Comparative effects of sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors on kidney function decline in Japanese individuals with type 2 diabetes.

BACKGROUND: Limited direct comparative studies exist in terms of the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on the kidney outcomes in Japanese individuals with type 2 diabetes. METHODS: This retrospective cohort study included 561 Japanese adults with type 2 diabetes, who were newly prescribed either an SGLT2i or a DPP4i and had an eGFR ≥ 30 mL/min/1.73 m2. The cohort comprised 207 women and 354 men, with a mean (± standard deviation) age of 63 (± 12) years. The exposure and outcome were SGLT2i or DPP4i initiation and eGFR slope during the overall follow-up period, restricted to participants who were followed for ≥2 years. We adopted the on-treatment analysis. Analysis of covariance was used to compare the adjusted eGFR slope between the two groups, incorporating 10 variables at baseline. RESULTS: During the median follow-up period of 3.4 years, least square mean (95% CI) eGFR slopes were -1.91 (-2.15, -1.67) and -1.12 (-1.58, -0.67) mL/min/1.73 m2/year in individuals treated with a DPP4i (n = 460) and an SGLT2i (n = 101), respectively, demonstrating statistical significance (p = 0.002). The robustness of this finding was strengthened by sensitivity analyses. CONCLUSIONS: This study provides potential evidence of the superiority of SGLT2is over DPP4is in slowing kidney function decline in Japanese adults with type 2 diabetes and eGFR ≥ 30 mL/min/1.73 m2.

Effects of simultaneous pancreas and kidney transplantation in Japanese individuals with type 1 diabetes and end-stage kidney disease.

This single-center observational cohort study aimed to assess the potential benefits of simultaneous pancreas and kidney transplantation (SPK) in terms of mortality and kidney graft outcomes in Japanese individuals with type 1 diabetes (T1D) and end-stage kidney disease (ESKD). We first compared all-cause mortality rates between 78 SPK recipients and 108 non-transplanted individuals with T1D and ESKD. To mitigate the bias stemming from immortal time before receiving SPK, we utilized Cox regression models treating SPK as a time-dependent covariate. Next, we compared all-cause mortality rates and kidney graft loss rates between 65 SPK recipients and 58 kidney transplantation alone (KTA) recipients. Multivariate Cox hazard models and Fine and Gray competing-risk models were employed. SPK recipients experienced significantly lower all-cause mortality rates than non-transplanted individuals, even after accounting for immortal time bias (p = 0.015 by log-rank test, hazard ratio [HR] = 0.334, p = 0.025). When comparing SPK and KTA recipients, no statistically significant difference was observed in mortality rates (HR = 0.627, p = 0.588 by Cox model; HR = 0.385, p = 0.412 by Fine and Gray model) or kidney graft loss rates (HR = 0.612, p = 0.436 by Cox model; HR = 0.639, p = 0.376 by Fine and Gray model). Dysglycemia-associated mortality were observed in non-transplanted individuals and KTA recipients, but not in SPK recipients. These findings highlight the potential life-saving impact of SPK compared with intensive insulin therapy and dialysis. Additionally, this study suggests that both SPK and KTA may offer comparable outcomes. These findings have significant implications for clinical decision-making in the context of organ transplantation for individuals with T1D and ESKD.

Association between 1-year changes in urinary albumin-to-creatinine ratio and kidney disease progression in Japanese individuals with diabetes: a historical cohort study.

BACKGROUND: The National Kidney Foundation recently proposed a ≥ 30% decrease in urinary albumin-to-creatinine ratio (UACR) over 0.5-2 years as a surrogate endpoint for chronic kidney disease (CKD) progression in individuals with baseline UACR > 30 mg/g. This historical cohort study aimed to determine the applicability of a decrease in UACR, within as little as 1 year, as a surrogate endpoint for Japanese individuals with type 2 diabetes mellitus (T2D). METHODS: A total of 5067 individuals with T2D were divided into three groups based on 1-year change in UACR: ≥ 30% decrease (UACR decreased group), < 30% decrease and < 30% increase (UACR unchanged group), or ≥ 30% increase (UACR increased group). The primary endpoint was a composite of a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or the initiation of kidney replacement therapy, whichever occurred first. RESULTS: At baseline, the proportions of individuals with normoalbuminuria, microalbuminuria, and eGFR ≥ 60 mL/min/1.73 m2 were 68.1%, 22.1%, and 75.5%, respectively. During a median follow-up of 6.8 years, 926 individuals (18.3%) reached the composite endpoint. Adjusted hazard ratios (vs. the UACR unchanged group) for the UACR decreased and increased groups were 0.758 (95% confidence interval [CI], 0.636-0.905; P = 0.002) and 1.304 (95% CI, 1.108-1.536; P = 0.001), respectively. CONCLUSIONS: These findings support the use of 1-year changes in UACR as a surrogate endpoint for the progression of CKD and the implementation of a ≥ 30% decrease in UACR as a positive efficacy endpoint in Japanese individuals with T2D and early-stage kidney disease.

