Consensus statement on screening, diagnosis, classification and treatment of endemic (Balkan) nephropathy.

Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers.

Effect of cyclosporine on steady-state pharmacokinetics of MPA in renal transplant recipients is not affected by the MPA formulation: analysis based on therapeutic drug monitoring data.

BACKGROUND: Two oral mycophenolic acid (MPA) formulations, immediate-release mycophenolate mofetil and enteric-coated mycophenolate sodium, have been shown to differ regarding some drug-drug interactions. The aim was to assess whether the effects of cyclosporine (CsA) on steady-state pharmacokinetics (PK) of MPA in renal transplant patients were affected by MPA formulation. METHODS: A prospective, stratified observational study based on therapeutic drug monitoring of MPA (6 total plasma concentrations over a 12-hour dosing interval, τ) in consecutive stable adult renal transplant recipients (n = 68). RESULTS: Patients treated with enteric-coated mycophenolate sodium (n = 45) or mycophenolate mofetil (n = 23) and with either CsA (microemulsion, n = 43) or tacrolimus (Tac) (immediate release, n = 25) were comparable regarding demographics, comorbidity, renal and liver functions, comedication, corticosteroid dose, CsA or Tac dose, and trough concentrations. Based on dose-normalized MPA concentrations and with adjustment for age, sex, body mass index, estimated glomerular filtration rate, and corticosteroid dose, CsA (as compared with Tac) consistently reduced MPA area under the concentration-time curve during the dosing interval at steady state overall [geometric mean ratio (GMR), 0.78; 95% confidence interval, 0.62-0.99] and by MPA formulation (by 22% and 21%, respectively), increased CLT/F,ss overall (1.31; 1.00-1.70) and by formulation (by 25% and 36%, respectively), reduced morning predose MPA concentration overall (0.59; 0.38-0.92) and by formulation (by 34% and 47%, respectively), increased peak-trough fluctuation overall (1.51; 1.06-2.17) and by formulation (by 58% and 45%, respectively), and prolonged tmax,ss overall (adjusted median difference 0.58, 0.04-1.12 hours) and by formulation (by 0.6 and 0.5 hours, respectively). CONCLUSIONS: Qualitatively and quantitatively, the effect of CsA on steady-state PK of MPA is not conditional on MPA formulation.

[Clinical guidelines for diagnosing, treatment and monitoring patients with testicular cancer--Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnika oboljelih od raka testisa Hrvatskoga Onkoloskog Drustva i Hrvatskoga Uroloskog Drustva Hrvatskoga Lijecnickog Zbora.

Testicular tumors are the most common solid tumors in men between 15 and 34 years of age. The worldwide incidence of these tumors has doubled in the past 40 years. Germ cell tumors comprise 95% of malignant tumors arising in the testes and they are classified either as seminoma or nonseminoma. Testicular cancers have a high cure rates even in disseminated stage of the disease. The chemotherapy mostly contributed to these results but surgery is an inevitable part of successful treatment. In a significant number of these patients treatment algorithms with minimum side effects are designed with the intention to maintain same cure rates as previously used, more aggressive therapy. The following text presents the clinical guidelines in order to standardize the procedures and criteria for diagnosis, management, treatment and follow-up of patients with testicular cancer in Republic of Croatia.

[Clinical guidelines for diagnosing, treatment and monitoring patients with bladder cancer--Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]. / Klinicke upute za dijagnostiku, lijecenje i pracenje bolesnika oboljelih od raka mokracnog mjehura Hrvatskoga Onkolokog Drustva i Hrvatskoga Uroloskog Drustva Hrvatskoga Lijecnickog Zbora.

Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia.

[Adhesiolysis and partial resection of terminal ileum in a patient with kidney transplantation and severe sclerosing peritonitis]. / Adhezioliza i parcijalna resekcija terminalnog ileuma u bolesnice s transplantiranim bubregom i teskim sklerozirajucim peritonitisom.

