Improving adherence to immunosuppression after liver or kidney transplantation in individuals with impairments in personality functioning - A randomized controlled single center feasibility study.

Introduction: Although adherence to immunosuppressive medication is the key factor for long-term graft survival today, 20-70% of transplant recipients are non-adherent to their immunosuppressive medication. Objective: A prospective, randomized, controlled single-center feasibility study was designed to evaluate the impact of a step guided multicomponent interprofessional intervention program for patients after kidney or liver transplantation on adherence to their immunosuppressive medication in daily clinical practice. Materials and methods: The intervention consisted of group therapy and daily training as well as individual sessions in a step guided approach. The primary endpoint of the study was adherence to immunosuppression as assessed with the "Basel Assessment of Adherence to Immunosuppressive Medications Scale" (BAASIS). The coefficient of variation (CV%) of Tacrolimus (TAC) through levels and the level of personality functioning was a secondary endpoint. We conducted six monthly follow-up visits. Results: Forty-one age- and sex-matched patients [19 females, 58.5 (SD = 10.56) years old, 22 kidney- and 19 liver transplantation] were randomized to the intervention- (N = 21) or control-group (N = 20). No differences between intervention- and control groups were found in the primary endpoint adherence and CV% of TAC. However, in further exploratory analyses, we observed that individuals with higher impairments in personality functioning showed higher CV% of TAC in the controls. The intervention might compensate personality-related susceptibility to poor adherence as evident in CV% of TAC. Discussion: The results of the feasibility study showed that this intervention program was highly accepted in the clinical setting. The Intervention group could compensate higher CV% of TAC after liver or kidney transplantation in individuals with lower levels of personality functioning and non-adherence. Clinical trial registration: ClinicalTrials.gov, identifier NCT04207125.

Vitamin D metabolism in living kidney donors before and after organ donation.

OBJECTIVES: Living kidney donors provide a unique setting to study functional and metabolic consequences after organ donation. Since the lack of data of the homoeostasis of numerous vitamin D metabolites in these healthy subjects, the aim of this study was to assess the vitamin D metabolism before and after kidney donation. METHODS: We investigated the 25-dihydroxyvitamin D2 (25[OH]D2), 25-dihydroxyvitamin D3 (25[OH]D3), 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), 24,25-dihydroxyvitamin D3 (24,25[OH]2D3), 25,26-dihydroxyvitamin D3 (25,26[OH]2D3), and the native vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in a well characterized study cohort of 32 healthy living kidney donors before and after organ donation. RESULTS: Thirty-two healthy subjects after kidney donation had significantly lower median (interquartile range) 1,25(OH)2D3 serum concentrations (88.6 [62.6-118.8] vs. 138.0 [102.6-152.4] pmol/L, p<0.001) and significantly higher median 25(OH)D2 serum levels (1.80 [1.19-2.19] vs. 1.11 [0.74-1.59] nmol/L, p=0.019) than before donation. Similar serum concentrations of 25(OH)D3 and 25,26(OH)2D3 were observed before and after donation. The 24,25(OH)2D3 blood levels distinctly decreased after organ donation (4.1 [2.3-5.3] vs. 5.3 [2.2-6.9] nmol/L, p=0.153). Native vitamin D2 (0.10 [0.08-0.14] vs. 0.08 [0.06-0.12] nmol/L, p=0.275) was slightly increased and vitamin D3 (1.6 [0.6-7.2] vs. 2.5 [0.9-8.6] nmol/L, p=0.957) decreased after kidney donation. CONCLUSIONS: Living kidney donors were found with decreased 1,25(OH)2D3 and 24,25(OH)2D3, increased 25(OH)D2 and consistent 25(OH)D3 and 25,26(OH)2D3 serum concentrations after organ donation. The current study advances the understanding on vitamin D metabolism suggesting that altered hydroxylase-activities after donation is accompanied by compensatory elevated dietary-related 25(OH)D2 blood concentrations.

