Presentation of glomerulocystic disease in a young onset diabetes: A case report.

RATIONALE: This case report presents a challenging medical scenario involving a young adult male who exhibited an unusual combination of symptoms, including abrupt weight loss, declining renal function, proteinuria, and concurrent onset of diabetes mellitus. Remarkably, the patient had no previous medical history or family history of similar conditions, necessitating a comprehensive investigation. PATIENT CONCERNS: On March 10, 2021, a 25-year-old male sought medical attention due to the aforementioned symptoms. Initial assessments revealed stage 5 chronic kidney disease, with elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels, as well as significant proteinuria. The only notable physical finding was obesity, and renal ultrasound showed normal-sized kidneys without cysts. DIAGNOSIS: A treatment plan was initiated to stabilize creatinine levels, including medications such as Glimepiride, Glyxambi, Bisoprolol, Amlodipine, and Valsartan. However, despite diligent medication management, proteinuria persisted, prompting further evaluation. A renal biopsy was performed on April 12th, 2023, leading to the diagnosis of glomerulocystic kidney disease with early-stage changes indicative of diabetic nephropathy. INTERVENTIONS: The patient continues to receive ongoing care and follow-up at our outpatient clinic to optimize therapeutic interventions and elucidate the underlying etiology of this complex clinical scenario. OUTCOMES: Ongoing investigations and therapeutic interventions are crucial to understand the underlying cause and optimize patient care in this intricate clinical scenario. LESSONS: This case underscores the complexity of diagnosing and managing a young adult presenting with concurrent renal dysfunction, proteinuria, and diabetes mellitus in the absence of prior underlying conditions. It highlights the importance of comprehensive evaluation and ongoing care in such challenging cases.

Efficacy and Safety of Dapagliflozin in Patients With Chronic Kidney Disease Across the Spectrum of Frailty.

BACKGROUND: A sizeable proportion of patients with chronic kidney disease (CKD) are reported to be frail. Here we examined the safety and efficacy of dapagliflozin in patients with CKD by frailty level. METHODS: Adults with CKD, with/without type 2 diabetes, with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5 000 mg/g were randomized to dapagliflozin (10 mg/day) or placebo. The primary endpoint was a composite of sustained ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from kidney or cardiovascular (CV) causes. RESULTS: Frailty index (FI), assessed by Rockwood cumulative deficit approach, was calculable in 4 303/4 304 (99.9%) patients: 1 162 (27.0%) in not-to-mildly frail (FI ≤0.210), 1 642 (38.2%) in moderately frail (FI 0.211-0.310), and 1 499 (34.8%) in severely frail categories (FI >0.311). Dapagliflozin reduced the risk of the primary composite endpoint across all FI categories (hazard ratios [95% confidence interval {CI}]: 0.50 [0.33-0.76], 0.62 [0.45-0.85], and 0.64 [0.49--0.83], respectively; p-interaction = 0.67). Results were similar for secondary outcomes including kidney composite outcome (sustained ≥50% eGFR decline, ESKD or death from kidney cause; p-interaction = 0.44), CV endpoint (heart failure hospitalization or CV death; p-interaction = 0.63), and all-cause mortality (p-interaction p = .42). Results were consistent when using FI as a continuous variable. Occurrence of serious adverse events was numerically lower in patients receiving dapagliflozin versus placebo in all FI categories (16.9% vs 20.1%, 26.3% vs 30.7%, and 42.9% vs 47.8%, in not-to-mildly, moderately, and severely frail categories, respectively). CONCLUSIONS: The relative benefit of dapagliflozin for all outcomes was consistent across all frailty categories, with no difference in associated safety.

Analysis of risk factors of infection in diabetic foot patients.

