www.ClinicalTrials.gov, study number NCT02730637.

Background In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP‐2] × [IGFBP7], a new US Food and Drug Administration–cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients. Hypothesis In patients with ADHF, urinary [TIMP‐2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality. Methods We enrolled 400 patients in the emergency department at Robert‐Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP‐2] × [IGFBP7] (units: [ng/mL]2/1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0. Results Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2–3 within 7 days. Urinary [TIMP‐2] × [IGFBP7] discriminated for AKI stage 2–3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72‐0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65‐0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2–3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP‐2] × [IGFBP7] >2.0 and AKI 2–3. Conclusions Urinary [TIMP‐2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.

Itch, impaired mental health and inflammation contribute to morbidity in dialysis patients. We therefore analysed laboratory results, intensity of itch and psychological tests in dialysis patients with pruritus, without and healthy people. The data was analysed by different statistical tests. This revealed 3 independent groups. One was mainly driven by itch, one by mental health and another by inflammatory parameters. Additionally, all 3 showed strong associations. This means inflammation, mental health and itch are some how interconnected in dialysis patients. Since all 3 comorbidities are associated with the risk of death, knowledge about the interdependence of these factors is important. Pruritus, impaired mental health and inflammation contribute to morbidity in end-stage renal disease. There are no studies on all 3 conditions. We therefore obtained inflammatory parameter data (C-reactive protein and interleukin-6), pruritus data and psychological test data (36-Item Short-Form Health Survey, "Allgemeine Depressionsskala" and Toronto Alexithymia Scale-20) for 19 dialysis patients with pruritus, 20 dialysis patients without pruritus and 15 healthy controls. Non-parametric hierarchical clustering revealed 3 clusters of parameters: one mainly driven by pruritus scores (chronic kidney disease-associated pruritus cluster), one by mental health scores (mental health cluster) and one by inflammatory parameters (inflammatory cluster). Factor analysis showed strong associations (mental health cluster/chronic kidney diseaseassociated pruritus cluster, r=-0.49; mental health cluster/inflammatory cluster, r=-0.52; inflammatory cluster/chronic kidney disease-associated pruritus cluster, r=0.48). For the first time, complete correlations between inflammation, mental health and pruritus in dialysis patients have been established. As all 3 conditions are associated with mortality, knowledge about their interdependence helps to understand endstage renal disease pathophysiology.

Background/Aims: Up to 50% patients requiring dialysis receive an urgent, unplanned start (UPS) to renal replacement therapy (RRT). Most of these are initiated with an intravenous catheter and commenced and maintained on hemodialysis (HD). Although peritoneal dialysis (PD) could be an equipotent initial modality for RRT, it is used less frequently as long-term RRT in UPS patients. This multicenter-study aimed to evaluate the impact of a structured, in-hospital education program and factors influencing PD rates, especially in UPS patients. Methods: Three German nephrology departments collaborated to implement an in-hospital education program. Retrospective analysis included 336 subjects and compared the rates of HD and PD in consecutive patients who started RRT 12 months prior (two centers) and for 12 months after (three centers) implementing the education program. Results: PD rates increased significantly (p < 0.05) by 66% in all planned and unplanned dialysis starts after implementation of a structured, patient-centered education program. A highly significant (p < 0.0001) rise in utilization of PD was found, especially in UPS patients. In logistic regression analysis, PD modality choice was significantly influenced by age (p < 0.0001) and gender (p = 0.006). Conclusions: A structured, patient-centered in-hospital education program increases the frequency of PD in patients needing unplanned RRT. PD modality choice is significantly higher in young (p < 0.0001) and male (p = 0.006) patients.

Introduction: In peritoneal dialysis (PD) patients, the peritoneal membrane is affected by glucose-based solutions used as peritoneal dialysate fluids. This exposure leads to changes of the membrane which may eventually culminate in fibrosis and method failure. In vitro or animal studies demonstrated that glucose transporters are upregulated upon exposure to these solutions. Expression studies of glucose transporters in human peritoneum have not been reported yet. Methods: Expression of SGLT-2, GLUT1, and GLUT3 in human peritoneal biopsies was analyzed by real-time polymerase chain reaction and Western blot analysis. The localization of these glucose transporters in the peritoneum was evaluated by immunohistochemistry using a Histo-Score. Results: Peritoneal biopsies of patients (healthy controls, uremic, PD, and encapsulating peritoneal sclerosis [EPS]) were analyzed. We found evidence of SGLT-2, GLUT1, and GLUT3 expression in the peritoneal membrane. Protein expression of SGLT-2 increases with PD duration and is significantly enhanced in EPS patients. All transporters were predominantly, but not exclusively, located adjacent to the vessel walls of the peritoneal membrane. Conclusion: Our study showed that SGLT-2, GLUT1, and GLUT3 were regularly expressed in the human peritoneum. SGLT-2 was particularly upregulated in PD patients with EPS, suggesting that this upregulation may be associated with pathological changes in the peritoneal membrane in this syndrome. Since preclinical studies in mice show that SGLT-2 inhibitors or downregulation of SGLT-2 ameliorated pathological changes in the peritoneum, SGLT-2 inhibitors may be potentially promising agents for therapy in PD patients that could reduce glucose absorption and delay functional deterioration of the peritoneal membrane in the long term.

