Unveiling the Unexpected: Why Doctors Should Look beyond the Lungs when Predicting COVID-19 Mortality.

INTRODUCTION: The main objective of this study was to identify the best combination of admission day parameters for predicting COVID-19 mortality in hospitalized patients. Furthermore, we sought to compare the predictive capacity of pulmonary parameters to that of renal parameters for mortality from COVID-19. METHODS: In this retrospective study, all patients admitted to a tertiary hospital between September 1st, 2020, and December 31st, 2020, who were clinically symptomatic and tested positive for COVID-19, were included. We gathered extensive data on patient admissions, including laboratory results, comorbidities, chest X-ray (CXR) images, and SpO2 levels, to determine their role in predicting mortality. Experienced radiologists evaluated the CXR images and assigned a score from 0 to 18 based on the severity of COVID-19 pneumonia. Further, we categorized patients into two independent groups based on their renal function using the RIFLE and KDIGO criteria to define the acute kidney injury (AKI) and chronic kidney disease (CKD) groups. The first group ("AKI&CKD") was subdivided into six subgroups: normal renal function (A); CKD grade 2+3a (B); AKI-DROP (C); CKD grade 3b (D); AKI-RISE (E); and grade 4 + 5 CKD (F). The second group was based only on estimated glomerular filtration rate (eGFR) at the admission, and thus it was divided into four grades: grade 1, grade 2+3a, grade 3b, and grade 4 + 5. RESULTS: The cohort comprised 619 patients. Patients who died during hospitalization had a significantly higher mean radiological score compared to those who survived, with a p value <0.01. Moreover, we observed that the risk for mortality was significantly increased as renal function deteriorated, as evidenced by the AKI&CKD and eGFR groups (p < 0.001 for each group). Regarding mortality prediction, the area under the curve (AUC) for renal parameters (AKI&CKD group, eGFR group, and age) was found to be superior to that of pulmonary parameters (age, radiological score, SpO2, CRP, and D-dimer) with an AUC of 0.8068 versus 0.7667. However, when renal and pulmonary parameters were combined, the AUC increased to 0.8813. Optimal parameter combinations for predicting mortality from COVID-19 were identified for three medical settings: Emergency Medical Service (EMS), the Emergency Department, and the Internal Medicine Floor. The AUC for these settings was 0.7874, 0.8614, and 0.8813, respectively. CONCLUSIONS: Our study demonstrated that selected renal parameters are superior to pulmonary parameters in predicting COVID-19 mortality for patients requiring hospitalization. When combining both renal and pulmonary factors, the predictive ability of mortality significantly improved. Additionally, we identified the optimal combination of factors for mortality prediction in three distinct settings: EMS, Emergency Department, and Internal Medicine Floor.

A case report: Acute kidney injury with progression to chronicity in an eldery woman.

Acute renal failure in elderly patients can be caused by a wide spectrum of diseases that usually have a cause outside the kidney. The most common causes include renal impairment as part of ANCA vasculitis, another category includes clonal plasmatic cell disease with light chain cast nephropathy; and there also exists an increasing number of drug-induced tubulointerstial damage. We present a case of iatrogenic less common form of acute failure in a 73-year-old woman, who did not suffer from any serious disease until then. Although the biopsy helped to determine the cause of the failure and thus affect subsequent therapy, the function did not return to the previous state and the patient progressed to CKD G3bA1 with serum creatinine values of around 170-140 µmol/l.

Can Renal Parameters Predict the Mortality of Hospitalized COVID-19 Patients?

INTRODUCTION: Our study aimed to analyze whether renal parameters can predict mortality from COVID-19 disease in hospitalized patients. METHODS: This retrospective cohort includes all adult patients with confirmed COVID-19 disease who were consecutively admitted to the tertiary hospital during the 4-month period (September 1 to December 31, 2020). We analyzed their basic laboratory values, urinalysis, comorbidities, length of hospitalization, and survival. The RIFLE and KDIGO criteria were used for AKI and CKD grading, respectively. To display renal function evolution and the severity of renal damage, we subdivided patients further into 6 groups as follows: group 1 (normal renal function), group 2 (CKD grades 2 + 3a), group 3 (AKI-DROP defined as whose s-Cr level dropped by >33.3% during the hospitalization), group 4 (CKD 3b), group 5 (CKD 4 + 5), and group 6 (AKI-RISE defined as whose s-Cr level was elevated by ≥50% within 7 days or by ≥26.5 µmol/L within 48 h during hospitalization). Then, we used eGFR on admission independently of renal damage to check whether it can predict mortality. Only 4 groups were used: group I - normal renal function (eGFR > 1.5 mL/s), group II - mild renal involvement (eGFR 0.75-1.5), group III - moderate (eGFR 0.5-0.75), and group IV - severe (GFR <0.5). RESULTS: A total of 680 patients were included in our cohort; among them, 244 patients displayed normal renal function, 207 patients fulfilled AKI, and 229 patients suffered from CKD. In total, a significantly higher mortality rate was found in the AKI and the CKD groups versus normal renal function - 37.2% and 32.3% versus 9.4%, respectively (p < 0.001). In addition, the groups 1-6 divided by severity of renal damage reported mortality of 9.4%, 21.2%, 24.1%, 48.7%, 62.8%, and 55.1%, respectively (p < 0.001). The mean hospitalization duration of alive patients with normal renal findings was 9.5 days, while it was 12.1 days in patients with any renal damage (p < 0.001). When all patients were compared according to eGFR on admission, the mortality was as follows: group I (normal) 9.8%, group II (mild) 22.1%, group III (moderate) 40.9%, and group IV (severe) 50.5%, respectively (p < 0.001). It was a significantly better mortality predictor than CRP on admission (AUC 0.7053 vs. 0.6053). CONCLUSIONS: Mortality in patients with abnormal renal function was 3 times higher compared to patients with normal renal function. Also, patients with renal damage had a worse and longer hospitalization course. Lastly, eGFR on admission, independently of renal damage type, was an excellent tool for predicting mortality. Further, the change in s-Cr levels during hospitalization reflected the mortality prognosis.

Glomerulonephritides associated with infections.

Glomerulonephritides associated with infections constitute an important group of diseases. Their occurrence is shifting from children and young people to elderly people. The rates of acute post-streptococcal glomerulonephritis, a condition with a good prognosis, are decreasing, and the rates of glomerulonephritides associated with various bacterial, viral, or parasitic infections, often with a poor prognosis, are increasing. Renal biopsy plays an important role in the diagnostic process. Manifestations of glomerulonephritis can be the initial sign of an occult infection. When evaluating renal biopsy specimens, certain signs may suggest this option, but it cannot be relied on completely. The search for an active infection is warranted in every patient with newly diagnosed glomerulonephritis. Hepatitis B and C serology is always performed, with other investigations depending on individual risk factors, clinical manifestations, and laboratory and histological findings. Failure to follow this rule may have serious consequences, in part because immunosuppressive therapy for glomerulonephritis can worsen the underlying infection and also because the progressive nature of parainfective glomerulonephritis cannot be reversed without eliminating the causative infection. Distinguishing between parainfective and autoimmune glomerulonephritis can be difficult, as there are no major differences in clinical manifestations, laboratory, and sometimes even histological findings. In the setting of the Czech Republic, important diseases include, in particular, staphylococcus infection-associated glomerulonephritis (SAGN) and, in general, infective endocarditis-associated glomerulonephritis, shunt nephritis, and other cases associated with foreign-material infection, such as catheters or electrodes. Among viral diseases, glomerulonephritides associated with the hepatitis B virus, hepatitis C virus, and the SARS CoV-2 virus are of major significance. The treatment of parainfectious glomerulonephritides involves elimination of the causative infection; only in rare cases, a combination of anti-infective treatment and mild immunosuppression can be indicated.

[More safe anticoagulant treatment - use of idarucizumab (Praxbind®): case reports from RE-VERSE AD study and clinical practice]. / Bezpecnejsí antikoagulacní lécba - pouzití idarucizumabu (Praxbind®): série kazuistik ze studie RE-VERSE AD a klinické praxe.

