Kidney Transplantation During COVID-19 Outbreak: Data From Public and Non-Public Dialysis Network.

BACKGROUND: The COVID-19 pandemic significantly affected medical services in Poland. All restrictions, additional procedures, and numerous infections among medical staff affected transplantation in the country. This study aimed to analyze reports prepared by the Polish Transplant Coordination Center Poltransplant and internal Fresenius Nephrocare Poland to assess differences in the number of patients who qualified for kidney transplantation and transplanted during the pandemic compared with a pre-pandemic year. METHODS: Official data from the Polish Transplant Coordinating Centre Poltransplant bulletin from 2019, 2020, and 2021 was analyzed to determine the number of patients on the waiting list for solid organ transplantation. The number of transplantations reported by Polish transplant centers was also considered. RESULTS: During the SARS-CoV-2 outbreak, the number of qualified and transplanted patients was significantly lower than in the pre-pandemic period. The worst data concerns the new qualifications, which were significantly lower in the first year of the pandemic due to all the restrictions implemented. The number of kidney transplant procedures provided during the 2-year pandemic period decreased significantly (-20.8%) in 2020, and in the second year, the negative trend continued (-0.8%). For private dialysis providers, the number of active patients on the waiting list for kidney transplantation was a bit better-it decreased from 265 to 239 in 2020 (-9.8%) and increased to 259 in 2021 (+8.4%). The decline in the number of patients treated in Fresenius Nephrocare dialysis centers was more significant, decreasing by 27.8% in 2020 compared with 2019. In 2021, the number of transplanted patients slightly increased by about 2.5%. CONCLUSIONS: The decrease in qualified and transplanted patients during the SARS-CoV-2 outbreak clearly shows the need to undertake multidisciplinary discussions among all stakeholders to create new procedures and processes that will help protect the health care system and patients in future crisis situations.

Green Dialysis: Let Us Talk about Dialysis Fluid.

BACKGROUND: Hemodialysis is one of the most resources consuming medical intervention. Due to its concept, the proper amount of dialysis fluid passed through dialyzer is crucial to obtain the expected outcomes. The most frequent source of dialysis fluid is production from liquid concentrate (delivered in containers or plastic bags) in dialysis machine. Alternatively, concentrates for dialysis may be produced in dialysis center by dilution in mixing devices dry or semidry premixed compounds connected with system of central dialysis fluid delivery system. Dialysate consumption depends on various factors like type of hemodialysis machine, session duration, prescribed flow, etc. Summary: Modern hemodialysis machines are equipped with the modules which automatically reduce flow rate of dialysis fluid to the patient blood flow and minimize dialysate consumption during preparation and after reinfusion. Smart using of available options offered by manufacturers allows to save additional portion of acid concentrate and water. The weight of concentrates to be delivered to the dialysis center is the major factor influencing the cost (financial and environmental) of transportation from the manufacturer to the final consumer. The crisis on the energy carriers market and extremely high fuel prices made the transportation cost one of the significant costs of the treatment, which must be bear by supplier and finally influence on the price of goods. KEY MESSAGES: The careful choice of the concentrate delivery system can improve cost-effectiveness of dialysis. Such solutions implemented in dialysis unit helps make significant savings and decrease the impact on natural environment by carbon footprint reduction.

How COVID-19 Outbreak Influenced Transplantation in Poland.

Announced by the World Health Organization in early 2020, the pandemic caused by SARS-CoV-2 infections has had a huge impact on healthcare systems around the world. Local and international authorities focused on implementing procedures to safeguard the health of the population. All regular daily activities were disrupted. Similar factors related to the global fight against the COVID-19 epidemic also had a large impact on transplantation activity. In this article, the authors present the number of patients qualified for transplantation, transplanted and waiting on the waiting list in Poland during the 2-year period of the pandemic. In the first year of the epidemic (2020), all transplantation figures dropped drastically, by as much as 20-30% compared with 2019. The most disturbing fact is that the number of transplants performed in 2022 is still lower than before the outbreak of the epidemic (2019 and earlier).

Kidney and lipids: novel potential therapeutic targets for dyslipidemia in kidney disease?

