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.

Acute interstitial nephritis with podocyte foot-process effacement complicating Plasmodium falciparum infection.

BACKGROUND: Malarial acute renal failure (MARF) is a component of the severe malaria syndrome, and complicates 1-5% of malaria infections. This form of renal failure has not been well characterized by histopathology. CASE PRESENTATION: A 44 year-old male presented to the emergency department with a 5-day history of fever and malaise after returning from Nigeria. A blood film was positive for Plasmodium falciparum. His creatinine was 616 µmol/L coming from a normal baseline of 89 µmol/L. He had a urine protein:creatinine ratio of 346 mg/mmol (4.4 g/L). He required dialysis. A renal biopsy showed acute interstitial nephritis with podocyte foot-process effacement. He was treated with artesunate and his renal function improved. At 1 year follow-up his creatinine had plateaued at 120 µmol/L with persistent low-grade proteinuria. CONCLUSION: Acute interstitial nephritis and podocyte foot-process effacement might be under-recognized lesions in MARF. Studying the mechanisms of MARF could give insight into the immunopathology of severe malaria.

Oxidation-Mediated Fingering in Liquid Metals.

We identify and characterize a new class of fingering instabilities in liquid metals; these instabilities are unexpected due to the large interfacial tension of metals. Electrochemical oxidation lowers the effective interfacial tension of a gallium-based liquid metal alloy to values approaching zero, thereby inducing drastic shape changes, including the formation of fractals. The measured fractal dimension (D=1.3±0.05) places the instability in a different universality class than other fingering instabilities. By characterizing changes in morphology and dynamics as a function of droplet volume and applied electric potential, we identify the three main forces involved in this process: interfacial tension, gravity, and oxidative stress. Importantly, we find that electrochemical oxidation can generate compressive interfacial forces that oppose the tensile forces at a liquid interface. The surface oxide layer ultimately provides a physical and electrochemical barrier that halts the instabilities at larger positive potentials. Controlling the competition between interfacial tension and oxidative (compressive) stresses at the interface is important for the development of reconfigurable electronic, electromagnetic, and optical devices that take advantage of the metallic properties of liquid metals.

The Irish living kidney donor program - why potential donors do not proceed to live kidney donation?

BACKGROUND: Living donation is not only a method to increase access to kidney transplantation but can also offer superior outcomes. We report the experience of the living donor (LD) program in the Republic of Ireland and explore reasons why potential donors do not proceed to live donation. METHODS: Retrospective cohort study of all potential donors from January 2000 to March 2014 who presented wishing to undergo donor work-up and their subsequent outcomes. RESULTS: A total of 956 donors for 496 recipients contacted the live kidney donation program of which 883 potential donors proceeded to the initial stage of assessment. The donor dropout rate at this stage was 64.2% (614/956 potential donors did not proceed to further evaluation). Thereafter, 269 (28.1%) donors underwent further assessment by the multidisciplinary team. In total, 93 (9.7%) donors were declined following this assessment with 176 (18.4%) donors ultimately proceeding to live kidney donation. The major reason for declining a donor was a medical contraindication (n = 63, 67.7%). In term of recipients, 54.2% (n = 269/496) had a potential donor proceed for further assessment of which 65.4% (n = 176/269) ultimately proceeding to live donation. CONCLUSION: Further evaluation of the declined donor group is warranted to allow for expansion of the LD program.

Tacrolimus trough-level variability predicts long-term allograft survival following kidney transplantation.

AIMS: The purpose of this study is to investigate tacrolimus trough-level variability from 3 to 12 months following transplantation and its association with allograft survival in renal transplant recipients. MATERIALS AND METHODS: In this observational cohort study, tacrolimus trough-level variability was used as the predictor of all-cause allograft failure (defined as return to dialysis) and patient survival (all-cause mortality). RESULTS: In total, 394 transplants were included in the analysis. Sixty-two transplants failed during the study. Tacrolimus trough-level variability across quartile groups were: Q1 median variability 12.5 %, range 4.76-15.71 % (n = 99), Q2 median variability 18.17 %, range 15.74-21.29 % (n = 96), Q3 median variability 24.63 % range 21.42-28.88 % (n = 100), Q4 median variability 36.91 %, range 28.91-81.9 % (n = 99). Higher tacrolimus trough-level variability was associated with inferior allograft survival in univariate models [hazard ratio per quartile increase (HR), 1.46, 95 % CI 1.16-1.83, p value = 0.001] and multivariate models (HR 1.36, 95 % CI 1.05-1.78, p value = 0.019). Higher tacrolimus trough-level variability was not associated with patient survival; univariate model (HR 1.25, 95 % CI 0.90-1.74, p value = 0.17), multivariate model (HR 1.25, 95 % CI 0.86-1.83, p value = 0.23). CONCLUSIONS: Inferior renal allograft survival was observed in recipients with higher variability in tacrolimus trough-levels.

