Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

[Oxidative stress in patients after kidney transplantation]. / Oxidacní stres u pacientu po transplantaci ledviny.

Successful kidney transplantation (KT) leads not only to normalization of renal excretory function, but also to modification of the metabolic and endocrine kidney function. The most common cause of morbidity and mortality in patients after KT are cardiovascular diseases which development is also associated with oxidative stress (OS). KT and the posttransplantation period are associated with increased OS that could gradually decrease. Some immunosuppressive drugs also contribute to increase of OS, especially compounds from a group of calcineurin inhibitors and thus indirectly contribute to increased risk of cardiovascular complications.

[Oxidative stress in patients on regular hemodialysis and peritoneal dialysis]. / Oxidacní stres u pacientu s náhradou funkce ledvin hemodialýzou a peritoneální dialýzou.

Hemodialysis and peritoneal dialysis are methods of blood purification, which partially replaced excretory renal function in patients with chronic renal failure, which was depleted regime, dietary and pharmaco-therapeutic remedy, and who are not eligible for kidney transplantation. Both two methods are accompanied by increased oxidative stress. In peritoneal dialysis particularly the composition of dialysis solution contributes to oxidative stress. In extracorporeal hemodialysis the oxidative stress is associated with the character of hemodialysis membranes, non-specific loss of low molecular weight antioxidants, activation of leukocytes (oxidative burst), feroteraphy, supplementation with low molecular weight antioxidants and other factors. To improve and maintain the quality of life of dialysis patients, the continuous monitoring of oxidative stress-related parameters as non-traditional risk factors for cardiovascular complications development is suitable.

[Oxidative stress in kidney disease patients]. / Oxidacní stres u pacientu s onemocnením ledvin.

Patients with chronic kidney disease are exposed to oxidative stress (OS) that contributes to deterioration of health. Decrease in renal excretory capacity contributes to the accumulation of pro-oxidative substances that are detrimental not only to kidney but to the whole organism including the cardiovascular system. Components of antioxidant system play an important role in the elimination of the OS. The monitoring of antioxidant levels and products of oxidative damage in these patients and the correct interpretation of relationship between these markers and the function of kidney and other organs may contribute to the more effective treatment and health improvement of the patients.

[Aetiology and a clinical picture of chronic renal failure]. / Etiologie a klinický obraz chronického selhání ledvin.

The term chronic renal failure (CRF) usually means the final stage of chronic kidney disease (CKD) with a decline in glomerular filtration rate (GF) below 0.25 mL/s. CRF is a world-wide serious health and economic issue with an increasing incidence and prevalence. CRF patients are, in comparison to other patients, hospitalized more often and for longer and, despite improvements in care, their quality of life is usually low and morbidity and mortality high. We present an overview of the most important CKD risk factors and the diseases most likely to result in CRF. Diabetic nephropathy, followed by various forms ofischemic renal disease and primary and secondary glomerulopathy, chronic tubulointerstitial nephritis and autosomal dominant polycystic kidney disease are the leading causes of CRF. We provide a brief overview of other disease states that may result in renal failure. Clinical manifestations of CRF are discussed, mainly cardiovascular, gastrointestinal, haematological and neurological symptoms. Breathlessness is a consequence of hypervolaemia, metabolic acidosis and anaemia. The disease often presents with symptoms, such as headache and visual disturbances, resulting from arterial hypertension. Gastrointestinal symptoms and fatigue, usually caused by anaemia, are frequent. Platelet dysfunction is manifested as an increased bleeding time. Paradoxically, apart form tendency to abnormal bleeding, CRF also tends to be associated with thromboembolic complications. Patients may experience itching, bone, joint and muscle aches, are more prone to infections. They may suffer from insomnia, concentration disorders and apathy. The signs of peripheral mixed sensory-motor neuropathy include paraesthesia, paresis and restless leg syndrome. However, renal failure may also be oligosymptomatic or asymptomatic. Cardiovascular complications are the most frequent cause of morbidity and mortality of CRF patients.

[An overview of the results of renal transplantation in the Czech Republic]. / Piehled výsledku transplantací ledvin v Ceské republice.

Renal (kidney) transplantation is now a routine and the most successful form of renal replacement therapy. There is a long tradition of renal transplantation in the Czech Republic, The first was performed as early as 1961 in Hradec Kralove, and the programme as such was launched in 1966 with the first successful transplantation at the Institute of Experimental Surgery (later Institute for Clinical and Experimental Medicine, Prague). At present, transplantations are being performed at 7 transplantation centres (IKEM Prague, Centre for Cardiovascular and Transplantation Surgery Brno, Faculty Hospitals Hradec Kralove, Plzen, Olomouc and Ostrava and Faculty Hospital Motol for children). From the programme launch until the end of 2010, 8,761 renal transplantations were performed, 364 in 2010 alone. One-year patient and cadaver renal allograft survival, transplanted in the CR between 2000 and 2009, is around 95% and 92%, respectively, and 5-year survival is 87% and 81%, respectively. As of 31st December 2009, a total of 3,771 patients lived with functional renal allograft in the Czech Republic and the proportion of patients with irreversible renal failure treated with transplantation has recently been around 40%.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

[Merkel cell skin carcinoma]. / Kozní karcinom z Merkelových bunek.

Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin inspection in high-risk immunocompromised patients must be stressed and suitable therapy must be indicated in suspected lesions.

[The infection of the arteriovenous hemodialysis access created with ePTFE prosthesis. Treatment based on experience or on modern examinations findings?]. / Infekce av spojky k hemodialze zalozené ePTFE interponátem. Lécba na základe zkuseností nebo podle nálezu moderních vyetrovacích metod?

The infected ePTFE prosthesis for hemodialysis threatens the patient with local complications such as occlusion, the tunnel infection and massive hemorrhage. These complications are associated with the loss of function of the fistula. Infected prosthesis can work as a source for metastatic infections (endocarditis, arthritis, pneumonia), and sepsis. In European countries, interposition of ePTFE graft usually represents the last option of angioaccess beside the catheterization of central venous system; hence attempts occur to maintain the fistula function despite the manifestation of infection. Authors evaluate the total graftectomy (TGE) and the partial graftectomy (PGE) on the basis of their knowledge and literature findings. They take a stand whether it is preferable to remove an infected graft according to experience or to proceed conservatively following the modern examinations (USG, microbiology, PET CT). According to the documented case-report they tend more to the solution based on experience. If the infection of graft is of gram-negative etiology the total graftectomy (TGE) is recommended.

Patients with IgA nephropathy have altered levels of immunomodulatory C19 steroids. Glucocorticoid therapy with addition of adrenal androgens may be the choice.

Glucocorticoid (GC) therapy is one of the methods of choices for treatment of autoimmune diseases (ADs). In addition, adrenal androgens are known as immunoprotective GC-antagonists. Adrenal steroids preferentially influence the Th1-components over the Th2 ones. We investigated steroid metabolome (using gas chromatography-mass spectrometry) in healthy controls (H), GC-untreated patients with ADs different from IgA nephropathy (U), GC-treated patients with ADs different from IgA nephropathy (T) and in patients with IgA nephropathy (IgAN), which were monitored on the beginning (N0), after one week (N1) and after one month (N2) of prednisolone therapy (60 mg of prednisolone/day/m(2) of body surface). Between-group differences were assessed by one-way ANOVA, while the changes during the therapy were evaluated by repeated measures ANOVA. The ANOVA testing was followed by Duncan's multiple comparisons. IgAN patients and patients with other ADs exhibited lack of adrenal androgens due to attenuated activity of adrenal zona reticularis (ZR). Androgen levels including their 7alpha-, 7beta-, and 16alpha-hydroxy-metabolites were further restrained by GC-therapy. Based on these results and data from the literature, we addressed the question, whether a combination of GCs with delta(5)-steroids or their more stable synthetic derivatives may be optimal for the treatment of antibodies-mediated ADs.

C1q complement component and -antibodies reflect SLE activity and kidney involvement.

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM

[Nonsteroidal antiinflammatory drugs and the kidney]. / Nesteroidní antirevmatika a ledviny.

Nonsteroidal antiinflammatory drugs (NSAIDs) have potentially important renal adverse effects. With regard to renal adverse effects there is no indication of significant differences between conventional NSAIDs and selective COX-2 inhibitors. Their nephrotoxicity has been well documented. Many of the renal abnormalities that are encountered as a result of NSAIDs use can be attributed to the inhibition of prostaglandins synthesis. The release of prostaglandins is particulary importent in high-risk patients, including patients with severe heart disease, liver disease, preexisting renal disease, elderly and patients with volume depletion. The common complication of NSAID use is retention of sodium and edema formation due to increased reabsorption of sodium and water in the loop of Henle and hyperkalemie due to diminished renin secretion. Nonsteroidal antiiflammatory drugs can induce two different forms of acute renal failure. Decreased prostaglandin synthesis can lead to reversible renal ischemia and hemodynamically-mediated acute renal failure. Second form of acute renal failure is acute interstitial nephritis. This type of interstitial nephritis is often accompanied by nephrotic syndrome due to minimal change disease. Nephrotic syndrome after NSAIDs treatments may be also associated with membranous nephropathy. Another complication of NSAIDs treatment is modest rise of systemic blood pressure in some hypertensive patients due to increase in renal and systemic vascular resistence. In patients consuming excessive amount of NSAIDs over a prolonged period of years papillary necrosis can occur. Exposure to large quantities of NSAIDs can probably induce in some patients chronic renal insufficiency.

