TY  - JOUR
AB  - BACKGROUND: Individuals on haemodialysis (HD) are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population due to end-stage kidney disease-induced immunosuppression. METHODS: A total of 26 HD patients experiencing SARS-CoV-2 infection after a third vaccination were matched 1:1 with 26 of 92 SARS-CoV-2-naïve patients by age, sex, dialysis vintage and immunosuppressive drugs receiving a fourth vaccination with a messenger RNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titres, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoCs), Omicron sublineage BA.1, BA.5 and BQ.1.1. The 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, 4 weeks after and 6 months after the fourth vaccination. RESULTS: A total of 52 HD patients received four coronavirus disease 2019 (COVID-19) vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sublineages after 6 months (P < .001 each). Those patients with a virus infection did not experience a reduction in real virus neutralization capacity after 6 months. Compared with the other Omicron VoC, the BQ.1.1 sublineage had the lowest virus neutralization capacity. CONCLUSIONS: SARS-CoV-2-naïve HD patients had significantly decreased virus neutralization capacity 6 months after the fourth vaccination, whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naïve HD patients a fifth COVID-19 vaccination might be reasonable 6 months after the fourth vaccination.
AU  - Platen, L.*
AU  - Liao, B.H.*
AU  - Tellenbach, M.*
AU  - Cheng, C.C.*
AU  - Holzmann-Littig, C.*
AU  - Christa, C.*
AU  - Dächert, C.*
AU  - Kappler, V.*
AU  - Bester, R.*
AU  - Werz, M.L.*
AU  - Schönhals, E.*
AU  - Platen, E.*
AU  - Eggerer, P.*
AU  - Tréguer, L.*
AU  - Küchle, C.*
AU  - Schmaderer, C.*
AU  - Heemann, U.*
AU  - Keppler, O.T.*
AU  - Renders, L.*
AU  - Braunisch, M.C.*
AU  - Protzer, U.
C1  - 68876
C2  - 53737
SP  - 2447-2460
TI  - Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients.
JO  - Clin. Kidney J.
VL  - 16
IS  - 12
PY  - 2023
SN  - 2048-8505
ER  - 

TY  - JOUR
AB  - Background: The hepatokine fetuin-A, released by the
       human liver, promotes pro-inflammatory effects of perivascular fat. The
       involvement of inflammation in type 2 diabetes mellitus (T2DM) can 
      affect the kidney and contribute to the development of diabetic kidney 
      disease. Therefore we examined the association of urinary fetuin-A 
      protein fragments with renal damage in T2DM patients. Methods: Urinary 
      peptides of 1491 individuals using proteome data available from the 
      human urine proteome database were analysed. Prediction of proteases 
      involved in urinary peptide generation was performed using the Proteasix
       tool. Results: We identified 14 different urinary protein fragments 
      that belong to the region of the connecting peptide (amino acid 301-339)
       of the total fetuin-A protein. Calpains (CAPN1 and CAPN2), matrix 
      metalloproteinase and pepsin A-3 were identified as potential proteases 
      that were partially confirmed by previous in vitro studies. 
      Combined fetuin-A peptides (mean of amplitudes) were significantly 
      increased in T2DM patients with kidney disease and to a lesser extent 
      with cardiovascular risk. Furthermore, fetuin-A peptide levels displayed
       a significant negative correlation with baseline estimated glomerular 
      filtration rate (eGFR) values (r = -0.316, P < 0.0001) and with the slope (%) of eGFR per year (r = -0.096,
       P = 0.023). A multiple regression model including fetuin-A peptide and 
      albuminuria resulted in a significantly improved correlation with eGFR (r = -0.354,
       P < 0.0001) compared with albuminuria, indicating an added value of 
      this novel biomarker. Conclusions: The urinary proteome analysis 
      demonstrated the association of fetuin-A peptides with impaired kidney 
      function in T2DM patients. Furthermore, fetuin-A peptides displayed 
      early signs of kidney damage before albuminuria appeared and therefore 
      can be used as markers for kidney disease detection.
AU  - Magalhães, P.*
AU  - Zürbig, P.*
AU  - Mischak, H.*
AU  - Schleicher, E.
C1  - 61248
C2  - 49784
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 269-276
TI  - Urinary fetuin-A peptides as a new marker for impaired kidney function in patients with type 2 diabetes.
JO  - Clin. Kidney J.
VL  - 14
IS  - 1
PB  - Oxford Univ Press
PY  - 2021
SN  - 2048-8505
ER  - 

TY  - JOUR
AB  - Recurrence of primary focal segmental glomerulosclerosis (FSGS) occurs in up to 50% of patients after kidney transplantation and is associated with poor allograft outcome. Novel therapeutic concepts directly target podocyte function via B7-1 with inconsistent response. We present the case of a 19-year-old patient with recurrent primary FSGS early after living donor kidney transplantation. Plasmapheresis and rituximab did not induce remission. Repetitive abatacept administration was able to achieve partial remission. Maintenance immunosuppression was subsequently switched to a belatacept-based calcineurin inhibitor-free immunosuppression, resulting in sustained complete remission with excellent allograft function throughout a follow-up of >56 months.
AU  - Mühlbacher, T.
AU  - Amann, K.*
AU  - Mahling, M.
AU  - Nadalin, S.*
AU  - Heyne, N.
AU  - Guthoff, M.
C1  - 62192
C2  - 50692
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 1691-1693
TI  - Successful long-term management of recurrent focalsegmental glomerulosclerosis after kidneytransplantation with costimulation blockade.
JO  - Clin. Kidney J.
VL  - 14
IS  - 6
PB  - Oxford Univ Press
PY  - 2021
SN  - 2048-8505
ER  - 

