Successful Kidney Transplantation Using Elderly Living Donor with Extremely Large Renal Cyst and Double Arteries.

The authors describe a kidney transplant procedure using a living donor with a large cyst and double arteries. Due to the lack of regular transplant activity from a deceased donors, we decided to use the, so called, expanded criteria living donors, which means older age (more than 65 years), hypertension, some structural anomalies of the kidneys (cysts, multiple renal arteries), ABO incompatible kidney transplant, etc. The surgical procedure was the unroofing of a large cyst and wadding with perirenal fat. The 10 years survival rate is quite successful and we can recommend it.

Pathohistomorphometric and Immuno-Histologic Changes in Early Arteriovenous Fistula Failure in Patients with Chronic Kidney Disease.

BACKGROUND: Hemodialysis is a prevalent treatment for the end-stage chronic kidney disease (CKD) worldwide. The primary arteriovenous fistula (AVF), widely considered the optimal hemodialysis access method, fails to mature in up to two-thirds of the cases. The etiology of the early AVF failure, defined as thrombosis or inability to use within three months post-creation remains less understood, and is influenced by various factors including patient demographics, surgical techniques, and genetic predispositions. Neointimal hyperplasia is a primary histological finding in stenotic lesions leading to the AVF failure. However, there are insufficient data on the cellular phenotypes and the impact of the preexisting CKD-related factors. This study aims to investigate the histological, morphometric, and immunohistochemical alterations in the fistula vein, pre-, peri-, and post-early failure. MATERIALS AND METHODS: Eighty-nine stage 4-5 CKD patients underwent standard preoperative assessment, including the Doppler ultrasound, before a typical radio-cephalic AVF creation. Post-failure, a new AVF was created proximally. The vein specimens were collected during the surgery, processed, and analyzed for morphometric analyses and various cellular markers, including Vimentin, TGF, and Ki 67. RESULTS: The study enrolled 89 CKD patients, analyzing various aspects of their condition and AVF failures. The histomorphometric analysis revealed substantial venous luminal stenosis and varied endothelial changes. The immunohistologic analysis showed differential marker expressions pre- and post-AVF creation. CONCLUSION: This study highlights the complexity of the early AVF failures in CKD patients. The medial hypertrophy emerged as a significant preexisting lesion, while the postoperative analyses indicated a shift towards neointimal hyperplasia. The research underscores the nuanced interplay of vascular remodeling, endothelial damage, and cellular proliferation in the AVF outcomes.

Proteomics Profiling of Bladder Cancer Tissues from Early to Advanced Stages Reveals NNMT and GALK1 as Biomarkers for Early Detection and Prognosis of BCa.

The high recurrence rate and invasive diagnostic and monitoring methods in bladder cancer (BCa) clinical management require the development of new non-invasive molecular tools for early detection, particularly for low-grade and low-stage BCa as well as for risk stratification. By using an in-solution digestion method and label-free data-independent LC-MS/MS coupled with ion mobility, we profiled the BCa tissues from initiation to advanced stages and confidently identified and quantified 1619 proteins (≥2 peptides). A statistically significant difference in abundance (Anova ≤ 0.05) showed 494 proteins. Significant correlation with stage with steady up or down with BCa stages showed 15 proteins. Testing of NNMT, GALK1, and HTRA1 in urine samples showed excellent diagnostic potential for NNMT and GALK1 with AUC of 1.000 (95% CI: 1.000-1.000; p < 0.0001) and 0.801 (95% CI: 0.655-0.947; p < 0.0001), respectively. NNMT and GALK1 also showed very good potential in discriminating non-invasive low-grade from invasive high-grade BCa with AUC of 0.763 (95% CI: 0.606-0.921; p = 0.001) and 0.801 (95% CI: 0.653-0.950; p < 0.0001), respectively. The combination of NNMT and GALK1 increased prognostic accuracy (AUC = 0.813). Our results broaden the range of potential novel candidates for non-invasive BCa diagnosis and prognosis.

Celiac-Like Duodenopathy Associated With Enteric-Coated Mycophenolate Sodium Immunosuppression in Renal Transplant Recipients: Report of 4 Cases.

