Long-term renal function following radical cystectomy and ileal conduit creation.

BACKGROUND: Treatment for bladder cancer includes radical cystectomy (RC) and urinary diversion; RC is associated with long-term morbidity, kidney impairment and mortality. AIM: To identify risk factors associated with postoperative long-term kidney function and mortality. METHODS: Retrospective study of patients with RC and urinary diversion in Beaumont Hospital from 1996 to 2016. We included patients who had follow-up at least 2 years post-procedure. We assessed estimated glomerular filtration rate (eGFR) preoperatively and yearly post-procedure, dialysis commencement and mortality. Cox and Fine-Gray regression analyses were applied; p-value < 0.05 was considered significant. RESULTS: We included 264 patients, median age 68.3 years, 73.7% males. The most common diagnosis was bladder cancer 93.3%, TNM stages T ≥ 2 75.9%, N ≥ 1 47.6% and M1 28%. The median eGFR preoperative was 65.8 ml/min/1.73m2 and after 2 years 58.2 ml/min/1.73m2 (p: 0.009); 5.3% required chronic dialysis and 32.8% had a decrease > 10 ml/min/1.73m2. Risk factors associated with ESKD and start dialysis included younger age (HR: 0.90, CI 95% 0.87-0.94) and lower pre-operative eGFR (HR: 0.97, CI 95% 0.94-1.00). Overall mortality was 43.2% and 54.1% at 5 and 10 years, respectively; risk factors were older age (HR: 1.04, CI 95% 1.02-1.06), tumour stage T ≥ 2 (HR: 2.22, CI 95% 1.39-3.54) and no chemotherapy (HR: 1.72, CI 95% 1.18-2.51). Limitations include retrospective design, absence of control group and single centre experience. CONCLUSIONS: Patients with RC are at risk of progressive kidney function deterioration and elevated mortality and the main risk factors associated were age and preoperative eGFR. Regular monitoring of kidney function will permit early diagnosis and treatment.

The potential for artificial intelligence to predict clinical outcomes in patients who have acquired acute kidney injury during the perioperative period.

Acute kidney injury (AKI) is a common medical problem in hospitalised patients worldwide that may result in negative physiological, social and economic consequences. Amongst patients admitted to ICU with AKI, over 40% have had either elective or emergency surgery prior to admission. Predicting outcomes after AKI is difficult and the decision on whom to initiate RRT with a goal of renal recovery or predict a long-term survival benefit still poses a challenge for acute care physicians. With the increasing use of electronic healthcare records, artificial intelligence may allow postoperative AKI prognostication and aid clinical management. Patients will benefit if the data can be readily accessed andregulatory, ethical and human factors challenges can be overcome.

Is Bigger Better? Living Donor Kidney Volume as Measured by the Donor CT Angiogram in Predicting Donor and Recipient eGFR after Living Donor Kidney Transplantation.

BACKGROUND: The role of kidney volume measurement in predicting the donor and recipient kidney function is not clear. METHODS: We measured kidney volume bilaterally in living kidney donors using CT angiography and assessed the association with the donor remaining kidney and recipient kidney (donated kidney) function at 1 year after kidney transplantation. Donor volume was categorized into tertiles based on lowest, middle, and highest volume. RESULTS: There were 166 living donor and recipient pairs. The mean donor age was 44.8 years (SD ± 10.8), and donor mean BMI was 25.5 (SD ± 2.9). The recipients of living donor kidneys were 64% male and had a mean age of 43.5 years (SD ± 13.3). Six percent of patients experienced an episode of cellular rejection and were maintained on dialysis for a mean of 18 months (13-32) prior to transplant. Kidney volume was divided into tertiles based on lowest, middle, and highest volume. Kidney volume median (range) in tertiles 1, 2, and 3 was 124 (89-135 ml), 155 (136-164 ml), and 184 (165-240 ml) with donor eGFR ml/min (adjusted for body surface area expressed as ml/min/1.73 m2) at the time of donation in each tertile, 109 (93-129), 110 (92-132), and 101 ml/min (84-117). The median (IQR) eGFR in tertiles 1 to 3 in kidney recipients at 1 year after donation was 54 (44-67), 62 (50-75), and 63 ml/min (58-79), respectively. The median (IQR) eGFR in tertiles 1 to 3 in the remaining kidney of donors at 1 year after donation was 59 (53-66), 65 (57-72), and 65 ml/min (56-73), respectively. CONCLUSION: Bigger kidney volume was associated with better eGFR at 1 year after transplant in the recipient and marginally in the donor remaining kidney.

