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1.
Vojnosanit Pregl ; 74(1): 81-4, 2017 Jan.
Article in English | MEDLINE | ID: mdl-29350897

ABSTRACT

Introduction: Aortoiliac occlusive disease and abdominal aortic aneurysm in patients with renal insufficiency on hemodialysis can significantly influence the success of renal transplantation. In the recent past, advanced atherosclerosis was considered as contraindication for renal transplantation. Complicated creation of vascular anastomoses and progression of occlusive or aneurysmal disease were the main reasons. Case report: We presented a 52-year-old man with a 5-year history of end-stage renal disease on haemodialysis. The patient was previously excluded from renal transplantation program because of severe aortoiliac atherosclerosis and abdominal aortic aneurysm. Resection of abdominal aortic aneurysm with occlusion of the iliac arteries and reconstruction with aortobifemoral synthetic grafts was performed and followed by cadaveric renal transplantation. Conclusion: Advanced atherosclerotic disease in aortoiliac segment requires elective vascular surgical reconstruction, as part of preparation for renal transplantation in patients with end-stage renal disease.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Arterial Occlusive Diseases/surgery , Blood Vessel Prosthesis Implantation/methods , Femoral Artery/surgery , Iliac Artery/surgery , Kidney Failure, Chronic/surgery , Kidney Transplantation , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortography/methods , Arterial Occlusive Diseases/complications , Arterial Occlusive Diseases/diagnostic imaging , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/instrumentation , Computed Tomography Angiography , Femoral Artery/diagnostic imaging , Humans , Iliac Artery/diagnostic imaging , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Male , Middle Aged , Polyethylene Terephthalates , Prosthesis Design , Treatment Outcome
2.
Vojnosanit Pregl ; 72(10): 932-6, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26665561

ABSTRACT

INTRODUCTION: Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and represents approximately 3.8% of all malignancies in adults. The incidence of renal cell carcinoma has been growing steadily and ranging from 0.6 to 14.7 for every 100,000 inhabitants. Patients with end-stage renal disease and acquired cystic kidney disease are at increased risk of developing RCC while undergoing dialysis treatment or after renal transplantation. CASE REPORT: We presented 3 patients undergoing hemodialysis, with acquired cystic kidney disease accompanied by the development of RCC. In all the patients tumor was asymptomatic and discovered through ultrasound screening in 2 patients and in 1 of the patients by post-surgery pathohistological analysis of the tissue of the kidney excised using nephrectomy. All the three patients had organ-limited disease at the time of the diagnosis and they did not require additional therapy after surgical treatment. During the follow-up after nephrectomy from 6 months to 7 years, local recurrence or metastasis of RCC were not diagnosed. CONCLUSION: Acquired cystic kidney disease represents a predisposing factor for the development of renal cell carcinoma in dialysis patients and requires regular ultrasound examinations of the abdomen aimed at early diagnosis of malignancies. Prognosis for patients with end-stage renal disease and RCC is mostly good because these tumors are usually of indolent course.


Subject(s)
Carcinoma, Renal Cell/etiology , Kidney Diseases, Cystic/complications , Kidney Failure, Chronic/therapy , Kidney Neoplasms/etiology , Renal Dialysis/adverse effects , Adult , Aged , Biopsy , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/surgery , Humans , Incidental Findings , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/surgery , Kidney Failure, Chronic/diagnosis , Kidney Neoplasms/diagnosis , Kidney Neoplasms/surgery , Middle Aged , Nephrectomy , Predictive Value of Tests , Risk Factors , Time Factors , Treatment Outcome
3.
Vojnosanit Pregl ; 72(1): 63-7, 2015 Jan.
Article in English | MEDLINE | ID: mdl-26043594

ABSTRACT

INTRODUCTION: Situs inversus totalis (SIT) represents a total vertical transposition of the thoracic and abdominal organs which are arranged in a mirror image reversal of the normal positioning. We presented a successful pre-dialysis kidney transplantation from a living sibling donor with SIT and the longest donor follow-up period, along with analysis of the reviewed literature. CASE REPORT: The pair for pre-dialysis kidney transplantation included a 68-year-old mother and 34-year-old daughter at low immunological risk. Comorbid- ities evidenced in kidney donors with previously diagnosed SIT, included moderate arterial hypertension and borderline blood glucose level. Explantation of the left donor kidney and its placement into the right iliac fossa of the recipient were performed in the course of the surgical procedure. A month after nephrectomy, second degree renal failure was noticed in the donor. A 20-month follow-up of the donor's kidney and graft in the recipient proved that their functions were excellent. CONCLUSION: In donors with previously di- agnosed SIT the multidisciplinary approach, preoperative evaluation of the patient and detection of possible vascular anomalies are required to provide maximum safety for the donor.


