Publications by authors named "Karl Lhotta"

99 Publications

The Triglyceride-Glucose Index and Obesity-Related Risk of End-Stage Kidney Disease in Austrian Adults.

JAMA Netw Open 2021 Mar 1;4(3):e212612. Epub 2021 Mar 1.

Agency for Preventive and Social Medicine, Bregenz, Austria.

Importance: It is unknown whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing end-stage kidney disease (ESKD). Because individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and ESKD risk through the TyG index seems plausible but has not been investigated.

Objective: To evaluate whether the TyG index is associated with ESKD risk and, if so, to what extent the TyG index mediates the association between BMI and ESKD.

Design, Setting, And Participants: A total of 176 420 individuals were recruited during routine health examinations to participate in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP), a prospective, population-based cohort study with participant enrollment between January 1, 1988, and June 30, 2005, and a mean follow-up of 22.7 years. Data analysis was conducted from March 1, 2020, to September 30, 2020.

Exposures: Body mass index and the logarithmized product of fasting triglyceride and glucose concentrations (TyG index), as determined during the baseline health examination.

Main Outcomes And Measures: End-stage kidney disease, as indicated by initiation of kidney replacement therapy, either dialysis or kidney transplantation.

Results: Of the 176 420 participants, 94 885 were women (53.8%); mean (SD) age was 42.5 (15.4) years. During a mean (SD) follow-up of 22.7 (6.9) years, 454 (0.3%) participants developed ESKD and 35 234 (20.0%) died. In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of ESKD, both with (hazard ratio [HR] per 1-SD increase, 1.68; 95% CI, 1.56-1.82) and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of BMI as a covariate. Mediation analysis using a newly proposed 2-stage regression method for survival data showed that a 5-point increase in BMI increased the risk of ESKD by 58% (HR [total association], 1.58; 95% CI, 1.43-1.75), and that 41.7% of the total association (95% CI, 31.6%-51.8%) was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25).

Conclusions And Relevance: This study found that the TyG index appeared to be associated with ESKD risk and mediates nearly half of the total association between BMI and ESKD in the general population. Public health efforts aiming at the reduction of body weight might decrease the kidney sequelae of insulin resistance and the burden of ESKD.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.2612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013829PMC
March 2021

SARS-CoV-2 infection and recurrence of anti-glomerular basement disease: a case report.

BMC Nephrol 2021 02 27;22(1):75. Epub 2021 Feb 27.

Department of Internal Medicine 3 (Nephrology and Dialysis), Feldkirch Academic Teaching Hospital, Carinagasse 47, A-6800, Feldkirch, Austria.

Background: Anti-glomerular basement membrane disease (GBM) disease is a rare autoimmune disease causing rapidly progressive glomerulonephritis and pulmonary haemorrhage. Recently, an association between COVID-19 and anti-glomerular basement membrane (anti-GBM) disease has been proposed. We report on a patient with recurrence of anti-GBM disease after SARS-CoV-2 infection.

Case Presentation: The 31-year-old woman had a past medical history of anti-GBM disease, first diagnosed 11 years ago, and a first relapse 5 years ago. She was admitted with severe dyspnoea, haemoptysis, pulmonary infiltrates and acute on chronic kidney injury. A SARS-CoV-2 PCR was positive with a high cycle threshold. Anti-GBM autoantibodies were undetectable. A kidney biopsy revealed necrotising crescentic glomerulonephritis with linear deposits of IgG, IgM and C3 along the glomerular basement membrane, confirming a recurrence of anti-GBM disease. She was treated with steroids, plasma exchange and two doses of rituximab. Pulmonary disease resolved, but the patient remained dialysis-dependent. We propose that pulmonary involvement of COVID-19 caused exposure of alveolar basement membranes leading to the production of high avidity autoantibodies by long-lived plasma cells, resulting in severe pulmonary renal syndrome.

Conclusion: Our case supports the assumption of a possible association between COVID-19 and anti-GBM disease.
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http://dx.doi.org/10.1186/s12882-021-02275-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914035PMC
February 2021

Genetic and Clinical Predictors of Age of ESKD in Individuals With Autosomal Dominant Tubulointerstitial Kidney Disease Due to Mutations.

Kidney Int Rep 2020 Sep 3;5(9):1472-1485. Epub 2020 Jul 3.

Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.

Introduction: Autosomal dominant tubulo-interstitial kidney disease due to mutations (ADTKD-) is a rare condition associated with high variability in the age of end-stage kidney disease (ESKD). The minor allele of rs4293393, located in the promoter of the gene, is present in 19% of the population and downregulates uromodulin production by approximately 50% and might affect the age of ESKD. The goal of this study was to better understand the genetic and clinical characteristics of ADTKD- and to perform a Mendelian randomization study to determine if the minor allele of rs4293393 was associated with better kidney survival.

Methods: An international group of collaborators collected clinical and genetic data on 722 affected individuals from 249 families with 125 mutations, including 28 new mutations. The median age of ESKD was 47 years. Men were at a much higher risk of progression to ESKD (hazard ratio 1.78,  < 0.001).

