High rates of psychological distress, mental health diagnoses and suicide attempts in people with chronic kidney disease in Ireland.

BACKGROUND: People with chronic kidney disease (CKD) experience high levels of psychological distress, which is associated with higher mortality and adverse health outcomes. Little is known about the rates of a range of mental health difficulties or rates of suicide attempts in people with CKD. METHODS: Individuals with CKD (n = 268; age range 18-94 years, mean = 49.96 years) on haemodialysis (n = 79), peritoneal dialysis (n = 46), transplant recipients (n = 84) and who were not on renal replacement therapy (RRT; n = 59) were recruited through the Irish Kidney Association social media pages and three Irish hospitals. Participants completed surveys to gather demographics and mental health histories, the Hospital Anxiety and Depression Scale (HADS) and the 12-item Short Form Health Survey (SF-12) to measure health-related quality of life (HRQoL). RESULTS: A total of 23.5% of participants self-reported they had received a mental health diagnosis, with depression (14.5%) and anxiety (14.2%) being the most common, while 26.4% of participants had experienced suicidal ideation and 9.3% had attempted suicide. Using a clinical cut-off ≥8 on the HADS subscales, current levels of clinically significant anxiety and depression were 50.7% and 35.4%, respectively. Depression levels were slightly higher for those on haemodialysis compared with those with a transplant and those not on RRT. Depression, anxiety and having a mental health diagnosis were all associated with lower HRQoL. CONCLUSIONS: People with CKD in Ireland experience high levels of psychological distress, mental health difficulties, suicidal ideation and suicide attempts. The identification of and intervention for mental health difficulties in CKD should be prioritised in clinical care.

Clinical Implementation and Initial Experience of Neutrophil Gelatinase-Associated Lipocalin Testing for the Diagnostic and Prognostic Assessment of Acute Kidney Injury Events in Hospitalized Patients.

INTRODUCTION: The use of novel kidney injury biomarkers has been shown to improve diagnostic assessment and prognostic prediction in various populations with acute kidney injury (AKI), but their use in a standard clinical practice have been rarely reported. METHODS: We reported the clinical implementation of neutrophil gelatinase-associated lipocalin (NGAL) measurement for routine AKI diagnostic workup of patients receiving nephrology consultation in a tertiary academic centre. Specific focus was made on the diagnostic performance to discriminate functional ("pre-renal") from intra-renal AKI and to predict AKI progression. RESULTS: Forty-five urine NGAL (uNGAL) and 25 plasma NGAL (pNGAL) samples in the first 50 consecutive patients were analysed. KDIGO Stage 1, 2, 3 AKI, and renal replacement therapy occurred in 10%, 40%, 50%, and 24% of cases, respectively. The uNGAL was lower in patients with transient AKI (<48 h) and no sign of urinary tract infections (37 [25-167] ng/mL) than sustained or progressive AKI (298 [74-1,308] ng/mL) (p = 0.016), while pNGAL did not discriminate transient (264 [100-373] ng/mL) from persistent AKI (415 [220-816] ng/mL) (p = 0.137). The median uNGAL level was 63 (35-1,123) ng/mL for functional/pre-renal AKI and 451 (177-1,315) ng/mL for intra-renal AKI (p = 0.043), while the pNGAL was 264 (114-468) and 415 (230-816) ng/mL (p = 0.235), respectively. CONCLUSION: NGAL, as part of the routine workup, is useful for diagnostic and prognostic assessment of new-onset AKI in clinical practice. Interpretation of an increased NGAL level should be clinically evaluated in its clinical context, particularly considering concomitant infection (urinary or systemic). Clinical adoption of emerging AKI biomarkers as diagnostic tests in clinical practice should be further encouraged.

Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in a tertiary nephrology centre.

Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3rd August, 2018 and 18th January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean ± SD BMI was 28.6 ± 5.8 kg/m2 (n = 374). Overweight and obesity class 1 were more common in males (P = .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean ± SD age, n (%) female and median[IQR] eGFR were 64.1 ± 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r = 0.21, P = .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m2 higher in those treated with 4-5 versus 0-1 antihypertensives (P = .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.

Paediatric asthma deaths in Ireland: 2006-2016.

