Cytomegalovirus Retinitis in a Patient Taking Upadacitinib: A Case Report.

Upadacitinib is a relatively new drug used to treat autoimmune diseases. However, patients treated with upadacitinib may develop infections. We report a case of cytomegalovirus (CMV) retinitis that developed during upadacitinib administration. A 79-year-old woman presented with progressively decreasing vision in both eyes. Her decimal best-corrected visual acuity (BCVA) was 0.2 in the right and 0.01 in the left eye. The patient was taking upadacitinib for one year. Fundus examination revealed vitreous opacities and extensive white retinal lesions with hemorrhage in both eyes. CMV was detected in the anterior aqueous humor, vitreous humor, and blood samples. We diagnosed her with panuveitis and CMV retinitis, performed a vitrectomy in both eyes, and administered intravenous ganciclovir and steroids. After treatment, her BCVA improved to 0.6 in the right and 0.1 in the left eye. Ophthalmologists and physicians should be aware of CMV infections in patients being treated with upadacitinib.

The use of anti-adrenergic agents as a predictor of acute kidney injury and delayed recovery of kidney function: the NARA-AKI cohort study.

Association of preoperative regular use of anti-adrenergic agents with postoperative acute kidney injury (AKI) and with trajectory of kidney function after AKI is still unknown. In a retrospective cohort study, adults undergoing non-cardiac surgery under general anesthesia were included. Obstetric or urological surgery, missing data, or preoperative dialysis was excluded. The exposure of interest was preoperative regular use of anti-adrenergic agents. The outcomes were AKI within 1 week postoperatively and trajectories of kidney function within 2 weeks postoperatively among patients with AKI. Multivariable logistic regression models were used to examine the association of anti-adrenergic agents with AKI. Linear mixed-effects models were used to compare the trajectories of postoperative kidney function after AKI between patients with and without anti-adrenergic agents. Among 5168 patients, 245 had used anti-adrenergic agents. A total of 309 (6.0%) developed AKI, and the use of anti-adrenergic agents was independently associated with postoperative AKI even after adjustment for preoperative and intraoperative potential confounders [odds ratio (95% confidence interval): 1.76 (1.14-2.71)]. The association was similar across preexisting hypertension or cardiovascular disease. Analyses restricted to patients with AKI suggested that the timing and stage of AKI were similar among those with and without anti-adrenergic agents; however, the recovery of kidney function was delayed among those with anti-adrenergic agents (P for interaction = 0.004). The use of anti-adrenergic agents was associated with postoperative AKI and delayed recovery of kidney function after AKI. Temporary withdrawal of anti-adrenergic agents during perioperative periods may contribute to prevent AKI and shorten the duration of AKI.

Risk of Lactic Acidosis in Hospitalized Diabetic Patients Prescribed Biguanides in Japan: A Retrospective Total-Population Cohort Study.

Patient data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) are used to assess the effect of biguanide administration on rates of lactic acidosis (LA) in hospitalized diabetes mellitus (DM) patients. In this retrospective cohort study (from April 2013 to March 2016), we compare DM inpatients prescribed biguanides to DM inpatients who were not prescribed biguanides to quantify the association between biguanides and incidence of LA. In total, 8,111,848 DM patient records are retrieved from the NDB. Of the 528,768 inpatients prescribed biguanides, 782 develop LA. Of the 1,967,982 inpatients not prescribed biguanides, 1310 develop LA. The rate ratio of inpatients who develop LA and are administered biguanides to those who developed LA without receiving biguanides is 1.44 (95% CI, 1.32-1.58). Incidence rates and rate ratios for both sexes are elevated in the group prescribed biguanides for patients aged 70 years and older, markedly in those 80 years and older: 40.12 and 6.31 (95% CI, 4.75-8.39), respectively, for men and 34.96 and 5.40 (95% CI, 3.91-7.46), respectively, for women. Biguanides should be used conservatively in patients older than 70 years, particularly for those with comorbidities, and with caution in patients 80 years and older.

Kidney function at 3 months after acute kidney injury is an unreliable indicator of subsequent kidney dysfunction: the NARA-AKI Cohort Study.

BACKGROUND: The relationship between kidney function at 3 months after acute kidney injury (AKI) and kidney function prognosis has not been characterized. METHODS: This retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia. Exclusion criteria included obstetric or urological surgery, missing data and preoperative dialysis. Linear mixed-effects models were used to compare estimated glomerular filtration rate (eGFR) slopes in patients with and without AKI. Multivariable Cox proportional hazard models were used to examine the associations of AKI with incident chronic kidney disease (CKD) and decline in eGFR ≥30%. RESULTS: Among 5272 patients, 316 (6.0%) developed AKI. Among 1194 patients with follow-up creatinine values, eGFR was stable or increased in patients with and without AKI at 3 months postoperatively and declined thereafter. eGFR decline after 3 months postoperatively was faster among patients with AKI than among patients without AKI (P = .09). Among 938 patients without CKD-both at baseline and at 3 months postoperatively-226 and 161 developed incident CKD and a decline in eGFR ≥30%, respectively. Despite adjustment for eGFR at 3 months, AKI was associated with incident CKD {hazard ratio [HR] 1.73 [95% confidence interval (CI) 1.06-2.84]} and a decline in eGFR ≥30% [HR 2.41 (95% CI 1.51-3.84)]. CONCLUSIONS: AKI was associated with worse kidney outcomes, regardless of eGFR at 3 months after surgery. Creatinine-based eGFR values at 3 months after AKI might be affected by acute illness-induced loss of muscle mass. Kidney function might be more accurately evaluated much later after surgery or using cystatin C values.

Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Predictors of early remission of proteinuria in adult patients with minimal change disease: a retrospective cohort study.

Previous studies reported conflicting results regarding an association between serum albumin concentration and the cumulative incidence of remission of proteinuria in adult patients with minimal change disease (MCD). The present study aimed to clarify the clinical impact of serum albumin concentration and the cumulative incidence of remission and relapse of proteinuria in 108 adult patients with MCD at 40 hospitals in Japan, who were enrolled in a 5-year prospective cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study (JNSCS). The association between serum albumin concentration before initiation of immunosuppressive treatment (IST) and the cumulative incidence of remission and relapse were assessed using multivariable-adjusted Cox proportional hazards models. Remission defined as urinary protein < 0.3 g/day (or g/gCr) was observed in 104 (96.3%) patients. Of 97 patients with remission within 6 month of IST, 42 (43.3%) developed relapse defined as ≥ 1.0 g/day (or g/gCr) or dipstick urinary protein of ≥ 2+. Serum albumin concentration was significantly associated with remission (multivariable-adjusted hazard ratio [95% confidence interval] per 1.0 g/dL, 0.57 [0.37, 0.87]), along with eGFR (per 30 mL/min/1.73 m2: 1.43 [1.08, 1.90]), whereas they were not associated with relapse. A multivariable-adjusted model showed that patients with high eGFR level (≥ 60 mL/min/1.73 m2) and low albumin concentration (≤ 1.5 g/dL) achieved significantly early remission, whereas those with low eGFR (< 60 mL/min/1.73 m2) and high albumin concentration (> 1.5 g/dL) showed significantly slow remission. In conclusion, lower serum albumin concentration and higher eGFR were associated with earlier remission in MCD, but not with relapse.

Time to remission of proteinuria and incidence of relapse in patients with steroid-sensitive minimal change disease and focal segmental glomerulosclerosis: the Japan Nephrotic Syndrome Cohort Study.

BACKGROUND: Minimal change disease (MCD) is characterized by a nephrotic syndrome usually steroid-sensitive and a high incidence of relapse of proteinuria. Previous cohort studies have reported conflicting results regarding the association between the time to remission and incidence of relapse. METHODS: This multicenter prospective cohort study included 102 adult patients with steroid-sensitive MCD or focal segmental glomerulosclerosis from a 5-year cohort study of primary nephrotic syndrome, the Japan Nephrotic Syndrome Cohort Study, who achieved remission of proteinuria within 2 months of immunosuppressive therapy (IST). The association between the time to remission of proteinuria after immunosuppressive therapy and incidence of relapse was assessed using Cox proportional hazards models adjusted for clinically relevant factors. RESULTS: Remission was observed at 3-7, 8-14, 15-21, 22-28, and 30-56 days after initiation of immunosuppressive therapy in 17 (16.7%), 37 (36.3%), 21 (20.6%), 13 (12.7%), and 14 (13.7%) patients, respectively. During a median observation period of 2.3 years after the end of the 2nd month after initiation of immunosuppressive therapy, 46 (45.1%) patients relapsed. The time to remission was associated with the incidence of relapse in an inverse U-shaped pattern (multivariable-adjusted hazard ratios [95% confidence intervals] of the time to remission of 3-7, 8-14, 15-21, 22-28, 30-56 days: 1.00 [reference], 1.76 [0.56, 5.51], 6.06 [1.85, 19.80], 5.46 [1.44, 20.64], and 2.19 [0.52, 9.30], respectively). CONCLUSION: The time to remission was identified as a significant predictor of relapse in steroid-sensitive patients.

Association of initial prednisolone dose with remission, relapse, and infectious complications in adult-onset minimal change disease.

BACKGROUND: A dose of 0.5-1 mg/kg/day of prednisolone (PSL) is administered for the initial treatment of minimal change disease (MCD). However, little is known about the optimal PSL dose for the initial treatment of MCD. METHODS: We conducted a retrospective multicenter cohort study of treatment-naive adult patients with MCD diagnosed by renal biopsy from 1981 to 2015 in whom PSL monotherapy was performed as the initial treatment. The exposure of interest was an initial median PSL dose of < 0.63 mg/kg/day (Group L) compared to ≥ 0.63 mg/kg/day (Group H). Cumulative remission and relapse after remission were compared between these groups using Cox regression adjusted for baseline characteristics. RESULTS: Ninety-one patients met the inclusion criteria. During a median follow-up of 2.98 years, 87 (95.6%) patients achieved complete remission, and 47.1% relapsed after remission. There was no significant difference in the remission rate between the groups at 4 weeks of follow-up (66.7 vs. 82.6%). The median time to remission in Group L was comparable to that in Group H (17.0 vs. 14.0 days). A multivariable Cox hazard model revealed that the initial PSL dose was not a significant predictor of remission. The cumulative steroid doses at 6 months, 1 year, and 2 years after treatment initiation were significantly lower in Group L than in Group H. CONCLUSION: The initial PSL dose was not associated with time to remission, remission rate, time to relapse, or relapse rate. Therefore, a low initial steroid dose may be sufficient to achieve remission.

External Validation of a Prediction Model for Acute Kidney Injury Following Noncardiac Surgery.

