Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study

The purpose of this study was to investigate the prevalence of tubular damage in short-term (less than five years) type 2 diabetes mellitus (T2DM) patients and to explore the correlation between tubular markers and their relationship with renal indices at different stages of diabetic nephropathy. A group of 101 short-term T2DM patients and 28 control subjects were recruited. Tubular markers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D: -glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1), as well as urinary albumin excretion were measured in voided urine. Glomerular filtration rate (GFR) was estimated via Macisaac's formula. The patients were further categorized into three groups, namely, the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, according to their urine albumin/creatinine ratio (UACR). Urinary tubular markers were compared and their correlations with renal indices [UACR and estimated GFR (eGFR)] were analyzed among the different diabetic groups. Compared with the control group, Urinary NGAL [median (IQR)][83.6(41.4-138.7) μg/gcr vs. 32.9(26.1-64.5) μg/gcr], NAG [13.5(8.7-17.9) U/gcr vs. 7.6(6.5-13.0) U/gcr] and KIM-1 [120.0(98.4-139.9) ng/gcr vs. 103.1(86.8-106.2) ng/gcr] in the T2DM were all markedly increased. For all patients, urinary NGAL had stronger positive correlations with UACR than NAG (R = 0.556 vs. 0.305, both P < 0.05). In addition, only urinary NGAL showed a negative correlation with eGFR (R = -0.215, P < 0.05). Urinary KIM-1, however, showed no significant difference among the three T2DM groups and did not correlate with either UACR or eGFR. As UACR increased from the normoalbuminuria to the last macroalbuminuria group, all of the markers increased. However, only the concentrations of NGAL were statistically different among the three diabetic groups. The correlation between the tubular markers and their relationships with the renal indices differed markedly among the three T2DM groups. In conclusion, these results suggest that tubular damage is common in short-term T2DM patients. Urinary NGAL may be a promising early marker for monitoring renal impairment in short-term T2DM patients.     

C3c deposition predicts worse renal outcomes in patients with biopsy‐proven diabetic kidney disease in type 2 diabetes mellitus

BackgroundAlthough extensive efforts have been paid to identify reliable predictors for renal outcomes of diabetic kidney disease (DKD) patients in type 2 diabetes mellitus (T2DM), there are still only a limited number of predictive factors for DKD progression. Increasing evidence reported the role of the overactivated complement system in the pathogenesis of DKD. Whether renal complement depositions are associated with renal outcomes of DKD in T2DM is of interest.MethodsA total of 213 biopsy‐proven DKD patients with T2DM were retrospectively recruited. Clinical and pathological data of the patients were analyzed. Kaplan‐Meier analysis and Cox regression analysis were performed to explore predictors of end‐stage renal disease (ESRD).ResultsDuring a median follow‐up of 23.0 (12.0, 39.0) months, 100/213 (46.9%) patients progressed to ESRD. C3c and C1q deposition were observed in 133/213 (62.4%) and 45/213 (21.1%) patients, respectively. Kaplan‐Meier analysis revealed patients with C3c or C1q deposition had significantly worse renal outcomes compared with those without C3c or C1q deposition (p = .001 and p < .001, respectively). Univariate and multivariate Cox regression analysis demonstrated proteinuria (per 1 g/24 h increase, hazard ratio [HR] 1.134, 95% confidence interval [CI] [1.079, 1.191], p < .001), interstitial fibrosis and tubular atrophy score (score 2 and 3 vs. 0 and 1, HR 3.925, 95% CI [1.855, 8.304], p < .001), and C3c deposition (per 1+ increase, HR 1.299, 95% CI [1.073, 1.573], p = .007) were independent predictors for ESRD in DKD patients with T2DM.ConclusionsC3c deposition in the kidney was associated with worse renal outcomes and was an independent predictor for ESRD in DKD patients with T2DM.     

Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study

Background and objectives

Liver fatty acid binding protein (L-FABP), kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and neutrophil gelatinase–associated lipocalin (NGAL) are urinary markers of tubular injury that may also be markers of chronic kidney damage. We evaluated the association of these markers with incident ESRD in a community-based sample from the Atherosclerosis Risk in Communities Study.

