Rheumatoid arthritis - medication dosage in chronic kidney disease.

Renal failure in the course of rheumatoid arthritis (RA) is a consequence of many factors, including drug-induced nephrotoxicity, comorbidities and chronic inflammation. Contemporary treatment strategies have reduced the incidence of renal failure in the population of RA patients. However, it remains a problem for approximately 25% of patients. Therefore, special attention should be paid to the potential need for dosage modifications of administered medications. Many drugs used in the therapy of rheumatic diseases have not been thoroughly studied for their safety in patients with reduced glomerular filtration, resulting in limited data in this area. The establishment of precise, transparent, and consistent dosage recommendations for antirheumatic drugs in chronic kidney disease would significantly facilitate the care of patients with RA. The following review provides a general summary of the available knowledge regarding the dosage of rheumatic medications in renal insufficiency and aims to highlight the need for further research in this area.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Pharmacokinetics of free and total mycophenolic acid in adult lupus nephritis patients-implications for therapeutic drug monitoring.

PURPOSE: To evaluate the relationship between total and free MPA pharmacokinetic (PK) parameters and renal outcome markers, and to verify whether conducting therapeutic drug monitoring (TDM) in lupus nephritis (LN) patients would be of value in routine clinical practice. METHODS: Eighty-four samples were collected from sixteen LN patients. Total and free MPA concentrations were measured at predose, 0.5 and 2 h after mycophenolate mofetil (MMF) intake. Area under the concentration time curve from 0 to 2 h (AUC0-2) and free fraction were calculated. RESULTS: High between-patient variability was observed (CV% of 53.5% for dose-normalized total MPA AUC0-2). A significant but weak correlation between dose-normalized total C0 and AUC0-2 was noted (r = 0.5699). Dose-normalized total C0 above 2.76 µg/mL·g may indicate patients with eGFR < 81 mL/min with sensitivity of 83.3% and specificity of 75.0%. Hypoalbuminemic LN patients demonstrated significantly elevated MPA free fraction when compared with patients with serum albumin concentration ≥ 3.5 g/dL (1.49 ± 0.64% vs 1.08 ± 0.75%). CONCLUSION: This study examined relationship between free and total pharmacokinetic MPA parameters as well as the effect of hypoalbuminemia on MPA plasma protein binding in adult LN patients. The study results suggest that TDM of MPA in LN seems to be a more reasonable approach than the fixed-dose protocol. Moreover, predose total MPA concentration may be a possible estimation of MPA exposure, while monitoring free rather than total MPA may be more beneficial in hypoalbuminemic patients.

Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group.

INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.

Different Relevance of Peripheral, Central or Nighttime Blood Pressure Measurements in the Prediction of Chronic Kidney Disease Progression in Patients with Mild or No-Proteinuria.

BACKGROUND/AIMS: Arterial hypertension is one of the leading factors aggravating the course of chronic kidney disease (CKD). It seems that the novel parameters used in the assessment of the blood pressure (BP) load (i.e. central blood pressure, nighttime blood pressure) may be more precise in predicting the cardiovascular risk and the progression of CKD in comparison with the traditional peripheral blood pressure measurements in the office conditions. The aim of the study was to assess the impact of the central, or nighttime blood pressure on the progression of CKD in patients with mild or no-proteinuria (autosomal, dominant polycystic kidney disease or IgA nephropathy). METHODS: In each of the enrolled 46 patients with CKD stage 3 or 4, serum creatinine concentration was assessed, eGFR (MDRD) was calculated, also central blood pressure and pulse wave velocity (PWV) was assessed and the 24-hour ambulatory blood pressure monitoring (ABPM) was conducted at the beginning of the study and then repeated after one-year observation period. RESULTS: During the observation period mean eGFR decreased from 44.1 (33.2-50.6) mL/min to 36.7 (29.7-46.3) mL/min. No significant differences were observed in the peripheral blood pressure or central blood pressure parameters. After one-year observation period the values of diastolic blood pressure dipping during the night significantly decreased from 16 (13-19) mmHg to 12 (10-15) mmHg; p< 0.05. The values of systolic dipping during the night or the mean BP values recorded in ABPM did not change significantly. Additionally, no significant differences in the PWV values were found. In the multivariate regression model the change of serum creatinine concentration was explained by the initial diastolic dipping values. CONCLUSION: 1. In patients with CKD stages 3 or 4 and mild or no- proteinuria, peripheral and central blood pressure did not change significantly during a one-year observation period despite the significant decline of eGFR and seems not to participate in the CKD progression. 2. Reduced magnitude of the diastolic dipping, which reflects the increase of diastolic blood pressure load during the nighttime, may play an important role in the pathogenesis of deterioration of kidney function in these patients.