Results: The allele frequency of the minor rs4293393 allele was only 11.6% versus the 19% expected ( < 0.01), resulting in Hardy-Weinberg disequilibrium and precluding a Mendelian randomization experiment. An score reflecting the severity of the trafficking defect of uromodulin mutants was found to be a promising predictor of the age of ESKD.

Conclusion: We report the clinical characteristics associated with 125 mutations. Male gender and a new score predict age of ESKD.
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http://dx.doi.org/10.1016/j.ekir.2020.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486199PMC
September 2020

Whole genome sequence analysis identifies a PAX2 mutation to establish a correct diagnosis for a syndromic form of hyperuricemia.

Am J Med Genet A 2020 11 9;182(11):2521-2528. Epub 2020 Aug 9.

Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, UK.

Hereditary hyperuricemia may occur as part of a syndromic disorder or as an isolated nonsyndromic disease, and over 20 causative genes have been identified. Here, we report the use of whole genome sequencing (WGS) to establish a diagnosis in a family in which individuals were affected with gout, hyperuricemia associated with reduced fractional excretion of uric acid, chronic kidney disease (CKD), and secondary hyperparathyroidism, that are consistent with familial juvenile hyperuricemic nephropathy (FJHN). However, single gene testing had not detected mutations in the uromodulin (UMOD) or renin (REN) genes, which cause approximately 30-90% of FJHN. WGS was therefore undertaken, and this identified a heterozygous c.226G>C (p.Gly76Arg) missense variant in the paired box gene 2 (PAX2) gene, which co-segregated with renal tubulopathy in the family. PAX2 mutations are associated with renal coloboma syndrome (RCS), which is characterized by abnormalities in renal structure and function, and anomalies of the optic nerve. Ophthalmological examination in two adult brothers affected with hyperuricemia, gout, and CKD revealed the presence of optic disc pits, consistent with optic nerve coloboma, thereby revising the diagnosis from FJHN to RCS. Thus, our results demonstrate the utility of WGS analysis in establishing the correct diagnosis in disorders with multiple etiologies.
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http://dx.doi.org/10.1002/ajmg.a.61814DOI Listing
November 2020

Sex- and age-specific variations, temporal trends and metabolic determinants of serum uric acid concentrations in a large population-based Austrian cohort.

Sci Rep 2020 05 5;10(1):7578. Epub 2020 May 5.

Agency for Preventive and Social Medicine, Bregenz, Austria.

Little is known about sex- and age-specific variations and temporal trends in serum uric acid (SUA) concentrations, the prevalence of hyperuricemia and its association with metabolic risk factors in the general population. Between January 1, 1985 and June 30, 2005 146,873 participants (42% women) were recruited. Prevalence of hyperuricemia was estimated applying a common (SUA > 360 µmol/L) and sex-specific cut-off points (women > 340 µmol/L, men > 420 µmol/L). At baseline, mean age was 41.2 years in men and 51.5 years in women, mean SUA concentration was 314.8 µmol/L and 243.6 µmol/L, respectively. Applying a common cut-off point, the prevalence of hyperuricemia was 18.5% in men and 4.4% in women and by sex-specific cut-off points it was 15.1% and 13.8%, respectively. SUA levels increased by 6.7 µmol/L per decade in men, but remained constant in women until the age of 50 years with a sharp increase by approximately 22 µmol/L per decade thereafter. In men and women, hyperuricemia was associated with obesity, hypertriglyceridemia and elevated gamma-glutamyl transferase. With increasing age SUA levels and the prevalence of hyperuricemia rise in a sex-specific manner. Above the age of 65 years, the sex-specific prevalence of hyperuricemia in women outreaches that in men.
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http://dx.doi.org/10.1038/s41598-020-64587-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200724PMC
May 2020

A hemodialysis patient with bone disease after pregnancy: a case report.

BMC Nephrol 2019 11 21;20(1):425. Epub 2019 Nov 21.

Department of Internal Medicine III, Academic Teaching Hospital Feldkirch, Carinagasse 47, Feldkirch, Austria.

Background: Pregnancy is rare in women on hemodialysis. Recommendations for the treatment of secondary hyperparathyroidism (sHPT) and preservation of bone health in pregnant dialysis patients are lacking.

Case Presentation: We present the case of a young woman with end-stage kidney disease (ESKD) due to lupus nephritis, who developed multiple brown tumors while on hemodialysis during her second pregnancy. During her first pregnancy sHPT was well controlled and no skeletal complications occurred. Before the second pregnancy she developed severe sHPT. During pregnancy, dialysis time was increased to 24 h per week, the patient was given oral calcitriol, and the dialysate calcium concentration was set at 1.5 mmol/l. In week 20 the patient complained about bone pain in her left hip. Magnetic resonance imaging revealed a cystic lesion compatible with a brown tumor. The baby was delivered in the 36th week by cesarean section. Further assessment identified multiple brown tumors of her skeleton, including the acetabulum, tibia, ribs, skull, thoracic spine and thumb. She required multiple orthopedic surgeries. Three months after pregnancy, etelcalcetide was started, which brought about a gradual improvement in her sHPT.

