Diagnosis of acute kidney injury (AKI) based on plasma creatinine often lags behind actual changes in renal function. Here, we investigated early detection of AKI using the plasma soluble urokinase ...plasminogen activator receptor (suPAR) and neutrophil gelatinase-sssociated lipocalin (NGAL) and observed the impact of early detection on prescribing recommendations for renally-eliminated medications. This study is a secondary analysis of data from the DISABLMENT cohort on acutely admitted older (≥65 years) medical patients (
= 339). Presence of AKI according to kidney disease: improving global outcomes (KDIGO) criteria was identified from inclusion to 48 h after inclusion. Discriminatory power of suPAR and NGAL was determined by receiver-operating characteristic (ROC). Selected medications that are contraindicated in AKI were identified in Renbase
. A total of 33 (9.7%) patients developed AKI. Discriminatory power for suPAR and NGAL was 0.69 and 0.78, respectively, at a cutoff of 4.26 ng/mL and 139.5 ng/mL, respectively. The interaction of suPAR and NGAL yielded a discriminatory power of 0.80, which was significantly higher than for suPAR alone (
= 0.0059). Among patients with AKI, 22 (60.6%) used at least one medication that should be avoided in AKI. Overall, suPAR and NGAL levels were independently associated with incident AKI and their combination yielded excellent discriminatory power for risk determination of AKI.
Summary A 72-year-old man with type 2 diabetes volunteered to participate in the control group of a clinical study. The study evaluated non-alcoholic fatty liver disease in patients with kidney ...disease. The patient was followed at a gastroenterology department due to Crohn’s disease and post-operative bile acid malabsorption. The patient had no symptoms or biochemical findings suggesting liver disease. Surprisingly, a transient elastography (FibroScan®) suggested advanced fibrosis with a median of 16.1 kPa. A liver biopsy showed non-alcoholic steatohepatitis (NASH)-cirrhosis. The diagnosis was only made incidentally and highlights how NASH-cirrhosis may be overlooked due to the lack of symptoms. Learning points Clinicians treating high-risk populations, including patients with type 2 diabetes and/or components of the metabolic syndrome, should be aware of the frequently occurring co-existence with non-alcoholic fatty liver disease (NAFLD) and especially non-alcoholic steatohepatitis (NASH). Liver enzymes may be in the normal range even in people with steatosis, NASH, or even cirrhosis. The diagnosis of NAFLD should include evaluation of hepatic fibrosis as this is the most important prognostic factor for liver-related complications and mortality. Guidelines about systematic screening for NAFLD in patients with type 2 diabetes are incongruent.
Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to ...inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on
Technetium-diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.
The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.
The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.
ClinicalTrials.gov NTC03741283 . Retrospectively registered on 14 November 2018.
Summary
To investigate the impact of kidney transplantation (KTx) on insulin sensitivity affecting glucose metabolism. 9 nondiabetic patients awaiting living donor KTx were examined prior to ...transplantation with an oral glucose tolerance test and a 3‐h hyperinsulinaemic–euglycaemic clamp. The clamp was repeated 6 months after KTx. Nine age‐, gender‐ and body mass index (BMI)‐matched individuals with normal kidney function served as controls. Endogenous glucose production and glucose disappearance rate (N = 6) were measured in a subgroup of patients with corresponding controls. Results presented as mean range. Two patients had pretransplant prediabetes, whereas all others had normal glucose tolerance. After KTx, average glucose infusion rate to maintain euglycaemia during clamp declined significantly from 15.1 9.1–23.7 to 9.8 2.8–14.6 μmol/kg/min (P < 0.01) with 20.2 9.9–33.7 μmol/kg/min in controls. Endogenous glucose production increased from 7.0 4.8–8.5 to 9.4 7.4–11.8 μmol/kg/min (P < 0.05) with 7.0 −3.8 to 10.1 μmol/kg/min in controls. Glucose disappearance rate was unchanged (18.1 12.9‐24.5 vs. 17.1 12.2‐22.7 μmol/kg/min, NS) with 22.3 14.6–34.3 in controls. In conclusion, insulin sensitivity is reduced 6 months after KTx and characterized mainly by impaired suppression of the endogenous glucose production.
Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of ...collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86,
< 0.0001; U-ETP/Cr AUC = 0.70,
= 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (
< 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92,
< 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (
= 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.
Introduction
This study examined the prevalence of microvascular and macrovascular complications in people receiving dialysis with and without diabetes and investigated independent risk factors for ...foot ulcers and lower‐extremity amputations.
Methods
We performed a cross‐sectional study of 119 individuals with diabetes and 219 individuals without diabetes receiving chronic dialysis during June 2019 at the Department of Nephrology, Rigshospitalet, University of Copenhagen, Denmark. Effects of diabetes and other risk factors were assessed by log‐binomial regression. Prevalence data were compared with a historical control group of 38 individuals with diabetes receiving dialysis examined in 2004 in the same department.
