Hiroo Kawarazaki

Who may not benefit from continuous renal replacement therapy in acute kidney injury

This study aimed to identify factors that may predict early kidney recovery (less than 48 hours) or early death (within 48 hours) after initiating continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. This is a multicenter retrospective observational study of 14 Japanese Intensive care units (ICUs) in 12 tertiary hospitals. Consecutive adult patients with severe AKI requiring CRRT admitted to the participating ICUs in 2010 (n = 343) were included. Patient characteristics, variables at CRRT initiation, settings, and outcomes were collected. Patients were grouped into early kidney recovery group (CRRT discontinuation within 48 hours after initiation, n = 52), early death group (death within 48 hours after CRRT initiation, n = 52), and the rest as the control group (n = 239). The mean duration of CRRT in the early kidney recovery group and early death group was 1.3 and 0.9 days, respectively. In multivariable regression analysis, in comparison with the control group, urine output (mL/h) (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03), duration between ICU admission to CRRT initiation (days) (OR: 0.65, 95% CI: 0.43–0.87), and the sepsis‐related organ failure assessment score (OR: 0.87, 95% CI; 0.78–0.96) were related to early kidney recovery. Serum lactate (mmol/L) (OR: 1.19, 95% CI: 1.11–1.28), albumin (g/dL) (OR: 0.52, 95% CI: 0.28–0.92), vasopressor use (OR: 3.68, 95% CI: 1.37–12.16), and neurological disease (OR: 9.64, 96% CI: 1.22–92.95) were related to early death. Identifying AKI patients who do not benefit from CRRT and differentiating such patients from the study cohort may allow previous and future studies to effectively evaluate the indication and role of CRRT.

Validity of low-intensity continuous renal replacement therapy*.

Objective:To study the hospital mortality of patients with severe acute kidney injury treated with low-intensity continuous renal replacement therapy. Design:Multicenter retrospective observational study (Japanese Society for Physicians and Trainees in Intensive Care), combined with previously conducted multinational prospective observational study (Beginning and Ending Supportive Therapy). Setting:Fourteen Japanese ICUs in 12 tertiary hospitals (Japanese Society for Physicians and Trainees in Intensive Care) and 54 ICUs in 23 countries (Beginning and Ending Supportive Therapy). Patients:Consecutive adult patients with severe acute kidney injury requiring continuous renal replacement therapy admitted to the participating ICUs in 2010 (Japanese Society for Physicians and Trainees in Intensive Care, n = 343) and 2001 (Beginning and Ending Supportive Therapy Beginning and Ending Supportive Therapy, n = 1,006). Interventions:None. Measurements and Main Results:Patient characteristics, variables at continuous renal replacement therapy initiation, continuous renal replacement therapy settings, and outcomes (ICU and hospital mortality and renal replacement therapy requirement at hospital discharge) were collected. Continuous renal replacement therapy intensity was arbitrarily classified into seven subclasses: less than 10, 10–15, 15–20, 20–25, 25–30, 30–35, and more than 35 mL/kg/hr. Multivariable logistic regression analysis was conducted to investigate risk factors for hospital mortality. The continuous renal replacement therapy dose in the Japanese Society for Physicians and Trainees in Intensive Care database was less than half of the Beginning and Ending Supportive Therapy database (800 mL/hr vs 2,000 mL/hr, p < 0.001). Even after adjusting for the body weight and dilution factor, continuous renal replacement therapy intensity was statistically different (14.3 mL/kg/hr vs 20.4 mL/kg/hr, p < 0.001). Patients in the Japanese Society for Physicians and Trainees in Intensive Care database had a lower ICU mortality (46.1% vs 55.3%, p = 0.003) and hospital mortality (58.6% vs 64.2%, p = 0.070) compared with patients in the Beginning and Ending Supportive Therapy database. In multivariable regression analysis after combining the two databases, no continuous renal replacement therapy intensity subclasses were found to be statistically different from the reference intensity (20–25 mL/kg/hr). Several sensitivity analyses (patients with sepsis, patients from Western countries in the Beginning and Ending Supportive Therapy database) confirmed no intensity-outcome relationship. Conclusions:Continuous renal replacement therapy at a mean intensity of 14.3 mL/kg/hr did not have worse outcome compared with 20–25 mL/kg/hr of continuous renal replacement therapy, currently considered the standard intensity. However, our study is insufficient to support the use of low-intensity continuous renal replacement therapy, and more studies are needed to confirm our findings.

Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy

PURPOSE We aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. METHODS This is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. RESULTS Approximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. CONCLUSION Sepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT.