Changes in bone mineral density and selected metabolic parameters over 24 months following renal transplantation.

Our aim was to evaluate changes in serum levels of selected bone metabolism indicators and bone density over 24 months following renal transplant. A partial objective was assessment of the effectiveness of prophylactic administration of vitamin D and calcium preparations to prevent progression of osteopathy after kidney transplantation. Forty patients after kidney transplantation were prophylactically given vitamins A and D (800 IU) and calcium (1000 mg) a day. During monitoring, the serum creatinine in all recipients was <200 micromol/L (subgroup A with creatinine concentration < 120 micromol/L versus subgroup B with creatinine 120 to 200 micromol/L). The concentration of serum parathormone, serum level of bone fraction of alkaline phosphatase, serum concentrations of phosphorus and calcium urinary 24-hour excretion of phosphorus and calcium were examined at 2 weeks and 2 years after transplantation. In the same time period, radiographs of thoracic, lumbar spine, and hip joints were obtained. Bone density (BMD) of the lumbar (L) spine and the hip was determined by dual-energy X ray (Lunar Prodigy). Two years after transplantation in subgroup A, the BMD showed decrease in 80% of recipients in the L spine area but hip showed a 15% BMD increase. In subgroup B, the BMD decreased in 95% recipients in L and hip and only 25% showed a BMD increase. No clinical or radiographic sign of fracture was detected in this group. We conclude that prophylactic administration of vitamin D and calcium is not sufficient to prevent the progression of osteopathy after renal transplantation. Changes in bone density evaluated after the kidney transplantation are affected by graft function.

Histomorphometric diagnostics of renal osteopathy in chronic dialysis patients at high risk of cardiovascular disease.

UNLABELLED: Chronic kidney disease-mineral and bone disorder (CKD-MBD) ranks among clinically and pathogenetically significant complications in patients with CKD. Numerous factors are involved in its development, and histomorphometric analysis of the bone tissue is still necessary for accurate diagnosis. METHODS: The open, pilot, prospective study aimed at performing a comprehensive histomorphometric bone analysis in 26 dialysis patients and assessing the relationships of different types of CKD-MBD to selected parameters of calcium and phosphate metabolism, densitometry, activity of parathyroid glands, presence of diabetes mellitus, and duration of dialysis treatment. RESULTS: Comparison of the histomorphometric characteristics demonstrated statistically significant correlations between the volume of bone trabeculae and s-procollagen 1 (.754) as well as s-calcitonin (.856). Similarly, there was a positive correlation between the size of tetracycline lines and volume of bone trabeculae (.705) and a strong negative correlation with the thickness of trabeculae (-.442). When assessing the serum levels of s-osteoprotegerin and serum RANKL, there was a correlation with osteoid thickness and bone trabeculae thickness. In case of s-osteoprotegerin, a statistical power was demonstrated in relation to osteoid thickness (.880); in case of s-RANKL, a statistical power was demonstrated in relation to the thickness of trabeculae (.830). When assessing the influence of dialysis duration, relationships to the volume of trabecular bone (.665) and volume of bone trabeculae (.949) were demonstrated. Finally, a relationship between s-1,25-hydroxyvitamin D and s-osteoprotegerin was observed (.739); also the relationships demonstrated were significantly lower volume of bone trabeculae in men (p = 0.067) and lower values of s-osteocalcin and s-procollagen 1 in diabetic patients (p = 0.014). CONCLUSION: The results provide new noninvasive possibilities of CKD-MBD detection that are based on selected serum parameters of bone metabolism. Presented are possibilities of noninvasive assessment of different types of CKD-MBD using serum osteomarkers in relation to comprehensive CKD-MBD histomorphometry.

[Infected arteriovenous fistulae for hemodialysis]. / Infikovaná arteriovenózní spojka k hemodialýze.

Angioaccess procedures for hemodialysis over a 12-year period were retrospectively reviewed to ascertain the frequency of infectious complications. A total of 571 angioaccess procedures were performed including 88 e-polytetrafluoroethylene (GORE) grafts. Early infectious complications occurred only in 5 autogenous fistulae. Late infectious complications occurred in 2.3% autogenous fistulae and in 7.95% ePTFE grafts. Infected arteriovenous fistula can be the cause of further complications (thrombosis, bleeding, aneurysm, sepsis) and demands surgical repair.

