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Objectives: Our aim in this study was to investigate the prospective association between diabetes distress assessed with Problem Areas in Diabetes (PAID) survey scores at baseline and the subsequent risk of development or progression of diabetic nephropathy in people with type 2 diabetes., Methods: Longitudinal data were acquired from 2,845 individuals with type 2 diabetes registered in a Japanese diabetes registry. A Cox proportional hazards model was used to adjust for possible confounders to examine the prospective association between baseline diabetes distress (PAID score ≥40) and the development or progression of albuminuria., Results: Mean patient age, body mass index, and glycated hemoglobin level were 64.8 years, 24.5 kg/m 2 , and 57.4 mmol/mol (7.5%), respectively. We did not observe a significant association between diabetes distress and the subsequent risk of diabetic nephropathy development from normoalbuminuria to microalbuminuria/macroalbuminuria (multivariable-adjusted hazard ratio [HR]=0.95 over 4.2 years, 95% confidence interval [CI] 0.77 to 1.17, p=0.640); however, we identified a significant association for progression from microalbuminuria to macroalbuminuria (multivariable-adjusted HR=1.34 over 7.0 years, 95% CI 1.01 to 1.80, p=0.045). Stratification by sex revealed a significant association between diabetes distress and the subsequent risk of progressing diabetic nephropathy (HR=1.45, 95% CI 1.06 to 1.98, p=0.019) in males, but not females (HR=1.42, 95% CI 0.95 to 2.14, p=0.087)., Conclusions: Diabetes distress at baseline, assessed using the PAID survey, was associated with a subsequent risk of progressing diabetic nephropathy independent of possible confounders in males, but not females, with type 2 diabetes., (Copyright © 2023 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: A urinary biomarker sensitive to glomerular functional or structural changes in diabetic kidney disease is required. This study examined whether urinary C-megalin reflects renal function or albuminuria in diabetes., Methods: This was a cross-sectional study involving 1576 patients with type 1 or 2 diabetes. The exposure variables were estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR), and the outcomes were urinary C-megalin excretion and concentration. Two-part models were used to examine the associations between eGFR and UACR with urinary C-megalin excretion or concentration., Results: The UACR was linearly associated with urinary C-megalin excretion (per 100 mg/gCr of UACR; 11.8 fM/gCr [95% CI 8.9-14.7]). There was no association between decreasing eGFR and increasing urinary C-megalin excretion. The UACR was also linearly associated with the urinary C-megalin concentration (per 100 mg/gCr of UACR, 7.7 fM/L [95% CI 5.8-9.6]). At eGFR values > 60 mL/min/1.73 m 2 , the eGFR and urinary C-megalin concentration were inversely linearly related (per 10 mL/min/1.73 m 2 decline, 7.7 fM/L [95% CI 0.2-15.1])., Conclusion: Urinary C-megalin excretion as well as concentration levels are potentially useful biomarkers to detect early changes in diabetic kidney disease., (© 2021. Italian Society of Nephrology.)