Celiac-like disease and celiac sprue associated with widespread use of mycophenolic acid are among the most frequent complications of renal transplant. Most cases have been observed in patients receiving mycophenolate mofetil; however, there have been rare instance after administration of enteric-coated mycophenolate sodium. Here, we describe 4 renal transplant recipients with celiac-like duodenopathy that occurred in association with enteric-coated mycophenolate sodium treatment in a time period of 14 to 19 years after living donor kidney transplant. Three of 4 patients had diarrhea, and all 4 patients had marked loss of body weight. Esophago-gastroduodenoscopy was not diagnostically helpful; however, randomly performed duodenal biopsies showed mild villous atrophy and intraepithelial lymphocytosis. Replacement of enteric-coated mycophenolate sodium with azathioprine was successful with stopping diarrhea, allowing regained body weight, and stabilization of renal function. This potential complication in kidney transplant recipients can occur more than a decade after transplant. Diagnosis and treatment initiation are urgent to cure this disease.

Potential Role of Seven Proteomics Tissue Biomarkers for Diagnosis and Prognosis of Prostate Cancer in Urine.

As the currently available tests for the clinical management of prostate cancer (PCa) are still far from providing precise diagnosis and risk stratification, the identification of new molecular marker(s) remains a pertinent clinical need. Candidate PCa biomarkers from the published proteomic comparative studies of prostate tissue (2002-2020) were collected and systematically evaluated. AZGP1, MDH2, FABP5, ENO1, GSTP1, GSTM2, and EZR were chosen for further evaluation in the urine of 85 PCa patients and controls using ELISA. Statistically significant differences in protein levels between PCa and BPH showed FABP5 (p = 0.019) and ENO1 (p = 0.015). A biomarker panel based on the combination of FABP5, ENO1, and PSA provided the highest accuracy (AUC = 0.795) for PCa detection. The combination of FABP5, EZR, AZGP1, and MDH2 showed AUC = 0.889 in PCa prognosis, with 85.29% of the samples correctly classified into low and high Gleason score (GS) groups. The addition of PSA to the panel slightly increased the AUC to 0.914. AZGP1, FABP5, and EZR showed significant correlation with GS, stage, and percentage of positive biopsy cores. Although validation using larger patient cohorts will be necessary to establish the credibility of the proposed biomarker panels in a clinical context, this study opens a way for the further testing of more high-quality proteomics biomarkers, which could ultimately add value to the clinical management of PCa.

Primary Renal Squamous Cell Carcinoma in Native Polycystic Kidney and Ureter 16 Years After Living Donor Kidney Transplant.

We describe a case of a 55-year-old woman with polycystic kidney disease who received a living donor kidney transplant 16 years earlier and was on immunosuppressive therapy with satisfactory renal function. The donor was her mother. The patient presented with flank pain on the right side and macrohematuria, and noncontrast computed tomography and magnetic resonance imaging led to the diagnosis of tumors in the remaining right native polycystic kidney and ureter, as well as secondary retroperitoneal dissemination. We performed right radical nephrectomy and ureterectomy with extirpation of 2 metastases; the left native kidney remained intact. Histology showed squamous metaplastic changes and invasive epithelial neoplasm in the lumen of the renal pelvis and ureter with extensive squamous differentiation positive for nuclear p63 as squamous cell immunohistochemical marker. After surgery, an immunosuppressive therapy with methylprednisolone was administered, without calcineurin inhibitors and mycophenolate mofetil. Twelve months later the patient was still alive, with a glomerular filtration rate of 29 mL/min. Needs remain for further treatment modalities in patients with primary squamous cell carcinoma in nonfunctioning kidneys and improvements in imaging technique accuracy.

Urinary Proteomics in Kidney Transplantation.

Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure.

Solitary Fibrous Tumor of Adrenal Gland and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare and still controversial entity. This type of tumor first appeared in the literature as a pleural lesion, but, over the last decades, it has been reported in many extrathoracic sites. As a tumor of the adrenal gland, SFT is still rare and very uncommon, thus extensive research among the English language literature has been performed. We present here a case report of an adrenal SFT which is compared to 11 other known cases. Our case report is from a patient with SFT on the left adrenal gland, followed by mild symptoms of abdominal discomfort and hypertension. Physical examination, laboratory, and radiological tests were performed. The patient underwent surgery and the material was sent for histopathologic analysis for a definite diagnosis. Regular follow up appointments were performed over the course of two years. No recurrence of the tumor has been detected. We explain the symptoms, diagnosis, treatment, and additionally we describe the results and implications of the findings reported in the literature. Correct diagnosis is mandatory for optimal management of solitary fibrous tumor patients.