Subject(s)
Kidney Transplantation , Living Donors , Situs Inversus/diagnosis , Adult , Aged , Comorbidity , Diagnostic Imaging , Female , Humans , Nephrectomy
4.
Vojnosanit Pregl ; 72(2): 196-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25831916

ABSTRACT

INTRODUCTION: Immunoglobulin D (IgD) myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy-as-sociated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. CASE REPORT: 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg). Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L) and renal failure dialysis rank: creatinine 1,408 micromol/L, urea 31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2 M components--massive in alpha 2 fraction of 71%; 7% in the discrete beta fraction, beta 2M / serum 110 mg / L, in urine 1.8 mg/L--extremely high; IgL kappa I lambda index 1:13 (reference value ratio 2:1). The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, lamda-light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission. CONCLUSION: The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and teamwork that can alter the course of this serious disease.


Subject(s)
Acute Kidney Injury/etiology , Immunoglobulin D/blood , Immunoglobulin lambda-Chains/blood , Multiple Myeloma/complications , Paraproteinemias/complications , Adult , Humans , Male , Multiple Myeloma/immunology
5.
Eur J Drug Metab Pharmacokinet ; 39(4): 243-53, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24356808

ABSTRACT

Tacrolimus is an immunosuppressant used for the prevention of kidney allograft rejection. The effects of comedication on tacrolimus trough concentrations (TTC) in kidney transplant recipients, subjected to basic immunosuppressant regime consisting of tacrolimus, corticosteroids and mycophenolate mofetil were investigated. This retrospective case series study involved 208 of these patients, with the outpatient examination recorded in the database of patients, at the unit of monitoring, with a total of 5,011 such examinations. Binary logistic regression analysis has shown that calcium channel blockers, diuretics and proton pump inhibitors (PPIs) significantly affected TTC (p < 0.001). PPIs significantly increased the number of examinations in which the TTC were in the recommended therapeutic range (from 5 to 15 ng/ml), as well as over the therapeutic range (p < 0.0001). When calcium channel blockers were added to PPIs, even more pronounced effect was obtained in comparison to triple-drug therapy only (p < 0.0001). In case a diuretic was given with a PPI, a significantly increased number of examinations with subtherapeutic TTC was observed when compared with PPI only (p = 0.0203). The combination of calcium channel blockers, diuretics and PPIs resulted in the number of examinations with TTC in the recommended therapeutic range not being different from the number of examinations with TTC in the triple-drug therapy only (p = 0.3829). ß-adrenergic antagonists can be administered without fear of affecting the tacrolimus optimal therapeutic concentrations. This was confirmed with all combinations of the examined drugs used in patients subjected to kidney transplantation concomitantly with ß blockers.


Subject(s)
Immunosuppressive Agents/blood , Kidney Transplantation , Tacrolimus/blood , Adolescent , Adult , Aged , Child , Cytochrome P-450 CYP2C19/genetics , Drug Interactions , Drug Monitoring , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Retrospective Studies
6.
Vojnosanit Pregl ; 70(9): 848-53, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24266313

ABSTRACT

BACKGROUND/AIM: Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNI-based immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. METHODS: In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 +/- 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 +/- 13 months. Nine patients (the group I) had early postransplant conversion after 4 +/- 3 months and 15 patients (the group II) late conversion after 46 +/- 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. RESULTS: Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 +/- 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 +/- 12.7 to 69 +/- 15 mL/min), while the increase in proteinuria (from 265 +/- 239 to 530.6 +/- 416.7 mg/day) and lipidemia (cholesterol from 4.71 +/- 0.98 to 5.61 +/- 1.6 mmol/L and triglycerides from 2.04 +/- 1.18 to 2.1 +/- 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 +/- 232 to 1639 +/- 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 +/- 28.09 to 47 +/- 21 mL/min) and significantly improved proteinuria (from 1639 +/- 1641 to 529 +/- 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 +/- 88 to 202 +/- 91 mmol/L), decrease in GFR (from 56.10 +/- 28.09 to 47 +/- 21 mL/day) and increased proteinuria (from 528.9 +/- 688 to 850 +/- 1083 mg/min). CONCLUSION: In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.