Aims: We aimed to determine the prospective association between proton pump inhibitor (PPI) use and the subsequent risk of the development or progression of albuminuria or eGFR., Methods: Longitudinal data of patients with diabetes were obtained from a large Japanese diabetes registry. To assess the independent correlation between PPI use and the development or progression of urine microalbuminuria, the time-varying Cox proportional hazards model was used with adjustment for potential confounders., Results: The mean patient age, body-mass index (BMI), and hemoglobin A1c (HbA1c) levels were 65.7 y, 24.5 kg/m 2 , and 7.5% (57.9 mmol/mol), respectively. In 1711 patients without albuminuria, we observed 599 cases with development of albuminuria over median follow-up of 4.0 years, and in 1279 patients with microalbuminuria, 290 cases with urinary albuminuria progression over 4.0 years, and 257 eGFR decline cases over 3.8 years. PPI use was not associated with the development of albuminuria (HR = 0.88; 95%CI, 0.77-1.01; p = .058), progression of albuminuria (HR = 1.24; 95%CI, 0.87-1.79; p = .236), nor eGFR decline (HR = 1.05; 95%CI, 0.81-1.34; p = .973) even in a propensity score-adjusted model with time-varyingly updating PPI use information., Conclusions: In conclusion, PPI use was not associated with the subsequent risk of development or progression of albuminuria, or eGFR decline in patients with diabetes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: To assess the association between dipstick hematuria and estimated glomerular filtration rate (eGFR) decline in Japanese patients with type 2 diabetes., Methods: Longitudinal data were obtained from 3068 Japanese patients with type 2 diabetes. To assess the independent association between dipstick hematuria and eGFR decline, we used Cox proportional hazard model adjusted for potential confounders., Results: Median follow-up period was 699.7days. Mean age, body mass index (BMI), and HbA1c level were 65.7years, 24.6kg/m 2 , and 7.5% (58.1mmol/mol), respectively. Positive dipstick hematuria was significantly associated with baseline eGFR and severity of albuminuria (p<0.001). The multivariable-adjusted hazard ratio for eGFR decline in patients with dipstick hematuria compared with those without dipstick hematuria was 2.19 [95% confidence interval (CI): 1.22-3.91]; this association remained significant even after the exclusion of patients who did not have diabetic retinopathy (hazard ratio: 2.39; 95% CI: 1.13-5.04)., Conclusion: Positive dipstick hematuria was associated with severity of albuminuria and renal function. A significant association was found between dipstick hematuria and increased risk of eGFR decline among patients with type 2 diabetes. Therefore, our results suggest that dipstick hematuria is perhaps indicative of more severe diabetic nephropathy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To assess the prospective association between baseline serum uric acid level and subsequent risk of development or progression in albuminuria., Methods: Longitudinal data were obtained from 2518 patients with type 2 diabetes in the development cohort and registered in a Japanese diabetes registry. To assess the independent correlations between baseline serum uric acid quartiles and either the development or progression of diabetic nephropathy for 2 years, the Cox proportional hazards model was used and adjusted for potential confounders., Results: The mean patient age, body mass index, and glycated hemoglobin (HbA1c) level were 66.1 years, 24.6 kg/m(2), and 7.5 % (57.6 mmol/mol), respectively. The baseline serum uric acid levels, with mean values of 3.6, 4.9, 5.8, and 7.3 mg/dL from the first to fourth quartiles, were significantly associated with the urinary albumin/creatinine ratio at baseline (p < 0.001). Baseline uric acid levels were not significantly associated with the development of nephropathy, but they were with the progression of nephropathy. The multivariable-adjusted hazards ratios for the progression from microalbuminuria to macroalbuminuria were 2.17 [95 % confidence interval (CI) 1.15-4.08; p = 0.016], 3.04 (95 % CI 1.67-5.53; p < 0.001), and 3.56 (95 % CI 1.83-6.93; p < 0.0011) for the first, third, and fourth quartiles of serum uric acid levels, respectively, as compared to that for the second quartile. We did not observe significant association between uric acid levels and change in estimated glomerular filtration rate., Conclusions: Low and high serum uric levels, independent of possible confounders, were associated with a subsequent risk of progression, not development, in albuminuria in type 2 diabetes patients. Therefore, serum uric acid levels may be useful for predicting the future risk of progression of microalbuminuria.

Objective: To assess the prospective association between baseline serum hs-CRP concentration and the subsequent risk of development or progression of diabetic nephropathy., Research Design and Methods: Longitudinal data were obtained from 2,518 patients with type 2 diabetes registered in a Japanese diabetes registry. To assess the independent correlations between serum baseline hs-CRP and either the development or progression of diabetic nephropathy 1 year later, the Cox proportional hazards model was used and adjusted for potential confounders., Results: The mean patient age, BMI, and HbA1c level were 66.1 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Baseline serum hs-CRP levels were significantly associated with the urinary albumin-to-creatinine ratio at baseline (P < 0.001). Multivariable adjusted hazard ratio for the development from normoalbuminuria to microalbuminuria was 1.31 (95% CI 0.80-2.17; P = 0.286), 1.55 (1.16-2.08; P = 0.003), and 1.57 (1.22-2.03; P = 0.001), respectively, for the second, third, and fourth quartiles of serum hs-CRP levels, showing a statistically significant linear trend across categories (P < 0.001). We did not observe a significant association between hs-CRP levels and the subsequent risk of diabetic nephropathy progression (P for trend = 0.575)., Conclusions: Serum hs-CRP levels, independent of possible confounders, were associated with a subsequent risk of developing, not progressing, diabetic nephropathy in type 2 diabetic patients. Serum hs-CRP may be useful for predicting the future risk of developing diabetic nephropathy., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

OBJECTIVE To assess the correlations between serum bilirubin levels and diabetic nephropathy development and progression in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Longitudinal data were obtained from 2,511 type 2 diabetic patients registered in a Japanese diabetes registry. To assess the independent correlations between serum bilirubin levels and either the development or progression of diabetic nephropathy, we used logistic regression analysis adjusted for potential confounders. RESULTS The median follow-up period was 503.4 days (range 238-777). The mean patient age, BMI, and HbA1c level was 65.2 years, 24.7 kg/m(2), and 7.5% (58.5 mmol/mol), respectively. Baseline serum bilirubin levels were significantly associated with the urinary albumin-creatinine ratio at baseline (P < 0.001) and 1 year after registration (P < 0.001). Multivariable adjusted odds ratios for progression from microalbuminuria to macroalbuminuria for the second, third, and fourth quartile of serum bilirubin levels were 0.89 (95% CI 0.49-1.58), 0.93 (0.47-1.83), and 0.33 (0.13-0.84), respectively, showing a statistically significant linear trend across categories (P = 0.032). However, this trend disappeared after adjustment for hemoglobin levels. CONCLUSIONS Serum bilirubin levels were associated with diabetic nephropathy progression in type 2 diabetic patients independent of possible confounders. Serum bilirubin levels might be the link in the correlation between hemoglobin levels and nephropathy progression.

Aims: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus.Methods: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model.Results: During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07-1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10-<30 mg/gCr) UACR.Conclusions: Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation. [ABSTRACT FROM AUTHOR]