Urinary biomarkers predict progression and adverse outcomes of acute kidney injury in critical illness.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation study is a prospective cohort study of critically ill patients (n = 717). We hypothesized that novel urinary biomarkers would predict progression of AKI and associated outcomes. METHODS: The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or 2 AKI to predict progression to higher AKI stage, renal replacement therapy (RRT) or death within 7 days of intensive care unit admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or death within 30 days. RESULTS: In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, 8 of the 14 biomarkers were independently associated with progression. The best predictors were cystatin C [adjusted odds ratio (aOR) 5.2; 95% confidence interval (CI) 1.3-23.6], interleukin-18 (IL-18; aOR 5.1; 95% CI 1.8-15.7), albumin (aOR 4.9; 95% CI 1.5-18.3) and neutrophil gelatinase-associated lipocalin (NGAL; aOR 4.6; 95% CI 1.4-17.9). Receiver-operating characteristics and net reclassification index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stages 1-3 AKI cases, IL-18, NGAL, albumin and monocyte chemotactic protein-1 were also independently associated with RRT or death within 30 days. CONCLUSIONS: Among 14 novel urinary biomarkers assessed, cystatin C, IL-18, albumin and NGAL were the best predictors of Stages 1-2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.

Nephrotoxicity from Vancomycin Combined with Piperacillin-Tazobactam: A Comprehensive Review.

BACKGROUND: Recent studies have identified the combination of vancomycin with piperacillin-tazobactam (VPT) to be associated with increased nephrotoxicity. Multiple, large cohort studies have found this widely used combination to have a higher risk of nephrotoxicity than other regimens in a variety of populations. SUMMARY: This review summarizes the epidemiology and clinical features of VPT-associated acute kidney injury (AKI). Potential mechanisms involved in the pathogenesis of this phenomenon are also discussed. Key Message: VPT-associated nephrotoxicity is a recently recognized clinical entity. Clinical strategies to minimize the risk of toxicity in this setting include antimicrobial stewardship, monitoring of kidney function, and emerging data supporting the potential role for novel biomarkers in predicting and managing AKI.

Biomarker Predictors of Adverse Acute Kidney Injury Outcomes in Critically Ill Patients: The Dublin Acute Biomarker Group Evaluation Study.

BACKGROUND: The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective 2-center observational study investigating the utility of urinary biomarker combinations for the diagnostic and prognostic assessment of acute kidney injury (AKI) in a heterogeneous adult intensive care unit (ICU) population. The objective of this study is to evaluate whether serial urinary biomarker measurements, in combination with a simple clinical model, could improve biomarker performance in the diagnostic prediction of severe AKI and clinical outcomes such as death and need for renal replacement therapy (RRT). METHODS: Urine was collected daily from patients admitted to the ICU, for a total of 7 post-admission days. Urine biomarker concentrations (neutrophil gelatinase-associated lipocalin [NGAL], α-glutathione S-transferase [GST], π-GST, kidney injury molecule-1 [KIM-1], liver-type fatty acid-binding protein [L-FABP], Cystatin C, creatinine, and albumin) were measured. Urine biomarkers were combined with a clinical prediction of AKI model, to determine ability to predict AKI (any stage, within 2 days or 7 days of ICU admission), or a -30-day composite clinical outcome (RRT - or death). RESULTS: A total of 257 (38%) patients developed AKI within 7 days of ICU admission. Of those who developed AKI, 106 (41%) patients met stage 3 AKI within 7 days of ICU admission and 208 patients of the entire study cohort (31%) met the composite clinical endpoint of in-hospital mortality or RRT within 30 days of ICU admission. The addition of urinary NGAL/albumin to the clinical model modestly improved the prediction of AKI, in particular severe stage 3 AKI (area under the curve [AUC] of 0.9 from 0.87, p = 0.369) and the prediction of 30-day RRT or death (AUC 0.83 from 0.79, p = 0.139). CONCLUSION: A clinical model incorporating severity of illness, patient demographics, and chronic illness with currently available clinical biomarkers of renal function was strongly predictive of development of AKI and associated clinical outcomes in a heterogeneous adult ICU population. The addition of urinary NGAL/albumin to this simple clinical model improved the prediction of severe AKI, need for RRT and death, but not at a statistically or clinically significant level, when compared to the clinical model alone.

Microvascular diabetes complications in a specialist young adult diabetes service.