This cross-sectional study assessed the risk factors for infection in 150 diabetic foot patients admitted to the Xiamen University Hospital between October 2020 and October 2022. Patients were categorised as infected (n = 80) or uninfected (n = 70) cohorts. The diabetic foot was evaluated using the American Diabetic Foot Grading system, whereas ulcers were categorised using Wagner's method. Analysed were patient-specific information, clinical data and risk factors including neuropathy, arterial disease and foot deformities. Our findings revealed no statistically significant differences between infected and uninfected cohorts concerning age, body mass index, gender, duration of diabetes or ankle-brachial index values (p > 0.05). However, infected group had a higher proportion of smokers and reduced socio-economic status (p < 0.05). Wagner grades indicated a greater severity in the infected group, with grade 3, grade 4 and grade 5 differing significantly (p < 0.05). Comparative analysis of ulcer characteristics revealed no statistically significant differences in ulcer surface area and depth, but the infected group had a higher prevalence of osteomyelitis and a greater number of ulcers (p > 0.05). Blood vessel complications, retinopathy, the presence of three or more ulcers, osteomyelitis and diabetic nephropathy were substantially more prevalent in the infected group, as determined by univariate analysis (p < 0.05). Subsequent multivariate logistic analysis revealed that patients with blood vessel complications, retinopathy, osteomyelitis, diabetic nephropathy and three or more ulcers were at increased risk for infection (p < 0.05). In addition, lifestyle factors, such as smoking, sedentary behaviour, inadequate foot hygiene, obesity and poor glycaemic control, were also associated with higher infection rates. A multivariate analysis of foot wound factors revealed that deeper, longer and recurrent lesions increased the likelihood of infection. Escherichia coli was the most frequently isolated bacterium from the infected group's bacterial culture, followed by Pseudomonas aeruginosa and Staphylococcus aureus. The study enhanced our comprehension of the multifactorial risk factors associated with infections in diabetic foot patients, highlighting the need for thorough clinical evaluation, lifestyle modification and vigilant infection control.

Anti-factor H antibody-positive C3 glomerulonephritis secondary to poststreptococcal acute glomerulonephritis with diabetic nephropathy.

Poststreptococcal acute kidney glomerulonephritis (PSAGN) has been seen in adults in recent years, especially in patients with type 2 diabetes mellitus, and the renal prognosis has not always been good. There have been cases of PSAGN in which complete remission was not achieved and hematuria and proteinuria persisted, leading to end-stage renal disease. Previous reports showed that the patients subjected to PSAGN have an underlying defect in regulating the alternative pathway of complement, and they identified that antibodies to the C3 convertase, C3 nephritic factors (C3NeF), are involved. C3NeF stabilizes C3 convertase, sustains C3 activation, and causes C3 glomerulonephritis (C3GN). On the other hand, factor H is a glycoprotein that suppresses the overactivation of the alternative pathway by decaying the C3 convertase. Anti-factor H (aFH) antibodies interfere with factor H and cause the same activation of the alternative pathway as C3NeF. However, a limited number of reports describe the clinical course of C3GN with aFH antibodies. We encountered a 49-year-old Japanese man with type 2 diabetes mellitus. He was referred to our hospital because of his elevated serum creatinine, proteinuria, hematuria, and developed edema on both legs. He was diagnosed as PSAGN at the first kidney biopsy, and his renal function improved and edema and hematuria disappeared, but proteinuria persisted after 5 months. He was diagnosed as C3GN at the second kidney biopsy. In our case, no C3NeF was detected. However, a high titer of aFH antibodies was detected in stored serum from the initial presentation, providing a unified diagnosis of aFH antibody-positive C3GN secondary to PSAGN. He progressed to end-stage renal disease (ESRD) and hemodialysis was started. The persistence of high levels of aFH autoantibodies may have caused C3GN secondary to PSAGN due to activating the alternative complement pathway, which eventually worsened the nephropathy and led to ESRD.

Characteristics of hospitalized elderly patients with CKD: a comparison between elderly and non-elderly CKD based on a multicenter cross-sectional study.

