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.

AHNAK2 Urinary Protein Expression as Potential Biomarker for Bladder Cancer Detection: A Pilot Study.

OBJECTIVE: This study aimed to measure the AHNAK2 urinary levels in bladder cancer patients. MATERIAL AND METHODS: This prospective case-control study enrolled 67 participants between January and March 2019 and were categorized into bladder cancer group (n=37), with histologically proven bladder can cer, and control group (n=30), with histologically verified benign lesions or with no bladder cancer indica tion during follow-up. Urine samples of 15 mL were collected in the mid-morning before cystoscopy/surger y and an enzyme-linked immunosorbent assay was performed as per the manufacturer's protocol. Bladder malignancies were classified according to the World Health Organization Tumor Classification. Group's associations were evaluated with the Student t-test, Spearman's rank correlation, and Mann-Whitney U test, while receiver operating curve was plotted for assessing the test's performance. RESULTS: Mean age of the bladder cancer group was 66.41 years (standard deviation=10.04, range=43-82 years) and the control group was 59.67 years (standard deviation=10.44, range=38-77 years). All bladder cancers were of the urothelial histotype, with the following pT distribution: pTa/papillary urothelial neoplasm of low malignant potential (n=19; 28.4%), Primary tumor (pT) in situ (n=4; 6%), pT1 (n=7; 10.4%), and pT≥2 (n=7; 10.48%). Mean AHNAK2 levels were higher in bladder cancer patients 49.08 pg/mL (standard deviation=114.91) compared to controls 5.28 pg/mL (standard devia tion=6.65), P < .05). Significant differences were noted between non-invasive bladder cancer (n=23; mean=7.14 pg/mL; standard deviation=7.26) and invasive bladder cancer (n=14; mean=117.99 pg/mL; standard deviation=168.08) and between non-muscle invasive bladder cancer (mean=23.19 pg/mL; standard deviation=66.93) and muscle-invasive bladder cancer (mean=160.05 pg/mL; standard devia tion=199.65) (P < .001). The result of the assays was given as follows: sensitivity: 64.19%, specificity: 66.67%, positive predictive value: 22.07%, negative predictive value: 92.37%, area under curve: 0.695, and 95% CI: 0.57-0.82. CONCLUSION: AHNAK2 protein could be used as bladder cancer surveillance biomarker. The inclusion of AHNAK2 levels in stratification nomograms might reduce the number of unnecessary cystoscopies.

Association of the chronic kidney disease urinary proteomic predictor CKD273 with clinical risk factors of graft failure in kidney allograft recipients.

BACKGROUND: Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes. METHODS: Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-h proteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273. RESULTS: CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = -0.29, P = 0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. CONCLUSIONS: Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.

The Importance of the World Kidney Day World Kidney Day - 11 March 2021 - Living Well with Kidney Disease.

World Kidney Day (WKD) is a global campaign to raise awareness of the importance of our kidneys to overall health and to reduce the frequency and impact of kidney disease and associated health problems worldwide. Kidney disease is a non-communicable disease (NCD) and currently affects around 850 million people worldwide. One in ten adults has chronic kidney disease (CKD). The global burden of CKD is increasing, and is projected to become the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume 2-3% of the annual healthcare budget in high-income countries. Crucially, kidney disease can be prevented and progression to end-stage kidney disease can be delayed with appropriate access to basic diagnostics and early treatment. This year World Kidney Day continues to raise awareness of the increasing burden of kidney diseases worldwide and to strive for kidney health for everyone, everywhere. During the pandemic with COVID 19 patients kidneys are also damaged, apart from the respiratory tract and other organs. It can lead to an increase in acute renal failure and consequent chronic kidney insufficiency, as well as number of deaths. Therefore, it is important to evaluate the renal function in each patient with COVID 19 virus. In the Republic of North Macedonia from 2006 to present day nephrologists and other medical personnel devoted to the early diagnosis, prevention and treatment of renal disease have participated in the activities of the World Kidney Day. These activities were supported by the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs, the Department of Nephrology at the Medical Faculty, the Macedonian Academy of Sciences and Arts, the Government of the Republic of North Macedonia, non-governmental nephrology organizations (NEFRON) and the media. There were lectures and presentation devoted to the various theme of the WKD, publications in journals, as well as activities for examination of the renal function of patients in the medical centers. The activities during the WKD contributed to the improvement of the nephrological protection of the citizens of the Republic of N. Macedonia.

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.

Can an increased nitric oxide level be accepted as non-invasive marker for sub/acute rejection of the kidney allograft?

