[Hygiene in nephrology]. / Hygiene in der Nephrologie.

Patients with chronic kidney diseases are particularly at risk of infections and must therefore be protected against the risks of infection in dialysis treatment. Viral hepatitis no longer plays a very prominent role in dialysis facilities because nosocomial transmission can be reliably avoided. Nowadays, patients colonized with multidrug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant gram-negative bacteria or vancomycin-resistant enterococci, are more common. Bloodstream infections, which particularly occur in dialysis via central venous catheters, are potentially very dangerous for patients. Regular surveillance and targeted interventions in the event of excessive infection numbers are necessary. The hygienic handling of dialysis fluids has now become established through decades of experience and is ensured through the use of quality management systems. The coronavirus crisis poses special challenges for dialysis centers.

[Waiting list management]. / Wartelistenpflege.

Listing a patient on the Eurotransplant waiting list for a kidney transplantation obliges transplant centers to ensure that an allocated organ can also be transplanted, as long as there are no acute recipient-specific medical or personal contraindications. Assessing the ability for transplantation over a period of up to 10 years between initiation of dialysis and an organ offer represents a major challenge in manpower and logistic efforts. The present article reviews specific aspects regarding waiting list management on the basis of current guideline recommendations and literature data.

[Diagnosis and treatment of chronic kidney disease]. / Diagnostik und Therapie der chronischen Nierenerkrankung.

Chronic kidney disease is defined by decreased glomerular filtration rate or proteinuria. Diabetic nephropathy and hypertensive renal damage are responsible for the majority of cases. The initiation of therapy has to consider if causal treatment of the underlying disease is possible and indicated. In all patients, even if specific treatment is not possible, therapy should aim at reducing progression of kidney failure. Chronic kidney diseases tend to intrinsic deterioration that persists after cessation of the causative damaging pathomechanism. Progression of disease can be delayed; the most important measures include strict blood pressure control, reduction of proteinuria, and avoidance of further renal harm. Kidney disease induces typical sequelae such as left ventricular hypertrophy, vascular calcification, anemia, and renal osteodystrophy. While these are well understood nowadays therapeutic options are limited. The uremic syndrome is to be avoided by renal replacement therapy.

[Multicenter trial for sudden hearing loss therapy - planning and concept]. / Multizentrische Studie zur Hörsturztherapie - Planung und Konzeption.

Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

[Indocyanine green elimination for the evaluation of liver function: prognostic value in patients with community-acquired sepsis]. / Indocyaningrün-Elimination als Maß der Leberfunktion : Prognostische Bedeutung bei Patienten mit ambulant erworbener Sepsis.

BACKGROUND: The aim of our clinical study was to correlate liver function measured by indocyanine green (ICG) elimination and clinical outcomes in patients with an early stage of community-acquired sepsis (CAS). MATERIALS AND METHODS: A total of 341 patients (≥ 18 years) presenting with suspicion of CAS or evidence of an infection and fulfillment of ≥ 2 systemic inflammatory response syndrome (SIRS) criteria were included in the observational study"Prognosis of early sepsis 2" (Prognose der frühen Sepsis 2, ProFS 2). Patients who had been hospitalized within the last 7 days were excluded. In a subgroup of these patients (n = 72) who were transferred to an intensive or intermediate care unit according to the clinical judgment of the treating physicians, ICG elimination (plasma disappearance rate, ICG-PDR; 15 min retention rate, ICG-R15) was assessed by using a noninvasive monitoring system (LiMON, PULSION Medical Systems, Germany). ICG-PDR and -R15 were determined on the day of admission (n = 72) and after 96 h (n = 34). The primary end point of the study was defined as death within 30 days. Secondary endpoints were need for renal replacement therapy, requirement for invasive mechanical ventilation, and length of stay in an intermediate or intensive care unit. RESULTS AND CONCLUSION: In contrast to patients with sepsis or severe sepsis, ICG elimination was found to be significantly impaired in patients with septic shock. Furthermore, a significant predictive value of ICG-PDR and -R15 on the day of admission for the need for subsequent renal replacement therapy (n = 12) was observed. In addition, reduced ICG elimination was associated with a longer stay in an intermediate or intensive care unit. However, ICG elimination on admission could not predict 30-day mortality (n = 14) or requirement of mechanical ventilation (n = 20).

[Clinical issues with uremia]. / Klinische Probleme der Urämie.

Uremia describes the consequences of intoxication in chronic renal failure with substances that are renally cleared in healthy individuals. Acute uremia is a syndrome of gastrointestinal symptoms, pericarditis, pleuritis, and central nervous system alterations ending with coma. These symptoms can be resolved by renal replacement therapy. In addition, chronic uremia can result in damage of multiple organ systems, which continues to advance despite dialysis therapy. This is caused by retention of toxins that cannot be adequately removed due to insufficient treatment time or a molecular weight range hampering elimination. Uremic toxins can be generated by the energy or nucleic acid metabolism, they can be proteins or large molecules that are altered chemically by the uremic milieu. Chronic uremia can influence the majority of long-term complications of chronic renal failure: systemic microinflammation, cardiovascular disease, immunodeficiency, malnutrition, anemia, bone metabolism, and polyneuropathy. There are few therapeutic options other than kidney transplantation.

Laparoscopic versus open bilateral nephrectomy in transplant recipients with medication-resistant hypertension: final results of a multicenter study with 15 years of follow-up.

BACKGROUND: The objective of this study was to evaluate the outcomes of laparoscopic bilateral nephrectomy (LBN) compared with open bilateral nephrectomy (OBN) in transplant recipients with medication-resistant hypertension. MATERIAL AND METHODS: Between 1994 and 2009, 66 renal transplant recipients underwent LBN due to poorly controlled hypertension. We compared them with 44 previous patients who underwent OBN. RESULTS: The mean operative times for LBN and OBN were 195.4 ± 60.1 minutes and 145.7 ± 30.2 minutes, respectively (P = .013). The mean hospital stays were 4.2 ± 2.1 in the LBN versus 10.3 ± 3.9 days in the OBN groups; the mean complication rates were 9.1% versus 18.2%, respectively. At follow-up, the blood pressure (mean value 130/90 mm Hg) in 45 patients (68.2%) among the LBN group was well controlled without the need for antihypertensive medications. In 19 patients (28.8%) significantly fewer antihypertensive drugs (1 or 2) were needed compared with the preoperative status. The remaining 2 patients (3%), both of whom had returned to hemodialysis due to chronic transplant rejection, remained on a combination of 3 or more antihypertensive drugs. Among the open surgery group, 23 subjects (52.3%) showed significantly decreased arterial blood pressure without needing medical therapy; 18 patients (40.9%) required 1 or 2 drugs and the remaining 3 (6.8%) were on a combination of 3 or more antihypertensives. The last cohort had returned to hemodialysis due to chronic transplant rejection. CONCLUSIONS: LBN showed a higher efficacy than open surgery to treat medication-resistant hypertension after renal transplantation, reducing the postoperative trauma and the morbidity rate in high-risk transplant recipients.

[Electrolyte disorders]. / Störungen des Elektrolytstoffwechsels.

Disorders of electrolyte balance are frequent and pathophysiologically complex. Sodium is responsible for a large part of the osmolarity of extracellular fluids. Therefore, pathological concentrations of serum sodium reflect the relation between sodium and water in the extracellular compartment rather than the total body sodium content. The causes of hypo- or hypernatremia can only be deduced if total body volume status is considered. Patients with hyponatremia and volume deficit should receive sodium chloride solution while patients with this disorder in the presence of volume overload need strict water restriction. In certain cases additional specific pharmacotherapy directed at the effects of antidiuretic hormone may be considered. Potassium and calcium are extracellular regulatory ions; their concentrations do not relevantly contribute to osmolarity and water distribution but to electrophysiologically relevant transmembrane potentials. These ions are influenced by active membrane transporters and regulated by several hormones. The rather small extracellular pools are overfilled or depleted by alterations of intake and excretion. In addition, several inborn or acquired defects of transmembrane transporters may severely alter their extracellular concentrations. Therapy needs to consider the specific mechanisms that led to the electrolyte disorder including modification of intake, excretion or extra-intracellular distribution.

CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients.

Migration of monocytes into the vessel wall contributes to the onset and progression of atherosclerosis. Because monocytes are a heterogeneous population, we determined potential associations between monocyte subsets and cardiovascular events in a prospective cohort of 94 dialysis patients followed for 35 months. The incidence of cardiovascular events and death measured by Kaplan-Meier plots and flow cytometric analysis of monocyte subsets showed that total leukocyte and monocyte numbers failed to predict event-free survival. Among monocyte subsets, a high CD14(++)CD16(+) monocyte number was associated with higher rates of cardiovascular events and death. In a multivariate proportional hazards model adjusted for classical cardiovascular risk factors, patients with CD14(++)CD16(+) monocyte numbers in the top quartile were at higher risk of cardiovascular events and death compared to patients in the lowest quartile. Our study suggests that the number of CD14(++)CD16(+) monocytes was independently associated with cardiovascular events and death in a high-risk population of dialysis patients.

Proinflammatory CD14+CD16+ monocytes are associated with subclinical atherosclerosis in renal transplant patients.

Atherosclerotic cardiovascular disease is a major cause of death in renal transplant (TX) recipients. Atherosclerotic lesions are characterized by monocytic infiltration. Circulating monocytes can be divided into functionally distinct subpopulations, among which CD14++CD16+ and CD14+CD16+ monocytes (summarized as CD16+ monocytes) are proinflammatory cells. We hypothesized that the frequency of circulating CD16+ monocytes is associated with subclinical atherosclerosis in TX patients. Monocyte subpopulations were quantified in 95 TX and 31 hemodialysis patients (HD). In TX patients, subclinical atherosclerosis was determined by carotid intima media thickness (IMT) measurement. TX patients had lower frequencies of CD16+ monocytes than HD patients. When stratifying by immunosuppressive treatment, patients on methylprednisolone (MP) therapy had fewer CD14+CD16+ monocytes than patients not receiving MP. CD14+CD16+ monocytes decrease very shortly after transplantation. CD14+CD16+ monocyte frequency correlated with IMT in TX recipients (r = 0.34, p < 0.001). This correlation was most pronounced among patients without MP treatment (r = 0.55, p = 0.02). In a multivariate regression analysis, the association of CD14+CD16+ monocytes with IMT was independent from traditional cardiovascular risk factors. The frequency of proinflammatory CD14+CD16+ monocytes is independently associated with subclinical atherosclerosis in transplant recipients. Further studies on the association between circulating leukocytes and atherosclerosis should take monocyte heterogeneity into account.

Cytokine gene polymorphism and progression of renal and cardiovascular diseases.

Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation and suppression. Both chronic kidney disease (CKD) and end-stage renal disease (ESRD) are characterized by elevated levels of proinflammatory cytokines and markers of inflammation. Cytokines may modulate the risk for progression of renal disease and the susceptibility to cardiovascular disease (CVD). Polymorphisms of cytokine genes may influence gene transcription and cytokine secretion and thereby modulate the risk of progression of renal and CVDs. The observed inconsistencies in the data regarding associations between single-nucleotide gene polymorphisms (SNPs) and their presumed phenotypic expression emphasize the need to recognize several conceptual and methodological aspects such as haplotypic rather than single SNP variations and the influence of pathway genes with synergistic or antagonistic effects that ultimately determine the phenotype. It is conceivable that when a patient with a high-risk cytokine genotype develops CKD, the risk for CVD is increased. Early interventions in CKD patients with high-risk genotypes may slow the progression of renal disease and also decrease CV mortality and morbidity.

[Differential diagnosis of urinary findings]. / Was hinter dem pathologischen Urinbefund steckt.

Classical urinalysis is extremely useful in the differential diagnosis of diseases of the kidneys and lower urinary tract. Although dipsticks are suitable for orientational purposes, when pathology is indicated, and when renal disease presents, they must be supplemented by urine microscopy or quantitative and qualitative protein electrophoresis to establish the diagnosis. Phase-contrast microscopy can distinguish glomerular from nonglomerular hematuria and thus guide the further diagnosis, and the detection of leukocytes and bacteria confirms the diagnosis of urinary tract infection. In asymptomatic patients microhematuria or proteinuria is detected more frequently with increasing age. A differentiated diagnostic strategy must be adapted to the individual risk of the patient, and must avoid overdiagnosis while not missing potentially serious pathology.

The interleukin-10 promoter genotype determines clinical immune function in hemodialysis patients.