Changes in urinary albumin as a surrogate for kidney disease progression in people with type 2 diabetes.

BACKGROUND: It remains unclear whether urinary albumin changes can predict subsequent kidney disease progression in people with diabetes. METHODS: This retrospective cohort study included 4570 Japanese adults with type 2 diabetes (T2D). The exposure was changes in urinary albumin-to-creatinine ratio (UACR) over 3 years, categorized into three categories: ≤ - 30%, minor change, or ≥ 30%. During the exposure period, eGFR decline was also examined and categorized into two categories: < 30% or ≥ 30% decline. The primary outcome was the composite of eGFR halving or initiation of kidney replacement therapy (KRT). The secondary outcome was the initiation of KRT. RESULTS: In the spline model, the hazard ratio for the primary outcome increased linearly on the log2 scale of UACR changes. When classified into six groups based on the categories of UACR changes and eGFR decline, people with a ≤ - 30% UACR change and < 30% eGFR decline had a 38% lower incidence of the outcome compared to those with a minor UACR change and < 30% eGFR decline. Meanwhile, the risk in those with a ≤ - 30% UACR change and ≥ 30% eGFR decline was 2.89 times. People with a ≥ 30% UACR change had the higher risk, regardless of whether a ≥ 30% eGFR decline occurred. Similar results were obtained in the secondary outcome. CONCLUSIONS: UACR changes can be a useful surrogate for kidney disease progression in people with T2D. However, when setting a decrease in UACR as the surrogate, it may be necessary to simultaneously evaluate kidney function decline.

Association of Estimated Glomerular Filtration Rate With Progression of Albuminuria in Individuals With Type 2 Diabetes.

OBJECTIVE: To elucidate the association of glomerular filtration rate (GFR) at baseline with subsequent progression of albuminuria in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a single-center retrospective cohort study of 6,618 Japanese adults with type 2 diabetes and urinary albumin-to-creatinine ratio of <300 mg/g, comprising 2,459 women and 4,159 men with a mean (± SD) age of 60 ± 12 years. The exposure was baseline estimated GFR (eGFR) (mL/min/1.73 m2), treated as a categorical variable and classified into five categories: ≥90, 75-90, 60-75, 45-60, and <45, as well as a continuous variable. The outcome was progression of albuminuria category (i.e., from normoalbuminuria to micro- or macroalbuminuria or from micro- to macroalbuminuria). Hazard ratios (HRs) for the outcome were estimated using the multivariable Cox proportional hazards model. In the analysis treating baseline eGFR as a continuous variable, the multivariable-adjusted restricted cubic spline model was used. RESULTS: During the median follow-up period of 6.3 years, 1,190 individuals reached the outcome. When those with a baseline eGFR of 75-90 mL/min/1.73 m2 were considered the reference group, HRs (95% CIs) for the outcome in those with a baseline eGFR of ≥90, 60-75, 45-60, or <45 mL/min/1.73 m2 were 1.38 (1.14-1.66), 1.34 (1.14-1.58), 1.81 (1.50-2.20), or 2.37 (1.84-3.05), respectively. Furthermore, the inverse J-shaped curve was more clearly shown by the spline model. CONCLUSIONS: This study of Japanese adults with type 2 diabetes suggests that both high and low GFRs are implicated in the pathogenesis of albuminuria progression.

Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study.

Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rß, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

Kidney outcomes and all-cause mortality in people with type 2 diabetes exhibiting non-albuminuric kidney insufficiency.

AIM/HYPOTHESIS: It remains unclear whether people with diabetes exhibiting non-albuminuric kidney insufficiency have higher risk of kidney function decline and mortality compared with those exhibiting preserved kidney function without albuminuria. Furthermore, information regarding the incidence of albuminuria in people with this unique phenotype is sparse. Here, we aimed to elucidate the risk of the kidney outcomes and all-cause mortality in people with diabetes exhibiting non-albuminuric kidney insufficiency. METHODS: In this retrospective cohort study, 8320 Japanese adults with type 2 diabetes were classified into four groups based on the presence of albuminuria and kidney insufficiency at baseline, defined as urinary albumin/creatinine ratio of equal to or above 30 mg/g and eGFR of less than 60 ml min-1 1.73 m-2, respectively. The primary composite kidney endpoint was a 50% decrease in eGFR from baseline or the initiation of kidney replacement therapy. The annual percentage change in eGFR slope and progression of albuminuria category were evaluated as the secondary and tertiary kidney endpoints, respectively. All-cause death was also set as the endpoint. RESULTS: Compared with people exhibiting non-albuminuric preserved kidney function, those with non-albuminuric kidney insufficiency had the higher risk for the primary kidney endpoint (HR 4.1; 95% CI 2.5, 6.7; p < 0.001), steep percentage change in eGFR slope (-1.96%/year vs -1.36%/year, p < 0.001), incidence of albuminuria (HR 2.1; 1.7, 2.6; p < 0.001) and all-cause mortality (HR 1.5; 1.2, 2.0; p = 0.003). In the sensitivity analyses treating the incidence of albuminuria as a competing risk, people with non-albuminuric kidney insufficiency still had higher risk for the primary kidney endpoint and all-cause mortality than those with non-albuminuric preserved kidney function (subdistribution HR 2.8; 1.4, 5.6; p = 0.004; and 1.6; 1.1, 2.2; p = 0.014, respectively). CONCLUSIONS/INTERPRETATION: People with type 2 diabetes exhibiting non-albuminuric kidney insufficiency had poorer kidney outcomes and life prognosis than those exhibiting non-albuminuric preserved kidney function.

Is Chronic Kidney Disease Affecting the Postoperative Complications of Vitrectomy for Proliferative Diabetic Retinopathy?

Chronic kidney disease (CKD) is a well-known risk factor for postoperative complications in several surgical fields. However, although prevalent among diabetic candidates for vitrectomy, the effect of CKD on vitrectomy outcomes remains unclear. This study aimed at clarifying the relationship between CKD and the occurrence of vitrectomy-related complications in patients with proliferative diabetic retinopathy (PDR). The 6-month incidences of vitreous hemorrhage (VH) and neovascular glaucoma (NVG) following vitrectomy for PDR were compared among the following groups: stages 1-2 CKD (60 patients), stages 3-5 CKD (70 patients not on hemodialysis), and hemodialysis (HD; 30 patients). We also determined whether the deterioration of the estimated glomerular filtration rate (eGFR) was associated with post-vitrectomy events. The incidence of VH was significantly higher in the stages 3-5 CKD group (43%) than in the stages 1-2 CKD (10%) and HD (10%) groups. NVG was more common in the stages 3-5 CKD group (17%) than in the stages 1-2 CKD (2%) and HD (0%) groups. The reduced estimated glomerular filtration rate (eGFR) was the only significant variable associated with post-vitrectomy VH and NVG. Patients with PDR and CKD, particularly those with lower eGFR, might be at risk for post-vitrectomy VH and NVG.

Cross-sectional and longitudinal associations between dipstick hematuria and chronic kidney disease in patients with type 2 diabetes.

AIMS: To examine the association of dipstick hematuria with kidney function and albuminuria in patients with type 2 diabetes (T2D). METHODS: A total of 7,945 patients with T2D were studied. In the cross-sectional study, patients were classified into 6 groups based on the stage of albuminuria and estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 at baseline. In the longitudinal study where patients were classified by the presence of hematuria, the primary composite endpoint was a 30% decrease in eGFR from baseline or the initiation of kidney replacement therapy. Other outcomes included eGFR slope and stage progression of albuminuria. RESULTS: Cross-sectionally, hematuria was more prevalent in patients with more advanced stages of albuminuria and with lower eGFR, independently of each other. In the longitudinal study, patients with hematuria experienced 50% increased incidence of the primary endpoint (p < 0.001). The eGFR slope was steeper in patients with hematuria than in those without hematuria (p < 0.001). On the other hand, hematuria was unlikely to be associated with the progression of albuminuria. CONCLUSIONS: In patients with T2D, dipstick hematuria was associated with prevalent albuminuria and reduced eGFR, as well as faster decline in kidney function but not higher risk of development or progression of albuminuria.

Effects of dietary protein intake on renal outcome and mortality in patients with advanced diabetic nephropathy.

BACKGROUND: The difficulty of adhering to a low-protein diet is a serious limitation of randomized controlled trials aimed at validating the efficacy of this therapy. In this observational study of patients with diabetic nephropathy, we examined the association of dietary protein intake (DPI) with renal outcome and mortality, taking into account the nutritional status. METHODS: We conducted a single-center historical cohort study of 449 adult Japanese patients with type 2 diabetes and the urinary albumin-to-creatinine ratio of ≥ 300 mg/g or estimated glomerular filtration rate of < 30 mL/min/1.73 m2. DPI was estimated with a formula using nitrogen levels in spot urine and body mass index. Malnutrition was defined as the Geriatric Nutritional Risk Index of ≤ 98. The primary and secondary endpoints were renal replacement therapy (RRT) initiation and mortality before RRT initiation, respectively. The Fine and Gray subdistribution hazard model was used to determine the relative effects of DPI on the respective endpoint. RESULTS: Decreased DPI was associated with lower incidence of RRT with an adjusted hazard ratio of 0.81 (95% confidence interval: 0.72-0.92, p < 0.001). The interaction between DPI and nutritional status with respect to mortality was significant (p interaction = 0.047). Decreased DPI was a risk factor for mortality in patients with malnutrition (p = 0.009) but not in those without malnutrition (p = 0.559). CONCLUSIONS: In patients with type 2 diabetic nephropathy, lower DPI was associated with lower incidence of RRT initiation, suggesting beneficial effects of a low-protein diet on kidneys. Conversely, lower DPI might lead to increased mortality in patients with malnutrition.

Vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy undergoing hemodialysis.

AIMS/INTRODUCTION: For diabetes patients undergoing hemodialysis, vitreous hemorrhage seems to be a hemodialysis-induced hemorrhagic complication because of the effect of systemic anticoagulation. However, it is unclear whether hemodialysis is associated with vitreous hemorrhage in diabetes patients. We therefore carried out this cohort study to clarify the relationship between hemodialysis and vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy. MATERIALS AND METHODS: This was a single-center, retrospective, cohort study. We compared the incidence of vitreous hemorrhage in non-vitrectomized proliferative diabetic retinopathy eyes between the hemodialysis group (145 eyes) and peritoneal dialysis group (36 eyes), which does not require the use of systemic anticoagulation (parallel-group study), and in hemodialysis patients in the 12-month period before and after the start of hemodialysis (before-after study). We also determined the risk factors for vitreous hemorrhage after the start of hemodialysis based on the patients' systemic and ophthalmic characteristics. RESULTS: There was no significant difference in the first-year incidence of vitreous hemorrhage between the hemodialysis (23.4%) and peritoneal dialysis groups (22.2%, P = 1.000). The incidence of vitreous hemorrhage in the dialysis period (23.4%) was significantly lower than that in the predialysis period (35.2%, P = 0.008). Only application of panretinal photocoagulation within the 6 months immediately before hemodialysis was significantly associated with the incidence of vitreous hemorrhage after the start of hemodialysis (P < 0.001). CONCLUSIONS: Hemodialysis therapy does not seem to be associated with a higher risk of vitreous hemorrhage in diabetes patients with proliferative diabetic retinopathy.

Rapid increase in the incidence of end-stage renal disease in patients with type 1 diabetes having HbA1c 10% or higher for 15 years.

The incidence of end-stage renal disease (ESRD) in Japanese patients with type 1 diabetes mellitus (T1DM) was investigated regarding the association between mean HbA1c values during follow-up and the duration of follow-up/illness. The study includes 988 patients diagnosed at ages younger than 30 yr. These patients were initially examined between 1962 and 1999, and HbA1 and/or HbA1c measurements were taken for at least 3 yr after 1980. The follow-up period was from the date of the first HbA1 or HbA1c measurement to the final measurement day, or HbA1c measurement day immediately before the development of ESRD. The condition progressed to ESRD in 63 patients (mean duration of illness: 23.6 yr). Cox regression analysis revealed that patients with HbA1c of ≥ 10% had a significantly increased higher risk than those with HbA1c under 8% (P < 0.0001). The HbA1c cut-off point was 10.0%. The HbA1c value was ≥ 10% at baseline and during follow-up in 128 patients. Assuming that HbA1c of ≥ 10% persisted since the time of diagnosis in these patients, the cumulative incidence of ESRD abruptly increased after 15 yr of illness. Thus, the incidence of ESRD increased after the persistence of HbA1c of ≥ 10% for 15 yr.

Temporal trends in the prevalence of albuminuria and reduced eGFR in Japanese patients with type 2 diabetes.