Stem cell mobilization in patients with dialysis-dependent multiple myeloma: Report of the Polish Myeloma Study Group.

INTRODUCTION: High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) improves the outcome of patients with multiple myeloma (MM). It seems that auto-HSCT is also a feasible therapeutic option in MM dialysis-dependent (MMDD) patients. However, to perform transplantation, a sufficient number of stem cells must be collected. MATERIALS AND METHODS: Given that data on mobilization of auto-HSC efficacy and safety in dialysis-dependent patients are limited, we report data from all Polish Centers belonging to the Polish Myeloma Study Group. Twenty-eight dialysis-dependent MM-patients were enrolled into this retrospective analysis. The study population comprised patients diagnosed between 2004 and 2015 in whom an attempt to collect auto-HSC was made (68%: women, median age: 56). Patients received granulocyte-colony stimulating factor (G-CSF) alone or in combination with chemotherapy and autologous peripheral blood stem cells (auto-PBSCs) were collected by leukapheresis. RESULTS AND CONCLUSIONS: The success rate in terms of obtaining sufficient number of CD34(+) cells/kg for an auto-HSCT (≥2 × 106 cells/kg body weight) during the first mobilization attempt was 92% (26/28 patients), and for 2 auto-HSCTs (≥4 × 106 cells/kg) - was 75% (21/28 patients). After the second mobilization attempt (undertaken in 8 patients), a sufficient number of CD34(+)/kg cells for an auto-HSCT was obtained for all patients and the number of CD34(+)/kg collected cells was sufficient for 2 auto-HSCT in 6 additional patients. Hematologic toxicity and infections were the most frequent complications. Higher doses of cytarabine (>1.6 g/m2 ) and cyclophosphamide (> 2 g/m2 ) should be avoided in MMDD patients due to toxicity. Further studies are needed to establish mobilization regimens, confirm their safety, and dosing in MMDD patients.

Dialysis-Related Parameters Influence Remodeling in the Venous Part of the Native Arteriovenous Fistula.

BACKGROUND: The aim of this study was to evaluate the association of hemodynamic parameters related to hemodialysis and antropometric parameters of patients with changes in the venous part of the arteriovenous fistula (AVF) at points of needling. METHODS: Two hundred forty-two hemodialysis (HD) patients (60.3% men), with median age 65 (interquartile range [IQR] 56-75) years, on HD treatment for a median of 49 (IQR 20-88) months with functioning fistula were recruited for the study. The history of vascular access, comorbidity, antropometric (body mass index, body surface area, and body composition), and dialysis-related parameters were analyzed. The cross-sectional area of upper extremity vessels were measured using ultrasound and included 2 points: A (arterial point for blood aspiration) and V (venous point for returning the blood after purification). The difference between A and V (A-V) was calculated. RESULTS: The median cross-sectional area of A was larger than V (1.04 [IQR 0.58-1.7] vs. 0.74 cm2 [IQR: 0.41-1.39], P <0.0001). The median difference between A and V (A-V) was 0.17 cm2 and positively correlated with mean blood flow (Qb), effective Kt/V, and time of AVF use. Other analyzed factors had no influence on A-V. In the multivariate analysis, the independent factor increasing the difference (A-V) was mean blood flow measured during HD sessions. CONCLUSIONS: The needling and utilization of AVF for hemodialysis may affect vein anatomy, namely causing dilatation at the arterial point and narrowing at venous point of AVF. We suggest that blood pump velocity of the dialysis machine may have an impact on these changes, but practical importance of these findings has to be elucidated. The significance of (A-V) factor in the prognosis of fistula complications should be further studied and confirmed in the prospective trials.