BACKGROUND: Asthma is the commonest chronic condition in childhood but mortality from asthma during childhood is a rare occurrence. No national review into asthma deaths in children in Ireland has been performed to date. AIM: The aim of this study was to review all cases of mortality from asthma in the paediatric population over a 10-year period in Ireland. The objective was to identify risk factors contributing to asthma deaths in children. METHODS: A retrospective chart review was performed on cases reported to the National Paediatric Mortality Register (NPMR) with asthma as the primary cause of death. RESULTS: Eleven cases were reported. Consent was obtained for six cases. Median age at death was 11.8 years. All patients presented to the Emergency Department (ED) in asystole. Fifty percent of patients had acute symptoms prior to the fatal episode. None of the patients was attending secondary services. Only 60% had a written personalised asthma action plan (PAAP). CONCLUSION: Our data suggests that most patients present in extremis and have little warning signs of severity of the attack. Better education on recognition of symptoms and initiation of action plans is required.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. CONCLUSION: Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

A deletion at CMV UL54 codon 524 without co-existing resistance-associated mutation at UL97 confers resistance to ganciclovir: A case report.

Sequencing of Cytomegalovirus (CMV) genes to investigate antiviral resistance is a growing area of interest as treatment for CMV infection becomes more widely available and used. Using conventional sequencing methods, we identified a deletion in UL54 gene, del524, which conferred resistance to ganciclovir in a renal transplant recipient, in the absence of a co-existing resistance-conferring mutation in UL97 gene. This case report reinforces that both UL97 and UL54 genes should be sequenced when exploring CMV antiviral resistance as mutations have been identified in both genes independently of each other.

The prevalence of occult hepatitis B virus (HBV) infection in a large multi-ethnic haemodialysis cohort.

BACKGROUND: Haemodialysis patients are at increased risk of exposure to blood borne viruses. To reduce transmission in the UK, all haemodialysis patients are regularly screened, and if susceptible to Hepatitis B virus (HBV) infection, vaccinated. METHODS: This retrospective study was undertaken to determine the HBV immune status in a large dialysis cohort and the prevalence of occult HBV infection, defined as the presence of anti-HBcore antibody (anti-HBcAb) and HBV DNA without detectable HB surface antigen (HBsAg). Information on HBV status was retrieved from haemodialysis patients under the care of The Royal Free Hospital, London, UK between 2009-2010. Available sera from 138 of 161 anti-HBcAb positive/HBsAg negative individuals were anonymised and tested for HBV DNA by a real time quantitative PCR. RESULTS: 15 (2%) of 793 patients had chronic HBV infection (HBsAg positive). 161 (20%) were anti-HBcAb positive but HBsAg negative suggesting past infection. 335 (54%) of the remaining 617 patients were considered immune following vaccination (anti-HBsAb > 10 IU/L). Three (2.2%) of the 138 anti-HBcAb positive, HBsAg negative patients had detectable HBV DNA (3, 5 and 9 IU/ml). Standard liver function tests were normal in these patients. CONCLUSIONS: In a large multi-ethnic London haemodialysis cohort, 20% patients had evidence of past HBV infection. Despite this, the prevalence of occult HBV was found to be low and the very low levels of HBV DNA detected are unlikely to pose a nosocomial transmission risk in the presence of robust vaccination and infection control measures.

Identification of ß2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.

PURPOSE: Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals. EXPERIMENTAL DESIGN: The study included 34 renal transplant patients with histologically proven CAN and 36 patients with normal renal transplant function. High-throughput proteomic profiles were generated from urine samples with three different ProteinChip arrays by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Following SELDI, a biomarker pattern software analysis was performed which led to the identification of a novel biomarker pattern that could distinguish patients with CAN from those with normal renal function. RESULTS: An 11.7 kDa protein identified as ß2 microglobulin was the primary protein of this biomarker pattern, distinguishing CAN from control patients (receiver operator characteristic [ROC]=0.996). SELDI-TOF-MS comparison of purified ß2 microglobulin protein and CAN urine demonstrated identical 11.7 kDa protein peaks. Significantly, higher concentrations of 2 microglobulin were found in the urine of patients with CAN compared with the urine of normal renal function transplant recipients (p<0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Although further validation in a larger more diverse patient population is required to determine if this ß2 microglobulin protein biomarker will provide a potential means of diagnosing CAN by noninvasive methods in a clinical setting, this study clearly shows a capability to stratify control and disease patients.

Acute kidney injury in patients admitted to a liver intensive therapy unit with paracetamol-induced hepatotoxicity.