Management of Multiple Renal Arteries and Unusual Venous Anatomy During Kidney Transplant: From a Simple Technical Problem to a Graft-Saving Procedure.

OBJECTIVES: Incidence of vascular anomalies in donor kidneys varies from 18% to 30% and presents a challenge for a transplant surgeon in kidney transplant. Here we present our personal experience for man - agement of the complicated and unexpected cases. MATERIALS AND METHODS: A total of 250 kidney transplants (226 living, 24 deceased) were performed in a period of 24 years; mean donor age was 55 years (range, 25-86 years), and mean recipient age was 38.6 years (range, 14-66 years). We analyzed the surgical techniques, complications and outcomes, rejection episodes, kidney function, and graft and patient survival rates. RESULTS: Of 250 nephrectomies, 209 had a single artery (83.6%), 34 had 2 arteries (13.6%), and 7 had 3 arteries (2.8%). Of 34 double arteries, 14 had 2 main arteries, 15 had a main and a polar artery, and 5 had an aortic Carrel patch after deceased donation. According to the size, type, and position, the anastomoses were performed with branches of hypogastric, epigastric inferior, iliac external, and main renal artery, intracorporeally or in bench surgery. Regarding veins, 1 double inferior vena cava, 1 left-side inferior vena cava, 4 retroaortic, 2 circumaortic, 10 large lumbar veins draining into the left renal veins, and 8 cases with 2 or more different size renal veins were managed. In 9 cases with short right renal vein, an extension with vena cava (a "Barry cavoplasty") was performed in deceased donor organs. No serious surgical complications related to vascular anomalies were observed. There were no statistical differences in 1-, 6-, and 12-month graft survival rates between the groups with or without vascular anomalies. CONCLUSIONS: Vascular anomalies should no longer be considered a contraindication for transplant, if careful anastomosis is performed in every case to avoid ischemia and further complications. Therefore, management of vascular anomalies could be a graftsaving procedure.

Detection of TMPRSS2-ERG Fusion Transcript in Biopsy Specimen of Prostate Cancer Patients: A Single Centre Experience.

INTRODUCTION: Prostate carcinoma is the most frequent malign neoplasm among men with an ever-growing incidence rate. TMPRSS2-ERG fusion transcript leads to the androgen induction of ERG proto-oncogenes expression, representing a high presence of oncogenes alteration among prostate tumour cells. AIM: The aim of this research was to detect and evaluate theTMPRSS2-ERG fuse transcript in the tissues of patients with prostate cancer, and establish a base of material of these samples for further genetic examination. MATERIALS AND METHODS: The research was a prospective clinical study that involved and focused on random sampling of 101 patients (62 with prostate cancer-study group and 39 with benign changes in the prostate-control group). Real time PCR analysis for detection of the TMPRSS2-ERG fusion transcript in prostate tissue was performed and also data from the histopathology results of tissues were used, as well as data for the level of PSA (prostate-specific antigen) in blood. RESULTS: TMPRSS2-ERG fusion transcript was detected in 20 out of 62 (32.2%) patients with prostate carcinoma and among no patients with benign changes whatsoever. There were no significant differences between patients with/without detected TMPRSS2-ERG fusion related to Gleason score. Among 50%, in the study group this score was greater than 7 per/for Median IQR=7 (6-8). Significant difference was recognized, related to the average value of PSA in favour of significantly higher value of PSA in the study group with prostate cancer, but there was also no significant difference between samples with prostate cancer who were with/without detected TMPRSS2-ERG fusion transcript related to PSA level. DISCUSSION: The results from this research are in accordance with the values and results from analyses done in several research centres and oncological institutes. CONCLUSION: The positive findings in small scale studies encourage the implementation of larger scale studies that will be enriched with results of genetic transcript in blood and urine and will define the positive diagnostic meaning of the TMPRSS-ERG fusion transcript.

Hypertension after Kidney Transplantation: Clinical Significance and Therapeutical Aspects.

