Diagnosis of lupus nephritis — the current status of knowledge

Poszukiwanie nowych wskaźników diagnostycznych, umożliwiających rozpoznanie i monitorowanie aktywności toczniowego zapalenia nerek jest aktualnie przedmiotem wielu badań. Biopsja nerki wciąż stanowi „złoty standard” diagnostyki, a rozpoznanie określonego typu nefropatii toczniowej ma wpływ na wybór schematu leczenia. W artykule przedstawiono wybrane klasyczne i nowe wskaźniki aktywności tocznia układowego i toczniowego zapalenia nerek, z uwzględnieniem biomarkerów najbardziej poszukiwanych — mających związek z rodzajem histopatologicznym nefropatii. Określenie cech, na podstawie których będzie można w sposób nieinwazyjny przewidywać i monitorować aktywność choroby, mogłoby umożliwić wczesną, a przez to skuteczniejszą optymalizację postępowania terapeutycznego. Możliwe, że rozwiązaniem będzie jednoczasowe oznaczenie kilku wskaźników, zarówno klasycznych, jak i nowych, i to właśnie okaże się w przyszłości najlepszym wskaźnikiem rokowniczym zajęcia nerek, oceny aktywności nefropatii i postaci toczniowego zapalenia nerek.The search for the novel biomarkers, enabling the diagnosis and monitoring of lupus nephritis activity is currently the subject of many studies. However, kidney biopsy is still the gold standard and the diagnosis of specific type of lupus nephritis affects the choice of treatment regimen. This article introduces classical, as well as recently discovered, indicators related to systemic lupus and lupus nephritis activity, including the most sought biomarkers — associated with histopathological type of nephropathy. Determination of features, which are able to provide non-invasively monitoring of the disease activity, will allow early and more efficient optimization of the therapeutic treatment. It is possible that measuring a number of biomarkers, both classical and novel, will be the best solution and the best prognostic indicator of renal involvement, evaluation of the activity and type of lupus nephritis

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry

Objective Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). Methods We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). Results Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3–12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06–9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05–6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3–25.5), skin involvement (OR = 4.4; 95% CI = 1.02– 19.6), and age > 65 (OR = 6.3; 95% CI = 1.18–33.7). Conclusions In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease

How to Distinguish Patients with pSS among Individuals with Dryness without Invasive Diagnostic Studies

In the course of pSS, inflammatory cell infiltration consists mainly of lymphocytes infiltrating exocrine glands, which leads to their impaired function. The characteristic feature is generalized dryness. The aim of this study was to attempt to answer the question whether it is possible to distinguish between patients with pSS and individuals with dryness caused by other pathologies without applying invasive studies. The study included 68 patients with pSS and 43 healthy controls with dryness. FS ≥ 1 was observed in 90% of patients with pSS (with or without dryness), and only in 23% of the control group (only with xerostomia). In the pSS group, anaemia (p=0.0085), lymphocytopenia (p=0.0006), elevated ERS (p=0.001), higher RF titer, and ANA antibodies were noted. Configuration of anti-SSA + SSB + Ro52 antibodies was characteristic for the pSS group. Considering the clinical symptoms, statistically significant differences were noted between pSS patients and the control group in frequency (p=0.02) and severity (p=0.042) of fatigue, lymphadenopathy, major salivary gland involvement, and photosensitivity to UV light. In conclusion, invasive methods are pivotal in pSS diagnosis in this salivary gland biopsy. Chronic fatigue syndrome is more common in pSS patients and can be subjective distinguishing factor in the group of people with dryness

Immune Response to Vaccination against COVID-19 in Breastfeeding Health Workers

Background: Initially, there were no data on the safety of COVID-19 vaccines in lactating women. The aim of our study was to evaluate the immune response to COVID-19 vaccinations in breastfeeding women. Methods: The study included 32 breastfeeding women who, regardless of the study, had decided to be vaccinated. Maternal serum and breast milk samples were simultaneously collected on days 8 ± 1, 22 ± 2, 29 ± 3, and 43 ± 4 after the first dose of the vaccine. The immune response was assessed by determining the presence of anti-SARS-CoV-2 IgG and IgA. Results: The breast milk IgG level was detectable (6.50 ± 6.74, median 4.7, and maximum 34.2 BAU/mL) and highly correlated to serum IgG level (rS 0.89; p < 0.001). The breast milk ratio of IgA to the cut-off value was higher in serum IgA-positive (4.18 ± 3.26, median 2.8, and maximum >10) than in serum IgA-negative women (0.56 ± 0.37, median 0.5, and maximum 1.6; p < 0.001). The highest concentrations of serum and breast milk antibodies were observed on day 29 ± 3 with a decrease on day 43 ± 4. Conclusion: The immune response to the vaccination against SARS-CoV-2 is strongest 7 ± 3 days after the second dose of the vaccine. Lactating mothers breastfeeding their children after vaccination against SARS-CoV-2 may transfer antibodies to their infant

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-β), 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

Molnupiravir When Used Alone Seems to Be Safe and Effective as Outpatient COVID-19 Therapy for Hemodialyzed Patients and Kidney Transplant Recipients

Background: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use in kidney transplant recipients and hemodialysis patients during the first months of 2022 in Poland. Methods: The retrospective observational cohort study at one kidney transplant center included 36 patients diagnosed with COVID-19 with an automated nucleic acid amplification test on nasopharyngeal swab specimens. All patients received molnupiravir for home-based therapy at a dose of 800 mg every 12 h orally for 5 days. Both kidney transplant recipients (n = 16) and hemodialysis patients (n = 20) presented a lot of comorbidities with a Charlson comorbidity index of 4.1 and 5.1, respectively. Results: Patients presented with fever, cough, and weakness followed by muscle and joint pain. Five kidney transplant recipients experienced acute kidney injury with a rise in serum creatinine level from 0.4 to 1.9 mg/dL. No serious side effects of molnupiravir therapy or interactions with immunosuppressive medications were observed. Symptoms of COVID-19 improved rapidly or resolved within 24–48 h of starting treatment. Conclusion: The study suggests the safety and efficacy of molnupiravir therapy alone early after the onset of SARS-CoV-2 infection, but further investigations should be performed to confirm our preliminary results. To the best of the authors’ knowledge, it is the first published report on molnupiravir use in end-stage kidney disease (ESKD) patients on hemodialysis and the third concerning kidney transplant recipients

Symptomatic respiratory Encephalitozoon cuniculi infection in renal transplant recipients

Objectives: Encephalitozoon spp. and Enterocytozoon bieneusi are intracellular parasitic fungi from the phylum Microsporidia, which initially localize to the intestine. As opportunistic pathogens, Encephalitozoon spp. in particular can disseminate to the respiratory tract, among other locations. Patients on life-long immunosuppression are at higher risk of such infections, mostly symptomatic. Methods: Sputum samples and bronchial washings from 72 renal transplant recipients and 105 patients with various respiratory diseases were screened for Encephalitozoon spp. and E. bieneusi by microscopic examination and genus-specific nested PCR followed by genotyping. Results: A total of 8.3% (6/72) of immunosuppressed renal transplant recipients and 1.9% (2/105) of patients with various respiratory diseases, both immunocompetent and immunosuppressed, were positive for respiratory microsporidial infection. All six transplant recipients were Encephalitozoon cuniculi-positive by PCR/sequencing and five of them suffered from respiratory symptoms. The presence of microsporidial spores was also confirmed microscopically in three of the transplant recipients. Of the two immunocompetent patients with various respiratory diseases, one had an E. cuniculi infection, while the second had an E. bieneusi infection. Conclusions: Life-long immunosuppression in renal transplant recipients increases the risk of respiratory infection by E. cuniculi. Microsporidia should be screened in respiratory samples of these patients, particularly when they have respiratory symptoms. Keywords: Encephalitozoon cuniculi, Enterocytozoon bieneusi, Renal transplant recipients, Life-long immunosuppression, Respiratory trac

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with the demographic and clinical characteristics of patients with ANCA-associated vasculitides

Introduction Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is characterized by the presence of proteinase-3(PR3) or myeloperoxidase(MPO) ANCA. In over 90% of cases, PR3-ANCA are associated with GPA. However, they are also rarely found in MPA and EGPA. On the other hand, MPO-ANCA being characteristic for MPA (>90% of cases), are also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. Patients and methods We conducted a multicenter study AAV patients (417–GPA, 106–MPA, 102-EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. Data were systematically collected according to a standardized protocol. Results In the ANCA positive group (anti-MPO, anti-PR3) male to female ratio was 1:1, whereas in ANCA negative subgroup - 1:2, regardless of the AAV diagnosis. Anti-MPO antibodies were present in a significantly older patients. Patients with MPO+ GPA and MPO+ EGPA were older than those with corresponding ANCA-negative GPA and EGPA as well as PR3+ AAV. Moreover, ANCA-negative AAV were characterized by a low risk of ESKD and death. Conclusions The presence and specificity of ANCA in AAV patients is related to sex and age, determines their organ involvement and influences mortality as previously shown. Patients with MPO-ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3-ANCA-positive patients are much more clinically heterogeneous. ANCA negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis