Complement Activation in Nephrotic Glomerular Diseases.

The nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood-urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches.

Age- and Sex-Specific Reference Values for Renal Volume and Association with Risk Factors for Chronic Kidney Disease in a General Population-An MRI-Based Study.

BACKGROUND: Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRFs). We analysed RV using magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) to find sex- and age-specific reference values for RV and to test the influence of several markers on RV. The main objective is to describe reference values for RV in people from the general population without kidney disease. METHODS: 1815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. RESULTS: The estimated glomerular filtration rate (eGFR), serum uric acid, and right and left RV were higher in men compared to women (all p < 0.001). Left kidneys were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside-down U-shaped relation in men. In multivariable linear regression models, current smoking (ß = 14.96, 95% CI 12.12; 17.79), BSA (ß = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (ß = 0.17, 95% CI 0.01; 0.32), and eGFR (ß = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right RV, whereas uric acid (ß = -0.03, 95% CI -0.05; -0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. CONCLUSION: Reference values for RV are different for age groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men showed a U-shaped correlation. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF in middle-aged males.

Carotid intima-media thickness and atherosclerotic plaques are associated with renal function decline: a 14-year longitudinal population-based study.

BACKGROUND: Chronic kidney disease (CKD) leads to increased morbidity and mortality. The underlying causes of CKD are often similar to those of atherosclerosis. We investigated whether carotid atherosclerotic parameters are associated with renal function decline. METHODS: Within the population-based Study of Health in Pomerania (SHIP), Germany, 2904 subjects were observed over 14 years. The carotid intima-media thickness (cIMT) as well as carotid plaques were measured by standardized B-mode ultrasound protocol. CKD is defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and albuminuria as urinary albumin-creatinine ratio (ACR) ≥30 mg/g. eGFR was calculated by the full age spectrum (FAS) equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Mixed models were applied to associate carotid parameters with change in renal function longitudinally and adjusted for confounding. RESULTS: The age range of the study sample was 25-86 years with a median of 54 years at baseline. In longitudinal analyses, subjects with high cIMT and the presence of plaques at baseline showed a greater decrease in eGFR (cIMT: FAS-eGFR: P < .001, CKD-EPI-eGFR: P < .001; plaques: FAS-eGFR: P < .001, CKD-EPI-eGFR: n.s.) as well as an increased risk of developing CKD during the follow-up (cIMT: FAS-eGFR: P = .001, CKD-EPI-eGFR: P = .04; plaques: FAS-eGFR: P = .008, CKD-EPI-eGFR: P = .001). There was no association between atherosclerotic parameters and the risk of developing albuminuria. CONCLUSIONS: cIMT and carotid plaques are associated with renal function decline as well as CKD in a population-based sample. Furthermore, the FAS equation adapts best to this study population.

Comorbid Depression and Diabetes Are Associated with Impaired Health-Related Quality of Life in Chronic Kidney Disease Patients.

Given the increasing prevalence of chronic kidney disease (CKD) and its impact on health care, it is important to better understand the multiple factors influencing health-related quality of life (HRQOL), particularly since they have been shown to affect CKD outcomes. Determinants of HRQOL as measured by the validated Kidney Disease Quality of Life questionnaire (KDQOL) and the Patient Health Questionnaire depression screener (PHQ-9) were assessed in a routine CKD patient sample, the Greifswald Approach to Individualized Medicine (GANI_MED) renal cohort (N = 160), including a wide range of self-reported data, sociodemographic and laboratory measures. Compared to the general population, CKD patients had lower HRQOL indices. Dialysis was associated with (1) low levels of physical functioning, (2) increased impairments by symptoms and problems, and (3) more effects and burden of kidney disease. HRQOL is seriously affected in CKD patients. However, impairments were found irrespective of eGFR decline and albuminuria. Rather, the comorbid conditions of depression and diabetes predicted a lower HRQOL (physical component score). Further studies should address whether recognizing and treating depression may not only improve HRQOL but also promote survival and lower hospitalization rates of CKD patients.

Potentially inappropriate medication in patients with chronic kidney disease and elderly patients.

BACKGROUND: Most patients with chronic kidney disease (CKD) are old, comorbid, and subjected to polypharmacy. This study describes prevalence and predictors of potentially inappropriate medication (PIM) in CKD patients. MATERIALS AND METHODS: Medication plans of CKD patients of the "Greifswald Approach to Individualized Medicine" cross-sectional study (GANI_MED) were checked for PIM based on kidney function (PIM-K) and PIM for elderly patients (PIM-E). PIM-K were defined by prescription instructions of product labeling. PIM-E were defined by BEERS, -PRISCUS, and FORTA criteria. Predictors for PIM were identified through multiple stepwise regression. RESULTS: 375 patients were included (age: 67.9 ± 13.5 years; estimated glomerular filtration rate (eGFR): 23.3 ± 18.6 mL/min/1.73m2; prescriptions: 11.1 ± 4.7). 44.5% of all CKD patients had PIM-K, and 43.2 to 79.0% of all elderly patients had PIM-E. Polypharmacy and reduced eGFR were predictors for PIM. The risk for PIM-K was increased by 3.8 (95% confidence interval (CI): 1.5 - 9.6) with 10 or more prescriptions and by 8.7 (95% CI: 1.3 - 58.5) with an eGFR below 30 mL/min/1.73m2. On average, elderly patients with 10 or more prescriptions had 3.0 ± 1.7 PIM-E. CONCLUSION: Polypharmacy, PIM-K, and PIM-E affect many CKD patients and can lead to adverse events. Deprescribing and targeted prescribing may improve the outcome of CKD patients and elderly patients.

Prevalence and risk factors of perirenal hyperintensities on T2-weighted MR imaging.

OBJECTIVES: To assess the prevalence and severity of perirenal hyperintensities (PRHs) on T2-weighted magnetic resonance imaging (MRI) and their risk factors in the general population. METHODS: 1752 participants (910 women, 842 men, median age: 52 years) of the Study of Health in Pomerania were included. A visual classification system was established to assess the severity of PRHs (stage 0: no PRHs visible to stage 3: extensive PRHs visible). The MRI-derived thickness of the perirenal and posterior pararenal space and additional risk factors were determined and associated with PRH stages. RESULTS: The overall prevalence of PRHs was 40.7% and was higher in men than in women. PRHs were more common around the left compared to the right kidney (p < 0.001). On both sides, the presence of PRHs was associated with age (p < 0.001). Multivariable-adjusted regression models revealed male sex (OR = 13.2, 95%CI 9.7; 17.9, p < 0.001), older age (OR = 1.1, 95%CI 1.1; 1.1, p < 0.001), higher body mass index (BMI; OR = 1.1, 95%CI 1.0; 1.1, p < 0.001), current smoking status (OR = 1.9, 95%CI 1.4; 2.6, p < 0.001), and greater thickness of the posterior pararenal space (OR = 1.2, 95%CI 1.2; 1.2, p < 0.001) as independent significant risk factors of left-sided PRHs. The same risk factors were confirmed for right PRHs. Glomerular filtration rate was not associated with PRHs on either sides (OR = 1.00, 95%CI 1.0;1.0, p > 0.05). CONCLUSIONS: PRHs are common in the general population, with a higher prevalence in men, elderly individuals, and around the left kidney. Furthermore, BMI, posterior pararenal space thickness, and current smoking, but not renal function itself, are associated with the presence of PRHs.

Staphylococcus aureus colonization in hemodialysis patients: a prospective 25 months observational study.

BACKGROUND: Dialysis patients are frequently exposed to Staphylococcus aureus due to stays in dialysis centers, hospitals or rest homes. The hemodialysis vascular access is a potential entry site for S. aureus, in particular when using a central venous catheter (CVC) which increases the risk of sepsis compared to arteriovenous (AV) fistula. We prospectively followed a cohort of 86 hemodialysis patients from an outpatient dialysis center over 25 months analyzing S. aureus carrier status, S. aureus infection rates and mortality. METHODS: Demographic data and patients´ medical histories were collected and followed from all hemodialysis patients. Blood samples, nasal swabs and swabs from the hemodialysis vascular access site were taken every six months for a period of 25 months and tested for S. aureus. Strains were cultured and further characterized by spa PCR and microarray-based genotyping. Resulting data were compared with those from the general population. RESULTS: In cross-sectional analyses, an average of 40% of hemodialysis patients were S. aureus carriers compared to 27% in the general population. Longitudinally, a total of 65% were S. aureus carriers: 16% were persistent carriers, 43% were intermittently colonized. The most common S. aureus lineage in the dialysis patient cohort was the clonal complex (CC) 8 and the spa type t008, while in the general population, the clonal complex CC30 dominates. During the study period, we observed six S. aureus-associated blood stream infections with one S. aureus attributable death. S. aureus carriers with an AV fistula were more densely colonized in the nasal mucosa compared to patients with a CVC. Overall mortality was lower for hemodialysis patients with a positive S. aureus carrier status compared to non-carriers (hazard ratio of 0.19). CONCLUSIONS: Compared to the general population, hemodialysis patients were more frequently colonized with S. aureus and displayed both different S. aureus colonization densities as well as lineages, possibly explained by more frequent exposure to health care environments. The lower overall mortality in carriers compared to non-carriers is intriguing and will be investigated in detail in the future. TRIAL REGISTRATION: ISRCTN 14385893 , 2. October 2018, retrospectively registered.

