Effect of stress hyperglycaemia on acute kidney injury in non-diabetic critically ill patients?

BACKGROUND: Stress hyperglycaemia (SH) and acute kidney injury (AKI) occur frequently in critically ill patients, and particularly non-diabetics are associated with adverse outcome. Data is scarce on the effect of SH on AKI. We assessed whether SH (i) preceded AKI, (ii) was a risk factor of subsequent AKI, and (iii) how SH and tubular injury interacted in AKI development in critically ill, non-diabetics. METHODS: Case-control study of 82 patients each with and without SH matched by propensity score for multiple demographic characteristics. AKI was defined by KDIGO criteria, SH either as blood glucose (BG) > 140 mg/dl (BG140), > 200 mg/dl (BG200), or stress hyperglycemia rate (SHR) ≥ 1.47 (SHR1.47) as measured 2 days before AKI. Urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) indicated tubular injury. RESULTS: In AKI, SH rates were frequent using all 3 definitions applied, but highest when BG140 was applied. SH by all 3 definitions was consistently associated with AKI. This was independent of established risk factors of AKI such as sepsis and shock. Increments of BG, urinary NGAL or cystatin C, and its products, were independently associated with the likelihood of subsequent AKI, demonstrating their reciprocal potentiating effects on AKI development. CONCLUSIONS: SH is frequent in critically ill, non-diabetics with AKI. SH was identified as an independent risk factor of AKI. Higher BG combined with tubular injury may potentiate their adverse effects on AKI.

Incidence, severity, risk factors and outcomes of acute kidney injury in older adults: systematic review and meta-analysis.

OBJECTIVES: Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75 years for whom data are scarce. METHODS: Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75 years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts. RESULTS: Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8 years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24). CONCLUSION: AKI is frequent in patients ≥ 75 years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.

Health-Related Quality of Life according to Renal Function: Results from a Nationwide Health Interview and Examination Survey.

BACKGROUND: Most studies on health-related quality of life (HRQoL) in chronic kidney disease (CKD) focus on patients with end-stage kidney disease although they represent a small proportion of patients with CKD. We aimed to analyze HRQoL according to glomerular filtration rate (GFR) categories in a population-based sample of adults living in Germany. METHODS: Data from the German health interview and examination survey conducted from 2008 to 2011 were used. Participants with valid interview and examination data aged 40-79 years were included (n = 5,159). Serum creatinine levels were used to calculate estimated GFR via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. We classified kidney function in GFR categories according to the Kidney Disease Improving Global Outcomes Initiative (KDIGO) guidelines on CKD: G1 (high): ≥90 mL/min/1.73 m2, G2 (normal): 60-89 mL/min/1.73 m2, G3a (mildly decreased): 45-59 mL/min/1.73 m2, G3b (moderately decreased): 30-44 mL/min/1.73 m2, G4/5 (severely decreased/end-stage kidney disease): <30 mL/min/1.73 m2. HRQoL was evaluated with the Short Form Health Survey (SF-36). Different multivariate linear and logistic regression models were used to analyze the association of HRQoL with GFR categories. RESULTS: Overall, 5.9% had a GFR <60 mL/min/1.73 m2 (corresponding to categories G3a, G3b, and G4/5). Compared to category G2 linear regression showed a decline in physical HRQoL in categories G3a (-2.34, p = 0.004), G3b (-5.37, p = 0.009), and G4/5 (-4.82, p = 0.117). No decline in mental HRQoL was detected with increasing GFR categories. Categories G3a to G4/5 were significantly associated with a low perceived general state of health (G3a: odds ratio [OR] = 2.03, p = 0.001; G3b: OR = 3.01, p = 0.009; G4/5: OR = 8.70, p = 0.016) when compared to category G2. CONCLUSION: In a representative sample of adults living in Germany, both physical HRQoL and the perceived general state of health are already significantly reduced in category G3a.

SARS-CoV-2: Viral Loads of Exhaled Breath and Oronasopharyngeal Specimens in Hospitalized Patients with COVID-19.