Individual uromodulin serum concentration is independent of glomerular filtration rate in healthy kidney donors.

OBJECTIVES: The mucoprotein uromodulin is considered to correlate with glomerular filtration rates (GFR) in patients with chronic kidney disease (CKD). Here we investigated how serum uromodulin is associated with measured GFR using inulin-clearance and GFR estimated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy subjects. METHODS: We assessed possible correlations between uromodulin serum concentrations, inulin-GFR and CKD-EPI-GFR in a well characterized study cohort of 112 healthy living kidney donors with two kidneys before and 64 with one kidney after kidney donation. A subgroup of 32 individuals, which presented data before and after nephrectomy, was assessed separately. RESULTS: All 112 healthy living kidney donors with two kidneys revealed individual serum uromodulin concentrations between 60.1 and 450.5 µg/L. Sixty-four healthy kidney donors after nephrectomy had significantly lower median (interquartile range) serum uromodulin concentrations (124 [101-166] vs. 185 [152-238] µg/L), inulin-GFR (67.3 [60.6-74.6] vs. 93.5 [82.1-104.4] mL/min/1.73 m2), and CKD-EPI-GFR (61.2 [53.1-69.7] vs. 88.6 [80.0-97.1] mL/min/1.73 m2) as compared to the 112 donors before donation (p<0.001). The subgroup of 32 subjects, which presented data before and after nephrectomy, showed almost the same pattern of kidney function. No statistically relevant associations were found between serum uromodulin and inulin-GFR or CKD-EPI-GFR regarding this healthy population. CONCLUSIONS: These novel findings indicate that - in contrast to patients with CKD - serum uromodulin concentrations are not correlated with measured and estimated GFR in healthy individuals.

Estimation versus measurement of the glomerular filtration rate for kidney function assessment in patients with cancer undergoing cisplatin-based chemotherapy.

Glomerular filtration rate (GFR) assessment is indicated before every administration of cisplatin. The optimal modality for this purpose [GFR measurement by urinary Creatinine Clearance (uCrCl) versus GFR estimation (eGFR) by the CKD-EPI formula versus both] is unclear. We investigated whether eGFR only is safe in this setting. Paired uCrCl and eGFR determinations from 470 cisplatin cycles from 121 patients were analyzed [median age: 55 years; most frequent tumor site: genitourinary (45%); palliative treatment: n = 41 (34%)]. Primary endpoint was the proportion of cycles with uCrCl < 50 ml/min/1.73m2 and eGFR ≥ 50 ml/min/1.73m2 (i.e. a "false negative" result when only determining eGFR). The primary endpoint occurred in 8 of 470 cisplatin cycles (1.7%, 95%CI 0.5-2.9). In all 8 events, uCrCl was lower than eGFR (mean uCrCl vs. eGFR: 43 versus 112 ml/min/1.73m2). The uCrCl was re-measured in all patients, and showed normal results in all but 1 patient. None of these events precluded the administration of cisplatin at the planned date, and no subsequent cases of acute nephrotoxicity occurred. Overall agreement between uCrCl and eGFR was low, with qualitative analysis suggesting frequent incompliance with 24-h urine collection. We conclude that an eGFR is sufficient for assessing kidney function in patients with cancer undergoing cisplatin therapy.

Employment Status and Associations with Workability, Quality of Life and Mental Health after Kidney Transplantation in Austria.