Conclusions: This case demonstrates that the combination of pregnancy and severe sHPT in dialysis patients can have deleterious consequences for bone health.
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http://dx.doi.org/10.1186/s12882-019-1603-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6873679PMC
November 2019

May Measurement Month 2017: an analysis of blood pressure screening results in Austria-Europe.

Eur Heart J Suppl 2019 Apr 24;21(Suppl D):D17-D20. Epub 2019 Apr 24.

Hospital Wels-Grieskirchen, Wels, Austria.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension (HTN), and statistical analysis followed the standard MMM protocol. In total, 2711 individuals (58.6% female) were screened during MMM17 in 56 centres. After multiple imputation, 1704 (62.9%) had HTN (≥140/90 mmHg). Of individuals not receiving antihypertensive medication, 764 (43.2%) were hypertensive. Of individuals receiving antihypertensive medication, 597 (63.5%) had uncontrolled BP. MMM17 was one of the largest BP screening campaigns undertaken in Austria. A large number of undiagnosed hypertensives was found and connected to a therapeutic strategy. An alarming number of uncontrolled but treated hypertensives should attract the attention of doctors and health care system in Austria.
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http://dx.doi.org/10.1093/eurheartj/suz053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479427PMC
April 2019

Successful pregnancy in a patient with pulmonary renal syndrome double-positive for anti-GBM antibodies and p-ANCA
.

Clin Nephrol 2019 Feb;91(2):101-106

Background: Antiglomerular basement membrane (anti-GBM) antibody disease is a rare condition causing pulmonary hemorrhage and necrotizing glomerulonephritis (pulmonary renal syndrome).

Case: We report a 30-year-old woman who presented with life-threatening pulmonary hemorrhage and an active urinary sediment, with normal glomerular filtration rate in the 13 week of pregnancy. Anti-GBM antibodies in serum were negative, but perinuclear antineutrophil cytoplasmatic antibodies (p-ANCA) were detected. A renal biopsy revealed necrotizing glomerulonephritis with linear IgG deposits along the glomerular basement membrane. A diagnosis of pulmonary renal syndrome caused by anti-GBM antibodies and p-ANCA (double-positive) was made. Plasma exchange was started but had to be changed to immunoadsorption because of an allergic reaction to fresh frozen plasma. Oral steroids were introduced. The patient also received one dose of intravenous cyclophosphamide followed by two 1-g doses of rituximab. The patient responded quickly to treatment with resolution of pulmonary hemorrhage and urinary abnormalities. The infant was delivered in the 38 week of pregnancy by caesarian section. It was small for age but otherwise completely healthy with a normal B-cell count.

Conclusion: To our knowledge, this is the first report of a double-positive pulmonary renal syndrome in pregnancy. Presentation in mid-pregnancy allowed for the application of cyclophosphamide without causing malformations and rituximab without B-cell depletion in the infant.
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http://dx.doi.org/10.5414/CN109584DOI Listing
February 2019

Alprostadil treatment of critical limb ischemia in hemodialysis patients : A retrospective single-center analysis.

Wien Klin Wochenschr 2019 May 12;131(9-10):209-215. Epub 2018 Nov 12.

Department of Internal Medicine 3, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria.

Background: Peripheral artery disease and critical limb ischemia are common in patients undergoing chronic hemodialysis treatment and are associated with a high rate of amputation and mortality. The effect of treatment with prostanoids in this specific group of patients is unknown.

Methods: A retrospective single-center analysis of hemodialysis patients with critical limb ischemia was performed who were treated with the prostanoid analogue alprostadil as an infusion during hemodialysis in the period from 2000 to 2013. The primary study outcome was a combined end-point including amputation and death 1 year after start of alprostadil. Kaplan-Meier curves were used to describe amputation-free survival and overall survival. A multivariable adjusted Cox proportional hazards model was calculated for the primary outcome.

Results: A total of 86 patients (60 males, 69.7%) were studied. The median alprostadil treatment period was 1.8 months. The 1‑year amputation-free survival was 41%. In 36% of patients an amputation was necessary and 35% died. Despite alprostadil treatment, 36% of the study patients additionally underwent an endovascular procedure and 16% had bypass surgery. Men had a significantly higher amputation rate (45%) than women (15%) (P = 0.009). Male sex and dialysis vintage were significantly associated with an increased risk for primary outcome CONCLUSIONS: Despite treatment with alprostadil the mortality, amputation rate and the need for revascularization procedures in hemodialysis patients with critical limb ischemia remained high. The outcome, however, was comparable with that of other treatment, such as endovascular procedures and bypass surgery. The effect of any current treatment strategy on amputation rate or mortality in that patient group remains uncertain.
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http://dx.doi.org/10.1007/s00508-018-1407-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927041PMC
May 2019

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health.

Kidney Int 2018 12 22;94(6):1227-1237. Epub 2018 Oct 22.

Department of Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology and Gastroenterology, Medical University of Vienna, Vienna, Austria.