BACKGROUND: SARS-CoV-2 seems mainly transmissible via respiratory droplets. We compared the time-dependent SARS-CoV-2 viral load in serial pharyngeal swab with exhaled breath (EB) samples of hospitalized COVID-19 patients. METHODS: In this prospective proof of concept study, we examined hospitalized patients who initially tested positive for SARS-CoV-2. Paired oronasopharyngeal swab and EB specimens were taken at different days of hospitalization. EB collection was performed through a simple, noninvasive method using an electret air filter-based device. SARS-CoV-2 RNA detection was determined with real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Of 187 serial samples from 15 hospitalized patients, 87/87 oronasopharyngeal swabs and 70/100 EB specimens tested positive. Comparing the number of SARS-CoV-2 copies, the viral load of the oronasopharyngeal swabs was significantly higher (CI 99%, P<<0,001) than for EB samples. The mean viral load per swab was 7.97 × 106 (1.65 × 102-1.4 × 108), whereas EB samples showed 2.47 × 103 (7.19 × 101-2.94 × 104) copies per 20 times exhaling. Viral loads of paired oronasopharyngeal swab and EB samples showed no correlation. CONCLUSIONS: Assessing the infectiousness of COVID-19 patients merely through pharyngeal swabs might not be accurate. Exhaled breath could represent a more suitable matrix for evaluating infectiousness and might allow screening for superspreader individuals and widespread variants such as Delta.

Tyrosine kinase inhibitors targeting vascular endothelial growth factor and the risk of aortic dissection-A pharmacovigilance analysis.

There are concerns by the United States Food and Drug Administration (FDA) regarding a potential link between tyrosine kinase inhibitors targeting vascular endothelial growth factor (VEGF-TKIs) and the risk of aortic dissection. Elevation of blood pressure induced by VEGF-TKIs has been discussed as part of the pathomechanism. To address this important safety issue, we conducted a large pharmacovigilance study assessing the risk of aortic dissection reporting associated with the use of VEGF-TKIs, thereby exploring the role of blood pressure. We queried the FDA Adverse Event Reporting System from 2004 to 2019 for reports including VEGF-TKIs and aortic dissection and estimated reporting odds ratios (RORs) and 95% confidence intervals (CIs) of aortic dissection associated with the use of VEGF-TKIs. Secondary analyses stratified by the strength of blood pressure elevation (≥10 mmHg vs. <10 mmHg increased systolic or diastolic bloods pressure) and pre-existing arterial hypertension. There were 81 reports of aortic dissection related to VEGF-TKIs during the study period. VEGF-TKIs were associated with an increased risk of aortic dissection reporting (ROR, 4.31; 95% CI, 3.43 to 5.42). The risk was higher among compounds strongly increasing blood pressure (ROR, 5.33; 95% CI, 3.88 to 7.32) than among compounds moderately increasing blood pressure (ROR, 2.79; 95% CI, 1.83 to 4.27). Pre-existing arterial hypertension did not modify the association. Overall, our study showed an increased risk of aortic dissection reporting associated with the use of VEGF-TKIs. Blood pressure elevation seems to play a role in the pathophysiology of this adverse effect.

Validation of the Clinical Frailty Scale for retrospective use in acute care.

PURPOSE: There is a considerable need to measure frailty retrospectively in clinical practice and research. We assessed agreement, accuracy, precision, and reliability of retrospectively compared with prospectively, and separately attained, retrospective Clinical Frailty Scale (CFS) scoring, respectively. METHODS: We studied 110 hospitalized patients aged ≥ 80 years, consisting of 70.9% females. Agreement was assessed by bias, accuracy by root mean square error (RMSE) and the percentages of one CFS scores within 20% and 30% of each other (P20 and P30), precision by interquartile ranges of the bias, and reliability by weighted Cohen's kappa (κ). RESULTS: Comparison of retrospective and prospective CFS scores demonstrated a modest bias of 0.26. Classification as robust, prefrail, or frail was generally correct in retrospectively compared to prospectively CFS scores. RMSE was low (0.28), while P20 and P30 values were high (90.0% and 96.6%, respectively). Precision of retrospective to predict prospective CFS scores was high with narrow interquartile ranges of 0 and 1. Reliability of retrospective with prospective CFS scores was high (κ = 0.89). Comparing two separately attained retrospective CFS scores demonstrated low bias (0.05) and RMSE (0.24), and a high P30 value (90.0%). Precision and interrater reliability of the comparison of retrospective CFS scores were high with narrow interquartile ranges and κ = 0.85. CONCLUSION: The retrospectively attained CFS score is a valid diagnostic instrument to measure frailty in older hospitalized patients with high agreement, accuracy, precision, and reliability compared to both prospective and separately attained CFS scores.

Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case-control studies.

BACKGROUND: Vitamin K antagonists (VKAs) are susceptible to drug-drug interactions. Non-VKA oral anticoagulants (NOACs) have a decreased sensitivity to pharmacokinetic interactions and might be therefore considered superior in patients treated with multiple drugs. The objective of this study was to compare the risk of serious bleeding associated with interacting drugs in German nursing home residents treated with VKA or NOAC. METHODS: Using claims data of new nursing home residents aged ≥ 65 years (2010-2014) we conducted separate nested case-control analyses within two cohorts of patients treated with VKA or NOAC, respectively. Cases were defined as patients hospitalized for serious bleeding. For each case, up to 20 controls were selected by risk-set sampling. Conditional logistic regression was used to obtain confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the risk of bleeding associated with VKA or NOAC use and interacting drugs compared with the use of the respective oral anticoagulant alone. RESULTS: Among 127,227 new nursing home residents, 16,804 patients received oral anticoagulation. Based on 372 cases and 7281 matched controls, the highest risk of bleeding in VKA users was observed for the concomitant use of antibiotics (aOR 3.00; CI 2.11-4.27) vs. VKA use alone, followed by non-steroidal anti-inflammatory drugs (1.66; 1.13-2.43). Among 243 NOAC cases and 4776 matched controls, elevated risks for bleeding were observed for the use of heparins (2.05; 1.25-3.36) and platelet inhibitors (1.92; 1.36-2.72). CONCLUSIONS: Concomitant medication needs to be prescribed cautiously and monitored closely in nursing home residents treated with oral anticoagulants.

Capnocytophaga canimorsus - a potent pathogen in immunocompetent humans - systematic review and retrospective observational study of case reports.

Purpose: Severe and fatal Capnocytophaga canimorsus infection has been described in immunocompromised patients. Data of C. canimorsus infection in immunocompetent and risk factors of severe courses are missing. Our aims were to describe the epidemiology of C. canimorsus infection and to identify potential risk factors of sepsis and fatal outcome.Methods: Observational study and systematic review of all cases reported in immunocompetent subjects between 2002 and 2019.Results: A total of 128 cases of C. canimorsus infection in immunocompetent individuals were reported. Male gender comprised 74.2%, the median age was 58 years and 47.7% were admitted with sepsis. Case-fatality rate was 29.7% and especially high in septic patients (55.7%). Transmission by bite (OR = 2.37, 95% CI: 1.05-6.52) and incubation time ≤3 d (OR = 7.98; 95% CI: 2.33-27.34) were identified as risk factors of sepsis on admission, and early wound cleansing as protective (OR = 0.42; 95% CI: 0.14-0.96). Sepsis (OR = 23.67; 95% CI: 2.85-197.89) and septic shock (OR = 45.50; 95% CI: 3.08-676.55) were risk factors of fatal outcome, whereas early wound cleansing (OR = 0.05; 95% CI: 0.01-0.72), initial penicillin therapy with beta-lactamase inhibitors (OR = 0.48; 95% CI: 0.16-0.92) and surgical removal of infectious focus (OR = 0.38; 95% CI: 0.06-0.95) were protective factors.Conclusions: Immunocompetent patients with C. canimorsus infection frequently develop sepsis. A shorter incubation period in cases of sepsis might be related to higher infectious dose. Fatal outcome may be prevented by early wound cleansing, initial use of penicillins in combination with beta-lactamase inhibitors and surgical removal of an infectious focus.

Being Licked by a Dog Can Be Fatal: Capnocytophaga canimorsus Sepsis with Purpura Fulminans in an Immunocompetent Man.

