RATIONALE: The use of cisplatin in patients with chronic kidney disease (CKD) is risky and depends on a number of factors. The optimal procedure in stage I of a non seminomatous germ cell tumor without proven lymphangioinvasion after orchiectomy is controversial and is the subject of a number of discussions due to the lack of randomized studies assessing individual treatment options. The adjuvant method of choice is surveillance or application of cisplatin-based chemotherapy with the risk of treatment related nephrotoxicity. Information about cisplatin safety in renal transplant patients is particularly limited. The aim of this paper is to share the experience with the application of adjuvant chemotherapy Bleomycin, Etoposide, Cisplatin (BEP) in high-risk patient with nonseminoma after kidney transplantation. PATIENT CONCERNS: We report a case report of rare group of high-risk patient with non-seminomatous germ cell testicular tumor (NSGCT) after kidney transplantation before application of adjuvant chemotherapy BEP. Patient presented with month-long discomfort in the scrotal area. Previously, he was treated with chronic kidney disease based on chronic glomerulonephritis, which was treated with repeated kidney transplantation. DIAGNOSIS: The ultrasound examination for a month-long discomfort in the scrotal area found a solid mass of the left testis. Radical inguinal orchiectomy confirmed NSGCT with the presence of lymphovascular invasion (LVI). Postoperative staging with computed tomography of the chest and abdomen did not show obvious dissemination of the disease. INTERVENTIONS: Reducing original dose of chemotherapeutics according to the recommendations of the summary of product characteristics led to only a transient increase in creatinine levels. OUTCOMES: The 5-year risk of relapse in surveillance was reduced to around 3% by applying cisplatin-based chemotherapy. LESSONS: Application of cisplatin-based chemotherapy is safe and effective in patients with CKD and in patients with a kidney transplant.
- MeSH
- adjuvantní chemoterapie MeSH
- bleomycin škodlivé účinky terapeutické užití MeSH
- chronická renální insuficience komplikace imunologie chirurgie MeSH
- cisplatina škodlivé účinky terapeutické užití MeSH
- etoposid škodlivé účinky terapeutické užití MeSH
- germinální a embryonální nádory komplikace farmakoterapie chirurgie MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- orchiektomie MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky terapeutické užití MeSH
- testikulární nádory komplikace farmakoterapie chirurgie MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Chronic kidney disease stage 5 (CKD5) dialysis patients who stay long term in uremic environment often exhibit several, poorly defined, immune impairments. In this study, we assessed peripheral virus-specific effector/memory cells and subpopulations of T, B and DC cells using ELISPOT and FACS methods in 74 low-risk kidney transplant candidates without anti-HLA antibodies, prior to transplantation in pre-emptive (never experienced dialysis) and dialysis cohorts. There was difference in circulating marginal zone B cells (MZB) (IgDhighCD27high) between dialysis patients and those receiving kidney grafts pre-emptively (P = .002). Patients treated on dialysis >12 months had also 4.2-fold greater risk of increased absolute numbers of MZB (95%CI:1.6-11.2; P = .004). There were no other differences in B-, T- and DC-cell subsets. Numbers of effector/memory T cells reactive to major opportunistic virus-specific antigens (CMV, BKV and EBV) were not affected by dialysis. Non-sensitised dialysis-treated patients displayed significantly more circulating MZB compared to those CKD5 patients that had never undergone dialysis therapy.
- MeSH
- antigeny CD27 metabolismus MeSH
- B-lymfocyty imunologie MeSH
- chronická renální insuficience imunologie terapie MeSH
- dendritické buňky imunologie MeSH
- dialýza MeSH
- dospělí MeSH
- ELISPOT MeSH
- imunologická paměť MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- slezina patologie MeSH
- T-lymfocyty imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronická renální insuficience * farmakoterapie imunologie ošetřování MeSH
- dialýza ledvin MeSH
- hemolyticko-uremický syndrom farmakoterapie imunologie MeSH
- kontraindikace MeSH
- lidé MeSH
- nemoci, jimž lze předcházet očkováním klasifikace MeSH
- transplantace ledvin MeSH
- vakcinace normy MeSH
- vakcíny klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20-40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.
- MeSH
- chronická renální insuficience imunologie MeSH
- glomerulonefritida imunologie MeSH
- IgA nefropatie imunologie MeSH
- imunoglobulin A imunologie MeSH
- komplement C3 imunologie MeSH
- komplement C5 imunologie MeSH
- ledviny imunologie MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by tissue deposition of a truncated monoclonal immunoglobulin heavy chain lacking the first constant domain. Pathophysiological mechanisms are unclear and management remains to be defined. Here we retrospectively studied 15 patients with biopsy-proven HCDD of whom 14 presented with stage 3 or higher chronic kidney disease, with nephrotic syndrome in 9. Renal lesions were characterized by nodular glomerulosclerosis, with linear peritubular and glomerular deposits of γ-heavy chain in 12 patients or α-heavy chain in 3 patients, without concurrent light chain staining. Only 2 patients had symptomatic myeloma. By serum protein electrophoresis/immunofixation, 13 patients had detectable monoclonal gammopathy. However, none of these techniques allowed detection of the nephrotoxic truncated heavy chain, which was achieved by immunoblot and/or bone marrow heavy chain sequencing in 14 of 15 patients. Serum-free kappa to lambda light chain ratio was abnormal in 11 of 11 patients so examined. Immunofluorescence studies of bone marrow plasma cells showed coexpression of the pathogenic heavy chain with light chain matching the abnormal serum-free light chain in all 3 tested patients. Heavy chain sequencing showed first constant domain deletion in 11 of 11 patients, with high isoelectric point values of the variable domain in 10 of 11 patients. All patients received chemotherapy, including bortezomib in 10 cases. Renal parameters improved in 11 patients who achieved a hematological response, as assessed by normalization of the free light chain ratio in 8 cases. Tissue deposition in HCDD relates to physicochemical peculiarities of both variable and constant heavy chain domains. Early diagnosis and treatment with bortezomib-based combinations appear important to preserve renal prognosis. Thus, monitoring of serum-free light chain is an indirect but useful method to evaluate the hematological response.