BACKGROUND: Paracetamol overdose can cause acute kidney injury (AKI) independent of its hepatotoxic effects. We aimed to determine the prevalence of AKI (AKI Network definition) in those with paracetamol-induced hepatotoxicity, identify factors associated with development, assess impact on the outcomes of patient survival and length of stay and determine the proportion of patients recovering renal function (estimated glomerular filtration rate > 60 mL/min) by the time of hospital discharge or transfer out. METHODS: Between 2000 and 2007, patients admitted to a tertiary referral liver intensive therapy unit (LITU) with paracetamol-induced hepatotoxicity were identified from a prospectively maintained database and evaluated. RESULTS: Those receiving a liver transplant were excluded (n = 54), leaving 302 patients. Renal function remained normal in 21%, the remainder developing AKI (Stages 1-8%, 2-6% and 3-65%). Vasopressor requirement, mechanical ventilation, higher admission phosphate and lower sodium levels along with a higher Day 3 lactate and lower haematocrit were associated with AKI. In survivors with AKI, 51% had recovery of renal function, while 7% remained dialysis dependant although none required it chronically. Overall, there was 25% mortality, all having Stage 3 AKI but AKI was only a univariate not multivariate predictor of reduced patient survival. AKI independently predicted longer length of stay. CONCLUSIONS: AKI is very common in critically ill patients with paracetamol-induced hepatotoxicity requiring LITU admission. Although outcomes are poorer with AKI than with normal renal function, they are better than those found in other intensive therapy unit populations. Gradual recovery of renal function is seen in all patients.

Critical care issues in patients after liver transplantation.

The majority of patients who undergo liver transplantation (LT) spend some time in the intensive care unit during the postoperative period. For some, this is an expected part of the immediate posttransplant recovery period, whereas for others, the stay is more prolonged because of preexisting conditions, intraoperative events, or postoperative complications. In this review, 4 topics that are particularly relevant to the postoperative intensive care of LT recipients are discussed, with an emphasis on current knowledge specific to this patient group. Infectious complications are the most common causes of early posttransplant morbidity and mortality. The common patterns of infection seen in patients after LT and their management are discussed. Acute kidney injury and renal failure are common in post-LT patients. Kidney injury identification, etiologies, and risk factors and approaches to management are reviewed. The majority of patients will require weaning from mechanical ventilation in the immediate postoperative period; the approach to this is discussed along with the approach for those patients who require a prolonged period of mechanical ventilation. A poorly functioning graft requires prompt identification and appropriate management if the outcomes are to be optimized. The causes of poor graft function are systematically reviewed, and the management of these grafts is discussed.

Risk score predicting decline in renal function postliver transplant: role in patient selection for combined liver kidney transplantation.

BACKGROUND: A combined liver and kidney transplantation (CLKT) is advocated for selected individuals with chronic kidney disease undergoing liver transplantation (LT). The aim was to develop a risk score to identify the patients whose estimated glomerular filtration rate (eGFR) would decline during the year post-LT to aid future patient selection for CLKT. METHODS: A training dataset of LT recipients was identified retrospectively from a prospectively compiled database (2000-2007). The eGFR was calculated at 1 year and those with an eGFR less than 30 mL/min were identified. Variables determined at the LT assessment were analyzed by logistic regression, discriminant function, and area under the receiver operating characteristic curve (AUC) analysis to develop the score. The score was validated in a prospective patient cohort. RESULTS: Three hundred sixty-eight LT recipients were followed up for 1 year (training dataset). The mean eGFR declined by 11.2+/-23.5 mL/min during that time (P<0.001). A pre-LT risk score to predict an eGFR less than 30 mL/min at 1-year post-LT was generated: -1.8+(1.5 if a history of hypertension)+(0.65 x proteinuria in g/24 hr)+(0.013 x serum creatinine in micromol/L)+(0.001 x duration of acute kidney injury or eGFR <60 mL/min in days). Reversible renal impairment should first be excluded. Progression was likely with a score more than 2.16. Sensitivity, specificity, and AUC were 99.2%, 100%, and 0.99, respectively. All, but one patient, in the validation cohort (n=149) were correctly classified. CONCLUSION: This information will complement previously published criteria for CLKT patient selection.

Renal biopsy in liver transplant recipients.

BACKGROUND: Renal impairment post-liver transplant (LT) is often attributed to calcineurin inhibitors (CNIs). A renal biopsy can be a useful tool but may be complicated in LT recipients. We aimed to determine the clinical scenarios that prompted a decision to perform a renal biopsy in this patient population, to assess histological findings and evaluate patient management and survival and renal outcome. METHODS: Information on clinical variables and renal histology was extracted from single-centre prospectively compiled databases from 1996 onwards. RESULTS: Over 2100 adults received an LT in the time period studied, and 54 of these (35 males and 19 females) were referred for renal review. Of these, 43% underwent a renal biopsy. They had a higher creatinine (P = 0.02), a greater deterioration in creatinine over the year prior to review and were more likely to be nephrotic (both P < 0.01). Histological findings included hypertensive changes (44%), CNI nephrotoxicity (48%), IgA nephropathy (9%), membranoproliferative glomerulonephritis (17%), acute tubular necrosis (4%), crescentic glomerulonephritis (4%) and diabetic nephropathy (9%). Major bleeding complications occurred in 17%. Treatment changed in the majority but, it was not significantly different in the two groups. Although initial renal function was worse in the biopsied group, final patient and renal survival did not differ between the two groups. CONCLUSION: A renal biopsy is a valuable tool in those with renal insufficiency and/or proteinuria and haematuria but the benefits must be weighed against the relatively high complication rate in LT recipients.

