Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

Changes in Treatment Conditions for Patients Receiving Hemodialysis at Nippon Medical School Hospital during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic has had an enormous impact on hemodialysis patients. This study investigated changes in hemodialysis treatment at our hospital after the start of the pandemic. METHODS: We analyzed data from the Diagnosis Procedure Combination (DPC) system. Data for inpatients receiving dialysis during collection periods A (before the COVID-19 pandemic) and B (after the start of the COVID-19 pandemic) were extracted and compared. The numbers of inpatients and new patients, the number of patients admitted (by department), duration of stay, mortality, place of residence, surgical procedures, and DPC classification were compared. RESULTS: There were no significant differences between periods in patient age, duration of hospital stay, number of new patients, number of ambulance transports, number of deaths, body mass index, comorbidities, laboratory variables before the first dialysis after hospitalization, or patient area of residence. Although differences were observed among the departments, the numbers of emergency dialysis inpatients and maintenance dialysis inpatients increased. The number of surgeries also increased overall, particularly for maintenance dialysis patients (p = 0.0273). The percentage of DPC III patients was significantly higher in period B (p = 0.0368). CONCLUSIONS: The number of surgeries performed on maintenance dialysis patients and the overall DPC III rate significantly increased after the start of the COVID-19 pandemic at our hospital, suggesting that COVID-19 worsened the condition of maintenance dialysis patients and prolonged hospital stays.

The efficacy and safety of ivabradine hydrochloride in hemodialysis patients with chronic heart failure.

INTRODUCTION: There is little evidence for ivabradine hydrochloride in patients undergoing hemodialysis. METHODS: In this open-label prospective interventional trial of hemodialysis patients with chronic heart failure, during 12 weeks of treatment, changes in Heart rate (HR), frequency of dialysis-related hypotension were examined, and we investigated health-related quality of life (HR-QOL) and adverse effects. RESULTS: 18 patients from 6 facilities were enrolled in the study. HR significantly decreased over time, from 87 ± 12.61/min at baseline to 75.85 ± 8.91/min (p = 0.0003), and systolic blood pressure also increased significantly (p < 0.0001). The frequency of dialysis-related hypotension was markedly reduced (p = 0.0001). The HR-QOL survey showed significant improvements in Social Functioning among others (p = 0.0178). No specific adverse events occurred. CONCLUSION: Ivabradine hydrochloride improved dialysis-related hypotension. Furthermore, the HR-QOL improvement effect were suggested. These results demonstrated the safety and effectiveness of ivabradine hydrochloride.

A possible role of classical complement pathway activation in the pathogenesis of immunoglobulin G nephropathy: a case report.

Immunoglobulin G (IgG) nephropathy refers to a rare group of diseases characterized by deposits of IgG in the mesangial region. However, IgG nephropathy is controversial as a single disease entity, and its pathogenesis remains to be elucidated. In the present report, we discuss a case of IgG nephropathy in which we observed activation of the classical complement pathway.A 47-year-old woman was admitted to our hospital with nephrotic syndrome. Light-microscopic examination revealed neither proliferative nor sclerotic lesions in the glomeruli. However, unusual and large deposits were observed in the paramesangial area. An immunofluorescence study revealed predominant IgG and C1q and slight C3 deposits in the paramesangial area, suggesting immune-complex-type glomerular disease. An electron microscopic study also revealed different sizes of non-organized electron-dense deposits with a similar pattern of distribution, which were accompanied by foot process effacement. Clinically, there was no evidence of systemic diseases, such as infectious or autoimmune diseases (including systemic lupus erythematosus). Based on these findings, she was diagnosed with IgG nephropathy and treated with prednisolone. Steroid therapy was effective, and complete remission was maintained.Additional immunological examination revealed that IgG deposits were polyclonal and consisted mainly of the IgG1 and IgG3 subclasses. Furthermore, staining was positive for C4d and C5b-9. The present findings indicate that the pathogenesis of IgG nephropathy in our patient may have involved activation of the classical complement pathway.

Long-Term Benefits of Treatment with Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Tolvaptan is the first effective drug treatment for autosomal dominant polycystic kidney disease (ADPKD) patients, but few long-term observations of the effects of tolvaptan have been reported. METHODS: In this single center, retrospective cohort study, we investigated nine patients who participated in a phase 3 trial of tolvaptan for ADPKD patients at our hospital between 2008 and 2014. Six of the patients discontinued tolvaptan at the end of the clinical trial and were defined as the discontinuation group, and three continued to take it; these were defined as the continuation group. The observation period was 3 years before and after the end of the tolvaptan trial, and we compared the following data in each group: serum creatinine, estimated glomerular filtration rate (eGFR), total kidney volume, serum sodium concentration, and urine specific gravity. RESULTS: eGFR was significantly improved after the end of the trial in the continuation group (P = 0.0446), but there was no significant change in the regression line before and after the end of the trial in the discontinuation group. The increases in mean total kidney volume rates over the 3 years before and after the trial were 0.01%/year vs. 0.067%/year in the discontinuation group (P = 0.0247). On the other hand, serum sodium concentration and urine specific gravity showed no change during the observation period. CONCLUSION: This study suggested that long-term administration of tolvaptan may improve renal function and inhibit total kidney volume growth.

Risk Factors for Early Peritoneal Dialysis Discontinuation: Importance of Heart Failure.

BACKGROUND: The number of patients on peritoneal dialysis (PD) in our hospital has increased during the past 5 years, but the number discontinuing PD has also increased. The purpose of this study was to identify the risk factors for PD discontinuation by analyzing the association between technical survival period (defined as the duration of PD) and various clinical factors. METHODS: We retrospectively investigated 87 patients who were started on PD at our hospital and attended regularly from April 2015 to March 2020, and we analyzed the association between technical survival period and various clinical factors. We also looked for associations between technical survival period and hospitalizations for heart failure, peritonitis, and exit-site infections among patients undergoing PD. RESULTS: The patients using renin-angiotensin-aldosterone system inhibitors (RASi) (P = 0.0218), those with left ventricular ejection fraction (LVEF) > 50% (P = 0.0194) when they started PD, and those with estimated glomerular filtration rate (eGFR) ≥ 6 (mL/min/1.73 m2) (P = 0.0013) at the initiation of PD showed significantly longer technical survival period, and those who were hospitalized for heart failure had significantly shorter period (P = 0.0008). CONCLUSION: Treatment of RASi, LVEF > 50% and eGFR ≥ 6 mL/ min/1.73 m2 when the initiation of PD and better volume control to prevent ultrafiltration failure and heart failure may improve technical survival period in patients undergoing PD.

Efficacy of a moisturizer for pruritus accompanied by xerosis in patients undergoing dialysis: A multicenter, open-label, randomized verification study.

Xerosis and pruritus are common in patients undergoing dialysis. These symptoms are treated with moisturizers, but limited evidence supports the efficacy of such treatment. Our exploratory study suggested the effectiveness of a heparinoid-containing product for xerosis in dialysis patients. We conducted a multicenter, open-label, randomized, before-after, parallel-group comparative study to verify the exploratory study results (Clinical Trial Registry: UMIN000029360). Seventy-one Japanese patients undergoing dialysis with chronic kidney disease and xerosis were randomly assigned to receive a heparinoid-containing product for 2 weeks (group A [n = 36]) or 8 weeks (group B [n = 35]). Patients were instructed to apply the study product based on the fingertip unit method. The efficacy endpoints were the water content of the stratum corneum (WCSC), skin dryness score, pruritus visual analog scale score, and Dermatology Life Quality Index. Safety was assessed by monitoring adverse events. The mean WCSC (arbitrary units) was 26.0 ± 9.6 in group A and 25.2 ± 10.0 in group B at the start of treatment (week 0), significantly increased to 39.0±12.5 in group A and 38.5 ± 11.0 in group B (P < 0.0001 for both vs week 0) by week 2, and then decreased only in group A. Thus, the WCSC at week 4 (the primary endpoint) remained significantly higher in group B (36.4 ± 12.2 vs 28.8 ± 10.4; P = 0.0068). Other endpoints improved during treatment with the study product. One patient developed a rash and erythema as treatment-related adverse events. In conclusion, 8 weeks' application of a heparinoid-containing product was effective for xerosis in patients undergoing dialysis.

Smoking is a Risk Factor for Endogenous Peritonitis in Patients Undergoing Peritoneal Dialysis.