Calcium and phosphate levels after kidney transplantation and long-term patient and allograft survival.

BACKGROUND: Non-traditional cardiovascular risk factors, including calcium and phosphate derangement, may play a role in mortality in renal transplant. The data regarding this effect are conflicting. Our aim was to assess the impact of calcium and phosphate derangements in the first 90 days post-transplant on allograft and recipient outcomes. METHODS: We performed a retrospective cohort review of all-adult, first renal transplants in the Republic of Ireland between 1999 and 2015. We divided patients into tertiles based on serum phosphate and calcium levels post-transplant. We assessed their effect on death-censored graft survival and all-cause mortality. We used Stata for statistical analysis and did survival analysis and spline curves to assess the association. RESULTS: We included 1525 renal transplant recipients. Of the total, 86.3% had hypophosphataemia and 36.1% hypercalcaemia. Patients in the lowest phosphate tertile were younger, more likely female, had lower weight, more time on dialysis, received a kidney from a younger donor, had less delayed graft function and better transplant function compared with other tertiles. Patients in the highest calcium tertile were younger, more likely male, had higher body mass index, more time on dialysis and better transplant function. Adjusting for differences between groups, we were unable to show any difference in death-censored graft failure [phosphate = 1.14, 95% confidence interval (CI) 0.92-1.41; calcium = 0.98, 95% CI 0.80-1.20] or all-cause mortality (phosphate = 1.10, 95% CI 0.91-1.32; calcium = 0.96, 95% CI 0.81-1.13) based on tertiles of calcium or phosphate in the initial 90 days. CONCLUSIONS: Hypophosphataemia and hypercalcaemia are common occurrences post-kidney transplant. We have identified different risk factors for these metabolic derangements. The calcium and phosphate levels exhibit no independent association with death-censored graft failure and mortality.

Factors associated with SARS-CoV-2 infection in patients attending an acute hospital ambulatory assessment unit.

To describe the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mild-to-moderate patients attending for assessment. This observational study was conducted in a Model 4 tertiary referral center in Ireland. All patients referred for SARS-CoV-2 assessment over a 4-week period were included. Patient demographics, presenting symptoms, comorbidities, medications, and outcomes (including length of stay, discharge, and mortality) were collected. Two hundred and seventy-nine patients were assessed. These patients were predominantly female (62%) with a median age of 50 years (SD 16.9). Nineteen (6.8%) patients had SARS-CoV-2 detected. Dysgeusia was associated with a 16-fold increased prediction of SARS-CoV-2 positivity (p = .001; OR, 16.8; 95% CI, 3.82-73.84). Thirteen patients with SARS-COV-2 detected (68.4%) were admitted, in contrast with 38.1% (99/260) of patients with SARS-CoV-2 non-detectable or not tested (p = .001). Female patients were more likely to be hospitalized (p = .01) as were current and ex-smokers (p = .05). We describe olfactory disturbance and fever as the main presenting features in SARS-CoV-2 infection. These patients are more likely to be hospitalized with increased length of stay; however, they make up a minority of the patients assessed. "Non-detectable" patients remain likely to require prolonged hospitalization. Knowledge of predictors of hospitalization in a "non-detectable" cohort will aid future planning and discussion of patient assessment in a SARS-CoV-2 era.

Acute kidney injury secondary to a combination of renin-angiotensin system inhibitors, diuretics and NSAIDS: "The Triple Whammy".

BACKGROUND: Renin-angiotensin system inhibitors (ACEI/ARB-II), diuretics and NSAIDs, a combination known as "Triple Whammy", can result in decreased glomerular filtration rate (GFR) and acute kidney injury (AKI). Objectives: To describe the incidence of AKI for each drug type and their combinations. To define the profile of patients admitted for drug-related AKI secondary to Triple Whammy drugs (AKITW), with an assessment of costs and mortality. METHODS: A retrospective observational 15-month study developed in three stages: - First: a cross-sectional stage to identify and describe hospitalizations due to AKITW. - Second: a follow-up stage of an outpatient cohort consuming these drugs (15,307 subjects). - Third: a cohort stage to assess costs and mortality, which compared 62 hospitalized patients with AKITW and 62 without AKI, paired by medical specialty, sex, age and comorbidity according to their Clinical Risk Groups. RESULTS: There were 85 hospitalization episodes due to AKITW, and 78% of patients were over the age of 70. The incidence of AKITW in the population was 3.40 cases/1000 users/year (95% CI: 2.59-4.45). By categories, these were: NSAIDs + diuretics 8.99 (95% CI: 3.16-25.3); Triple Whammy 8.82 (95% CI: 4.4-17.3); ACEI/ARB-II + diuretics 6.87 (95% CI: 4.81-9.82); and monotherapy with diuretics 3.31 (95% CI: 1.39-7.85). Mean hospital stay was 7.6 days (SD 6.4), and mean avoidable costs were estimated at €214,604/100,000 inhabitants/year. Mortality during hospitalization and at 12 months was 11.3% and 38.7% respectively, and there were no significant differences when compared with the control group. CONCLUSIONS: Treatment with ACEI, ARB-II, diuretics and/or NSAIDs shows a high incidence of hospitalization episodes due to AKI; diuretics as monotherapy or dual and triple combination therapy cause the highest incidence. AKITW involves high health care costs and avoidable mortality.

Fracaso renal agudo secundario a combinación de inhibidores del sistema renina-angiotensina, diuréticos y AINES. 'La Triple Whammy' / Acute kidney failure secondary to a combination of renin-angiotens in system inhibitors, diuretics and NSAIDS. The 'Triple Whammy'

Introducción: Inhibidores del sistema renina-angiotensina (IECAS/ARA II), diuréticos y AINES, combinación conocida como 'Triple Whammy', pueden producir descenso de filtradoglomerular y fracaso renal agudo (FRA). Objetivos: Describir la incidencia de FRA para cada tipo de fármaco y sus combinaciones. Caracterizar el perfil de paciente que ingresa por FRA extrahospitalario secundario a fármacos de la Triple Whammy (FRAETW), evaluando costes y mortalidad. Métodos: estudio observacional retrospectivo realizado durante 15 meses y desarrollado en tres etapas:- 1º Etapa transversal de identificación y descripción de los ingresos hospitalarios por FRAETW.- 2º Etapa de seguimiento de una cohorte ambulatoria consumidora de estos fármacos (15.307 consumidores)- 3º Etapa de cohortes para evaluar costes y mortalidad, contrastando 62 pacientes ingresados con FRAETW, con 62 pacientes sin FRA, apareados por especialidad médica, sexo, edad y comorbilidad según Clinical Risk Groups. Resultados: 85 ingresos por FRAETW, 78% mayores de 70 años. Incidencia poblacional de FRAETW: 3,40 casos/1.000 consumidores/año (IC95% 2,59-4,45). Por categorías: AINES + diuréticos 8,99 (IC95% 3,16-25,3), la 'Triple Whammy' 8,82 (IC 95% 4,4-17,3), IECA/ARA II+ diuréticos 6,87 (IC95% 4,81-9,82) y la monoterapia con diuréticos 3,31(IC95% 1,39-7,85). Estancia media 7,6 días (DE 6,4), estimándose coste medio evitable de 214.604 Euros/100.000habitantes/año. Mortalidad del 11,3% durante el ingreso y del 38,7% a los 12 meses, sin diferencias significativas con los controles. Conclusiones: El tratamiento con IECA, ARA II, diuréticos y/o AINES presenta elevada incidencia de ingreso por FRA, siendo los diuréticos en monoterapia, doble y triple terapia combinada los que ocasionan la mayor incidencia. El FRAETW supone elevados costes sanitarios y muertes evitables (AU)

Introduction: Renin-angiotens in system inhibitors (ACEIs/ARBs), diuretics and non-steroidalanti-inflammatory drugs (NSAIDs) - a combination also known as the Triple Whammy(TW) - can reduce the glomerular filtration rate (GFR) and lead to acute kidney injury (AKI). Objective: To study the incidence of AKI due to any type or combination of drugs. To describe patient profiles admitted for outpatient AKI due to TW drugs (AKI-TW), hospital costs and mortality. Methods: This was a 15-month retrospective observational study, developed in 3 stages:- First stage: Cross-sectional description of outpatient AKI-TW hospitalisation episodes.- Second stage: Outpatient drug consumer cohort follow-up (15,307 individuals).- Third stage: Mortality and costs evaluation. It included 62 patients with AKI-TW and62 without, paired by medical specialty, gender, age and comorbidity according to the Clinical Risk Groups (CRG) system. Results: There were 85 hospitalisation episodes attributed to AKI-TW; 78% of cases were older than 70 years. Incidence of AKI-TW was 3.40 cases/1000 users/year (95% CI: 2.59-4.45). Double therapy with NSAIDs + diuretics was 8.99 (95%CI 3.16-25.3); Triple Whammy was 8.82 (95% CI 4.4-17.3); double therapy with ACEIs/ARBs + diuretics 6.87 (95% CI 4.81-9.82); and diuretics in monotherapy 3.31(95% CI 1.39-7.85). Mean stay for cases was 7.6 days (SD6.4) and total avoidable costs were Euros 214,604/100,000 inhabitants/year. Mortality during hospital stay and at 12 months was 11.3% and 40.3% respectively, without significant differences between groups. Conclusions: Triple Whammy therapy is associated with a high incidence of hospital admission for AKI. Diuretics in monotherapy, double and combined triple therapy are associated with a high incidence of AKI. AKI-TW involves high hospital costs andavoidable mortality (AU)

The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis.

BACKGROUND: The aim of this work was to analyze the number and distribution of circulating monocytes, and of their CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in treatment-naive patients with rheumatoid arthritis (RA), and to determine their value in predicting the clinical response to methotrexate (MTX) treatment. METHODS: This prospective work investigated the number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, in 52 untreated patients with RA before MTX treatment, and at 3 and 6 months into treatment, using flow cytometry. RESULTS: The absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-), CD14(+high)CD16(+) and CD14(+low)CD16(+) subset cells, were significantly higher in MTX non-responders than in responders and healthy controls before starting and throughout treatment. Responders showed normal numbers of monocytes, and of their subset cells, over the study period. The pre-treatment absolute number of circulating monocytes, and the numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, were found to be predictive of the clinical response to MTX, with a sensitivity and specificity of >70% and >88%, respectively. CONCLUSIONS: Treatment-naive patients with RA showed an anomalous distribution of circulating monocyte subsets, and an anomalous number of cells in each subset. A higher pre-treatment number of circulating monocytes, and higher numbers of CD14(+high)CD16(-) and CD14(+high)CD16(+) subset cells, predict a reduced clinical response to MTX in untreated patients with RA.

Molecular mediators of favism-induced acute kidney injury.

Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury.

Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis.

INTRODUCTION: The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFα) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment. METHODS: This prospective work investigated the number of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNFα treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control. RESULTS: Non-responder patients with RA show an increased number of monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNFα treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders. CONCLUSIONS: The absolute number of circulating monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.

Loss of surface antigens is a conserved feature of apoptotic lymphocytes from several mammalian species.

Human lymphocytes lose the expression of lineage antigens (LAgs) along apoptosis. Our aim was to extent our previous studies of LAg loss to rodent species, quantifying LAg expression on apoptotic murine lymphocytes using flow cytometry to measure alterations in cell permeability, phosphatidylserine exposure and caspase activation of CD3, CD5, CD4, CD8, CD19 and CD28 LAgs in highly purified lymphocyte populations. We found loss of expression by apoptotic cells of all LAgs studied in the three species analyzed except for CD3 antigen in mouse. We also found an early, rapid and dramatic reduction in the expression of CD28 by early apoptotic cells. We found several homologies across the three species in the kinetic of loss of several LAgs such as CD5, CD4 and CD28. These data suggest that the loss of expression of LAgs by apoptotic lymphocytes is a common and conserved feature of lymphocytes undergoing apoptosis in several mammalian species.

Inhaled IL-2 induces systemic immunomodulation in patients with renal cell carcinoma and lung metastasis.

The peripheral blood lymphocytes of eight patients with metastatic renal cell carcinoma, and of eight healthy volunteers were analyzed by four-color flow cytometry to characterize the immunophenotypic alterations manifested, determine the prevalence of lymphocyte apoptosis, and detect evidence of the systemic effect of inhaled IL-2. The T, B and NK lymphocytes of untreated patients were found to have undergone profound changes characterized by an increase in susceptibility to both spontaneous and mitogen-induced ex vivo apoptosis, a modified distribution of the main lymphocyte populations in the peripheral blood, and alterations in activation status. An increase in the proportion of regulatory T cells was also seen in these patients. Treatment with inhaled IL-2, however, normalized the rate of apoptosis in all the lymphocyte subpopulations studied, as well as their distribution and activation status. These findings demonstrate that inhaled IL-2 has systemic immunomodulatory effects.