Identification of Apolipoprotein AI as a serum biomarker of chronic kidney disease in liver transplant recipients, using proteomic techniques.

Chronic kidney disease (CKD) is a common complication post-orthotopic liver transplantation (OLT). Development of CKD is detected by monitoring serum urea and creatinine, however disease can occasionally be at an advanced stage before they become abnormal. Therefore, more accurate parameters are required. In order to identify novel biomarkers of CKD, serum was obtained from 47 OLT recipients with CKD (glomerular filtration rate <60 mL/min) and 23 with normal renal function (glomerular filtration rate >90 mL/min). Using the proteomic technique SELDI-TOF-MS, three protein biomarkers (55.6 kDa, 9.5 kDa and 11.4 kDa) were identified that, together, could stratify patients into cases or controls with a sensitivity and specificity of 93.6 and 91.3%, respectively. The area under the curve was 0.94. The primary splitter of the groups at 55.6 kDa was an alternative version of a molecule at 27.8 kDa, which was subsequently identified by 1-D SDS-PAGE and LC-ESI-MS/MS to be Apolipoprotein AI. Protein expression was shown to be reduced in CKD, by both ELISA (p = 0.057) and Western blot analysis (p = 0.003). Apolipoprotein AI is a novel, accurate marker of CKD post-OLT. It does require further validation in a large, more diverse patient population but could potentially improve detection of CKD.

Chronic kidney disease post-liver transplantation.

BACKGROUND: Renal disease is a recognized complication of orthotopic liver transplantation (OLT). We aimed to determine the incidence of all stages of chronic kidney disease (CKD), as defined in the Kidney Disease Outcomes Quality Initiative Guidelines. We also wanted to determine the risk factors for development of CKD and its impact on patient survival. METHODS: All patients who underwent cadaveric OLT, from January 1993 until July 2004, were analysed. The glomerular filtration rate (GFR) was determined using the equation developed by the Modification of Diet in Renal Disease Study. Thirty potential risk factors were examined by univariate and multivariate ordinal logistic regression analysis. Kaplan-Meier survival analysis, the log-rank test and Cox regression analysis were performed to evaluate the survival data. RESULTS: A total of 230 patients were included (107 males and 123 females) with a mean age of 47.7 years (4.5-70.35). Mean follow-up was 5.57 years (0.53-16.5). The following was the 10 year cumulative incidence for each stage of CKD: 0/1, 9.61%; 2, 53.71%; 3, 56.77%; 4, 6.11%; 5, 2.62%. Female gender, age, pre-OLT proteinuria, lower GFR from 1 year and higher creatinine from 6 months were associated with progression of CKD. The use of tacrolimus had a favourable impact. A GFR <30 ml/min, the need for re-transplantation and fulminant hepatic failure were all associated with reduced patient survival. CONCLUSIONS: Moderate CKD was very prevalent. We identified the risk factors for progression of CKD and also that severe CKD was associated with reduced patient survival.

Pulmonary renal syndrome due to anti-GBM and IgM C-ANCA disease requiring the use of novel therapeutic agents.

There are several known causes for the clinical syndrome of pulmonary hemorrhage and acute renal failure. Here, we report a unique case of a 50-year-old man presenting in this manner. The initial diagnosis was one of antiglomerular basement membrane (anti-GBM) disease that responded well to steroids, cyclophosphamide, and plasma exchange (PE). The pulmonary hemorrhage resolved, but he remained dialysis dependent. However, despite falling anti-GBM titers, the symptoms relapsed and standard therapy was reinitiated with limited success. The anti-GBM antibody titer fell to zero despite clinical deterioration, prompting a search for an alternative diagnosis. He was found to be IgM anti-proteinase-3 antineutrophil cytoplasmic antibody (C-ANCA) positive. The pulmonary hemorrhage responded successfully to the use of intravenous immunoglobulin and the antilymphocyte monoclonal antibody CD52. To our knowledge, this is the first known case of IgM C-ANCA in association with anti-GBM disease. As such, it highlights the predominance of pulmonary hemorrhage in this condition, as well as the need to consider alternative therapies in refractory cases.