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and ex vivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased ex vivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.
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http://dx.doi.org/10.1016/j.kint.2018.08.031DOI Listing
December 2018

Floating kidneys associated with Eisenmenger syndrome.

Kidney Int 2018 Nov;94(5):1029

3rd Department of Internal Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

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http://dx.doi.org/10.1016/j.kint.2018.05.010DOI Listing
November 2018

Treatment of Concurrent Thrombotic Thrombocytopenic Purpura and Graves' Disease: A Report on Two Cases.

Case Rep Endocrinol 2018 9;2018:5747969. Epub 2018 Aug 9.

Department of Nuclear Medicine, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

Graves' disease (GD) and thrombotic thrombocytopenic purpura (TTP) are autoimmune diseases caused by autoantibodies against the TSH receptor (TRAb) and the enzyme ADAMTS13. We here report on two patients with concurrent GD and TTP, who achieved sustained remission of both conditions with the TTP treatment regimen and thiamazole. Both patients suffered from relapsing TTP and were diagnosed with GD concomitantly at the time of relapse. They were treated with steroids, plasma exchange, rituximab, and thiamazole. This therapy induced complete remission of TTP. TRAb levels also decreased rapidly and both patients developed subclinical hypothyroidism three and five weeks later. Our observations suggest that TTP and GD may be concomitant and that GD possibly triggers a relapse of TTP. The combination of thyrostatic treatment and immunosuppression with PE, rituximab, and steroids is able to induce rapid and prolonged remission of GD.
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http://dx.doi.org/10.1155/2018/5747969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106962PMC
August 2018

Anti-Laminin-332-Schleimhautpemphigoid mit laryngealer Beteiligung - adjuvante Behandlung mit Immunadsorption und Rituximab.

J Dtsch Dermatol Ges 2018 Jul;16(7):897-900

Klinik für Dermatologie, Allergologie und Venerologie, Universität zu Lübeck, Lübeck, Deutschland.

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http://dx.doi.org/10.1111/ddg.13569_gDOI Listing
July 2018

Anti-laminin 332 mucous membrane pemphigoid with laryngeal involvement - adjuvant treatment with immunoadsorption and rituximab.

J Dtsch Dermatol Ges 2018 Jul 21;16(7):897-900. Epub 2018 Jun 21.

Department of Dermatology, Allergology and Venereology, Lübeck University, Lübeck, Germany.

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http://dx.doi.org/10.1111/ddg.13569DOI Listing
July 2018

Long-term risk for end-stage kidney disease and death in a large population-based cohort.

Sci Rep 2018 05 16;8(1):7729. Epub 2018 May 16.

Agency for Preventive and Social Medicine, Bregenz, Austria.

Knowledge of metabolic risk factors for end-stage kidney disease (ESKD) in the general population is limited when considering the competing event death in risk analysis. The aim of our prospective observational study was to investigate how blood pressure and metabolic factors might influence the risks for ESKD and death before ESKD in a large Austrian population-based cohort with long-term follow-up. 177,255 participants (53.8% women; mean age 42.5 years) were recruited between 1988 and 2005 and linked to the Austrian Dialysis and Transplant Registry and the National Mortality Registry. Over a mean follow-up of 16 years 358 participants reached ESKD and 19,512 participants died. Applying fully adjusted cause-specific Cox proportional hazards models elevated fasting blood glucose, hypertension, hypertrigylceridemia and hypercholesterolemia were associated with a higher relative risk for ESKD than for death before ESKD, whereas elevated γ-glutamyltransferase was associated with an increased relative risk of death but not ESKD. Results were similar using continuous or categorical exposure variable measures in the general cohort but differed in selected high-risk populations. These findings might help improve the design of renal risk factor modification trials and kidney disease awareness and prevention programs in the general population, which may ultimately decrease the burden of ESKD.
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http://dx.doi.org/10.1038/s41598-018-26087-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955909PMC
May 2018

Functional Characterization of the Disease-Associated N-Terminal Complement Factor H Mutation W198R.

Front Immunol 2017 13;8:1800. Epub 2017 Dec 13.

MTA-ELTE "Lendület" Complement Research Group, Department of Immunology, ELTE Eötvös Loránd University, Budapest, Hungary.

Dysregulation of the complement alternative pathway is involved in the pathogenesis of several diseases, including the kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). In a patient, initially diagnosed with chronic glomerulonephritis, possibly C3G, and who 6 years later had an episode of aHUS, a heterozygous missense mutation leading to a tryptophan to arginine exchange (W198R) in the factor H (FH) complement control protein (CCP) 3 domain has previously been identified. The aim of this study was to clarify the functional relevance of this mutation. To this end, wild-type (FH1-4) and mutant (FH1-4) CCPs 1-4 of FH were expressed as recombinant proteins. The FH1-4 mutant showed decreased C3b binding compared with FH1-4. FH1-4 had reduced cofactor and decay accelerating activity compared with the wild-type protein. Hemolysis assays demonstrated impaired capacity of FH1-4 to protect rabbit erythrocytes from human complement-mediated lysis, and also to prevent lysis of sheep erythrocytes in human serum induced by a monoclonal antibody binding in FH CCP5 domain, compared with that of FH1-4. Thus, the FH W198R exchange results in impaired complement alternative pathway regulation. The heterozygous nature of this mutation in the index patient may explain the manifestation of two diseases, likely due to different triggers leading to complement dysregulation in plasma or on cell surfaces.
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http://dx.doi.org/10.3389/fimmu.2017.01800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733548PMC
December 2017

An unusual case of acute kidney injury after colonoscopy.