Bite infections caused by Capnocytophaga canimorsus are rare. Severe and fatal infections are more frequently reported in patients with immunodeficiency, splenectomy or alcohol abuse. We describe the case of a 63-year-old man who developed flu-like symptoms and presented after some delay with severe sepsis and purpura fulminans. He was found to be infected with C. canimorsus without a bite injury and did not demonstrate immunodeficiency or any other typical predisposition. Despite extensive intensive care, his conditions deteriorated and he died from multiorgan failure. LEARNING POINTS: Pet owners with banal, for instance flu-like, symptoms should urgently seek medical advice when symptoms are unusual.Capnocytophaga canimorsus infection should be considered and empirical antibiotic therapy immediately started or adjusted in the presence of purpura fulminans in the absence of animal bites or immunodeficiency.

Combined use of drugs inhibiting the renin-angiotensin system: prescribing patterns and risk of acute kidney injury in German nursing home residents.

BACKGROUND/AIMS: In 2012, the European Medicines Agency reviewed the safety of dual renin-angiotensin system (RAS) blockade because of potentially increased risks for inter alia acute kidney injury (AKI). Since residents of nursing homes are particularly vulnerable to adverse drug outcomes, the aims of our study were to describe RAS-inhibiting drug use in German nursing home residents and examine the risk of AKI associated with dual RAS blockade. METHODS: Based on claims data, a nested case-control study within a cohort of RAS-inhibiting drug users was conducted. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) were obtained for the risk of AKI associated with dual RAS blockade. Subgroup analyses were performed in patients with diabetes or chronic kidney disease and both comorbidities. RESULTS: Of all 127,227 nursing home residents, the study cohort included 64,567 (50.7%) who were treated with at least one RAS-inhibiting drug. More than three quarters of the study population were female (77.1%). Mean age was 86.0 ± 6.8 years. Most residents were treated with angiotensin-converting enzyme inhibitors (77.8%), followed by angiotensin II receptor blockers (21.6%) and aliskiren (0.2%). Annual prevalence of dual RAS blockade declined from 9.6 (95% CI 7.8-11.8) in 2010 to 4.7 (95% CI 4.0-5.4) per 1,000 users in 2014. In the overall cohort, AKI was not significantly associated with dual RAS blockade (aOR 1.99; 0.77-5.17). However, significantly increased aORs were observed when considering patients with diabetes (3.47; 1.27-9.47), chronic kidney disease (4.74; 1.24-18.13) or both (11.17; 2.65-47.15). CONCLUSIONS: Prescribing of drugs inhibiting the RAS is common in German nursing homes. Though the prevalence of dual RAS blockade declined, our study showed an increased risk of AKI in patients with diabetes and/or chronic kidney disease. Therefore, cautious use is warranted in these vulnerable patients.

Proteomics and Metabolomics for AKI Diagnosis.

Acute kidney injury (AKI) is a severe and frequent condition in hospitalized patients. Currently, no efficient therapy of AKI is available. Therefore, efforts focus on early prevention and potentially early initiation of renal replacement therapy to improve the outcome in AKI. The detection of AKI in hospitalized patients implies the need for early, accurate, robust, and easily accessible biomarkers of AKI evolution and outcome prediction because only a narrow window exists to implement the earlier-described measures. Even more challenging is the multifactorial origin of AKI and the fact that the changes of molecular expression induced by AKI are difficult to distinguish from those of the diseases associated or causing AKI as shock or sepsis. During the past decade, a considerable number of protein biomarkers for AKI have been described and we expect from recent advances in the field of omics technologies that this number will increase further in the future and be extended to other sorts of biomolecules, such as RNAs, lipids, and metabolites. However, most of these biomarkers are poorly defined by their AKI-associated molecular context. In this review, we describe the state-of-the-art tissue and biofluid proteomic and metabolomic technologies and new bioinformatics approaches for proteomic and metabolomic pathway and molecular interaction analysis. In the second part of the review, we focus on AKI-associated proteomic and metabolomic biomarkers and briefly outline their pathophysiological context in AKI.

Permanent Decline of Renal Function after Infrarenal Abdominal Aortic Aneurysm Repair-Frequency and Risk Factors.