Design, setting, participants, & measurements

This was a matched case-control study of 135 patients with ESRD and 186 controls who were matched on sex, race, kidney function, and diabetes status at baseline (Atherosclerosis Risk in Communities Study visit 4, 1996–1998). Urinary KIM-1 indexed to creatinine (Cr), NAG/Cr, NGAL/Cr, and L-FABP/Cr were measured in stored spot urine samples from the baseline examination. Associations of KIM-1/Cr, NAG/Cr, and NGAL/Cr with patients with incident ESRD through 2008 were modeled continuously and categorically (quartiles) using conditional logistic regression. L-FABP/Cr was modeled only categorically because of a large number of measurements below the lower limit of detection for the assay (2.4 ng/ml).

Results

No significant associations were observed for NAG/Cr, NGAL/Cr, or L-FABP/Cr with ESRD. Those in the highest category for KIM-1/Cr had a higher risk of ESRD compared with those with undetectable biomarker levels (reference group) in unadjusted models (odds ratio, 2.24; 95% confidence interval, 1.97 to 4.69; P=0.03) or adjustment for age (odds ratio, 2.23; 95% confidence interval, 1.06 to 4.67; P=0.03). This association was attenuated with additional adjustment for baseline kidney function (odds ratio, 2.02; 95% confidence interval, 0.95 to 4.31; P=0.07 after additional adjustment for eGFR and natural log of the urinary albumin-to-creatinine ratio). No association between KIM-1/Cr and ESRD was found when KIM-1/Cr was analyzed as a continuous variable.

Conclusions

Elevated urinary KIM-1/Cr may be associated with a higher risk of incident ESRD, but it does not add to risk prediction after accounting for traditional markers of kidney function in this population.     

Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis

BackgroundPrediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients.AimsTo evaluate use of serum and urine biomarkers to predict HRS.MethodsWe prospectively recruited Child’s B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-β-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated.Results43 patients were included. 12 (27.9%) developed HRS at 7.3 ± 5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001–1.012, p = 0.014; RR 1.973, 95% CI 1.002–3.886, p = 0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72 ng/mL and 1.499 ng/mL respectively (AUCs 0.84, p = 0.005; and 0.78, p = 0.008).ConclusionUrinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.     

Utility of urinary biomarkers as a diagnostic tool for early diabetic nephropathy in patients with type 2 diabetes mellitus

Introduction

Renal tubulo-interstitial damage has an important role in the pathogenesis of early diabetic nephropathy. Urinary biomarkers can help in the detection of early nephropathy in type 2 diabetic patients. The aim of this study was to estimate the levels of urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in type 2 diabetic patients with early diabetic nephropathy & to compare them with diabetic patients without nephropathy and to correlate urinary NGAL and cystatin-C levels with microalbuminuria in them.

Chronic kidney disease incidence, and progression to end-stage renal disease, in HIV-infected individuals: a tale of two races

BACKGROUND: Little is known about the racial differences in the incidence and progression of HIV-related chronic kidney disease (CKD) that underlie African American-white disparities in HIV-related end-stage renal disease (ESRD). METHODS: In a cohort in Baltimore, Maryland, we measured CKD incidence, glomerular filtration rate (GFR) slope, and progression to ESRD in 3332 African American and 927 white HIV-infected subjects. RESULTS: A total of 284 subjects developed CKD, 100 (35%) of whom subsequently developed ESRD. African American subjects were at slightly increased risk for incident CKD, compared with white subjects (hazard ratio [HR], 1.9 [95% confidence interval {CI}, 1.2-2.8]). However, once CKD had commenced, the African American subjects developed ESRD markedly faster than did the white subjects (HR, 17.7 [95% CI, 2.5-127.0]), and, correspondingly, their GFR decline after diagnosis of CKD was 6-fold more rapid (P < .001). In the subset of African American subjects for whom kidney-biopsy data were available, progression to ESRD was significantly faster than that in white subjects with CKD, irrespective of the presence of HIV-associated nephropathy. CONCLUSIONS: The results of this study suggest that African American-white disparities in HIV-related ESRD are explained predominantly by a more aggressive natural disease history in African Americans and less by racial differences in CKD incidence.     