Subject(s)
Calcineurin Inhibitors , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/etiology , Sirolimus/therapeutic use , Adult , Azathioprine/therapeutic use , Biomarkers/blood , Creatinine/blood , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/immunology , Female , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Proteinuria/immunology , Sirolimus/administration & dosage , Time Factors , Treatment Outcome
7.
Vojnosanit Pregl ; 70(4): 411-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23700948

ABSTRACT

INTRODUCTION: Renal artery stenosis (RAS) is narrowing of one or both renal arteries or their branches. Clinically sig nificant stenosis involves narrowing of the lumen, which is approximately 80%. The two most common causes of its occurrence are atherosclerosis and fibromuscular dyspla sia. Percutaneous transluminal renal angioplasty (PTRA) with stent implantation is an effective treatment modality that leads to lower blood pressure and improvement of kidney function. CASE REPORT: We presented 4 patients with significant stenosis of one or both renal arteries fol lowed by the development of arterial hypertension and re nal insufficiency. The causes of RAS were atherosclerosis in two patients and fibromuscular dysplasia in one patient. One of the patients had renal artery stenosis of trans planted kidney that developed 9 month after transplanta tion. In all the patients, in addition to clinical signs, dop pler screening suspected the existence of significant renal artery stenosis. The definitive diagnosis was made by ap plying computed tomographic angiography (CTA) of renal arteries in 3 of the patients and in 1 patient by percutaneus selective angiography. All the patients were treated by ap plication of PTRA with stent implantation followed by improvement/normalization of blood pressure and kidney function. CONCLUSION: Application of PTRA with stent implantation is an effective treatment of significant steno sis of one or both renal arteries followed by renal insuffi ciency.


Subject(s)
Angioplasty , Kidney/physiopathology , Renal Artery Obstruction/therapy , Adult , Humans , Male , Middle Aged , Radiography, Interventional , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/physiopathology
9.
Transfus Apher Sci ; 43(2): 141-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20667786

ABSTRACT

Anti-A/B depletion efficacy and clinical outcome for 22 ABO-incompatible kidney transplants were investigated. Preconditioning by anti-CD20 therapeutic plasma exchange (TPE) by Cobe-Spectra (CaridianBCT USA) and simplified extracorporeal immunoadsorption (ECIA) as well as triple immunosuppression (tacrolimus/mycophenolate-mofetil/steroid) were performed. The use of TPE with ECIA resulted in a high in vivo anti-A/B depletion, 94.23±4.2% for IgG and 95.26±3.2% for IgM. The mean anti-A/B titers on day 0 were: IgG=1.27±1.03 and IgM=2.20±1.47. One HLA cross-match positive patient (beside ABO-incompatibility) subjected to double-dose anti-CD20 and intensive TPE-treatment had no allograft rejection. The level of serum creatinine ranged from 100 to 156 µmol/L in the entire group of patients during postoperative follow-up (up to 36 months). One recipient (with sepsis and multi organ distress syndrome) lost kidney function in early posttransplant period. ABO-incompatible (n=2) and ABO-compatible (n=3) kidney recipients had severe anemia and bleeding episodes. They were efficiently treated using original "multi-manner" apheresis. Our study represents a clear demonstration that the combination of TPE with ECIA and anti-CD20 is effective in anti-A/B depletion. This therapeutic approach is feasible in clinical setting showing satisfactory short-term results although verification of long-term effects needs to be confirmed in a larger study. The rapid beneficial outcome of "multi-manner" apheresis strongly supports the future use of this therapeutic modality for efficient oxygenation and advanced engraftment.