INTRODUCTION: Altered lipid distribution and metabolism may lead to the development and/or progression of chronic kidney disease (CKD). Dyslipidemia is a major risk factor for CKD and increases the risk of cardiovascular events and mortality. Therefore, lipid-lowering treatments may decrease cardiovascular risk and prevent death. AREAS COVERED: Key players involved in regulating lipid accumulation in the kidney; contribution of lipids to CKD progression, lipotoxicity, and mitochondrial dysfunction in kidney disease; recent therapeutic approaches for dyslipidemia. EXPERT OPINION: The precise mechanisms for regulating lipid metabolism, particularly in kidney disease, are poorly understood. Guidelines for lipid-lowering therapy for CKD are controversial. Several hypolipemic therapies are available, but compared to others, statin therapy is the most common. No clinical trial has evaluated the efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in preventing cardiovascular events or improving kidney function among patients with CKD or kidney transplant recipients. Attractive alternatives, such as PCSK9-small interfering RNA (siRNA) molecules or evinacumab are available. Additionally, several promising agents, such as cyclodextrins and the FXR/TGR5 dual agonist, INT-767, can improve renal lipid metabolism disorders and delay CKD progression. Drugs targeting mitochondrial dysfunction could be an option for the treatment of dyslipidemia and lipotoxicity, particularly in renal diseases.

Vaccination and COVID-19 in Polish Dialysis Patients: Results from the European Clinical Dialysis Database.

Background: Patients with end-stage kidney disease undergoing hemodialysis are particularly vulnerable to severe COVID-19 as a result of older age and multimorbidities. Objectives: Data are still limited and there are no published data on mortality in hemodialyzed patients in Poland, in particular when vaccines became available. We assessed the epidemiologic and clinical data of patients with laboratory-confirmed COVID-19 and assessed the mortality in 2019, 2020, and 2021, as well as the vaccination rate in 2021. Patients and Methods: Retrospectively collected data from 73 Fresenius Nephrocare Poland hemodialysis centers and one public unit were analyzed. Results: In 2021, the vaccination rate was 96%. The unadjusted mortality (number of deaths divided by number of patients) in 2019 was 18.8%, while the unadjusted (after exclusion of COVID-related deaths) mortality in 2020 was 20.8%, and mortality in 2021 was 16.22%. The prevalence of cardiovascular deaths in 2019 and 2020 was almost identical (41.4% vs. 41.2%, respectively), and in 2021, the figures increased slightly to 44.1%. The prevalence of sudden cardiac deaths in 2019 was higher than in 2020 (19.6% vs. 17.3%, respectively) and consequently decreased in 2021 (10.0%), as well as strokes (6.2% vs. 5.4%, and 3.31% in 2021), whereas deaths due to gastrointestinal tract diseases were lower (2.5% vs. 3.2%, and 2.25% in 2021), diabetes complications (0.5% vs. 1.3%, and 0.5% in 2021), sepsis (5.1% vs. 6.3%, and 8.79% in 2021), respiratory failure (1.2 vs. 1.6%, and 2.83% in 2021), and pneumonia (1.4% vs. 2.0%, and 0.82%). There were 1493 hemodialyzed COVID-19 positive patients, and among them, 191 died in 2020 (12.79%). In 2021, there were 1224 COVID-19 positive patients and 260 died (21.24%). The mortality of COVID-19 positive dialyzed patients contributed 13.39% in 2020 and 16.21% in 2021 of all recorded deaths. Conclusions: The mortality among HD patients was higher in 2021 than in 2020 and 2019, despite the very high vaccination rate of up to 96%. The higher non-COVID-19 mortality may be due to the limited possibility of hospitalization and dedicated care during the pandemic. This information is extremely important in order to develop methods to protect this highly vulnerable patient group. Prevention plays a key role; other measures are essential in the mitigation and spread of COVID-19 in HD centers.

Main Barriers to the Introduction of a Home Haemodialysis Programme in Poland: A Review of the Challenges for Implementation and Criteria for a Successful Programme.