Prevalence of renal cysts and association with risk factors in a general population: an MRI-based study.

PURPOSE: To assess the prevalence and size of renal cysts and to analyze associated risk factors in a general population using magnetic resonance imaging (MRI). METHODS: Data of 2063 participants (1052 women) of the Study of Health in Pomerania who underwent whole-body MRI were included. Renal cyst prevalence was calculated separately for men and women and for 10-year age groups. The association between risk factors and occurrence of renal cysts was estimated. RESULTS: The prevalence of renal cysts was 27% and higher in men (34%) than in women (21%; p < 0.001). Renal cyst prevalence increased from 14% in the youngest age group (20-29 years) to 55% in the oldest age group (≥ 70 years) for men and from 7% to 43% for women (both p < 0.001). In the subset of participants with renal cysts, the total mean number was higher in men (1.9) compared to women (1.6, p = 0.012) and was significantly associated with age. Mean renal cyst size was higher in men (1.50 cm) compared to women (1.18 cm, p < 0.001). Male sex (OR 1.83, 95% CI 1.47; 2.26), older age (OR 1.05, 95% CI 1.04; 1.06, per 1-year increment), and hypertension (OR 1.27, 95% CI 1.00; 1.61) were associated with higher renal cyst prevalence. In additional analyses, current smoking and ex-smoking showed a significantly higher risk for renal cysts (OR 1.47, 95% CI 1.05; 2.05 and OR 1.38, 95% CI 1.04; 1.82, respectively). CONCLUSIONS: The prevalence, number, and mean size of renal cysts are higher in men compared to women and are associated with age. In addition, renal cyst prevalence is higher in hypertensive and smoking subjects.

[Nursing Internship Internal Medicine: Evaluation and Influences on the Attitude towards the Specialization]. / Pflegepraktikum Innere Medizin: Evaluation und Einflüsse auf die Einstellung zum Fach.

Background German medical students have to perform a nursery internship of three month duration. While this internship is widely discussed, there is a lack of student evaluation data. Objectives Here, for the first time, student evaluation of a nursery internship in internal medicine (IM) is investigated. Moreover, the question was raised, whether the early experience during this internship may influence students' attitude towards the specialty. Methods In a nation-wide online-survey, 767 German medical students (mean age 22.8 years; 58 % female) evaluated a nursery internship on an IM ward concerning integration in medical teams, teachers, structure and quality of teaching, and satisfaction. Multivariate comparisons were conducted following the question, whether students could imagine choosing IM for a clinical elective after this nursery internship. Results 71 % of the students felt well integrated in the medical team, most was learned from the nurses, and most students indicated having acquired nursing skills. Only 19 % evaluated the structure of the internship as good, and 40 % indicated that they reached the learning goals. Students who could imagine performing an IM clinical elective (52 %) gave best evaluations on all items. Conclusions A successful nursery internship can promote students' interest in the specialty of internal medicine. But, there is a strong need for improvement in structure and content, including the, to date missing, definition of learning targets, regarding this first practical experience in medical studies.

[Management of Patients with CKD in Clinical Practice]. / Chronische Nierenerkrankungen ­ was der Praktiker wissen sollte.

Chronic kidney disease (CKD) affects between 3 and 17 % of the population in Europe, especially elderly persons. CKD is a clinical syndrome which may develop in patients with e. g. diabetes mellitus, arterial hypertension or autoimmune diseases. A poorer renal function - especially in old age - is to be considered irrespective of the medication. Many antibiotics and painkillers require dose adjustments. Therapy should be done in a manner which is suitable for indication. Polypharmacy should be avoided as far as possible. Diuretics and RAAS inhibitors are useful drugs in therapy of CKD. Changes of lifestyle are important, so as weight reduction, restriction of salt and fructose, sufficient drinking, strict control of blood glucose, blood pressure and hypercholesterolaemia. Additional acute lesions have to be avoided ("acute-on-chronic renal failure").