Subject(s)
ABO Blood-Group System , Adsorption , Kidney Transplantation/methods , Adult , Antigens, CD20/chemistry , Blood Group Incompatibility , Female , Humans , Immune System , Immunoglobulin G/chemistry , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Steroids/administration & dosage , Tacrolimus/administration & dosage , Time Factors
10.
Int Surg ; 95(4): 343-9, 2010.
Article in English | MEDLINE | ID: mdl-21309419

ABSTRACT

A possible complication after donor nephrectomy is a decrease in glomerular filtration rate. The goal of our investigation is to estimate the function of the remaining donor kidney in the first 6 months after nephrectomy using the equations Cockcroft-Gault, Modification of Diet in Renal Disease 1 (MDRD1) and MDRD2. In addition to basic age and sex data, we collected standard biochemical data from blood: creatinine, blood urea nitrogen, and albumin. Blood samples and diuresis were taken at -1, 0, 1, 2, 3, 7, and 14 days, and after 6 months. Our results show that glomerular filtration rate decreases after nephrectomy and stabilizes after 6 months in values significantly lower compared with predonation values. Both MDRD estimations show that these donors after nephrectomy are patients in the third degree of chronic kidney disease, and we can predict that older donors and those with comorbidities very soon will need a treatment for chronic kidney disease. For glomerular filtration rate estimation, we recommend the MDRD2 equation. All donors must have long-term follow-up and treatment, because there is a possibility of eventual cardiovascular and metabolic diseases.


Subject(s)
Glomerular Filtration Rate , Kidney Transplantation , Living Donors , Nephrectomy , Albumins/metabolism , Blood Urea Nitrogen , Creatinine/blood , Female , Humans , Male , Middle Aged , Risk Factors , Time Factors
11.
Vojnosanit Pregl ; 67(12): 998-1002, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21417103

ABSTRACT

BACKGROUND: In countries without a national organization for retrieval and distribution of organs of the deceased donors, problem of organ shortage is still not resolved. In order to increase the number of kidney transplantations we started with the program of living unrelated - spousal donors. The aim of this study was to compare treatment outcome and renal graft function in patients receiving the graft from spousal and those receiving ghe graft from living related donors. METHOD: We retrospectively identified 14 patients who received renal allograft from spousal donors between 1996 and 2009 (group I). The control group consisted of 14 patients who got graft from related donor retrieved from the database and matched than with respect to sex, age, kidney disease, immunological and viral pretransplant status, the initial method of the end stage renal disease treatment and ABO compatibility. In the follow-up period of 41 +/- 38 months we recorded immunosuppressive therapy, surgical complications, episodes of acute rejection, CMV infection and graft function, assessed by serum creatinine levels at the beginning and in the end of the follow-up period. All patients had pretransplant negative cross-match. In ABO incompatible patients pretransplant isoagglutinine titer was zero. RESULTS: The patients with a spousal donor had worse HLA matching. There were no significant differences between the groups in surgical, infective, immunological complications and graft function. Two patients from the group I returned to hemodialysis after 82 and 22 months due to serious comorbidities. CONCLUSION: In spite of the worse HLA matching, graft survival and function of renal grafts from spousal donors were as good as those retrieved from related donors.


Subject(s)
Kidney Transplantation , Living Donors , Spouses , Female , Histocompatibility , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged
12.
Vojnosanit Pregl ; 66(2): 117-22, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19281122

ABSTRACT

BACKGROUND/AIM: Due to improved methods for removal of ABO isoagglutinins and novel immunosuppressive protocols, short and long-term outcome in blood group incompatible is similar to blood group compatible kidney transplantation. The aim of this study was to determine the efficacy of our original method for removal of ABO isoagglutinins from the blood in ABO-incompatible kidney allograft recipients. METHOD: Between 2006 and 2008 twelve patients were transplanted from ABO incompatible living donors. Titers of ABO isoagglutinins were 4-128 (IgG). Immunosuppressive therapy started 14 days before kidney transplantation with rituximab, followed by a triple therapy (prednisone + tacrolimus + mycophenolate mofetil) and the first plasma exchange (PE) procedure, in which one plasma volume was substituted with albumin and saline on day 7 before transplantation. For selective extracorporeal immunoadsorption, the removed plasma was mixed with donor blood type filtered red blood cells, centrifuged and the supernatant separated and preserved. In the next PE procedure, the removed plasma was replaced with immunoadsorbed plasma, and so on. Titers of ABO agglutinins, renal allograft function and survival were followed-up. RESULTS: The pre-transplant treatment consisting of 1-5 PE procedures and immunosuppressive therapy resulted in target ABO agglutinins titers below 4. During a 10-24 month follow-up three patients had an early acute rejection, one patient acute rejection and hemolytic anemia, two patients surgical complications and one of them lost his graft. In the post-transplant period, the titers of ABO antibodies remained below 4. All the patients had stable kidney allograft function with mean serum creatinine +/- SD of 129 +/- 45 micromol/l at the end of the study. CONCLUSION: Our method for removal of ABO antibodies was effective in a limited series of patients and short-term follow-up.


