Prevalence and Management of Chronic Pain, Including Neuropathic Pain, in Dialysis Patients with End-Stage Renal Disease.

BACKGROUND Chronic kidney disease (CKD) is a growing global health concern. Chronic pain, as a common symptom of CKD, particularly among patients with end-stage renal disease (ESRD), is influenced by complications, dialysis procedures, and comorbidities. We aimed to evaluate chronic pain and probable neuropathic pain in 96 dialysis patients with ESRD using the Douleur Neuropathique 4 (DN4) questionnaire. MATERIAL AND METHODS A total of 96 patients from a single dialysis center were enrolled for the purpose of this study. ESRD was caused by diseases causing kidney damage, such as diabetes. The average duration of maintenance dialysis was 4.6±5.67 years. Comorbidities, functional and mental assessment, and pharmacological treatment data were collected using a questionnaire. The satisfaction with life scale was also used. Chronic pain was defined as lasting more than 3 months. The DN4 was used to determine the neuropathic component of pain. RESULTS Chronic pain was observed in 63.5% of the study participants, with 47.5% of them reporting the presence of neuropathic pain accompanied by a neuropathic component. Significantly more patients with chronic pain reported mood disorders and reduced life satisfaction, but there was no difference in their activities of daily living-assessed functional status or duration of dialysis. Patients experiencing chronic pain received non-steroidal anti-inflammatory drugs, paracetamol, and opioids. CONCLUSIONS Chronic pain, especially with a neuropathic component, is highly prevalent in patients with CKD, and its treatment remains ineffective. Undiagnosed components of pain can contribute to underdiagnosis and inadequate therapy. Further studies and staff education are needed to address this important issue.

Inflammation and Oxidative Stress in Diabetic Kidney Disease: The Targets for SGLT2 Inhibitors and GLP-1 Receptor Agonists.

The incidence of type 2 diabetes (T2D) has been increasing worldwide, and diabetic kidney disease (DKD) remains one of the leading long-term complications of T2D. Several lines of evidence indicate that glucose-lowering agents prevent the onset and progression of DKD in its early stages but are of limited efficacy in later stages of DKD. However, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor (GLP-1R) agonists were shown to exert nephroprotective effects in patients with established DKD, i.e., those who had a reduced glomerular filtration rate. These effects cannot be solely attributed to the improved metabolic control of diabetes. In our review, we attempted to discuss the interactions of both groups of agents with inflammation and oxidative stress­the key pathways contributing to organ damage in the course of diabetes. SGLT2i and GLP-1R agonists attenuate inflammation and oxidative stress in experimental in vitro and in vivo models of DKD in several ways. In addition, we have described experiments showing the same protective mechanisms as found in DKD in non-diabetic kidney injury models as well as in some tissues and organs other than the kidney. The interaction between both drug groups, inflammation and oxidative stress appears to have a universal mechanism of organ protection in diabetes and other diseases.

What is the prognostic value of reduced eGFR?

Introduction of the definition and classification of chronic kidney disease (CKD) according to the KDOQI guidelines in 2002 served as a turning point in nephrology. On one hand, the new definition has allowed for the standardization of terminology, on the other hand, however, it has led to a rapid growth in CKD diagnoses. Another issue is the strengthening of the assumption, that diagnosis of CKD is associated with further progressive kidney dysfunction until reaching the end stage renal disease (ESRD). Clinical practice, however, provides evidence that not all patients diagnosed with CKD reach ESRD and eventually require renal replacement therapy (RRT), and in many cases CKD does not progress. AIM: The aim of the study was to assess practical information for a clinician provided by eGFR and its changes during the follow-up of a patient as regards the RRT prognosis and mortality risk. MATERIALS AND METHODS: The study group consisted of patients with CKD treated in the regional outpatient clinic. Progression was assessed by determining a linear trend line for eGFR results. Based on its course and the value of the coefficient of determination R2, four types of eGFR trajectories were identified: linear progression type (G2), nonlinear progression type (G1), improvement type (G3), undetermined eGFR change type (G4). RESULTS: The study group consisted of 65 patients 58.5% females, age mean 69 ± 12.8 years. The mean annual eGFR change in the entire group was -1.67±11.7 ml/min/1.73m2/year. During the study, 6.2% of patients began RRT (hemodialysis), and 9.2% died. Despite the evident tendency towards higher mortality in the group characterized by progression (G1+G2) as compared to the group without progression (G3+G4), the difference did not reach statistical significance (p=0.617). However, the comparison of groups with the baseline eGFR value above and below 45 ml/min/1.73 m2 differentiated the two groups that statistically differed in mortality (p=0.044). CONCLUSIONS: The baseline eGFR was not a significant predictor of future renal outcomes (ESRD, RRT). However, eGFR below 45 ml/min/ 1.73m2 was associated with a significantly higher mortality risk (p=0.036). Moreover, the groups with the fastest and with improved eGFR were characterized by the highest mortality.

Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study.

BACKGROUND Arterial hypertension (HT) is a leading cause of cardiac hypertrophy and heart failure. Ubiquitin-specific peptidase 18 (USP18) has been recently described as a factor that prevents myocardial dysfunction. The present study measured serum USP18 levels in normotensive (n=29), isolated diastolic hypertensive (n=20), and systolic-diastolic hypertensive (n=30) male participants and correlated these results with biochemical parameters that are included in routine assessments of patients with hypertension. MATERIAL AND METHODS Seventy-nine men, aged 24 to 82 years (mean=50.8±11.4 years), were included in the study. None of the participants had ever been treated for HT. Blood and urine parameters were assessed using routine techniques. Serum USP18 levels were measured by enzyme-linked immunosorbent assay. RESULTS The means and 95% confidence intervals (CIs) of USP18 levels in the HT(-), iDHT(+), and HT(+) groups were 69.3 (22.1-116.5) pg/ml, 90.1 (29.0-151.3) pg/ml, and 426.7 (163.1-690.3) pg/ml, respectively. In the HT(+) group, the mean serum USP18 level was 6.2-times higher than in the HT(-) group (p=0.014) and 4.7-times higher than in the iDHT(+) group (p=0.19). The partial correlation analysis that was adjusted for risk factors of arteriosclerosis indicated that USP18 levels were correlated with systolic blood pressure, pulse pressure, and heart rate. CONCLUSIONS This preliminary study found that serum USP18 levels were significantly higher in drug-naive male participants with arterial hypertension compared with normotensive controls. USP18 exerts cardiovascular-protective effects. Elevations of USP18 levels may indicate a counterregulatory process that is engaged during increases in pressure in the left ventricle.

WNT4 Expression in Primary and Secondary Kidney Diseases: Dependence on Staging.

BACKGROUND/AIMS: WNT4 protein is important for kidney development. Its expression was found to be altered in experimental models of chronic kidney disease (CKD). However, the expression of the WNT4 gene has yet not been studied in human renal biopsy samples from patients with broad spectrum of glomerular disease and at different stages of CKD. Thus, the aim of the study was to assess the WNT4 gene expression in renal biopsies of 98 patients using the real-time PCR technique. MATERIALS: In order to assess the relative amounts of mRNA, in samples of patients with manifestation of different renal diseases and separately at different stages of CKD, by QPCR, total RNA was isolated from human kidney tissues collected during renal biopsies. Results of blood and urine samples assessment were used to calculate the correlations of biochemical parameters with WNT4 gene expression in both studied groups. RESULTS: After pathomorphological evaluation, 49 patients were selected as presenting the most common cases in the studied group. Among the patients who developed focal segmental glomerulosclerosis (FSGS; n = 13), IgA nephropathy (IgAN; n = 10), IgAN with morphological presentation of focal segmental glomerulosclerosis (IgAN/FSGS; n = 8), membranous nephropathy (MN; n = 12), and lupus nephritis (LN; n = 6) were included in the analysis. We found that the level of WNT4 mRNA was higher in kidney specimens obtained from patients with MN as compared to those diagnosed with LN or IgAN. A correlation between WNT4 gene expression and serum albumin and cholesterol levels was observed in patients with FSGS, while WNT4 mRNA levels correlated with plasma sodium in patients diagnosed with LN. After consideration of 98 patients, based on the KDIGO classification of CKD, 20 patients were classified as CKD1 stage, 23 as stage 2, 13 as stage 3a, 11 as stage 3b, 13 as stage 4, and 18 as stage 5. WNT4 gene expression was lower in the CKD patients in stage 2 as compared to CKD 3a. Correlations of WNT4 mRNA level at different stages of CKD with indices of kidney function and lipid metabolism such as serum levels of HDL and LDL cholesterol, TG, urea, creatinine, sodium, and potassium were also found. CONCLUSIONS: Our results suggest that altered WNT4 gene expression in patients with different types of glomerular diseases and patients at different stages of CKD may play a role in kidney tissue disorganization as well as disease development and progression.