INTRODUCTION: Home dialysis in Poland is restricted to the peritoneal dialysis (PD) modality, with the majority of dialysis patients treated using in-centre haemodialysis (ICHD). Home haemodialysis (HHD) is an additional home therapy to PD and provides an attractive alternative to ICHD that combines dialysis with social distancing; eliminates transportation needs; and offers clinical, economic, and quality of life benefits. However, HHD is not currently provided in Poland. This review was performed to provide an overview of the main barriers to the introduction of a HHD programme in Poland. MAIN FINDINGS: The main high-level barrier to introducing HHD in Poland is the absence of specific health legislation required for clinician prescribing of HHD. Other barriers to overcome include clear definition of reimbursement, patient training and education (including infrastructure and experienced personnel), organisation of logistics, and management of complications. Partnering with a large care network for HHD represents an alternative option to payers for the provision of a new HHD service. This may reduce some of the barriers which need to be overcome when compared with the creation of a new HHD service and its supporting network due to the pre-existing infrastructure, processes, and staff of a large care network. CONCLUSIONS: Provision of HHD is not solely about the provision of home treatment, but also the organisation and definition of a range of support services that are required to deliver the service. HHD should be viewed as an additional, complementary option to existing dialysis modalities which enables choice of modality best suited to a patient's needs.

Lack or insufficient predialysis nephrology care worsens the outcomes in dialyzed patients - call for action.

The phenomenon of patients with advanced renal failure accepted for dialysis at a late stage in the disease process (late referral [LR]) is known almost from the beginning of dialysis therapy. It may also be associated with worse outcomes. The aim of the study was to assess the effect of referral time on the outcomes, such as number of hospitalizations, length of stay, kidney transplantation, and mortality. A study of 1303 patients with end-stage renal failure admitted for dialysis in the same period in Fresenius Nephrocare Poland dialysis centers was initiated. The type of vascular access during the first dialysis was accepted as the criterion differentiating LR (n = 457 with acute catheter) from early referral (ER; n = 846). The primary endpoint was the occurrence of death during the 13-month observation. By the end of observation, 341 (26.2%) of patients died. The frequency of death was 18.1 for ER and 37.9 for LR per 1000 patient-months. It can be estimated that 52.1% (95% CI: 40.5-61.5%) of the 341 deaths were caused by belonging to the LR group. Patients from LR group had longer hospitalizations, more malignancies, lower rate of vascular access in the form of a-v fistula, higher comorbidity index. It seems that establishing a nephrological registry would help to improve the organization of care for patients with kidney disease, particularly in the pandemic era.

Cognitive Impairment and Kidney Transplantation: Underestimated, Underrecognized but Clinically Relevant Problem.

BACKGROUND: Chronic kidney disease (CKD) affects the crosstalk between organs in the body and vast majority of studies were devoted to the interactions between the kidneys and the cardiovascular system. As of today, there is more evidence of the kidney and the central nervous system connections. SUMMARY: Indeed, CKD and in particular dialysis therapy is linked to the increased prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment, and depression. Both traditional cardiovascular risk factors (such as diabetes, hypertension, and lipid disorders), nontraditional risk factors (such as uremic toxins, anemia, and secondary hyperparathyroidism) may predispose CKD patients to neurological disorders. Likewise, cognitive problems occur more commonly in kidney transplant recipients, regardless of age, than in the general population, but the prevalence is still understudied. Cognitive impairment is associated with a higher risk of hospitalization, mortality, decreased quality of life, or health care costs in kidney transplant recipients. Here, we review (i) the potential clinical impact of kidney transplantation on cerebrovascular and neurological complications, (ii) evaluation of patients with cognitive impairment for kidney transplantation (iii) the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, and (iv) unmet medical needs. KEY MESSAGES: Cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem. The screening for cognitive declines after kidney transplantation is not yet a routine practice. Several prospective and cross-sectional studies reported improvement across some of the assessed cognitive domains after transplantation.

Kidney Transplant Recipients Have Higher Malignancy Prevalence Than Hemodialyzed Patients.

