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Background Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. Methods This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal prognosis in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and other antihypertensive drugs-treated group over 2 years. Results Antihypertensive treatment effectively reduced blood pressure from 222 ± 4/142 ± 3 to 140 ± 3/87 ± 2 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 3.3 to 41.1 ± 4.1mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34–0.92] for RASi(+) and RASi(-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB, β-blocker, α-blockers, or diuretics. Conclusions Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with other antihypertensive drugs.

The number of new dialysis patients, particularly among the elderly population, has been globally increasing. In Japan, patients aged ≥65 years and ≥75 years comprised 72% and 45% of patients on dialysis in 2018, respectively. Few studies have reported seasonal variations in the initiation of dialysis. We investigated the seasonal prevalence of the emergent hemodialysis initiation in the elderly.We reviewed 479 elderly patients who initiated hemodialysis between January 2006 and December 2018. Early elderly patients were defined as patients aged between 65 and 74 years, and late elderly patients were defined as those aged ≥75 years. Emergent hemodialysis initiation was defined as initiation with a temporary vascular catheter without elective permanent vascular access or unplanned hemodialysis initiation due to patients requiring critical care regardless of elective permanent vascular access. The information collected included age, sex, and details of the initiation of hemodialysis.The early elderly group consisted of 199 patients, and the late elderly group consisted of 279 patients. In the late elderly group, hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.018). Moreover, emergent hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.009). Emergent hemodialysis initiation due to fluid overload was most frequent in winter, followed by autumn, spring, and summer (p 0.001). Among late elderly patients who initiated hemodialysis, 78% did not have permanent hemodialysis access at the time of the initiation of hemodialysis.In the late elderly group, hemodialysis initiation and emergent hemodialysis initiation were significantly more frequent in the winter than in the remaining seasons. In addition, emergent hemodialysis initiation due to fluid overload was most frequent in winter in the late elderly group.

Hypouricemia in kidney transplant (KT) recipients is rare since they usually have subnormal kidney function which raises serum uric acid level. Recently, interests in pathogenesis of hypouricemia have been increasing due to the understanding of the role of uric acid transporter in renal hypouricemia (RHUC). We herein report the case of RHUC consequently developed in a KT recipient from a living donor with RHUC diagnosed by the detailed urinary and genetic test. A 73-year-old Japanese man underwent KT, and the donor was his wife who had hypouricemia [serum uric acid (S-UA) 0.6 mg/dL]. Nine months after KT, the recipient’s S-UA was low (1.5 mg/dL) with serum creatinine (S-Cr) of 1.56 mg/dL, and fractional excretion of UA (FEUA) was high (59.7%; normal

Introduction: Visceral fat area (VFA) is known to increase after initiation of peritoneal dialysis (PD). However, the factors contributing to the increase in VFA in long-term PD patients have not been sufficiently elucidated. The present study investigated factors that affect VFA in patients who continue PD for ≥3 years. Methods: Twenty patients (63.1 ± 10.3 years, 9 men, 11 diabetic patients) between January 2008 and January 2015 were included. VFA, subcutaneous fat area (SFA) and waist circumference at initiation and follow-up were measured at the level of the umbilicus by computed tomography using an image analysis system. Change in VFA was defined as the value obtained by dividing VFA at the final follow-up by that at the initiation. The correlations between clinical parameters at initiation and changes in VFA were analyzed. Results: There was no significant change in body weight (57.6 ± 10.4 vs 58.3 ± 7.8 kg, P = 0.296) during the mean final follow-up period of 55 ± 13 months, although VFA increased significantly (103.6 ± 39.2 vs 122.6 ± 38.3 cm2, P = 0.030). Although subcutaneous fat area (SFA) did not change (124.7 ± 52.3 vs 124.5 ± 49.2 cm2, P = 0.989), waist circumference increased significantly (79.4 ± 8.4 vs 83.7 ± 6.9 cm, P = 0.010). SFA (r = −0.735, P < 0.001), waist circumference (r = − 0.644, P = 0.002), high-density lipoprotein cholesterol (HDL-C) (r = 0.487, P = 0.029), and age (r = 0.507, P = 0.023) correlated significantly with changes in VFA. Conclusions: VFA might increase with long-term PD in patients with end-stage kidney disease who have high HDL-C, small SFA, and small waist circumference at initiation.

Arteriovenous fistula (AVF) is one of the vascular complications after allograft biopsy, and their reported incidence rates range widely. Transcatheter embolization (TE) is a common AVF treatment in kidney allografts. However, information on AVF incidence and features and TE outcomes in Japanese kidney transplant (KT) recipients is lacking. This study investigated 270 protocol or clinically indicated kidney allograft biopsies in 129 KT recipients during 2010–2016 at a single-center using standardized methods (16-gauge needle and ultrasound guidance). We recorded the incidence and clinical features of AVF using currently recommended standardized methods of allograft biopsy and TE outcomes regarding allograft function up to 12 months after the procedure in Japanese KT recipients. AVF incidence was 2.6% (seven cases). The time from biopsy to AVF diagnosis was 7 (median, interquartile range: 5–117, range: 1–318) days. The time from biopsy to AVF diagnosis was significantly shorter in symptomatic cases (gross hematuria) than in asymptomatic cases (median 6 vs. 117 days, p = 0.034). Symptomatic patients underwent TE within a shorter time (0–6 days) than asymptomatic patients (25–104 days). There were no complications, and allograft function was stable up to 12 months after TE despite using contrast media and partial renal infarction. AVF does occur in certain probabilities. AVF formation can occur without apparent bleeding and exist for a long time after allograft biopsy. TE is a safe and immediate treatment for AVF in kidney allograft.

Background Preeclampsia (PE) refers to the development of hypertension and new-onset proteinuria or progressive organ damage (especially kidney) in a previously normotensive pregnant women after 20 weeks of gestation. Thus, new-onset nephrotic syndrome due to PE before 20 weeks of gestation seems to be rare, making its diagnosis difficult in this time period. Case presentation A 28-year-old woman presented with a new-onset nephrotic syndrome at 16 weeks of gestation. A high dose of oral glucocorticoids (prednisolone, 40 mg) was initiated for presumed glomerulonephritis since she presented with severe nephrotic syndrome before 20 weeks of gestation, however, the treatment was not effective. At 21 weeks of gestation, we confirmed that the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio was very high (sFlt-1, 13,400 pg/mL; PlGF, 21.9 pg/mL; serum sFlt-1/PlGF ratio 611.9). Therefore, we diagnosed nephrotic syndrome due to PE, and oral glucocorticoids were discontinued. After she underwent a cesarean section at 24 weeks & 3 days, we performed a kidney biopsy. Focal segmental sclerotic lesions with epithelial cell hyperplasia and foam cells in the tubular poles were seen on light microscopy. On immunofluorescence tests, C4d staining showed linear peripheral patterns in the glomeruli. Electron microscopy revealed diffuse subendothelial edema with focal foot process effacement. The histological diagnosis was severe glomerular endotheliosis with focal segmental glomerulosclerosis. Furthermore, the histology of placenta was consistent with PE. Eight months after delivery, her proteinuria disappeared completely. Conclusions We not only confirmed an abnormal serum sFlt-1/PlGF ratio but also presented the histology compatible with pure PE in the kidney and placenta in a case of nephrotic syndrome before 20 weeks of gestation. The serum sFlt-1/PlGF ratio may be useful in determining the treatment strategy for atypical cases of pregnant women with nephrotic syndrome, particularly before 20 weeks of gestation.

Hyponatremia is one of the most common electrolyte abnormalities. Overcorrection of severe hyponatremia can result in serious neurological complications such as osmotic demyelination syndrome, but the incidence and risk factors of overcorrection and osmotic demyelination have not been thoroughly investigated.This is a single-center retrospective cohort study of 50 patients admitted through the emergency department with initial serum sodium (serum Na) 125 mEq/L between January 2015 and December 2017. Incidence and risk factors of overcorrection and osmotic demyelination were examined. Overcorrection was defined as an increase in serum sodium concentration 10 mEq/L at 24 h and/or 18 mEq/L at 48 h, respectively.Six patients (12%) and one patient (2%) had overcorrection at 24 h and 48 h, respectively. A total of 5 (10%) patients had a brain MRI completed after overcorrection, and no patient showed radiologic evidence of osmotic demyelination. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection in univariable analysis (p 0.001; p = 0.006, respectively).Among patients admitted with severe hyponatremia, overcorrection occurred in 14%. Symptomatic hyponatremia at presentation and 3% saline use were associated with the risk of overcorrection.

Background: The levels of circulating tumor necrosis factor receptor (TNFR) 1 and 2 help predict the future decline of estimated glomerular filtration rate (eGFR) chiefly in patients with diabetes. It has been recently reported that the change ratio in TNFR1 by SGLT2 inhibitor treatment is also related with future GFR decline in patients with diabetes. The aims of this study are to investigate the association between baseline TNFR levels and early change in TNFR levels by the non-purine selective xanthine oxidase inhibitor, febuxostat, and future eGFR decline chiefly in chronic kidney disease (CKD) patients without diabetes.Methods: We conducted a post-hoc analysis of the FEATHER study on patients with asymptomatic hyperuricemia and CKD stage 3, who were randomly assigned febuxostat 40 mg/day or matched placebo. This analysis included 426 patients in whom baseline stored samples were available. Serum TNFR levels at baseline were measured using enzyme-linked immunosorbent assay. Those levels were also measured using 12-week stored samples from 197 randomly selected patients.Results: Compared with placebo, short-term febuxostat treatment significantly decreased the median percent change from baseline in serum uric acid (−45.05, 95% CI −48.90 to −41.24 mg/dL), TNFR1 (1.10, 95% CI−2.25 to 4.40), and TNFR2 (1.66, 95% CI −1.72 to 4.93), but not TNFR levels. Over a median follow-up of 105 weeks, 30 patients (7.0%) experienced 30% eGFR decline from baseline. In the Cox multivariate model, high levels of baseline TNFR predicted a 30% eGFR decline, even after adjusting for age, sex, systolic blood pressure, high sensitivity C-reactive protein, uric acid, and presence or absence of febuxostat treatment and diabetes, in addition to baseline albumin to creatinine ratio and eGFR.Conclusion: Early change in circulating TNFR levels failed to predict future eGFR decline; however, regardless of febuxostat treatment, the elevated baseline level of TNFR was a strong predictor of 30% eGFR decline even in chiefly non-diabetic CKD patients with asymptomatic hyperuricemia.

High daily pill burden affects quality of life and mortality. High interdialytic weight gain (IDWG) is associated with increased mortality. We examined the association between pill burden and IDWG in hemodialysis patients. This cross-sectional study was conducted in six dialysis centers in Japan in June 2017. The exposure was the number of daily tablets, and outcome was defined as 1 day of relative IDWG divided by post-dialysis weight from the previous session. Among 188 outpatients (mean age, 68.7 [SD, 10.3] years; men, 67.0%; median dialysis vintage, 76.0 [interquartile range, 36.5, 131.5] months), the mean number of daily tablets was 19.7 ± 9.9, and mean relative weight gain was 3.5 ± 1.2%. Multiple linear regression analysis showed a regression coefficient of 0.021 (95% confidence interval: 0.004-0.039), indicating that one additional tablet prescription increased the IDWG by 0.021%. In hemodialysis patients, the daily pill burden was a significant, independent risk for increased relative IDWG.