Prevalence of Chronic Pain, Particularly with Neuropathic Component, and Its Effect on Overall Functioning of Elderly Patients.

BACKGROUND The prevalence of chronic pain among the elderly is high (estimated at 25-85%) and may adversely affect their everyday functioning, although it is often unrecognized. MATERIAL AND METHODS The aim of this study was to assess the prevalence of chronic pain, especially with the neuropathic component, and its effect on overall functioning of elderly patients. We enrolled 145 subjects older than 60 years (nursing home residents, or patients of outpatient geriatric clinic). Information on co-morbidities, functional and mental status, and medications was obtained using a questionnaire. Chronic pain was defined as lasting >3 months and the presence of neuropathic component was detected using the DN4 Questionnaire (Douleur Neuropathique en Questions). RESULTS The mean age of patients was 76±9.68 years. Chronic pain was reported by 78% of participants and 32% reported neuropathic pain with neuropathic component (DN4 score ≥4 points). Patients complaining of chronic pain significantly more often presented mood disorders and lower satisfaction with life (particularly those with the highest pain intensity), with no difference in functional status according to the ADL (Activities of Daily Living) tool. Participants with chronic pain were treated with paracetamol (45%), non-steroidal anti-inflammatory drugs (25%), and opioids (24%). CONCLUSIONS The prevalence of chronic pain, particularly with neuropathic component, in the elderly population seems to be higher than expected based on previous reports, and its treatment appears to be ineffective. This problem requires further research and dissemination of knowledge on the diagnosis and treatment of chronic pain among health care workers caring for elderly patients on a daily basis.

Diagnosis and Treatment of Metabolic Acidosis in Patients with Chronic Kidney Disease - Position Statement of the Working Group of the Polish Society of Nephrology.

Metabolic acidosis is commonly found in patients with chronic kidney disease (CKD), and its causes are: impaired ammonia excretion, reduced tubular bicarbonate reabsorption and insufficient renal bicarbonate production in relation to the amount of acids synthesised by the body and ingested with food. As the consequence, numerous metabolic abnormalities develop, which may lead to dysfunction of several organs. In observational studies, it has been found that CKD patients with metabolic acidosis are characterised by faster progression of kidney disease towards end stage kidney failure, and by increased mortality. Results of interventional studies suggest that alkali therapy in CKD patients slows progression of kidney disease. In view of these facts, the members of "The Working Group of the Polish Society of Nephrology on Metabolic and Endocrine Abnormalities in Kidney Diseases" have prepared the following statement and guidelines for the diagnosis and treatment of metabolic acidosis in CKD patients. Measurement of bicarbonate concentration in venous plasma or venous blood to check for metabolic acidosis should be performed in all CKD patients and metabolic acidosis in these patients should be diagnosed when the venous plasma or venous blood bicarbonate concentration is lower than 22 mmol/l. In patients with metabolic acidosis and CKD, oral sodium bicarbonate administration is recommended. The goal of such a treatment is to achieve a plasma or blood bicarbonate concentration equal to or greater than 22 mmol/l.

[Heparin-induced hyperkalaemia - a case report]. / Hiperkaliemia zalezna od heparyny ­ opis przypadku.

Heparins are drugs commonly used in the prevention and treatment of thromboembolic complications. It is also common to be aware of the complications of their use, such as increased risk of bleeding or induction of throbocytopenia. However, it should not be forgotten that in about 7% of patients the use of heparins may lead to the significant hyperkalaemia. AIM: The aim of this study was to draw attention to the rare, but potentially fatal complication of heparin treatment. CASE REPORT: Here we present the case of the 85-year-old man with the several co-morbid conditions, who developed hyperkalaemia during hospitalization. Hyperkalaemia was resistant to typical conventional treatment. It occured that the reason for this complication was hypoaldosteronism caused by the use of low molecular weight heparin in the prophylactic dose. Kaliaemia normalization was achieved not until the fludrocortisone was used. Heparin induced hyperkalaemia occurs in about 7-8% treated patients. Therefore, it is not a rare complication, but given the prevalence of heparin use and the potential number of patients with this complication, it is rarely diagnosed. Potentially because hyperkalaemia is usually asymptomatic and because heparin treatment is usually temporal. The reported case of a patient with asymptomatic heparin induced hyperkalaemia proves that in everyday practice we may face this complication, and its diagnosis and proper treatment is possible only if we remember about this risk.

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.

[Osteoporosis and vascular calcification in rheumatoid arthritis - the role of osteoprotegerin and sclerostin]. / Osteoporoza i kalcyfikacja naczyn w reumatoidalnym zapaleniu stawów ­ rola osteoprotegeryny i sklerostyny.

Disorders of bone tissue metabolism and increased frequency of cardiovascular diseases are among the well-known, extra-articular complications of rheumatoid arthritis (ra). The mechanisms leading to local and generalized loss of bone tissue as well as those promoting calcification of vessels are similar. Recently, a great interest has aroused among the studies related to the meaning of the RANKL/RANK/OPG system and the Wnt/ß-catenin signaling pathway, as biological links between the bone and vascular systems. In the course of ra, lowering of the mineral density of bones and intensification of vascular calcification seem to be associated with the increase of plasma concentration of osteoprotegerin (OPG) and sclerostin - the regulatory proteins of the RANKL/RANK/OPG system and the Wnt/ß-catenin pathway. Molecular mechanisms associated with the osteoblasts' activation and repression of bone resorption in the future can become the target of a precise, combination therapy in osteoporosis and calcification changes. The article presents the role of the RANKL/RANK/ OPG system and the Wnt/ß-catenin pathway in the pathogenesis of disorders of bone tissue metabolism and calcification of vessels in ra, with particular emphasis on the role of OPG and sclerostin.

Kidney disease in the elderly: biopsy based data from 14 renal centers in Poland.

BACKGROUND: Longer life expectancy is associated with an increasing prevalence of kidney disease. Aging itself may cause renal damage, but the spectrum of kidney disorders that affect elderly patients is diverse. Few studies, mostly form US, Asia and West Europe found differences in the prevalence of some types of kidney diseases between elderly and younger patients based on renal biopsy findings, with varied proportion between glomerulopathies and arterionephrosclerosis as a dominant injury found. Here, for the first time in Eastern Europe we analyzed native kidney biopsy findings and their relationship to clinical characteristics at the time of biopsy in elderly individuals (aged ≥65) in comparison to younger adults (aged 18-64). METHODS: Biopsy and clinical data from 352 patients aged ≥65 were retrospectively identified, analyzed and compared with a control group of 2214 individuals aged 18-64. All kidney biopsies studied were examined at Medical University of Warsaw in years 2009-14. RESULTS: In elderly patients the leading indication for biopsy was nephrotic range proteinuria without hematuria (34.2%) and the most prevalent pathologic diagnoses were: membranous glomerulonephritis (MGN) (18.2%), focal segmental glomerulosclerosis (FSGS) (17.3%) amyloidosis (13.9%) and pauci immune glomerulonephritis (12.8%). Hypertension and age-related lesions very rarely were found an exclusive or dominant finding in a kidney biopsy (1.7%) and a cause of proteinuria (1.1%) in elderly individuals. There were 18.2% diabetics among elderly individuals, and as much as 75% of them had no morphologic signs of diabetic kidney disease in the renal biopsy. Amyloidosis, MGN, pauci immune GN, crescentic GN and light and/or heavy chain deposition disease (LCDD/HCDD) were more frequent whereas IgA nephropathy (IgAN), lupus nephritis (LN) and thin basement membrane disease (TBMD) were less common among elderly than in younger patients. CONCLUSIONS: Proteinuria, a dominating manifestation in elderly patients subjected to kidney biopsy was most commonly related to glomerulopathies. The relatively high prevalence of potentially curative kidney diseases in elderly individuals implicates the importance of renal biopsy in these patients.