BACKGROUND: Peritonitis is one of the most common complications in patients undergoing peritoneal dialysis, (PD) but it is difficult to predict or prevent. In this study, we analyzed the risk of endogenous peritonitis in patients receiving PD. METHODS: We included all patients who underwent PD at our hospital from April 2015 to March 2020. There were 22 cases of peritonitis, including 18 cases of endogenous peritonitis without evidence of exit-site infection or technical failure. We evaluated older age, female sex, obesity, diabetes, diverticulosis, and constipation as potential important risk factors for endogenous peritonitis and included these as confounding factors, along with a current or previous history of smoking, in univariate logistic regression models. RESULTS: A previous or current history of smoking (p = 0.0065) was the most significant risk factor for endogenous peritonitis in the univariate logistic regression model. In addition, smoking was the most significant independent risk factor for endogenous peritonitis (p = 0.0034) in multivariate logistic regression models. Diabetes was also significant in univariate and multivariate logistic regression analysis. CONCLUSIONS: Smoking is a significant independent risk factor for endogenous peritonitis in patients undergoing PD. Cessation of smoking may lower the risk of endogenous peritonitis in this patient group.

Lower Limb Ulcer Associated with Peritonitis in Patients Undergoing Peritoneal Dialysis.

PURPOSE: Peritoneal dialysis (PD)-related peritonitis and lower limb ulcer are the important complications in patients undergoing PD. Although the association between lower limb ulcer and peritonitis in patients undergoing PD is unclear, based on our clinical experience and the clinical importance of the complications in patients undergoing PD, we hypothesized that lower limb ulcer is associated with peritonitis in patients on PD. PATIENTS AND METHODS: In this single center, retrospective cohort study, we studied 87 patients who started undergoing PD at our hospital from April 2015 to March 2020. We compared these 8 patients with lower limb ulcer with the other 79 patients without lower limb ulcer. We compared between the patients in the objection period of this study about peritonitis using Log rank test, and used the unpaired t-test and Fisher's exact test to compare the clinical factors between the two groups. Moreover, we used univariate and multivariate logistic regression analyses to study the association of PD-related peritonitis with the clinical factors. RESULTS: The period developed first peritonitis of the patients on PD with lower limb ulcer was significant shorter than those without lower limb ulcer in Log rank test (P = 0.011). The Fisher's exact test and unpaired t-test showed that the difference in the prevalence of PD-related peritonitis (P = 0.009), peritonitis/patient years (P = 0.036), the BMI (P = 0.007) and icodextrin (P = 0.001) were significant. Lower limb ulcer had significant associations with peritonitis in patients on PD in both univariate [odds ratio (OR) 8.461, 95% confidence interval (CI) 1.854-45.60, P = 0.006] and multivariate [OR 7.169, 95% CI 1.519-39.480, P = 0.013] logistic regression analysis. CONCLUSION: In conclusion, lower limb ulcer may be associated with peritonitis in patients undergoing PD. Further large-scale, prospective studies are required to confirm these results.

Peritoneal Catheter Removal for Peritoneal Dialysis-Related Peritonitis Caused by Gram-Negative, Rod-Like Pseudomonas aeruginosa Infection During Antibiotic Therapy for Enterococcus faecalis.

Peritonitis is a common complication of peritoneal dialysis (PD) and can result in PD catheter removal, permanent hemodialysis, and, potentially, death. Prediction and prevention of PD-related peritonitis are thus extremely important. In 2016, the International Society for Peritoneal Dialysis published guidelines for patients with peritonitis undergoing PD. The guidelines cover most cases of PD-related peritonitis caused by bacteria and include clear indications for catheter removal. However, difficulties often arise when deciding the timing of catheter removal. When multiple enteric organisms are identified in a culture of dialysis effluent, peritonitis may be caused by intra-abdominal pathology, which is associated with substantial mortality. In such cases, catheter removal is considered. In this report, we describe a case in which, during antibiotic therapy for PD-related peritonitis due to Enterococcus faecalis alone, the patient developed a relapse of peritonitis caused by a newly detected Gram-negative, rod-like Pseudomonas aeruginosa. He required catheter removal because of the possibility of peritonitis recurrence. Although additional study is required, early catheter removal may be effective when a new organism is detected during antibiotic therapy for PD-related peritonitis caused by an organism not meeting the definition of refractory peritonitis.

Efficacy of a Moisturizer for Pruritus Accompanied With Asteatosis in Dialysis Patients: An Open-Label, Randomized, Exploratory Study.

BACKGROUND: In dialysis patients, skin disorders (dryness and itching) are frequently observed and treated with a moisturizer, in the absence of clear evidence of efficacy. STUDY DESIGN: An open-label, randomized, before/after, parallel-group, comparative/exploratory study. SETTING & PARTICIPANTS: 12 Japanese patients with chronic kidney failure undergoing maintenance hemodialysis who presented with dry skin and itching. INTERVENTION: Patients received a topical heparinoid moisturizer as the study drug for 2 weeks from the first day of the study treatment, followed by either a 2-week washout (group A: 6 participants) or further 2-week treatment (group B: 6 participants). OUTCOMES: The primary end point was change in water content in the stratum corneum in the hypochondrium. Secondary end points included change in visual analogue scale itching score and subjective evaluations of symptoms. To evaluate safety, adverse events were also investigated. MEASUREMENTS: Water content of the stratum corneum, dryness/itching improvement rating, itching visual analogue scale/duration of itching, photographic evaluation of skin symptoms, principal investigator's overall assessment of study drug, and adverse events. RESULTS: Mean water content of the stratum corneum in the combined groups significantly increased at week 2 (51.2 arbitrary units [AU] vs treatment start day, 31.6 AU; P<0.001), but significantly decreased at week 4 in group A, in which patients discontinued treatment with the study drug (39.4 AU; P = 0.005). Other efficacy end points, including the visual analogue scale itching score, were also improved by treatment with the study drug, but such improvement was not sustained after discontinuation of treatment. There were no adverse events related to the study treatment. LIMITATIONS: Only Japanese patients were included in the study, with a small sample size. CONCLUSIONS: Continuous application of the topical heparinoid moisturizer increased water content in the stratum corneum and lessened itching in dialysis patients. FUNDING: Maruho Co, Ltd. TRIAL REGISTRATION: Registered at the University Hospital Medical Information Network Clinical Trials Registry with study number UMIN000017016.

Comparison of immunosuppressive therapies for IgA nephropathy after tonsillectomy: three-course versus one-course steroid pulse combined with mizoribine.

PURPOSE: It has been reported that steroid pulse therapy for IgA nephropathy improves renal prognosis. However, because of the side effects, steroid dose must be restricted to some cases. Treatment effects of steroid on cases already presenting with reduced renal function are unknown. In this study, we performed tonsillectomy in patients with IgA nephropathy and conducted a comparative study about subsequent immunosuppressive therapy. METHODS: Subjects were patients younger than 70 years of age diagnosed with IgA nephropathy by renal biopsy. Treatment protocols were a single-course steroid pulse combined with mizoribine during a period from August 2006 to June 2010 (Group A; n = 34) and a three-course steroid pulse during a period from July 2010 to March 2013 (Group B; n = 32). Primary end points were excretory amounts of proteinuria, disappearance of proteinuria and hematuria, and exacerbation of renal function. RESULTS: In both the groups, proteinuria decreased significantly 12 months after treatment, and no significant difference in alleviation effects on proteinuria was found between groups. eGFR increased significantly 12 months after treatment in Group A, whereas it tended to decrease in Group B. As for the preservation effect on eGFR, Group A showed significantly higher preservation of eGFR. Similar results were shown in the patients whose eGFR at the start of the treatment was less than 60 mL/min/1.73 m(2). CONCLUSIONS: Single-course steroid pulse therapy combined with mizoribine was considered to have a protective effect on the renal function in IgA nephropathy, especially accompanying renal dysfunction.

[Diuretic agent].

This clause explains a diuretic as an antihypertensive agent. A diuretic is a medicine used as a first-line agent also in the present. As an antihypertensive agent, a thiazide-type diuretic drug is used in many cases. Use of furosemide is not recommended other than a chronic kidney disease patient. Considering future medical economics, it is desirable to use a diuretic drug positively.

A case of secondary focal segmental glomerulosclerosis associated with malignant hypertension.