Novel Urinary Biomarkers in Detecting Acute Kidney Injury,Persistent Renal Impairment,and All-Cause Mortality Following Decongestive Therapy in Acute Decompensated Heart Failure

BackgroundNew urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18), are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1, and IL-18 for the occurrence of AKI, persistent renal impairment, and mortality in ADHF.Methods and ResultsEighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1, and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1, and IL-18 were modestly correlated with each other (Spearman ρ ≤0.61) and poorly correlated with estimated glomerular filtration rate (eGFR; Spearman ρ ≤0.28). None predicted AKI, defined as a 25% decrease in eGFR, during the index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr ≥0.3 mg/dL after 6 months compared with baseline (area under the receiver operating characteristic curve 0.674; P = .013). Urinary IL-18 was also significantly associated with all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.16–1.87; P = .001).ConclusionsLike urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.     

Association of non-HDL-C/HDL-C ratio and its dynamic changes with incident type 2 diabetes mellitus: The Rural Chinese Cohort Study

BackgroundWe aimed to evaluate the association of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and its dynamic changes with incident type 2 diabetes mellitus (T2DM).MethodsA total of 11,487 nondiabetic participants ≥18 years old in rural China were recruited in 2007–2008 and followed up in 2013–2014. A Cox proportional-hazards model was used to assess the risk of incident T2DM by quartiles of baseline non-HDL-C/HDL-C ratio and dynamic absolute and relative changes in non-HDL-C/HDL-C ratio, estimating hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsRisk of incident T2DM was increased with quartiles 2, 3, and 4 versus quartile 1 of baseline non-HDL-C/HDL-C ratio (HR 1.46 [95% CI 1.08–1.98], 1.51 [1.12–2.03], and 2.16 [1.62–2.88], P_trend < 0.001). As compared with stable non-HDL-C/HDL-C ratio during follow-up, an absolute gain in non-HDL-C/HDL-C ratio was associated with increased risk of T2DM (HR 1.67 [95% CI 1.25–2.24] for quartile 3 and 2.00 [1.52–2.61] for quartile 4). A relative increase in non-HDL-C/HDL-C ratio was also associated with increased risk of T2DM (HR 1.56 [95% CI 1.19–2.04] for quartile 3 and 1.97 [1.49–2.60] for quartile 4). Subgroup analyses showed that the association of non-HDL-C/HDL-C ratio with T2DM risk remained consistent.ConclusionsIncreased non-HDL-C/HDL-C ratio is associated with increased risk of incident T2DM among rural Chinese adults, so the index may be an important indicator for identifying individuals at T2DM risk.     

Changes of the tubular markers in type 2 diabetes mellitus with glomerular hyperfiltration

Aim

To assess whether glomerular hyperfiltration (GHF) could result in renal tubular damage in type 2 diabetes mellitus (T2DM) patients.

Methods

Reference value of estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals based on serum CysC levels. GHF was defined as an eGFR exceeding the sex-specific 97.5th percentile in non-diabetic individuals. In the present study, 30 with GHF, 58 with norm-GFR T2DM, and 24 healthy controls were recruited. Tubular markers, such as urinary N-acetyl-β-d-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1), as well as serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), were measured and compared. The correlation of these markers with eGFR was analyzed in the GHF group.

Results

The GHF group had higher urinary NGAL and KIM-1 levels but lower serum NGAL level than the norm-GFR and control groups. Slightly decreased serum NGAL and increased urinary NGAL levels were also noted in the norm-GFR group compared with those of the controls. There was no statistical difference in the urinary NAG values among the three groups. Correlation analysis showed that eGFR was positively related to fasting blood glucose (FBG), HbA1c, urinary NGAL, and KIM-1, but negatively with serum NGAL in the GHF group.

Conclusion

Higher urinary tubular damage markers were found in T2DM patients with GHF than the norm-GFR and control groups, probably a direct proof that GHF is a deleterious factor for diabetic nephropathy.     