[Measurements of vancomycin concentrations in the blood - a method of personalization the antibiotic therapy in patients with chronic kidney disease]. / Pomiary stezen wankomycyny we krwi ­ metoda personalizacji antybiotykoterapii u chorych na przewlekla chorobe nerek.

Therapeutic Drug Monitoring is a recognized method of personalizing treatment, having particular application in patients with chronic kidney disease who have frequent infections, requiring administration of vancomycin. International guidelines indicate the need to adjust the dose of the drug to the state of renal function. The recommended therapeutic ranges of minimum and maximum levels should be achieved in order to increase the effectiveness and safety of treatment. AIM: The aim of this study was to evaluate the usefulness of measuring the concentration of vancomycin in patients with chronic kidney disease due to bacterial infection. MATERIALS AND METHODS: The study included 96 adult patients with chronic kidney disease of varying severity treated with vancomycin Patients were divided into 3 groups: treated by haemodialysis (hd), after renal transplantations (ktx), do not require renal replacement therapy (nef). In subjects were examined the minimum and maximum concentrations of vancomycin in steady-state and were compared with recommended therapeutic ranges. RESULTS: Statistically significant decrease of inflammatory markers was observed only in patients treated with dialysis. In the other groups not significant changes in values of inflammatory parameters were confirmed. Trough concentrations of vancomycin marked in patients were consistent with the recommendation of EUCAST, but exceeded the value recommended by the manufacturers of the drug. Considering absolute values of the minimum concentrations, only about 50% of patients achieved the therapeutic range (58% for recommendation EUCAST and 36% for the manufacturer's instructions). Peak concentration values indicated in dialyzed patients were below the prescribed range of 20-50 mg/l and averaged 17.7 mg / l. In the other subgroups they were correct. The rating of the absolute values of the peak concentrations of vancomycin also showed that only 46% (64% in the ktx, 30% - hd and 53% - nef) was within the recommended range, while 50% were classified as concentrations of sub-therapeutic (36% in the ktx, 42% of the nef group and 65% in hd). CONCLUSIONS: Vancomycin concentrations measured in patients with chronic kidney disease, both minimum and maximum, were not fully comply with the recommended therapeutic ranges, despite the use of doses determined based on a calculation of glomerular filtration rate. This points to the need for particularly careful monitoring of therapy and analysis of antibiotic concentrations to improve the effectiveness and reduce the incidence of undesirable consequences of treatment.

Geriatric syndromes in patients with chronic kidney disease.

The recent epidemiologic data pointed out, that the general number of patients on hemodialysis is steadily increasing, especially in group of elderly patients over 75 years old. The geriatric syndromes are a multietiological disorder related to physiological aging and partly associated with comorbid conditions. Frailty, falls, functional decline and disability, cognitive impairment and depression are main geriatric syndromes and occurs in patients with impaired renal function more often than among general population. The causes of higher prevalence of those syndromes are not well known, but uremic environment and overall renal replacement therapy may have an important impact on its progress. The patient with geriatric syndrome require comprehensive treatment as well as physical rehabilitation, psychiatric cure and support in everyday activities. Herein below we would like to review recent literature regarding to particular features of main geriatric syndromes in a group of nephrological patients.

[Vascular access in diabetic patients. Are these patients "difficult"?]. / Dostep naczyniowy u chorych na cukrzyce. Czy sa to chorzy problematyczni?

