[High burden of disease in patients with ANCA-associated vasculitis : A claims data study in Germany]. / Hohe Krankheitslast bei Patienten mit ANCA-assoziierter Vaskulitis : Versorgungsdatenstudie in Deutschland.

BACKGROUND & OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare chronic autoimmune diseases characterized by recurrent systemic inflammation provoking multiple morbidities. AAV patients suffer from various organ manifestations and treatment-related severe adverse effects. This retrospective study investigated the concrete burden of AAV disease on patients in Germany. METHODS: Based on anonymized longitudinal German statutory health insurance (SHI) claims data from the years 2011-2016, a representative cohort of approximately 3 million insured persons was used to identify patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and selected clinical aspects were systematically assessed. RESULTS: The most frequent concomitant morbidities of GPA and MPA were renal and respiratory disorders. Severe renal involvement occurred in 11.6% of GPA and 24.3% of MPA patients within 15 quarters of diagnosis. Severe infections developed in one third of AAV patients within the first three quarters post-diagnosis. The annual rate of major relapses was 5-8%. AAV patients with renal impairment or infections showed increased annual mortality rates of 14.4 and 5.6%, respectively. CONCLUSION: Based on this analysis of German health care data, disease-specific assumptions regarding the burden on AAV patients were confirmed and concretized for the German context. AAV patients suffer from a high burden of morbidity, including multiple disease manifestations, relapses, and severe complications due to AAV treatment.

[Telemonitoring and eHealth for arterial hypertension : Status quo and perspectives]. / Telemonitoring und E-Health bei arterieller Hypertonie : Status quo und Perspektiven.

Home blood pressure monitoring in combination with cointerventions can contribute to a better blood pressure control. More complex telemonitoring projects have shown promising initial results in studies in primary care and also in certain patient groups (e.g. pregnant women). The integration into the clinical routine is of crucial importance because "stand-alone" solutions have yet to show convincing effects on blood pressure. The new German Digital Care Act (Digitale-Versorgung-Gesetz, DVG) provides a framework to introduce, validate and prescribe digital applications in routine care financed by the Statutory Health Insurance, when positive effects on care have been confirmed and they are listed in the register of the digital healthcare applications (Verzeichnis der digitalen Gesundheitsanwendungen, DiGA).

Kidney injury enhances renal G-CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo.

Kidney injury significantly increases overall mortality. Neutrophilic granulocytes (neutrophils) are the most abundant human blood leukocytes. They are characterized by a high turnover rate, chiefly controlled by granulocyte colony stimulating factor (G-CSF). The role of kidney injury and uremia in regulation of granulopoiesis has not been reported. Kidney transplantation, which inherently causes ischemia-reperfusion injury of the graft, elevated human neutrophil expression of the surface glycoprotein CD177. CD177 is among the most G-CSF-responsive neutrophil genes and reversibly increased on neutrophils of healthy donors who received recombinant G-CSF. In kidney graft recipients, a transient rise in neutrophil CD177 correlated with renal tubular epithelial G-CSF expression. In contrast, CD177 was unaltered in patients with chronic renal impairment and independent of renal replacement therapy. Under controlled conditions of experimental ischemia-reperfusion and unilateral ureteral obstruction injuries in mice, renal G-CSF mRNA and protein expression significantly increased and systemic neutrophilia developed. Human renal tubular epithelial cell G-CSF expression was promoted by hypoxia and proinflammatory cytokine interleukin 17A in vitro. Clinically, recipients of ABO blood group-incompatible kidney grafts developed a larger rise in neutrophil CD177. Their grafts are characterized by complement C4d deposition on the renal endothelium, even in the absence of rejection. Indeed, complement activation, but not hypoxia, induced primary human endothelial cell G-CSF expression. Our data demonstrate that kidney injury induces renal G-CSF expression and modulates granulopoiesis. They delineate differential G-CSF regulation in renal epithelium and endothelium. Altered granulopoiesis may contribute to the systemic impact of kidney injury.

[Lung ultrasound in patients with SARS-CoV-2 infection]. / Lungenultraschall bei Patienten mit SARS-CoV-2-Infektion.

After taking a patient's history and physical examination, lung ultrasound can immediately reveal numerous causes and complications in patients suffering from respiratory tract infection and/or dyspnea. It can thus facilitate decisions on further diagnostic and first therapeutic procedures, even in patients with a SARS-CoV­2 infection who present to the emergency room. This review article highlights the typical findings of lung ultrasound in patients with COVID-19 and discusses its value compared to other imaging methods.

Circulating factors cause proteinuria in parabiotic zebrafish.

Proteinuria can be induced by impairment of any component of the glomerular filtration barrier (GFB). To determine the role of circulating permeability factors on glomerular damage, we developed a parabiosis-based zebrafish model to generate a common circulation between zebrafish larvae. A morpholino-mediated knockdown of a podocyte specific gene (nephronectin) was induced in one zebrafish larva which was then fused to an un-manipulated fish. Notably, proteinuria and glomerular damage were present in the manipulated fish and in the parabiotically-fused partner. Thus, circulating permeability factors may be induced by proteinuria even when an induced podocyte gene dysregulation is the initiating cause.

The nephrology eHealth-system of the metropolitan region of Hannover for digitalization of care, establishment of decision support systems and analysis of health care quality.

BACKGROUND: Even though a high demand for sector spanning communication exists, so far no eHealth platform for nephrology is established within Germany. This leads to insufficient communication between medical providers and therefore suboptimal nephrologic care. In addition, Clinical Decision Support Systems have not been used in Nephrology until now. METHODS: The aim of NEPHRO-DIGITAL is to create a eHealth platform in the Hannover region that facilitates integrated, cross-sectoral data exchange and includes teleconsultation between outpatient nephrology, primary care, pediatricians and nephrology clinics to reduce communication deficits and prevent data loss, and to enable the creation and implementation of an interoperable clinical decision support system. This system will be based on input data from multiple sources for early identification of patients with cardiovascular comorbidity and progression of renal insufficiency. Especially patients will be able to enter and access their own data. A transfer to a second nephrology center (metropolitan region of Erlangen-Nuremburg) is included in the study to prove feasibility and scalability of the approach. DISCUSSION: A decision support system should lead to earlier therapeutic interventions and thereby improve the prognosis of patients as well as their treatment satisfaction and quality of life. The system will be integrated in the data integration centres of two large German university medicine consortia (HiGHmed ( highmed.org ) and MIRACUM ( miracum.org )). TRIAL REGISTRATION: ISRCTN16755335 (09.07.2019).

[Two case reports on resistant hypertension]. / Zwei Fallberichte zur therapierefraktären Hypertonie.

Primary aldosteronism (PA) is a frequent cause of resistant hypertension. The clinical presentation is heterogeneous, but a suppressed or low normal renin (especially with ACE inhibitors or sartans) should raise suspicion for primary aldosteronism, even when aldosterone levels are in the normal range. Diagnosis of unilateral hormone production from an adrenal adenoma (Conn syndrome), which is curable by surgery, requires adrenal vein sampling, which should be performed in experienced centers.

[Diagnosis and treatment of kidney involvement in plasma cell diseases : Renal involvement in multiple myeloma and monoclonal gammopathies]. / Diagnose und Therapie der Nierenbeteiligung bei Plasmazellerkrankungen : Renale Beteiligung bei multiplem Myelom und monoklonalen Gammopathien.

BACKGROUND: Kidney involvement is a common complication in patients with plasma cell diseases. OBJECTIVE: This article outlines the spectrum of renal involvement in plasma cell dyscrasia and describes diagnostic and therapeutic measures to guide clinical management. MATERIAL AND METHODS: Evaluation and discussion of the current literature as well as existing guidelines and recommendations of professional societies. RESULTS: The clinical manifestations of renal involvement in plasma cell disorders are heterogeneous and range from acute cast nephropathy in multiple myeloma to rare forms of glomerulonephritis. The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe kidney involvement caused by monoclonal gammopathy but without evidence for underlying malignancy. Light chain cast nephropathy is the most common renal manifestation in multiple myeloma, whereas monoclonal immunoglobulin deposition disease (MIDD) and renal light chain (AL) amyloidosis can be found in multiple myeloma and MGRS. Decisive is the extended hematological diagnostics in order to exclude the presence of a hematological neoplasm. The treatment of renal involvement in monoclonal gammopathies involves the reduction of the plasma cell clone with cytoreductive treatment. The reduction of the monoclonal protein in serum is prognostically relevant for the renal response to treatment. In the case of histological evidence of a light chain cast nephropathy, high cut-off dialysis is recommended to reduce the free light chains in serum. CONCLUSION: The spectrum of renal manifestations in plasma cell dyscrasia has been expanded, particularly since the introduction of the term MGRS. Diagnostic and therapeutic management remain an interdisciplinary challenge.

