Activity of daily life dependency predicts the risk of mortality in patients with COVID-19 undergoing hemodialysis: a retrospective analysis of a single center with nosocomial outbreak.

Background: We experienced a nosocomial outbreak of coronavirus disease 2019 (COVID-19) from November 2020 to February 2021, during the third wave of the pandemic in Japan. Methods: We retrospectively assessed the characteristics and data of 20 inpatients undergoing hemodialysis who were hospitalized for treatment of diseases other than COVID-19 during the COVID-19 nosocomial outbreak ("inpatient," IP), and of 10 outpatients undergoing hemodialysis who were hospitalized for the care of COVID-19 under outpatient visits ("outpatient," OP). Results: Eleven patients in the IP group (55%) and one in the OP group (10%) died. Kaplan-Meier analysis showed that the IP group died more rapidly than the OP group (p = 0.02). Multivariate analysis among all hemodialysis patients showed that the IP group was not at risk of mortality independently; however, the activity of daily life (ADL) dependency was found to be an independent factor in increasing the risk of mortality (hazard ratio: 7.618). Conclusion: Our findings show that the nosocomial infected group has a worse prognosis, although it is not an independent predictor for the risk of mortality. ADL dependency could predict the risk of mortality in all hemodialysis patients with COVID-19 during the third wave pandemic in Japan.

ANCA-Negative Vasculitis in Eosinophilic Granulomatosis with Polyangiitis Complicated with Membranous Nephropathy: A Case Report and Brief Literature Review.

Renal involvement in eosinophilic granulomatosis with polyangiitis (EGPA) typically occurs in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive cases presenting with rapidly progressive renal insufficiency and urinary abnormalities induced by primarily necrotizing crescentic glomerulonephritis (NCGN). Recently, ANCA-negative EGPA has also been reported to manifest with renal involvement, such as NCGN or non-NCGN, including membranous nephropathy (MN). Herein, we report a 70-year-old female who presented with purpura on the lower legs, upper limb numbness, renal dysfunction (eGFR, 20.5 ml/min/1.73 m2), and eosinophilia (eosinophils, 37,570/µl). MPO-and PR3-ANCA were negative, and urinalysis revealed urine protein (0.63 g/day) but without red blood cells in the urine sediment. Thus, she was diagnosed with ANCA-negative EGPA with rapidly progressive renal dysfunction. A renal biopsy revealed vasculitis in the interlobular arteries without NCGN, with the vasculitis being complicated by MN. Micrograph findings on fluorescence immunostaining contained both primary and secondary characteristics of MN (dominance of IgG subclass 4 more than subclass 1 vs. negativity of PLA2R and THSD7A). After treatment with prednisolone, her eosinophil counts normalized, and renal dysfunction improved. Furthermore, urine protein did not increase above 1.0 g/day during the clinical course. This is a rare case of ANCA-negative EGPA presenting with acute renal dysfunction without NCGN and subclinical MN with unknown etiology. It is important to recognize that EGPA pathology varies widely throughout the disease course, and the clinical course of subclinical MN should be carefully assessed in further follow-ups.

The impact of tonsillectomy combined with steroid pulse therapy in patients with advanced IgA nephropathy and impaired renal function.

BACKGROUND: Preventing progression to end-stage renal disease (ESRD) in advanced IgA nephropathy (IgAN) patients with impaired renal function remains challenging. We analyzed the efficacy of tonsillectomy combined with steroid pulse therapy (TSP). METHODS: In this retrospective analysis, IgAN patients with proteinuria > 0.5 g/day and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were divided into three groups: patients treated with TSP (TSP group; n = 23), oral prednisolone (oPSL group; n = 41), and conservative therapy (CONS group, n = 51). We analyzed the clinical and histological backgrounds, remission of urinary findings, and renal survival rate to a 25% decline in eGFR from baseline, and incidence of ESRD. RESULTS: There were significant differences in the patients' backgrounds among the groups. Therefore, we adjusted the background using propensity score marching between TSP group and oPSL or CONS group. The 5-year remission rate of hematuria was significantly higher in the TSP group than in the oPSL group, and that of both hematuria and proteinuria was significantly higher in the TSP group than in the CONS group. The 10-year renal survival rate was significantly higher in the TSP group than in the oPSL and CONS groups. In a multivariate Cox regression analysis, TSP was found to be an independent factor for the 25% decline in eGFR in entire cohort. The adverse effect frequency in the TSP group was similar to the CONS group. CONCLUSIONS: TSP can effectively induce remission of urinary abnormality and improve the prognosis without frequent adverse effects in IgAN patients with impaired renal function.