PURPOSE: We undertook a multicenter epidemiological survey among hospitalized patients with chronic kidney disease (CKD), aiming to reveal the characteristics of elderly CKD by comparing it with non-elderly CKD. METHODS: Medical records were obtained from 18 military hospitals across China from 1 January 2009 to 31 December 2011. The characteristics of chronic kidney disease in the elderly were analyzed through comparing with those in younger patients with chronic kidney disease. RESULTS: A total of 380,461 hospitalized patients were included in the database, with 25,826 (6.8%) diagnosed with CKD. Unlike non-elderly, the top-three causes of chronic kidney disease among elderly patients were diabetic nephropathy (24.1%), hypertension-related renal impairment (20.9%), and primary glomerular disease (11.1%). 71.6% of the elderly patients with CKD had more than one comorbidities and the number of morbidities increased with age. In-hospital mortality of the elderly was significantly higher than those of younger patients (3.3% vs. 1.0%). Multiple logistic regression analysis showed that age, CKD 5 stage, acidosis, cardiovascular and cerebrovascular diseases, infection disease, neoplasm, and dementia were independent risk factors for death from CKD in the elderly. The median length of stay (LOS) was similar between elderly and younger CKD patients. The median cost was higher for elderly CKD patients than for younger CKD patients. Among elderly individuals with CKD, LOS, and hospitalization costs also increased with an increase in the number of coexisting diseases. CONCLUSIONS: Diabetic nephropathy,  and hypertension-related kidney injury were the leading causes of chronic kidney disease in elderly patients, which is different from the non-elderly. Elderly patients with chronic kidney disease were more likely to have a higher burden of comorbidities, which were associated with worse in-hospital outcomes.

Endostatin, soluble tumour necrosis factor receptor 1 and soluble tumour necrosis factor receptor 2 cannot predict new onset of microalbuminuria in patients with type 2 diabetes.

AIMS: Inflammation and angiogenesis play an important role in the development of early diabetic kidney disease. We investigated the association of soluble Tumour Necrosis Factor Receptor 1 (sTNF-R1), sTNF-R2 and endostatin with new onset microalbuminuria in normoalbuminuric patients with diabetes mellitus type 2. METHODS: We conducted a case control study to assess serum levels of sTNF-R1, sTNF-R2 and endostatin in 169 patients with new onset microalbuminuria and in 188 matched normoalbuminuric, diabetic controls. Baseline serum samples from participants of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) and observational follow-up (ROADMAP-OFU) studies were used. RESULTS: Endostatin and sTNF-R1 but not sTNF-R2 were increased at baseline in patients with future microalbuminuria. In the multivariate analysis, each log2 increment in endostatin levels was associated with an increase of only 6% in the risk of development of microalbuminuria (adjusted HR (95% CI) 1.006 (1.001-1011). sTNF-R1 and sTNF-R2 levels were conversely associated with microalbuminuria, but the results did not reach statistical significance. The respective adjusted HRs (95% CI) were 1.305 (0.928-1.774) and 0.874 (0.711-1.074). CONCLUSIONS: sTNF-R1 and sTNF-R2 failed to predict the occurrence of microalbuminuria in normoalbuminuric patients with type 2 diabetes. Likewise, the utility of endostatin in predicting new onset proteinuria is limited.

Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points.

BACKGROUND: Angiopoietin 2 regulates endothelial function partially mediated by vascular endothelial growth factor-A (VEGF-A) and may play a role in diabetic kidney disease (DKD). We assessed the association of angiopoietin 2 and VEGF-A with cardiorenal outcomes and investigated the effect of canagliflozin on angiopoietin 2 and VEGF-A concentrations. METHODS: Two thousand five hundred sixty-five study participants with DKD and available plasma samples treated with canagliflozin or placebo in the Canagliflozin and Kidney Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial were included. Angiopoietin 2 and VEGF-A concentrations were measured at baseline, year 1, and year 3. The primary composite end point of the trial was a composite of kidney failure, doubling of the serum creatinine level, and kidney or cardiovascular death. RESULTS: Patients with the highest baseline quartile of angiopoietin 2, but not VEGF-A, concentration had the highest risk clinical profile. Treatment with canagliflozin significantly lowered concentrations of angiopoietin 2 (adjusted geometric mean ratio: 0.94; 95% confidence interval, 0.92 to 0.95; P < 0.001), but not VEGF-A. In multivariable-adjusted modeling, each 50% increment in log baseline angiopoietin 2 concentrations was associated with a higher risk of primary composite outcome (hazard ratio, 1.27; 95% confidence interval, 1.13 to 1.43). Angiopoietin 2 change at year 1 compared with baseline explained 10% of the effect of canagliflozin on the primary composite outcome. VEGF-A concentrations were not associated with outcomes, alone or in combination with angiopoietin 2. CONCLUSIONS: Higher angiopoietin 2 levels were associated with cardiorenal risk among individuals with DKD independent of VEGF-A. Canagliflozin lowered angiopoietin 2 concentrations. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy, NCT02065791 .

