoclonal immunoglobulin's overproduction as found in MG. Clinical picture of LCDD reflects multiorgan character of disorder, while renal lesions rank among the most frequent, serious and best documented ones. Clinical data referring to a group of six patients, treated in our nephrologic department are presented. Diagnosis of LCDD was established on basis of the renal biopsy finding. Renal functions were decreased at the time of diagnosis in all patients, whereas haemodialysis treatment was started in one patient. On conclusion therapeutic possibilities of LCDD are discussed, in which number symptomatic therapy of renal failure is combined with corticosteroids therapy and cytostatic therapy; prognosis of most patients remains serious.

[Renal infiltration in lymphoma--diagnosis in renal biopsy (case report)]. / Infiltrace ledvin lymfomem--diagnóza pri renální biopsii (kazuistika).

A case story of a patient with renal biopsy (RB) proven infiltration with lymphoma is given. RB in patient with known malignancy and onset of renal failure was indicated with regard to an atypical picture of kidney involvement (non-enlarged kidneys, without any structural changes typical for tumour mass presence). Though spread of the primary tumour to the kidney is not uncommon, involvement severe enough to impair renal function is unusual and occurs primarily with rapidly growing haematologic malignancies; diagnosis is being established by renal biopsy only rarely.

Transjugular renal biopsy. Our experience with 67 cases.

BACKGROUND: Transjugular renal biopsy (TJRB) is still a novel technique of renal tissue sampling exploiting the transjugular route. TJRB should be performed particularly in situations when the percutaneous route is precluded, i.e. especially in patients with clotting disorders. In the past, only a few papers reported the experience with larger numbers of patients. The goal of this paper is to analyze our experience with TJRB. METHODS AND RESULTS: From 1993 to 1999, 67 patients, mean age 49.8 years (SD +/- 10.2), male/female ratio 40/27, underwent TJRB. Fifty-two patients (78%) suffered from renal insufficiency and 19 of them (28%) were on dialysis treatment at the time of TJRB. Arterial hypertension was recorded in 42%. The combined kidney and liver biopsy (46%) and clotting disorders (39%) were the most frequent indications for performing TJRB. Renal tissue was yielded in 53 patients (79%) but a sample sufficient for histological diagnosis was taken in 49 (73%), reaching on average 10.8 glomeruli. Altogether 19 different histological entities were disclosed and out of them, vascular nephrosclerosis (12%), necrotizing and crescentic glomerulonephritis, IgA nephropathy (IgAN) and amyloidosis (three latter per 10%) represented the most frequent diagnoses. TJRB was combined with liver biopsy in 31 patients (46%) and/or hepatic vein catheterization in 22 patients (33%) confirming portal hypertension in 8. The clinically significant liver histology was found in 20 patients, of them cirrhosis/fibrosis in 8, chronic hepatitis in 4 and steatosis in 5. Among those 20 patients, IgAN was disclosed as the most common renal diagnosis (6). Clinically symptomatic complications were recorded in 12 cases (18%) but 9 of them suffered from clotting disorders. Complications included development of subcapsular hematoma in 6 cases, macroscopic hematuria in 4 cases, and hypovolemic hemorrhagic shock in 2. One patient had to undergo surgical treatment. Dividing the patients into a subgroup with or without clotting disorders, the complication rate was 34 vs. 7%. CONCLUSIONS: TJRB is a new diagnostic method, which, looking at its indications, facilitates the diagnosis of glomerulopathies in patients who could not be considered for percutaneous renal biopsy, particularly due to clotting disorders. The technical aspect of this procedure plays a fundamental role in the final risk/benefit ratio but if done correctly it involves acceptable risk and is well tolerated.

Long term treatment of IgA nephropathy with cyclosporine A.

20-50% of patients with IgA nephropathy (IgAN) reach end-stage renal failure. Yet a standard treatment for those with progressive course and/or great proteinuria is lacking. We treated 6 patients with biopsy proven IgAN, proteinuria over 3.5 g/24 h and S-creatinine less than 200 micromol/L non-responding to corticosteroids administered for 3 months. They were given cyclosporine A (CsA) 5 mg/kg bw/day then titrated aiming at a serum concentration of 70-150 ng/mL for one year tapered to discontinuation in 9 months. Prednisone 5-10 mg on alternate days was given with CsA. Proteinuria (g/day) decreased from 4.66 +/- 0.43 to 1.38 +/- 0.29 (p < 0.01) after 1 month and to 0.59 +/- 0.14 (p < 0.001) after 1 year of treatment and remained lower than baseline 2 years from the beginning (1.44 +/- 0.27, p < 0.001). GFR (creatinine clearance) did not change during the first month (1.25 +/- 0.21 mL/s vs 1.38 +/- 0.29 mL/s), but decreased after 1 year (1.05 +/- 0.14 mL/s, p < 0.05). After two years it increased to 1.17 +/- 0.16, NS from baseline. We also calculated the ratio of proteinuria to the GFR (mg/L) to assess the role of hemodynamic changes in the decrease of proteinuria. This ratio was 53.80 + 6.47 before therapy, it decreased after 1 month (11.56 +/- 1.7, p < 0.05) and further after 1 year (6.78 + 1.45, p < 0.01). Three months after discontinuation it was still 14.32 +/- 1.00, p < 0.05 from baseline. In conclusion, CsA significantly lowered moderate to high proteinuria in 6 patients with IgAN. Significant decrease of the proteinuria/GFR ratio suggests some non-hemodynamic mechanism of CsA action. The therapy was well tolerated and side-effects were not so severe as to require CsA withdrawal.

[Plasma leptin levels in patients with kidney diseases of various etiologies]. / Plazmatické hladiny leptinu u pacientu s ledvinovým onemocnením ruzné etiologie.

BACKGROUND: Leptin is a new hormone influencing food intake, energy expenditure and body weight. This protein is produced by adipocytes, exerts its effects on brain, endocrine pancreas and other organs by activating transmembrane receptors and is cleared from plasma mainly by the kidneys. The aim of our study was to compare plasma concentrations of leptin in our nephrological out-patients and controls. METHODS AND RESULTS: We examined 36 diabetic patients with various stages of nephropathy, 12 males with nephrotic syndrome due to membranous nephropathy, 15 dialysis patients and 11 controls. Leptin was assessed in plasma by ELISA. There was a significant difference between plasma levels of leptin in males and females (7.7 +/- 11.4 vs 17.6 +/- 17.3, p < 0.001) and in dialysis and non-dialysis patients (19.6 +/- 16.5 vs 10.7 +/- 14.5, p < 0.05). There was also a difference between dialysed and non-dialysed men (15.1 +/- 16.2 vs 5.9 +/- 9.2, p < 0.05). We found no difference between men with and without nephrotic syndrome and between BMI or age. There was a positive correlation of leptin with diabetic and non-diabetic women. There was positive correlation of P-leptin with serum creatinine in non-dialysed women (r = 0.68, p < 0.001) and a negative correlation with S-albumin in nephrotic men (r = -0.65, p < 0.05). CONCLUSIONS: Women have higher plasma leptin concentrations than men and dialysis patients have higher concentrations than non-dialysed patients. Apart from the positive correlation with S-creatinine in non-dialysed women. There was positive correlation with S-albumin in nephrotic men there were no correlations with renal function, BMI, age, S-cholesterol, S-triglycerides and S-albumin.

[Relation between plasma levels of IGF-I, leptin and TNF-alpha in diabetics]. / Vztah plazmatických hladin IGF-I, leptinu a TNF-alfa u diabetiku.

BACKGROUND: TNF-alpha, IGF-I and leptin are agents which influence insulin resistance, they play probably a part in the pathogenesis of diabetic nephropathy and influence mutually their production. The objective of the submitted investigation was to assess whether there exist relations between their concentrations in the plasma of diabetic patients. METHODS AND RESULTS: The authors examined 37 patients aged 18-67 years from a diabetic clinic, 10 with normal albuminuria and normal renal function, 12 with microalbuminuria and 15 with macroalbuminuria and/or reduced renal function. TNF alpha, IGF-I and leptin were assessed in plasma, using commercial kits, by the ELISA method. IgF-I in plasma correlated inversely with glycated haemoglobin (r = -0.20, p < 0.05). In women a correlation was found between IGF-I and TNF-alpha concentrations (r = 0.65, p < 0.01). No other mutual correlations were found between concentrations of the investigated substances and between cytokine concentrations and serum creatinine, glycated haemoglobin, the blood glucose level and body mass index. CONCLUSIONS: IGF-I plasma levels correlate inversely with glycated haemoglobin and in women with the TNF-alpha level. No other correlations were found between IGF-I. TNF-alpha and leptin plasma levels. The levels do not correlate with age, renal function and compensation of diabetes.

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis.

BACKGROUND: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. METHODS: Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. RESULTS: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05). CONCLUSIONS: Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.

[Soluble cytokinin receptors in renal vasculitis and lupus nephritis]. / Solubilní receptory pro cytokiny u renální vaskulitidy a lupoidní nefritidy.