- MeSH
- biopsie MeSH
- bortezomib terapeutické užití MeSH
- chronická renální insuficience farmakoterapie imunologie patologie MeSH
- fluorescenční protilátková technika MeSH
- glomerulonefritida farmakoterapie imunologie patologie MeSH
- imunoglobuliny - alfa-řetězce analýza MeSH
- imunoglobuliny - gama-řetězce analýza genetika MeSH
- imunoglobuliny - kappa-řetězce analýza MeSH
- imunoglobuliny - lambda-řetězce analýza MeSH
- kombinovaná farmakoterapie MeSH
- ledviny účinky léků imunologie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nefrotický syndrom farmakoterapie imunologie patologie MeSH
- nemoc z těžkých řetězců farmakoterapie genetika imunologie patologie MeSH
- nemoci ledvin farmakoterapie imunologie patologie MeSH
- paraproteinemie farmakoterapie imunologie MeSH
- polymerázová řetězová reakce MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Francie MeSH
Drugs interfering with the renin-angiotensin-aldosterone system (RAAS) improved the prognosis in patients with hypertension, heart failure, diabetes and chronic kidney disease. However, combining different drugs brought no further benefit while increasing the risk of hyperkalemia, hypotension and acute renal failure. This was so with combining angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptors type 1 antagonists (ARB). Dissimilarly, in animal disease models this dual therapy proved clearly superior to single drug treatment and became the optimal standard regime for comparison with other treatments. This review analyzes the causes of the discrepancy of effects of the dual therapy between animal experiments versus clinical studies, and is focused on the outcomes in chronic kidney disease. Discussed is the role of species differences in RAAS, of the variability of the disease features in humans versus relative stability in animals, of the genetic uniformity in the animals but not in humans, and of the biased publication habits of experimental versus clinical studies. We attempt to understand the causes and reconcile the discordant findings and suggest to what extent dual RAAS inhibition should be continued in animal experiments and why its application in the clinics should be limited to strictly selected groups of patients.
- MeSH
- akutní poškození ledvin chemicky indukované imunologie prevence a kontrola MeSH
- blokátory receptoru 1 pro angiotenzin II aplikace a dávkování MeSH
- chronická renální insuficience farmakoterapie imunologie MeSH
- druhová specificita MeSH
- hyperkalemie chemicky indukované imunologie prevence a kontrola MeSH
- hypertenze chemicky indukované imunologie prevence a kontrola MeSH
- inhibitory ACE aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- medicína založená na důkazech MeSH
- modely nemocí na zvířatech * MeSH
- renin-angiotensin systém účinky léků imunologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- studie RITUXVAS,
- MeSH
- ANCA-asociované vaskulitidy * farmakoterapie imunologie komplikace mortalita MeSH
- azathioprin terapeutické užití MeSH
- B-lymfocyty cytologie MeSH
- chronická renální insuficience etiologie farmakoterapie imunologie MeSH
- chronické selhání ledvin etiologie MeSH
- cyklofosfamid * terapeutické užití MeSH
- glukokortikoidy terapeutické užití MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- randomizované kontrolované studie jako téma MeSH
- recidiva MeSH
- rituximab MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- komentáře MeSH
- srovnávací studie MeSH
OBJECTIVES: The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown. METHODS: Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m(2)/week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6 months followed by azathioprine (n=11, control group). RESULTS: The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. CONCLUSIONS: At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. TRIAL REGISTRATION NUMBER: ISRCTN28528813.
- MeSH
- ANCA-asociované vaskulitidy komplikace farmakoterapie imunologie MeSH
- azathioprin terapeutické užití MeSH
- B-lymfocyty cytologie MeSH
- chronická renální insuficience farmakoterapie etiologie imunologie MeSH
- chronické selhání ledvin etiologie MeSH
- cyklofosfamid terapeutické užití MeSH
- glukokortikoidy terapeutické užití MeSH
- granulomatóza s polyangiitidou komplikace farmakoterapie imunologie MeSH
- imunosupresiva terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikroskopická polyangiitida komplikace farmakoterapie imunologie MeSH
- myší monoklonální protilátky terapeutické užití MeSH
- počet lymfocytů MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- MeSH
- adaptivní imunita MeSH
- bakteriální translokace MeSH
- chronická renální insuficience * imunologie metabolismus mikrobiologie MeSH
- chronické selhání ledvin imunologie metabolismus mikrobiologie MeSH
- imunologická tolerance MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- permeabilita * MeSH
- podvýživa imunologie metabolismus mikrobiologie MeSH
- přirozená imunita MeSH
- střeva * imunologie metabolismus mikrobiologie MeSH
- uremie imunologie metabolismus mikrobiologie MeSH
- zánět imunologie metabolismus mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- komentáře MeSH
