Peritoneal Expression of SGLT-2, GLUT1, and GLUT3 in Peritoneal Dialysis 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.

Under-recognition of Acute Kidney Injury after Cardiac Surgery in the ICU Impedes Early Detection and Prevention.

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality; therefore, prevention is important. The aim of this study was to systematically assess AKI incidence after cardiac surgery as documented in clinical routine compared to the real incidence because AKI may be under-recognized in clinical practice. Further, its postoperative management was compared to Kidney Disease: Improving Global Outcomes (KDIGO) recommendations because recognition and adequate treatment represent the fundamental cornerstone in the prevention and management of AKI. METHODS: This retrospective single-center study included n = 100 patients who underwent cardiac surgery with cardiopulmonary bypass. The coded incidence of postoperative AKI during intensive care unit stay after surgery was compared to the real AKI incidence. Furthermore, conformity of postoperative parameters with KDIGO recommendations for AKI prevention and management was reviewed. RESULTS: We found a considerable discrepancy between coded and real incidence, and conformity with KDIGO recommendations was found to be relatively low. The coded incidence was significantly lower (n = 12 vs. n = 52, p < 0.05), representing a coding rate of 23.1%. Regarding postoperative management, 90% of all patients had at least 1 episode with mean arterial pressure <65 mm Hg within the first 72 h. Furthermore, regarding other preventive parameters (avoiding hyperglycemia, stopping angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, avoiding contrast media, and nephrotoxic drugs), only 10 patients (20.8%) in the non-AKI group and in 5 (9.6%) subjects in the AKI group had none of all the above potential AKI-promoting factors. CONCLUSIONS: AKI recognition in everyday clinical routine seems to be low, especially in lower AKI stages, and the current postoperative management still offers potential for optimization. Possibly, higher AKI awareness and stricter postoperative management could already achieve significant effects in prevention and treatment of AKI.

Gender-Specific Differences of Renal Heat Tolerance in Older Adults during Heat Waves.

BACKGROUND: Heat waves are known to cause increased morbidity and mortality in susceptible populations like old and functionally impaired people. The objective of the study was to assess renal tubular stress, a predictor for development of acute kidney injury, during heat waves in Central Europe. As a marker of renal tubular stress tissue inhibitor of metalloproteinases-2 [TIMP-2]·insulin-like growth factor binding protein-7 [IGFBP7], a new FDA-cleared renal tubular stress biomarker, was used. MATERIALS AND METHODS: 68 residents from facilities of sheltered housing with urine samples collected at heat waves in 2015 and at control visits were included. Urinary [TIMP-2]·[IGFBP7] was compared between the heat waves and the control visits. Multivariate linear models were adjusted for age, frailty index, and functional comorbidity index. RESULTS: The median age was 82.0 years, 82.3% were women. The percentage of elevated levels of urinary [TIMP-2]·[IGFBP7] (>0.3 [ng/mL]2/1,000) in the total study population was higher at the heat waves than at the control visits (25.0% vs. 17.7%). The effect of the heat waves on urinary [TIMP-2]·[IGFBP7] was stronger in men than in women: The percentage of elevated levels was 75.0% in men and 14.3% in women. In the multivariate analysis, the mean urinary [TIMP-2]·[IGFBP7] was 0.48 (95% CI 0.25; 0.70) (ng/mL)2/1,000 higher in men than in women. Except gender, a number of additional variables did not show an association with urinary [TIMP-2]·[IGFBP7] at the heat waves or the control visits. CONCLUSIONS: At heat waves, urinary [TIMP-2]·[IGFBP7] was elevated and higher in men than in women. This suggests gender-specific differences in renal heat tolerance in older people.

[Diuretics as a problem-Pharmacokinetics, pharmacodynamics, use in edema or hypertension]. / Diuretika als Problem ­ Pharmakokinetik und -dynamik, Einsatz bei Ödemen oder Hypertonie.

BACKGROUND AND OBJECTIVE: Diuretics are key elements of the pharmacotherapy of diseases in internal medicine. Currently, they are particularly used in the treatment of edema and hypertension. For the treatment with diuretics some rules exist that help to improve the effectiveness and success. The article explains these rules, especially regarding combination treatment and meaningful dose escalation. Additionally, the side effects of treatment are critically discussed. RESULTS AND CONCLUSION: There is little evidence for the influence of diuretics in the treatment of edema on prognostic factors, such as mortality and comorbidities. For an improvement of the prognosis other substances are more important, e.g. angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers; however, diuretics in the treatment of hypertension show clear positive effects on the endpoints. In recent years a problem of side effects was demonstrated (skin cancer). Comparing the benefits regarding prognosis in the treatment of hypertension with the side effects, the administration but with appropriate protective measures seems to be warranted.

Urinary [TIMP-2]·[IGFBP7]-guided randomized controlled intervention trial to prevent acute kidney injury in the emergency department.

BACKGROUND: Early detection and prevention of acute kidney injury (AKI) is important to reduce morbidity and mortality. Discovery of early-detection biomarkers has enabled early preventive approaches. There are no data on early biomarker-guided intervention with nephrological consultation in emergency departments (EDs). METHODS: In this prospective randomized controlled intervention trial, patients at high risk for AKI were screened with urinary [TIMP-2]·[IGFBP7] in the ED of Robert-Bosch-Hospital (Stuttgart, Germany). We screened 257 eligible patients of whom 100 met the inclusion criteria, with urinary [TIMP-2]·[IGFBP7] >0.3, and were included. The intervention group received immediate one-time nephrological consultation after randomization, implementing Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommendations on AKI. The primary outcome was the incidence of moderate to severe AKI within the first day after admission. Secondary outcomes were AKI occurrence within 3 days after admission, need for renal replacement therapy (RRT), length of hospital stay and death. RESULTS: The primary outcome did not differ significantly (P = 0.9) between the groups, neither within the first day nor within the first 3 days after admission. The intervention group had significantly (P < 0.05) lower serum creatinine (SCr) on Day 2 and lower maximum SCr and tended (P = 0.08) to have higher urine output (UOP) at Day 3 than the non-intervention group. No patient in the intervention group needed RRT (0 versus 3) during the hospital stay (P = 0.09). CONCLUSIONS: One-time routine nephrologist-guided application of the KDIGO bundle in ED patients with a risk for AKI cannot currently be recommended. However, due to the uniform trend of study endpoints in favour of intervention, further trials to investigate larger cohorts of more severely ill patients are warranted. TRIAL REGISTRATION: www.ClinicalTrials.gov, study number NCT02730637.

Strong Associations Between Inflammation, Pruritus and Mental Health in Dialysis Patients.

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 disease-associated 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 end-stage renal disease pathophysiology.

Remote Monitoring of Automated Peritoneal Dialysis Patients: Assessing Clinical and Economic Value.

BACKGROUND: For chronic kidney disease patients who progress to end-stage renal disease, survival is dependent on renal replacement therapy in the form of kidney transplantation or chronic dialysis. Peritoneal dialysis (PD), which can be performed at home, is both more convenient and less costly than hemodialysis that requires three 4-h visits per week to the dialysis facility and complicated equipment. Remote therapy management (RTM), technologies that collect medical information and transmit it to healthcare providers for patient management, has the potential to improve the outcomes of patients receiving automated peritoneal dialysis (APD) at home. OBJECTIVE: Estimate through a simulation study the potential impact of RTM on APD patients use of healthcare resources and costs in the United States, Germany, and Italy. METHODS: Twelve APD patient profiles were developed to reflect potential clinical scenarios of APD therapy. Two versions of each profile were created to simulate healthcare resource use, one assuming use of RTM and one with no RTM. Eleven APD teams (one nephrologist, one nurse) estimated resources that would be used. RESULTS: Results from U.S., German, and Italian clinicians found that RTM could avoid use of 59, 49, and 16 resources over the 12 profiles, respectively. Estimated reduced utilization across the three countries ranged from one to two hospitalizations, one to four home visits, two to five emergency room visits, and four to eight unplanned clinic visits. Total savings across all scenarios were $23,364 in the United States, $11,477 in Germany, and $7,088 in Italy. CONCLUSION: In a simulated environment, early intervention enabled by RTM reduced healthcare resource utilization and associated costs.