Most of the kidney transplanted patients develop arterial hypertension after renal transplantation. Together with very well-known and usual risk factors, post-transplant hypertension contributes to the whole cardiovascular morbidity and mortality in the kidney transplant population. The reasons of post-transplant hypertension are factors related to donors and recipients, immunosuppressive therapy like Calcineurin Inhibitors (CNI) and surgery procedures (stenosis and kinking of the renal artery and ureteral obstruction). According to Eighth National Committee (JNC 8) recommendations, blood pressure > 140/90 mmHg is considered as hypertension. The usual antihypertensive drugs used for the control of hypertension are Calcium channel blockers (CCB), Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin -II receptor blockers (ARB), B- blockers and diuretics. Follow the KDIGO guidelines the target blood pressure < 140/90 mmHg for patients without proteinuria and < 125/75 mmHg in patients with proteinuria is recommended. Better control of post-transplant hypertension improves the long-term graft and patient's survival.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer.

INTRODUCTION: Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). OBJECTIVE: The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIALS AND METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. RESULTS: UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. CONCLUSIONS: The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Laparoscopic Adrenalectomy: First Single-Center Experience in the Balkans.

INTRODUCTION: Laparoscopic adrenalectomy has become the preferred approach for removal of the adrenal gland for the management of benign or malignant functioning or nonfunctioning adrenal masses. We aimed to present our initial experience with this procedure. In addition, we compare the clinical outcomes of laparoscopic (LA) vs. the open adrenalectomies (OA) performed at our institutions. Also we report a case of successful laparoscopic treatment of splenic artery aneurism involving laparoscopic splenectomy. PATIENTS AND METHODS: A retrospective analysis of the data of all patients who underwent adrenalectomy at three institutions, over the last 12-year period, since the laparoscopic adrenal surgery was introduced in our country. All patients were assessed regarding the demographic data, hormonal status, operative time, estimated blood loss, complications, size of the tumor, number of patients requiring blood transfusion, hospital stay and conversion to open surgery for LA. RESULTS: Thirty five consecutive patients, aged from 33 to 67 (average age 54 years) underwent unilateral LA adrenalectomy during the study period including 14 right and 21 left sided. The laparoscopic procedure was successfully completed in all except 4 cases, which were converted to open surgery to control bleeding from the avulsed adrenal veins. LA proved superior to OA, resulting in less estimated blood loss, shorter operating time, shorter time to resumption of oral intake, shorter postoperative hospital stay and less analgesic requirements. During the follow-up of 3 to 36 months no tumor recurrence and/or metastasis developed. CONCLUSIONS: Our results concur with other retrospective reviews comparing laparoscopic and open adrenalectomy, demonstrating unequivocal advantages in terms of reduced length of hospital stay, blood loss, return of bowel function, functional recovery and post-operative morbidity.

Severe Endothelial Damage in Chronic Kidney Disease Patients Prior to Haemodialysis Vascular Access Surgery.

BACKGROUND: Hemodialysis as an efficient therapy for advanced CKD is the most used treatment modality all over the world. Even though primary AVF is widely accepted as a best permanent vascular access in hemodialysis patients, up to 60% of all fistulas fail to mature. The pathogenesis of early fistula failure is not very well understood. Many general and local factors are involved: patient's age, sex, primary renal disease, small vessel's diameter, presence of accessory veins, prior venipunctures, surgical skill, genetics, etc. Histological investigations have confirmed the neointimal venous hyperplasia as a major pathological finding in stenotic lesions of AVF failure, due to local inflammation, oxidative stress and migration and proliferation of myofibroblasts, fibroblasts and endothelial cells. MATERIALS AND METHODS: A total of 89 patients with stadium 4-5 of CKD are involved in the study. A typical radio-cephalic AVF is created in all patients. Part of the fistula vein was taken for histological, immunohistochemical (Vimentin, TGF ß and KI67) and morphometric analysis. Appriopriate statistical method was applied. RESULTS: Up to 80% of the patients showed some degree of endothelial changes at the time of creation of AVF, among them 19 pts with substantial intimal hyperplasia, 51 with medial hypertrophy and 19 pts with normal histology. Almost two thirds of the patients did not have expression of TGFß. More than 95% had some expression of Vimentin. None of the patients had expression of the marker KI 67. CONCLUSION: Medial hypertrophy is predominant preexisting pathohistological lesion prior the AVF creation, despite the presence of neointimal hyperplasia. The absence of TGFß expression in majority of our patients could suggest that inflammation and oxidative stress are developing later, after vascular access surgery. The dominant cells within the stenosis in the veins are myofibroblasts. Their increased presence maybe a reason why some patients are prone to developing venous endothelial changes as a results of exaggerated vascular endothelial response to the effect of uremia, hypertension and other insults.

