Interleukin-6 and epidermal growth factor as noninvasive biomarkers of progression in chronic glomerulonephritis.

Several cytokines and chemokines are involved in the pathogenesis and progressive injury of renal tissues in patients with primary chronic glomerulonephritis (CGN). The objective of this study was to determine whether the urinary excretion of interleukin-6 (IL-6), transforming growth factor ß1 (TGFß1), monocytes chemoattractant protein (MCP-1), soluble tumor necrosis factor receptor 1 (sTNFR1), and epidermal growth factor (EGF) in patients with newly recognized CGN can serve as prognostic biomarkers in patients with newly recognized CGN and whether they can be effective in predicting a progressive reduction of renal function in prospective observation. The study included 150 Caucasian patients. UIL-6, UTGFß1, UMCP-1, UsTNFR1, and UEGF were measured using enzyme-linked immunosorbent assay (ELISA) methods (Quantikine R&D System). UIL-6, UTGFß1, UMCP-1, and UsTNFR1 were significantly higher, yet UEGF excretion was significantly lower in nephrotic patients, in patients with estimated glomerular filtration rate (eGFR) < 60/min/1.73 m2 at presentation, as well as in the progressor (PG) subgroup. In a multivariate regression analysis basal eGFR correlated with UsTNFR1, UIL-6, and UEGF excretion, although in the follow-up, ΔeGFR (delta estimated glomerular filtration rate) significantly correlated only with UEGF excretion. A logistic regression analysis showed that the most significant independent risk factors for the deterioration of renal function with time are initial high (>11.8 pg/mgCr) UIL-6 excretion, initial low (<15.5 ng/mgCr) urinary UEGF excretion, and male gender. In patients with newly diagnosed CGN, UIL-6, and UEGF can serve as prognostic biomarkers for the progression of the disease.NEW & NOTEWORTHY Baseline high urinary interleukin-6 (IL-6) excretion and low urinary epidermal growth factor (EGF) excretion and particularly high IL-6/EGF ratio were stronger predictive factors of the progression of the deterioration of the kidney function than initial estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or proteinuria. In patients with newly diagnosed chronic glomerulonephritis, UIL-6 and UEGF can serve as prognostic biomarkers for the progression of the disease.

IgA nephropathy associated with coeliac disease.

Coeliac disease (CD) is an autoimmune disorder of the small intestine triggered by ingested gluten from barley, rye and wheat. It can be associated with other autoimmune conditions, such as type 1 diabetes, autoimmune thyroiditis and hepatitis, Sjögren's syndrome and IgA nephropathy (IgAN). We describe here a case of a 24-year-old man with the above-mentioned atypical form of coeliac disease for whom the diagnosis started with renal disorder. The diagnosis of nephrotic syndrome was established and the coexistence with CD was also suspected. In fact, immunoglobulin (Ig) A and IgG antibodies against endomysium and against gliadin were detected in serum of the patient and the endoscopic biopsy of the duodenum revealed stage 3B CD. Percutaneous kidney biopsy was also performed. Class I IgAN was diagnosed. Gluten-free diet, ACE inhibitor and oral iron were introduced to the patient. The improvement of clinical and laboratory disorders of CD as well as gradual remission of the nephrotic syndrome were observed. In conclusion, there may be a small group of patients with IgAN coexisting with CD in whom a gluten-free diet seems to be the treatment of choice for the resolution of kidney disease.

A case of bizarre posttransplant anti-glomerular basement membrane disease.

The non-collagenous (NC1) domain of α3 and α5 chains of type IV collagen are eminent targets of abnormal immune response in anti-glomerular basement membrane (anti-GBM) disease, which can be diagnosed by the presence of strong linear IgG staining along GBM detected by direct immunofluorescence. The presence of linear GBM fixation in renal allograft is a rare finding. We observed a 33-year-old male with de novo renal failure in a kidney transplant. An examination of a kidney biopsy specimen revealed, in light microscopy, mild mesangial hypercellularity together with mild focal interstitial fibrosis and sparse inflammatory infiltrate. In immunofluorescence microscopy strong linear IgG staining along the capillary walls was seen. Serum anti-GBM antibodies were negative and no mutation in exons coding NC1 domains of α3 and α5 chains of type IV collagen were detected. We described a rare case of a patient with atypical anti-GBM disease in renal allograft, caused probably by the same process which affected the native kidneys.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

Preliminary observations on the association between serum IL-6 and hydration status and cardiovascular risk in patients treated with peritoneal dialysis.