Changes in serum tumor markers in type 2 diabetes mellitus with microalbuminuria.

Objectives: The objective of this study was to investigate changes in serum tumor markers in type 2 diabetes mellitus (T2DM) with microalbuminuria and analyze the relationship between tumor markers and microalbuminuria. Methods: A total of 956 T2DM patients aged 40-70 years hospitalized in the Department of Endocrinology, Xinhua Hospital, China, affiliated with Shanghai Jiaotong University School of Medicine, were enrolled from January 2018 to December 2020. The sample comprised 313 T2DM patients with microalbuminuria and 643 T2DM patients with normal urinary microalbumin levels. After assessing the changes in serum tumor markers in T2DM with microalbuminuria, we analyzed the risk of microalbuminuria by the serum tumor marker category using multiple logistic regression analysis. Results: Serum CEA, CA199, CA125, CA153, CA211, SCC, CA242, and CA50 levels were significantly higher in T2DM patients with microalbuminuria than in those without microalbuminuria, while serum AFP levels were lower in the microalbuminuria group (P < 0.05). Following adjustment of confounders, serum CEA, CA211, and SCC were independently associated with microalbuminuria in T2DM. An ROC curve was used to estimate the cutoff point of tumor markers for microalbuminuria. Taking the values under the cutoff points as a reference, values for CEA, CA211, and SCC above the cutoff points indicated a significantly high risk of microalbuminuria. The OR of increased CEA for microalbuminuria was 2.006 (95%CI 1.456-2.765), the OR of increased CA211 for microalbuminuria was 1.505 (95%CI 1.092-2.074), and the OR of increased SCC for microalbuminuria was 1.958 (95%CI 1.407-2.724). Conclusion: Several serum tumor markers were related to microalbuminuria in T2DM. Serum tumor markers such as CEA, SCC, and CA211 may indicate early diabetic nephropathy, particularly when elevated in combination.

Therapeutic improvements of nifedipine controlled-release tablets combined with sacubitril valsartan on patients with diabetic nephropathy complicated with hypertension.

This study aimed to evaluate the efficacy of nifedipine controlled-release tablets combined with sacubitril valsartan in diabetic nephropathy (DN) patients with hypertension. One hundred and twelve DN patients with hypertension were enrolled. They were randomly divided into the control group (treated with nifedipine controlled-release tablets combined with valsartan) and the observation group (treated with nifedipine controlled-release tablets combined with sacubitril valsartan). Renal function, endothelial function and inflammatory response were examined. After three-months treatment, the levels of clinical indexes (glycosylated hemoglobin, fasting blood glucose, systolic and diastolic blood pressure), renal function indicators (urinary albumin excretion rate, blood urea nitrogen, serum creatinine and cystatin C), endothelial function indicators (microalbumin, angiotensin II, thrombomodulin and cartilage oligomeric matrix protein) and inflammatory response factors (interleukin-6 and tumor necrosis factor-α) in the observation group were significantly lower than those in the control group. Nifedipine controlled-release tablets combined with sacubitril valsartan could effectively alleviate the progression of DN combined with hypertension.

A Mendelian randomization study on causal effects of 25(OH) vitamin D levels on diabetic nephropathy.

BACKGROUND: Vitamin D supplementation is associated with a lower incidence of diabetic nephropathy (DN); however, whether this association is causative is uncertain. METHODS: We used two-sample Mendelian randomization to examine the causal influence of vitamin D on diabetic nephropathy in 7,751 individuals with type I diabetes-related nephropathy (T1DN) and 9,933 individuals with type II diabetes-related nephropathy (T2DN). Meanwhile, we repeated some previous studies on the influence of KIM-1 (kidney injury molecule 1) and body mass index (BMI) on DN. Additionally, to test the validity of the instruments variable for vitamin D, we conducted two negative controls Mendelian randomization (MR) on breast and prostate cancer, and a positive control MR on multiple sclerosis. RESULTS: Results of the MR analysis showed that there was no causal association between 25(OH)D with the early/later stage of T1DN (early: OR = 0.903, 95%CI: 0.229 to 3.555; later: OR = 1.213, 95%CI: 0.367 to 4.010) and T2DN (early: OR = 0.588, 95%CI: 0.182 to 1.904; later: OR = 0.904, 95%CI: 0.376 to 2.173), nor with the kidney function of patients with diabetes mellitus: eGFRcyea (creatinine-based estimated GFR) (Beta = 0.007, 95%CI: -0.355 to 0.369)) or UACR (urinary albumin creatinine ratio) (Beta = 0.186, 95%CI: -0.961 to 1.333)). CONCLUSIONS: We found no evidence that Vitamin D was causally associated with DN or kidney function in diabetic patients.

Soluble TNFR1 Levels in Type 2 Diabetes and its Association with Stages of Proteinuria.

AIMS: Early identification of at-risk individuals for diabetic nephropathy would help in preventing or delaying end-stage renal failure. We measured the levels of circulating soluble tumor necrosis factor receptor 1 (sTNFR1) in various stages of proteinuria (MAC) to determine the association of this marker with diabetic nephropathy. MATERIALS AND METHODS: The study was performed on 160 subjects, and a case-control methodology was employed. Type 2 diabetic subjects were recruited based on albuminuria and were grouped as (1) normoalbuminuria (NA); (2) microalbuminuria (MIC); (3) MAC; (4) normal glucose tolerance (NGT) subjects who served as healthy controls. sTNFR1 levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: Soluble tumor necrosis factor receptor 1 (sTNFR1) levels were highest in the MAC group, followed by the microMAC group. The sTNFR1 levels were not statistically different between the NGT and NA groups. On regression models, sTNFR1 was associated with MIC [odds ratio (OR)- 6.491, 95% confidence interval (CI)-1.868-22.55] and MAC (OR per standard deviation-15.28; 95% CI-3.76-62.15; p < 0.001) even after controlling for all the possible confounding factors. Receiver operator curve (ROC) analysis revealed sTNFR1 cut-point of 1832 pg/mL had a C-statistic of 0.685 to discriminate MI from NA with 52% sensitivity. Whereas the sTNFR1 cut-point of 2050 pg/mL with a C-statistic of 0.8177 had 77% sensitivity for identifying MAC. CONCLUSION: Soluble tumor necrosis factor receptor 1 (sTNFR1) is significantly associated with MIC and MAC group in type 2 diabetes, and this suggests a potential early diagnostic biomarker role of sTNFR1 for MAC among Asian Indians.

Dose-response relationship between dietary antioxidant intake and diabetic kidney disease in the US adults with diabetes.