Long-term cholecalciferol administration in hemodialysis patients: a single-center randomized pilot study.

BACKGROUND: Data on the potent pleiotropic extraskeletal effects of vitamin D have renewed interest in its use in selected populations, including patients with chronic kidney disease, but the available data are still insufficient to make recommendations. This study assessed the long-term effect of small cholecalciferol doses on serum vitamin D, parathormone (PTH), and bone mineral density (BMD) in hemodialysis patients. MATERIAL/METHODS: Nineteen patients with serum 25(OH)D <20 ng/mL were randomized into cholecalciferol (2000 IU 3×/week) and no-treatment groups, then observed for 1 year. Patients with hypercalcemia, hyperphosphatemia, and receiving vitamin D/calcimimetics were excluded. Serum 25(OH)D, 1,25(OH)2D, PTH, and alkaline phosphatase activity were examined every 2 months and BMD was measured before and after the study. RESULTS: We observed normalization of serum 25(OH)D with an increase in medians from 11.3 to 44.9 ng/mL (P=0.02) in the cholecalciferol group and no change in the controls (P<0.001). Simultaneously, median serum 1,25(OH)2D increased from 18.2 to 43.1 pmol/L (P=0.02) in the cholecalciferol group and from 10.6 to 21.2 pmol/L (P=0.02) in controls (P=0.013). The treatment was associated with a small increase in serum calcium, but serum phosphate, PTH, alkaline phosphatase, and BMD remained unchanged in both groups. CONCLUSIONS: Oral cholecalciferol at a dose of 2000 IU/3×/week is an effective and safe way to treat vitamin D deficiency in hemodialysis patients, leading to a significant increase in serum 1,25(OH)2D. However, it was insufficient to suppress the activity of parathyroid glands or to significantly change BMD.

Unusual manifestation of crystalline light chain tubulopathy in patient with multiple myeloma: case report and review of the literature.

Multiple myeloma (MM) is the second most common hematological malignancy, with an annual incidence in Europe and the USA of about 4-6 cases per 100,000. Several forms of renal disease are found in the course of MM, including: cast nephropathy, light chain (LC) deposition disease and primary amyloidosis. Less frequent forms include: acute and chronic tubulopathies, neoplastic plasma cell infiltration and interstitial nephritis. In this paper, we discuss a case of 53-year-old male patient with MM who presented with massive proteinuria (24 g/24 h), mild renal insufficiency (eGFR 43 mL/min), and Fanconi-like syndrome (as reflected by normoglycemic glycosuria). In kidney biopsy glomeruli were normal, whereas abundant AFOG-positive deposits were found in the cytoplasm of proximal tubular epithelial cells. These deposits were strongly positive for kappa light chains on immunofluorescence. Electron microscopy revealed electron-dense, intracytoplasmic crystalloid deposits of variable shape (needle-shaped, round and rectangular), and size in the proximal tubular cells. This unusual variant of microscopic renal lesions in the course of MM coupled with coincidence of Fanconi-like and nephrotic syndrome as a clinical manifestation has not been reported to date.

[Recommendations for prevention of community-acquired pneumonia with bacteremia as the leading form of invasive pneumococcal infections in the population of people over 50 years of age and risk groups above 19 years of age]. / Rekomendacje dotyczace profilaktyki pozaszpitalnego zapalenia pluc z bakteriemia jako wiodacej postaci inwazyjnych zakazen pneumokokowych w populacji osób powyzej 50 roku zycia oraz w grupach ryzyka powyzej 19 roku zycia.

Invasive pneumococcal disease (IPD) is a main cause of mortality associated with pneumococcal infections. Although, IPD is regarding mainly small children and persons in the age > 65 years, the investigations showed that because of IPD exactly sick persons are burdened with the greatest mortality in the older age, rather than of children. The most frequent form of IPD is community acquired pneumonia (CAP) with the bacteremia. The presence of even a single additional risk factor is increasing the probability of the unfavorable descent of pneumococcal infection. The risk factors for IPD and/or pneumonia with bacteremia apart from the age are among others asthma (> 2 x), chronic obstructive pulmonary disease (COPD), sarcoidosis (4 x), idiopathic pulmonary fibrosis (5 x), bronchiectases (2 x), allergic alveolitis (1.9 x) and pneumoconiosis (2 x), type 1 diabetes (4.4 x), type 2 diabetes (1.2 x), autoimmune diseases (e.g. rheumatoid arthritis (4.2 to 14.9 x), kidney failure with the necessity to dialysis (12 x), immunosuppression, cardiovascular disease, alcoholism and cancers. Examinations show that the best method of IPD and CAP preventing are pneumococcal vaccinations. On the market for ages 23-valent polysaccharide vaccine (PPV23) is available covering close the 90% of IPD triggering stereotypes. Her role in preventing CAP is uncertain and the immunological answer after vaccination at older persons and after revaccination is weak. Widely discussed disadvantageous effects of growing old of the immunological system show on the benefit from applying the immunization inducing the immunological memory, i.e. of conjugated vaccines which are activating the T-dependent reply and are ensuring the readiness for the effective secondary response. Examinations so far conducted with conjugated 7-valent and 13-valent (PCV13) vaccines at persons in the age > 50 years are confirming these expectations. Also sick persons can take benefits from PCV13 applying back from so-called IPD risk groups in the age > 19 years. At these work research findings were described above PPV23 and PCV13 at adults and world recommendations of applying both vaccines in risk groups from 19 years up to the advanced years. Also Polish recommendations of optimum applying of these vaccines were presented. They are recommending applying PCV13 at first in them, while PPV23, if to her readings exist should be given to > or = 8 of weeks from PCV13. In persons > or = 19 years which earlier received 1 or should receive more PPV23 doses first PCV13 dose should be given after the year or later than the last PPV23 dose, and then again PPV23 > or = 8 of weeks from PCV13 and the second PPV23 dose not earlier than 5 years from last PPV23. If the PPV23 application seems to be justified, it is irrespective of the more previous state vaccination against pneumococci, PCV13 should be given to as first.

Ubiquitin-Specific Protease 18 in Chronic Kidney Disease-Another Emerging Biomarker to Consider?

Ubiquitin-specific protease 18 (USP18) is a protein recognized for its dual enzymatic and non-enzymatic nature. It is involved in many physiological processes like the cell cycle and cell signaling. It also suppresses heart muscle remodeling upon an increase in the afterload. The role of USP18 in kidney pathology remains unknown. The objective of the study was to assess the relationship between serum and urine USP18 levels, the factors contributing to cardiovascular risk, and the markers of kidney disease activity at different stages of chronic kidney disease (CKD). One hundred participants, aged between 24 and 85 years (mean 53.1 ± 17.1 years), were included. Five groups (n = 20 each) were recruited according to their renal status (healthy individuals, patients with proteinuric glomerulonephritis, patients with non-proteinuric CKD, patients who were treated with hemodialysis, and kidney transplant recipients). The measurements of serum and urine USP18 levels were performed using ELISA. The median serum USP18 level was the highest in healthy participants (1143.0 pg/mL) and kidney transplant recipients (856.6 pg/mL), whereas, in individuals with different forms of CKD, it fitted within the range of 402.1-471.9 pg/mL. Urinary USP18 reached the highest level in the group of CKD patients not yet on dialysis (303.3 pg/mL). Only in this group did it correlate with serum creatinine and urea concentrations. Our results suggest the inhibition of cardioprotective USP18 signaling when kidney function is impaired. Moreover, an increased level of urinary USP18 may indicate chronic tubular damage.

Ten-Year Outcomes in Patients Undergoing Simultaneous Coronary and Renal Angiography-Does Renal Artery Stenosis Matter?

Background: We aimed to characterize the population of consecutive patients undergoing coronary angiography with simultaneous renal artery angiography and assess prognostic factors at a 10 year follow-up. Methods: The KORONEF study was a prospective, single-center, observational, and descriptive study with 492 patients included. We analyzed several baseline demographics, clinical and periprocedural characteristics, and laboratory data, and we assessed the results of coronary angiography and renal artery angiography. Results: The study population consisted of 37.2% women, and the mean age was 64.4 ± 9.9 years (min. 30 years, max. 89 years). Angiography revealed significant renal artery stenosis (RAS) in 35 (7.1%) patients. Among patients with significant RAS (≥50%), we observed more women (57.1% vs. 35.7%, p = 0.011), and patients were older (69.1 ± 10.4 years vs. 64.0 ± 9.7 years, p = 0.005). In the whole population, all-cause death was reported in 29.9% of patients, myocardial infarction (MI) rate-in 11.8%, and stroke-in 4.9%. In the multivariable analysis, independent predictors of death were age 65-75 years (HR 2.88), age > 75 years (HR 8.07), diabetes (HR 1.59), previous MI (HR 1.64), chronic kidney disease (HR 2.22), unstable angina (HR 0.37), and left ventricular ejection fraction > 60% (HR 0.43). Conclusions: Over a 10 year follow-up, the all-cause death rate was 29.9%, showing no statistically significant differences between patients with and without significant RAS.

Antibodies against Nε-homocysteinylated proteins in patients on different methods of renal replacement therapy.

BACKGROUND: High levels of antibodies against Nε-homocysteinylated (Nε-Hcy) proteins have been observed in patients on long-term hemodialysis (HD). We sought to investigate whether these antibodies are present in patients on peritoneal dialysis (PD) in comparable titers and to characterize the factors that determine levels of those antibodies in both patient groups. METHODS: The study involved 80 patients on HD and age- and sex-matched 75 subjects on PD. Serum IgG antibodies against Nε-Hcy-albumin and -hemoglobin were determined using in-house enzyme-linked immunosorbent assays. Total homocysteine (tHcy), folate, 8-isoprostaglandin F2α (8-iso-PGF2α) and paraoxonase-1 (PON-1) activity were also measured. RESULTS: Patients on PD and those on HD had similar levels of anti-Nε-Hcy-albumin [absorbancy at 490 nm: 0.571 (0.519-0.609) vs. 0.583 (0.523-0.625), p=0.41, respectively] and anti-Nε-Hcy-hemoglobin antibodies [0.659 (0.597-0.705) vs. 0.664 (0.597-0.722), p=0.60, respectively]. In both groups levels of the antibodies correlated with tHcy (r from 0.54 to 0.77, p<0.0001), 8-iso-PGF2α (r from 0.57 to 0.77, p<0.0001), and folate (r from -0.59 to -0.74, p<0.0001) levels, but not with the cause of renal disease, dialysis vintage, a history of coronary artery disease or PON-1 activity. In the multivariate logistic regression, after adjustment for potential confounders, plasma tHcy was the independent predictor of antibodies against Nε-Hcy-proteins irrespective of the method of dialysis. CONCLUSIONS: Levels of antibodies against Nε-Hcy-proteins are similar in patients on long-term PD and HD. The level of tHcy is the only independent predictor of both antibodies irrespective of the dialysis method.