INTRODUCTION: Systemic inflammation, as defined by elevated blood IL-6, is a strong independent predictor of peritoneal dialysis (PD) patient survival. The present study has aimed to determine whether there exists a particular "phenotype" associated with high systemic IL-6 that characterizes PD patients in terms of their fluid status and cardiac parameters. METHODS: Fifty-seven prevalent PD patients were classified according to serum concentrations of IL-6. The degree of overhydration was assessed by bioimpedance analysis (BIA). Echocardiography and serum concentrations of NT-proBNP and troponin T were used to assess cardiovascular risk. RESULTS: Patients with high serum IL-6 were older, more often diabetic, treated with PD for longer, and significantly more overhydrated. There was a significant correlation between serum IL-6, hydration status (r=0.38; p=0.002) and serum albumin (r=-0.35; p=0.009). Multivariate regression analysis confirmed a strong association of overhydration, hypoalbuminemia, and systemic IL-6 concentration. Patients with high IL-6 had significantly increased levels of both NT-proBNP (r=0.36; p=0.006) and TnT (r=0.50; p<0.001) in the absence of abnormalities in echocardiography. CONCLUSIONS: High systemic IL-6 identifies PD patients with increased cardiovascular risk that is significantly related to overhydration. Thus, the measurement of serum IL-6 may contribute to the more accurate assessment of cardiovascular status in patients undergoing PD.

Patterns of glomerular disease based on 4-year kidney biopsy material analyzed by light microscopy and immunofluorescence: a retrospective single-center analysis in Poland.

The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.

Cardiac Troponin T and Hydration Status as Prognostic Markers in Hemodialysis Patients.

This study aimed to assess cardiac troponin T (cTnT) and hydration state as cardiovascular (CV) risk markers in hemodialysis (HD) patients. Two hundred and forty one patients were divided according to HD vintage into two groups: SV (HD ≤24 months) and LV. Water balance was assessed with overhydration (OH%; bioimpedance analysis) and daily diuresis (DD); CV dysfunction with cTnT and heart ultrasound; nutrition with subjective global assessment (SGA), cholesterol (TC) and albumin. SV had lower OH% (2.8 vs. 3.5, p < 0.05) and higher DD (1,161 vs. 637 ml, p < 0.001), while LV had higher cTnT (0.1 ± 0.04 vs. 0.1 ± 0.07 ng/ml, p < 0.05) and lower interventricular septum thickness (IVS; 13.4 vs. 14.5 mm, p < 0.05). Nutritional state as reflected by lower TC was worse in LV (184.7 vs. 169.5 mg/dl, p < 0.05). Mortality was higher in patients in the LV group (15 vs. 27 deaths, p < 0.05). OH% correlated inversely with albumin (r = -0.36, p < 0.001), TC (r = -0.31, p < 0.001) and cTnT (r = -0.4, p < 0.001). cTnT correlated positively with IVS (r = 0.39, p < 0.001), SGA (r = 0.23, p = 0.001) and mortality rate (r = 0.21, p < 0.01), and negatively with DD (r = -0.34, p < 0.001) and albumin (r = -0.25, p < 0.001). Longer dialysis vintage associates with CV dysfunction, overhydration and increased mortality, which may be predicted with OH% and cTnT. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=376603.

Conversion From Immediate-Release to Prolonged-Release Tacrolimus in Kidney Transplant Patients With Tremor: A Case Series Study.