Kidney transplantation (KTx) in end-stage renal disease is associated with a significant increase in quality of life (QoL) and self-perceived health, optimally leading to the maintenance of employment or return to work (RTW) in working-age patients. The aim of this study was to assess individual factors including the QoL and mental health of kidney transplant recipients (KTRs) associated with employment after transplantation. A cross-sectional study including working-age patients with a history of KTx after 2012 was conducted at two Austrian study centers (Vienna and Graz). Brief Symptom Inventory (BSI-18), World Health Organization Quality of Life (WHOQOL-Bref) and Workability Index (WAI) were assessed along with detailed questionnaires on employment status. Out of n = 139 KTRs (43.2 ± 9.07 years; 57.6% male), 72 (51.8%) were employed. Employed patients were more frequently in a partnership (p = 0.018) and had higher education levels (p = 0.01) and QoL scores (<0.001). Unemployed KTRs reported fatigue and mental health issues more often (p < 0.001), and had significantly higher anxiety, depression and somatization scores (BSI-18). In unadjusted logistical regression, workability score (WAS; odds ratio (OR) = 3.39; 95% confidence interval (CI) = 1.97-5.82; p < 0.001), partnership (OR = 5.47; 95% CI 1.43-20.91; p = 0.013) and no psychological counseling after KTx (OR = 0.06; 95% CI = 0.003-0.969; p = 0.048) were independently associated with employment. Self-assessed mental health, workability and QoL were significantly associated with employment status after KTx. Thus, in order to facilitate RTW after KTx in Austria, vocational rehabilitation and RTW programs addressing KTRs should focus on increasing social support and care for their mental health.

Massive open online courses (MOOCs) for long-distance education in geriatric medicine across Europe : A pilot project launched by the consortium of the project "Screening for Chronic Kidney Disease among Older People": SCOPE project.

PURPOSE: To cover the increasing need for professional knowledge, skills and competences in the care of older people, new learning techniques have been developed. Using the Internet to provide educational material has come into focus of many academic institutions as the learning content can easily be transferred to a larger audience. Since the first launch of a "massive open online course" (MOOC) in 2008, this educational format has raised increasing interest among education experts. The current publication provides insight into the new format of MOOCs in general and specifically describes a MOOC developed by a Pan-European Consortium "Screening for Chronic Kidney Disease (CKD) among Older People across Europe" (SCOPE), a project funded by the European Commission under the umbrella of the Horizon 2020 program. METHODS: Technical background, learning theories and content of the MOOC of the SCOPE project are presented in this overview. RESULTS: The MOOC of the SCOPE project is provided on the MOOC ICT platform iMoox. The courses are built up of video clips, textual descriptions, graphics, animations and audio designed with a clear structure and learning goals. The concise video clips with a maximum length of 15-20 min are equipped with additional learning material such as documents, links and asynchronous communication opportunities. CONCLUSION: MOOCs are recognized as a contemporary approach to transfer required knowledge and skills not only in general but also in geriatric medicine, as the health and social care environment is ever-changing and becoming more complex.

The chronic kidney disease epidemiology collaboration equation combining creatinine and cystatin C accurately assesses renal function in patients with cirrhosis.

BACKGROUND: Accurate measurement of renal function in cirrhotic patients is still challenging. To find the best test for the determination of the true glomerular filtration rate (GFR) in cirrhotic patients this study prospectively compared measured (m)GFR, the gold standard, with estimated (e)GFR using equations based on serum levels of creatinine and cystatin C. METHODS: GFR was measured by sinistrin clearance using the bolus method in 50 patients with cirrhosis (Child Turcotte Pugh score A, B and C) and 24 age-matched healthy subjects as controls. Measured (m)GFR was compared to eGFR using bias, accuracy 10 % and 30 %, as well as correlation coefficients. RESULTS: Creatinine-based equations generally overestimated GFR in patients with cirrhosis and showed a bias (average difference between mGFR and eGFR) of -40 (CG), -12 (MDRD) and -9 (CKD-EPI-Cr) ml/min/1.73 m(2). Cystatin C-based equations underestimated GFR, especially in patients with Child Turcotte Pugh score C (bias 17 ml/min/1.73 m(2)for CKD-EPI-CysC). Of these equations, the CKD-EPI equation that combines creatinine and cystatin C (CKD-EPI-Cr-CysC) showed a bias of 0.12 ml/min/1.73 m(2) as compared to measured GFR. CONCLUSIONS: The CKD-EPI equation that combines serum creatinine and cystatin C measurements shows the best performance for accurate estimation of GFR in cirrhosis, especially at advanced stages.

