Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy.

BACKGROUND: Studies on kidney function and histological findings in diabetic nephropathy (DN) with low urinary protein (UP) are few. We examined the differential impact of histological changes on kidney outcomes between non-proteinuric and proteinuric DN. METHODS: Patients diagnosed with DN by renal biopsy during 1981-2014 were divided into non-proteinuric (UP ≤ 0.5 g/day) and proteinuric (UP > 0.5 g/day) DN. The Cox proportional hazard model was used to examine the association of glomerular lesions (GLs) and interstitial fibrosis and tubular atrophy (IFTA) with end-stage kidney disease (ESKD) development after adjusting for relevant confounders. RESULTS: The non-proteinuric and proteinuric DN groups included 197 and 199 patients, respectively. During the 10.7-year median follow-up period, 16 and 83 patients developed ESKD in the non-proteinuric and proteinuric DN groups, respectively. In the multivariable Cox hazard model, hazard ratios (HRs) [95% confidence intervals (CIs)] of GL and IFTA for ESKD in proteinuric DN were 2.94 [1.67-5.36] and 3.82 [2.06-7.53], respectively. Meanwhile, HRs [95% CIs] of GL and IFTA in non-proteinuric DN were < 0.01 [0-2.48] and 4.98 [1.33-18.0], respectively. IFTA was consistently associated with higher incidences of ESKD regardless of proteinuria levels (P for interaction = 0.49). The prognostic impact of GLs on ESKD was significantly decreased as proteinuria levels decreased (P for interaction < 0.01). CONCLUSIONS: IFTA is consistently a useful predictor of kidney prognosis in both non-proteinuric and proteinuric DN, while GLs are a significant predictor of kidney prognosis only in proteinuric DN.

Utility of serum ß2-microglobulin for prediction of kidney outcome among patients with biopsy-proven diabetic nephropathy.

AIM: To examine whether serum ß2-microglobulin (ß2-MG) could improve the prediction performance for kidney failure with replacement therapy (KFRT) among patients with diabetic nephropathy (DN). METHODS: Patients with biopsy-proven DN at Nara Medical University Hospital were included. The exposure of interest was log-transformed serum ß2-MG levels measured at kidney biopsy. The outcome variable was KFRT. Multivariable Cox regression models and competing-risk regression models, with all-cause mortality as a competing event, were performed. Model fit by adding serum ß2-MG levels was calculated using the Akaike information criterion (AIC). The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indexes were used to evaluate the improvement of predictive performance for 5-year cumulative incidence of KFRT by serum ß2-MG levels. RESULTS: Among 408 patients, 99 developed KFRT during a median follow-up period of 6.7 years. A higher serum ß2-MG level (1-unit increase in log-transformed serum ß2-MG level) was associated with a higher incidence of KFRT, even after adjustments for previously known clinical and histological risk factors (hazard ratio [95% confidence interval {CI}]: 3.30 [1.57-6.94] and subdistribution hazard ratio [95% CI]: 3.07 [1.55-6.06]). The addition of log-transformed serum ß2-MG level reduced AIC and improved the prediction of KFRT (NRI and IDI: 0.32 [0.09-0.54] and 0.03 [0.01-0.56], respectively). CONCLUSIONS: Among patients with biopsy-proven DN, serum ß2-MG was an independent predictor of KFRT and improved prediction performance. In addition to serum creatinine, serum ß2-MG should probably be measured for DN.

Synergistic effect of proteinuria on dipstick hematuria-related decline in kidney function: The Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: The effect of isolated hematuria without proteinuria on kidney function decline, and the modification by the severity of proteinuria in general population are not fully elucidated. METHODS: Participants were included in the Japan Specific Health Checkups Study between 2008 and 2014. The exposure of interest was the frequency of dipstick hematuria during the observation. In each proteinuria frequency category (non-, occasional, persistent), hematuria-related decline in the eGFR rate was examined by analysis of covariance (ANCOVA). eGFR decline trajectories were also assessed using mixed-effects models. RESULTS: Among the 552,951 participants, 146,753 (26.5%) had hematuria, and 56,021 (10.1%) and 8,061 (1.5%) had occasional and persistent proteinuria, respectively. During the median follow-up of 3.0 years, annual change in eGFR decline in participants with hematuria was significantly faster than in those without hematuria (mean [95% confidence interval]: - 0.95 [- 0.98 to - 0.92] vs - 0.86 [- 0.87 to - 0.84] mL/min/1.73 m2/year; P < 0.001). In ANCOVA, the hematuria-related annual eGFR decline rate increased as proteinuria frequency categories increased (differences in annual eGFR decline rate between participants with and without hematuria: 0.08 [0.06 to 0.09] in participants with non-proteinuria category, 0.17 [0.15 to 0.18] in occasional proteinuria category, and 0.68 [0.65 to 0.71] mL/min/1.73 m2/year in persistent proteinuria category; P for interaction < 0.001). Similar results were obtained by the linear mixed-effect model. CONCLUSIONS: Proteinuria has a synergistic effect on dipstick hematuria-related decline in kidney function. Among the general population without proteinuria throughout the observational period, the "isolated hematuria"-related eGFR decline was statistically significant but the difference was small.

Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy-proven diabetic kidney disease: A multicenter cohort study.

AIMS/INTRODUCTION: This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes. MATERIALS AND METHODS: We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event. CONCLUSIONS: This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria.

Trace proteinuria detected via dipstick test is associated with kidney function decline and new-onset overt proteinuria: the Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: Microalbuminuria is associated with mortality, cardiovascular disease, and end-stage kidney disease. The association between trace proteinuria (detected via dipstick test) and kidney outcomes is unclear. METHODS: This nationwide longitudinal study used data from the Japan Specific Health Checkups Study conducted during 2008-2014. The frequency of trace proteinuria (detected via dipstick test) during first two visits was used as an exposure variable (TrUP 0/2, no trace proteinuria; TrUP 1/2, detected once; TrUP 2/2, detected twice), and kidney outcomes were evaluated. The association between the frequency of trace proteinuria and incidence of 1.5-fold increase in serum creatinine levels and overt proteinuria was analyzed using Cox regression analysis. Trajectories of estimated glomerular filtration rate (eGFR) were compared using a mixed-effect model. RESULTS: Among 306,317 participants, 3188 and 17,461 developed a 1.5-fold increase in serum creatinine levels and new-onset overt proteinuria, respectively, during the median follow-up period of 36.2 months. The adjusted hazard ratio (HR) and 95% confidence interval (CI) for 1.5-fold increase in serum creatinine level in the TrUP 1/2 and TrUP 2/2 groups, compared to TrUP 0/2 group, were 1.23 (1.07-1.42) and 1.39 (1.01-1.92), respectively, and the adjusted HR (95% CI) for overt proteinuria were 2.94 (2.83-3.06) and 5.14 (4.80-5.51), respectively. The eGFR decline rates in the TrUP 1/2 and TrUP 2/2 groups were higher than that in the TrUP 0/2 group (p for interaction < 0.001). CONCLUSIONS: Trace proteinuria (detected via dipstick test) was associated with subsequent kidney function decline and overt proteinuria in the general population.

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.

Height loss is associated with decreased kidney function: The Japan Specific Health Checkups (J-SHC) Study.

AIM: Height loss that occurs with aging is a common phenomenon associated with musculoskeletal abnormalities, such as osteoporosis and sarcopenia. Notably, such height loss is also associated with poor outcomes, including cardiovascular disease and mortality. In this study, we investigated the relationship between height loss and kidney outcome. METHODS: This longitudinal study includes data from the Japan Specific Health Checkups Study from 2008 to 2014. Height loss was estimated using the first three visits (visits 1-3), and kidney outcomes were evaluated using data from the following visits (visit 3 to the last visit). The annual height change for each participant was estimated using mixed-effects model, and participants were divided into five groups according to the quintile of the rate. The association between height change and the incidence of 1.5-fold increase in serum creatinine level from baseline was analyzed using Cox regression analysis. The decline rates of estimated glomerular filtration rate among the groups were compared using a mixed-effects model. RESULTS: In total, 187 682 participants were included in the analyses. The median rate of height change was -0.11 cm/year. The adjusted hazard ratio (95% confidence interval) for 1.5-fold increase in serum creatinine level in participants with the steepest category of height decline (Q1; Quintile 1) was 1.45 (1.26-1.67) compared with the reference (Q4; Quintile 4). The decline of the estimated glomerular filtration rate in Q1 (-1.25 mL/min/1.73 m2 /year) was significantly higher than that of the reference: Q4 (-0.92 mL/min/1.73 m2 /year) (P for interaction <0.001). CONCLUSION: Height loss is associated with a rapid decline in kidney function. Geriatr Gerontol Int 2023; 23: 282-288.

