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.

Multidisciplinary Team Care Delays the Initiation of Renal Replacement Therapy in Diabetes: A Five-year Prospective, Single-center Study.

Objective Although recent reports have highlighted the benefits of multidisciplinary team care (MTC) for chronic kidney disease (CKD) in slowing the progress of renal insufficiency, its long-term effects have not been evaluated for patients with diabetes mellitus (DM). We compared the renal survival rate between MTC and conservative care (CC). Methods In this five-year, single-center, prospective, observational study, we examined 24 patients (mean age 65.5±12.1 years old, men/women 18/6) with DM-induced CKD stage ≥3 in an MTC clinic. The control group included 24 random patients with DM (mean age 61.0±12.8 years old, men/women 22/2) who received CC. MTC was provided by a nephrologist and medical staff, and CC was provided by a nephrologist. Results In total, 10 MTC and 20 CC patients experienced renal events [creatinine doubling, initiation of renal replacement therapy (RRT), or death due to end-stage CKD]. During the five-year observation period, there were significantly fewer renal events in the MTC group than in the CC group according to the cumulative incidence method (p=0.006). Compared to CC, MTC significantly reduced the need for urgent initiation of hemodialysis (relative risk reduction 0.79, 95% confidence interval [CI] 0.107-0.964). On a multivariate analysis, MTC (hazard ratio [HR], 0.434, 95% CI 0.200-0.939) and the slope of the estimated glomerular filtration rate during the first year (HR, 0.429 per 1 mL/min/m2/year, 95% CI 0.279-0.661) were negatively associated with renal events. Conclusion MTC for DM-induced CKD is an effective strategy for delaying RRT. Long-term MTC can demonstrate reno-protective effects.

Early responsiveness to continuous erythropoietin receptor activator predicts renal prognosis and is determined by a novel antioxidative marker in non-dialysis chronic kidney disease: a prospective, observational, single-center study.

BACKGROUND: Responsiveness to erythropoietin-stimulating agents (ESAs) is important for anemia management in chronic kidney disease (CKD). We assessed the effects of a continuous erythropoietin receptor activator (CERA) on renoprotection beyond anemia management and the correlation between the responsiveness to ESAs and oxidative stress markers in CKD. METHODS: This single-center, prospective, observational study was conducted over 24 months. We administered CERA to 35 non-dialysis patients with hemoglobin (Hb) < 11 g/dL and examined the results of the serum diacron-reactive oxygen metabolite (dROMs) test for oxidative stress markers and biological antioxidant potential (BAP) test for antioxidant markers. We then examined the renoprotective effects of CERA and the responsiveness to CERA. RESULTS: Eighteen patients experienced renal events (doubling of serum creatinine levels, decreased estimated glomerular filtration rate to < 6.0 mL/min/1.73 m2, or initiation of renal replacement therapy), seventeen of which survived. Kaplan-Meier analysis showed that responsiveness to CERA during the initial 3-month treatment period was a good predictor of renal events. Moreover, a high response to CERA during the 3 months independently suppressed renal events (hazard ratio, 0.344). High BAP levels at baseline were significantly associated with high responsiveness to CERA during the initial 3-month treatment period. CONCLUSION: Responsiveness to CERA during the first 3 months was an important indicator of CKD progression. Moreover, BAP test results determined responsiveness to CERA. This is the first report to show how antioxidant levels can be a potential marker of CERA's ability to control anemia in CKD patients.

PKD1 mutation may epistatically ameliorate nephronophthisis progression in patients with NPHP1 deletion.

We report a patient with adult-onset nephronophthisis (NPHP) that was identified a homozygous full gene deletion of NPHP1 and a heterozygous PKD1 mutation. We suggest that the PKD1 mutation may have epistatically ameliorated NPHP disease progression and that the screening of larger cohorts for similar possible epistatic effects is needed.

MMP-9 inhibition by ACE inhibitor reduces oxidized LDL-mediated foam-cell formation.

AIM: Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to block matrix metalloproteinase (MMP)-9 activity, which plays a role in atherogenesis. MMP-9 activity of macrophages is increased during foam cell formation. To investigate the contribution of ACEIs to foam cell formation, we studied the effects of an ACEI, imidaprilat, on THP-1 macrophages and the underlying molecular mechanisms in vitro. METHODS AND RESULTS: Pre-treatment of THP-1 macrophages with imidaprilat (100 nmol/L, 4 hours) significantly decreased foam cell formation induced by oxidized LDL (OxLDL). Imidaprilat reduced the protein level of MMP-9 in THP-1 macrophages and attenuated OxLDL-induced MMP-9 activity in the culture supernatants. Indeed, pretreatment of THP-1 macrophages with an MMP-2/9 inhibitor (20 micromol/L, 4 hours) attenuated OxLDL-induced foam-cell formation. Imidaprilat or the MMP-2/9 inhibitor blocked OxLDL-induced expressions of LOX-1 and scavenger receptor-A (SR-A), but not that of CD36, in THP-1 macrophages. In addition, OxLDL-induced activation of p38 mitogen-activated protein kinase (MAPK) and ERK, but not JNK, was blunted by imidaprilat or the MMP-2/9 inhibitor. Finally, siRNA against MMP-9 inhibited foam cell formation as well as lipid accumulation in THP-1 macrophages. CONCLUSION: These findings suggest that imidaprilat reduces OxLDL-triggered foam-cell formation in THP-1 macrophages via modulation of MMP-9 activity and may indicate a novel antiinflamma-tory mechanism of imidaprilat in atherogenesis.