The Effect of Mammalian Target of Rapamycin Versus Calcineurin Inhibitor-based Immunosuppression on Measured Versus Estimated Glomerular Filtration Rate After Orthotopic Liver Transplantation.

INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors have been proposed to preserve renal function in patients after orthotopic liver transplantation (OLT) based on estimated glomerular filtration rate (eGFR). The presented study evaluated their effect on renal function in comparison to calcineurin inhibitors (CNIs) defined by measured GFR. METHODS: Renal function was measured in patients on mTOR-based (n=28) or on CNI-based (n=51) immunosuppression after OLT by performing inulin clearance (IC) as well as eGFR based on the Modification of Diet in Renal Disease (MDRD4) Study and the chronic kidney disease epidermiology (CKD-EPI) formula at baseline, 6, 12, 18, and 24 months. Statistical analysis was performed by using analysis of variance and serial measurement testing. RESULTS: The MDRD4 and the IC values differed significantly at study inclusion in both groups (mTOR and CNI group, P=0.001), whereas the CKD-EPI and the IC values did not. Estimated GFR by the MDRD4 results declined throughout the study period in patients on CNI and in patients on mTOR (CNI, 81 vs. 61 mL/min/1.73 m(2), P=0.01; 82 vs. 60 mL/min/1.73 m(2), P=0.01), whereas CKD EPI and measured GFR did not change throughout the study period in the CNI. CONCLUSION: The use of eGFR especially the MDRD-based formula, in OLT patients, leads to incorrect interpretation of their renal function.

Glomerular filtration rate (GFR) determination via individual kinetics of the inulin-like polyfructosan sinistrin versus creatinine-based population-derived regression formulae.

BACKGROUND: In renal patients estimation of GFR is routinely done by means of population-based formulae using serum creatinine levels. For GFR determination in the creatinine-blind regions or in cases of reno-hepatic syndrome as well as in critical cases of live kidney donors individualized measurements of GFR (mGFR) employing the kinetics of exogenous filtration markers such as the inulin-like polyfructosan sinistrin are necessary. The goal of this study is to compare mGFR values with the eGFR values gained by the Modification of Diet in Renal Disease (MDRD4) and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formulae. METHODS: In 170 subjects comprising persons with normal renal function or with various stages of kidney diseases (CKD 1-4) GFR was measured by application of intravenous bolus of sinistrin and assessment of temporal plasma concentration profiles by means of pharmacokinetic methods (mGFR). Comparisons of mGFR with MDRD4- and CKD-EPI-derived eGFR values were performed by means of linear regression and Bland-Altman analyses. RESULTS: Reasonable agreement of mGFR and eGFR values was observed in patients with poor renal function [GFR below 60 (ml/min)/1.73 m²]. In cases of normal or mildly impaired renal function, GFR determination by MDRD4 or CKD-EPI tends to underestimate GFR. Notably, there is practically no difference between the two eGFR methods. CONCLUSIONS: For routine purposes or for epidemiological studies in cases of poor renal function eGFR methods are generally reliable. But in creatinine-blind ranges [GFR above 60 (ml/min)/1.73 m²] eGFR values are unreliable and should be replaced by clinically and physiologically suitable methods for mGFR determination. CONSORT: http://www.consort-statement.org/index.aspx?o=1190.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine-based equations.

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr- and CysC-based equations including the Chronic kidney disease (CKD)-EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft-Gault, Hoek, Larsson, and the CKD-EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty-five percent had a GFR < 60 ml/min/1.73 m(2) according to the IC. The Larsson, the Hoek and the CKD-EPI-CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr-based equations showed less bias than CysC-based formulas with a similar precision. All CysC-based equations were superior as compared with sCr-based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m(2).

Acute effect of a soy protein-rich meal-replacement application on renal parameters in patients with the metabolic syndrome.