Preoperative serum uric acid predicts incident acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is a frequent complication and several risk factors increasing its incidence have already been characterized. This study evaluates the influence of preoperative increased serum uric acid (SUA) levels in comparison with other known risk factors on the incidence of AKI following cardiac surgery. METHODS: During a period of 5 month, 247 patients underwent elective coronary artery bypass grafting, valve replacement/ repair or combined bypass and valve surgery. Datas were prospectively analyzed. Primary endpoint was the incidence of AKI as defined by the AKI criteria comparing patients with preoperative serum uric acid (SUA) levels below versus above the median. Multivariate logistic regression analysis was used to identify independent predictors of postoperative AKI. RESULTS: Thirty (12.1%) of the 247 patients developed postoperative AKI, 24 of 30 (80%) had preoperative SUA- levels above the median (≥373 µmol/l) (OR: 4.680, CI 95% 1.840; 11.904, p = 0.001). In the multivariate analysis SUA levels above the median (OR: 5.497, CI 95% 1.772; 17.054, p = 0.003), cardiopulmonary bypass (CPB) time > 90 min (OR: 4.595, CI 95% 1.587; 13.305, p = 0.005), cardiopulmonary bypass (CPB) > 30 kg/m2 (OR: 3.208, CI 95% 1.202; 8.562; p = 0.02), and preoperative elevated serum-creatinine levels (OR: 1.015, CI 95% 1.001; 1.029, p = 0.04) were independently associated with postoperative AKI. CONCLUSIONS: Serum uric acid is an independent risk marker for AKI after cardiac surgery. From all evaluated factors it showed the highest odds ratio.

[Herbal medicines for psychiatric disorders]. / Phytotherapie bei psychiatrischen Erkrankungen.

BACKGROUND: In Germany herbal medicines are traditionally frequently used. They represent an important therapeutic option, especially in self-medication. METHODS: Current systematic review articles and meta-analyses were evaluated and summarized with respect to the evidence of phytotherapeutic drugs for selected psychiatric indications. RESULTS: Apart from the use of St. John's wort for depression, no other herb has so far shown convincing evidence. CONCLUSION: Due to the promising effects and the low side effect potential within the existing studies, further randomized controlled trials (e. g. for Passiflora incarnata, Rhodiola rosea and Lavendula officinalis) are definitely indicated.

[Pathophysiology and treatment of IgA nephropathy]. / Pathophysiologie und Therapie der IgA-Nephropathie.

The IgA nephropathy is the most frequent form of glomerulonephritis worldwide. In approximately 30% of patients a reduction in the glomerular filtration rate of approximately 50% is observed within 10 years. Patients with IgA nephropathy form IgG autoantibodies against galactose-deficient IgA1 antibodies. This results in deposition of these antibodies in the mesangium and activation of complement with mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis and atrophying interstitial fibrosis. The basic treatment for patients with IgA nephropathy consists of removing risk factors, in particular hypertension, with blockade of the renin-angiotensin-aldosterone system. Immunosuppressives were also investigated in various studies but a clear advantage was not observed.

[Human genetics in atypical hemolytic uremic syndrome-its role in diagnosis and treatment]. / Humangenetik beim atypischen hämolytisch-urämischen Syndrom ­ Rolle in Diagnostik und Therapie.

The atypical hemolytic uremic syndrome (aHUS), one of the three major forms of thrombotic microangiopathy, is characterized by genetic alterations in the area of the complement cascade, which can be detected in 40%-60% of all patients with aHUS. Mutations in over 10 different genes have now been identified. The most frequent and clinically relevant of these are mutations that result in a decreased or absent function of factor H, the formation of hybrid genes, or the formation of autoantibodies against factor H. Although genetics are not required for the diagnosis of aHUS, it is of great importance for the decision on how long to treat with the C5 inhibitor eculizumab. Also, knowledge of genetic alterations is absolutely essential if a living related donor is considered, in order to protect the living donor and recipient from developing aHUS.

[Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation]. / Abdominalchirurgie trifft Nephrologie: Wichtige nephrologische Aspekte vor und nach Nieren- bzw. Lebertransplantation.

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation.

[Organ transplantation in Germany: Critical examination in times of scarce resources]. / Organtransplantation in Deutschland: Kritische Betrachtung in Zeiten knapper Ressourcen.

Organ transplantation over the last 40 years has developed into a standardized successful procedure for the replacement of heart, kidney liver, lung, and pancreas. During this time, treatment strategies have greatly improved and novel procedures such as living related organ donation have been introduced. Despite these improvements, the number of organ transplants has stalled in recent years. In the face of increasing numbers of patients on the waiting list for organ transplantation, this situation is unacceptable and ways to improve the situation of organ transplantation have to be found.The reasons for the stagnant situation in organ transplantation are manifold and include lack of awareness in the general population, insufficient organ procurement in hospitals as well as problems in organ allocation. The criteria for organ allocation have been unfairly reported to EUROTRANSPLANT by some of the presently 44 centers in order of more rapidly receive an organ for their patients on the waiting list. The evolving discussions around this so-called transplantation scandal has further eroded support for organ transplantation in Germany. A critical assessment and a well-defined plan are necessary to improve the situation, increase the number of transplanted organs, and reduce the unacceptably long waiting time for patients in Germany.

[Weakness of the extremities in a 73-year-old male patient]. / 73-jähriger Patient mit Kraftlosigkeit in den Extremitäten.

A patient undergoing cyclosporine therapy presented with muscle weakness. This was preceded by diarrhea and treated with ciprofloxacin. Rhabdomyolysis was diagnosed clinically and biochemically. This was presumably drug-induced triggered by a combined therapy with cyclosporine, amlodipine, simvastatin and ciprofloxacin. The case presented demonstrates that during therapy with several substances which inhibit the degradation of simvastatin, the additional administration of ciprofloxacin should be considered with extreme caution.

[Rehabilitation after kidney transplantation: Old problems and new structures]. / Rehabilitation nach Nierentransplantation: Alte Probleme und neue Strukturen.

Kidney transplantation is currently the best therapeutic option for patients with end stage renal disease. Alternative treatment with hemo- or peritoneal dialysis is associated with higher comorbidities, higher morbidity/mortality, and reduced quality of life. Thus, a major aim in posttransplant care is to develop strategies to increase transplant survival and reduce known risk factors and comorbidities. In this overview, we propose a concept to include rehabilitation clinics in all aspects of the transplant process. This concept includes pretransplant care on the waiting list to prepare the patient for the transplant, the direct postoperative treatment phase, and repeated and risk adapted stays in rehabilitation clinics during long-term follow-up to address specific and individual problems.

Long-term impact of CMV infection on allografts and on patient survival in renal transplant patients with protocol biopsies.

Cytomegalovirus (CMV) infection is a frequent complication of early posttransplantation. This study examines its impact on chronic allograft changes, long-term graft loss, and patient survival. We studied 594 patients who had protocol biopsies at 6 wk, and 3 and 6 mo posttransplantation. Chronic allograft changes were evaluated according to the updated Banff classification [interstitial fibrosis/tubular atrophy (IF/TA), vascular and glomerular lesions]. Follow-up data were available for up to 10 yr. CMV infection was diagnosed in 153 of 594 patients (26%) in the first year after transplantation, mostly within the first 3 mo. Graft survival was reduced in patients with CMV (P = 0.03) as well as the combined allograft/patient survival (P = 0.008). Prevalence of IF/TA at 6 wk after transplantation was already threefold higher in patients who experienced CMV infection later on compared with patients without CMV (P = 0.005). In multivariate analyses, CMV viremia or disease was not a significant factor for graft loss or death. In conclusion, patients with CMV infection posttransplantation show more chronic allograft changes early on, even before CMV infection, and development of IF/TA is not more prevalent in patients with CMV. Our data do not support a significant role of CMV in patient and graft outcomes.