Dynamic observation of mechanically-injured mouse femoral artery reveals an antiinflammatory effect of renin inhibitor.

OBJECTIVE: The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system. METHODS AND RESULTS: Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6-7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8+/-9.3/10(-2) mm(2)), whereas that was significantly reduced in the mice with aliskiren (18.4+/-4.4, P<0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-alpha-activated HUVECs (P<0.05). Interestingly, TNF-alpha-induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs. CONCLUSIONS: Our in vivo and in vitro findings indicate a pivotal role for renin inhibition in vascular inflammation independent of blood pressure.

The characteristics of relapse in adult-onset minimal-change nephrotic syndrome.

BACKGROUND: Although minimal-change nephrotic syndrome (MCNS) is highly steroid-responsive, the frequency of relapses in some patients is high, necessitating the administration of repeated courses of prednisolone in high doses. It is, therefore, necessary to identify factors that can predict this increased risk of relapse in some patients in order to establish useful treatment methods to reduce the risk. METHODS: To clarify the factors that might increase the risk of relapses, the data of 82 Japanese adult patients with MCNS receiving treatment at our department were analyzed retrospectively. Of the total, 55 patients (67.1%) experienced relapse after showing an initial response. We divided the patients into two groups; namely, the nonrelapse group (n = 27) and the relapse group (n = 55), and compared the clinico-pathophysiological characteristics between the two groups. RESULTS: Significantly increased serum immunoglobulin E (IgE) levels (P = 0.0002) and increased frequency of steroid side effects were observed in the relapse group as compared to the nonrelapse group. CONCLUSIONS: To develop effective therapeutic modalities, it is important to have a thorough understanding of the clinico-pathophysiological characteristics of MCNS patients showing relapse.

Characteristics of patients on hemodialysis therapy for more than 30 years.

Since its experimental introduction in 1960, hemodialysis has become a widely performed and relatively safe procedure. Therapeutic strategies have been developed, and the numbers of long-term survivors of hemodialysis therapy have been increasing. Hemodialysis therapy was introduced at Sangenjaya Hospital in October 1970, and the 16 patients who have survived for more than 30 years on hemodialysis therapy since its introduction at the hospital were enrolled in this study to investigate the characteristics of long-term hemodialysis patients. For comparison, 50 patients on hemodialysis for less than 30 years were also studied (21 patients with <10 years hemodialysis, 13 with 10-20 years hemodialysis and 16 with 20-30 years hemodialysis). Background information (age, gender, and cause of renal disease), dialysis dose (single pool [sp.] Kt/V), mineral metabolism (serum phosphate), anemia management (serum hemoglobin), and nutrition (serum albumin and reduced interdialytic weight gain) were assessed. Hemodialysis was instituted at 28.7 +/- 6.4 years of age. The primary cause of end-stage renal disease was chronic glomerulonephritis in all of the patients except one, and in that patient it was polycystic kidney disease. As an index of the dialysis dose, sp. Kt/V was 1.2 +/- 0.11. As an index of mineral metabolism, serum phosphate was 5.4 +/- 0.9 mg/dL. As an index of anemia management, serum hemoglobin was 10.2 +/- 1.2 g/dL. As indexes of nutrition, serum albumin was 4.0 +/- 0.2 g/dL and interdialytic weight gain was 4.43 +/- 1.36%. The sp. Kt/V-value, serum phosphate, serum hemoglobin and interdialytic weight gain did not differ between the four different hemodialysis duration groups. Serum albumin was lower in the >30 group (4.0 +/- 0.2 g/dL) than in the <10 group (4.2 +/- 0.3 g/dL) (P = 0.046). As the duration of hemodialysis has increased, the age at hemodialysis induction has become younger. The cause of the renal failure was chronic glomerulonephritis in most of the cases. None had diabetic nephropathy. Improvement of the prognosis of patients with diabetic nephropathy is required. Most of the indexes of these patients nearly satisfied the recommended values.

Effect of uni-adrenalectomy on blood pressure in a patient with excessive adrenal 18-hydroxy-11-deoxycorticosterone production bilaterally.

A 46-year-old woman was presented with mineralocorticoid excess syndrome and a large mass originating from the right adrenal gland. Clinical examination before right adrenalectomy revealed elevated serum concentrations of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) both systemically and in the adrenal veins bilaterally. Histopathological and immunohistochemical analyses of the surgical specimen demonstrated adrenal hyperplasia of outer fasciculata cells, and the presence of cystic mass. The adrenalectomy ameliorated her blood pressure (BP) from 156/96 mmHg to 148/87 mmHg with a concomitant increase of serum potassium concentration from 3.1 mEq/l to 3.5 mEq/l. These results suggest that uni-adrenalectomy is, at least in part, effective in ameliorating not only BP but also potassium concentration in a patient of adrenal hyperplasia with excessive bilateral 18-OH-DOC production.