Impact of an in-Hospital Patient Education Program on Choice of Renal Replacement Modality in Unplanned Dialysis Initiation.

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.

Offering Patients Therapy Options in Unplanned Start (OPTiONS): Implementation of an educational program is feasible and effective.

BACKGROUND: Patients with unplanned dialysis start (UPS) have worse clinical outcomes than non-UPS patients, and receive peritoneal dialysis (PD) less frequently. In the OPTiONS study of UPS patients, an educational programme (UPS-EP) aiming at improving care of UPS patients by facilitating care pathways and enabling informed choice of dialysis modality was implemented. We here report on impact of UPS-EP on modality choice and clinical outcomes in UPS patients. METHODS: This non-interventional, prospective, multi-center, observational study included 270 UPS patients from 26 centers in 6 European countries (Austria, Germany, Denmark, France, United Kingdom and Sweden) who prior to inclusion presented acutely, or were being followed by nephrologists but required urgent dialysis commencement by an acutely placed CVC or PD catheter. Effects of UPS-EP on choice and final decision of dialysis therapy and outcomes within 12 months of follow up were analysed. RESULTS: Among 270 UPS patients who had an unplanned start to dialysis, 214 were able to receive and 203 complete UPS-EP while 56 patients - who were older (p = 0.01) and had higher Charlson comorbidity index (CCI; p < 0.01) - did not receive UPS-EP. Among 177 patients who chose dialysis modality after UPS-EP, 103 (58%) chose PD (but only 86% of them received PD) and 74 (42%) chose HD (95% received HD). Logistic regression analysis showed that diabetes 1.88 (1.05 - 3.37) and receiving UPS-EP, OR = 4.74 (CI, 2.05 - 10.98) predicted receipt of PD. Patients choosing PD had higher CCI (p = 0.01), higher prevalence of congestive heart failure (p < 0.01) and myocardial infarction (p = 0.02), and were more likely in-patients (p = 0.02) or referred from primary care (p = 0.02). One year survival did not differ significantly between PD and HD patients. Peritonitis and bacteraemia rates were better than international guideline standards. CONCLUSIONS: UPS-EP predicted patient use of PD but 14% of those choosing PD after UPS-EP still did not receive the modality they preferred. Patient survival in patients choosing and/or receiving PD was similar to HD despite age and comorbidity disadvantages of the PD groups.

Renal effects of metallothionein induction by zinc in vitro and in vivo.

BACKGROUND: Metallothionein (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. METHODS: MTT 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). CONCLUSIONS: We 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT00399256 . Retrospectively registered 11/13/2006.

Medical diagnosis as a linguistic game.

BACKGROUND: We present a formalized medical knowledge system using a linguistic approach combined with a semantic net. METHOD: Diseases are defined and coded by natural linguistic terms and linked via a complex network of attributes, categories, classes, lists and other semantic conditions. RESULTS: We have isolated more than 4600 disease entities (termed pathosoms using a made-up word) with more than 100.000 attributes sets (termed pathophemes using a made-up word) and a semantic net with more than 140.000 links. All major-medical thesauri like ICD, ICD-O and OPS are included. CONCLUSIONS: Memem7 is a linguistic approach to medical knowledge approach. With the system, we performed a proof of concept and we conclude from our data that our or similar approaches provides reliable and feasible tools for physicians given a formalized history taking is available. Our approach can be considered as both a linguistic game and a third opinion to a set of patient's data.

Urinary [TIMP-2]·[IGFBP7] - Novel Biomarkers to Predict Acute Kidney Injury.