Diabetics with stage V chronic kidney disease (CKD) on hemodialysis (HD) are considered as "difficult patients", because of problems with creation of the vascular access. There is controversy regarding the results and recommendations for preparation of the vascular access in these patients. The aim of this retrospective study was to evaluate the results of creating different types of arteriovenous fistula (AVFs) in consecutive series of patients starting dialysis treatment. The analysis was performed in 741 patients (385 females and 356 males), average age 61.4±7 years, who started dialysis treatment in our department between January 2005 and December 2012. Native AVFs were created in all patients. No patients received an AVF requiring synthetic graft material. The number of patients with diabetic nephropathy was 166 (22.4%). Among them, 30 (18%) had type 1 diabetes and 136 (82%) type 2. In this group the occurrence of calcification in the forearm artery was estimated on the basis of physical examination, Allan's test, Doppler ultrasound and forearm X-ray. In a subgroup of patients with atherosclerotic changes in the arterial system the frequency of failed AVFs was analyzed. These results were compared with the group without diabetes. The number of procedures necessary for successfu AVF creation and type of access was counted in both groups. The assessment of the procedure frequency and AVF location in diabetic and in non-diabetic patients was made by χ² test with Yates correction. In the group of 166 patients with diabetes, in 100 cases (60%) atherosclerotic changes in forearm arteries were observed. In a subgroup of 30 patients with type 1 diabetes atherosclerosis was observed in 17 adults (57%). In this subgroup creation of a suitable forearm AVF in the first procedure in 9 patients was possible and in the other 8 cases the atherosclerotic changes necessitated repeated procedures and were an important obstacle to create the AVF. In the subgroup of 136 patients with type 2 diabetes, atherosclerosis in the forearm artery was observed in 83 cases (61%). In this subgroup the creation of a native AVF was possible in 40 patients during the first procedure and in 43 cases additional intervention was needed, but only in 8 cases was atherosclerosis the cause of fistula failure. Generally, among 166 patients only in 16 cases (10%) did atherosclerosis present an important obstacle for AVF creation, but the number of necessary procedures to create one functioning AVF was significantly greater in this population (2 v 2.7, p=0.0001). A functioning AVF in patients with diabetes was found significantly frequently in the arm localization in comparison to non-diabetic patients (4.3 v 2%, p=0.0478). Atherosclerotic changes in forearm arteries in diabetic patients appear in 60% of hemodialysis patients and make it difficult to create an AVF only in 10% of diabetic patients, but it is possible to create a native AVF in 90% of diabetic patients, although this requires more procedures. In patients with diabetes, AVF in the wrist region should be preferred.

The clinical complexity among patients with systemic, chronic diseases.

OBJECTIVES: This study aimed to assess the clinical complexity of patients with chronic systemic diseases (systemic lupus erythematosus [SLE] and ANCA-associated vasculitis [AAV]) using the INTERMED Self-Assessment questionnaire (IMSA) to determine the most important factors responsible for this phenomenon in these patients. METHODS: This was a cross-sectional, observational study. Questionnaires were used to evaluate biopsychosocial complexity (IMSA), quality of life (Short Form Survey [SF-36]), mental state (General Health Questionnaire - 28 [GHQ-28] and Hospital Anxiety and Depression Scale [HADS]), and acceptance of illness (Acceptance of Illness Scale [AIS]). RESULTS: The final analysis included 81 patients. There was a moderate correlation between clinical complexity (total IMSA score) and quality of life related to mental health (SF-36) and mental state (GHQ-28) in patients with SLE. However, in patients with AAV, clinical complexity had a strong relationship with physical health-related quality of life and a moderate relationship with mental health-related quality of life. Stepwise regression analysis showed that low mental health-related quality of life is a predictor of higher complexity in SLE. The predictors of high clinical complexity in AAV were low physical and mental health-related quality of life and aggravated depressive symptoms (HADS). Other principal factors of clinical complexity were employment status, place of residence, social functioning, and illness duration. CONCLUSION: This study confirmed the importance of holistic attitudes and complex healthcare among patients with chronic diseases.

Changes of Dissociative Properties of Hemoglobin in Patients with Chronic Kidney Disease.