BACKGROUND: Activation of various cytokines, e.g. TNF alpha, IL-1 and/or IL-6 may play important role in the pathogenesis of renal vasculitis and lupus nephritis (LN). Systemic effects of these cytokines may be modulated by their circulating soluble receptors. Plasma levels of cytokine receptors may thus be also markers of the activation of these cytokines. METHODS AND RESULTS: Plasma levels of TNF alpha, its soluble receptor p75 (sTNF-RII), IL-6 and soluble IL-6 receptor (sIL-6R) were measured using ELISA in 17 pts with ANCA-positive renal vasculitis (12 active-ANCA-A, 7 in remission ANCA-R), 9 pts with active lupus nephritis (LN) and 5 healthy subjects. Pts with LN had in comparison with controls increased plasma levels of TNF alpha, sTNF-RII, IL-6 and sIL-6R. Pts with ANCA-A had also in comparison with controls increased plasma levels of TNF alpha, sTNF-RII and sIL-6R, but plasma levels of IL-6 were not significantly increased dut to great standard deviation. Pts with ANCA-R had in comparison with controls increased plasma levels of sTNF-RII, but plasma levels of TNF alpha were in ANCA-R significantly lower than in ANCA-A. While the ratio TNF alpha/sTNF-RII was significantly lower in all groups of pts than in controls, the ratio IL-6R/sIL-6R was in comparison with controls significantly increased only in LN. CONCLUSIONS: While increased plasma levels of TNF alpha may be nonspecific marker of the activity of ANCA-positive renal vasculitis and LN, plasma levels of sTNF-RII are increased also in pts with ANCA-positive renal vasculitis in remission. Increased plasma levels of sTNF-RII may interfere with systemic effects of TNF alpha, but may also prolong the lifetime of its active form. Plasma levels of sIL-6R are increased both in ANCA-A and in LN, but their increase is, however, much less pronounced than that of sTNF-RII and cannot effectively block systemic effects of IL-6.

Influence of plasma exchange on serum levels of cytokines and adhesion molecules in ANCA-positive renal vasculitis.

BACKGROUND: Increased serum levels of proinflammatory cytokines may contribute to the organ damage in active antineutrophil cytoplasmic antigen (ANCA)-positive renal vasculitis. Plasma exchange (PE) may influence the activity of vasculitis not only by removing pathogenic autoantibodies, but also by lowering the serum levels of circulating cytokines. METHODS: Serum levels of IL-1beta, IL-1ra, IL-6, IL-8, ICAM-1 and VCAM-1 were measured using ELISA in 10 patients with active ANCA-positive renal vasculitis (5 patients with Wegener's granulomatosis, WG, and 5 patients with microscopic polyangiitis, MPA) during the course of therapeutic PE. Cytokines and adhesion molecules were measured in samples of serum obtained at the beginning and at the end of the 1st, 3rd and 5th PE and in samples of filtrate obtained during the same PE. RESULTS: In comparison with controls, patients with ANCA had higher serum levels of IL-1ra, IL-8, ICAM-1 and VCAM-1 before the 1st PE. Serum levels of IL-6, IL-8, ICAM-1 and VCAM-1 were increased in patients with MPA, and the serum levels of all the cytokines and adhesion molecules measured in patients with WG were increased. At the end of the PE course there were decreases in the serum levels of IL-1ra and VCAM-1 in ANCA patients and IL-1ra and ICAM-1 in WG patients. Single PE in ANCA patients led only to a decrease in serum levels of ICAM-1 and VCAM-1. On the other hand, there was no change in serum levels of IL-1beta and IL-8, and the serum levels of IL-1ra and IL-6 even increased at the end of a single PE, in spite of high levels of all cytokines and adhesion molecules in the plasma filtrate. CONCLUSION: Serum levels of soluble adhesion molecules decrease after PE, but serum levels of proinflammatory cytokines are not reduced even by a PE course. Removal of these substances by PE is obviously counteracted by their increased production, possibly further stimulated by the contact of blood with the synthetic membrane. The insufficient influence of PE on the elimination of proinflammatory cytokines may partially explain its limited effect in some patients with ANCA-positive renal vasculitis.

[Laboratory findings and serum levels of amyloid A and soluble interleukin-2 receptors in patients with renal amyloidosis]. / Laboratorní nálezy a hodnoty sérového amyloidu A a solubilního receptoru pro interleukin 2 u nemocných s amyloidózou ledvin.

BACKGROUND: Renal amyloid involvement results either from primary or secondary amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course depends not only on the type of basic process but reflects also time of diagnosis and possibility to influence the basic process. METHODS AND RESULTS: We analyzed laboratory and clinical data of patients with bioptically proven renal amyloidosis. We found renal amyloidosis in 27 patients from an overall number of 750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had laboratory signs of nephrotic syndrome, all patients had various degree of proteinuria. Impaired renal function were found in more than 50% of patients, in 6 of them we had to start renal replacement therapy. 8 pts died. Complications of severe nephrotic syndrome were the causes of death in majority of cases. We have started investigation of some amyloid precursors and cytokines in patients with AA and AL amyloidosis. We compared the results with group of patients with vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and soluble receptor for interleukin 2 (sIL-2R). CONCLUSIONS: Clinical features and laboratory findings in our patients with renal amyloidosis approximately are in accordance with literary data. Plasmatic level of SAA was increased not only in the group of patients with AA amyloidosis, but also in the group of vasculitis. Urinary sIL-2R was significantly increased in patients with AA amyloidosis in comparison with healthy controls.

Effect of 1 year cyclosporine A treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study.

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.

[Cytokines and adhesion molecules in renal vasculitis and lupus nephritis]. / Cytokiny a adhezní molekuly u renální vaskulitidy a lupoidní nefritidy.

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.