Kidney Int 2017 04;91(4):989

Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria. Electronic address:

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http://dx.doi.org/10.1016/j.kint.2016.11.020DOI Listing
April 2017

Management of secondary hyperparathyroidism: practice patterns and outcomes of cinacalcet treatment with or without active vitamin D in Austria and Switzerland - the observational TRANSIT Study.

Wien Klin Wochenschr 2017 May 13;129(9-10):317-328. Epub 2017 Jan 13.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

Secondary hyperparathyroidism is a complex disorder requiring an individualized multicomponent treatment approach. This study was conducted to identify treatment combinations used in clinical practice in Austria and Switzerland and the potential to control this disorder. A total of 333 adult hemodialysis and peritoneal dialysis patients were analyzed. All patients received conventional care prior to initiation of a cinacalcet-based regimen. During the study, treatment components, e.g. cinacalcet, active vitamin D analogues and phosphate binders, were adapted to individual patient requirements and treatment dynamics were documented. Overall, the mean intact parathyroid hormone (iPTH) increased from 64.2 pmol/l to 79.6 pmol/l under conventional therapy and decreased after cinacalcet initiation to 44.0 pmol/l after 12 months (mean decrease between baseline and 12 months -45%). Calcium remained within the normal range throughout the study and phosphorus ranged around the upper limit of normal. The Kidney Disease: Improving Global Outcomes (KDIGO) target achievement for iPTH increased from 44.5% of patients at baseline to 65.7% at 12 months, corrected calcium from 58.9% to 51.9% and phosphorus from 18.4% to 24.4%. On average, approximately 30% of patients adapted their regimen from one observation period to the next. The reasons for changing a given regimen were to attain or maintain any of the bone mineral markers within recommended targets and to avoid developments to extreme values. Some regional differences in practice patterns were identified. No new safety signals emerged. In conclusion, cinacalcet appears to be a necessary treatment component to achieve recommended targets. The detailed composition of the treatment mix should be adapted to patient requirements and reassessed on a regular basis.
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http://dx.doi.org/10.1007/s00508-016-1153-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429358PMC
May 2017

Response to active hepatitis B vaccination and mortality in incident dialysis patients.

Vaccine 2017 02 31;35(5):814-820. Epub 2016 Dec 31.

Department of Nephrology and Dialysis, Feldkirch Academic Teaching Hospital, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria. Electronic address:

All patients with advanced chronic kidney disease or on renal replacement therapy should receive active hepatitis B vaccination. The aim of this retrospective cohort study was to investigate the association between the immune response to hepatitis B vaccination and all-cause, cardiovascular or infection-related mortality in incident dialysis patients starting dialysis between 2001 and 2008 (n=426) in two Austrian dialysis centers. Vaccination response was defined as follows: absent anti-HBs antibody titer or a titer <10IU/L was classified as non-response, seroconversion (SC) was defined as a titer ⩾10IU/L, and seroprotection (SP) as a titer ⩾100IU/L. Kaplan-Meier survival curves and multivariable adjusted Cox Proportional Hazards Models were used to determine the association between vaccination response and all-cause, cardiovascular and infection-related mortality. Of all patients 207 (48.6%) were non-responders, SC was observed in 219 (51.4%), SP in 118 (27.7%) patients. During a median follow-up of 51.2 months 228 (53.5%) patients died. Patients with SP and SC showed a significantly lower all-cause (p<0.001 for both) and cardiovascular mortality (p=0.006 for SP, p=0.01 for SC). SP and SC were independently associated with a significant risk reduction for all-cause mortality (SP: HR 0.69, 95% CI 0.49-0.97, p=0.03; SC: HR 0.72, 95% CI 0.55-0.95, p=0.02). In conclusion, achieving seroconversion and seroprotection after active hepatitis B vaccination is associated with significantly reduced all-cause mortality in incident dialysis patients. This simple and readily available tool allows estimation of patient survival independently of other well-known key parameters such as age, gender, the presence of diabetes and markers of malnutrition and inflammation.
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http://dx.doi.org/10.1016/j.vaccine.2016.12.032DOI Listing
February 2017

Acute Kidney Injury Treated with Dialysis outside the Intensive Care Unit: A Retrospective Observational Single-Center Study.

PLoS One 2016;11(9):e0163512. Epub 2016 Sep 27.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

Introduction: The number of patients suffering from acute kidney injury requiring dialysis (AKI-D) is increasing. Whereas causes and outcome of AKI-D in the intensive care unit (ICU) are described extensively, few data exist about AKI-D patients treated outside the ICU. Aim of this study was to identify the causes of AKI-D, determine in-depth the comorbid conditions and outcome of this particular patient group and identify possibilities for its prevention.