Background: The ability of hemoglobin to bind and dissociate oxygen is crucial in delivering oxygen to tissues and is influenced by a range of physiological states, compensatory mechanisms, and pathological conditions. This may be illustrated by the oxyhemoglobin dissociation curve (ODC). The key parameter for evaluating the oxygen affinity to hemoglobin is p50. The aim of this study was to evaluate the impact of hemodialysis on p50 in a group of patients with chronic kidney disease (CKD). An additional goal was to assess the correlation between p50 and the parameters of erythropoiesis, point-of-care testing (POCT), and other laboratory parameters. Methods: One hundred and eighty patients (106 male, 74 female), mean age 62.5 ± 17 years, with CKD stage G4 and G5 were enrolled in this cross-sectional study. Patients were divided into two groups, including 65 hemodialysis (HD) patients and 115 patients not receiving dialysis (non-HD). During the standard procedure of arteriovenous fistula creation, blood samples from the artery (A) and the vein (V) were taken for POCT. The causes of CKD, as well as demographic and comorbidity data, were obtained from medical records and direct interviews. Results: The weekly dose of erythropoietin was higher in HD patients than in non-HD patients (4914 ± 2253 UI vs. 403 ± 798 UI, p < 0.01), but hemoglobin levels did not differ between these groups. In the group of non-HD patients, more advanced metabolic acidosis (MA) was found, compared to the group with HD. In arterial and venosus blood samples, the non-HD group had significantly lower pH, pCO2 and HCO3-. This group had a higher proportion of individuals with MA with HCO3- < 22 mmol/L (42% vs. 24%, p < 0.01). The absolute difference of p50 in arterial and venous blood was determined using the formula Δp50 = (p50-A) - (p50-V). Δp50 was significantly higher in the HD group in comparison to non-HD (0.08 ± 2.05 mmHg vs. -0.66 ± 1.93 mmHg, p = 0,02). There was a negative correlation between pH and the p50 value in arterial (pH-A vs. p50-A, r = -0.56, p < 0.01) and venous blood (pH-V vs. p50-V, r = -0.45, p < 0.01). In non-HD patients, hemoglobin levels correlated negatively with p50 (r = -0.29, p < 0.01), whereas no significant relation was found in HD patients. Conclusions: The ODC in pre-dialysis CKD (non-HD) patients is shifted to the right due to MA, and this is an additional factor influencing erythropoiesis. Hemodialysis restores the natural differences in hemoglobin's dissociation characteristics in the arterial and venous circulation.

Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Novel PKD1 mutations - the effect on clinical phenotype of ADPKD patients in Lower Silesia.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development and progressive enlargement of cysts in the kidneys. The diagnosis of ADPKD is usually determined by criteria of renal ultrasound imaging of the development and number of cysts. However, in atypical cystic disease, for the recognition of ADPKD, DNA-based assays may be required. MATERIALS AND METHODS: In the present study PCR amplified fragments of the PKD1 gene (covering exons 15 and 43- 44) from genomic DNA of 134 Lower Silesia patients were analyzed for mutations and polymorphisms. Among them, the clinical significance of different PKD1 mutations was investigated in 81 persons. RESULTS: Eight new, previously undescribed, and 2 recurrent mutations were discovered. The presence of 3 known polymorphisms was confirmed. Seven of the 8 new discovered mutations were heterozygous. DISCUSSION: The results of the present study demonstrated that the frequency of genetic abnormalities in the analyzed fragments of the PKD1 gene in the Lower Silesian population is smaller than previously reported. Moreover, we could not detect deletions and insertions, which are often present is these regions of the PKD1 gene, which may be due to the limited number of screened patients. We conclude that none of the discovered changes in the PKD1 gene had any effect on clinical phenotype of the disease.

Antiphospholipid Syndrome in Renal Allograft Recipients-A Long-Term Multicenter Analysis.

Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown. Aim: The aim of the study was to assess renal allograft function and survival in recipients with APS. Methods: Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. Results: The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Conclusions: Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.

Neurotrophin-4 and Brain-Derived Neurotrophic Factor Serum Levels in Renal Transplant Recipients with Chronic Pruritus.