The beneficial effects of renin-angiotensin system inhibitors (RASI) on IgA nephropathy with tubulointerstitial lesions categorized by Oxford classification.

BACKGROUND: Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin-angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported. METHODS: In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression. RESULTS: After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14-0.47 g/gCre) and it was similar in APA group (0.95-0.85 g/gCre). 20 year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039). CONCLUSION: RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.

The Renoprotective Effects of Docosahexaenoic Acid as an Add-on Therapy in Patients Receiving Eicosapentaenoic Acid as Treatment for IgA Nephropathy: A Pilot Uncontrolled Trial.

Objective Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been reported to have beneficial effects in patients with IgA nephropathy (IgAN). Although DHA and EPA have different mechanisms of action, no study to date has assessed their individual actions in patients with IgAN. This study therefore analyzed the effects administering DHA in addition to EPA for the treatment of IgAN. Methods Twenty-one IgAN patients who were being treated with EPA (1,800 mg/day) were switched to EPA (1,860 mg/day) and DHA (1,500 mg/day). The changes in their clinical parameters from 6 months before to 6 months after switching treatment were analyzed. Results The triglyceride levels did not change during treatment with EPA alone, but tended to decrease-although not to a statistically significant extent-after the switch. The patients' low-density-lipoprotein cholesterol, blood pressure, proteinuria, and hematuria levels were similar before and after switching. The estimated glomerular filtration rate (eGFR) tended to decrease during EPA therapy, but became stable after switching and the median %⊿eGFR changed from -7.354% during EPA therapy to +1.26% during the 6 months after switching to EPA and DHA therapy (p=0.00132), and renal the function remained stable for another 6 months. Moreover, the median %⊿eGFR during the 6 months after switching was significantly higher in comparison to IgAN patients who were treated with EPA alone as a control (-3.26%, p=0.0361). No clinical parameters were independently associated with a stable renal function without switching to DHA/EPA. Conclusion The addition of DHA to EPA stabilized the renal function of IgAN patients, and it seemed that there were pleiotropic effects beyond the improvement of the clinical parameters.

The Improvement of the Outcome of Osmotic Demyelination Syndrome by Plasma Exchange.

A 71-year-old Japanese woman presented with progressive fatigue, lethargy, dysarthria and a gait disorder. Her laboratory data revealed hyponatremia (Na 101 mEq/L), and we started correcting her serum sodium level. Within a few days, she became comatose, bedridden, and was intubated. We diagnosed osmotic demyelination syndrome (ODS) and started performing plasma exchange (PE) on the 39th day of hospitalization. She fully recovered after starting PE, and was discharged on foot unassisted. PE can be a beneficial treatment in patients with chronic ODS.

[Rituximab therapy in the treatment of anti-neutrophil cytoplasmic antibody (ANCA) -positive interstitial pneumonia: case report].

We report a patient treated with rituximab for interstitial pneumonia (IP) associated with microscopic polyangiitis (MPA) and who was undergoing hemodialysis. A 59-year-old woman who had been treated with tacrolimus for 1 year for rheumatic arthritis was referred to the Department of Nephrology for fatigue, fever, weight loss, and rapidly developing renal dysfunction. On the first admission, severe renal dysfunction, proteinuria, hematuria, and an elevated titer of MPO-ANCA were observed, and the woman was diagnosed with rapidly progressive glomerulonephritis because of MPA. At that point, IP was found to be present but not active. Although steroid semipulse therapy following an initial prednisolone (PSL) administration of 40 mg/day, IVCY, and plasma exchange were administered, renal dysfunction did not recover, and the patient required maintenance hemodialysis. Upon discharge, a high titer of MPO-ANCA was continuously observed. Nine months after the initiation of hemodialysis, respiratory discomfort and desaturation developed. Interstitial shadow and ground glass opacity were seen on a CT scan, and the patient was diagnosed with exacerbation of interstitial pneumonia caused by MPA recurrence. At the second admission, acute findings identified by imaging techniques had improved. However, the high titer of MPO-ANCA continued in spite of the steroid semi-pulse therapy following PSL administration, and rituximab corresponding to 200 mg/weekly for 1 month was also administered. The dose of rituximab was decreased subsequently because the patient was judged to be compromised by the hemodialysis. At the same time, internal administration of sulfamethoxazole/trimethoprim was initiated. After the rituximab treatment, MPO-ANCA antibodies gradually decreased, and the respiratory condition improved. Five months after the rituximab treatment, respiratory dysfunction recurred. Based on the CT findings and a high level of ß-D-glycan, the patient was diagnosed with ARDS due to pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment.