Continuous Renal Replacement Therapy for a Patient with Severe COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health threat. It is a respiratory disease, and acute kidney injury (AKI) is rare; however, if a patient develops severe AKI, renal replacement therapy (RRT) should be considered. Recently, we had a critically ill COVID-19 patient who developed severe AKI and needed continuous RRT (CRRT). To avoid the potential risk of infection from CRRT effluents, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic material in the effluents by qRT-PCR, and low copy numbers of the viral genome were detected. Due to unstable hemodynamic status in critically ill patients, CRRT should be the first choice for severe AKI in COVID-19 patients. We suggest prevention of clinical infection and control during administration of RRT in the acute phase of COVID-19 patients with AKI or multiple organ failure.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Detection of SARS-CoV-2 in Hemodialysis Effluent of Patient with COVID-19 Pneumonia, Japan.

We report detection of severe acute respiratory syndrome coronavirus 2 RNA in hemodialysis effluent from a patient in Japan with coronavirus disease and prolonged inflammation. Healthcare workers should observe strict standard and contact precautions and use appropriate personal protective equipment when handling hemodialysis circuitry from patients with diagnosed coronavirus disease.

Delirium is independently associated with early mortality in elderly patients starting hemodialysis.

BACKGROUND: Delirium is an independent predictor of death in patients undergoing dialysis for end-stage renal disease (ESRD). However, it is unknown whether delirium during hospitalization at the start of hemodialysis (HD) in elderly populations is associated with early mortality. METHODS: We conducted a retrospective cohort study to investigate the association between delirium and early mortality in the elderly after starting HD. The cohort consisted of patients ≥ 75 years who started dialysis for ESRD at the National Center for Global Health and Medicine from 2010 to 2017 and at Yokosuka Kyosai Hospital from 2007 to 2011. Delirium was defined as patients who showed new symptoms of transient confused thinking and reduced awareness of their environment and were prescribed antipsychotic medications. The primary outcome was death within 1 year. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. A multinomial logistic regression was used to identify the determinants of patients developing delirium. RESULTS: We enrolled 259 patients (males, 60%); 33 patients were diagnosed with delirium. The primary outcome was observed in 19 patients with delirium (58%) and 24 patients without delirium (11%) (p < 0.01). Delirium was independently associated with all-cause mortality within 1 year after starting HD (hazard ratio 7.82, 95% confidence interval 4.26-14.3; adjusted hazard ratio 7.16, 95% confidence interval 3.49-14.7). Delirium was positively correlated with "cognitive impairment" as well as "the use of steroids." CONCLUSION: Delirium is independently associated with early mortality in the elderly after starting HD.

Anion gap predicts early mortality after starting hemodialysis in the elderly.

BACKGROUND: Serum anion gap (AG) has recently been proven to represent a biomarker for predicting prognosis in patients with end-stage renal disease (ESRD). However, whether change in AG (ΔAG) at the time of starting hemodialysis predicts mortality after starting hemodialysis in elderly patients with ESRD remains unknown. METHODS: This retrospective cohort investigated the association between ΔAG and mortality after starting hemodialysis in the elderly. The cohort comprised patients ≥ 75 years old who started hemodialysis for ESRD at National Center for Global Health and Medicine between 2010 and 2017 and at Yokosuka Kyosai Hospital between 2007 and 2011. Patients were stratified into three groups (G1-3) based on ΔAG, calculated according to the equation: ΔAG = sodium - (chloride + bicarbonate) - 12. The primary outcome was death within 1 year of starting hemodialysis. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. RESULTS: We enrolled 254 patients (59% male). Median ΔAG was 2.6 (G1: > 3, n = 111; G2: 0-3, n = 103; G3: < 0, n = 40). The primary outcome was observed in 43 patients. Hazard ratios (HRs) were significantly higher for G1 and G3 than for G2 (G1: HR 2.47, 95% confidence interval 1.13-5.37; G3: HR 3.86, 95% confidence interval 1.62-9.16). Adjusted HRs (aHRs) were significantly higher for G1 and G3 than for G2 (G1: aHR 3.06, 95% confidence interval 1.23-7.62; G3: aHR 3.12, 95% confidence interval 1.10-8.78). CONCLUSIONS: A J-curve phenomenon is evident between ΔAG and early mortality after starting hemodialysis in the elderly.

Accuracy analysis of intrahepatic fat density measurements using dual-energy computed tomography: Validation using a test phantom.

BACKGROUND: Currently, no standardized method for measuring intrahepatic fat density via conventional computed tomography (CT) exists. OBJECTIVE: We aim to quantify intrahepatic fat density via material decomposition analysis using rapid kilovolt peak-switching dual-energy (RSDE) CT. METHODS: Homogenized porcine liver and fat (lard) were mixed in various ratios to produce phantoms for fat density verification. The actual fat density was measured on the basis of the phantom volume and weight, and these measurements were used as reference densities. The fat and liver mass attenuation coefficients, which were used as the material basis pairs, were employed in the material decomposition analysis. Then, the measured fat density of each phantom was compared with the reference densities. RESULTS: For fat content differences exceeding 2%, the measured fat density for the phantoms became statistically significant (p < 0.01). The correlation between the reference densities and RSDE-measured fat densities was reasonably high (R > 0.9997); this indicates the validity of this analysis method. CONCLUSIONS: Intrahepatic fat density can be measured using the mass attenuation coefficients of fat and liver in a material decomposition analysis. Given the knowledge of the accuracy and the limitations found in this study, our method can quantitatively evaluate fat density.

Acute renal failure following exposure to metallic mercury.

Mercury exists in three forms: elemental, inorganic, and organic. Each form produces a unique profile of toxicity. Acute poisoning with inorganic salts is well-known, but few reports are available regarding oral elemental (metallic) mercury intoxication. Ingestion of metallic mercury is usually of no concern because of poor gastrointestinal absorption. We report a very rare case of acute renal failure (ARF) following ingestion of metallic mercury. A 67-year old man swallowed an unknown quantity of metallic mercury in a suicide attempt. He developed severe pneumonitis and ARF with anuria. The whole blood mercury concentration was extremely high (157.7 µg/dl). In this case, inhalation of vaporized mercury might have contributed to the significant systemic absorption, but chelating therapy was not performed because of severe renal failure. Hemodialysis was performed 13 times and discontinued 26 days after mercury ingestion. Consequently, the patient recovered normal renal function.

Multiple myeloma and kidney disease.

Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.

[Case of serious HIV-associated nephropathy resulting in the introduction of hemodialysis].

A previously healthy 46-year-old black man visited the other hospital because of fever, appetite loss and nausea. Renal dysfunction, liver injury, and a highly markedly elevated LDH level were found. Abdominal CT demonstrated enlarged liver, spleen, kidney and lymph nodes. Human immunodeficiency virus (HIV) was serologically positive. His serum BUN, creatinine and potassium were 74.9 mg/dL, 11.78 mg/dL, and 5.6 mEq/L, respectively. After admission, anuria persisted and the progression of renal failure continued despite various treatment methods, necessitating the introduction of maintenance hemodialysis(HD). A kidney biopsy was performed to confirm classical HIV-associated nephropathy (HIVAN). Antiretroviral therapy (ART) was started. Although urine was transiently excreted, HD could not be discontinued. It has been reported that HIVAN is too difficult to treat and that kidney dysfunction seldom recovers. HIVAN is well-known to occur frequently in black HIV-infected patients. However, in Japan, there have been only a few reports describing patients with serious HIVAN and renal failure necessitating HD. We present here a very rare case with HIVAN, with reference to some recent findings.

Adjuvant diagnosis of tuberculosis in hemodialysis patients using fourth generation interferon γ releasing assay.

INTRODUCTION: Dialysis patients have a 10-25 times higher risk of reactivation of tuberculosis (TB). In this study, we investigated the diagnostic ability of QuantiFERON (QFT)-plus for TB in hemodialysis patients. QFT-plus, an interferon gamma release assay, is characterized by its use of CD4 and CD8 T cell signals. METHODS: Hemodialysis patients aged 20 years or older who underwent QFT-plus measurement in our hospital were included, inclusion criteria being fever above 37°C, high inflammatory response, and infiltrative pulmonary shadows. RESULTS: Forty-six patients were enrolled. Of these, 15% were QFT positive, 4% were diagnosed with active TB, 76% were QFT negative, 8% had inconclusive results. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 87.5%, 28%, and 100%, respectively. CONCLUSIONS: QFT-plus may be useful for the diagnosis of active TB in dialysis patients. Further studies in cohorts with larger sample sizes are expected.

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Association of intraoperative gross hematuria with acute kidney injury after cytoreductive surgery.

Objectives: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has been established in the management of peritoneal carcinomatosis. Although it is still necessary to take adequate measures against major postoperative complications including acute kidney injury (AKI), consensus is lacking on how to assess and stratify risk for patients with postoperative AKI after CRS-HIPEC. The aim of this retrospective cohort study was to investigate the association of intraoperative gross hematuria as a surrogate marker of ureter injury with postoperative AKI incidence. Methods: This retrospective cohort study investigated patients without impaired preoperative kidney function who underwent CRS-HIPEC at a single referral center, and evaluated the relationship between intraoperative gross hematuria and incidence of postoperative AKI as defined by the Kidney Disease Improving Global Outcomes practice guidelines. Logistic regression analysis was performed to calculate the odds ratio of intraoperative gross hematuria for AKI, adjusting for confounding factors and other risk factors for AKI. Results: We enrolled 185 patients (males, 37%). Twenty-five patients developed intraoperative gross hematuria. Postoperative AKI occurred in 10 (40%) of 25 patients with hematuria and 28 (17.5%) of 160 patients without hematuria. The crude odds ratio for exposure to hematuria was 3.14 (95% confidence interval, 1.30-7.60; p=0.020) for postoperative AKI. Adjusted odds ratio as estimated by multivariate logistic regression was 4.57 (95% confidence interval, 1.55-13.45; p=0.006). Conclusions: Intraoperative gross hematuria is significantly associated with postoperative AKI incidence after CRS-HIPEC.

Allogeneic islet transplantation with monitoring of islet-specific cellular autoimmunity in a Japanese patient with type 1 diabetes: A case report.

Here, we report a case of allogeneic islet transplantation in Japan. A 48-year-old man received intraportal islet transplantation (5,945 islet equivalent/kg), and stabilization of blood glucose levels and suppression of hypoglycemia were achieved. In the present case, we used our original assessment method to detect the responses of the recipient's T cells to islet autoantigens over time to monitor cellular autoimmunity. Other markers could not predict graft dysfunction in advance, but our method detected the activation of islet antigen-specific CD8+ T-cell responses before the deterioration of pancreatic ß-cell function, indicating the possibility of the non-invasive detection of pancreatic ß-cell damage due to recurrent autoimmunity.

Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy.

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis.

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.

Factors associated with recovery of renal function in patients with multiple myeloma who were treated with hemodialysis.

BACKGROUND: The presence of renal failure in patients with multiple myeloma (MM) has been considered an ominous prognostic factor associated with a significantly decreased life expectancy. The prognostic factors have seldom been analyzed to predict discontinuation of hemodialysis (HD) therapy in MM patients with renal failure after HD initiation. It is clinically very important to predict whether HD can be discontinued after introducing HD in such patients. METHODS: All medical and HD records were reviewed in MM patients who underwent HD in the National Center for Global Health and Medicine Hospital between January 1995 and May 2009. Thirty-two patients with MM had undergone HD. The clinical features and the factors that might be associated with recovery of renal function leading to discontinuation of HD in MM patients with severe renal failure were examined. RESULTS: The factors associated with recovery of renal function and discontinuation of HD were: low International Staging System (ISS) score (p = 0.0034); high response to chemotherapy (p = 0.036); low serum Ca (p = 0.006); low Cr (p = 0.019), and low serum ß2-microglobulin (sß2M) (p = 0.002). On multivariate analysis, low serum Ca and sß2M were significantly associated with HD discontinuation. Moreover, discontinuing HD was the significant factor associated with improved overall survival in MM patients who required HD at least once. CONCLUSION: sß2M and Ca were the laboratory parameters that were significant, independent prognostic factors for predicting the probability of recovery from severe renal failure and discontinuation of HD in MM patients who needed HD at least once.

The First Case of Eosinophilic Granulomatosis with Polyangiitis Simultaneously Demonstrating Various Clinical Manifestations with Retroperitoneal Fibrosis and Membranous Nephropathy.

The first case of eosinophilic granulomatosis with polyangiitis (EGPA) simultaneously demonstrating various clinical manifestations, including retroperitoneal fibrosis (RPF) causing hydronephrosis and membranous nephropathy (MN) leading to nephrotic syndrome, is presented. There have been no previous case reports demonstrating the simultaneous onset of these three disease categories with significant complex pathologies. This case was successfully managed by providing adequate combination therapies according to each disease category, leading to complete remission (CR) of all three diseases. In conclusion, we believe this case is extremely rare and clinically suggestive, and that these findings can be applied to a future phenotype-tailored treatment strategy for EGPA.

Antiepoetin antibody-related pure red cell aplasia: successful remission with cessation of recombinant erythropoietin alone.

An elderly patient with pure red cell aplasia (PRCA) with antierythropoietin (anti-EPO) antibodies is described. PRCA due to alloimmunization is a rare and severe complication of recombinant human erythropoietin (rHu-EPO) therapy. Most reported patients with PRCA were cured primarily by immunosuppressive drug therapy. The patient in this case, however, did not want to receive any immunosuppressive drugs. Therefore, rHu-EPO injection was simply discontinued, the severe anemia gradually improved, and the hemoglobin approached normal range. This case is very rare and significant in that there have been few such elderly patients with rHu-EPO-induced PRCA in whom PRCA remission was achieved, with decreasing antibody titers, after cessation of rHu-EPO alone. Further cases are needed to assess how PRCA should be treated in patients with anti-EPO antibodies.

A Novel Uremic Score Reflecting Accumulation of Specific Uremic Toxins More Precisely Predicts One-Year Mortality after Hemodialysis Commencement: A Retrospective Cohort Study.

Uremic toxins (UTs) generally accumulate in patients developing end-stage renal disease (ESRD). Although some kinds of UTs cause early death after starting hemodialysis (HD), it remains unknown whether the degree of excessive accumulation of various UTs is associated with worsening of prognosis. We retrospectively conducted this cohort study consisting of adult patients developing ESRD who initiated HD at the National Center for Global Health and Medicine from 2010 to 2019. We created a new uremic score, which was defined as the aggregate score of the following variables reflecting uremic state: elevated blood urea nitrogen, ß2-microglobulin, and anion gap before starting HD. The primary outcome was early mortality within 1-year after HD commencement. The hazard ratio (HR) and 95% confidence interval (CI) for a one-point increase in uremic score was calculated with Cox proportional hazard models adjusted by baseline conditions. We included 230 participants, 16 of whom experienced the primary outcome of early mortality after HD commencement. Uremic score was significantly associated with the primary outcome (crude HR: 1.91, 95% CI 1.16-3.14; adjusted HR: 4.19, 95% CI 1.79-9.78). Our novel uremic score, reflecting accumulation of specific UTs, more precisely predicts early mortality after HD commencement.

Quality of life and pain in patients with thalidomide embryopathy in Japan.

BACKGROUND: The aim of this study was to assess psychological/psychiatric problems and quality of life (QOL) in patients with thalidomide embryopathy (TE), with a specific focus on pain, including pain severity and the effects of coping strategies for pain. METHODS: A questionnaire survey was conducted to evaluate the severity of pain experienced by patients with TE, pain management strategies, time perspective, mental health status, and QOL. Of 67 patients with TE who underwent a health checkup, 51 respondents who gave valid responses were included in analysis. RESULTS: GHQ-28 suggested that 41.2% of respondents appeared to potentially have psychiatric disorders. The mean scores of QOL were still within a normal range. There is no significant differences were found between limb disability group and hearing impairment group in QOL or mental health status. About 82.4% of respondents reported that they experience physical pain, and the use of the cognitive coping strategy "catastrophizing" to cope with pain was significantly associated with mental health status and QOL. CONCLUSION: This study demonstrate that although some patients with TE have some form of mental health problem, they still maintain a normal range QOL despite their disabilities. In addition, pain was not as strongly associated with mental health problems and QOL as would be expected, and variables such as "catastrophizing" to cope with pain appear to potentially be associated with reduced mental health and QOL.