[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.

Melkersson-Rosenthal syndrome in the context of sarcoidosis: a case report.

BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.

[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).

[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.

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.

Characterizing renal involvement in Hermansky-Pudlak Syndrome in a zebrafish model.

Hermansky-Pudlak Syndrome (HPS) is a rare disease caused by mutations in the genes coding for various HPS proteins. HPS proteins are part of multi-subunit complexes involved in the biogenesis of organelles from the lysosomal-endosomal-system. In humans, this syndrome is characterized by the presence of albinism, platelet dysfunction and pulmonary fibrosis. The renal component to the disease remains unstudied and untreated in patients with HPS. Here we demonstrate that in humans, HPS proteins have a high renal expression with active transcription of HPS1, 3, 4 and 5 in human podocyte cell culture, suggesting that impaired function of HPS proteins could directly impact renal function. Therefore, we developed a zebrafish model to study the renal involvement of HPS proteins in proteinuric kidney disease. Remarkably, knockdown of HPS genes in zebrafish causes glomerular injury with edema, proteinuria and structural changes of the glomerular filtration barrier. Moreover, reduced expression of HPS proteins in zebrafish recapitulates other important disease hallmarks, like hypopigmentation and accumulation of intracellular debris characteristic of lysosomal disorders. In conclusion, we present a valid zebrafish model that highlights the previously underestimated relevance of renal disease in HPS. This draws attention to the therapeutic options available to manage this component of the syndrome.

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).

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.

Predictors of Outcomes of Living Kidney Donation: Impact of Sex, Age and Preexistent Hypertension.

CONTEXT: Living kidney donation is considered a safe procedure with excellent outcomes. The great demand for organs has changed the suitability criteria for donation and older or hypertensive donors are increasingly accepted. METHODS: We reviewed the charts of 200 adults who donated a kidney at the University Hospital Hannover. Data regarding diastolic, systolic, mean blood pressure, renal function, and proteinuria at baseline and post-donation follow-up visits were recorded. A Mann-Whitney U test was performed to compare the post-nephrectomy development of blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria between men and women, hypertensives and normotensives, and older (≥65 years) and younger (<65 years) donors. Multivariable time-dependent Cox regression models were used to evaluate eGFR decline post-donation, after adjustment for covariates. RESULTS: The majority of donors were female (64.5%), and 29.0% had pre-existing hypertension. The mean age at donation was 49 years, and 9.5% were older than 65 years. During a median follow-up of 3 years, no significant differences in proteinuria and change in renal function were observed between both sexes or hypertensive and normotensive donors. In contrast, older donors exhibited a faster decline in renal function. Mean eGFR (chronic kidney disease epidemiology collaboration equation) pre-donation was 99.6 ± 21.9 mL/min in younger donors and 77.6 ± 17.7 mL/min in older donors (P < .001). The respective mean values at the last follow-up visit were 81.3 ± 24.0 and 46.8 ± 17.9 mL/min (P < .001). After adjustment for sex and preexisting hypertension, compared to younger donors, older donors had a 2.39 hazard ratio for eGFR decline. CONCLUSION: Older adults display a faster decline in renal function after donation and thus should be carefully evaluated for suitability before donation.

[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.