Association of triglycerides to high-density lipoprotein cholesterol ratio with incident cardiovascular disease but not end-stage kidney disease among patients with biopsy-proven diabetic nephropathy.

Increased triglycerides (TG) and decreased high-density lipoprotein cholesterol (HDL-C) are dyslipidemias characteristic of diabetes. Here, we aimed to examine associations of TG/HDL-C ratio with cardiovascular disease (CVD) and kidney dysfunction among patients with diabetic nephropathy. This retrospective observational study consists of patients with biopsy-proven diabetic nephropathy at Nara Medical University Hospital. Exposure of interest was TG/HDL-C ratio measured at kidney biopsy. Outcome variables were kidney histological findings, incident CVD and end-stage kidney disease (ESKD). Multivariable logistic regression models and Cox proportional hazard models were used to examined these associations. A total of 353 subjects were divided into quartiles based on TG/HDL-C ratio: Quartile 1 (reference), <1.96; Quartile 2, 1.96-3.10; Quartile 3, 3.11-4.55; and Quartile 4, ≥4.56. TG/HDL-C ratio was not a predictor of any histological findings in fully adjusted models. During median follow-up periods of 6.2 and 7.3 years, 152 and 90 subjects developed CVD and ESKD, respectively. Higher TG/HDL-C ratio was independently associated with higher incidences of CVD even after adjustments for potential confounders (hazard ratio [95% confidence interval] for Quartile 3 vs. reference; 1.73 [1.08-2.79] and Quartile 4 vs. reference; 1.86 [1.10-3.17]). Although there was a weak association between TG/HDL-C ratio and ESKD in the univariable model, the association was not significant in fully adjusted models. In conclusion, among patients with biopsy-proven diabetic nephropathy, higher TG/HDL-C ratio was independently associated with higher incidences of CVD but not with kidney outcomes, suggesting different impact of TG/HDL-C ratio on cardiorenal outcomes.

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.

The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. Since most patients have a relatively benign renal prognosis, long-term follow-up is required. During such a long course of disease, relapse of IgAN is occasionally observed after upper respiratory tract infection or without any trigger. However, little is known about the impact of relapse on long-term renal outcomes. METHODS: In this retrospective cohort study of biopsy-proven primary IgAN, we analyzed the association of 5-year therapeutic responsiveness (relapse) with the subsequent development of end-stage kidney disease (ESKD) using a 5-year landmark analysis (Cox model) and explored predictors of relapse from histological and clinical data at baseline. RESULTS: Among 563 patients from the exploratory cohort, most relapses (13.7%) occurred within 5 years after treatment. Using 5-year landmark analysis, among 470 patients, 79 developed ESKD during a median follow-up period of 155 months. Even after adjustment for clinicopathological relevant confounders, hazard ratios (95% confidence intervals) in the relapse and non-responder groups compared with the remission group were 2.86 (1.41-5.79) and 2.74 (1.48-5.11), respectively. Among 250 patients who achieved remission within 5 years, proteinuria, eGFR, mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, and crescent, but not interstitial fibrosis/tubular atrophy, were independent predictors of 5-year relapse in multivariable logistic regression analysis, CONCLUSIONS: Both relapsers and non-responders had similarly strong association with ESKD in patients with IgAN. We also confirmed the predictors of relapse 5 years after renal biopsy, which may guide the treatment strategies for patients with IgAN who occasionally relapse after remission.