Subject(s)
ABO Blood-Group System/immunology , Agglutinins/immunology , Blood Group Incompatibility/therapy , Kidney Transplantation , Plasma Exchange , Plasmapheresis , Female , Humans , Immunosorbent Techniques , Immunosuppressive Agents , Kidney Transplantation/immunology , Living Donors , Male , Middle Aged
13.
Pathol Res Pract ; 205(5): 295-302, 2009.
Article in English | MEDLINE | ID: mdl-19117689

ABSTRACT

The aim of the study was to assess the characteristics of histopathological changes in 120 young males, both recruits and soldiers, who had undergone successful renal biopsy due to asymptomatic urinary abnormalities. The patients were subdivided into a group with isolated microhematuria (IMH-62 patients) and a group with asymptomatic microhematuria and proteinuria (MHP-58 patients). Light, immunofluorescence, and electron microscopy revealed that MHP was associated with more severe morphological changes, than IMH. The latter group included 6 subjects with normal biopsies and 13 subjects with minor abnormalities found only in two patients with MHP. The frequencies of particular nephropathies in the groups with IMH and MHP were as follows: 35% and 55% for IgA nephritis, 24% and 31% for non-IgA mesangioproliferative glomerulonephritis (GN), 2% and 3% for focal proliferative GN, 3% and 3% for diffuse proliferative GN, 5% and 1% for thin basement membrane nephropathy, respectively. Rebiopsy, performed in eight patients due to worsening of proteinuria during the follow-up period, showed evidence of progression of morphological changes. Patients with IMH had significantly less prominent histopathological changes than patients with MHP. Therefore, renal biopsy cannot be recommended for patients with IMH unless specific indications are present.


Subject(s)
Hematuria/etiology , Kidney Diseases/pathology , Proteinuria/etiology , Adult , Biopsy , Fluorescent Antibody Technique , Humans , Kidney Diseases/complications , Male , Microscopy, Electron, Transmission
14.
Vojnosanit Pregl ; 65(2): 119-27, 2008 Feb.
Article in Serbian | MEDLINE | ID: mdl-18365668