BACKGROUND: Urine microscopy is an established technique to assess kidney disease, and can add valuable information about the mechanism of damage. However, it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in practice. A rapid biomarker test that identifies patients from the emergency department (ED) who are likely to have positive urine microscopy findings would enable more efficient use of this technique. METHODS: Four hundred patients were enrolled in the ED; thereof 362 patients had available both tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2]·[IGFBP7] and urine score (U-Score) data at enrollment. U-Score was assessed through urine microscopy as described previously. RESULTS: Fifteen (4%) of 362 patients had a U-Score >0. When patients were stratified into 3 groups using the validated [TIMP-2]·[IGFBP7] cutoffs of 0.3 and 2.0, the proportion of patients with a positive U-Score increased across the 3 strata from 1 to 6 to 24% (p < 0.001). At the 0.3 cutoff, [TIMP-2]·[IGFBP7] had a sensitivity of 87%, specificity of 62% and negative predictive value (NPV) of 99% for prediction of a positive U-Score. At the 2.0 cutoff, specificity increased to 95% and positive predictive value (PPV) increased to 24%. CONCLUSIONS: In ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources. SUMMARY: Urine microscopy is an established technique to assess acute kidney injury and can add valuable information about the mechanism of damage; however it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in clinical practice. We have shown in ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources.

The Influence of Thyroid Function, Inflammation, and Obesity on Risk Prediction of Acute Kidney Injury by Cystatin C in the Emergency Department.

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.

Offering Patients Therapy Options in Unplanned Start: Development and Implementation of an Education Program for Unplanned-Start Patients.

Unplanned start of dialysis is still a common and important problem for dialysis units in Europe and across the world: 30%-50% of patients can commence therapy in that way. Such patients are known to experience increased morbidity and mortality, to make greater demands on health care resources, and to be less likely to receive their dialysis modality choice. We therefore aimed to meet the specific needs of unplanned-start patients by developing and implementing an Unplanned Start Educational Programme in dialysis units. The new program--which is intended to effectively influence the clinical pathway for patients and to equip health care professionals with the tools necessary to support and optimize the process of unplanned dialysis start--was created with the support of 5 dialysis units and academic experts in patient education. It involves process mapping of patient flows so as to recognize the key steps in the management of unplanned dialysis. Following its successful development, the Unplanned Start Educational Programme was delivered to patients. To evaluate the effectiveness of the program, an observational study, Offering Patients Therapy Options in Unplanned Start, had the primary outcome of measuring the impact of the education program on dialysis modality choice (peritoneal dialysis or hemodialysis).

Telephone Health Coaching and Remote Exercise Monitoring (TeGeCoach) in Peripheral Arterial Occlusive Disease.

BACKGROUND: Supervised exercise programs are used to treat intermittent claudication (IC). Home-based exercise programs have been developed to lower barriers to participation. We studied the effects of one such exercise program (TeGeCoach) on self-reported walking ability in patients with IC. METHODS: In a pragmatic multicenter randomized controlled trial (registration number NCT03496948), 1982 patients with symp - tomatic IC insured by one of three German statutory health insurance funds received either telephone health coaching with remote exercise monitoring (TeGeCoach; n = 994) or routine care (n = 988). The primary outcome was the change in Walking Impairment Questionnaire (WIQ) scores after 12 and 24 months in the intention-to-treat population. The secondary outcomes were healthrelated quality of life, symptoms of depression or anxiety, health competence, patient activation, alcohol use, and nicotine depen - dence. RESULTS: There was a significant group difference in WIQ score in favor of TeGeCoach (p < 0.0001), amounting to 6.30 points at 12 months (Bonferroni-corrected 95% CI [4.02; 8.59], Cohen's d = 0.26) and 4.55 points at 24 months ([2.20; 6.91], d = 0.19). Some of the secondary outcomes also showed positive results in favor of TeGeCoach at 12 months with small effect sizes (d ≥ 0.20), including physical health-related quality of life and patient activation. The average daily step count was not higher in the TeGeCoach group. CONCLUSION: Significant improvements regarding symptom burden demonstrate the benefit of a home-based exercise program and thus expand the opportunities for guideline-oriented treatment of IC. Future studies should additionally address the effect of home-based exercise programs on clinical variables by means of, for example, the 6-minute walk test.

TIMP-2 and IGFBP7 in human kidney biopsies in renal disease.