INTRODUCTION: Chronic pruritus (CP) is a common symptom defined as a sensation that provokes the desire to scratch and which lasts for at least 6 weeks. CP remains a problem for up to 21.3% of renal transplant recipients (RTRs). Our research aimed to establish the possible association between serum levels of neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) and the presence and intensity of CP in RTR. METHODS: The study was performed on a group of 129 RTRs, who were divided according to the presence or absence of pruritus in the previous 3 days. The assessment of pruritus was performed with the use of a numeric rating scale (NRS), 4-Item Itch Questionnaire (4IIQ), and Itchy Quality of Life (Itchy QoL). A total of 129 blood samples with a volume of 9 ml were drawn from RTRs during the monthly routine control. Serum levels (pg/mL) of NT-4 and BDNF were measured by the ELISA. RESULTS: Pruritic RTRs have statistically significantly higher serum concentrations of NT-4 serum level compared to non-pruritic RTRs (229.17 ± 143.86 pg/mL and 153.08 ± 78.19 pg/mL [p = 0.024], respectively). Moreover, a statistically significant difference between pruritic and non-pruritic RTRs with healthy controls was shown (p < 0.001 and p < 0.001, respectively). Although there was a numerically higher serum concentration of BDNF in pruritic RTRs (32.18 ± 7.31 pg/mL vs. 31.58 ± 10.84 pg/mL), the difference did not reach statistical significance. No statistically significant difference was also seen in BDNF serum levels between RTRs and healthy controls. Furthermore, there was a statistically significant, positive correlation between serum concentration of NT-4 and NRS score (p = 0.008, r = 0.357). CONCLUSIONS: The results indicate higher NT-4 serum concentration in RTRs with pruritus compared to RTRs without pruritus. Furthermore, the study revealed a statistically significant, positive correlation between the serum concentration of NT-4 and NRS score.

Coping of Chronically-Ill Patients during the COVID-19 Pandemic: Comparison between Four Groups.

In many countries, the COVID-19 pandemic led to healthcare reorganization limiting access to diagnostic or therapeutic procedures for chronically-ill patients. In this article, we describe the psychological consequences and coping strategies of several groups of chronically-ill patients. During the cross-sectional survey conducted in 2020, we enrolled 398 patients with four different chronic conditions (psoriasis, multiple sclerosis, and patients who have undergone a kidney transplant or received dialysis). The study sample was examined regarding the experienced stress levels (Perceived Stress Scale) and coping strategies (Brief-COPE). All four groups of patients most commonly declared using problem-focused coping strategies and least commonly reported the use of avoidant coping. Higher levels of perceived stress strongly correlated with self-blaming. The participants who declared previous psychiatric treatment or psychotherapy were more likely to use self-blaming, behavioral disengagement, substance use, and avoidant coping, while previous psychotherapy additionally correlated with emotion-focused coping. Group comparison identifies patients with a chronic neurological disease, such as multiple sclerosis, at higher risk of a less beneficial coping profile than kidney transplant recipients. Further focus on education and early interventions in at-risk individuals is needed, and widely targeted mental health programs are indicated in order to improve the mental health of patients suffering from chronic diseases.

Are in clinical practice measurements of concentrations and the calculation of mycophenolate mofetil pharmacokinetic parameters needed for optimizing therapy in patients with renal diseases or kidney transplantation?