ABSTRACT

BACKGROUND/AIM: Cyclosporine (CyA) therapeutic drug monitoring (TDM) through the measurement of drug concentration in blood two hours after the administration (C2), and/or according to the calculated value of the area under the concentration-time curve during the first four hours following administration (AUC(0-4)) shows favourable correlation with clinical manifestations in patients with kidney transplantation (Tx). The aim of this study was to analyze clinical efficiency and usability of TDM CyA through C2 and AUC(0-4) in the group of our kidney transplanted patients during the first 24 months following Tx. METHODS: The study included 50 patients who had undergone kidney Tx using living donors at the Clinic of Nephrology Military Medical Academy, from 1996 to 2003. The first group (group C2) consisted of 25 patients in whom CyA dose was adjusted according to the target C2 and AUC(0-4) (calculated by the regression formula based on C1, C2 and C3), while the second group (group CO) consisted of 25 "historical" patients in whom the dose of this drug was adjusted according to CO. RESULTS: On the 6th day the average daily dose of CyA in the group C2 was 10.1 +/- 0.8 mg/kg, while in the group CO it was 7.6 +/- 1.6 (p < 0.05). One month following the Tx, daily drug doses were quite similar in the two observed groups (6.2 mg/kg in CO and 6.6 mg/kg in group C2, p = NS). In the group C2, target C2/AUC(0-4) (C2 1700 ng/ml, AUC(0-4) 4400 ng h/ml) on the sixth day was achieved in 36.3%, and on day 14 in 76% of the patients. The target AUC(0-4), in relation with C2, in each observed time interval was reached in the higher number of patients. Maximum CyA concentrations in the group C2 were registered 2 hours following the administration (C2), when compared with the concentrations registered after the first and the third hour (C1 and C3). In relation with C1 and C3, C2 concentration correlated most favorably with AUC(0-4), both on the 6th (r = 0.85) and on the 9th day (r = 0.87). During the first three months following the Tx, in the group CO, 10 episodes (40%) of acute cell rejection (AR) were registered, while in the group C2, two episodes (8%, p = 0.07) were registered; in the observed period covering the first two years, a total of 13 (52%) AR episodes in the group CO and 5 AR episodes (20%) in the group C2 (p = 0.03) were registered. All of five episodes of steroid resistant AR were registered in the group CO. In the group C2, all five patients with AR had lower C2 during AR: the average C2 at the moment of AR was 933.8 ng/ml, and in the patients without rejections was 1364.2 ng/ml (p = 0.008). In the same group, the average C0 at the moment of AR was 263.2 ng/ml, and 240.0 ng/ml (p = 0.486) in the patients without AR. In the C0 group, average C0 concentration at the moment of AR was 227.1 ng/ml, while in the patients without AR it was 227.7 ng/ml (p = 0.95). Totally 68% of the patients showed signs of acute CyA nephrotoxicity during the first year in the group C2, and 52% in the group CO (p = 0.38). In seven patients (28%) of the group C2 and six patients of the group C0 (24%, p = 0.96) in the first two years following Tx, administration of CyA was interrupted due to nephrotoxicity. Overall graft function was good in both groups during the period of two years. One graft was lost in the group CO due to chronic allograft nephropathy. The patients in the group C2 had better early and the same late graft function. Five patients in the group C2 who did not reach the target C2/AUC during the first 30 days, did not have more AR or worse graft function, comparing with the patients who reached the target concentrations. CONCLUSION: In the patients with CyA TDM through with the C2 and AUC(0-4), AR frequency was considerably lower, and AR episodes had a milder flow than in those with CyA TDM through the CO. The drug concentration in blood two hours after administration (C2) was a good predictor of acute graft rejection, while CO failed to point to the patients with the insufficient drug concentration. Higher drug doses were administered in the group C2 during the first month following Tx, and these patients did not show significantly higher frequency of acute nephrotoxicity and more frequent requirement of the drug use interruption. Graft function in both groups was good during the period of two years. CyA dose determination through C2 and AUC(0-4) is efficient TDM method, relatively simple for use in day to day clinical practice.


Subject(s)
Cyclosporine/pharmacokinetics , Drug Monitoring , Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation , Adolescent , Adult , Area Under Curve , Cyclosporine/adverse effects , Cyclosporine/therapeutic use , Female , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Middle Aged
15.
Vojnosanit Pregl ; 64(6): 385-90, 2007 Jun.
Article in Serbian | MEDLINE | ID: mdl-17687942

ABSTRACT

BACKGROUND/AIM: [corrected] Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease characterized by a retroperitoneal fibrotic tissue that often involve the ureters, leading to the obstructive nephropathy and variable impairment of renal function. Findings strongly suggest an autoimmune etiology. Surgery, medical treatment with immunosuppressive drugs, or a combination of both are proposed. The optimal treatment has not been established yet. The aim of this study was to present our experience with combined immunosuppressive therapy of IRF, steroids (S) and mycophenolate mofetil (MMF). METHODS: We prospectively followed four patients with IRF from January 2004 to December 2006. Three patients had an active disease with bilateral hydronephrosis. In the two of them acute renal failure was presented, and ureteral catheters were inserted in one in order to manage ureteral obstruction. One patient has came to our unit with a relapse of IRF and incipient chronic renal failure after the prior therapy with ureterolysis and immunosuppressive drugs (azathioprine and tamoxifen). All patients received steroids and MMF. Two patients were treated with intravenous methylprednisolone pulses (250 mg each), for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. The other two patients received oral prednisone at the same dose. Prednisone was gradually tappered to a maintenance dose of 10 mg/kg/day. Simultaneously, all patients received MMF, initially 1 g/day with the increase to 2 g/day. RESULTS: After four weeks of the therapy all symptoms disappeared, as well as a hydronephrosis with a decrease of erythrocyte sedimentation rate and Creactive protein (CRP) to normal level in all patients. Three patents remain in remission untill the end of the follow up. One patient had a relapse because of stopping taking the therapy after six months. He was treated by oral prednisone 0.5 mg/kg/day, which was gradually decreased. After twelve weeks hydronephrosis disappeared and CRP returns to the normal level. CONCLUSION: The combination of steroids and mycophenolate mofetil led to the remission of IRF with a strong and quick immunosuppressive effect. It also provided avoiding the long-term use of high steroid dose and surgical procedures.