The lower limit of intensity to control uremia during continuous renal replacement therapy

IntroductionThe recommended lower limit of intensity during continuous renal replacement therapy (CRRT) is 20 or 25 mL/kg/h. However, limited information is available to support this threshold. We aimed to evaluate the impact of different intensities of CRRT on the clearance of creatinine and urea in critically ill patients with severe acute kidney injury (AKI).MethodsThis is a multicenter retrospective study conducted in 14 Japanese ICUs in 12 centers. All patients older than 18 years and treated with CRRT due to AKI were eligible. We evaluated the effect of CRRT intensity by two different definitions: daily intensity (the mean intensity over each 24-h period) and average intensity (the mean of daily intensity during the period while CRRT was performed). To study the effect of different CRRT intensity on clearance of urea and creatinine, all patients/daily observations were arbitrarily allocated to one of 4 groups based on the average intensity and daily intensity: <10, 10-15, 15-20, and >20 mL/kg/h.ResultsTotal 316 patients were included and divided into the four groups according to average CRRT intensity. The groups comprised 64 (20.3%), 138 (43.7%), 68 (21.5%), and 46 patients (14.6%), respectively. Decreases in creatinine and urea increased as the average intensity increased over the first 7 days of CRRT. The relative changes of serum creatinine and urea levels remained close to 1 over the 7 days in the “<10” group. Total 1,101 daily observations were included and divided into the four groups according to daily CRRT intensity. The groups comprised 254 (23.1%), 470 (42.7%), 239 (21.7%), and 138 observations (12.5%), respectively. Creatinine and urea increased (negative daily change) only in the “<10“ group and decreased with the increasing daily intensity in the other groups.ConclusionsThe lower limit of delivered intensity to control uremia during CRRT was approximately between 10 and 15 mL/kg/h in our cohort. A prescribed intensity of approximately 15 mL/kg/h might be adequate to control uremia for patients with severe AKI in the ICU. However, considering the limitations due to the retrospective nature of this study, prospective studies are required to confirm our findings.

External Validation for Acute Kidney Injury Severity Scores: A Multicenter Retrospective Study in 14 Japanese ICUs.

Background/Aims: Acute kidney injury (AKI) is associated with high mortality. Multiple AKI severity scores have been derived to predict patient outcome. We externally validated new AKI severity scores using the Japanese Society for Physicians and Trainees in Intensive Care (JSEPTIC) database. Methods: New AKI severity scores published in the 21st century (Mehta, Stuivenberg Hospital Acute Renal Failure (SHARF) II, Program to Improve Care in Acute Renal Disease (PICARD), Vellore and Demirjian), Liano, Simplified Acute Physiology Score (SAPS) II and lactate were compared using the JSEPTIC database that collected retrospectively 343 patients with AKI who required continuous renal replacement therapy (CRRT) in 14 intensive care units. Accuracy of the severity scores was assessed by the area under the receiver-operator characteristic curve (AUROC, discrimination) and Hosmer-Lemeshow test (H-L test, calibration). Results: The median age was 69 years and 65.8% were male. The median SAPS II score was 53 and the hospital mortality was 58.6%. The AUROC curves revealed low discrimination ability of the new AKI severity scores (Mehta 0.65, SHARF II 0.64, PICARD 0.64, Vellore 0.64, Demirjian 0.69), similar to Liano 0.67, SAPS II 0.67 and lactate 0.64. The H-L test also demonstrated that all assessed scores except for Liano had significantly low calibration ability. Conclusions: Using a multicenter database of AKI patients requiring CRRT, this study externally validated new AKI severity scores. While the Demirjians score and Lianos score showed a better performance, further research will be required to confirm these findings.

Safety of Monitoring Viral and Liver Function Markers in Patients With Prior Resolved Hepatitis B Infection After Kidney Transplantation.

BACKGROUND Hepatitis B virus (HBV) infection is a risk factor of mortality in kidney transplant recipients. However, information on the risk of HBV reactivation in kidney recipients with prior resolved HBV infection is limited. This study aimed to evaluate the safety of simply monitoring viral and liver markers in living donor kidney transplantation (LDKT) recipients with prior resolved HBV infection. METHODS We retrospectively examined the clinical records of LDKT recipients. Changes in the levels of alanine aminotransferase, aspartate aminotransferase, hepatitis B surface antigen (HBs Ag), surface antibody, core antibody, and HBV-DNA after transplantation were evaluated, and the occurrence of de novo HBV-related hepatitis and allograft function were monitored. RESULTS Of 61 consecutive LDKT patients, seven had prior resolved HBV infection. Four patients underwent ABO-compatible LDKT, whereas two underwent ABO-incompatible LDKT. The median age was 64 years (range, 61-69 years), and two patients were women. The causes of end-stage kidney disease were diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis. Five patients were referred to hepatologists. The history of HBV vaccination was not confirmed in all patients. Prophylaxis with entecavir was administered to two patients with ABO-incompatible LDKT before transplantation. All patients tested negative for HBs Ag and HBV-DNA throughout observation, and none developed de novo HBV-related hepatitis or graft loss. CONCLUSIONS Patients with HBV infection without HBV DNA positivity are eligible for kidney transplants without antiviral therapy, even those on rituximab therapy. Monitoring viral and liver markers combined with hepatologist consultations may ensure safe follow-up in LDKT recipients with prior resolved HBV infection.

Urinary Tract Reconstruction Using Uretero-Ureteral End-To-Side Anastomosis in Kidney Transplant Recipients

BACKGROUND In kidney transplant recipients, the most widely used method for the reconstruction of the urinary pathway is ureteroneocystostomy, which may be difficult in cases with disused atrophic bladder. In this study, we evaluated kidney transplant recipients who underwent uretero-ureteral end-to-side anastomosis (UUA) in urinary reconstruction due to disused atrophic bladder. METHODS To clarify the effectiveness of this method, we retrospectively reviewed the clinical records of kidney transplant recipients in our hospital. RESULTS A total of 9 recipients with urinary reconstruction using UUA were evaluated. All of these patients had a history of long-term hemodialysis before transplantation, accompanied by complete anuria and small capacity of the bladder. In 4 patients, cranial native ureter was ligated, whereas it was not ligated in the remaining 5 patients. In 2 of 4 patients with cranial ligation, hydronephrosis developed in the native kidney with no further treatment being required. No patients experienced urinary tract complications including hydronephrosis in the graft, urine extravasation, or urinary tract infection in the follow-up period (757.6 ± 491.3 days). Allograft function was maintained well in all patients (serum creatinine level, 1.08 ± 0.23 mg/dL). CONCLUSIONS Although UUA is not a routine method of urinary reconstruction in kidney transplantation, it can be safely performed and should be a surgical option, especially for recipients with disused atrophic bladder. The ligation of cranial native ureter may lead to hydronephrosis of the native kidney, and it is tentatively concluded that UUA without native ureteral ligation is clinically feasible.

Challenges for Preventing the Metabolic Syndrome in Kidney Transplant Recipients, Initial Report: Survey of the Current State of Affairs Before Acting

OBJECTIVE To prevent the metabolic syndrome preventive in kidney transplant recipients, we measured changes in body composition parameters using bioelectrical impedance analysis (BIA), and measuring renal function, blood tests, quality of life, and consciousness of life improvement. The usefulness of BIA was investigated. SUBJECTS AND METHODS Out of all kidney transplant recipients being treated at an outpatient clinic, 20 (13 males and 7 females) gained ≥ 5 kg after transplantation. We investigated changes after 6 months of physical activity versus initiation. RESULTS After the initiation of body composition parameters using BIA, consciousness of life improvement changed, and measured body composition values and blood data did not worsen. Both systolic and diastolic blood pressures tended to decrease after initiation. CONCLUSIONS Detailed visualization of body composition in addition to the body weight and body mass index, as well as guidance based on the results promoted changes in consciousness, enhanced self-efficacy, and increased motivation for the prevention of the metabolic syndrome, suggesting that BIA is a useful tool in the management of weight gain after kidney transplantation.

Validity of low-efficacy continuous renal replacement therapy in critically ill patients

The 1980s saw the use of continuous arteriovenous hemofiltration whose intensity hemofiltration rate was only 3 or 4 mL kg⁻¹ h⁻¹. With the installation of a blood pump, this dose went up to 8 or 10 mL kg⁻¹ h⁻1, and continued to increase, reaching about 20 mL kg⁻¹ h⁻¹ by the year 2000. Some studies found that a higher dose could be beneficial, and the world rapidly followed the trend, increasing the dose up to 35 mL kg⁻¹ h⁻¹. Then, two randomized control trials, namely the VA/NIH Acute Renal Failure Trial Network study and the RENAL study, came along in succession which changed the Kidney Disease: Improving Global Outcomes (KDIGO) recommendation to 20 to 25 mL kg⁻¹ h⁻¹. However, no good evidence exists to support this. Our recent multicenter retrospective studies from the JSEPTIC CRRT database show that the Japanese continuous renal replacement therapy dose of (14.3 mL kg⁻¹ h⁻¹) does not seem to have worse outcomes when compared with a higher dose.

Collagenous Colitis Associated with Rabeprazole in a Peritoneal Dialysis Patient.

endoscopic appearance of CMV colitis is variable; round-shaped ulcers are the most distinctive features, but not specific. The definitive diagnosis requires histopathologic evidence of viral cytopathic effects, and the sensitivity is augmented by immunohistochemistry or polymerase chain reaction (PCR) for CMV deoxyribonucleic acid (DNA) (3,4). The colitis in our patient was not self-limited, but subsequently improved with ganciclovir therapy. A meta-analysis of immunocompetent patients with CMV colitis reported a lower rate of spontaneous remission (18.8%) and a mortality of 56% in individuals with renal failure, diabetes mellitus, pregnancy, or untreated cancer (1). Antiviral therapy is probably beneficial to patients with comorbidities or persistent symptoms. In conclusion, the presence of B. fragilis in PD peritonitis is more commonly associated with intra-abdominal pathologic states, and CMV colitis should be considered even in the absence of immunosuppression.