Background: Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are markers of tubular stress and urinary [TIMP-2]*[IGFBP7] is an established biomarker for risk assessment of acute kidney injury. There are no studies of expression profiles or localization of these markers in human renal tissue with confirmed renal disease. Methods: We analysed 37 kidney biopsies of patients with renal disease and 10 non-diseased control biopsies for TIMP-2 and IGFBP7 expression using immunohistochemistry. Changes in glomerular morphology were evaluated by a semi-quantitative glomerulosclerosis score (GSI) and tubular interstitial changes were graded by the tubular injury score (TSI) using periodic acid-Schiff-stained paraffin sections. Interstitial fibrosis and tubular atrophy (IF/TA) were graded according to the Banff classification. Urinary [TIMP-2]*[IGFBP7] was collected at the time of biopsy. Results: TIMP-2 and IGFBP7 had significantly greater expression in kidney biopsies from patients with renal disease compared with control tissue, especially in the tubular compartment. Here, IGFBP7 was detected in proximal and distal tubules while TIMP-2 was predominantly localized in the collecting ducts. Renal injury significantly correlated with staining intensity for TIMP-2 and IGFBP7: GSI weakly correlated with glomerular TIMP-2 (r = 0.36) and IGFBP7 (r = 0.35) and TSI correlated with tubular TIMP-2 (r = 0.41) and IGFBP7 (r = 0.43). Urinary [TIMP-2]*[IGFBP7] correlated weakly with the histopathological damage score but not with glomerular and tubular expression. Conclusion: Our findings underline the role of TIMP-2/IGFBP7 as an unspecific marker of renal injury that is already in use for early detection of acute kidney injury.

Algorithm-based detection of acute kidney injury according to full KDIGO criteria including urine output following cardiac surgery: a descriptive analysis.

BACKGROUND: Automated data analysis and processing has the potential to assist, improve and guide decision making in medical practice. However, by now it has not yet been fully integrated in a clinical setting. Herein we present the first results of applying algorithm-based detection to the diagnosis of postoperative acute kidney injury (AKI) comprising patient data from a cardiac surgical intensive care unit (ICU). METHODS: First, we generated a well-defined study population of cardiac surgical ICU patients by implementing an application programming interface (API) to extract, clean and select relevant data from the archived digital patient management system. Health records of N = 21,045 adult patients admitted to the ICU following cardiac surgery between 2012 and 2022 were analyzed. Secondly, we developed a software functionality to detect the incidence of AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, including urine output. Incidence, severity, and temporal evolution of AKI were assessed. RESULTS: With the use of our automated data analyzing model the overall incidence of postoperative AKI was 65.4% (N = 13,755). Divided by stages, AKI 2 was the most frequent maximum disease stage with 30.5% of patients (stage 1 in 17.6%, stage 3 in 17.2%). We observed considerable temporal divergence between first detections and maximum AKI stages: 51% of patients developed AKI stage 2 or 3 after a previously identified lower stage. Length of ICU stay was significantly prolonged in AKI patients (8.8 vs. 6.6 days, p <  0.001) and increased for higher AKI stages up to 10.1 days on average. In terms of AKI criteria, urine output proved to be most relevant, contributing to detection in 87.3% (N = 12,004) of cases. CONCLUSION: The incidence of postoperative AKI following cardiac surgery is strikingly high with 65.4% when using full KDIGO-criteria including urine output. Automated data analysis demonstrated reliable early detection of AKI with progressive deterioration of renal function in the majority of patients, therefore allowing for potential earlier therapeutic intervention for preventing or lessening disease progression, reducing the length of ICU stay, and ultimately improving overall patient outcomes.

The effect of telephone health coaching and remote exercise monitoring for peripheral artery disease (TeGeCoach) on health care cost and utilization: results of a randomized controlled trial.