Tracing all patients who received insured dialysis treatment in Japan and the present situation of their number of deaths.

BACKGROUND: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR). METHODS: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014-2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases- and deaths. RESULTS: Compared with the JRDR, the NDB had about 6-7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6-10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes. CONCLUSION: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies.

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.

Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study.

BACKGROUND: Prognosticating disease progression in patients with diabetic kidney disease (DKD) is challenging, especially in the early stages of kidney disease. Anemia can occur in the early stages of kidney disease in diabetes. We therefore postulated that serum hemoglobin (Hb) concentration, as a reflection of incipient renal tubulointerstitial impairment, can be used as a marker to predict DKD progression. METHODS: Drawing on nationally representative data of patients with biopsy-proven DKD, 246 patients who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 at renal biopsy were identified: age 56 (45-63) years; 62.6% men; Hb 13.3 (12.0-14.5) g/dL; eGFR 76.2 (66.6-88.6) mL/min/1.73 m2; urine albumin-to-creatinine ratio 534 (100-1480) mg/g Crea. Serum Hb concentration was divided into quartiles: ≤12, 12.1-13.3, 13.4-14.5 and ≥14.6 g/dL. The association between serum Hb concentration and the severity of renal pathological lesions was explored. A multivariable Cox regression model was used to estimate the risk of DKD progression (new onset of end-stage kidney disease, 50% reduction of eGFR or doubling of serum creatinine). The incremental prognostic value of DKD progression by adding serum Hb concentration to the known risk factors of DKD was assessed. RESULTS: Serum Hb levels negatively correlated with all renal pathological features, especially with the severity of interstitial fibrosis (ρ = -0.52; P < 0.001). During a median follow-up of 4.1 years, 95 developed DKD progression. Adjusting for known risk factors of DKD progression, the hazard ratio in the first, second and third quartile (the fourth quartile was reference) were 2.74 [95% confidence interval (CI) 1.26-5.97], 2.33 (95% CI 1.07-5.75) and 1.46 (95% CI 0.71-3.64), respectively. Addition of the serum Hb concentration to the known risk factors of DKD progression improved the prognostic value of DKD progression (the global Chi-statistics increased from 55.1 to 60.8; P < 0.001). CONCLUSIONS: Serum Hb concentration, which reflects incipient renal fibrosis, can be useful for predicting DKD progression in the early stages of kidney disease.

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.

Association between chronic kidney disease and new-onset dyslipidemia: The Japan Specific Health Checkups (J-SHC) study.

BACKGROUND AND AIMS: Dyslipidemias are common among patients with chronic kidney disease (CKD) and are a major risk factor for cardiovascular disease. This study aimed to investigate the association between early-stage CKD and new-onset dyslipidemia for each lipid profile. METHODS: This nationwide longitudinal study included data from the Japan Specific Health Checkups (J-SHC) Study. New-onset dyslipidemia was indicated by hypertriglyceridemia (High-TG; ≥150 mg/dL), hyper-LDL cholesterolemia (High-LDL-C; ≥140 mg/dL), or hypo-HDL chelesterolemia (Low-HDL-C; <40 mg/dL) levels according to the guideline of Japan Atherosclerosis Society, or High-TG/HDL-C ratio (≥3.5) which was a good predictor of atherosclerosis. The incidence of new-onset dyslipidemia was compared between participants with and without CKD. Survival curves were used to analyze the incidence of each dyslipidemia. RESULTS: Of 289,462 participants with a median follow-up period of 3 years, the incidence of High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratios were 64.4/1000 person-years, 83.1/1000 person-years, 14.5/1000 person-years, and 39.6/1000 person-years, respectively. The adjusted hazard ratios (95% confidence intervals) for High-TG, High-LDL-C, Low-HDL-C, and High-TG/HDL-C ratio were 1.09 (1.05-1.13), 0.99 (0.95-1.04), 1.12 (1.05-1.18), and 1.14 (1.09-1.18), respectively, in CKD participants as compared to non-CKD participants. Decreased eGFR and presence of proteinuria were independently associated with higher risks for new-onset of High-TG, Low-HDL-C, and High-TG/HDL-C ratios. CONCLUSIONS: CKD was associated with a higher risk of new-onset High-TG, Low-HDL-C, and High-TG/HDL-C ratios, but not High-LDL-C, in the general population. These CKD-specific lipid abnormalities may explain the residual risk for CKD-related cardiovascular disease.