BACKGROUND: Subclinical and acute rejections (SAR/AR) continue to have a negative impact on graft survival. The aim of our study was to analyze allograft rejection and nitric oxide (NO) levels in patients with protocol- and clinically-indicated biopsies in relationship with other causes of allograft dysfunction, and to evaluate the clinical impact of NO measurement as non-invasive marker for early diagnosis of SAR/AR. METHODS: In 45 living-related kidney transplants, serum NO levels were measured at: 20 min after reperfusion (NO1); on days 1 (NO2), 5 (NO3), and 14 (NO4); and at the first (NO5) and sixth (NO6) months after transplantation (Tx). Protocol biopsies (Bx) were performed at the first and sixth months after Tx. RESULTS: 38 (42.2%) Bx showed histological features of (SAR), 4 (4.5%) Bx showed mild tubulointerstitial rejection, while 48 (53.3%) Bx had no histological signs of SAR/AR. Significantly higher (NO3) levels were found in patients with AR and (NO5)/(NO6) in SAR as compared to other causes of allograft dysfunction occurred within the first posttransplant month (delayed graft function, urinary tract infection, and cyclosporine toxicity). Sensitivity/specificity for cut-off NO level of 70 µmol/l were 69.2% and 88.4% in AR, and 78.9% and 75.4% for the level of 50 µmol/l in SAR patients, respectively. CONCLUSIONS: Our study reports significantly higher serum NO levels at day 5 and a gradual decrease at day 14 (prior to and at the time of clinically manifested AR), and at 1- and 6-month protocol biopsies in SAR patients as compared to all other causes of renal dysfunction. NO measurement may have a satisfactorily diagnostic performance as a useful non-invasive marker not only for AR, but also for SAR patients.

The improvement in kidney transplant program in R. Macedonia--what are the clues?

Kidney transplantation (KTx) is the best treatment option in patients with chronic kidney disease (CKD). Health-economics data favour the KTx in comparison with any type of dialysis procedure, but the multidisciplinary approach and required high level of organisational infrastructure are frequent impediments for its availability in the majority of developing countries. A living donor kidney transplant (LDKTx) programme has been developed in the Republic of Macedonia since 1977 but without a real continuum in the following years. There was a great success with 15 cadaveric kidneys transplanted (1987-1989) followed by an average of 13.5 KTx per year in the period 1996-2011. Because of the scarce organ donation and transplant activities in the majority of Balkan countries the question remains what could be done in order to enable organ transplantation as the basic human right for the best treatment option in patients with CKD. In addition to the possible increase in the number of LDKTx, prerequisites for a deceased donor (DD) programme would be the creation of an official waiting list of candidates for DD transplantation, organizational and infrastructural networking and raising public awareness on the number of potential deceased donors through permanent media presentation. Our involvement in the South-eastern Europe Health Network (SEEHN) initiative and the support from the newly created Regional Health Development Centre (RHDC) on Organ Donation and Transplant Medicine established in Croatia (Zagreb) was shown as successful for improvement of the KTx programme. At the very first professional meeting (27-28 May, 2011 in Skopje, Macedonia), the organ donation and transplantation needs of each country within the SEE geographical region were addressed and action plans for further steps on how to proceed were established. Hence, the number of professionals (including vascular surgeons) involved in KTx was increased along with the substantial increase in the reimbursement per transplant procedure at the Urology Department. Nowadays, we are pleased to report 24 successfully performed LDKTx in 2012, and in 2013 for 7 months 28 transplantations, awaiting 40 KTx at the end of the year. Prospectively, we should initiate the deceased donor programme, even in order to sustain the already established high number of transplantation per month/year, since the potential for LDKTx may be exhausted. We also hope to be supportive for regional collaboration and transplantation of CKD patients from the neighbouring countries (Albania and Kosovo), and eventually to establish regional networking in deceased donor procurement, exchange and allocation practice.

Acute fulminant hepatatis in kidney transplant recipient after repeated sevoflurane anesthesia--a case report and literature review.

INTRODUCTION: A liver dysfunction induced by halogenated volatile anaesthetics is considered as a significant diagnostic problem. The aim of our report was to describe the first case of lethal hepatic failure in a female patient undergoing kidney transplantation (KTx) from a living donor after repeated sevoflurane anaesthesia. CASE PRESENTATION: A 47-year-old hypertensive and diabetic female patient received kidney from her 70-year-old mother. There was an immediate graft function and around 800 ml of blood loss on the abdominal drains, which gradually decreased after the erythrocyte and fresh frozen plasma (FFP) substitution. On the first postoperative (p.o.) day she gradually became anuric and overweighed at the next day undergoing dialysis. Because of prolonged hypotension and somnolence she required reintubation. The second day transaminases increased (AST&ALT>700, LDH>1200 U/L). On the third p.o. day she was urgently reoperated because of a sudden excessive bleeding. However, there was a rather slow flow of tears from the whole operative field that was even more excessive after the operation with signs of a consumptive coagulopathy. She was adequately substituted until the bleeding stopped more than 24 hrs after its onset. The new laboratory results showed further increase in transaminazes (3300 U/L-ALT, 5100-AST, 8900-LDH) and ultrasound investigation confirmed an extensive toxic hepatic lesion. On the fourth p.o. night the patient was stable, diuresis rate was at 100 ml/hour, but in the morning she became hyposaturated because of an increased bronchial secretion. The dialysis could not improve the cardio-respiratory insufficiency and she died 30min later. CONCLUSIONS: This case report suggests that sevoflurane can lead to a severe hepatotoxicity in at-risk individuals with repeated sevoflurane anaesthesia, having renal failure, in those with a preoperative known history of cardiovascular disorders, as well as in those with excessive extracellular volume. A particular precaution should be considered in cases of an elective surgery including organ transplantation.

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.