Changes over time have been shown in renal manifestations in individuals with diabetes in the United States; however, whether the trends are shared across ethnicities is unknown. We conducted this single-center serial cross-sectional study to determine temporal changes in albuminuria and reduced kidney function in Japanese patients with type 2 diabetes. This study included adult Japanese patients with type 2 diabetes who first visited our institute between 2004 and 2013. Temporal changes during the 10 years in the frequency of albuminuria ( ≥ 30 mg/g creatinine) and reduced eGFR ( < 60 mL/min/1.73 m2) were analyzed using the univariate and multivariate logistic regression analyses and Granger causality test. 5331 Japanese patients with type 2 diabetes, 1892 women and 3439 men, with the mean age of 56 ± 13 years, were studied. There was no change in the prevalence of albuminuria in the univariate analysis; however, a significantly decreasing trend was observed after adjustment for several covariates. On the other hand, patients with reduced eGFR significantly increased over time, although the statistical significance disappeared after adjustment for the covariates, including levels of serum uric acid and hemoglobin and use of renin-angiotensin inhibitors. The Granger causality test showed that time series for use of RAS inhibitors and BMI had a causative role in time series for reduced eGFR. In conclusion, prevalence of albuminuria decreased and that of reduced eGFR remained stable after adjustment for clinical characteristics in Japanese patients with type 2 diabetes during the last decade.

Effects of uric acid on kidney function decline differ depending on baseline kidney function in type 2 diabetic patients.

BACKGROUND: Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. METHODS: In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. RESULTS: There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. CONCLUSIONS: The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.

Brachial-ankle pulse wave velocity, but not ankle-brachial index, predicts all-cause mortality in patients with diabetes after lower extremity amputation.

We examined whether brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI) are predictors for mortality in diabetic patients after lower extremity amputation. This was an observational historical cohort study of 102 Japanese diabetic patients after first non-traumatic lower extremity amputation, with a mean age of 63 years (standard deviation 12 years). The end-point was all-cause mortality. During the mean follow-up period of 3.3 years, 44 patients reached the end-point. In both univariate and multivariate analyses, baPWV (m/s) (hazard ratio [HR] 1.05 and 1.04, both P < 0.01, respectively), but not ABI (HR 0.38 and 0.89, P = 0.08 and 0.86, respectively), was a significant predictor for the end-point. When baPWV (above or below the median [21.8 m/s]) and ABI (normal [0.9-1.4] or not) were analyzed as categorical variables, the results were similar. In conclusion, baPWV, but not ABI, might be a predictor for all-cause mortality in diabetic patients after lower extremity amputation.

Quality of life in Japanese patients with type 1 diabetes and end-stage renal disease undergoing simultaneous pancreas and kidney transplantation.

We conducted this cross-sectional study to assess quality of life (QOL) in Japanese patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) undergoing simultaneous pancreas and kidney transplantation (SPK). Japanese patients with T1DM without diabetic nephropathy (N = 10), and those undergoing chronic dialysis (N = 52), kidney transplantation alone (KTA, N = 25), and SPK (N = 16) were studied. Comprehensive health-related QOL was assessed using the Short Form 36 version 2 (SF-36v2). Emotional functioning in diabetes was measured by the Problem Area In Diabetes (PAID) scale. Severity of impaired hypoglycemic awareness was assessed using the Clarke hypoglycemic score. SPK patients had significantly higher (or tended to have higher) subscale and summary SF-36 scores than dialysis patients and KTA patients. PAID scores were significantly lower in SPK patients than in dialysis patients and KTA patients. Clarke hypoglycemic scores were also significantly lower in SPK patients than dialysis patients. In KTA and dialysis patients, there were no significant differences in the SF-36 subscale/summary scores, PAID scores, or Clarke hypoglycemic scores. In conclusion, QOL for Japanese patients receiving SPK may be superior to that of dialysis patients and KTA patients. Whether SPK actually improves QOL needs to be clarified in longitudinal studies.

Effects of statins on the kidneys in patients with type 2 diabetes.