AIM: The effects of dietary antioxidants on numerous diseases have been widely studied. However, the evidence regarding composite dietary antioxidant index (CDAI) and diabetic kidney disease (DKD) in individuals with diabetes is scarce. This study aimed to investigate the associations of CDAI with DKD and mortality in adults with diabetes mellitus (DM). METHODS: This study utilized data from 5676 adult DM participants from the National Health and Nutrition Examination Survey (NHANES) of 2007-2018. The study followed up on death outcomes by linking the data to records from the National Death Index until December 31, 2019. CDAI was evaluated using a well-established method that included six food-sourced antioxidants derived from 24-h dietary recall: selenium, zinc, vitamin A, vitamin C, vitamin E and carotenoids. The regression models were used to estimate the relationships of CDAI with DKD and mortality in diabetic individuals. RESULTS: The weighted mean CDAI level for the 5676 participants, which represented 31.36 million noninstitutionalized residents of the US, was 0.33. Based on CDAI quartiles, participants were classified into four groups. CDAI levels were significantly associated with age, gender, race, physical activity, estimated glomerular filtration rate and the prevalence of albuminuria, DKD and hyperuricemia. DKD occurred in 36.44% of diabetic participants, and higher CDAI levels were independently associated with a lower risk of DKD (OR 0.74, 95%CI 0.59-0.94, p for trend = 0.004) in diabetic individuals after multivariate adjustment. During a median follow-up of 67 months (38-104 months), a total of 1065 (15.80%) diabetic individuals died from all causes. Diabetic individuals with higher CDAI levels (Q4) demonstrated a lower risk of all-cause mortality (HR 0.67, 95% CI: 0.52-0.86, p for trend = 0.01) after adjusting for age, gender and race. CONCLUSIONS: Maintaining an adequate antioxidant diet, as reflected in higher CDAI levels, may lower the risk of DKD and mortality in diabetic individuals. These findings offer a promising approach to managing diabetes and highlight the potential of food-based antioxidants as a preventative measure. Further research is warranted to explore the underlying mechanism linking dietary antioxidants and DKD and mortality in diabetic individuals.

Retinal microvascular changes in diabetic patients with diabetic nephropathy.

BACKGROUND: To explore the characteristics of retina microvascular changes in patients with diabetic nephropathy (DN) and its risk factors. METHODS: Retrospective, observational study. 145 patients with type 2 diabetic mellitus (DM) and DN were included in the study. Demographic and clinical parameters were obtained from medical records. Presence of diabetic retinopathy (DR), hard exudates (HEs) and diabetic macular edema (DME) were evaluated according to the color fundus images, optical coherence tomography (OCT) and fluorescence angiography (FFA). RESULTS: DR accounted for 61.4% in type 2 DM patients with DN, of which proliferative diabetic retinopathy (PDR) accounted for 23.6% and sight threatening DR accounted for 35.7%. DR group had significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004), HbA1c (P = 0.037), Urine albumin creatine ratio (ACR) (p < 0.001) and lower level of estimated glomerular filtration rate (eGFR) (P = 0.013). Logistic regression analysis showed DR was significantly associated with ACR stage (p = 0.011). Subjects with ACR stage3 had higher incidence of DR compared with subjects with ACR stage1 (OR = 24.15, 95%CI: 2.06-282.95). 138 eyes of 138 patients were analyzed for HEs and DME, of which 23.2% had HEs in posterior pole and 9.4% had DME. Visual acuity was worse in HEs group than in non-HEs group. There was significant difference in the LDL-C cholesterol level, total cholesterol (CHOL) level and ACR between HEs group and non-HEs group. CONCLUSIONS: A relatively higher prevalence of DR was found in type 2 DM patients with DN. ACR stage could be recognized as a risk factor for DR in DN patients. Patients with DN needs ophthalmic examination more timely and more frequently.

[Correlation between morphological characteristics of retinal microvessels and diabetic kidney disease in patients with type 2 diabetes mellitus based on a machine learning model].

Objective: To explore the correlation between the morphological characteristics of retinal microvessels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data and fundus photography of patients with T2DM treated in the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were retrospectively collected and analyzed. According to the presence of abnormal renal function, the patients were divided into DKD group and control group. The morphology and structure of fundus vessels were digitized by U-Net depth convolution neural network, and the correlation between fundus vascular morphology and DKD was analyzed by multivariate logistic regression. Results: A total of 648 patients with T2DM were enrolled, including 410 males and 238 females, and aged (53±10) years. There were 398 and 250 cases in control and DKD groups, respectively. Meanwhile, 1 296 fundus images were collected. Compared with control group, the male ratio (68.4% vs 60.1%, P=0.032), age [(54±9) vs (52±10) years, P=0.005], blood pressure [(136.8±17.3) vs (130.3±15.4) mmHg（1 mmHg=0.133 kPa）, P<0.001], total cholesterol [(4.5±1.4) vs (4.2±1.0) mmol/L, P=0.009], triglyceride [M (Q1, Q3)][1.7 (1.2, 3.0) vs 1.4 (1.0, 2.3) mmol/L, P<0.001] and Cystatin C [(0.9 (0.8, 1.0) vs 0.8 (0.7, 0.9) mg/L, P<0.001] were higher in the DKD group, while high-density lipoprotein [(1.0±0.3) vs (1.1±0.3) mmol/L, P=0.001] was lower in the DKD group. Multivariate logistic regression analysis showed that the risk of DKD in the third quartile (right eye: OR=1.825, 95%CI: 1.204-2.768, P=0.005) and fourth quartile (left eye: OR=1.929, 95%CI: 1.218-3.055, P=0.005) was higher than that in the lowest quartile of vascular curvature after adjusting for age and gender. The increase of average diameter of retinal vein was associated with the risk of DKD (left eye: OR=1.044, 95%CI: 1.013-1.075, P=0.005). The decrease of vascular fractal dimension (fourth quartile of left eye: OR=0.444, 95%CI: 0.199-0.987, P=0.046) and retinal vascular density (the second and fourth quartile of the right eye: OR=0.639, 95%CI: 0.409-0.998, P=0.049; OR=0.534, 95%CI: 0.331-0.864, P=0.010) were related to the risk of DKD. Conclusions: The abnormal morphological characteristics of retinal microvessels are related to the occurrence of DKD. The increase of retinal vein diameter and the decrease of retinal vessel density correlate with the occurrence of DKD.

Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

BACKGROUND: Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD. METHODS: This case-cohort study included Chronic Renal Insufficiency Cohort participants with baseline diabetes, estimated glomerular filtration rate <60 mL/min/1.73 m2, and without prior history for each outcome. The primary outcome was incident ASCVD (time to first myocardial infarction, stroke or peripheral artery disease event) and secondary outcome was incident heart failure. The subcohort comprised randomly selected participants meeting entry criteria. Plasma and urine ADMA, SDMA and TMAO concentrations were determined by liquid chromatography-tandem mass spectrometry. Associations of uremic solute plasma concentrations and urinary fractional excretions with outcomes were evaluated by weighted multivariable Cox regression models, adjusted for confounding covariables. RESULTS: Higher plasma ADMA concentrations (per standard deviation) were associated with ASCVD risk [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.01-1.68]. Lower fractional excretion of ADMA (per standard deviation) was associated with ASCVD risk (HR 1.42, 95% CI 1.07-1.89). The lowest quartile of ADMA fractional excretion was associated with greater ASCVD risk (HR 2.25, 95% CI 1.08-4.69) compared with the highest quartile. Plasma SDMA and TMAO concentration and fractional excretion were not associated with ASCVD. Neither plasma nor fractional excretion of ADMA, SDMA and TMAO were associated with incident heart failure. CONCLUSION: These data suggest that decreased kidney excretion of ADMA leads to increased plasma concentrations and ASCVD risk.

Association of Obesity Indices with Diabetic Kidney Disease and Diabetic Retinopathy in Type 2 Diabetes: A Real-World Study.