BACKGROUND: Modern pharmacotherapy requires an individual approach to patients, taking into account changes in pharmacokinetics in pathological states and between-subject variability. This procedure is of particular importance in immunosuppressive drug therapy. In recent years, the attention has been paid to the usefulness of calculating the kinetic parameters of the drug in the optimization of the immunosuppressive treatment. OBJECTIVES: To assess the possibility of using mycophenolic acid (MPA) concentration measurements in order to optimize pharmacotherapy in patients with kidney diseases or after kidney transplantation. MATERIAL AND METHODS: The study included 103 patients with renal diseases (group 1) and after kidney transplantation (group 2), treated at the Department of Nephrology and Transplantation Medicine at the University Clinical Hospital, Wroclaw, Poland. The concentrations of MPA were measured using Enzyme Multiplied Immunoassay Technique (EMIT®) method. A total of 193 pharmacokinetic profiles were performed. RESULTS: The median of initial (C0) concentration for all patients was 2.09 mg/L, in group 1 - 2.06 mg/L and in group 2 - 2.11 mg/L. The median concentration at 30 min after drug administration (C30) was 11.72 mg/L in the whole study group, in group 1 - 11.52 mg/L and in group 2 - 12.72 mg/L. The median concentration at 120 min after the drug administration (C120) was 4.73 mg/L, 4.45 mg/L and 5.57 mg/L, respectively. The median area under the curve from C0 to C120 (AUC)0-120 was 15.77 h × mg/L for the entire study group, in group 1 - 15.46 h × mg/L and in group 2 - 16.78 h × mg/L. Using the Spearman's rank correlation coefficient for both groups, statistically significant (p < 0.05) correlations were found between 1) C0 and C30, 2) C0 and C120, 3) C0 and AUC0-120, 4) C0 and the daily dose, 5) C30 and AUC0-120, and 6) C30 and the morning dose. There were also statistically significant correlations between C120 and AUC0-120. Moreover, in group 1, a statistically significant correlation (p < 0.05) was found between 1) C120 and the daily dose, 2) C120 and albumin, 3) C120 and C30, and 4) C120 and AUC0-120. In the group 2, a statistically significant correlation was found between C120 and the morning dose. CONCLUSIONS: Measurements of MPA concentrations are useful for optimizing immunosuppression in patients requiring an individualized treatment.

High Serum IL-31 Concentration Is Associated with Itch among Renal Transplant Recipients.

Chronic itch (CI) is a common symptom caused by both dermatological and systemic disorders. CI is also a frequent, burdensome symptom among renal transplant recipients (RTR); however, its pathophysiology is not fully understood. The aim of this study was to assess the differences in concentration of IL-31 among itchy RTR. The study was performed on a group of selected 129 RTRs (54 itchy and 75 non-itchy patients). Itch severity was assessed with the use of the numeral rating scale (NRS) and the 4-item itch questionnaire (4IIQ). Every subject had his blood drawn to measure the concentration of IL-31. The results were subsequently compared and correlated. The mean concentration differed significantly between RTR suffering from itch (602.44 ± 534.5 pg/mL), non-itchy RTR (161.49 ± 106.61 pg/mL), and HC (110.33 ± 51.81 pg/mL) (p < 0.001). Post-hoc analysis revealed a statistically significantly increased IL-31 serum concentration in itchy RTR in comparison to the non-itchy RTR group (p < 0.001) and HC (p < 0.001). No significant difference was observed in IL-31 serum levels between non-itchy RTRs and HC. No correlation between IL-31 and itch intensity was found. The results of our study clearly demonstrate the association between IL-31 levels and CI in patients after renal transplantation.

Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy.

Focal segmental glomerulosclerosis (FSGS) involves podocyte injury. In patients with nephrotic syndrome, progression to end-stage renal disease often occurs over the course of 5 to 10 years. The diagnosis is based on a renal biopsy. It is presumed that primary FSGS is caused by an unknown plasma factor that might be responsible for the recurrence of FSGS after kidney transplantation. The nature of circulating permeability factors is not explained and particular biological molecules responsible for inducing FSGS are still unknown. Several substances have been proposed as potential circulating factors such as soluble urokinase-type plasminogen activator receptor (suPAR) and cardiolipin-like-cytokine 1 (CLC-1). Many studies have also attempted to establish which molecules are related to podocyte injury in the pathogenesis of FSGS such as plasminogen activator inhibitor type-1 (PAI-1), angiotensin II type 1 receptors (AT1R), dystroglycan(DG), microRNAs, metalloproteinases (MMPs), forkheadbox P3 (FOXP3), and poly-ADP-ribose polymerase-1 (PARP1). Some biomarkers have also been studied in the context of kidney tissue damage progression: transforming growth factor-beta (TGF-ß), human neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), and others. This paper describes molecules that could potentially be considered as circulating factors causing primary FSGS.