Advanced abdominal arterial calcification sparing kidney allograft--case report.

Excess and progressing arterial calcification is a frequent finding in patients with chronic kidney disease and in diabetics. Vascular calcification present in patients on dialysis, usually continues to progress (although possibly with slower rate) in patients after kidney transplantation. These observations are limited mostly to aorta and coronary arteries; virtually no data exist on progression in vascular calcification within the vasculature of transplanted kidney. The case report presents the patient with diabetes and non-functioning renal transplant back on dialysis with extremely severe intra-abdominal artery calcification, sparing renal artery of transplanted kidney. Calcification did not develop within transplanted kidney despite 10 years of exposition to diabetic environment and a few years of chronic kidney disease after transplantation, including CKD-T stage 5 for at least one year after re-starting of dialysis. To the best of our knowledge, this is the second report ever describing sparing of kidney graft from calcification despite disseminated calcification in other vascular beds. It is tempting to speculate that some "intrinsic" factors exist within the transplanted kidney that protects it from calcification despite exposure to procalcifying milieu of diabetes and uremia.

Kidneys in heart failure: Impact of flozins.

Chronic kidney disease (CKD) and heart failure (HF) represent two modern diseases of civilization and are closely related. According to the concept of cardio-renal and reno-cardiac syndromes, most patients with CKD are affected by cardiovascular disease (CVD), and CVD (including HF) is one of the factors not only promoting progression of established CKD but also triggering its onset and development. Treatment of CVD and HF in CKD patients remains challenging since CKD patients are characterized by extremely diverse and strongly expressed risk profiles, and the data from well-designed clinical trials addressing this population are scarce. Nevertheless, it seems that most of the drugs used in the treatment of CVD and HF (including beta-blockers, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blocking agents, mineralocorticosteroid receptor antagonists, and sacubitril/valsartan) are of similar efficacy in patients with glomerular filtration rate (GFR) ranging between 45 and 60 ml/min/1.73 m² (although higher prevalence of side effects may limit their use). The data on cardiovascular (CV) drug efficacy in patients with lower GFR values (i.e. below 30-45 ml/min/1.73 m²) remain limited. In this review, we focused on the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of CVD and HF in CKD patients with or without diabetes. SGLT2i are clearly cardioprotective in a wide spectrum of estimated GFR although the data for HF patients with respect to urine albumin-creatinine ratio (UACR) are scarce, and for those with significantly reduced estimated GFR are still not available or not convincing, even after completion of large-scale high-quality major cardiovascular outcome trials (CVOT) in type 2 diabetes mellitus (T2DM) or trials with flozins in CKD and HF.

Patterns of Dickkopf-3 Serum and Urine Levels at Different Stages of Chronic Kidney Disease.

Dickkopf 3 (Dkk3) is a WNT/ß-catenin signaling pathway regulator secreted by tubular epithelial cells upon the influence of different stressors. Recently Dkk3 was described as a biomarker of tubular cell injury and a tool that may estimate the risk of chronic kidney disease (CKD) progression. The data about Dkk3 concentrations at particular stages of CKD are lacking. The aim of this study was to measure serum and urine Dkk3 levels in patients with different 'renal status' and evaluate its role as a biomarker of renal damage. One hundred individuals, aged between 24 and 85 years (mean 53.1 ± 17.1), were enrolled in the study. Five groups of 20 subjects each were recruited based on their kidney function. Serum and urine Dkk3 levels were measured by ELISA. The highest median urinary Dkk3 normalized to urinary creatinine was found in patients with established CKD (7051 pg/mg). It was two times higher in renal transplant patients (5705 pg/mg) than in healthy individuals (2654 pg/mg) and the glomerulonephritis group (2470 pg/mg). Urinary Dkk3 was associated with serum creatinine in participants with established CKD and following transplantation. Our results confirm the potential role of Dkk3 as a biomarker of an ongoing renal injury.