中性粒细胞/淋巴细胞比值和血小板/淋巴细胞比值与2型糖尿病患者肾小管损伤的相关性研究

目的探讨中性粒细胞/淋巴细胞(NLR)和血小板/淋巴细胞(PLR)与2型糖尿病(T2DM)患者肾小管损伤的相关性。方法收集2018年9月至2019年9月于中南大学湘雅三医院住院治疗的268例T2DM患者,根据尿白蛋白/肌酐比值(UACR),将其分为正常白蛋白尿组(UACR<30 mg/g)、微量白蛋白尿组(30 mg/g≤UACR<300 mg/g)和大量白蛋白尿组(UACR≥300 mg/g)。收集纳入患者的一般临床资料。空腹抽取肘静脉血检测血常规以及糖化血红蛋白、超敏C反应蛋白(hs-CRP)等生化指标,计算NLR、PLR和预估肾小球滤过率(eGFR),并检测尿α1微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)、视黄醇结合蛋白(RBP)、尿肌酐(Ucr),以α1-MG/Ucr、β2-MG/Ucr和RBP/Ucr作为反映肾小管损伤的指标。采用χ2检验、方差分析及非参数检验对各组指标的差异进行比较,采用Spearman相关分析法分析各炎性指标与肾损伤标志物的相关性,采用受试者工作特征(ROC)曲线分析模型预测价值。结果大量白蛋白尿组(94例)的NLR和PLR明显高于正常白蛋白尿组(94例)和微量白蛋白尿组(80例),微量白蛋白尿组NLR高于正常白蛋白尿组,差异有统计学意义(均P<0.05)。随着NLR、PLR四分位数的递增,患者UACR及RBP/Ucr、α1-MG/Ucr、β2-MG/Ucr逐渐升高,差异具有统计学意义(均P<0.05)。Spearman相关分析显示,NLR、PLR与UACR、RBP/Ucr、α1-MG/Ucr、β2-MG/Ucr均呈正相关(r=0.254~0.385,均P<0.01),与eGFR呈负相关(r=-0.328、-0.151,均P<0.01)。ROC曲线显示,NLR判定UACR>30 mg/g、eGFR<60 ml·min^-1·(1.73 m²)^-1及肾小管损伤的曲线下面积(AUC)分别为0.700、0.679、0.717、0.702、0.737,灵敏度分别为75.29%、85.87%、80.88%、83.74%、85.59%,均优于PLR(AUC分别为0.639、0.639、0.659、0.644、0.676,灵敏度分别为58.05%、75.00%、63.24%、65.04%、58.56%)和hs-CRP(AUC分别为0.597、0.559、0.618、0.644、0.653,灵敏度分别为62.50%、30.12%、63.93%、68.42%、70.87%)。结论NLR和PLR与T2DM患者肾小管损伤密切相关,NLR在综合反映肾小球及肾小管损伤方面优于PLR和hs-CRP。     

Bidirectional association between depressive symptoms and type 2 diabetes mellitus: The China Health and Retirement Longitudinal Study

ObjectiveTo prospectively examine the bidirectional relationship between depressive symptoms and type 2 diabetes mellitus (T2DM) among middle-aged and elderly Chinese.MethodsParticipants were enrolled in 2011–2012 (Wave 1) and followed up in 2013–2014 (Wave 2) and 2015–2016 (Wave 3) in the China Health and Retirement Longitudinal Study. Depressive symptoms were evaluated by the Chinese language version of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) at three waves. T2DM was assessed by biochemical biomarkers at Wave 1 and reported physician-diagnosis at Wave 2 and 3. Cox proportional hazards regression was applied to calculate hazard ratio (HR) and 95% confidence intervals (CIs) for the bidirectional association.ResultsParticipants with baseline depressive symptoms were 1.33 times as likely to develop T2DM (HR, 1.33; 95% CI: 1.06, 1.66), compared to their counterparts after adjusting for demographic characteristics and T2DM risk factors. The risk of T2DM increased linearly with higher severity of depression as determined by a higher CESD-10 score (P for trend ? 0.001). In addition, baseline T2DM was associated with increased risk of incident depressive symptoms (1.15; 1.00, 1.31) and persistent depressive symptoms (1.35; 1.03, 1.77).ConclusionThere is a positive bidirectional association between depressive symptoms and T2DM in middle-aged and elderly Chinese.     