application/pdf, Nephrology. 2019, 24 (1), P.50-55

Background Hypernatremia is one of the most commonly encountered electrolyte disorders in the emergency department (ED). Few studies have reported the seasonal fluctuations of the prevalence of hypernatremia with conflicting results. We investigated the seasonal prevalence of hypernatremia in an emergency department in Japan. Methods A total of 12,598 patients presented to the ED between January 2015 and December 2017 were reviewed. The adult group aged between 18 and 64 years old consisted of 5427 patients and the elderly group aged over 65 years consisted of 7171 patients. Information collected included age, sex, serum sodium, and serum creatinine. Hypernatremia was defined as a serum sodium leve1 > 145 mEq/L, and moderate to severe hypernatremia was defined as a serum sodium level ≥ 150 mEq/L. Results The prevalence of hypernatremia was significantly higher in the elderly group than in the adult group (2.6% vs. 0.7%; p p r = − 0.34, p = 0.04). Conclusions Hypernatremia is prevalent in the elderly and the prevalence is highest during the winter. Special attention should be paid in the elderly patients to prevent hypernatremia especially in the winter.

The long-term prognosis of patients with IgA nephropathy (IgAN) who present with preserved renal function and minimal proteinuria is not well described. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival and clinical remission. We studied Japanese patients with biopsy-proven IgAN who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and proteinuria

Dysnatremia is one of the most commonly encountered electrolyte disorders in the emergency department (ED). Few studies have reported the prevalence of dysnatremia in elderly patients without chronic kidney disease (CKD). We investigated the prevalence of dysnatremia in elderly patients without CKD in an emergency department in Japan.We reviewed 10,558 patients presenting to the ED between July 2015 and December 2017. The adult group consisted of 4562 patients aged between 18 and 64 years old, and the elderly group consisted of 5996 patients aged over 65 years. Information collected included age, gender, serum sodium and serum creatinine. Hyponatremia was defined as serum sodium level 135 mEq/L, and severe hyponatremia was defined as a serum sodium level 125 mEq/L. Hypernatremia was defined as a serum sodium level 145 mEq/L, and moderate to severe hypernatremia was defined as a serum sodium level ≧ 150 mEq/L.In the adult group, the prevalence of hyponatremia was 2.8% in patients without CKD and 10.3% in patients with CKD (P 0.001). On the other hand, in the elderly group, the prevalence of hyponatremia was 14.8% in patients without CKD and 12.9% in patients with CKD (P = 0.034). In the adult group, the prevalence of hypernatremia was 0.7% in patients without CKD and 2.0% in patients with CKD (P = 0.003). Similarly, in the elderly group, the prevalence of hypernatremia was 1.5% in patients without CKD and 3.5% in patients with CKD (P 0.001).In elderly patients, the prevalence of hyponatremia was higher in patients without CKD than in patients with CKD. Special attention should be paid to elderly patients without CKD in order to prevent severe hyponatremia.

Background Hyponatremia is one of the most commonly encountered electrolyte disorders in emergency department (ED). Seasonal fluctuations of the prevalence of hyponatremia has been reported. We investigated the impact of age on the seasonal prevalence of hyponatremia in the emergency department in Japan. Methods Total of 8377 patients presented to the ED between January 2015 and December 2016 were reviewed. The adult group aged between 18 and 64 years old consisted of 3656 patients and the elderly group aged over 65 years consisted of 4721 patients. Information collected included age, sex, serum sodium, and serum creatinine. Hyponatremia was defined as a serum sodium leve1

Peritoneal dialysis (PD) is recognized as an excellent method of dialysis because the therapy is gentle, continuous, and cost-effective. However, a large number of patients must unfortunately transfer from PD to hemodialysis because of peritonitis or fluid overload in the early phase after PD initiation. In the present study, we reviewed clinical indicators before PD initiation to try to identify predictive factors for early withdrawal from PD.For this retrospective cohort study at two hospitals between March 2003 and October 2016, we defined withdrawal from PD as the induction of combination therapy, transfer to hemodialysis, or death. Data about clinical indicators before PD induction-namely age, sex, presence of diabetes mellitus, past history of cardiovascular disease (CVD), body mass index, primary kidney disease, and blood biochemistry-were collected from medical records. The primary outcome was duration of PD until withdrawal.We analyzed 151 PD patients (median age: 62.5 years; 94 men; 74 with diabetes mellitus; median duration of PD: 30.2 months). Univariate Cox regression analysis showed that the hazard ratio (HR) for withdrawal was 1.08 [95% confidence interval (CI): 1.04 to 1.12; p0.001] per 1 mg/L increase in β