Two-year longitudinal trajectory patterns of albuminuria and subsequent rates of end-stage kidney disease and all-cause death: a nationwide cohort study of biopsy-proven diabetic kidney disease.

INTRODUCTION: Data on the association between longitudinal trajectory patterns of albuminuria and subsequent end-stage kidney disease (ESKD) and all-cause mortality in diabetic kidney disease (DKD) are sparse. RESEARCH DESIGN AND METHODS: Drawing on nationally representative data of 329 patients with biopsy-proven DKD and an estimated glomerular filtration rate above 30 mL/min/1.73 m2 at the time of biopsy, we used joint latent class mixed models to identify different 2-year trajectory patterns of urine albumin to creatinine ratio (UACR) and assessed subsequent rates of competing events: ESKD and all-cause death. RESULTS: A total of three trajectory groups of UACR were identified: 'high-increasing' group (n=254; 77.2%), 'high-decreasing' group (n=24; 7.3%), and 'low-stable' group (n=51; 15.5%). The 'low-stable' group had the most favorable risk profile, including the baseline UACR (median (IQR) UACR (mg/g creatinine): 'low-stable', 109 (50-138); 'high-decreasing', 906 (468-1740); 'high-increasing', 1380 (654-2502)), and had the least subsequent risk of ESKD and all-cause death among the groups. Although there were no differences in baseline characteristics between the 'high-decreasing' group and the 'high-increasing' group, the 'high-decreasing' group had better control over blood pressure, blood glucose, and total cholesterol levels during the first 2 years of follow-up, and the incidence rates of subsequent ESKD and all-cause death were lower in the 'high-decreasing' group compared with the 'high-increasing' group (incidence rate of ESKD (per 1000 person-years): 32.7 vs 77.4, p=0.014; incidence rate of all-cause death (per 1000 person-years): 0.0 vs 25.4, p=0.007). CONCLUSIONS: Dynamic changes in albuminuria are associated with subsequent ESKD and all-cause mortality in DKD. Reduction in albuminuria by improving risk profile may decrease the risk of ESKD and all-cause death.

Impact of self-reported walking habit on slower decline in renal function among the general population in a longitudinal study: the Japan Specific Health Checkups (J-SHC) Study.

BACKGROUND: Association between physical activity and decline in renal function among the general population is not fully understood. METHODS: This is a longitudinal study on subjects who participated in the Japanese nationwide Specific Health Checkup program between 2008 and 2014. The exposure of interest was baseline self-reported walking habit. The outcomes were annual change and incidence of 30% decline in estimated glomerular filtration rate (eGFR). Changes in eGFR were compared using a linear mixed-effects model. Cox proportional hazard models were used to examine the association between self-reported walking habit and 30% decline in eGFR. RESULTS: Among 332,166 subjects, 168,574 reported walking habit at baseline. The annual changes in eGFR [95% confidence interval (CI)] among subjects with and without baseline self-reported walking habit were - 0.17 (- 0.19 to - 0.16) and - 0.26 (- 0.27 to - 0.24) mL/min/1.73 m2/year, respectively (P for interaction between time and baseline self-reported walking habit, < 0.001). During a median follow-up of 3.3 years, 9166 of 314,489 subjects exhibited 30% decline in eGFR. The incidence of 30% decline in eGFR was significantly lower among subjects with self-reported walking habit after adjustment for potential confounders including time-varying blood pressure, body mass index, lipid profile, and hemoglobin A1c, with hazard ratio (95% CI) of 0.93 (0.89-0.97). Sensitivity analysis restricted to subjects with unchanged self-reported walking habit from baseline or analysis with time-varying self-reported walking habit yielded similar results. CONCLUSIONS: Self-reported walking habit was associated with significantly slower decline in eGFR. This association appeared to be independent of its effects on metabolic improvement.

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.