BACKGROUND: Soy protein is used for meal replacement therapy in obesity, however the influence on renal function parameters is not adequately investigated. This study evaluates glomerular filtration rate (GFR) and renal plasma flow (RPF) in patients with the metabolic syndrome and healthy controls after ingestion of different amounts of soy protein. METHODS: 10 patients with the metabolic syndrome but no signs of kidney disease and 10 healthy controls ingested 1 g protein/kg body weight of a commercial soy-yoghurt-honeypreparation. The patient group was also given a protein challenge of 0.3 g/kg body weight. RESULTS: Baseline GFR and RPF both were significantly higher in the patient group (147 ± 34.8 vs. 116 ± 21.1 ml/min, p=0.01 and 848 ± 217 vs. 637 ± 121 ml/min, p=0.02) and were strongly correlated with body weight. Use of different algorithms to estimate GFR resulted in underestimation of GFR, particularly in the patients with the metabolic syndrome. The challenge with an acute protein load of 1g protein per kilogram body weight induced a significant increase in GFR and RPF in healthy controls (GFR: +12.6 ± 11.0 % (p=0.01), RPF: +13.6 ± 15.6 % (p=0.04)) and even more in patients with the metabolic syndrome (GFR: +31.5 ± 32.2 % (p=0.01); RPF: +19.4 ± 22.7 % (p=0.02)). The ingestion of 0.3 g protein/ kg body weight did not induce significant changes. CONCLUSIONS: Basic renal function is changed in patients with the metabolic syndrome, even without microalbuminuria. In addition, there is an elevated susceptibility for protein load. However, the protein amount recommended for use in soy-protein based meal replacement therapy induced no significant changes.

Cystatin C does not detect acute changes in glomerular filtration rate in early diabetic nephropathy.

BACKGROUND: The measurement of renal functional reserve (acute change in glomerular filtration rate [GFR] after protein load) allows the detection of sub-clinical renal dysfunction and has prognostic implications in diabetes. Our aim was to test cystatin C as an index of GFR and renal functional reserve. METHODS: GFR was measured by C(Sinistrin) at baseline and after protein load in 28 diabetic patients with serum creatinine <1.2 mg/dL. The C(Sinistrin) was compared with cystatin C, serum creatinine, creatinine clearance, and Cockcroft-Gault formula. RESULTS: Baseline C(Sinistrin) ranged from 67-172 mL/min. Regression analysis showed an overall low relationship between C(Sinistrin) and the indirect markers of GFR. The highest correlation with C(Sinistrin) was obtained for cystatin C clearance (R(2) = 0.58, r = 0.76, p < 0.001), the 1/serum cystatin C (R(2) = 0.58, r = 0.76, p < 0.001), and serum cystatin C (R(2) = 0.52, r = 0.72, p < 0.001). Renal functional reserve was preserved in 6 of 28 patients. There was no significant change in cystatin C in response to protein load. CONCLUSION: Wide variation in baseline GFR emphasizes the need for the early detection of renal dysfunction. Cystatin C correlated best with C(Sinistrin) at baseline, but did not detect renal functional reserve.

Mycoplasma hominis and Ureaplasma urealyticum in patients with sterile pyuria.

OBJECTIVES: Mycoplasma hominis and Ureaplasma urealyticum are associated with various diseases of the urogenital tract, but they are usually not detected by routine microbiological diagnosis. The aim of this study was to asses the prevalence of these organisms in patients with sterile pyuria. METHODS: From December 2000 to June 2001 all urine samples sent in to microbiological diagnosis, which yielded > or =500 leucocytes/ml and <10(4) bacteria/ml, were collected for this study. Thirty-three samples from 30 patients (female: 21, male: nine; median age: 60 years, range: 23-91 years) met these criteria and were subjected to PCR for detection of M. hominis and U. urealyticum, respectively. RESULTS: M. hominis and U. urealyticum were detected in 2 (7%) and 6 samples (20%), respectively. With regard to the underlying diseases of the patients, glomerulonephritis was significantly associated with the detection of urogenital mycoplasmas (p=0.02). CONCLUSION: The prevalence of M. hominis and U. urealyticum found in this study corresponds to the expected prevalence in the general population. This finding does not indicate an association of sterile pyuria with urogenital mycoplasma infection/colonization.

Quantitative analysis of sinistrin in serum with high-performance liquid chromatography for renal function testing.

Sinistrin, as inulin, is widely used as a marker for renal function testing. A reliable and accurate method with a simple sample preparation for the quantitative determination of sinistrin would be of advantage. We developed a high-performance liquid chromatography (HPLC)-based method with electrochemical detection for the quantitative measurement of sinistrin in serum and plasma. Sample preparation is easy and includes enzymatic removal of glucose, deproteinization, acid hydrolysis of sinistrin, and HPLC separation of fructose. The recovery of sinistrin from serum is the same as that from water and is near 100%. The method presented has a linear range up to 500 mg/L. The results from our method are in agreement with a fully enzymatic quantification (regression coefficient 1.01, coefficient of variation 0.97). Sinistrin concentrations in aqueous solutions can be measured down to 2mg/L with a coefficient of variation of 5.7%. Quantification in serum is primarily limited by its physiological fructose content. The sensitivity of the described method is sufficient for its use in renal function testing. We describe a method for quantification of sinistrin which allows accurate measurements especially at low concentrations and low sample volumes. This laboratory method may be used for obtaining sinistrin pharmacokinetics in renal function testing.

Renal functional reserve in patients with Type 1 diabetes mellitus.

AIM: Decreased renal functional reserve might precede incipient diabetic nephropathy in patients with Type 1 diabetes. The aim of this study was to assess the relationship between renal functional reserve and easily assessable estimates of systemic endothelial dysfunction in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. METHODS: Renal functional reserve was calculated as the relative change in glomerular filtration rate after protein ingestion. Glomerular filtration rate was measured using pharmacokinetic compartmental analysis of single-shot plasma sinistrin clearance. We measured the activity of von Willebrand factor and concentrations of C-reactive protein and apolipoprotein B, as easily assessable estimates of systemic endothelial dysfunction. RESULTS: Twenty-two patients were studied. Renal functional reserve was inversely associated with activity of von Willebrand factor (R=-0.431, p=0.045) and, in a multivariate model, with concentration of C-reactive protein (R=0.652, p=0.031). CONCLUSION: Renal functional reserve is inversely associated with concentration of C-reactive protein in normoalbuminuric patients with Type 1 diabetes and diabetic retinopathy. This finding provides evidence that decreased renal functional reserve might reflect endothelial dysfunction. We speculate that decreased renal functional reserve might possibly show as an early marker of diabetic nephropathy.

Effect of hemodialysis on the antioxidative properties of serum.

In patients with chronic renal failure undergoing regular hemodialysis (HD), oxidative stress is involved in the development of dialysis-related pathologies. The aim of the study was to measure the effect of HD treatment on the general antioxidative status of serum with special consideration of the specific oxidizability of lipids and proteins. Indicators for the oxidative/antioxidative status of plasma were monitored at the beginning and at the end of a dialysis session on the arterial and venous side of the dialyzer. A decrease in the antioxidant status was accompanied by an increased oxidizability of proteins as well as lipids during HD treatment. During the first passage of the dialyzer, the lag time of lipid oxidation decreased from 114.0+/-19.8 to 81.5+/-18.9 min, the lag time of protein oxidation decreased from 105.0+/-24.6 to 72.9+/-21.3 min and the total antioxidative status decreased from 518+/-24 to 252+/-124 microM trolox equivalents. The carbonyl content of serum proteins was high in patients with end stage renal disease (ESRD) (3.9+/-1.1 vs. 0.9+/-0.1 nmol/mg in controls) but did not change significantly during dialysis procedure. Our data demonstrate that the susceptibility of serum lipids and proteins to oxidative modification is severely increased by HD treatment.