BACKGROUND: Permanent renal function decline, and development and deterioration of chronic kidney disease (CKD) are associated with serious complications. How frequent is renal function decline after infrarenal abdominal aortic aneurysm (iAAA) repair according to current definitions and what are its risk factors, especially potentially modifiable ones? METHODS: Retrospective observational study including all patients with elective or urgent iAAA repair from 2007 to 2011. The primary outcome was renal function decline in the first year after iAAA repair, defined as permanent reduction of estimated glomerular filtration rate (eGFR) ≥20% from baseline and/or end-stage renal disease (ESRD), all in the first year after iAAA repair. According to current Kidney Disease Improving Global Outcomes guidelines, CKD and periprocedural AKI were defined and classified. Multivariate Cox proportional hazards model was used to assess associations of the primary end point with potential risk factors. RESULTS: Two hundred sixty-eight patients with iAAA repair were studied, 61 patients (22.7%) developed declining eGFR ≥20% and/or ESRD. The primary end point was independently associated with preexisting CKD (hazard ratio [HR] 3.14 [1.61-6.09]), renal artery stenosis (RAS) ≥70% (HR 4.34 [1.49-12.67]), open aortic aneurysm repair (OAR) (HR 1.69 [1.14-2.68]), and periprocedural AKI (HR 15.25 [7.49-31.05]). When comparing the subsets of patients with and without OAR and periprocedural AKI, these 2 modifiable risk factors had an additive impact. Declining eGFR ≥20% and/or ESRD was most frequent in patients receiving OAR who developed AKI. CONCLUSIONS: A permanent decline of renal function 1 year after iAAA repair is frequent. Preexisting CKD, RAS ≥70%, OAR, and periprocedural AKI are independent risk factors, the latter 2 with additive effect.

Acute kidney injury after abdominal aortic aneurysm repair: current epidemiology and potential prevention.

PURPOSE: Acute kidney injury (AKI) is a severe complication after infrarenal abdominal aortic aneurysm (iAAA) repair. Little data are available whether endovascular aneurysm (EVAR) or open aortic repair (OAR) differs with respect to AKI frequency and severity, consecutive development of chronic kidney disease (CKD) and potentially preventable and modifiable risk factors of AKI. PATIENTS AND METHODS: We assessed AKI rates, AKI stages and CKD applying current, complete definitions from the kidney disease improving global outcomes initiative in propensity-score-matched cohorts of all patients with elective and urgent iAAA repair at our institution from 2007 to 2011. Risk factors were analysed using multivariate logistic regression analyses. RESULTS: From 268 patients, we identified 91 matched pairs who had undergone either EVAR or OAR. The AKI rate was 13.2% with EVAR versus 41.8% with OAR (P < 0.001). AKI was significantly less severe in EVAR. OAR patients lost more glomerular filtration rate (- 11.3 vs. - 6.5%; P = 0.02) and developed more frequently CKD (14.3 vs. 3.2%; P < 0.001) 3 months after iAAA repair. EVAR, circulatory shock, radiocontrast media, rhabdomyolysis and sepsis were identified as potentially preventable or modifiable risk factors of AKI. CONCLUSIONS: AKI is significantly less frequent and severe in iAAA patients after EVAR as compared to OAR. Furthermore OAR patients demonstrate a higher CKD rate. The identified risk factors may be prevented or modified as a bundle of measures especially in patients with pre-existing CKD to reduce AKI and its severity after iAAA repair.

Use of oral anticoagulants in German nursing home residents: drug use patterns and predictors for treatment choice.

AIMS: Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA. METHODS: Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years. RESULTS: Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%. CONCLUSIONS: NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Inappropriate Medication in Non-Hospitalized Patients With Renal Insufficiency: A Systematic Review.

OBJECTIVES: Renal insufficiency is common among older patients and, accordingly, renally excreted drugs may require an adjustment in dosage for them. Rates of non-adherence to renal dosing guidelines range from 19% to 70% across all settings, with the highest rate occurring in outpatient care. However, there is a paucity of research in this field. The main objective of this systematic review is to assess how often drugs are inappropriately prescribed in non-hospitalized patients with renal insufficiency. DESIGN: A systematic literature search was performed. Data were identified from three electronic databases: PubMed, CINAHL, and Scopus. Studies were included if they reported quantitative data on inappropriate drug use with respect to renal function in non-hospitalized patients. RESULTS: Our search strategy resulted in 2,403 hits, of which 18 articles satisfied the criteria for inclusion. Mean estimated glomerular filtration rate ranged from 36.0 to 60.4 mL/min. Prevalence of renally inappropriate drug use ranged from 1% to 37% in outpatient settings other than nursing homes, and from 6% to 43% in nursing homes. Eight of the studies we included identified predictors for use of drugs inappropriate for kidney function. Most frequently determined risk factors were increasing age and a high number of prescribed drugs. CONCLUSION: Lack of dose adjustment for renal impairment seems to be a common problem, even in outpatients. However, the differences in methodologies used in these studies hampered any direct comparison. Accepted and comparable standards regarding the drugs included in the studies as well as estimation of renal function would be beneficial.

Acute kidney injury prediction in cardiac surgery patients by a urinary peptide pattern: a case-control validation study.

BACKGROUND: Acute kidney injury (AKI) is a prominent problem in hospitalized patients and associated with increased morbidity and mortality. Clinical medicine is currently hampered by the lack of accurate and early biomarkers for diagnosis of AKI and the evaluation of the severity of the disease. In 2010, we established a multivariate peptide marker pattern consisting of 20 naturally occurring urinary peptides to screen patients for early signs of renal failure. The current study now aims to evaluate if, in a different study population and potentially various AKI causes, AKI can be detected early and accurately by proteome analysis. METHODS: Urine samples from 60 patients who developed AKI after cardiac surgery were analyzed by capillary electrophoresis-mass spectrometry (CE-MS). The obtained peptide profiles were screened by the AKI peptide marker panel for early signs of AKI. Accuracy of the proteomic model in this patient collective was compared to that based on urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) ELISA levels. Sixty patients who did not develop AKI served as negative controls. RESULTS: From the 120 patients, 110 were successfully analyzed by CE-MS (59 with AKI, 51 controls). Application of the AKI panel demonstrated an AUC in receiver operating characteristics (ROC) analysis of 0.81 (95 % confidence interval: 0.72-0.88). Compared to the proteomic model, ROC analysis revealed poorer classification accuracy of NGAL and KIM-1 with the respective AUC values being outside the statistical significant range (0.63 for NGAL and 0.57 for KIM-1). CONCLUSIONS: This study gives further proof for the general applicability of our proteomic multimarker model for early and accurate prediction of AKI irrespective of its underlying disease cause.

Renal Insufficiency and Medication in Nursing Home Residents. A Cross-Sectional Study (IMREN).

BACKGROUND: Nursing home residents often suffer from a multiplicity of medical conditions and take many different drugs. Many drugs are eliminated via the kidneys and thus require dose adjustment in patients with renal insufficiency. This is the first study to address the prevalence of renal insufficiency among nursing home residents in Germany, and the extent to which such persons take drugs that are contraindicated or incorrectly dosed because of renal insufficiency. METHODS: We carried out a cross-sectional study in nursing homes in the German regions of Bremen and Lower Saxony. Data were collected by nursing staff and given to us anonymously. Whenever the nursing home data did not include a current creatinine value, the patient's general practitioner was asked to supply this value. The estimated creatinine clearance (eCCr) was calculated with the Cockcroft-Gault formula. RESULTS: 852 residents of 21 nursing homes were included in the study; eCCr values were obtainable for 685 (80.4%) of them (average age, 83.3 years; 75.2% female). 48.2% of these patients (95% confidence interval [CI] 41.8-54.5) had moderate renal insufficiency (eCCr 59-30 mL/min), and 15.5% (95% CI 12.4-18.6) had severe renal insufficiency (eCCr <30 mL/min). 19.7% were regularly taking at least one medication that was contraindicated or incorrectly dosed in the light of renal insufficiency. Predictors for such inappropriate drug use were advanced age, female sex, arterial hypertension, and polypharmacy. The drugs that were most often inappropriately used were metformin, ramipril, and potassium chloride. CONCLUSION: Nursing home residents often suffer from renal insufficiency and should therefore have their creatinine levels measured regularly. A knowledge of the creatinine level is a prerequisite for the proper adjustment of drug doses (if necessary). A practical and compact summary of dose-adjustment recommendations for patients with renal insufficiency would be desirable but is not yet available.

Use of nonsteroidal anti-inflammatory drugs and renal failure in nursing home residents-results of the study "Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes".

BACKGROUND: Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure. METHODS: Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated. RESULTS: In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate < 30 ml/min) in 106 residents (15.5 %). Approximately one-fifth was treated with at least one nonsteroidal anti-inflammatory drug in both the total study population (20.3 %) and that with severe renal failure (20.8 %). With one exception, all residents prescribed nonsteroidal anti-inflammatory drugs with severe renal failure were treated with at least one nonsteroidal anti-inflammatory drug that was contraindicated due to the underlying renal function. CONCLUSIONS: Notwithstanding their classification as potentially inappropriate medications and underlying contraindications, use of nonsteroidal anti-inflammatory drugs is common among nursing home residents with severe renal failure.

Polypharmacy and Renal Failure in Nursing Home Residents: Results of the Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes (IMREN) Study.

BACKGROUND: Polypharmacy has become an emerging public health issue in recent years, since use of multiple medications or polypharmacy is beneficial for many conditions, but may also have negative effects like adverse drug reactions. The risk further increases in patients with chronic renal failure, a comorbidity very frequent in nursing home residents. Since more than 50% of all drugs were renally excreted, dose adjustments in patients with renal failure are required. OBJECTIVE: To assess polypharmacy in German nursing homes, in particular in residents with renal failure. METHODS: Multi-center cross-sectional study in 21 nursing homes in Bremen and Lower Saxony/Germany. Baseline data were analysed using descriptive statistics. Multivariable logistic regression model and 95% confidence intervals were used to study the association of renal failure and polypharmacy. RESULTS: Of all 852 residents, the analysis comprised those 685 with at least one serum creatinine value so that the estimated creatinine clearance could be calculated. Of those, 436 (63.6%) had a severe or moderate renal failure, defined as estimated creatinine clearance <60 mL/min. Polypharmacy (5-9 drugs) was found in 365 (53.3%) and excessive polypharmacy (≥10 drugs) in 112 (16.4%) residents. Diuretics and psycholeptics were the most commonly used drug classes. Severe renal failure (estimated creatinine clearance <30 mL/min) was associated with polypharmacy (OR: 2.8, 95% CI 1.4-5.7). CONCLUSION: Both, polypharmacy and renal failure are common in German nursing home residents and an association of both could be found. Further studies are needed to assess the appropriateness of polypharmacy in these patients.

[Medical services for nursing home residents : Results of the study on inappropriate medication in patients with renal insufficiency in nursing homes]. / Ärztliche Versorgung von Pflegeheimbewohnern : Ergebnisse der Studie "Inappropriate medication in patients with renal insufficiency in nursing homes".

BACKGROUND: In Germany approximately 800,000 people are living in nursing homes. Outpatient medical treatment is provided by general practitioners (GP) and a variety of medical specialists. While nearly all residents have regular contact with GPs, care by specialists differs between the various disciplines. AIM: In this study an assessment of medical treatment for nursing home residents by GPs and specialists was made and compared with the available diagnoses. MATERIAL AND METHODS: Between October 2014 and April 2015 a cross-sectional study was conducted in nursing homes in Bremen and the surrounding areas. Anonymized data based on residents' files were collated by nursing staff. Every contact with various specialists within the preceding 12 months was assessed and grouped into (a) no physician visit, (b) resident visited physician and (c) physician visited resident. Analyses were stratified for age, sex and level of care dependency as well as dementia and further comorbidities. RESULTS: A total of 852 residents in 21 nursing homes were included (mean age 83.5 years, 76.5 % female) in the study. Dementia was diagnosed in 57.7 %. Nearly all residents had had contact with their GP in the previous 12 months, mostly by home visits (96.9 %). The majority (54.5 %) had not seen a dentist in the preceding 12 months and 25.4 % had been visited by a dentist. Of the residents 47.4 % were visited by a neurologist or psychiatrist but only 4.5 % visited these specialists in their practice. Higher care dependency and younger age were associated with more frequent visits by neurologists and psychiatrists. Contact rates to ophthalmologists (29.3 %) and urologists (20.5 %) were less frequent. A diagnosis of diabetes mellitus had no influence on the contact rate with ophthalmologists. CONCLUSION: Medical care by specialists is characterized by huge variations. Besides a frequent contact rate with GPs there seems to be an undersupply regarding care by dentists and ophthalmologists.