[Histologic findings in protocol biopsies of transplanted kidneys]. / Histologické nálezy v protokolárních biopsiích transplantovaných ledvin.

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurRence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppression nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.

[Alport's syndrome]. / Alportuv syndrom.

After a historical introduction the authors analyze contemporary views on the aetiology, pathogenesis and genetics, they characterize the clinical picture and histopathological findings in Alport's syndrome. They emphasize that Alport's syndrome is more frequent than generally reported and that it deserves therefore appropriate attention in the differential diagnosis of renal diseases. They draw attention to the results of most recent genetic research which makes it possible to detect gene carriers of Alport's syndrome as well as early prenatal and postnatal diagnosis of this most frequently progressing hereditary nephritis.

[Endogenous erythropoietin in patients on regular dialysis therapy]. / Endogenní erytropoetin u nemocných v pravidelném dialyzacním lécení.

In a group of 66 patients with chronic renal failure having regular dialyzation treatment the serum concentration of endogenous erythropoietin (EPO), haemoglobin levels (Hb), haematocrit (Ht) and serum creatinine (Cr) were assessed. The examined subjects were never treated with recombinant erythropoietin and deficiency of iron, folic acid and vitamin B12 was ruled out. Endogenous EPO was assessed by the authors own RIA method, normal values being 24-42 mU/ml. The mean EPO concentration in the whole group of patients was 37.4 +/- 15.3 mU/ml, whereby 12 patients had an EPO serum concentration higher than the upper range of normal values. Between EPO concentrations and Hb values a certain positive correlation was found (r = 0.42). A similar relationship was revealed also between EPO concentrations and Ht values (r = 0.41). Patients with EPO values higher than 42 mU/ml had, as compared with the other patients, significantly higher values of erythrocytes (p .001). Statistical analysis did not reveal any relationship between EPO and Cr concentrations (r = -0.04). A low negative correlation was found between Cr and Hb values (r = -0.31) and between Cr and Ht values (r = -0.25). In the discussion the authors analyze the contemporary state of the problem of anaemia in chronic renal failure. Based on hitherto assembled knowledge they formulated the hypothesis ascribing considerable pathogenetic importance in the development of anemia to reduced sensitivity of bone marrow to EPO, probably as a result of retention of uraemic toxins and inhibitors of erythropoiesis. Inadequate EPO formation could be only a factor which makes it impossible for the developing anaemia to compensate and is due to an animpaired feedback at the level of recognition of the hypoxic signal.

[The significance of plasmapheresis in the treatment of acute liver failure]. / Význam plazmaferézy v lécbe akutního selhání jater.

The authors describe the use of plasmapheresis in the treatment of acute hepatic failure in viral hepatitis with a fulminant course. Plasmapheresis was used with regard to severe trombocytopenia and manifestations of haemorrhagic diathesis. In the discussion they draw attention to the importance of supportive methods in the treatment of acute hepatic failure and to perspectives of liver transplantations in this context.

[Erythropoietin and erythropoiesis after kidney transplantation]. / Erytropoetin a erytropoéza po transplantaci ledviny.

In a group of 15 patients after the first transplantation of a cadaverous kidney the authors monitored for the period of one month the serum erythropoietin concentration (Epo), haemoglobin levels (Hb), the haematocrit (Ht) and serum creatinine (Cr). The objective of the investigation was to evaluate in relation to serum concentrations of Epo and the function of the graft. Erythropoietin was examined by the authors own method before and after transplantation during the first 10 days daily and then on the 12th, 15th, 20th, 25th and 30th day. Normal values are 22-44 mU/ml. The mean Epo value before transplantation was 41.9 +/- 18.8 mU/ml. After transplantation the highest mean value of Epo was recorded on the second day when it reached a value of 102.8 +/- 144 mU/ml. The mean Epo serum concentration at the end of the study was 45.9 +/- 20.9 mU/ml and did not differ significantly from values recorded before transplantation. Between Hb and Ht values and Epo serum concentrations no correlation was revealed. Conversely, statistical analysis revealed a close inverse relationship between the drop of creatininaemia and the rise of Hb and Ht values. From the results of the investigation ensues that the decisive condition for the onset of the erythropoietic response after renal transplantation is adjustment of the milieu interiéur, induced by the restored excretory function of the graft which creates prerequisites for a normal response of the bone marrow to Epo.