BACKGROUND/AIM: Tremor is common with tacrolimus treatment and is linked with peak blood drug concentrations. We investigated the effect of switching from immediate-release tacrolimus (IR-TAC) to MeltDose prolonged-release tacrolimus (LCPT) on tremor in kidney transplant recipients experiencing tremor at therapeutic levels of IR-TAC. METHODS: The Activities of Daily Living Subscale (ADL, range 0-48, lower = better) of the Essential Tremor Rating Scale was used to assess the effect of therapy change on speech, occupational impairment and social activities over a 12-month follow-up period. RESULTS: The study included 18 patients (mean age = 45.6 y, range 26-73; median (IQR) time from transplant = 1.1 y (0.6-1.5), with baseline IR-TAC trough concentrations (C0) ranging from 4.2 to 9.4 ng/mL (mean C0 = 6.7 ± 1.3 ng/mL). After the switch to LCPT, the mean ADL score improved from baseline 11.2 to 8.4 after 7 to 14 days (an 18% improvement, P < .001). This improvement was sustained after 3 months (ADL score = 5.0, 46% improvement vs baseline), 6 months (ADL score = 4.4, 48% improvement vs baseline), and 12 months (ADL score = 3.6, 63% improvement vs baseline); all P < .001. Despite a 40% reduction in LCPT daily doses (mean -1.9 mg/day compared to IR-TAC), the achieved C0 was constant during the course of the 12-month observation (P = .755). The renal function remained stable after conversion (eGFR 12 months vs baseline = +1.1 mL/min/1.73 m2, 95% CI: -5.6 to +7.9). CONCLUSION: Conversion to LCPT may alleviate symptom burden and improve daily activities in kidney transplant recipients experiencing tremor within therapeutic IR-TAC concentrations.

Corrigendum to "WCN23-0458 Assessment of Omeprazole and Famotidine Effect on the Pharmacokinetics of Tacrolimus in Patients After Kidney Transplant"Kidney International Reports, Volume 8, Issue 3, Supplement, March 2023, Page S392.

[This corrects the article DOI: 10.1016/j.ekir.2023.02.881.].

Assessment of serum concentration and urinary excretion of tumor necrosis factor receptor 1 and 2 and their potential as markers of immunoglobulin A nephropathy activity.

BACKGROUND: Tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) can be cleaved from the cell surface and circulate alone or in combination with tumor necrosis factor alpha (TNF-α). These soluble receptors may play a key role in regulating the inflammatory response. OBJECTIVES: The study aimed to evaluate the role of TNFRs in regulating the inflammatory response in immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: The study included 26 patients with newly diagnosed and biopsy-confirmed IgAN and 20 healthy controls. Study material included blood and fresh urine collected the morning before kidney biopsy and therapy. The serum concentrations of TNFR1 (STNFR1) and TNFR2 (STNFR2) and urinary excretion of TNFR1 (UTNFR1) and TNFR2 (UTNFR2) were determined with immunoassay. Subsequently, the data were evaluated statistically. RESULTS: The STNFR1 and STNFR2 levels were higher in IgAN patients than in healthy subjects (4747.87 pg/mL and 2817.62 pg/mL compared to 2755.68 pg/mL (95% CI: from -2948.41 to -1035.97; p = 0.001) and 1437.83 pg/mL (95% CI: from -1958.50 to -419.60; p = 0.001). The power of the test was 98.5% for STNFR1 and 96% for STNFR2. Urinary concentrations only increased for TNFR1 (3551.29 compared to 2338.95 pg/mg of creatinine (Cr) (95% CI: from -2247.03 to -177.66; p = 0.023). The STNFR1 marker was characterized by a sensitivity of 73.08% and a specificity of 90.00% (p < 0.001). CONCLUSIONS: Our results suggest that TNFR1 and TNFR2 are good markers of TNF-α pathway activation in IgAN patients.

Urgent Implantation of Peritoneal Dialysis Catheter in Chronic Kidney Disease and Acute Kidney Injury-A Review.

Acute kidney injury (AKI) and sudden exacerbation of chronic kidney disease (CKD) frequently necessitate urgent kidney replacement therapy (UKRT). Peritoneal dialysis (PD) is recognized as a viable modality for managing such patients. Urgent-start peritoneal dialysis (USPD) may be associated with an increased number of complications and is rarely utilized. This review examines recent literature investigating the clinical outcomes of USPD in CKD and AKI. Relevant research was identified through searches of the MEDLINE (PubMed), Scopus, Web of Science, and Google Scholar databases using MeSH terms and relevant keywords. Included studies focused on the emergency use of peritoneal dialysis in CKD or AKI and reported treatment outcomes. While no official recommendations exist for catheter implantation in USPD, the impact of the technique itself on outcomes was found to be less significant compared with the post-implantation factors. USPD represents a safe and effective treatment modality for AKI, although complications such as catheter malfunctions, leakage, and peritonitis were observed. Furthermore, USPD demonstrated efficacy in managing CKD, although it was associated with a higher incidence of complications compared to conventional-start peritoneal dialysis. Despite its cost-effectiveness, PD requires greater technical expertise from medical professionals. Close supervision and pre-planning for catheter insertion are essential for CKD patients. Whenever feasible, an urgent start should be avoided. Nevertheless, in emergency scenarios, USPD does remain a safe and efficient approach.

No association of monocyte chemoattractant protein-1 -2518 A/G polymorphism with the risk of primary glomerulonephritis in the Polish population.

Various studies have indicated that chemokines such as monocyte chemotactic protein-1 (MCP-1) play an important role in the pathogenesis of primary glomerulonephritis (GN) and other glomerular diseases. Moreover, patients with primary GN display aberrant galactosylation of the O-linked carbohydrate moieties of IgA. Therefore, we analysed the distribution of the functional MCP-1 -2518 A > G (rs 1024611) and 1 beta 1,3-galactosyltransferase (C1GalT1) 1365 A > G (rs1047763) polymorphic variants in patients with primary GN (n = 144) and controls (n = 437) in a sample of the Polish population. We did not find a significant difference in the prevalence of the MCP-1 -2518 A > G and C1GalT1 1365 A > G polymorphisms in patients with primary GN and healthy individuals. Odds Ratio (OR) for GN patients with the MCP-1 -2518 GG genotype was 0.869 (95% CI = 0.410-1.840, P = 0.7130), and OR of the -2518 GG and -2518AG genotypes was 1.004 (95% CI = 0.689-1.464, P = 0.9836). OR for C1GalT1 1365AA genotype was 0.484 (95% CI = 0.181-1.293, P = 0.1402) and OR of the 1365AA and 1365AG genotypes was 0.839 (95% CI = 0.573-1.228, P = 0.3651). We also did not observe a difference in the distribution of alleles between patients and controls. The MCP-1 -2518 G allelic OR was 0.976 (95% CI = 0.725-1.314, P = 0.8744). The OR for the C1GalT1 1365A allele was 0.816 (95% CI = 0.596-1.118, P = 0.205). Moreover, there was no significant association between the MCP-1 -2518 A > G and C1GalT1 1365 A > G genotypes with different morphological types of primary GN or clinical manifestations. Our observations indicate that the MCP-1 -2518 A > G and C1GalT1 1365 A > G polymorphisms might not be a risk factor in the incidence of primary GN in the Polish population.

Assessment of primary care physicians' knowledge of chronic kidney disease in Poland.

Chronic kidney disease (CKD) affects 10-15% of the adult population worldwide and is a major societal problem. A latent course of the disease and little alarming, gradually increasing symptoms usually do not cause concern in patients and diagnostic vigilance in physicians. CKD is most often diagnosed in its end-stage when treatment options are extremely limited. This study aims to assess the knowledge of CKD among primary care physicians (PCPs) in Poland. A CAWI survey was conducted based on an authors' own questionnaire that consisted of two parts. The first part concerned patients' socioeconomic data while the second part consisted of nine single- and multiple-choice questions assessing knowledge of the criterion for diagnosis, risk factors, diagnostic evaluation, and course of CKD. A total of 610 physicians took part in the survey, including 502 (82.3%) who fully completed the questionnaire. Women accounted for 83.1% of the study group. The mean age of the study group was 37.4 ± 10.1 years. Specialists or resident physicians in family medicine accounted for 79.9% of respondents and 93.8% of physicians are those who mainly work in primary care settings. In the knowledge test, the mean score obtained by physicians was 6.5 ± 1.3 out of possible 9, with only 2.4% of respondents answering all questions correctly. According to the survey, 78.4% of respondents correctly indicated the criterion for the diagnosis of CKD, while only 68.9% identified a test for increased urinary albumin loss as the one of the greatest diagnostic values in the early stages of CKD. More than half, 63.1%, of physicians selected the correct set of answers in the multiple-choice question regarding CKD risk factors. Despite a fairly high level of knowledge among family medicine physicians regarding the causes, risk factors and course of CKD, there is a need for further education and an increase in the factual information held by this professional group, especially that the vast majority of PCPs declare a desire to expand their knowledge and believe that this will help them in their daily clinical practice.