Importance: The Simple Postoperative AKI Risk (SPARK) index is a prediction model for postoperative acute kidney injury (PO-AKI) in patients undergoing noncardiac surgery. External validation has not been performed. Objective: To externally validate the SPARK index. Design, Setting, and Participants: This single-center retrospective cohort study included adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011. Those with obstetric or urological surgery, estimated glomerular filtration rate (eGFR) of less than 15 mL/min/1.73 m2, preoperative dialysis, or an expected surgical duration of less than 1 hour were excluded. The study was conducted at Nara Medical University Hospital. Data analysis was conducted from January to July 2021. Exposures: Risk factors for AKI included in SPARK index. Main Outcomes And Measures: PO-AKI, defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours or 150% compared with preoperative baseline value or urine output of less than 0.5 mL/kg/h for at least 6 hours within 1 week after surgery, and critical AKI, defined as either AKI stage 2 or greater and/or any AKI connected to postoperative death or requiring kidney replacement therapy before discharge. The discrimination and calibration of the SPARK index were examined with area under the receiver operating characteristic curves (AUC) and calibration plots, respectively. Results: Among 5135 participants (2410 [46.9%] men), 303 (5.9%) developed PO-AKI, and 137 (2.7%) developed critical AKI. Compared with the SPARK cohort, participants in our cohort were older (median [IQR] age, 56 [44-66] years vs 63 [50-73] years), had lower baseline eGFR (median [IQR], 82.1 [71.4-95.1] mL/min/1.73 m2 vs 78.2 [65.6-92.2] mL/min/1.73 m2), and had a higher prevalence of comorbidities (eg, diabetes: 3956 of 51 041 [7.8%] vs 802 [15.6%]). The incidence of PO-AKI and critical AKI increased as the scores on the SPARK index increased. For example, 10 of 593 participants (1.7%) in SPARK class A, indicating lowest risk, experienced PO-AKI, while 53 of 332 (16.0%) in SPARK class D, indicating highest risk, experienced PO-AKI. However, AUCs for PO-AKI and critical AKI were 0.67 (95% CI, 0.63-0.70) and 0.62 (95% CI, 0.57-0.67), respectively, and the calibration was poor (PO-AKI: y = 0.24x + 3.28; R2 = 0.86; critical AKI: y = 0.20x + 2.08; R2 = 0.51). Older age, diabetes, expected surgical duration, emergency surgery, renin-angiotensin-aldosterone system blockade use, and hyponatremia were not associated with PO-AKI in our cohort, resulting in overestimation of the predicted probability of AKI in our cohort. Conclusions and Relevance: In this study, the incidence of PO-AKI increased as the scores on the SPARK index increased. However, the predicted probability might not be accurate in cohorts with older patients with more comorbidities.

Incidence of lower limb amputation in people with and without diabetes: a nationwide 5-year cohort study in Japan.

INTRODUCTION: This study was conducted to investigate the incidence and time trend of lower limb amputation (LLA) among people with and without diabetes. RESEARCH DESIGN AND METHODS: This retrospective population-based cohort study was based on the national claims data in Japan, comprising a total population of 150 million. Data of all individuals who had LLA from April 2013 to March 2018 were obtained. We analysed the sex-adjusted and age-adjusted annual LLA rate (every fiscal year) in people with and without diabetes for major and minor amputation. To test for time trend, Poisson regression models were fitted. RESULTS: In the 5-year period, 30 187 major and 29 299 minor LLAs were performed in Japan. The sex-adjusted and age-adjusted incidence of major and minor LLAs was 9.5 (people with diabetes, 21.8 vs people without diabetes, 2.3, per 100 000 person-years) and 14.9 (people with diabetes, 28.4 vs people without diabetes, 1.9, per 100 000 person-years) times higher, respectively, in people with diabetes compared with those without. A significant decline in the annual major amputation rate was observed (p<0.05) and the annual minor amputation rate remained stable (p=0.63) when sex, age and people with and without diabetes were included as dependent variables. CONCLUSIONS: This is the first report of the national statistics of LLAs in Japan. The incidence of major and minor LLAs was 10 and 15 times higher, respectively, in people with diabetes compared with those without. A significant decline in the major amputation rate was observed, and the annual minor amputation rate remained stable during the observation period. This information can help to create an effective national healthcare strategy for preventing limb amputations, which affect the quality of life of patients with diabetes and add to the national healthcare expenditure.

Anemia following acute kidney injury after noncardiac surgery and long-term outcomes: the NARA-AKI cohort study.

Background: This study was conducted to investigate whether acute kidney injury (AKI) is an independent predictor of anemia and whether anemia following AKI is a mediator of mortality after AKI. Methods: This is a retrospective cohort study. Adults with noncardiac surgery from 2007 to 2011 were included. Obstetric or urological surgery, missing data or preoperative dialysis were excluded. Subjects were followed until the end of 2015 or lost to follow-up. Exposures of interest were postoperative AKI. Outcome variables were hematocrit values at 3, 6 and 12 months postoperatively and mortality. Associations between AKI and hematocrit or association between AKI and mortality were examined by multivariable linear regression or Cox regression, respectively. Results: Among 6692 subjects, 445 (6.6%) developed AKI. Among those with postoperative data, AKI was independently associated with lower hematocrit at 3, 6 and 12 months postoperatively, with coefficients of -0.79 [95% confidence interval (CI) -1.47 to -0.11; n = 1750], -1.35 (-2.11 to -0.60; n = 1558) and -0.91 (-1.59 to -0.22; n = 2463), respectively. Higher stages or longer duration of AKI were associated with more severe anemia. AKI was associated with higher mortality after 3 months postoperatively with a hazard ratio of 1.54 (95% CI 1.12-2.12). Further adjustment with hematocrit at 3 months attenuated the association. The mediation effect was significant (P = 0.02) by mediation analysis. Conclusions: AKI was an independent predictor of anemia following AKI. Higher mortality associated with AKI was at least partially mediated by anemia following AKI. Whether correction of anemia following AKI improves mortality requires further research.

Microscopic hematuria is a risk factor for end-stage kidney disease in patients with biopsy-proven diabetic nephropathy.

INTRODUCTION: There are fewer reports about whether the presence of hematuria affects the progression of chronic kidney disease in patients with diabetic nephropathy. We analyzed whether microscopic hematuria in diabetic nephropathy is a risk factor for end-stage kidney disease (ESKD). RESEARCH DESIGN AND METHODS: The present study was a retrospective cohort study of patients with biopsy-proven diabetic nephropathy. We recruited 397 patients with diabetic nephropathy, which was confirmed by renal biopsy between June 1981 and December 2014 and followed them until October 2018 or death. Patients with microscopic hematuria before renal biopsy were defined as the hematuria group (n=91), and the remainder as the no-hematuria group (n=306). The main outcome was the occurrence of ESKD, which was defined by the requirement of permanent renal replacement therapies. RESULTS: The systolic and diastolic blood pressure, serum creatinine and proteinuria were significantly higher, and the estimated glomerular filtration rate was significantly lower in the hematuria group compared with the no-hematuria group. Pathological evaluations revealed that glomerular, tubulointerstitial and vascular lesions in the hematuria group were significantly more severe. During a median of 10.1 years, 44 and 52 patients developed ESKD in the hematuria group and the no-hematuria group, respectively. Survival analyses showed that the incidence of ESKD was significantly higher in the hematuria group compared with the no-hematuria group (log-rank, p<0.0001). The multivariable Cox proportional hazards models revealed a significant association between hematuria and the incidence of ESKD after adjusting for clinically relevant factors, including proteinuria and renal pathology (adjusted HR 1.64, 95% CI 1.03 to 2.60). The subgroups of men, proteinuria ≥0.5 g/day, and systolic blood pressure ≥132 mm Hg showed a stronger association between hematuria and ESKD than their opposing subgroups. CONCLUSIONS: Microscopic hematuria is a risk factor for ESKD in diabetic nephropathy, independent of proteinuria and renal pathology.

Relationship between initial peritoneal dialysis modality and risk of peritonitis.

Peritonitis is a critical complication of peritoneal dialysis (PD). Investigators have reported the risk of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD), but the available evidence is predominantly based on observational studies which failed to report on the connection type. Our understanding of the relationship between peritonitis risk and PD modality thus remained insufficient. We studied 285 participants who began PD treatment between 1997 and 2014 at three hospitals in Nara Prefecture in Japan. We matched 106 APD patients with 106 CAPD patients based on their propensity scores. The primary outcome was time to first episode of peritonitis within 3 years after PD commencement. In total, PD peritonitis occurred in 64 patients during the study period. Patients initiated on APD had a lower risk of peritonitis than did those initiated on CAPD in both the unadjusted and adjusted models. The hazard ratio (HR) and 95% confidence interval (CI) for the primary endpoint were 0.30 (0.17-0.53) in the fully adjusted model including connection type. In the matched cohort, APD patients had a significantly lower risk of peritonitis than did CAPD patients (log-rank: p < 0.001, HR 0.32, 95% CI 0.16-0.59). The weighting-adjusted analysis of the inverse probability of treatment yielded a similar result (HR 0.35, 95% CI 0.18-0.67). In conclusion, patients initiated on APD at PD commencement had a reduced risk of peritonitis compared with those initiated on CAPD, suggesting APD may be preferable for prevention of peritonitis among PD patients.