Background/Aims: There is a growing role for emergency departments (ED) in assessing acute kidney injury (AKI) for hospital admissions but there are few studies addressing acute kidney injury biomarkers and confounding factors in the ED. Cystatin C (CysC), a newer renal biomarker, is influenced by thyroid function, inflammation and obesity. This study aims to be the first study to address the impact of these parameters in the ED. Methods: Admitted patients (n=397) were enrolled in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) was recorded for AKI classification by Kidney Diseases Improves Global Outcome (KDIGO) criteria. CysC, thyroid stimulating hormone (TSH), thyroxine (T4), C-reactive protein (CRP) and body mass index (BMI) were registered at enrollment in the ED. Serum samples were collected at enrollment, after 6 hours and in the following mornings (day 1 to day 3). The correlation of CysC and sCr was studied on a two variable logistic regression model. A linear predictor was computed to predict minimal AKI stage and area under the curve (AUC) was calculated. Results: Of 397 patients enrolled for classification by KDIGO AKI criteria, n=152 (38%) developed AKI, n=69 (17.4%) reached AKI stage I, n=70 (17.6%) AKI stage II, and n=13 (3%) AKI stage III. Although a correlation between CRP and CysC levels was shown (rho=0.376), this didn't affect the predictive ability for AKI according to our data. We compared receiver operating characteristic (ROC) curves (DeLong test) of CysC to ROC curves of CysC with the additional variables TSH, BMI, and CRP respectively. Our data shows that addition of CRP, TSH, or BMI does not improve prediction of AKI stage beyond prediction based solely on CysC levels. Conclusions: CysC is known to be influenced by thyroid function, inflammation and obesity, but in our large ED population there was no significant impact of these factors on the diagnostic accuracy of CysC to detect AKI in ED patients.

Introduction: Platinum-based chemotherapy (PBC) is a potent antineoplastic treatment, but cisplatin nephrotoxicity is often the limiting factor. Identifying the patients who are at risk for developing platinum-induced renal injury is an important issue. We tested urinary TIMP2·IGFBP7, a new US Food and Drug Administration (FDA)-cleared test to assess the risk of acute kidney injury (AKI), in a cohort of patients with malignant neoplastic disease receiving PBC. Patients and methods: A total of 58 patients with malignant neoplastic disease were enrolled in this study, of whom 32 patients had both urine samples and subsequent serum creatinine values available for detecting AKI within 72 hours. Urine samples were collected within 6 hours prior to PBC application and within 12 hours after the end of chemotherapy administration. We examined the predictive ability of TIMP2·IGFBP7 for the development of AKI as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria within 72 hours after the administration of chemotherapy. Operating characteristics were determined for the previously validated TIMP2·IGFBP7 cutoff of 0.3 (ng/mL) 2 /1000. Results: Four (12.5%) patients developed AKI within 72 hours. Primary disease was lymphoma in 13 patients (40.6%) and solid tumors in 19 patients (59.4%). Eight patients (25.0%) received carboplatin and 24 (75.0%) cisplatin. TIMP2·IGFBP7 after PBC administration discriminated for the risk of AKI with an area under the receiver operating characteristic curve (AUC; 95% confidence interval) of 0.92 (0.80-1.00). At the cutoff of 0.3 for TIMP2·IGFBP7, sensitivity was 50%, specificity was 87%, negative predictive value was 95% and positive predictive value was 25% for the prediction of AKI within 72 hours. Conclusion: Urinary TIMP2·IGFBP7 measured in specimens gathered after PBC may be a useful tool to early identify patients who are at risk for developing platinum-induced AKI.

BackgroundMetallothionein (MTT) is an endogenous antioxidant that can be induced by both zinc (Zn) and ischemia. In kidneys, increased MTT expression exerts a putative protective role in diabetes and hypoxia. Our goal was to further investigate the behavior of MTT under the influence of Zn and hypoxia in vitro and in vivo.MethodsMTT expression was measured in vitro in cell cultures of proximal tubular cells (LCC-PK1) by immune-histochemistry and real-time PCR after incubation with increasing concentrations of Zn under hypoxic and non-hypoxic conditions. In addition, in vivo studies were carried out in 54 patients to study MTT induction through Zn. This is a sub-study of a prospective, randomized, double-blind trial on prevention of contrast-media-induced nephropathy using Placebo, Zn and N-Acetylcysteine. Blood samples were obtained before and after 2 days p.o. treatment with or without Zn (60 mg). ELISA-based MTT level measurements were done to evaluate the effects of Zn administration. For in vivo analysis, we considered the ratio of MTT to baseline MTT (MTT1/MTT0) and the ratio of eGFR (eGFR1/eGFR0), correspondingly.Results In vitro quantitative immuno-histochemical analysis (IHC) and real-time PCR showed that at increasing levels of Zn (5, 10, and 15 μg/ml) led to a progressive increase of MTTs: Median (IQR) expression of IHC also increased progressively from 0.10 (0.09–0.12), 0.15 (0.12–0.18), 0.25 (0.25–0.27), 0.59 (0.48–0.70) (p < 0.0001). Median (IQR) expression of PCR: 0.59 (0.51–1.72), 1.62 (1.38–4.70), 3.58 (3.06–10.42) and 10.81 (9.24–31.47) (p < 0.0001). In contrast, hypoxia did not change MTT-levels in vitro (p > 0.05). In vivo no significant differences (p = 0.96) occurred in MTT-levels after 2 days of Zn administration compared with no Zn intake. Nevertheless, there was a significant correlation between MTT (MTT1/MTT0) and eGFR (eGFR1/eGFR0) in case of Zn administration (rho = −0.49; 95%-CI: −0.78 to −0.03; p = 0.04).ConclusionsWe found that Zn did induce MTTs in vitro, whereas hypoxia had no significant impact. In contrast, no significant increase of MTTs was detected after in vivo administration of Zn. However, there was a significant negative correlation between MTT and eGFR in vivo in case of Zn administration, this could indicate a protective role of MTTs in a setting of reduced kidney function, which is possibly influenced by Zn.Trial registrationClinicalTrials.gov Identifier: NCT00399256. Retrospectively registered 11/13/2006.