A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.

Granulomatous interstitial nephritis with CTLA-4 haploinsufficiency: a case report.

BACKGROUND: Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential inhibitory regulator of immune activation. CTLA-4 haploinsufficiency is known to be associated with dysregulation of FOXP3+ regulatory T cells, hyperactivation of effector T cells, and lymphocytic infiltration of multiple organs. However, there have only been a few reports of renal involvement with CTLA-4. Herein, we present a case of acute granulomatous tubulointerstitial nephritis (TIN) in a patient with CTLA-4 haploinsufficiency. CASE PRESENTATION: A 44-year-old man presented with a 3-week history of fever and malaise, and subsequently developed acute kidney injury (AKI) a few days after treatment with levofloxacin (LVFX). A kidney biopsy and immunohistochemical staining revealed granulomatous TIN with dominantly infiltrating CD4+ T cells. General symptoms and renal impairment showed improvement after discontinuation of LVFX and initiation of oral steroids. However, they worsened following steroid tapering. Further, a colon biopsy analysis showed similar findings to the renal tissue analysis. We suspected that granulomatous TIN was possibly associated with CTLA-4 haploinsufficiency. Therefore, the patient was transferred to another hospital for further treatment of CTLA-4 haploinsufficiency using immunosuppressive agents. CONCLUSIONS: There have been few reports regarding renal involvement of CTLA-4 haploinsufficiency. In the present case, granulomatous TIN could have arisen due to instability of immune regulatory functions, such as CTLA-4 haploinsufficiency, and treatment with LVFX could have triggered immunologic activation and severe inflammation as well as renal dysfunction.

Severe hypokalemia in the emergency department: A retrospective, single-center study.

Background and Aims: Hypokalemia is one of the most common problems in the emergency department (ED). Severe hypokalemia, defined as a serum potassium level ≤2.5 mEq/L, is a relatively uncommon electrolyte disorder, and few studies have reported its prevalence, etiology, symptoms, and management in the ED. Therefore, we aimed to investigate them in this study. Methods: This retrospective single-center study included adult patients whose serum potassium levels were measured in the ED between 2012 and 2019. Data including age, sex, serum potassium levels, and serum creatinine levels were collected from the electronic medical records. Results: The serum potassium levels of 21,616 adult patients were measured. The median age of these patients was 73 years (range: 57-83 years), and 38% were men. The prevalence of severe hypokalemia was 0.4%. The most common symptom of symptomatic severe hypokalemia was weakness (p = 0.001). Malnutrition, use of Japanese herbal medicine, and use of diuretics were the main causes of severe hypokalemia. Sixty-one patients (70%) underwent electrocardiography. Fifty-nine patients (68%) received treatment for severe hypokalemia within one day of the visit. Conclusion: The management of severe hypokalemia in the ED may be suboptimal. Emergency physicians should be vigilant to avoid missing hypokalemia.

Seasonal Changes in the Prevalence of Hyperkalemia in the Emergency Department: A Single Center Study.

Background: Hyperkalemia is an electrolyte disorder frequently encountered in the emergency department. There are few studies on seasonal variation in the prevalence of hyperkalemia. The aim of this study was to investigate the seasonal changes in the prevalence of hyperkalemia in the emergency department. Materials and Methods: We retrospectively reviewed a total of 24,085 patients presented to the emergency department between January 2012 and December 2020. Age, gender, serum potassium level, and serum creatinine level were recorded. The definition used for hyperkalemia was a serum potassium level of ≥ 5.5 mEq/L. Renal function was divided into two categories: preserved (eGFR ≥ 60 mL/min/1.73 m2) or reduced (eGFR < 60 mL/min/1.73 m2). Results: The prevalence of hyperkalemia was 2.1% in patients with preserved renal function and was 11.9% in patients with reduced renal function (p < 0.001). The prevalence of hyperkalemia was highest in winter, followed by spring, autumn, and summer in patients with preserved renal function (p < 0.001) and those with reduced renal function (p < 0.001). There was a linear correlation between monthly weather temperature and the prevalence of hyperkalemia in patients with preserved renal function (r = -0.392; p < 0.001) and those with reduced renal function (r = -0.487; p < 0.001). Conclusions: we found that the prevalence of hyperkalemia was significantly higher in winter for both patients with preserved renal function and those with reduced renal function.

Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis: A case report.

RATIONALE: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. PATIENT CONCERNS: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. DIAGNOSIS: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. INTERVENTIONS: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. OUTCOMES: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. LESSONS: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.

Combined cyclosporine and prednisolone therapy using cyclosporine blood concentration monitoring for adult patients with new-onset minimal change nephrotic syndrome: a single-center pilot randomized trial.

BACKGROUND: Minimal change nephrotic syndrome (MCNS) responds well to steroids, but some patients show frequent relapses. Long-term steroid administration leads to various adverse effects. We previously reported the effectiveness in refractory nephrosis patients of administrating microemulsified CyA (ME-CyA) once before meals and setting the target value of the CyA blood concentration at 2 h after ME-CyA administration (C2) to 600-1200 ng/ml. On this trial we evaluate the effectiveness and safety of ME-CyA for suppressing relapse of adult new-onset MCNS patients using C2 monitoring. METHODS: Adult new-onset MCNS patients were randomly allocated to a ME-CyA + prednisolone group ("CyA + PSL") (n = 11) and a PSL-alone group ("PSL-alone") (n = 10). The drug administration period was 18 months followed by an observation period of 12 months. RESULTS: The duration of remission tended to be longer in CyA + PSL with C2 >600 ng/ml than in PSL-alone (P = 0.112). The relapse rate up to 18 months was significantly lower in CyA + PSL with C2 >600 ng/ml than in PSL-alone (P = 0.02). C2 was significantly higher in the patients with no relapse at 18 months than that in the patients with relapse (P = 0.048). In CyA + PSL, the total dose of PSL was significantly reduced compared with PSL-alone (P = 0.002). Cosmetic adverse effects tended to be fewer in CyA + PSL. CONCLUSIONS: The combination treatment regimen of ME-CyA and PSL with C2 >600 ng/ml has potential to be an important treatment option for adult new-onset MCNS patients. However, after ME-CyA dosage reduction and discontinuation, the relapse rate increased. It is thus necessary to establish a better dose-reduction method.

Impact of vascular access intervention therapy on cardiac load in hemodialysis patients.

Vascular access intervention therapy (VAIVT) has been positioned as the first choice of treatment for stenosis lesions frequently observed in arteriovenous fistula (AVF) for hemodialysis patients in Japan. Furthermore, increased blood flow can provide a stable dialysis. In contrast, it has been reported that excess blood flow of AVF causes high-output heart failure. Although VAIVT is used to increase blood flow of AVF, the impact of VAIVT on cardiac load has been rarely reported. We examined the factors associated with cardiac load in hemodialysis patients undergoing VAIVT by measuring levels of α human atrial natriuretic polypeptide (hANP) and brain natriuretic peptide (BNP) before and after VAIVT. Data were extracted on hemodialysis patients who underwent measurements of αhANP and BNP in before and after VAIVT at our facility and related facilities between February 2014 and December 2014. Nineteeen patients (median age, 73.0 [66.5-80.5] years; male, 52.6%; 36.8% with diabetes; median duration of dialysis treatment, 50.0 [21-109] months) were enrolled in this study. Flow volume of AVF was higher after VAIVT than that before VAIVT (442.0 vs. 758.0 mL/minute, P < 0.001). Moreover, resistance index (RI) of AVF after VAIVT was lower than that before VAIVT (0.61 vs. 0.53, P < 0.01). Although αhANP did not change before and after VAIVT (55.6 vs. 54.9 pg/mL, P = 0.099), BNP after VAIVT was significantly higher than that before VAIVT (145.2 vs. 175.0 pg/mL, P < 0.05). Factors correlated with the increase in BNP were flow volume of AVF before VAIVT (r = -0.458, P = 0.049) and levels of BNP before VAIVT (r = 0.472, P = 0.041). There was no significant correlation between the increase in αhANP with flow volume of AVF before VAIVT, levels of αhANP before VAIVT. Patients with high levels of BNP and low flow volume of AVF before VAIVT were considered to have a high risk of developing heart failure after VAIVT.

Hyponatremic Chloride-depletion Metabolic Alkalosis Successfully Treated with High Cation-gap Amino Acid.

Chloride (Cl)-depletion alkalosis (CDA) develops due to the loss of Cl-rich body fluid, i.e., vomiting or diuretics use, and is typically treated with a chloride-rich solution such as normal saline (NS). Although NS is one of the most utilized Cl-rich solutions, high cation-gap amino acid (HCG-AA) predominantly comprises Cl and less sodium, making HCG-AA more efficient in correcting CDA. We herein report a case of CDA with chronic hyponatremia after frequent vomiting, which was successfully treated with HCG-AA without overcorrecting hyponatremia or causing hypervolemia. HCG-AA may be more beneficial than NS for treating hyponatremic or hypervolemic metabolic alkalosis.

Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD.

BACKGROUND: To improve outcomes in patients with chronic kidney disease (CKD), it is important to identify prognostic factors for end-stage renal disease (ESRD) as well as cardiovascular disease (CVD). This study assessed urinary concentrations of albumin, N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP), as predictors of ESRD and CVD. METHODS: A prospective, observational, multicenter study, comprising 244 Japanese outpatients with CKD who had a follow-up period of at least 3 months. The primary endpoint was the first onset of a nonfatal or fatal CVD event and progression to ESRD, defined as myocardial infarction, stroke, or artery revascularization (coronary, carotid or peripheral), and initiation of dialysis. RESULTS: During a median follow-up of 3.8 years, the primary endpoint occurred in 39 (15.8 %) patients. Irrespective of diabetes, high urinary L-FABP correlated with the development of ESRD and CVD. The areas under the receiver-operator characteristic curves (AUCs) for predicting the primary endpoint for urinary concentrations of L-FABP, albumin, and NAG were 0.825, 0.797, and 0.722, respectively. Cox regression analyses, which were adjusted for factors known to influence the primary endpoint, including patient characteristics, and serum and urinary parameters, demonstrated that the primary outcome was associated with high urinary L-FABP and low eGFR [p = 0.049, hazard ratio = 1.341 (95 % CI 1.005-1.790); and p < 0.000, hazard ratio = 0.953 (95 % CI 0.930-0.976), respectively]. CONCLUSIONS: Urinary L-FABP may be a useful prognostic marker of progression to ESRD and the onset of CVD in patients with CKD.

Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events.

PURPOSE: Contrast medium (CM) induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP) increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP). METHODS: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29). Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. RESULTS: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05) and 24 hours (P<0.005) after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17), but not in those without cardiovascular events (n=12). The parameter with the largest area under the curve (0.816) for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine) between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27-19.13; P=0.021). CONCLUSION: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk stratification of onset of cardiovascular events.

Does elevation of serum creatinine in patients with chronic hepatitis C under therapy of telaprevir mean renal impairment?

AIM: Treatment with telaprevir (TVR) entails adverse side-effects including anaemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C. METHODS: Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (i) patients with an increase in SCr during the treatment (n = 8), and (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were evaluated. RESULTS: Although there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase-in-SCr group during the triple therapy. The SCr level returned to the pre-treatment level after cessation of TVR. There were no differences in urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre-treatment tended to be higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR. CONCLUSION: Elevation of SCr levels with TVR therapy may not suggest renal impairment.

Change in skin perfusion pressure after the creation of upper limb arteriovenous fistula for maintenance hemodialysis access.

Arteriovenous fistula (AVF) is the most important vascular access method for hemodialysis (HD). However, ischemic steal syndrome occasionally develops. This study evaluated the change in skin perfusion pressure (SPP) after the creation of upper limb AVF and analyzed the relationship between blood flow measurements and the change in SPP. The subjects included 21 patients who underwent radiocephalic AVF creation for the first time between November 2012 and September 2013. We measured SPP on the palm side of the third finger of both hands and assessed blood flow measurements using ultrasound examination before and after the creation of AVF. The subjects consisted of 15 men and 6 women (average age: 65.3 ± 12.7 years, including 12 diabetic patients). Observational period between before and after surgery was 4.9 ± 5.2 days. None of the patients had ischemic steal syndrome after the creation of AVF. Skin perfusion pressure tended to decrease after creation of AVF on the finger of AVF side (100.0 ± 20.9 vs. 87.9 ± 26.5 mmHg, P = 0.063). In contrast, SPP did not change in the limb without AVF (97.9 ± 20.7 vs. 101.0 ± 19.4 mmHg, P = 0.615). The rate of change in SPP was significantly decreased on the finger of AVF side compared with that of limb without AVF (0.055% vs. -0.112%, P = 0.014). There was no correlation between the change in SPP and blood flow measurements. Skin perfusion pressure is possible to detect ischemic steal syndrome after the creation of upper limb AVF.

Subcutaneous pathway diversion for peritoneal dialysis catheter salvage.

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.

[Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan].

Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

Urinary liver type fatty acid binding protein in diabetic nephropathy.

Deterioration of diabetic nephropathy (DN) is largely determined by the degree of tubulointerstitial changes rather than the extent of histological changes in the glomeruli. Therefore, a tubular marker that accurately reflects tubulointerstitial damage may be an excellent biomarker for early detection or prediction of DN. Liver-type fatty-acid binding protein (L-FABP) is a 14 kDa small molecule that is expressed in the cytoplasm of human proximal tubules. In vivo experimental studies revealed that renal L-FABP gene expression was up-regulated by various stresses that cause tubulointerstitial damage, such as massive proteinuria, hyperglycemia, hypertension, ischemia and toxins, and that urinary excretion of L-FABP was increased. Recent clinical studies of patients with type 1 or type 2 diabetes demonstrated that urinary excretion of L-FABP derived from proximal tubules is a suitable biomarker for predicting and monitoring deterioration of renal function in DN. Moreover, therapeutic interventions with renoprotective effects reduced urinary L-FABP concentrations. Therefore, urinary L-FABP measured using the Human L-FABP ELISA Kit developed by CMIC Co., Ltd. (Tokyo, Japan) was confirmed as a newly established tubular biomarker by the Ministry of Health, Labour and Welfare in Japan in 2010. This review article summarizes the clinical significance of urinary L-FABP in DN.

Usefulness of urinary biomarkers in early detection of acute kidney injury after cardiac surgery in adults.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery. Urinary liver-type fatty acid-binding protein (L-FABP) reflects the presence of renal tubular injury. The aim of the present study was to evaluate the utility of urinary L-FABP compared with other urinary biomarkers for the early detection of postoperative AKI among adult patients undergoing cardiac surgery. METHODS AND RESULTS: Patients were divided into the AKI (n=48) and non-AKI groups (n=37) according to whether they developed postoperative AKI within 48h after surgery. Changes in various biomarkers were evaluated. Urine and serum samples were obtained from each patient at the following time points: before the operation, immediately after the operation, and 3, 6, 18, 24, and 48h postoperatively. The urinary L-FABP level was significantly higher in the AKI group than in the non-AKI group at every time point, while other biomarkers did not show such a tendency. The biomarker with the largest area under the curve at every time point for predicting the onset of AKI was urinary L-FABP. On multiple logistic regression analysis, the urinary L-FABP level before operation and within the first 6h after cardiac surgery was significantly associated with the onset of AKI. CONCLUSIONS: Urinary L-FABP is a useful biomarker for early detection of AKI and is a good early predictor of the onset of AKI.