A 21-year-old female patient was diagnosed with horseshoe kidney at the age of 10. She had been treated with peritoneal dialysis from 2005 to 2009, when she received kidney from a deceased donor. The posttransplant course was complicated by development of Pseudomonas aeruginosa and Candida sepsis. Reduced immunosuppression resulted in acute rejection, which demanded graphtectomy 2 months after transplantation. She restarted peritoneal dialysis for additional 2 years. In March 2011, she received her second transplant with excellent function. Nine months after the transplantation, she developed ascites, with early satiety and vomiting. MSCT revealed severe encapsulating sclerosing peritonitis. Her overall condition deteriorated, so she underwent adhesiolysis with resection of incarcerated terminal ileum. Due to acute allograft rejection, urgent graphtectomy was performed. Currently, she is receiving everolimus and dialysis successfully, with excellent overall status.

[Spontaneous retroperitoneal bleeding caused by rupture of the native kidney oncocytoma twelve years after renal transplantation]. / Spontani retroperitonealni hematom kao posljedica krvarenja iz neprepoznatog tumora nativnog bubrega u bolesnika 12 godina nakon transplantacije bubrega.

Renal transplantation is the method of choice for renal replacement therapy in the majority of patients. Immunosuppressive drugs may increase the risk of developing malignancies. We present a case of a patient having undergone different renal replacement methods over 25 years. He had good graft function at 12 years of transplantation. Development of spontaneous retroperitoneal hematoma caused by rupture of the native kidney oncocytoma was complicated with sepsis and deterioration of graft function. We emphasize the importance of regular ultrasonography follow-up of native kidney, which is challenging because of fibrous changes.

[Renal transplantation in the elderly: characteristics of donor and recipient]. / Transplantacija bubrega kod starijih osoba--vaznost obiljezja darivatelja i primatelja.

Aging is a natural process that occurs in all tissues and organs resulting in a decreasing functional capacity. Aging of the population results in an increased number of elderly patients who require replacement of renal function. Renal transplantation is the method of choice for this group of patients if they have no contraindications for immunosuppressive therapy. The lack of donors is the main obstacle for renal transplantation. However, the use of organs from elderly donors for transplantation in elderly recipients is an appropriate method of renal replacement therapy in this group of patients.

[Preemptive kidney transplantation in children--experience in UHC Zagreb]. / Preemptivna transplantacija bubrega u djece--iskustvo KBC-a Zagreb.

AIM: To discuss preemptive kidney transplantation outcomes in children with end stage kidney disease. METHODS: We present the data of patients younger than 18 years who were transplanted without previous dialysis in our Clinic. We retrospectively analyzed data available in medical health records. RESULTS: Preemptive living donor kidney transplantation was performed in 6 patients younger than 18 years. Creatinine clearance before transplantation was 9 +/- 4.15 ml/min (range = 2.7-12.3 ml/min, median = 8.5 ml/min). Currently, serum creatinine in patients with functioning graft is 139.4 +/- 60.9 micromol/l (range = 72-237 micromol/l, median = 130 micromol/l). One, three and five year graft survival was 100%. Overall graft and patient survival in the follow-up period was 83.3% and 100%, respectively. After 10 years one patient started with dialysis due to chronic graft rejection. CONCLUSION: From medical and socioeconomic point of view preemptive transplantation is optimal method for treatment of children with end-stage kidney disease. Membership in Eurotransplant should increase the number of preemptive transplantations in Croatia.

[Evolution of arteriovenous fistula between renal artery and vein in renal allograft after percutaneous nephrostomy in a renal transplant recipient]. / Evolucija arteriovenske fistule renalne arterije i vene bubreznog alografta nakon perkutane nefrostomije u bolesnika s transplantiranim bubregom.

Percutaneous urologic intervention has been accepted as a standard method to identify the etiology of graft dysfunction, or for treatment of urinary obstruction. Although ultrasound-guided procedure is a relatively safe method, arteriovenous fistula (AVF) is an important complication that is sometimes encountered. In this report, we present a renal transplant patient in whom an AVF and renal vein pseudoaneurysm after percutaneous nephrostomy were diagnosed. Surgical approach was not indicated for preservation of renal function. A 50-year-old man was admitted with obstructive uropathy 11 months after cadaveric renal transplantation. Percutaneous nephrostomy was performed under ultrasound guidance. Doppler sonography and angiography revealed an AVF between the main renal artery for lower pole of the graft and renal vein, with formation of a venous pseudoaneurysm. Careful monitoring during the next 7 years after iatrogenic AVF and venous pseudoaneurysm formation resulted in preservation of renal graft function and improvement of the patient's quality of life. Radiological interventional procedure with vascular graft-stent placement was indicated because of rapid pseudoaneurysm enlargement and high risk of its rupture. Interventional endovascular graft-stent placement is a safe procedure for exclusion of renal allograft and AVF from circulation without indication for open surgery in high-risk transplanted patients. According to our opinion, radiological interventional or surgical procedure in transplanted patients with AVF and pseudoaneurysm should be considered as the treatment of choice only in patients who have clinical symptoms or rapid growth of AVF with a high risk of pseudoaneurysm rupture.

Double, ectopic blind-end ureter: a case report.

We report a case of a complete, ectopic blind-ending ureteral duplication in a 26-year-old man who presented with the symptoms of an acute urinary tract infection for the first time. Since anamnestic data and clinical examination indicated a complicated urinary infection he was referred for further examination. On the left side, the imaging studies revealed a normal ureter draining the lower pole of the kidney and a blind-ending ureter with ectopia in the seminal vesicle. The patient recovered completely following surgical removal of the blind-ending ureter.

Immunolocalization and mRNA expression of bone morphogenetic protein-6 in human clear cell renal carcinoma.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily of proteins. Dysregulation of BMP signaling has been suggested in the carcinogenesis of different organs. We determined BMP-6 mRNA and protein expression in localized human clear cell renal carcinoma (CCRC), obtained from 20 patients who underwent nephrectomy, by the real-time polymerase chain reaction and immunohistochemistry. 15/20 patients exhibited higher BMP-6 mRNA expression in malignant than in healthy renal tissue relative to the PBGD expression (p < 0.05). Immunostaining intensity for BMP-6 in healthy renal tissue ranged from 0 to 2 (average 0.9), as well as in renal clear cell carcinoma (average 1.1). Seven of 20 (35%) healthy tissue samples failed to stain with BMP-6 antibody, compared to 2/20 (10%) tumor samples (p < 0.05). BMP-6 immunostaining was positive in 18/20 CCRC samples. Staining was localized in the cytoplasm and/or membrane of malignant cells. Malignant tissue had significantly higher BMP-6 mRNA expression than healthy tissue. There was no significant correlation between BMP-6 mRNA and protein expression with disease presentation, disease progression and patients' characteristics. Long-term follow-up of our patients is needed to determine the possible role of increased expression of BMP-6 in CCRC.

Hypoproteinemia as a prognostic risk factor for arteriovenous fistula failure.

INTRODUCTION: Any vascular access is of limited duration with many factors which influence survival in patients on chronic hemodialysis (HD). Hypoproteinemia as a marker of chronic illness is common among chronic HD patients. Our aim was to analyze the survival of the primary arteriovenous fistula (AVFs) and the risk factors which influence their patency and to test the hypothesis that patients with normal values of serum proteins have lower risk of AVF failure compared to patients with hypoproteinemia. METHODS: Seven hundred thirty-four consecutive patients were included who underwent creation of an AVF. The patients were prospectively followed-up for 2 years. Only patients with AVF function after a month from its creation were analyzed. The patients were divided into two subgroups, with normal and low serum protein levels (<65 g/L). FINDINGS: At follow-up 497 (67.7%) AVFs were still functional while 237 (32.3%) AVFs failed due to thrombosis or stenosis. Serum proteins and AVFs created on the forearm were positive predictors while diabetes was a negative predictor of longer AVF survival (P < 0.001; P = 0.003; P = 0.043). When comparing patients with normal and low serum protein levels (<65 g/L), mean survival time was significantly longer in patients with normal serum levels (P < 0.001). DISCUSSION: In this study, hypoproteinemia was an independent prognostic marker for AVF failure at 2 years. Hypoproteinemia, based on our results, is an independent, more sensitive and prognostic marker of possible vascular access failure than the presence of other common factors which influence shorter AVF survival.

[Arterial hypertension in renal transplant recipients]. / Hipertenzija nakon transplantacije bubrega.