Independent and joint associations of non-exercise cardiorespiratory fitness and obesity with risk of type 2 diabetes mellitus in the Rural Chinese Cohort Study

Background and aimsAn association between cardiorespiratory fitness (CRF) and type 2 diabetes mellitus (T2DM) has not been established in the Chinese population. This study aimed to estimate the independent and joint associations of CRF and obesity with T2DM incidence in the rural Chinese population.Methods and resultsWe conducted a prospective study of 11,825 non-T2DM subjects among rural Chinese adults. Cox regression models were used to estimate the independent and joint associations between CRF and obesity exposure on T2DM. Restricted cubic splines were used to model the dose–response association. During a median follow-up of 6.01 years, 835 participants developed T2DM. In comparison to quartile 1 of CRF, the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of quartiles 2, 3, 4 were 0.75 (0.61–0.91), 0.54 (0.43–0.68), and 0.42 (0.32–0.55), respectively. When stratified by sex, the results were similar. Joint analyses showed that overweight/obesity-unfit individuals had a 2.28 times higher risk of developing T2DM than the normal weight-fit referent (HR 2.28, 95% CI 1.84–2.83; P_interaction <0.001). The risk for the overweight/obesity-fit category (HR 1.61, 95% CI 1.21–2.15) was larger than for the normal weight-unfit category (HR 1.38, 95% CI 0.97–1.95) versus the normal weight-fit referent. Similar joint associations for waist circumference and CRF with T2DM were also observed.ConclusionA negative association was observed between CRF and risk of T2DM. Overweight/obese or abdominal obesity and unfit participants showed the highest risks of T2DM. It is therefore strongly recommended that fitness-enhancing be encouraged for the prevention of T2DM, especially among obesity participants.     

Biomarkers for early detection of sickle nephropathy

Renal complications affect nearly 30-50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, noninvasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for nephropathy in 116 patients with sickle cell disease, analyzing urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β1 (TGF-β), together with conventional renal biomarkers (urine albumin and osmolality, and serum creatinine and cystatin C estimated GFR) during routine clinic visits when patients were at steady-state/baseline. We observed a distinct biomarker pattern: KIM-1 and NAG emerged as biomarkers with a strong association with albuminuria. Surprisingly, and in contrast to other acute/chronic renal disorders, NGAL, L-FABP, and TGF-β levels did not show any relationship with albuminuria in patients with SCA. Our study identifies potential biomarkers for SN, and suggests longitudinal validation of these biomarkers for early detection of SN, so that therapeutic interventions can be applied before renal damage becomes irreversible.     

Association between serum total cholesterol level and renal outcome in systemic lupus erythematosus

OBJECTIVE: To determine whether an elevated serum total cholesterol level in a first-available sample obtained at a systemic lupus erythematosus (SLE) clinic is associated with worse renal outcome in patients with SLE. METHODS: Survival analysis methods were used on prospectively gathered data on 1,060 patients with SLE who were registered in the University of Toronto Lupus Databank. The effect of total cholesterol and 15 additional variables on the outcomes of renal deterioration, end-stage renal disease (ESRD), and death was assessed using Cox proportional hazards methods. RESULTS: In 474 (45%) of the 1,060 patients, the total cholesterol level exceeded 5.2 mmoles/liter. In the entire study group, the median total cholesterol level was 5.1 mmoles/liter (range 1.6-17.1). During a mean followup period of 8.8 years, 93 patients (9%) experienced renal deterioration, 42 patients (4%) had ESRD, and 161 deaths occurred, 48 (30%) of which were associated with renal dysfunction (renal death), and 113 (70%) of which were not associated with renal dysfunction (nonrenal death). Kaplan-Meier survival estimates for each outcome were statistically significantly different between patients with normal versus those with elevated total cholesterol levels (cutoff 5.2 mmoles/ liter), with a worse outcome observed among those with an elevated total cholesterol concentration. In multivariate analyses, total cholesterol level (hazard ratio [HR] 1.17, 95 confidence interval [95% CI] 1.01-1.36), serum creatinine level (HR 1.06, 95% CI 1.04-1.07), proteinuria (HR 2.44, 95% CI 1.25-4.76), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (HR 1.44, 95% CI 1.16-1.80), and corticosteroid dose (HR 1.01, 95% CI 1.00-1.02) were associated with renal deterioration. Significant predictors of ESRD were baseline proteinuria (HR 6.24, 95% CI 1.96-19.88) and serum creatinine level (HR 1.15, 95% CI 1.08-1.22). The total cholesterol level was correlated with death (HR 1.20, 95% CI 1.11-1.29), retaining statistical significance for renal death (HR 1.33, 95% CI 1.20-1.47) but not for nonrenal death (HR 1.12, 95% CI 0.99-1.25). CONCLUSION: Those results indicate that an elevated serum total cholesterol level in a first-available sample obtained at an SLE clinic is associated with adverse renal outcomes and mortality.     