RE-VERSE AD, a prospective multicentric cohort study, examined the effect of idarucizumab on 2 cohorts of patients anticoagulated with dabigatran - in cohort A in patients with uncontrollable or life threatening bleeding, in cohort B in patients who undergo acute surgery. Within the study patients were intravenously administered 5 g antidote divided into 2 doses per 2.5 g within 15 min to eliminate the anticoagulation effect of dabigatran. A series of case studies is presented to describe the use of idarucizumab within the RE-VERSE AD study and in clinical practice in the period of 2015-2016 at the University Hospital Hradec Králové. The included examples illustrate the benefit of dabigatran as the only drug so far from the group of direct oral anticoagulants which has an antidote.Key words: antidote - bleeding - dabigatran - direct oral anticoagulants - DOAC - high risk of bleeding - idarucizumab - intervention.

Clinical case: idelalisib-induced immunoglobulin flare.

IgM flare is a transient, treatment-induced, increase of monoclonal IgM levels in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) patients. Until recently this phenomenon was observed in patients treated with Cladribine and Rituximab. Here we report a case of a heavily pretreated chronic lymphocytic leukemia patient with an atypically high immunoglobulin production who developed clinically significant immunoglobulin flare following Idelalisib treatment.

The most common founder pathogenic variant c.868G > A (p.Val290Met) in the NPHS2 gene in a representative adult Czech cohort with focal segmental glomerulosclerosis is associated with a milder disease and its underdiagnosis in childhood.

Background: Genetic focal segmental glomerulosclerosis (FSGS) is caused by pathogenic variants in a broad spectrum of genes that have a variable representation based on subjects' ethnicity and/or age. The most frequently mutated autosomal recessive gene in FSGS is NPHS2. In this study, we analyzed the spectrum of NPHS2 variants and their associated phenotype in Czech adult FSGS patients. Methods: A representative cohort of 234 adult patients with FSGS, derived from 225 families originating from all regions of Czechia, was analyzed by massively parallel sequencing. In this study, we focused on the comprehensive analysis of the NPHS2 gene. The histological classification of FSGS followed the Columbia classification. Results: We detected seven (3%) cases bearing homozygous or compound heterozygous pathogenic NPHS2 variants. A single pathogenic variant c.868G > A (p.Val290Met) was found in the majority of NPHS2-positive cases (86%; 6 out of 7) in histologically confirmed instances of FSGS. Its allele frequency among unrelated NPHS2-associated FSGS patients was 50% (6/12), and Haplotype analysis predicted its origin to be a result of a founder effect. There is an identical V290M-related haplotype on all V290M alleles spanning a 0,7 Mb region flanking NPHS2 in Central European FSGS populations. The phenotype of the p.Val290Met NPHS2-associated FSGS demonstrated a later onset and a much milder course of the disease compared to other NPHS2 pathogenic variants associated with FSGS. The mean age of the FSGS diagnosis based on kidney biopsy evaluation was 31.2 ± 7.46 years. In 50% of all cases, the initial disease manifestation of proteinuria occurred only in adulthood, with 83% of these cases not presenting with edemas. One-third (33%) of the studied subjects progressed to ESRD (2 out of 6) at the mean age of 35.0 ± 2.82 years. Conclusions: We identified the most prevalent pathogenic variant, p.Val290Met, in the NPHS2 gene among Czech adult FSGS patients, which has arisen due to a founder effect in Central Europe. The documented milder course of the disease associated with this variant leads to the underdiagnosis in childhood. We established the histopathological features of the NPHS2-associated adult FSGS cases based on the Columbia classification. This might improve patient stratification and optimize their treatment.

Bioptically Proven "Anticoagulation-Related Nephropathy" Induced by Dual Antiplatelet Therapy.

Anticoagulation-related nephropathy (ARN) is a significant and underdiagnosed complication in patients who receive anticoagulation therapy. It is characterized by acute kidney injury in the setting of excessive anticoagulation defined as an international normalized ratio > 3.0 in patients treated with warfarin. A definitive diagnosis is made by renal biopsy showing acute tubular necrosis with obstruction of the tubuli by red blood cell casts. However, the evidence shows that ARN can occur during treatment with novel oral anticoagulants as well. Although it has been suggested that antiplatelet therapy, such as aspirin, might contribute to coagulopathy (and therefore the hypothetical risk of ARN), there are no reports of ARN induced by antiplatelet therapy according to our knowledge. It is also reported that glomerular lesions (i.e., kidney disease) represent a risk factor for ARN. We present a case of an 82-year-old man who developed biopsy-proven ARN after the administration of dual antiplatelet therapy with no previous anticoagulation treatment and normal coagulation tests.