Arterial hypertension develops in up to 80% of renal transplant recipients. Uncontrolled hypertension induces left ventricular hypertrophy, heart failure and death, but also promotes deterioration of allograft function. Cadaveric transplantation, delayed graft function, renal artery stenosis, presence of native kidneys, increased body weight and therapy with calcineurin inhibitors and steroids have been associated with an increased incidence of hypertension after kidney transplantation. Cyclosporine increases both systemic and renal vascular resistance, enhances sympathetic activation, endothelin production and, possibly, decreases vascular relaxation by decreasing the generation of nitric oxide. Tacrolimus has less pronounced prohypertensive role after renal transplantation. Corticosteroids contribute to the development of hypertension, since their withdrawal results in a significant decrease of blood pressure in the majority of patients. Renal artery stenosis occurs in almost 12% of hypertensive renal transplant recipients. It is a correctable cause of hypertension, and for this reason should be investigated in all suspected patients. Doppler ultrasonography is used as the screening method that is highly sensitive and specific in the hands of a well-experienced investigator. However, dependence of the method on the experience of the investigator is its major drawback. Magnetic resonance angiography and spinal computed tomography angiography are useful noninvasive methods, but arteriography remains a method for establishing the definitive diagnosis. Percutaneous balloon angioplasty, with or without placement of the stent, is successful in the majority of patients, but with a high incidence of restenoses (20%). Surgery is indicated for stenoses that cannot be treated with angioplasty or that recur. Auto-transplantation of the kidney with complex stenoses of graft arteries is useful in selected cases. Posttransplant hypertension should be aggressively treated to prevent the development of end-organ damage. Every effort should be invested in reducing immunosuppression when appropriate, together with salt restriction and weight reduction. Calcium channel blockers have good antihypertensive properties accompanied with minimization of cyclosporine-induced renal vasoconstriction. Angiotensin-converting enzyme inhibitors (ACEi) should be used in patients with proteinuria. Renal function should be carefully monitored after their introduction since they may cause transitory deterioration of glomerular filtration and/or hyperkaliemia. ACEi can induce anemia in renal transplant recipients, side effect that is often used in the treatment of posttransplant erythrocytosis. All other antihypertensive drugs could be used, with minoxidil being the most potent one. Patients with resistant hypertension should be investigated for the presence of renal artery stenosis. After exclusion of rejection, renal artery stenosis and recurrent disease, in cases of severe hypertension, native kidneys laparoscopic nephrectomy should be considered.

Association of cyclooxygenase-2 immunoreactivity with tumor recurrence and disease progression in superficial urothelial bladder cancer.

AIMS AND BACKGROUND: The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. METHODS: In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. RESULTS: COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. CONCLUSIONS: COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.

[Laparoscopic treatment of functioning adrenal tumors]. / Laparoskopsko lijecenje funkcionalno aktivnih tumora nadbubrezne zlijezde.

INTRODUCTION: Laparoscopy is now a widely used method for removal of functioning and non-functioning adrenal tumors. This paper reports our experience in laparoscopic transperitoneal removal of functioning adrenal tumors including pheochromocytoma, Cushing's disease and aldosteronoma. METHODS: Between May 2001 and April 2006, 29 patients underwent laparoscopic adrenalectomy for pheochromocytoma. In 37 patients (10 patients with bilateral adrenalectomy) adrenalectomy was performed for Cushing's disease, while 28 patients had aldosteronoma. In 2 patients adrenalectomy was performed for virilizing adenoma. RESULTS: All laparoscopic adrenalectomies were finished successfully, and no open surgery was necessary. Major postoperative complications were not observed. Mean hospital stay was 3 days. No patient required blood transfusion. CONCLUSIONS: Laparoscopic adrenalectomy for functioning adrenal tumors proved a safe and minimally invasive procedure. Laparoscopic adrenalectomy, in comparison with open surgery, has numerous advantages, including a shorter length of stay, shorter time to return to preoperative level of activity, better cosmetic effect, and decrease in postoperative pain.

Changes in bone mineral density in patients with prostate cancer treated with androgen deprivation therapy.