Subject(s)
Glucocorticoids/administration & dosage , Immunosuppressive Agents/administration & dosage , Methylprednisolone/administration & dosage , Mycophenolic Acid/analogs & derivatives , Retroperitoneal Fibrosis/drug therapy , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Prednisone/therapeutic use , Retroperitoneal Fibrosis/complications , Ureteral Obstruction/etiology
16.
Transfus Apher Sci ; 36(3): 225-33, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17572153

ABSTRACT

There is a need for improvement of the detection and treatment of the antibody-mediated graft rejection for ABO-incompatible kidney transplant recipients. With the development of novel pre-conditioning protocols, which employ anti-CD20 antibody, therapeutic plasma exchange plus extracorporeal immunoadsorption and standard immunosuppression application, together with the use of more sensitive and objective assays for immunological monitoring, patients that were not candidates for kidney transplant in the past, are now being transplanted. We have designed a pre-conditioning protocol for ABO-incompatible kidney transplants based on TPE plus our own simple "closed-circuit" immunoadsorption technique - combined by anti-CD20, standard immunosuppressive treatment, and without splenectomy. The results obtained in this study strongly support our hypothesis leading to the conclusion that this protocol can be used successfully, with high-quality ABO antibody depletion (p<0.001) and beneficial clinical findings. The application of this protocol is safe, and not associated with alteration in normal plasma constituent levels or with occurrence of any side effects of apheresis or clinical consequences. Finally, this pre-conditioning protocol radically reduces the treatment-cost. Definitive conclusions can only be drawn from larger, randomized, controlled clinical trials.


Subject(s)
ABO Blood-Group System/immunology , Antibodies/therapeutic use , Blood Group Incompatibility/drug therapy , Immunosorbent Techniques , Kidney Transplantation/methods , Adult , Antigens, CD20/immunology , Female , Graft Rejection/prevention & control , Humans , Kidney Transplantation/immunology , Male , Middle Aged , Pilot Projects
17.
Med Pregl ; 60 Suppl 2: 151-4, 2007.
Article in Serbian | MEDLINE | ID: mdl-18928183

ABSTRACT

INTRODUCTION: Kidney transplantation is nowadays considered the most sophisticated method of treatment of chronic terminal renal insufficiency. The advancement in surgical technique and the use of new immunosuppressive medications provide a longer survival period of both the patient and the graft. MATERIAL AND METHODS: The objective of this paper is a retrospective presentation of the ten-year monitoring of kidney transplantation in patients undergoing peritoneal dialysis performed at the Military Medical Academy. RESULTS AND DISCUSSION: During that period, 32 patients underwent the transplantation (18 men and 14 women of the average age of 32.48+/-2.1). The total of 34 transplantations were performed, out of which 2 were retransplantations. Patient monitoring period was 7-92 months. The immunosuppressive therapy was quadrupled in 17 (50%) patients and tripled in 17 (50%) of them. The loss of the graft in the early period following the transplantation occurred in 5 (15.6%) patients due to trombosis a. renalis, out of whom two were retransplantation cases. Registered surgical vascular complications included 5 (15.6%) bleeding, 4 (12.5%) hematomes and 6 (18.7%) lymfocells. Delayed graft function occurred in 5 (14.7%) and acute rejection in 7 (20.5%) patients while the disease reccured in 2 patients. As for the complications, rejection without the loss of graft was registered in 4 (12.5%) pts, ureter stenosis in 3 (8.82%) pts, bacterial infections in 4 (12.5%) pts and reactivation of CMV infections in 9 (26.4%) pts. Our patients are observed for the maintenance of stable medium volume of serum creatinine (which is 123.6 +/-10.2 umol/l in the early stage and 133.24+/-11.1 umol/l in the end of the monitoring period as well as the medium volume of clearence creatinine (which is 64.80+/-3.5 ml/min at the early phase of monitoring period and 69.47+/-3.3 ml/min. in the end). CONCLUSION: Our group of renal transplantation patients, undergoing peritoneal dialysis was with stable renal function registered through the monitoring period.