BACKGROUND AND AIMS: The provision of medical care to young adults with type 1 diabetes mellitus is challenging. The aim of this study was to determine the rates of microvascular complications and their progression among patients with type 1 diabetes mellitus attending a specialist young adult diabetes service in Ireland. METHODS: A retrospective review of 62 (male 56.5%) patients with type 1 diabetes mellitus attending the young adult diabetes service at our institution was undertaken. Data was recorded across two time points, clinic registration and at 5 years following initial contact. RESULTS: The mean ± SD age at first attendance was 17.4 ± 2.0 years. Mean ± SD duration of diabetes was 6.3 ± 3.9 years with most patients treated using multiple daily insulin injections (75.8%). diabetic retinopathy rate at first attendance was 17.7% and after 5 years was 37.1% (p = 0.003). The majority of cases were background retinopathy. The prevalence of diabetic kidney disease was 6.4% and this remained unchanged at follow-up. Mean ± SD HbA1c improved from 76.1 ± 22.4 mmol/mol (9.1 ± 4.2%) to 69.1 ± 14.9 mmol/mol (8.5 ± 3.5%), p = 0.044. Duration of diabetes was the only clinical variable associated with retinopathy risk at 5 years on multiple regression analysis (p = 0.037). CONCLUSIONS: Diabetic retinopathy is prevalent in young adults with type 1 diabetes attending specialist secondary care diabetes services. Duration of diabetes was the strongest determinant of retinopathy risk.

Novel Biomarkers of Drug-Induced Kidney Injury.

There is an expanding body of literature regarding the utility of novel biomarkers in drug-induced kidney injury (DIKI) and other forms of acute kidney injury (AKI). The authors could not thoroughly review this topic without referring to and acknowledging this work. Included is a list of additional articles (see Supplementary Reading List) that have been referenced, but not cited within the body of the text. These references have provided data used within this article and have allowed the authors to discuss the epidemiology of DIKI, its classification, the utility of specific biomarkers, and the impact that comorbid illness and medications can have on their levels.

Biomarkers of drug-induced kidney injury.

PURPOSE OF REVIEW: Drug-induced kidney injury (DIKI) is an important and potentially modifiable cause of acute kidney injury (AKI). The reliance on traditional markers of kidney injury to diagnose DIKI impedes early detection. Biomarkers of DIKI that facilitate early diagnosis and the identification of high-risk patients are essential to ameliorate the clinical burden of this complication. RECENT FINDINGS: Recent progress in this area supports the potential utility of several biomarkers for the diagnosis of DIKI, for the prediction of outcomes and also for monitoring responses to potential nephrotoxic or beneficial therapies. Data regarding the impact of clinically relevant factors, such as chronic kidney disease, on biomarker levels represents a further recent advancement. Emerging novel biomarkers include microRNAs, which are showing promise as markers of drug-induced tubular damage. They may also have a role in elucidating the molecular mechanisms of AKI. SUMMARY: There is compelling evidence to support the use of biomarkers for the early detection of DIKI. Ongoing research is required to delineate their role in prognostication and for the prediction of outcomes. The inclusion of biomarkers in more clinical studies of DIKI would be a welcome advance, which may accelerate their integration into clinical diagnostics.

Peritoneal dialysate effluent and serum CA125 concentrations in stable peritoneal dialysis patients.

INTRODUCTION: CA125 in peritoneal dialysis (PD) effluent dialysate has been used as a surrogate biomarker for the health of the peritoneum in PD patients. However CA125 is synthesised by epithelial cells and as such is not specific for the peritoneum, and most studies have only measured peritoneal CA125, without serum CA125 values. As such we wished to determine the factors which influenced PD effluent CA125 in a large contemporaneous cohort. METHODS: We measured dialysate effluent CA125 in PD patients attending for routine assessment of peritoneal membrane function with a peritoneal equilibration test (PET), with corresponding serum CA125. RESULTS: Serum and dialysate CA125 were measured in 205 PD patients; 59.0 ± 16.8 years, median PD treatment 3 (2-20) months, 59 % male, 42.4 % diabetic, with 31.2 % treated by continuous ambulatory peritoneal dialysis, 22 % by automated overnight peritoneal dialysis cycler (APD) and 46.8 % by APD with a day time exchange. The median serum CA125 was 21 (13-38) U/ml, with an effluent 4 h PD PET effluent of 20 (11.5-36.5) U/ml. PET PD effluent dialysate was associated with PET dialysate total protein (ß 12.9, p < 0.001), serum CA125 (ß 0.109, p = 0.002), residual renal function (ß 0.53, p = 0.018) and age (ß 0.145, p = 0.042) and negatively with the number of PD cycles/day (ß -2.19, p = 0.001). There was no association with prior peritonitis episodes. CONCLUSION: PD effluent CA125 concentrations were associated with peritoneal protein losses and increased by the usage of higher glucose dialysates to compensate for loss of residual renal function.

Familial MPGN - a case series: a clinical description of familial membranoproliferative glomerulonephritis amongst three Irish families.

Genetic factors have been implicated in the pathogenesis of certain cases of MPGN. Familial cases of all three histological subtypes have been described. Genetic defects in the control of complement pathways appear to be at the root of many hereditary forms of MPGN. Here we describe a series of three families with familial MPGN. We have identified 3 individuals with a diagnosis of idiopathic MPGN, each with a sibling with the same diagnosis. Data collected included age at presentation, histological findings and age at commencement of renal replacement therapy. A family pedigree was generated for each family as well as a description of the long-term clinical course and transplant outcomes of affected individuals. We have identified male and female affected individuals in this series of three families. The progression to end-stage kidney disease was universal amongst affected individuals. The majority of cases were successfully transplanted. Recurrence in a transplanted kidney occurred in only one individual. This series of familial MPGN provides further evidence for a genetic basis for the disease. Additional studies on these three families will further our knowledge of the underlying mutations in hereditary MPGN and contribute to the understanding of complement-mediated renal disease.

The use of palliative care services amongst end-stage kidney disease patients in an Irish tertiary referral centre.

BACKGROUND: Although patients with end-stage kidney disease (ESKD) have a shortened life expectancy, their end-of-life (EOL) care is suboptimal. The aim of this study was to review the utilization of specialist palliative care (SPC) in patients with ESKD in Dublin, Ireland. METHODS: We conducted a retrospective chart review of prevalent patients with ESKD who died between January 2005 and December 2009 at a tertiary referral centre. We recorded SPC referrals, modality of renal replacement therapy, age and place of death. RESULTS: Of 131 included patients, 88 (67.2%) were male, mean age at death was 63.2 ± 15.1 years and 102 (77.9%) were treated with haemodialysis. Forty-eight patients (36.7%) were referred to SPC, who were involved in the patients' management for a median of 12 days (range 0-907) before death. A total 104 patients (79.4%) died in an acute hospital, 19 (14.5%) died at home, 3 (2.3%) died in an inpatient hospice and the place of death was unknown for 5 patients (3.8%). Dialysis was withdrawn prior to death in 50 patients (38.1%), with a median time to death after withdrawal of dialysis of 6 days (0-105 days). A discussion regarding the withdrawal of dialysis was more frequently held with family member(s) rather than the patient. CONCLUSIONS: SPC was involved in the antemortem care of ∼1/3 of the patients with the majority of referrals placed at a late stage. Given the short timeframe until death once dialysis is withdrawn, it is imperative that appropriate EOL care is instituted. This study identifies an underutilization of SPC and improved integration of palliative care and nephrology services may optimize EOL care for patients with ESKD.

Peritoneal dialysis in an ageing population: a 10-year experience.

BACKGROUND: Chronic kidney disease (CKD) is becoming increasingly prevalent and there are increasing numbers of older patients with advanced CKD. Peritoneal dialysis (PD) is a potential treatment. This study aims to compare PD outcomes in age-defined populations in the largest PD centre in the Republic of Ireland over 10 years. METHODS: We retrospectively identified all adult patients, over the age of 50 years, who commenced PD as their first modality of renal replacement therapy (RRT) between 1 January 1998 and 31 December 2008 at our institution. Primary outcome was patient survival; secondary outcomes were technique failure, peritonitis-free survival, transplantation and hospitalisations. RESULTS: One hundred and forty-eight patients with a mean age of 63 years were included. Twenty-two patients were on assisted PD, the majority of whom were aged 70 years or over (P = 0.001). There were no differences in patient survival or technique failure by age group, Charlson Co-Morbidity Index (CCI), modified-CCI or adjusted CCI. Renal transplantation occurred predominantly in younger patients (P = 0.001) with lower m-CCI (P = 0.001) and a-CCI (P = 0.002) who performed PD independently (P = 0.004). Older patients required longer hospital stays to initiate PD (P = 0.004). Assisted PD was not associated with an increase in early complications or technique failure but death rates were higher (P = 0.002). CONCLUSION: This study shows PD to be an acceptable modality of renal replacement therapy in elderly patients, with no observed differences in survival, technique survival or complication rates. Co-morbidities appear to play a stronger role in predicting survival than age alone. Assisted PD is a viable option in those unable to undergo PD independently.