Rationale & Objective Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking. Study Design Randomized, double-blind, placebo-controlled trial. Setting & Participants 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan. Intervention Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks. Outcomes The primary end point was the slope (in mL/min/1.73 m2 per year) of estimated glomerular filtration rate (eGFR). Secondary end points included changes in eGFRs and serum uric acid levels at 24, 48, 72, and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy. Results Of 443 patients who were randomly assigned, 219 and 222 assigned to febuxostat and placebo, respectively, were included in the analysis. There was no significant difference in mean eGFR slope between the febuxostat (0.23 ± 5.26 mL/min/1.73 m2 per year) and placebo (−0.47 ± 4.48 mL/min/1.73 m2 per year) groups (difference, 0.70; 95% CI, −0.21 to 1.62; P = 0.1). Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria (P = 0.005) and for whom serum creatinine concentration was lower than the median (P = 0.009). The incidence of gouty arthritis was significantly lower (P = 0.007) in the febuxostat group (0.91%) than in the placebo group (5.86%). Adverse events specific to febuxostat were not observed. Limitations GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded. Conclusions Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia. Funding Funded by Teijin Pharma Limited. Trial Registration Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.

Background: Sall1 is a transcription factor that best identifies stem cells present in the mouse embryonic kidney. Mutations in Sall1 gene in mice can lead to dysgenesis of kidney, while in humans it results in the Townes-Brocks syndrome, which is associated with the kidney agenesis. Unlike the embryonic kidney, Sall1 expression in the adult kidney is largely unknown. We hypothesized that similar to the embryonic kidney, Sall1 expression can identify stem cells present in the adult kidney. Accordingly in this study, we identified Sall1-expressing cells in the adult mouse kidney, determined their role in kidney regeneration following ischemia-reperfusion injury (IRI), and sought the effect of age on Sall1 expression. Methods and Results: By immunofluorescence Sall1-expressing cells were identified in the proximal tubule at the cortico-medullary junction and constituted 0.5% of all tubular cells. Rare Sall1-positive cells were also identified in the outer cortex and distal tubules. Sall1 expression was not seen in the glomerular, interstitial, or vascular compartments. Following IRI, 90% of Sall1-expressing cells proliferated and 5% of Sall1-positive cells showed asymmetrical cell division with one of the two adjacent Sall1-positive cells incorporating chlorodeoxyuridine (CldU). Following IRI, there was an increase in Sall1 expression at 4 and 12 h, a decrease at 5 and 10 days, and baseline expression at day 30 by quantitative polymerase chain reaction (qRT-PCR) and Western blot analysis. There was no age-related change in Sall1 expression as determined by qRT-PCR, Western blot analysis, and immunofluorescence. Conclusions: We conclude that Sall1-expressing cells are present in the adult mouse kidney, predominantly in the proximal tubules. Sall1-expressing cells proliferate following IRI and some of the Sall1-positive cells undergo asymmetrical cell division. Therefore, Sall1 is a promising marker for identification of stem cells present in the adult mouse kidney.

Post-transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein-Barr virus (EBV) infection. A 70-year-old woman underwent a live unrelated, ABO-incompatible renal transplant for end-stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of 'early lesions of PTLD' according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV-positive PTLD by in situ hybridization for EBER (EBV-encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post-transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Infusion of renal side population (SP) cells, enriched with adult stem-like cells, can ameliorate acute renal failure. We investigated the effects of an angiotensin II type 1 (AT(1)) receptor antagonist, valsartan on SP cell changes in renal injury by ureteral obstruction. Renal SP fraction was reduced by 38%, and the number of cells expressing CD45, a marker of hematopoietic system, in renal SP cells was increased in obstructed kidneys. Valsartan attenuated renal injury and the associated SP profile changes. Angiotensin AT(1) receptor blockade may exert regenerative effect by preserving adult stem-like cells such as SP cells in the kidney.

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.