Subject(s)
Kidney Failure, Chronic/therapy , Kidney Transplantation , Peritoneal Dialysis , Adult , Female , Humans , Male
18.
Vojnosanit Pregl ; 60(3): 299-304, 2003.
Article in Serbian | MEDLINE | ID: mdl-12891726

ABSTRACT

BACKGROUND: This paper presents our experience with cytologic examination of urine in diagnosing renal allograft dysfunction. METHODS: The study group included 23 patients with renal allograft dysfunction, selected from 56 patients who underwent renal transplantation. Etiologic diagnosis was made according to the clinical picture, histological findings during allograft biopsy, and cytologic examination of urine. Urine sediment was obtained in cytocentrifuge and was air dried and stained with May Grunwald Giemsa. RESULTS: Out of 23 patients with allograft dysfunction in 18 (78.3%) patient it was caused by acute rejection, and in 5 (8.9%) patients by allograft infarction, cyclosporine nephrotoxicity, acute tubular necrosis and chronic nephropathy. In eighteen patients (78.3%) cytologic examination of urine was pathologic, while in 16 (70%) clinical and histology findings coincided with urine cytology findings. Out of 18 patients with acute allograft rejection in 15 patients cytologic examination of urine coincided with acute rejection. Out of 7 patients with expressed cyclosporine nephrotoxicity, in 5 cytologic examination of urine confirmed the cause of allograft dysfunction, as well as in one of 2 patients with acute tubular necrosis. Cytologic examination of urine indicated parenchymal damage in 2 patients with recurrent disease (membranoproliferative and focal sclerosing glomerulonephritis). In 4 of 5 patients suffering from chronic rejection in a year's monitoring period, urine sediment periodically consisted of lymphocytes, neutrophilic leucocytes, monocyte/macrophages, tubular cells and cylindres, without the predominance of any cell type. In 3 patients allograft dysfunction was caused by infective agents (bacteria, fungus, cytomegalovirus). CONCLUSION: Cytologic examination of urine might be an alternative to histological in diagnosing acute allograft rejection and acute tubular necrosis or nephrototoxicity. Also it might indicate parenchymal disease while the importance of urine cytology in chronic allograft nephropathy needs to be investigated further.


Subject(s)
Graft Rejection/urine , Kidney Diseases/urine , Kidney Transplantation , Postoperative Complications , Urine/cytology , Cytodiagnosis , Graft Rejection/diagnosis , Humans , Kidney Diseases/diagnosis , Kidney Diseases/etiology , Kidney Tubular Necrosis, Acute/diagnosis , Kidney Tubular Necrosis, Acute/urine , Recurrence
19.
Vojnosanit Pregl ; 60(1): 35-41, 2003.
Article in Serbian | MEDLINE | ID: mdl-12688110

ABSTRACT

BACKGROUND: Acute rejection of allograft is one of the most serious complications of renal transplantation that requires fast and precise diagnostic approach. In this paper our experience in cytologic urinalysis as a diagnostic method of the acute renal allograft rejection was reviewed. METHODS: The study group included 20 of 56 patients with transplanted kidneys who were assumed for the acute allograft rejection according to allograft dysfunction and/or urine cytology findings. Histological findings confirmed allograft rejection in 4 patients. Urine sediment obtained in cytocentrifuge was air-dried and stained with May-Grunwald-Giemsa. Acute allograft rejection was suspected if in 10 fields under high magnification 15 or more lymphocytes with renal tubular cells were found. RESULTS: Acute transplant rejection occurred in 32.1% patients. In 15 patients clinical findings of the acute renal allograft rejection corresponded with cytological and histological findings (in the cases in which it was performed). Three patients with clinical signs of the acute allograft rejection were without cytological confirmation, and in 2 patients cytological findings pointed to the acute rejection, but allograft dysfunction was of different etiology (acute tubular necrosis, cyclosporine nephrotoxicity). In patients with clinical, cytological and histological findings of the acute allograft rejection urine finding consisted of 58% lymphocytes, 34% neutrophilic leucocytes and 8% monocytes/macrophages on the average. The accuracy of cytologic urinalysis related to clinical and histological finding was 75%. CONCLUSION: Urine cytology as the reliable, noninvasive, fast and simple method is appropriate as the a first diagnostic line of renal allograft dysfunction, as well as for monitoring of the graft function.


Subject(s)
Graft Rejection/diagnosis , Kidney Transplantation , Urine/cytology , Acute Disease , Cytodiagnosis , Graft Rejection/urine , Humans
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