BACKGROUND: Immune dysfunction and the impaired hepatitis B vaccination response are complications of chronic renal failure that are tightly associated with inflammation induced by uremia and blood-membrane contacts. Proinflammatory cytokines, such as interleukin (IL)-6, are counter-regulated by IL-10 with a large interindividual variability. Part of the variability of cytokine production is genetically determined since polymorphisms in the cytokine gene promoters lead to high or low production. The aim of this study was to detect the genetic influence of the IL-10 promoter on immune function of chronic hemodialysis patients. METHODS: The IL-10 genotype (polymorphic bases at positions -1082 and -819) was determined in 272 chronic hemodialysis patients using highly specific PCR and related to the patients' response to a triple vaccination against hepatitis B. Secretion of IL-10 and IL-6 by peripheral blood leucocytes in vitro was determined by ELISA. RESULTS: The prevalence of the IL-10 genotypes in dialysis patients with well-preserved immune function (vaccination responders) was similar to the general population. In contrast, prevalence of the -1082G* allele (associated with high production of IL-10) was low in the nonresponders. The relative risk of vaccination nonresponse in patients homozygous for the -1082A* allele was 1.394 (95% CI, 1.091 to 1.781, P < 0.05) compared to those homozygous for -1082G*. There was no relationship between the IL-10 genotype and the type of renal disease. CONCLUSIONS: The IL-10 genotype determines IL-10 production in dialysis patients, which down-regulates uremia- and dialysis-induced chronic inflammation and helps to preserve immune defense functions.

Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation.

BACKGROUND: Immunosuppressive treatment in transplant patients frequently causes infectious complications with cytomegalovirus (CMV). The extent of CMV replication can be followed by a number of diagnostic methods. There is, however, no simple diagnostic tool to assess the quality of the cellular antiviral immune response of an individual patient. This would be of particular importance for therapy decisions, as patients with detectable virus load do not necessarily develop CMV-related disease. Using a rapid whole blood assay, the frequencies of CMV-reactive CD4 and CD8 T cells were followed after renal transplantation to characterize their relative contribution in the containment of CMV infection. METHODS: T cells from transplant patients ands healthy control persons were stimulated with CMV antigen in vitro. Based on specific cellular activation and induction of intracellular cytokines, the frequency of CMV-reactive CD4 and CD8 T cells was determined using flow cytometry. Viral load quantified using the "hybrid-capture" assay. RESULTS: The absence of CMV complications in long-term transplant recipients is reflected by stable virus-specific T-cell frequencies, which do not differ from healthy CMV-positive controls. In contrast, during the first months after transplantation, clinical symptoms are preceded by a decrease in CMV-reactive CD4 T-cell frequencies and an increase in CMV load. CONCLUSIONS: The individual immune response and CMV replication are critically balanced and can be characterized by assesing both viral load and antiviral T cells. Our experimental design allows the identification of patients with sufficient, insufficient, or absent T-cell activity and can serve as diagnostic tool to facilitate decisions on antiviral therapy.

Strong depletion of CD14(+)CD16(+) monocytes during haemodialysis treatment.

BACKGROUND: The immune defect in haemodialysis (HD) patients is associated with a monocytic dysfunction, including an increased production of proinflammatory cytokines. Monocytes fall into subpopulations comprising CD14(++)CD16(-) and CD14(+)CD16(+) cells. Circulating numbers of the latter can rapidly increase during infectious episodes and inflammation. METHODS: We determined the amount of CD14(+)CD16(+) monocytes in HD patients and characterized their fate during HD treatment. In 34 HD patients and 17 healthy controls, the distinct cell populations were determined by differential blood counts and flow cytometry. Cells from 14 HD patients were analysed at the start, 10, 30 and 120 min thereafter, and at the end of HD treatment. RESULTS: Before HD, patients show a monocytosis with a strongly increased CD14(+)CD16(+) subpopulation. Early during HD treatment, circulating leukocyte numbers decrease, with monocytes being most profoundly influenced. Interestingly, among them, sequestration is most pronounced in the CD14(+) CD16(+) subpopulation. After 30 min, approximately 83+/-9% of CD14(+)CD16(+) cells are removed from circulation. This sequestration does not differ between patients treated with polyamide or haemophan membranes. The sequestration is a short-lived temporary effect and cell numbers are replenished within 120 min of treatment for the entire monocyte population. Beyond that time point, cellular activation by the dialyser membrane becomes visible. Reappearence kinetics of CD14(+)CD16(+) monocytes is slower; however, initial numbers are reached by the end of treatment. CONCLUSION: Haemodiaysis leads to temporary removal of monocytes from the bloodstream followed by the reappearance of activated cells. This might contribute to the state of chronic microinflammation, which is reflected by high levels of CD14(+)CD16(+) monocytes.