The Irish Kidney Gene Project--Prevalence of Family History in Patients with Kidney Disease in Ireland.

BACKGROUND: The prevalence of kidney disease (KD) due to inherited genetic conditions in Ireland is unknown. The aim of this study was to characterise an adult kidney disease population in Ireland and to identify familial clusters of kidney disease within the population. METHODS: This was a multicenter cross-sectional study of patients with kidney disease in the Republic of Ireland, from January 2014 to September 2014, recruiting from dialysis units and out-patient renal departments. A survey was performed by collecting data on etiology of kidney disease and whether a family history of kidney disease exists. Medical records were cross-referenced to confirm the etiology of kidney disease. RESULTS: A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17-94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was reported by 629 participants (34.2%). Excluding polycystic kidney disease (n = 134, 7.3%), a positive family history was reported by 495 participants (26.9%). Kidney disease due to an unknown etiology was the commonest etiology in the non-polycystic kidney disease group with a positive family history (10.6%, n = 67). Kidney diseases that are not classically associated with familial inheritance including tubulo-interstitial kidney disease, congenital abnormalities of the kidney and urinary tract and glomerulonephritis demonstrated familial clustering. CONCLUSION: In an Irish non-polycystic kidney disease population, 26.9% reports a positive family history. The commonest etiology of kidney disease in the positive family history cohort, excluding autosomal dominant polycystic kidney disease, was kidney disease due to unknown etiology. Examining families with kidney disease provides an opportunity to better understand disease pathogenesis and potentially identify genetic predispositions to kidney disease.

Prevention of sudden cardiac death in hemodialysis patients.

One quarter of all hemodialysis patients will succumb to sudden cardiac death (SCD), a rate far exceeding that observed in the general population. A high prevalence of atherosclerotic coronary artery disease amongst patients with end-stage kidney disease (ESKD) partly explains this exaggerated risk. However, uremia and dialysis related factors are also of critical importance. Interventions aimed at preventing SCD have been inadequately studied in patients with ESKD. Data extrapolated from non-renal populations cannot necessarily be applied to hemodialysis patients, who possess relatively unique risk factors for SCD including "uremic cardiomyopathy", electrolyte shifts, fluctuations in intravascular volume and derangements of mineral and bone metabolism. Pending data derived from proposed randomized controlled clinical trials, critical appraisal of existing evidence and the selective application of guidelines developed for the general population to dialysis patients are required if therapeutic nihilism, or excessive intervention, are to be avoided. We discuss the evidence supporting a role for medical therapies, dialysis prescription refinements, revascularization procedures and electrical therapies as potential interventions to prevent SCD amongst hemodialysis patients. Based on current best available evidence, we present suggested strategies for the prevention of arrhythmia-mediated death in this highly vulnerable patient population.

C3 glomerulopathy: clinicopathologic features and predictors of outcome.

BACKGROUND AND OBJECTIVES: The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. RESULTS: Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. CONCLUSIONS: Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.

Neuropathy in the hemodialysis population: a review of neurophysiology referrals in a tertiary center.

This was a retrospective observational study of neurophysiology referrals over 8 years from a tertiary referral center in Ireland. A total of 68 of the 73 referrals yielded one or more abnormalities. Thirty-nine (53%) patients had one or more mononeuropathies; iatrogenic mononeuropathies believed to be associated with arterio-venous fistula creation occurred in 15 patients. Polyneuropathy was identified in 43 patients (59%). Access to an experienced neurophysiology department offers valuable insight into dialysis-associated neuropathies, especially when associated with arterio-venous fistulae.

Re-infection following sustained virological response with a different hepatitis C virus genotype: implications for infection control policy.

We report the case of a 45-year-old haemodialysis patient who achieved a sustained virological response (SVR) following pegylated interferon therapy for hepatitis C virus (HCV) genotype 2 infection. He was subsequently cohorted with other HCV-infected dialysis patients and became re-infected with HCV genotype 3a. Epidemiological and molecular investigations identified a highly viraemic HCV genotype 3a-infected dialysis patient as the likely source of this infection. This critical incident informed a revision to local and national infection control policy regarding the dialysis management of patients who achieve an SVR following anti-viral treatment.