5. Uro-Oncology Winter Congress.

The 5th Uro-oncology Winter Congress was held in Skopje, at the Macedonian Academy of Sciences and Arts on January 30 - February 03, 2013. The Congress was co-organized by the Macedonian Academy of Sciences and Arts, the Istanbul University, the Turkish Urology Association, Macedonian Society of Urology and the Ministry of Health of the Republic of Macedonia. Topics of the Congress were tumors of urinary tract (kidney, vesica urinaria) and prostate. The latest achievements in the diagnosis and treatment of the above-mentioned disease were presented. Around 300 participants from the Balkans took part at the meeting. There were simultaneous sessions on different uro-oncological issues with around 60 presentations. In addition, there were poster presentations and training courses. It is important to point out that we had a session with participation of Balkan uro-oncologists - Balkan Urology Session, which is the first time in recent years.

Use of expanded criteria in living kidney donors - the crucial factor for improvement of the kidney transplant programme in Republic of Macedonia.

Renal transplantation is surely the best treatment for Chronic Kidney Disease (CKD) patients in both developed and developing countries. Due to the tragic events in former Yugoslavia at the beginning of the nineties, it was not possible to develop a really good clinical practice in the field of transplantation. Facing the lack of Deceased Donor Donation Transplantation and any organ-sharing among the Balkan countries, we introduced a large and very ambitious living donor transplant programme including what were called expanded criteria living donors. In the period of the past 20 years elderly (above 65 years), unrelated (emotionally related), marginal and ABO incompatible living donors were accepted. Due to the skilled surgical team, powerful immunosupression and HLA compatibility testing, the results were promising and the number of complications very low. The authors concluded that use of an expanded criteria living donor is fully acceptable, especially in developing countries, and could ameliorate the severe organ shortage in the region.

Cyclosporine nephrotoxicity and early posttransplant hyperkalemia in living-donor renal recipients: report of 4 cases.

OBJECTIVES: Hyperkalemia is an electrolyte disorder that may occur during the first few months after a renal transplant, in patients undergoing cyclosporine immunosuppression. We present our experience with cyclosporine-associated hyperkalemia in living-donor renal transplant recipients, with isolated clinically relevant hyperkalemia soon after surgery. MATERIALS AND METHODS: We report 4 living-donor renal recipients with hyperkalemia soon after transplant. RESULTS: Severe unexpected hyperkalemia (7.5- 9.4 mmol/L) was noted in our patients 12, 20, 22, and 34 days after transplant. The C2 cyclosporine concentration was within recommended range or slightly greater than 1200 ng/mL. The hypertonic glucose/insulin treatment along with potassium diet was without results. A reduction in daily cyclosporine dosages, along with 1- to 2-week administration of fludrocortisone was effective. The patients became normokalemic taking a standard, triple-drug immunosuppression protocol, and were discharged home with normal renal function. There were no repeat episodes of hyperkalemia in any of the patients during 12 months of follow-up. CONCLUSIONS: Cyclosporine should be considered a cause of hyperkalemia in renal transplant recipients. Successful treatment with fludrocortisone confirms that transitional pseudohypoaldosteronism has a potential nephrotoxic effect of cyclosporine. We recommend close monitoring of the cyclosporine concentration and administering fludrocortisone when treating hyperkalemia in renal transplant recipients.

The outcome of commercial kidney transplant tourism in Pakistan.

The lack of cadaver organs for transplantation motivates some Balkan patients to go to developing countries to buy a kidney. We have followed 36 patients who received kidney transplants in Lahore and Rawalpindi, Pakistan. The patients had not been cleared for transplantation with a standard pre-transplant work-up: 80% were hepatitis-C virus (HCV) or HBsAg positive. During follow-up, seven patients died. Sixteen patients experienced wound infections with post-operative hernias, and three patients developed peri-renal hematomas. Six abscesses and four lymphoceles occurred, and four urinary fistulas were surgically treated. Nephrectomy was performed in three patients because of renal artery thrombosis. Nine patients developed active hepatitis C, and four patients manifested cytomegalovirus disease. Three patients developed steroid diabetes, and three patients experienced acute myocardial infarction. Nine patients had one or more rejection episodes. Urinary tract infection with Pseudomonas or Escherichia occurred frequently. The one-yr patient and graft survival rates were 80% and 68%, respectively. Paid unregulated renal transplantation is not recommended for both ethical reasons and because of an association with excessive morbidity and mortality.