Incidence of End Stage Renal Disease among Type 1 Diabetes: A Nationwide Cohort Study in Taiwan

The aim of our study was to estimate the risk of end-stage renal disease (ESRD) in type 1 diabetes mellitus (T1DM) in Taiwanese people; in addition, our goal was to determine how the age, year, and sex at registration of T1DM affects the risk.Population-based cohort study.A nationwide cohort study of 7203 Taiwanese patients with T1DM registered in 1999 to 2010 was followed up until ESRD, death, or the end of follow-up on December 31, 2010.Annual age-, sex-, and calendar year-specific incidence rates of ESRD of the general population were used to calculate the standardized incidence ratio (SIR) of ESRD in relation to T1DM.The SIR of ESRD for male and female patients with T1DM was significantly increased at 25.85 (95% CI 23.40–28.29) and 28.08 (95% 25.45–30.71), respectively; the peak was at age 15 to 29 years for both genders. The cumulative incidence of ESRD was similar in male and female patients but was significantly higher in patients ≥ 30 years old than in patients <30 years old (10.25% vs. 3.57%, P < 0.001). Patients aged <15 years had a significantly lower risk of ESRD as compared to those aged 15 to 29 years; patients aged 30 to 44 (adjusted HR, 1.491) and 45 to 60 years (adjusted HR, 2.111) showed significantly increased hazards. Our data also demonstrated a lower risk of ESRD in patients who were registered in later years than in earlier years.The risk of ESRD is substantially increased in T1DM in the ethnic Chinese population. The continuously declining risk of ESRD in T1DM may advocate the use of a multidisciplinary chronic kidney disease care system in Taiwan.     

Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

Background and aimsRenal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians.Methods and resultsWe observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males.ConclusionsOur findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.     

A combined cardiorenal assessment for the prediction of acute kidney injury in lower respiratory tract infections

BackgroundThe accurate prediction of acute kidney injury (AKI) is an unmet clinical need. A combined assessment of cardiac stress and renal tubular damage might improve early AKI detection.MethodsA total of 372 consecutive patients presenting to the Emergency Department with lower respiratory tract infections were enrolled. Plasma B-type natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured in a blinded fashion at presentation. The potential of these biomarkers to predict AKI was assessed as the primary endpoint. AKI was defined according to the AKI Network classification.ResultsOverall, 16 patients (4%) experienced early AKI. These patients were more likely to suffer from preexisting chronic cardiac disease or diabetes mellitus. At presentation, BNP (334 pg/mL [130-1119] vs 113 pg/mL [52-328], P <.01) and NGAL (269 ng/mL [119-398] vs 96 ng/mL [60-199], P <.01) levels were significantly higher in AKI patients. The predictive accuracy of presentation BNP and NGAL levels was comparable (BNP 0.74; 95% confidence interval [CI], 0.64-0.84 vs NGAL 0.74; 95% CI, 0.61-0.87). In a combined logistic model, a joint BNP/NGAL approach improved the predictive accuracy for early AKI over either biomarker alone (area under the receiver operating characteristic curve: 0.82; 95% CI, 0.74-0.89). The combined categorical cut point defined by BNP >267 pg/mL or NGAL >231 ng/mL correctly identified 15 of 16 early AKI patients (sensitivity 94%, specificity 61%). During multivariable regression analysis, the combined BNP/NGAL cutoff remained the independent predictor of early AKI (hazard ratio 10.82; 95% CI, 1.22-96.23; P = .03).ConclusionA model combining the markers BNP and NGAL is a powerful predictor of early AKI in patients with lower respiratory tract infection.     