BACKGROUND: Effects of statins on kidneys in diabetic patients remain unclear. METHODS: This was an observational, historical cohort study of type 2 diabetic patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. We studied 412 patients newly prescribed statins, and 946 controls without a prescription history of statins (including the follow-up period). Outcomes were annual change in eGFR, ≥30 % decrease in eGFR from baseline, and progression of albuminuria, analyzed using a propensity score matching. RESULTS: A total of 168 pairs were matched for propensity score. Annual eGFR change (mL/min/1.73 m2/year) in the statin group was greater than in controls (-2.24 vs. -1.56, p = 0.024). The hazard ratio of the statin group (vs. controls) for ≥30 % decrease in eGFR and progression of albuminuria was 1.74 (p = 0.082) and 0.85 (p = 0.624), respectively. When the statin group was classified by differences in statin solubility, eGFR change and hazard ratio for ≥30 % decrease in eGFR in the lipophilic statin group were greater than in controls (-2.64 vs. -1.71, p = 0.031 and 2.15, p = 0.049); however, the outcomes in the hydrophilic statin group were not different (-2.35 vs. -1.71, p = 0.106 and 1.08, p = 0.827). The hazard ratio of lipophilic and hydrophilic statin group (vs. controls) for progression of albuminuria was 1.31 (p = 0.552) and 0.69 (p = 0.367). In the analyses using the unmatched cohort, similar results were obtained. CONCLUSIONS: Statins have no beneficial effects on kidneys in diabetic patients. In fact, lipophilic statins might have potential harmful effects on kidney function.

Switching from subcutaneous insulin injection to oral vildagliptin administration in hemodialysis patients with type 2 diabetes: a pilot study.

We conducted this pilot study to examine efficacy and safety of switching from subcutaneous injection of insulin to oral administration of a DPP-4 inhibitor, vildagliptin, in type 2 diabetic patients undergoing hemodialysis. Consecutive type 2 diabetic patients on hemodialysis who were switched from insulin to vildagliptin between August 2010 and April 2011 were extracted from the hospital database. In patients whose post-switch increase in glycated albumin (GA) levels was <1.5 % without resuming insulin at least 24 weeks, the switch was defined as efficacious. In patients who resumed insulin therapy due to worsening of glycemic control or in patients whose GA levels increased by 1.5 % or more, the switch was considered inefficacious. To predict patients in whom switch to vildagliptin proved efficacious, receiver-operating characteristic (ROC) analysis and logistic regression analysis were performed. A total of 20 patients were extracted; insulin dose was 12 ± 4 units/day; levels of GA and HbA1c was 21.0 ± 3.7 % and 6.5 ± 0.6 %, respectively. Among them, 11 patients were efficaciously switched to vildagliptin. ROC analysis and logistic analysis showed that patients with a shorter duration of diabetes, as well as lower levels of GA and HbA1c, appeared to have a higher likelihood of successful treatment switches. None of the patients developed hypoglycemic symptoms, ketoacidosis, or serious adverse events. In conclusion, efficacious change from insulin to vildagliptin was possible in approximately a half of type 2 diabetic dialysis patients. Long-term follow-up studies including large number of patients are needed to confirm these results.

Hypoglycemia Observed on Continuous Glucose Monitoring Associated With IGF-2-Producing Solitary Fibrous Tumor.

CONTEXT: Tumors producing IGF-2 (IGF-2oma) are a major cause of spontaneous hypoglycemia. The treatment mainstay is surgical resection. Many case reports note resolution of hypoglycemia after IGF-2oma resection; however, outcomes are variable according to tumor type. We report a case of resolving hypoglycemia, observed on continuous glucose monitoring, after resection of an IGF-2-producing solitary fibrous tumor of pleura and review the current literature. CASE REPORT: A 69-year-old woman presented with impaired consciousness because of hypoglycemia. An IGF-2oma was diagnosed as the cause for hypoglycemia because of decreased serum insulin and IGF-1, the presence of a pleural tumor, and a high-molecular-weight form of serum IGF-2 detected by Western immunoblot. Surgical resection was performed; pathological examination demonstrated a solitary fibrous tumor with low-grade malignancy. Continuous glucose monitoring showed reversal of hypoglycemia after tumor resection. Approximately 2 years after resection, the patient has no signs of tumor recurrence or hypoglycemia. CONCLUSIONS: An IGF-2-producing solitary fibrous tumor of pleura in this case caused hypoglycemia. From a search of the literature of 2004-2014, 32 cases of IGF-2oma with hypoglycemia that underwent radical surgery were identified; in 19 (59%) patients, hypoglycemia was reversed, and there was no subsequent recurrence. The remaining 13 (41%) patients experienced tumor recurrence or metastasis an average of 43 months after initial tumor resection. The tumor of the present case was a low-grade malignancy. Regular follow-up with biomarker monitoring of glucose metabolism and assessment of hypoglycemic symptomatology, in conjunction with imaging tests, is important for detecting possible tumor recurrence and metastasis.