Better remission rates in elderly Japanese patients with primary membranous nephropathy in nationwide real-world practice: The Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. METHODS: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. RESULTS: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. CONCLUSIONS: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Pre-operative proteinuria and post-operative acute kidney injury in noncardiac surgery: the NARA-Acute Kidney Injury cohort study.

BACKGROUND: Little is known about the association between pre-operative proteinuria and post-operative acute kidney injury (AKI) in noncardiac surgery. METHODS: This is a retrospective cohort study. Adults who underwent noncardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data for analyses or pre-operative dialysis were excluded. Exposure of interest was pre-operative proteinuria, defined as (+) or more by dipstick test. The outcome variable was post-operative AKI, defined by Kidney Disease: Improving Global Outcomes criteria, within 1 week after surgery. Multivariable logistic regression analyses were performed. RESULTS: Among 5168 subjects, 309 (6.0%) developed AKI. Pre-operative proteinuria was independently associated with post-operative AKI, with an odds ratio (OR) [95% confidence interval (CI)] of 1.80 (1.30-2.51). A sensitivity analysis restricted to elective surgery yielded a similar result. As proteinuria increased, the association with AKI became stronger [OR (95% CI) 1.14 (0.75-1.73), 1.24 (0.79-1.95), 2.75 (1.74-4.35) and 3.95 (1.62-9.62) for urinary protein (+/-), (+), (2+) and (3+), respectively]. Subgroup analyses showed proteinuria was especially associated with post-operative AKI among subjects with renin-angiotensin system inhibitors, other anti-hypertensives, hypoalbuminemia or impaired renal function (P for interaction = 0.05, 0.003, 0.09 or 0.02, respectively). CONCLUSIONS: In noncardiac surgery, pre-operative proteinuria was independently associated with post-operative AKI. Subjects with proteinuria should be managed with caution to avoid AKI peri-operatively.

Positive association between intra-operative fluid balance and post-operative acute kidney injury in non-cardiac surgery: the NARA-AKI cohort study.

BACKGROUND: Little is known about the association between intra-operative fluid balance (IFB) and post-operative acute kidney injury (AKI) in non-cardiac surgery. METHODS: This is a retrospective cohort study. Adults who underwent non-cardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data, or pre-operative dialysis were excluded. Exposure of interest was IFB, defined as (amount of fluid administration - urine output - amount of bleeding)/body weight. Outcome variable was post-operative AKI within 1 week after surgery. Data were analyzed using logistic regression models and restricted cubic spline (RCS) analysis. RESULTS: Among 5168 subjects, AKI was observed in 309 (6.0%). Higher IFB (per 1 standard deviation) was independently associated with post-operative AKI after adjustment for potential confounders (odds ratio [95% confidence interval] of 1.18 [1.06-1.31]). The RCS curve showed an increase in expected probability of AKI associated with increase in IFB above 40 mL/kg. Subgroup analyses indicated higher IFB was especially associated with AKI among those with lower serum albumin, higher C-reactive protein, or positive proteinuria. The association was similar across intra-operative urine output or amount of bleeding (p for interaction 0.34 and 0.47, respectively), suggesting the association was not due to intra-operative oliguria or large amount of bleeding necessitating volume resuscitation. CONCLUSIONS: Higher IFB was independently associated with increase in post-operative AKI. Excessive fluid administration might have caused renal congestion and subsequent AKI. Avoiding fluid overload might be important in prevention of AKI.