Focal segmental glomerulosclerosis (FSGS) is associated with various clinicopathological conditions, including hypertension. We report here a case of secondary FSGS associated with malignant hypertension. A 33-year-old man with a 1-month history of visual impairment and headache visited the Department of Ophthalmology at our hospital and was found to have hypertensive retinopathy and severe hypertension (230/160 mmHg). He was referred to our department based on suspected renal dysfunction. His blood pressure on admission was 250/130 mmHg. Physical examination and laboratory tests revealed hypertensive cardiac dysfunction, focal brain edema, renal dysfunction (serum creatinine, Cr 7.07 mg/dl, blood urea nitrogen, BUN 49.9 mg/dl), massive proteinuria (10.7 g/day), and thrombotic microangiopathy. Funduscopy showed exudate, hemorrhage, and papilledema. The cause of secondary hypertension could not be identified. He was treated for primary malignant hypertension, but required hemodialysis 3 days after admission due to anuria. Treatment with antihypertensive agents resulted in the gradual recovery of renal function, although heavy proteinuria continued with nephrotic syndrome. Renal biopsy performed 1 month after admission showed features of malignant nephrosclerosis with secondary FSGS. Hemodialysis was discontinued following further improvement in renal function and the most recent laboratory tests showed proteinuria 1.8 g/day and persistent renal dysfunction (BUN 36.5 mg/dl, Cr 3.14 mg/dl). Malignant hypertension may cause various injuries, including glomerular endothelial and epithelial cell injuries in glomerular hypertension and hyperfiltration, increase of the renin-angiotensin-aldosterone system, and endothelial-epithelial interaction, resulting in the development of secondary FSGS and heavy proteinuria.

A patient with idiopathic cholesterol crystal embolization: effectiveness of early detection and treatment.

A 72-year-old man was admitted to our hospital because of progressive renal dysfunction persisting for 1.5 months. Physical examination showed livedo reticularis of the toes of both feet, peripheral edema, and gait disturbance due to the toe pain. The levels of blood urea nitrogen (50.0 mg/dL) and creatinine (2.81 mg/dL) were elevated, and eosinophilia (10%, 870/µL) was noted. A biopsy of the area of livedo reticularis revealed cholesterin crystals. The patient had not undergone angiography, anticoagulation therapy, or antithrombotic treatment. Idiopathic cholesterol crystal embolization was diagnosed. Transesophageal echocardiography revealed intimal thickening of the aorta and plaque. Oral steroid therapy was started because of the progressive renal dysfunction. After steroid therapy, the symptoms improved. Early diagnosis and treatment are important. Renal dysfunction is a common symptom in elderly patients. Cholesterol crystal embolization should also be considered as a cause of unexplained renal dysfunction, especially in such patients.

[Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis].

It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three courses of steroid semi-pulse therapy and post therapy with steroids and MZR were combined, his proteinuria and serum Cre level decreased and stagnated ascites markedly decreased. The two cases were diagnosed as having secondary IgA nephropathy induced by the deposition of the IgA1 derived mainly from the intestinal tract, which had increased in the blood due to alcoholic liver cirrhosis. Active use of immune system suppressor therapy was effective.

Methylprednisolone pulse therapy combined with mizoribine following tonsillectomy for immunoglobulin A nephropathy: clinical remission rate, steroid sparing effect, and maintenance of renal function.

BACKGROUND: The long-term prognosis of immunoglobulin A nephropathy (IgAN) is reportedly poor. In Japan, tonsillectomy-steroid pulse therapy has frequently been used for treatment of early IgAN, with favorable outcomes. However, steroid usage is sometimes limited due to adverse reactions. To reduce the total dose of steroids, we have been using mizoribine (MZR) in combination with tonsillectomy-steroid pulse therapy since 2004. Here we report a retrospective evaluation of our protocol outcome. METHODS: Forty-two patients aged <70 years with histopathologically confirmed IgAN and an estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m(2) or higher were enrolled. After giving informed consent, all the patients underwent bilateral tonsillectomy. One week later, intravenous methylprednisolone pulse therapy (500 mg/day) was administered for 3 days, followed by oral prednisolone (30 mg/day and tapered to 0 over 7 months) and MZR (150 mg/day for 11 months). The complete remission (CR) rate and renoprotective effect were assessed. RESULTS: The CR rate at 6, 12, and 24 months was 33.3, 69.1, and 76.2%, respectively. Despite a relatively low total steroid dose, renal function was satisfactorily maintained for 24 months or longer with no relapse. The eGFR in patients with stage 3 chronic kidney disease was significantly improved at 6 months after start of treatment. Three patients (7.1%) had mild and transient adverse events. CONCLUSION: This protocol appears to be highly effective and safe for IgAN patients with renal dysfunction.