BACKGROUND: Kidney transplant is the preferred therapy for end-stage kidney disease; however, it has been associated with some serious complications, including malignancy, which became the second leading cause of death among kidney allograft recipients. The aim of this study was to assess the prevalence of malignancy in hemodialyzed patients and in kidney transplant recipients. METHODS: A cross-sectional study was conducted in 114 prevalent hemodialyzed patients, including 7 on the waiting list and 350 kidney allograft recipients. Hemodialyzed patients and kidney allograft recipients did not differ in regard to sex, dialysis vintage, and cause of end-stage renal failure, but were significantly older. RESULTS: Among wait-listed patients, only 1 had a history of malignancy (gastric cancer stage G1). Among kidney allograft recipients, in 70 patients, malignancy developed (in total 20% of the studied population). The leading malignancy was skin cancer (18 cases), followed by post-transplant lymphoproliferative disorder (PTLD) in 10 cases, lung cancer (small cell and non-small cell lung cancer; 4 cases), renal cell carcinoma (3 cases), brain cancer (glioma; 3 cases), colorectal cancer (3 cases), Kaposi sarcoma (2 cases), Merkel carcinoma (2 cases), metastatic disease of unknown origin (2 cases), and other 23 malignancies were in a single patient (including 1 leukemia and 1 multiple myeloma). Twenty-six deaths were recorded in kidney allograft recipients with malignancy, mainly in PTLD, Kaposi sarcoma, Merkel carcinoma, sarcoma, glioma, and melanoma. CONCLUSIONS: Despite the lower prevalence of malignancy on hemodialyzed population, cancer screening in both potential transplant recipients and kidney allograft recipients is a prerequisite, because nowadays there is a scarcity of data in this area. It may be due to previous immunosuppression, long-term dialysis vintage, immunocompromised status, and immunosuppressive therapy after transplant, in particular in high-risk patients.

Haematological disorders following kidney transplantation.

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management.

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis.

ABSTRACT: The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Current Status of Renal Anemia Pharmacotherapy-What Can We Offer Today.

Chronic kidney disease (CKD) is one of the fastest-growing major causes of death internationally. Better treatment of CKD and its complications is crucial to reverse this negative trend. Anemia is a frequent complication of CKD and is associated with unfavorable clinical outcomes. It is a devastating complication of progressive kidney disease, that negatively affects also the quality of life. The prevalence of anemia increases in parallel with CKD progression. The aim of this review is to summarize the current knowledge on therapy of renal anemia. Iron therapy, blood transfusions, and erythropoietin stimulating agents are still the mainstay of renal anemia treatment. There are several novel agents on the horizon that might provide therapeutic opportunities in CKD. The potential therapeutic options target the hepcidin-ferroportin axis, which is the master regulator of iron homeostasis, and the BMP-SMAD pathway, which regulates hepcidin expression in the liver. An inhibition of prolyl hydroxylase is a new therapeutic option becoming available for the treatment of anemia in CKD patients. This new class of drugs stimulates the synthesis of endogenous erythropoietin and increases iron availability. We also summarized the effects of prolyl hydroxylase inhibitors on iron parameters, including hepcidin, as their action on the hematological parameters. They could be of particular interest in the out-patient population with CKD and patients with ESA hyporesponsiveness. However, current knowledge is limited and still awaits clinical validation. One should be aware of the potential risks and benefits of novel, sophisticated therapies.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = -0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = -0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma.

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-ß superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival (p = 0.06). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.

New Markers of Renal Failure in Multiple Myeloma and Monoclonal Gammopathies.

* Correspondence: kasiajanda@op [...].

Malignancy Prevalence in Waitlisted Potential Kidney Transplant Recipients Is Very Low Relative to Patients After Kidney Transplantation.

Kidney transplantation improves quality of life, prolongs survival, and is cost-effective, but bears some serious complications including malignancy. The aim of this study was to assess the prevalence of malignancy in dialyzed patients on the waiting list and in kidney allograft recipients. The cross-sectional study was conducted in 50 prevalent patients on the waiting list and 300 kidney allograft recipients. Patients who had been registered in the cadaver kidney waiting list and kidney allograft recipients did not differ in regard to age, sex, dialysis vintage, and causes of end-stage renal failure. In waitlisted patients, only 3 had a history of malignancy. In kidney allograft recipients, 52 patients developed malignancy. The leading malignancy was skin cancer with 9 cases, followed by post-transplant lymphoproliferative disorder in 5 cases, Kaposi sarcoma in 2 cases, brain cancer in 2 cases, Merkel carcinoma in 2 cases, lung cancer (small cell and non--small cell), unknown origin in 2 cases, and the other 22 malignancies were in single patients (including 1 leukemia and 1 multiple myeloma). Seventeen deaths were recorded in kidney allograft recipients with malignancy mainly in post-transplant lymphoproliferative disorder, Kaposi sarcoma, Merkel carcinoma, sarcoma, and brain cancer. Concluding, waitlisted patients represent a very selected and healthier dialyzed population. Guidelines for cancer screening in both potential transplant recipients and kidney allograft recipients should be developed as nowadays a scarcity of data exists in this matter. Minimization of immunosuppressive regimen should be considered, in particular, in high-risk patients.