TY  - JOUR
AB  - Background: Uromodulin, a tissue-specific tubular glycoprotein, has recently emerged as a promising biomarker for kidney function and tubular integrity. However, the association of serum uromodulin (sUmod) with renal function decline is still unknown in an older general population. Methods: We analysed the association of sUmod with the estimated glomerular filtration rate (eGFR) and albuminuria in 1075 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study, ages 62-81 years, at baseline and prospectively after a mean follow-up time of 6.5 years (n = 605) using logistic and linear regression models as well as receiver operating characteristics (ROC) analyses. Results: Cross-sectionally, sUmod was positively associated with eGFR (β = 0.31 ± 0.02 per higher standard deviation sUmod; P < 0.001) and inversely associated with the urinary albumin:creatinine ratio (β = -0.19 ± 0.04; P < 0.001) after adjustment for sex, age, body mass index, arterial hypertension, prediabetes and diabetes. After multivariable adjustment including baseline eGFR, sUmod was not associated with incident chronic kidney disease (CKD), defined as a decrease in eGFR <60 mL/min/1.73 m2 after 6.5 years of follow-up {odds ratio [OR] 1.02 [95% confidence interval (CI) 0.77-1.36] per higher SD sUmod} but was inversely associated with advanced CKD, defined as incident eGFR <45 mL/min/1.73 m2 [OR 0.64 (95% CI 0.42-0.98)]. The ROC showed no added predictive value of sUmod for kidney function decline in the fully adjusted model. Conclusions: Higher sUmod was inversely associated with progression to advanced kidney disease but does not provide additional predictive value for the development of CKD in elderly participants of the population-based KORA study.
AU  - Then, C.
AU  - Then, H.L.*
AU  - Lechner, A.
AU  - Thorand, B.
AU  - Meisinger, C.
AU  - Heier, M.
AU  - Peters, A.
AU  - Koenig, W.*
AU  - Rathmann, W.*
AU  - Scherberich, J.*
AU  - Seissler, J.
C1  - 61322
C2  - 49789
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 205-211
TI  - Serum uromodulin and decline of kidney function in older participants of the population-based KORA F4/FF4 study.
JO  - Clin. Kidney J.
VL  - 14
IS  - 1
PB  - Oxford Univ Press
PY  - 2021
SN  - 2048-8505
ER  - 

TY  - JOUR
AB  - Background: Uromodulin is a kidney-specific glycoprotein synthesized in tubular cells of Henle's loop exerting nephroprotective and immunomodulatory functions in the urinary tract. A small amount of uromodulin is also released into the systemic circulation, where its physiological role is unknown. Serum uromodulin (sUmod) has been associated with metabolic risk factors and with cardiovascular events and mortality, where these associations were partly stronger in men than in women. In this study, we investigated the associations of sUmod with biomarkers of subclinical inflammation in a population-based sample of women and men. Methods: Associations of sUmod with 10 biomarkers of subclinical inflammation were assessed in 1065 participants of the Cooperative Health Research in the Region of Augsburg (KORA) F4 study aged 62-81 years using linear regression models adjusted for sex, age, body mass index, estimated glomerular filtration rate and diabetes. Analyses were performed in the total study sample and stratified by sex. Results: sUmod was inversely associated with white blood cell count, high-sensitive C-reactive protein, interleukin (IL)-6, tumour necrosis factor-α, myeloperoxidase, superoxide dismutase-3, IL-1 receptor antagonist and IL-22 after multivariable adjustment and correction for multiple testing (P < 0.001 for each observation). There was a trend towards a stronger association of sUmod with pro-inflammatory markers in men than in women, with a significant P for sex interaction (<0.001) regarding the relation of sUmod with IL-6. Conclusions: sUmod was inversely associated with biomarkers of subclinical inflammation in older participants of the KORA F4 study. The association of sUmod with IL-6 differed between women and men. Future research should focus on whether the immunomodulatory properties of sUmod are one explanation for the association of sUmod with cardiovascular outcomes and mortality.
AU  - Then, C.
AU  - Herder, C.
AU  - Then, H.*
AU  - Thorand, B.
AU  - Huth, C.
AU  - Heier, M.
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Koenig, W.*
AU  - Rathmann, W.*
AU  - Roden, M.*
AU  - Stumvoll, M.*
AU  - Maalmi, H.*
AU  - Meitinger, T.*
AU  - Lechner, A.
AU  - Scherberich, J.*
AU  - Seissler, J.
C1  - 62418
C2  - 50861
CY  - Great Clarendon St, Oxford Ox2 6dp, England
SP  - 1618-1625
TI  - Serum uromodulin is inversely associated with biomarkers of subclinical inflammation in the population-based KORA F4 study.
JO  - Clin. Kidney J.
VL  - 14
IS  - 6
PB  - Oxford Univ Press
PY  - 2021
SN  - 2048-8505
ER  -