Osteoporosis is a complication of permanent androgen deprivation in men with prostate carcinoma, following either bilateral orchiectomy or treatment with GnRH agonists. The present approach to the problem of osteoporosis includes prevention, adequate follow-up and appropriate treatment as an imperative of contemporary urological and endocrinological management of these patients. Bone densitometry was performed in 18 patients who were on GnRH agonists treatment during 1-3 years. The patients under therapy were followed clinically, PSA (prostate-specific antigen) values were determined and bone scintigraphy was performed. The bone mineral density values in 13 patients indicated osteopenia, whereas in one patient the finding was compatible with osteoporosis. Four patients had normal bone mineral density findings. Bone densitometry should be performed before initiation of treatment with GnRH agonists in order to quantify the therapy-related bone loss. Prevention of development of osteoporosis and its complications depends on the assessment of pharmacological treatment in this group of patients, including e.g. bisphosphonates and possible intermittent androgen deprivation.

Virilizing adrenal cancer and bail-out nephrectomy.

We report a rare case of virilizing adrenal cancer with tumorous invasion of the left renal vein in which a retroperitoneal adrenalectomy with bail-out nephrectomy was performed. A tumor thrombus infiltrated the wall of the left adrenal vein and extended into the left renal vein. Initially, a kidney sparing procedure with partial tangential excision of the involved renal vein wall was performed. After positive vein margins were confirmed with intraoperative histology, the indication for nephrectomy was made. To the authors' awareness, this is the first report of a virilizing adrenal cancer with a tumor thrombus infiltration of the renal vein and surgical tendency for kidney preservation.

Immunocompetence in non-seminomatous testicular cancer patients before any treatment and one year after completion of therapy.

BACKGROUND: Assessment of immunocompetence in non-seminomatous testicular cancer (NSTC) patients. MATERIALS AND METHODS: In the peripheral blood of 43 patients with NSTC, lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell activity as well as neutrophil and monocyte phagocytic functions were studied. RESULTS: The proportion and number of T- and B- lymphocytes, lymphocyte reactivity to mitogens as well as neutrophil and monocyte phagocytic functions were equal in patients with localized disease and in those with metastatic disease and they not differ from those in controls. The NK cell number and NK cell activity, however, were significantly impaired in both patient groups. The patients with metastatic disease had a lower NK cell activity than those with localized disease. One year after the completion of anticancer treatment, the NK cell number and cytotoxic activity recovered in both groups of patients. CONCLUSION: These results suggest that patients with NSTC are primarily deficient in NK cell number and their cytotoxic function influence the host's ability to control the proliferation and spread of tumor cells.

Lymphocyte subsets, lymphocyte reactivity to mitogens, NK cell activity and neutrophil and monocyte phagocytic functions in patients with bladder carcinoma.

OBJECTIVE: Assessment of immunocompetence in bladder transitional cell carcinoma (TCC) patients. PATIENTS AND METHODS: In 34 untreated patients with bladder TCC, lymphocyte subsets were measured together with lymphocyte reactivity to mitogens, NK cell activity and neutrophil and monocyte phagocytic functions. The data obtained were correlated with both the tumor spread and the grade. RESULTS: In patients with superficial carcinoma, the proportion of CD4+ cells, the reactivity of lymphocytes to mitogens and NK cell activity was significantly lower than in controls. In patients with invasive disease, the CD4/CD8 ratio, lymphocyte reactivity to mitogens and NK cell activity was significantly diminished when compared with the controls and with patients with superficial carcinoma. Neutrophil and monocyte killing was significantly lower than in controls. Patients with high-grade tumors had a significantly lower CD4/CD8 ratio and lymphocyte reactivity to mitogens than patients with low-grade tumors. CONCLUSION: These findings indicate gross immunological abnormalities in TCC patients which correlate with stage and grade of tumor.

Renal autotransplantation in management of bilateral ureteral mortar shell injuries: a case report.

We present a 36-year-old female patient who was injured in the pelvic region by a mortar shell fragment. The trauma comprised a complex lesion to both ureters, to the urinary bladder, and to the pelvic brim. The ruptured urinary bladder was sutured and a bilateral ureterocutaneostomy was performed in a hospital near the front line. Because of a large scar and the right ureter necrosis, a kidney autotransplant was performed 3 months later. A left ureterocystoneostomy was done. Five years later, because of urosepsis and hydronephrosis caused by a ureteral calculus, a nephrostomy was placed in the proximal right ureter, antibiotic treatment was prescribed, and the calculus was managed by crushing the stones using extracorporeal shock wave lithotripsy. Ten years after the initial trauma, the patient is well, has normal micturition, and both of her kidneys are functioning normally.