Effectiveness of Oral Nirmatrelvir/Ritonavir vs. Intravenous Three-Day Remdesivir in Preventing Progression to Severe COVID-19: A Single-Center, Prospective, Comparative, Real-Life Study.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. METHODS: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. RESULTS: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07-0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01-0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. CONCLUSION: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

Clinical Outcome of Kidney Transplant Recipients with C1q-Binding De Novo Donor Specific Antibodies: A Single-Center Experience.

Complement activation by HLA antibodies is a key component of immune-mediated graft injury. We examined the clinical outcomes of kidney transplant recipients with complement-fixing de novo donor-specific antibodies (dnDSA) who were followed in our center. The C1q-binding ability was retrospectively assessed in 69 patients with dnDSA and mean fluorescence intensity (MFI) values > 2000 out of the 1325 kidney transplant recipients who were screened for DSA between 2015 and 2019. Luminex IgG single antigen beads (SAB)and C1q-SAB assays (One Lambda) were used. C1q-binding dnDSA was identified in 32/69 (46.4%) of the patients. Significantly higher MFI values were observed in C1q-positive DSA (18,978 versus 5840, p < 0.001). Renal graft biopsies were performed in 43 of the kidney transplant recipients (62.3%) with allograft dysfunction. Antibody-mediated rejection (ABMR) was detected in 29/43 (67.4%) of the patients. The incidence of ABMR was similar among patients with C1q-binding and non-C1q-binding DSA (51.7% vs. 48.3%, p = 0.523). Graft loss occurred in 30/69 (43.5%) of the patients at a median time of 82.5 months (IQR 45-135) from DSA detection. C1q-binding DSA was present in more patients who experienced graft loss (53.1% vs. 35.1%, p = 0.152). Higher MFI values and inferior clinical outcomes occurred in most of the kidney transplant recipients with C1q-binding dnDSA.

Treatment of HIV-Associated Lupus-like Membranous Nephropathy with Tacrolimus: A Case Report and Review of the Literature.

Renal complications of HIV infection are common and histologically diverse. Besides HIV-associated nephropathy, which is the most well-defined glomerular disorder, immune-complex-mediated glomerulonephritis (HIVICK) is also encountered in the setting of HIV infection and may occasionally present with "lupus-like" features by light microscopy and immunofluorescence. Management of HIVICK remains controversial and mainly focuses on HIV viremia suppression with combined antiretroviral therapy. Immunosuppressive therapy may be used in order to mitigate the renal inflammation induced by the immune complex deposition. Data regarding the use of immunosuppressants in HIVICK are very limited, mostly including corticosteroids and mycophenolate acid analogues. Herein, we present the case of a 40-year-old HIV-infected Caucasian man with nephrotic syndrome, renal impairment, and a "lupus-like" membranous pattern in the kidney biopsy, who achieved a partial response of his proteinuria with a tacrolimus-based regimen in combination with antiretroviral therapy.

Pregnancy in Women With Preexisting Glomerular Diseases: A Single-Center Experience.

AIM: Women with glomerular diseases are often of childbearing age. Besides lupus nephritis, data regarding pregnancy in patients with glomerular diseases are limited, posing a challenging task to attending nephrologists. This study aimed to investigate the pregnancy outcomes and the impact on the underlying glomerular disease among women followed in our institution. METHODS: A single-center retrospective cohort study of women with biopsy-proven glomerular diseases who experienced pregnancy between 2010 and 2020. We analyzed data before, during, and after gestation. RESULTS: A total of 22 women, 13 women with primary and 9 women with secondary glomerular diseases, were included in this study. Most patients (82%) had received immunosuppressive treatment at various times before pregnancy. All the women were in remission, either complete (62%) or partial (38%), with well-preserved renal function (82%) before conception. A total of 30 live births and 1 stillbirth were recorded; the rate of preterm delivery was 23%. Renal function and proteinuria remained stable during pregnancy. Preeclampsia was observed in 6.7% of patients and disease relapse in 6.9% of the pregnancies. CONCLUSION: Pregnancy was associated with a low frequency of adverse events in women with underlying glomerular diseases, provided they have quiescent disease and preserved renal function.

Plasma Exchange in ANCA-Associated Vasculitis: A Narrative Review.

Therapeutic plasma exchange (TPE) is an adjunctive intervention to immunosuppression for the treatment of severe renal involvement or lung hemorrhage in patients with ANCA-associated vasculitis (AAV). Patients with AAV have an increased risk for progression to end-stage kidney disease (ESKD) or death despite advances in immunosuppressive therapy. The potential pathogenicity of ANCA makes TPE a reasonable treatment approach for the life-threatening complications of AAV. The efficacy of intensive TPE in rapidly progressive glomerulonephritis was originally described in small studies almost four decades ago. Further randomized trials examined the addition of TPE to standard of care, exhibiting mixed results in both patient and renal survival. The largest clinical trial to date, PEXIVAS, failed to demonstrate a clear benefit for TPE in severe AAV. In light of new evidence, the role of TPE remains controversial across the vasculitis medical community. The purpose of this review is to summarize the clinical indications and the current available data for the use of TPE in patients with severe AAV.

Clinicopathologic features and treatment outcomes of patients with fibrillary glomerulonephritis: A case series.

ABSTRACT: Fibrillary glomerulonephritis (FGN) is a diverse glomerular disease with poor renal prognosis. The optimal therapeutic approach remains undetermined, as treatment outcomes vary across different studies.We retrospectively reviewed the medical data of 10 patients diagnosed with biopsy-proven FGN at our center between 2004 and 2019. Clinical and histological features, as well as therapeutic regimens and treatment response, are reported.The patients were predominantly men (2.5/1 men-female ratio) with a mean age at diagnosis of 46.5 years (IQR: 41.5-59.5). The median proteinuria and creatinine levels at presentation were 2.55 g/day (IQR: 0.4-8.9) and 1.35 mg/dl (IQR: 0.94-1.88), respectively. Four out of 10 patients presented with nephrotic syndrome, 5 patients with nephritic syndrome and 1 with isolated microscopic hematuria. Light microscopy showed mesangial proliferative (n = 7), membranoproliferative-like (n = 2), and diffuse sclerosing patterns (n = 1). Rituximab was used in 7/10 patients, either as monotherapy (n = 3) or combined with cyclophosphamide and corticosteroids (n = 4). Patients who were treated with immunosuppression had higher median levels of creatinine (1.40 mg/dl) and proteinuria (3.5 g/d) compared to those who received supportive treatment alone (0.94 mg/dl and 0.6 g/d, respectively). After a median follow-up of 30 months (IQR:18-66.5), 4 out of 7 patients (57%) treated with immunosuppression achieved a clinical response, 1 had persistent renal dysfunction and 2 patients progressed to end-stage renal disease.The present case series extends the existing literature on the clinical features and outcomes of FGN, as well as the use of rituximab-based regimens for the treatment of the disease. Further research is needed to establish the proper management of the disease.

De Novo Minimal Change Disease following Vaccination with the Pfizer/BioNTech SARS-CoV-2 Vaccine in a Living Kidney Donor.

Coronavirus disease 2019 has developed as a pandemic. Immunization with the introduction of vaccines against COVID-19 seems be the only way to end this pandemic. We report on a case of a kidney donor, who developed minimal change disease (MCD) within 4 days post-vaccination with the SARS-CoV-2 BNT162b2 mRNA vaccine (Pfizer/BioNTech). She donated her kidney to her husband 4 years ago. After receiving the 1st vaccine dose, she presented with nephrotic syndrome, with complete remission 5 days later. She proceeded with the second dose of the BNT162b2 vaccine at the appointed time. Two days later, she presented with a relapse of full-blown nephrotic syndrome with preserved renal function. We performed an ultrasound-guided percutaneous kidney biopsy and the final diagnosis was consistent with minimal change disease. Oral prednisolone was promptly initiated at a dosage of 1 mg/kg daily and complete remission was achieved 10 days later. More data about this rare appearance of de novo glomerular diseases after SARS-CoV-2 vaccination are emerging and should be interpreted rigorously.

A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients' Lives and Allografts.

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

A Patient with Cryoglobulinemic Membranoproliferative GN (MPGN) Who Survived COVID-19 Disease: Case Presentation and Current Data of COVID-19 Infection in Dialysis and Transplanted Patients in Greece.

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Case of an unusual diagnosis of primary antiphospholipid syndrome with multiple clinical complications.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by the presence of antiphospholipid antibodies in association with thrombotic events and/or obstetric complications. Renal involvement is not infrequent in both primary and secondary APS. Kidney manifestations comprise a wide range of clinical features, including hypertension, major renal vessel thrombosis or microvascular endothelial injury, also described as APS nephropathy. In the absence of a thrombotic event, clinical manifestations of APS are often non-specific. We recently encountered a case of primary APS in a young male with newly diagnosed hypertension and renal impairment. The diagnosis of APS was initially suspected by his kidney biopsy findings, when electron microscopy examination showed the features of chronic microangiopathy, and was later confirmed by a triple positive antiphospholipid antibody profile and multiple organ involvement.