Results
We found that persons with diabetes had a twofold higher risk ratio of current (unadjusted risk ratio 2.2 95% CI 1.1, 4.7) and previous foot ulcer (2.5 1.7, 3.7) and a fourfold higher risk ratio of lower‐extremity amputation (4.2 2.1, 8.6) in comparison with persons without diabetes (all p < .05). Furthermore, persons with diabetes had a 70% increased risk ratio of myocardial infarction (1.7 1.0–2.8, p = .041). In multivariable‐adjusted analysis, current foot ulcer was independently associated with previous foot ulcer (adjusted risk ratio 4.0 95% CI 1.8, 8.9), while lower‐extremity amputation was independently associated with diabetes (3.8 1.8, 8.2) and male sex (4.1 1.5, 11.3) (all p < .01).
Conclusions
Individuals with diabetes receiving dialysis had a higher prevalence of foot ulcer, lower‐extremity amputation and myocardial infarction compared to individuals without diabetes. Previous foot ulcer was the most important risk factor for current foot ulcer, while diabetes and male sex were important risk factors for lower‐extremity amputation.
Over the past decades, there has been a general improvement in the prognosis of people with diabetes; however, it is unclear what the consequences of these improvements are in relation to complications among people receiving dialysis. This study examined the prevalence of micro‐ and macrovascular complications in people receiving dialysis with and without diabetes, and found that individuals with diabetes had a higher prevalence of foot ulcer, amputation and myocardial infarction compared to individuals without diabetes.
Glucagon is a major regulator of metabolism and drugs targeting the glucagon receptor (GCGR) are being developed. Insight into tissue and cell-specific expression of the GCGR is important to ...understand the biology of glucagon and to differentiate between direct and indirect actions of glucagon. However, it has been challenging to localize the GCGR in tissue due to low expression levels and lack of specific methods. Immunohistochemistry has frequently been used for GCGR localization, but antibodies targeting G-protein-coupled-receptors may be inaccurate. We evaluated all currently commercially available GCGR antibodies. The antibody, ab75240 (Antibody no. 11) was found to perform best among the twelve antibodies tested and using this antibody we found expression of the GCGR in the kidney, liver, preadipocytes, pancreas, and heart. Three antibody-independent approaches all confirmed the presence of the GCGR within the pancreas, liver and the kidneys. GCGR expression should be evaluated by both antibody and antibody-independent approaches.
Identifying patients at high risk of developing kidney disease could lead to early clinical interventions that prevent or slow disease progression. Soluble urokinase plasminogen activator receptor ...(suPAR) is an inflammatory biomarker thought to be involved in the pathogenesis and development of kidney disease. We aimed to determine whether elevated plasma suPAR measured at hospital admission is associated with incident kidney disease in patients presenting to the emergency department.
This was a retrospective registry-based cohort study performed at the Emergency Department of Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. Patients were included in the study from November 2013 to March 2017 and followed until June 2017. Patients were excluded if they were diagnosed with kidney disease or died prior to index discharge. Plasma suPAR was measured at hospital admission, and the main outcome was time to incident kidney disease, defined by ICD-10 diagnosis codes for both chronic and acute kidney conditions. Association between suPAR and time to incident kidney disease was assessed by Cox proportional hazard regression analysis.
In total, 25,497 patients (median age 58.1 years; 52.5% female) were admitted to the emergency department and followed for development of kidney disease. In multivariable Cox regression analysis adjusting for age, sex, eGFR, CRP, cardiovascular disease, hypertension, and diabetes, each doubling in suPAR at hospital admission was associated with a hazard ratio of 1.57 (95% CI: 1.38-1.78,
< 0.001) for developing a chronic kidney condition and 2.51 (95% CI: 2.09-3.01,
< 0.001) for developing an acute kidney condition.
In a large cohort of acutely hospitalized medical patients, elevated suPAR was independently associated with incident chronic and acute kidney conditions. This highlights the potential for using suPAR in risk classification models to identify high-risk patients who could benefit from early clinical interventions. The main limitation of this study is its reliance on accurate reporting of ICD-10 codes for kidney disease.
Patients undergoing lung transplantation (LTx) experience a rapid decline in glomerular filtration rate (GFR) in the acute postoperative period. However, no prospective longitudinal studies directly ...comparing the performance of equations for estimating GFR in this patient population currently exist.
In total, 32 patients undergoing LTx met the study criteria. At pre-LTx and 1-, 3-, and 12-weeks post-LTx, GFR was determined by
Cr-EDTA and by equations for estimating GFR based on plasma (P)-Creatinine, P-Cystatin C, or a combination of both.
Measured GFR declined from 98.0 mL/min/1.73 m
at pre-LTx to 54.1 mL/min/1.73 m
at 12-weeks post-LTx. Equations based on P-Creatinine underestimated GFR decline after LTx, whereas equations based on P-Cystatin C overestimated this decline. Overall, the 2021 CKD-EPI combination equation had the lowest bias and highest precision at both pre-LTx and post-LTx.
Caution must be applied when interpreting renal function based on equations for estimating GFR in the acute postoperative period following LTx. Simplified methods for measuring GFR may allow for more widespread use of measured GFR in this vulnerable patient population.
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