Increased risk of end-stage renal disease among hip fracture patients

BackgroundInflammation-related microvasculr disease, albuminuria, and rapid deterioration of renal function can accelerate the development of end-stage renal disease (ESRD). The role of hip fracture (HFr), a disorder that involves inflammation, in the development of ESRD has not been fully investigated. This study explored whether HFr increases the risk of ESRD.MethodsTaiwan National Health Insurance inpatient claims were used to identify 83,550 patients newly diagnosed with HFr from 2000 to 2006, and 83,550 age- and sex-matched patients without HFr were randomly selected for comparison. Hazards of ESRD combined with HFr, comorbidities, including hypertension, hyperlipidemia, peripheral arterial disease, osteoporosis and asthma, and general health status, with Charlson comorbidity index (CCI), were assessed using data to the end of 2011.ResultsESRD risk was 1.42-fold higher (95% confidence interval [CI]:1.29–1.33) in the HFr cohort than in the control group, which was computed using the Cox proportional model. Age-specific analysis revealed that the adjusted hazard ratios (aHRs) of ESRD for HFr patients increased slightly as age increased, with an aHR of 1.56 (95% CI:1.35–1.81) for patients 65–74 years old, which gradually decreased to 0.88 (95% CI:0.66–1.18) for patients ≥ 85 years old. ESRD risk increased as HFr severity increased, with an aHR of 6.71 (95% CI:5.90–7.63) for patients with severe HFr.ConclusionThis study is the first to report that HFr, in combination with underlying osteoporosis-related chronic illness, microvascular disease and chronic inflammation, is associated with an increased risk of ESRD, particularly among relatively younger people.     

2型糖尿病患者尿液MMP-9及MMP-9／NGAL活性检测及其临床意义

目的探讨2型糖尿病（T2DM）患者尿液中基质金属蛋白酶9（MMP-9）及MMP-9／中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的活性与T2DM的关系。方法应用明胶酶谱法对35例健康人和142例T2DM患者的尿液进行检测。结果（1）急性并发症组尿液中MMP-9及MMP-9／NGAL的活性及其检出率明显高于对照组及单纯糖尿病组（P〈0．01）;（2）慢性并发症组尿液MMP-9及MMP-9／NGAL的活性及其检出率也明显高于对照组（P〈0．01）,肾损害亚组MMP-9活性明显高于无肾损害亚组（P〈0．05）,且其活性随病程呈抛物线型变化趋势。结论通过对MMP-9及MMP-9／NGAL活性的检测,可预测炎症、应激的发生,MMP-9及MMP-9／NGAL可作为糖尿病肾损害的早期诊断指标。     

Association of renal transplantation with reduced risk of myocardial infarction and ischemic stroke in ANCA-associated vasculitis: An observational cohort study

ObjectiveMyocardial infarction and ischemic stroke are leading causes of cardiovascular (CV) morbidity and mortality in ANCA-associated vasculitis (AAV), especially for the 20% with end-stage renal disease (ESRD). We assessed the impact of renal transplantation on the risk of myocardial infarction and stroke among patients with ESRD due to AAV.MethodsWe identified patients from the United States Renal Data System with ESRD due to AAV between 2000 and 2016. We examined the association between renal transplantation and the risk of non-fatal and fatal myocardial infarction or ischemic stroke among waitlisted patients using Medicare claims and death data through 2017. We used time-varying Cox proportional hazards models with age as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for myocardial infarction and ischemic stroke events among patients who received a renal transplant compared to those who remained on the waitlist.ResultsOf 1029 waitlisted patients, 593 (58%) were transplanted over a mean of 5.7 years. There were 17 events (4.6/1,000 person-years) in the transplanted group and 40 events (13.7/1,000 person-years) in the group that remained waitlisted. A renal transplant was associated with a 78% lower risk of myocardial infarction or ischemic stroke (HR=0.22, 95% CI 0.11 to 0.47). These findings persisted across sex and age groups and when censoring patients after living donor transplantation.ConclusionsAmong AAV patients with ESRD, renal transplantation can substantially reduce the risk of myocardial infarction and ischemic stroke. Improving access to transplantation for this population may further improve outcomes.