Background: Diabetic microvascular complications mainly include diabetic kidney disease (DKD) and diabetic retinopathy (DR). Obesity was recognized as a risk factor for DKD, while the reported relationship between obesity and DR was inconsistent. Moreover, whether the associations can be attributed to C-peptide levels is unknown. Methods: Data from 1142 sequential inpatients with T2DM at Xiangyang Central Hospital between June 2019 and March 2022 were extracted retrospectively from the electronic medical record system. The associations between four obesity indices (body mass index (BMI), waist-hip circumference ratio (WHR), visceral fat tissue area (VFA), and subcutaneous fat tissue area (SFA)) and DKD and DR were evaluated. Whether the associations can be attributed to C-peptide levels was also explored. Results: Obesity was a risk factor for DKD after adjusting for sex, HbA1c, TG, TC, HDL, LDL, smoking history, education, duration of diabetes, and insulin use (obesity indices: BMI (OR 1.050: 95% CI: 1.008-1.094; P = 0.020); WHR (OR 10.97; 95% CI: 1.250-92.267; P = 0.031); VFA (OR 1.005; 95% CI: 1.001-1.008; P = 0.008)), but it became insignificant after further adjusting for fasting C-peptide. The associations between BMI, WHR, VFA, and DKD might be U-shaped. Obesity and FCP tended to protect against DR; however, they became insignificant after adjusting for multiple potential confounders. C2/C0 (the ratio of the postprandial serum C-peptide to fasting C-peptide) was a protective factor for both DKD (OR 0.894, 95% CI: 0.833-0.959, P < 0.05) and DR (OR 0.851, 95% CI: 0.787-0.919; P < 0.05). Conclusions: Obesity was a risk factor for DKD, and the effect may be attributable to C-peptide, which represents insulin resistance. The protective effect of obesity or C-peptide on DR was not independent and could be confounded by multiple factors. Higher C2/C0 was associated with both decreased DKD and DR.

Diagnostic efficacy of cystatin-c in association with different ACE genes predicting renal insufficiency in T2DM.

Diabetic nephropathy (DN) seems to be the major cause of chronic kidney disease that may finally lead to End Stage Renal Disease. So, renal function assessment in type 2 diabetes mellitus (T2DM) individuals is very important. Clearly, DN pathogenesis is multifactorial and different proteins, genes and environmental factors can contribute to the onset of the disease. We assessed sensitive and specific biomarkers (in blood and urine) which can predict kidney disease susceptibility among T2DM patients. Serum cystatin-c (cyst-c) in blood and urinary hemeoxygenase (HO-1) in addition to ACE I/D polymorphism and ACE G2350A genotypes. Hundred and eight T2DM patients and 85 controls were enrolled. Serum cystatin-c and urinary (HO-1) were tested by ELISA. Genetic determination of both ACE I/D polymorphism and ACE G2350A genotypes was performed by PCR for all participants. Significant rise in serum cystatin-c and urinary HO-1 levels were shown in diabetic groups compared with control group. Moreover, GG genotype of ACE G2350A gene in diabetic group was associated with rise in serum cystatin-c and urinary HO-1 compared with control group. Mutant AA genotype demonstrated increase in urinary HO-1. DD polymorphism was associated with rise in serum creatinine and cyst-c in diabetic group. Positive correlation was seen between duration of diabetes and serum cyst-c and between serum glucose and urinary (HO-1) in diabetic group. The results from this study indicated an association of serum cystatin-c with GG genotype of ACE G2350A in conjugation with DD polymorphism of ACE I/D which could be an early predictor of tubular injury in T2DM diabetic patients.

Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease.

Importance: Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events. Objective: To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE). Design, Setting, and Participants: This prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021. Exposures: Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories. Main Outcomes and Measures: The main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria. Results: Of 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models. Conclusions and Relevance: In this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

Impact of albuminuria on the various causes of death in diabetic patients: a nationwide population-based study.

Diabetes mellitus (DM) is a well-known risk factor for mortality, and the risk is exacerbated by coexisting diabetic kidney disease (DKD). We aimed to explore the impact of DM on each cause of mortality according to kidney function and the presence of albuminuria. Data on subjects with DM were extracted from the Nationwide Health Insurance Database of South Korea between 2009 and 2012. Subjects were divided by eGFR and albuminuria into five groups. To evaluate the risk of diabetes, we used the Cox proportional hazards model. A total of 2,614,662 patients were enrolled in this study. Most causes of death showed a higher incidence in an advanced stage of DKD. In addition to all-cause mortality and cardiovascular death, the risk of death from neoplasms and diseases of the endocrine, respiratory, and digestive systems is increased by albuminuria. The synergistic effect of a reduced eGFR and the presence of albuminuria was prominent in death from circulatory diseases, and endocrine and metabolic diseases. The risk for mortality was different according to the stage of DKD. Even in patients with a favorable eGFR, the presence of albuminuria significantly increased the risk for mortality, especially that due to cardiovascular causes.