Methods: We retrospectively studied all AKI-D patients treated outside the ICU in a single nephrology referral center between January 2010 and June 2015. Data on comorbid conditions, renal function and drug therapy prior to AKI-D, and possible causal events were collected. Patients were grouped into those with renal hypoperfusion as the predominant cause of AKI-D (hemodynamic group) and those with other causes (non-hemodynamic group).

Results: During 66 months 128 patients (57% male, mean age 69.3 years) were treated. AKI-D was community-acquired in 70.3%. The most frequent comorbidities were hypertension (62.5%), chronic kidney disease (CKD) (58.9%), coronary artery disease (CAD) (46.1%), diabetes (35.9%) and heart failure (34.1%). Most patients were prescribed diuretics (61.7%) and inhibitors of the renin-angiotensin-aldosterone system (RASI) (57.8%); 46.1% had a combination of both. In the 88 patients with hemodynamic AKI-D (68.8%) the most frequent initiating events were diarrhea (39.8%), infections (17.0%) and acute heart failure (13.6%). In the 40 patients with non-hemodynamic AKI-D (31.2%) interstitial nephritis (n = 15) was the prominent diagnosis. Patients with hemodynamic AKI-D were older (72.6 vs. 62.1 years, p = 0.001), suffered more often from CKD (68.2% vs. 33.3%, p = 0.003), CAD (54.5% vs. 27.5%, p = 0.004) and diabetes (42.0% vs. 22.5%, p = 0.033), and were more frequently on diuretics (75.0% vs. 32.5%, p<0.001), RASI (67.0% vs. 37.5%, p = 0.002) or their combination (58.0% vs. 20.0%, p<0.001). Twenty-two (17.2%) patients died and 27 (21.1%) patients died or developed end-stage renal disease.

Conclusion: AKI-D treated outside the ICU is most often caused by renal hypoperfusion. It predominantly afflicts elderly patients with one or more comorbid conditions, who are treated with diuretics and RASI and have an acute illness leading to volume depletion. Early discontinuation of these drugs may be a successful strategy to avoid AKI-D in vulnerable patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163512PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038962PMC
September 2016

Anthropometric and Metabolic Risk Factors for ESRD Are Disease-Specific: Results from a Large Population-Based Cohort Study in Austria.

PLoS One 2016 18;11(8):e0161376. Epub 2016 Aug 18.

Agency for Preventive and Social Medicine, Bregenz, Austria.

Background: Anthropometric and metabolic risk factors for all-cause end-stage renal disease (ESRD) may vary in their impact depending on the specific primary renal disease.

Methods: In this Austrian population-based prospective cohort study (n = 185,341; 53.9% women) the following data were collected between 1985 and 2005: age, sex, body mass index (BMI), fasting blood glucose (FBG) from 1988, blood pressure, total cholesterol (TC), triglycerides (TG), gamma-glutamyl transferase (GGT) and smoking status. These data were merged with the Austrian Dialysis and Transplant Registry to identify ESRD patients. Cox proportional hazards models were applied to calculate hazard ratios (HR) for all-cause ESRD as well as for cause-specific ESRD due to the following primary renal diseases: autosomal dominant polycystic kidney disease (ADPKD), vascular nephropathy (VN), diabetic nephropathy (DN) and other diseases (OD).

Results: During a mean follow-up of 17.5 years 403 participants developed ESRD (ADPKD 36, VN 97, DN 86, and OD 184). All parameters except TG and GGT were significantly associated with all-cause ESRD risk. Particular cause-specific ESRD risk factor patterns were found: for ADPKD increased risk from hypertension (HR 11.55); for VN from smoking (HR 1.81), hypertension (HR 2.37), TG (≥5.70 vs. <1.17 mmol/L: HR 9.27); for DN from smoking (HR 1.77), BMI (≥30 vs. 18.5-24.9 kg/m2: HR 7.55), FBG (≥6.94 vs. <5.55 mmol/L: HR 7.67), hypertension (HR 1.08), TG (≥5.70 vs. <1.17 mmol/L: HR 2.02), GGT (HR 2.14); and for OD from hypertension (HR 2.29), TG (≥5.70 vs. <1.17 mmol/L: HR 6.99) and TC (≥6.22 vs. <5.18 mmol/L: HR 1.56).

Conclusions: Particular anthropometric and metabolic ESRD risk factors differ in importance depending on the primary renal disease. This needs to be considered for future preventive and therapeutic strategies addressing cause-specific ESRD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161376PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990261PMC
July 2017

Successful Treatment of Focal Segmental Glomerulosclerosis after Kidney Transplantation with Plasma Exchange and Abatacept in a Patient with Juvenile Rheumatoid Arthritis.

Case Rep Transplant 2016 20;2016:7137584. Epub 2016 Mar 20.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria.

Recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation is difficult to treat. Recently a series of four patients unresponsive to plasma exchange (PE) and rituximab, who were successfully treated with abatacept, has been reported. We present a 26-year-old Caucasian patient who suffered from juvenile rheumatoid arthritis and developed severe proteinuria eleven days after transplantation. An allograft biopsy was suggestive of recurrent focal segmental glomerulosclerosis. He did not respond to PE therapy. A first dose of abatacept produced partial remission. Four weeks later proteinuria again increased and a second biopsy showed progression of disease. After another ineffective course of PE he was given a second dose of abatacept, which was followed by rapid, complete, and sustained resolution of proteinuria. This treatment caused a significant increase in BK and JC viremia. Whether abatacept ameliorated proteinuria via an effect on podocytes or on the patient's primary disease remains speculative.
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http://dx.doi.org/10.1155/2016/7137584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818792PMC
April 2016

[Management of secondary hyperparathyroidism-current impact of parathyroidectomy].

Wien Med Wochenschr 2016 May 25;166(7-8):254-8. Epub 2016 Feb 25.

Abteilung für Nephrologie und Dialyse, Akademisches Lehrkrankenhaus LKH Feldkirch, Carinagasse 47, 6800, Feldkirch, Österreich.

Parathyroidectomy still presents an adequate and efficient therapeutic option for the management of refractory secondary hyperparathyroidism (sHPT). Dependent on the selected surgical technique it allows the highest rate of "laboratory cure" of sHPT. The question remains as to whether these improvements translate into clinical long-term benefits regarding the sHPT-associated vascular calcification and the increased risk for cardiovascular morbidity and mortality as well as overall mortality. Recent large observational studies point in this direction but definite evidence through prospective randomized controlled trials is still lacking.
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http://dx.doi.org/10.1007/s10354-016-0444-3DOI Listing
May 2016

Autosomal dominant tubulointerstitial kidney disease caused by uromodulin mutations: seek and you will find.

Wien Klin Wochenschr 2016 Apr 25;128(7-8):291-4. Epub 2016 Jan 25.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, 6800, Feldkirch, Austria.

Background: Uromodulin (UMOD)-associated kidney disease belongs to the group of autosomal dominant interstitial kidney diseases and is caused by mutations in the UMOD gene. Affected patients present with hyperuricemia, gout, and progressive renal failure. The disease is thought to be very rare but is probably underdiagnosed.

Methods: Two index patients from two families with tubulointerstitial nephropathy and hyperuricemia were examined, including blood and urine chemistry, ultrasound, and mutation analysis of the UMOD gene. In addition, other available family members were studied.

Results: In a 46-year-old female patient with a fractional excretion of uric acid of 3 %, analysis of the UMOD gene revealed a p.W202S missense mutation. The same mutation was found in her 72-year-old father, who suffers from gout and end-stage renal disease. The second index patient was a 47-year-old female with chronic kidney disease and gout for more than 10 years. Her fractional uric acid excretion was 3.5 %. Genetic analysis identified a novel p.H250Q UMOD mutation that was also present in her 12-year-old son, who had normal renal function and uric acid levels.

Conclusion: In patients suffering from chronic tubulointerstitial nephropathy, hyperuricemia, and a low fractional excretion of uric acid mutation, analysis of the UMOD gene should be performed to diagnose UMOD-associated kidney disease.
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http://dx.doi.org/10.1007/s00508-015-0948-7DOI Listing
April 2016

Sex- and Time-Dependent Patterns in Risk Factors of End-Stage Renal Disease: A Large Austrian Cohort with up to 20 Years of Follow-Up.

PLoS One 2015 31;10(8):e0135052. Epub 2015 Aug 31.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Vorarlberg Institute for Vascular Investigation and Treatment, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

Objective: We investigated the association between metabolic factors and End-Stage Renal Disease (ESRD) and quantified the magnitude of their influence dependent on sex and time of exposure up to 20 years.

Material And Methods: A prospective cohort study was conducted to determine risk factors for the development of ESRD. From 1988 to 2005 185,341 persons (53.9% women) participated in the "Vorarlberg Health Monitoring and Promotion Programme" (VHM&PP). Data on body mass index (BMI), fasting blood glucose (FBG), systolic (BPsys) and diastolic (BPdia) blood pressure, total cholesterol (TC), triglycerides (TG), gamma-glutamyltransferase (GGT) and smoking status were collected. Data of the population-based VHM&PP were merged with the Austrian Dialysis and Transplant Registry. Cox proportional hazards models were applied to calculate hazard ratios (HRs) for ESRD, stratified by sex and 5-year time intervals.

Results: During a mean follow-up of 17.5 years 403 patients (39.1% women) developed ESRD. Significant risk factors were: BMI (per 1 kg/m2) HR 1.04 (95% CI 1.01-1.06), FBG (per 1 mmol/L) HR 1.09 (1.05-1.12), BPsys (per 5 mmHg) HR 1.10 (1.07-1.14), BPdia (per 5 mmHg) HR 1.09 (1.03-1.15), TG (per 1 mmol/L) HR 1.07 (1.02-1.13), TC (per 1 mmol/L) HR 1.22 (1.13-1.32). We observed a sex-specific risk pattern with an increased ESRD risk for men for increasing TG and smoking, and for women for increasing BMI and GGT. In time interval analyses BPsys and TC were associated with early ESRD onset, whereas BMI, FBG, BPdia and GGT were associated with later onset.

Conclusions: Anthropometric and metabolic factors are differentially associated with the long-term risk for ESRD in a sex- and time-dependent manner. Consideration of these patterns in preventive and therapeutic strategies could have an impact on ESRD incidence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135052PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555650PMC
May 2016

Efficacy and safety of body weight-adapted oral cholecalciferol substitution in dialysis patients with vitamin D deficiency.

BMC Nephrol 2015 Aug 4;16:128. Epub 2015 Aug 4.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, A-6800, Feldkirch, Austria.

Background: Vitamin D deficiency is highly prevalent in dialysis patients. Whether substitution of native vitamin D in these patients is beneficial is a matter of ongoing discussion, as is the optimal dosing schedule. The purpose of this study was to investigate the efficacy and safety of a body-weight adapted oral dosing regimen of cholecalciferol in dialysis patients.

Methods: In a prospective single-center study 56 prevalent dialysis patients with a baseline 25OHD3 level <20 ng/mL received 100 IU of cholecalciferol per kg body weight once weekly orally for 26 weeks. 25OHD3 was measured at baseline and at study end, iPTH every three months, serum calcium and phosphorous monthly. Concurrent medication including phosphate binders, calcitriol and cinacalcet and dialysate calcium concentration remained unchanged throughout the study.

Results: Baseline 25OHD3 was 9.9 ± 4.1 ng/mL and increased to 26.1 ± 8.8 ng/mL (P = 0.01). Fourteen patients (27 %) achieved a level > 30 ng/mL and all others above 20 ng/mL. Cinacalcet therapy was positively associated with the increase in 25OHD3 (P = 0.024). The plasma iPTH level significantly decreased from median 362 pg/mL to 297 pg/mL (P = 0.01). This decline was more pronounced in patients with higher baseline iPTH levels (P < 0.01) and differed significantly dependent on concurrent calcitriol therapy. A significant iPTH decrease was observed in patients receiving calcitriol (P = 0.031). Serum calcium and phosphorous did not change significantly throughout the study period. Cholecalciferol substitution was well tolerated without adverse effects.

Conclusion: The dosing regimen of oral cholecalciferol supplementation with 100 IU per kg body weight per week for 26 weeks in dialysis patients with vitamin D deficiency causes a significant increase in 25OHD3 close to the supposed target level of 30 ng/mL and a significant reduction in iPTH, without affecting serum calcium or phosphorous levels.
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http://dx.doi.org/10.1186/s12882-015-0116-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523023PMC
August 2015

Streptococcus uberis and Staphylococcus aureus forefoot and blood stream co-infection in a haemodialysis patient: a case report.

BMC Nephrol 2015 May 28;16:73. Epub 2015 May 28.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Carinagasse 47, A-6800, Feldkirch, Austria.

Background: Streptococcus uberis, the most frequent cause of mastitis in lactating cows, is considered non-pathogenic for humans. Only a few case reports have described human infections with this microorganism, which is notoriously difficult to identify.

Case Presentation: We report the case of a 75-year-old male haemodialysis patient, who developed a severe foot infection with osteomyelitis and bacteraemia. Both Streptococcus uberis and Staphylococcus aureus were identified in wound secretion and blood samples using mass spectrometry. The presence of Streptococcus uberis was confirmed by superoxide dismutase A sequencing. The patient recovered after amputation of the forefoot and antibiotic treatment with ampicillin/sulbactam. He had probably acquired the infection while walking barefoot on cattle pasture land.

Conclusion: This is the first case report of a human infection with Streptococcus uberis with identification of the microorganism using modern molecular technology. We propose that Staphylococcus aureus co-infection was a prerequisite for deep wound and bloodstream infection with Streptococcus uberis.
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http://dx.doi.org/10.1186/s12882-015-0069-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446856PMC
May 2015

Hafnia alvei Urosepsis in a Kidney Transplant Patient.

Case Rep Transplant 2015 15;2015:863131. Epub 2015 Apr 15.

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, 6800 Feldkirch, Austria.

Hafnia alvei, a gram-negative facultative anaerobic, rod-shaped bacterium, is a rare cause of infection in humans. We report on a renal transplant patient who developed H. alvei pyelonephritis and urosepsis. The source of infection remains enigmatic but is most likely the intestinal tract. Appropriate antibiotic therapy with cefepime followed by oral ciprofloxacin brought about rapid resolution of symptoms and complete recovery. H. alvei may cause severe infection in transplant patients without predisposing factors such as hospitalization, invasive procedures, or antibiotic treatment.
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http://dx.doi.org/10.1155/2015/863131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413887PMC
May 2015

End-stage renal disease from renal metastases.

Kidney Int 2015 Jan;87(1):246

Department of Nephrology and Dialysis, Academic Teaching Hospital Feldkirch, Feldkirch, Austria.

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http://dx.doi.org/10.1038/ki.2014.140DOI Listing
January 2015