BACKGROUND: Peripheral artery disease (PAD) is the third most prevalent atherosclerotic cardiovascular disease. In 2016, costs per patient associated with PAD exceeded even the health-economic burden of coronary heart disease. Although affecting over 200 million people worldwide, a clear consensus on the most beneficial components to be included in home-based exercise programs for patients with peripheral artery disease is lacking. The aim of the study was to examine the health care use and costs caused by the 12-month patient-centered 'Telephone Health Coaching and Remote Exercise Monitoring for Peripheral Artery Disease' (TeGeCoach) program in a randomized controlled trial. METHODS: This is a two-arm, parallel-group, open-label, pragmatic, randomized, controlled clinical trial (TeGeCoach) at three German statutory health insurance funds with follow-up assessments after 12 and 24-months. Study outcomes were medication use (daily defined doses), days in hospital, sick pay days and health care costs, from the health insurers' perspective. Claims data from the participating health insurers were used for analyses. The main analytic approach was an intention-to-treat (ITT) analysis. Other approaches (modified ITT, per protocol, and as treated) were executed additionally as sensitivity analysis. Random-effects regression models were calculated to determine difference-in-difference (DD) estimators for the first- and the second year of follow-up. Additionally, existing differences at baseline between both groups were treated with entropy balancing to check for the stability of the calculated estimators. RESULTS: One thousand six hundred eighty-five patients (Intervention group (IG) = 806; Control group (CG) = 879) were finally included in ITT analyses. The analyses showed non-significant effects of the intervention on savings (first year: - 352€; second year: - 215€). Sensitivity analyses confirmed primary results and showed even larger savings. CONCLUSION: Based on health insurance claims data, a significant reduction due to the home-based TeGeCoach program could not be found for health care use and costs in patients with PAD. Nevertheless, in all sensitivity analysis a tendency became apparent for a non-significant cost reducing effect. TRIAL REGISTRATION: NCT03496948 (www. CLINICALTRIALS: gov), initial release on 23 March 2018.

Influence of thyroid function on different kidney function tests.

BACKGROUND/AIMS: The commonly used kidney function tests have limitations, especially in thyroid dysfunction. Therefore, we studied the most commonly used kidney function tests in patients with hypo- and hyperthyroidism and after reaching euthyroidism. METHODS: Prospective case series in 16 patients with thyroid dysfunction. Serum creatinine, 24-hour creatinine clearance, calculated glomerular filtration rate (GFR) by Cockroft-Gault, estimated GFR (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration equation, serum cystatin C, eGFR based on cystatin C, eGFR based on a combined (cystatin C and creatinine) formula and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured in hypo- and hyperthyroidism and after gaining euthyroidism. RESULTS: When free thyroxine (fT(4)) normalized in hypothyroid patients, creatinine decreased and creatinine-based eGFR increased significantly. In contrast, cystatin C increased and eGFR based on cystatin C decreased significantly. There was no significant change in NGAL levels. When fT(4) normalized in patients with hyperthyroidism, creatinine increased and creatinine-based eGFR decreased significantly. In contrast, cystatin C decreased and cystatin-C-based GFR increased significantly. There was no significant change in NGAL levels. CONCLUSIONS: Thyroid function has a major influence on the vast majority of kidney function tests. Cystatin C is strongly influenced by the thyroid function and should be avoided in thyroid disorders. There was no effect on the plasma NGAL levels. The recommended kidney function test is a measurement of creatinine-based eGFR.

Tubulointerstitial nephritis in active tuberculosis - a single center experience.

BACKGROUND: Tuberculosis (TB) is a common disease worldwide, but kidney affection, i.e. tubulointerstitial nephritis (TIN) caused by Mycobacterium tuberculosis is rare. More frequent in patients with TB is drug induced TIN, i.e. the result of intensive antitubercular treatment. PATIENTS AND METHODS: In the time between April 2005 until August 2011 data from all patients (4 male, 1 female) with clinical evidence of active TB and significant renal disease were collected. All patients were treated with antitubercular treatment according to standard protocols. All patients underwent kidney biopsy due to progressive renal failure and all of the renal biopsies revealed an interstitial inflammation with eosinophilia. Epitheloid granulomata were found in 3 of 5 patients, whereas caseating granulomata were found in only one patient. No patient had sterile leucozyturia and all patients were negative for Mycobacterium tuberculosis on PCR; of note, none of the renal biopsies examined were positive for acid and alcohol fast bacilli by Ziehl-Neelsen staining. CONCLUSIONS: TB associated TIN is rare, but needs a rapid recognition and an early treatment. Kidney biopsy should be performed in patients with TB and renal disease to ensure the diagnosis of renal involvement of active TB and established correct treatment (intensifying TB treatment or changing TB therapy in drug induced TIN). Additionally, negative PCR of the histopathological samples should not exclude TB associated TIN and sterile leukocyturia is less common than expected.