Can Overnutrition Lead to Wasting?-The Paradox of Diabetes Mellitus in End-Stage Renal Disease Treated with Maintenance Hemodialysis.

BACKGROUND: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). METHODS: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. RESULTS: DM patients had lower albumin (3.93 (3.61-4.20) vs. 4.10 (3.80-4.30) g/dL, p < 0.01), total cholesterol (158 (133-196) vs. 180 (148-206) mg/dL, p < 0.01), and creatinine (6.34 (5.08-7.33) vs. 7.12 (5.70-8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0-15.0) vs. 11.0 (9.0-13.0) points, p < 0.001), BMI (27.9 (24.4-31.8) vs. 25.6 (22.9-28.8) kg/m2, p < 0.001), fat tissue index (15.0 (11.4-19.6) vs. 12.8 (9.6-16.0) %, p < 0.001), and overhydration (2.1 (1.2-4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality-both all-cause and cardiovascular-were observed in DM patients. CONCLUSIONS: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation.

The role of anti-HLA antibodies in transplant rejection is well-known but the injury associated with non-HLA antibodies is now widely discussed. The aim of our study was to investigate a role of non-HLA antibodies in hand allografts rejection. The study was performed on six patients after hand transplantation. The control group consisted of: 12 kidney transplant recipients and 12 healthy volunteers. The following non-HLA antibodies were tested: antibody against angiotensin II type 1 receptor (AT1R-Ab), antibody against endothelin-1 type-A-receptor (ETAR-Ab), antibody against protease-activated receptor 1 (PAR-1-Ab) and anti-VEGF-A antibody (VEGF-A-Ab). Chosen proinflammatory cytokines (Il-1, IL-6, IFNγ) were used to evaluate the post-transplant humoral response. Laboratory markers of endothelial activation (VEGF, sICAM, vWF) were used to assess potential vasculopathy. The patient with the highest number of acute rejections had both positive non-HLA antibodies: AT1R-Ab and ETAR-Ab. The same patient had the highest VEGF-A-Ab and very high PAR1-Ab. All patients after hand transplantation had high levels of laboratory markers of endothelial activation. The existence of non-HLA antibodies together with multiple acute rejections observed in patient after hand transplantation should stimulate to look for potential role of non-HLA antibodies in humoral injury in vascular composite allotransplantation.

Overhydration as a modifiable cardiovascular risk factor in patients undergoing hemodialysis.

Introduction: Cardiovascular mortality in patients with end-stage renal disease (ESRD) remains high despite advances in dialysis techniques. This can be attributed to several traditional and nontraditional risk factors. Overhydration seems to be one of the promising cardiovascular risk factors that could be targeted to improve survival. Objectives: We aimed to assess the effect of chronic overhydration as well as changes in the degree of overhydration over time on cardiovascular and all-cause morbidity and mortality in patients undergoing hemodialysis. Patients and methods: We enrolled 511 patients with ESRD undergoing hemodialysis. The hydration status was assessed with whole-body bioimpedance spectroscopy. Patients were divided into 4 subgroups according to baseline hydration status. Additionally, patients with at least 2 follow-up visits (n = 277) were classified into 4 subgroups according to changes in the hydration status over time. Results: Statistical analysis showed that male sex (P <⁠0.001), diabetes (P <⁠0.001), cardiac insufficiency (P <⁠0.001), smoking (P = 0.049), and cerebrovascular events (P = 0.007) were significant risk factors for overhydration. Cardiovascular toxicity of overhydration was reflected by elevated levels of N-terminal pro-B-type natriuretic peptide (P <⁠0.001) and cardiac troponin T (P <⁠0.001). Albumin and total cholesterol levels were the lowest in patients with severe overhydration (P <⁠0.001). Mortality was lower in patients with normal hydration status and mild overhydration (P <⁠0.001) as well as in those with stable low or descending overhydration pattern (P = 0.002). Conclusions: We showed that the degree of overhydration is significantly associated with the incidence of cardiovascular complications and prognosis in patients with ESRD undergoing hemodialysis.

Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond.

Current therapy for Anderson-Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020-2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson-Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson-Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

Is home-based therapy in Fabry disease the answer to compelling patients' needs during the COVID-19 pandemic? Survey results from the Polish FD Collaborative Group.

BACKGROUND: Fabry disease (FD) is an X-linked disorder related to a deficiency of the lysosomal enzyme alpha-galactosidase A. In Poland, enzyme replacement therapy (ERT) for FD is offered by the National Health Fund only at selected hospital infusion centers. Patients with FB are considered at a high risk of developing complications from COVID-19. Some patients omitted infusions due to fear of infection or outbreaks in hospitals. Lack of alternative infusion sites hampered the situation. OBJECTIVES: To analyze the impact of the SARS-CoV-2 pandemic on FD patients, especially their fears and expectations, the Polish FD Collaborative Group collaborated on a survey project. MATERIAL AND METHODS: Between September and November 2020, we distributed a customized survey exploring expectations and fears among FD subjects. RESULTS: Fifty-five individuals (35 receiving ongoing ERT) from different FD centers completed the study. The median age was 40 years [IQR 25; 50], and gender distribution was almost equal (27 F; 28 M). One-fourth of FD patients reported severe disability limiting transportation for infusions that, in the opinion of the other 25% of responders, consumed >4 h. Forty-four (80%) of all would prefer home infusions performed by a nurse (n = 37, 67.3%) or by a trained non-medical person (n = 7, 12.7%), while 8 (14.5%) patients would choose a local hospital. As expected, transportation time (in one direction) was longer in those preferring home infusions (89.4 ±63 vs 36.2 ±67 min; p = 0.02). Also, those with more severe FD manifestation would prefer home infusions to treatment in FD centers (p = 0.03). The vast majority of respondents (n = 46; 83%) would not change their preferences after pandemic termination. CONCLUSIONS: To maintain ERT, FD patients prefer home infusions or those given in the nearest hospital, especially during a pandemic.

Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?

BACKGROUND: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. METHODS: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. RESULTS: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = -0.319, p = 0.009; r = -0.341, p = 0.005; r = -0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). CONCLUSIONS: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients.

Urinary excretion of soluble tumour necrosis factor receptor 1 as a marker of increased risk of progressive kidney function deterioration in patients with primary chronic glomerulonephritis.

BACKGROUND: The effects of tumor necrosis factor α (TNF α), a potent proinflammatory cytokine, in the kidneys are mediated by two membrane receptors (TNFR), TNFR1 and TNFR2. The expression of both TNF and TNFRs increases in several kidney diseases and is associated with the shedding of the receptors out of the cell membranes. In an experimental model of glomerulonephritis (GN), elevated concentrations of TNFRs in serum and TNFRs excretion in urine were demonstrated. The aim of this study was evaluation of urinary excretion of TNFR1 and its relationship with the clinical markers of kidney injury in patients with GN. The value of basal urinary TNFR1 excretion as a prognostic indicator of the progression of kidney function impairment was also assessed. MATERIAL AND METHODS: Fifty-five patients with newly diagnosed, biopsy-proven primary GN were included in the study. In all patients, and in 20 healthy subjects, UTNFR1 was measured using an ELISA . In the patients, risk factors of the progression of impairment of kidney function (reduced eCcr, nephrotic syndrome, hypertension and intensity of morphological lesions in the kidneys) were evaluated. The appropriate treatment was then introduced and the patients were in follow-up for 4 years. The progression of kidney function impairment was defined as a reduction of eCcr > 5 mL/min/1.73 m2 /year during follow-up. The association of basal TNFR1 excretion with the progression was evaluated. RESULTS: Urinary excretion of TNFR1 in the patients with GN (4039.2 ± 3801.5 pg/mgCr) was greater than in the healthy subjects (1358.9 ± 927.8 pg/mgCr, P < 0,00002). A significant negative correlation between TNFR1 excretion and eCcr (Sr=0.464, P < 0.01) and a positive correlation between TNFR1 excretion and proteinuria (Sr = 0,463, P < 0.01) were found. In 13 patients, a marked reduction of eCcr was observed during follow-up. Logistic regression analysis revealed that TNFR1 excretion > 3863.3 pg/mgCr predicts progression of renal function impairment along with advanced interstitial fibrosis in the kidney biopsy specimens at presentation. CONCLUSION: Markedly elevated urinary TNFR1 excretion may be considered as a good marker of an activated TNFα-pathway in patients with newly diagnosed GN and as a potentially modifiable risk factor of progressive kidney function impairment.