Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative.
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ABSTRACT:
SUBMITTER: Piscitelli P
PROVIDER: S-EPMC5468280 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
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Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative.
Piscitelli Pamela P Viazzi Francesca F Fioretto Paola P Giorda Carlo C Ceriello Antonio A Genovese Stefano S Russo Giuseppina G Guida Pietro P Pontremoli Roberto R De Cosmo Salvatore S
Scientific reports 20170612 1
We evaluated 2,656 patients with type 1 diabetes mellitus and preserved renal function from the database of the Italian Association of Clinical Diabetologists network to identify clinical predictors for the development of chronic kidney disease. We measured estimated glomerular filtration rate (eGFR), urinary albumin excretion, HbA1c, lipids, blood pressure. Over a 5-year period 4.3% (n = 115) developed reduced eGFR (<60 ml/min/1.73 m<sup>2</sup>), 18.0% (n = 477) albuminuria, and 21.0% (n = 559 ...[more]
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Project description:UnlabelledThe identification of clinical predictors for the development of chronic kidney disease is a critical issue in the management of patients with type 2 diabetes mellitus.We evaluated 27,029 patients with type 2 diabetes mellitus and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m and normoalbuminuria from the database of the Italian Association of Clinical Diabetologists network. Primary outcomes were eGFR <60 mL/min/1.73 m and normoalbuminuria; albuminuria and eGFR ≥60 mL/min/1.73 m; and eGFR <60 mL/min/1.73 m and albuminuria. Secondary outcomes were eGFR <60 mL/min/1.73 m and albuminuria.MeasurementseGFR from serum creatinine by chronic kidney disease epidemiology collaboration equation (CKD-EPI), urinary albumin excretion, HbA1c, triglycerides, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), blood pressure, and body mass index.Over a 4-year period, 33.2% of patients (n = 8973) developed chronic kidney disease, 10.3% (n = 2788) showed a decline in eGFR <60 mL/min/1.73 m, 18.4% (n = 4978) developed albuminuria, and 4.5% (n = 1207) developed both features. Relative risk ratios (RRRs) for age (1.37, P < 0.001 by 5 years), sex (0.77, P < 0.001 for being male), body mass index (1.03, P < 0.001 by 1 kg/m), triglycerides (1.02, P < 0.001 by 10 mg/dL), and LDL-c (0.97, P = 0.004 by 10 mg/dL) were independently related to the onset of eGFR reduction. Age (1.08, P < 0.001 by 5 years), sex (1.36, P < 0.001 for being male), body mass index (1.02, P < 0.001 by 1 kg/m), triglycerides (1.01, P = 0.02 by 10 mg/dL), HDL-c, and LDL-c (0.97, P = 0.008 and 0.99, P = 0.003 by 5 and 10 mg/dL, respectively) were related to the onset of albuminuria. HbA1c and the intensity of antihypertensive treatment showed a weaker association with renal outcome.Reduction in eGFR and albuminuria showed distinct sets of risk factors, suggesting that different mechanisms are involved in the development of these 2 components of diabetic kidney disease.
| S-EPMC5058807 | biostudies-literature
Project description:We evaluated gender-differences in quality of type 1 diabetes (T1DM) care. Starting from electronic medical records of 300 centers, 5 process indicators, 3 favorable and 6 unfavorable intermediate outcomes, 6 treatment intensity/appropriateness measures and an overall quality score were measured. The likelihood of women vs. men (reference class) to be monitored, to reach outcomes, or to be treated has been investigated through multilevel logistic regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence intervals (95%CIs). The inter-center variability in the achievement of the unfavorable outcomes was also investigated. Overall, 28,802 subjects were analyzed (45.5% women). Women and men had similar age (44.5±16.0 vs. 45.0±17.0 years) and diabetes duration (18.3±13.0 vs. 18.8±13.0 years). No between-gender differences were found in process indicators. As for intermediate outcomes, women showed 33% higher likelihood of having HbA1c ?8.0% (OR = 1.33; 95%CI: 1.25-1.43), 29% lower risk of blood pressure ?140/90 mmHg (OR = 0.71; 95%CI: 0.65-0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI: 0.65-0.81) than men, while BMI, LDL-c and GFR did not significantly differ; treatment intensity/appropriateness was not systematically different between genders; overall quality score was similar in men and women. Consistently across centers a larger proportion of women than men had HbA1c ?8.0%, while a smaller proportion had BP ?140/90 mmHg. No gender-disparities were found in process measures and improvements are required in both genders. The systematic worse metabolic control in women and worse blood pressure in men suggest that pathophysiologic differences rather than the care provided might explain these differences.
| S-EPMC5047461 | biostudies-literature
Project description:BackgroundWe described, in a large sample of patients with type 1 diabetes mellitus (T1DM) and GFR ≤ 60 mL/min/1.73 m2 (with or without albuminuria), the differences in the clinical features associated with the two different chronic kidney disease phenotypes and we investigated, in a subset of patients, the modulating role of albuminuria on kidney disease progression.MethodsClinical data of 1395 patients with T1DM were extracted from electronic medical records.ResultsAlbuminuria was detected in 676 (48.5%) patients, with the remaining 719 (51.5%) patients having normoalbuminuric renal impairment. Those with albuminuria showed an evident worse cardiovascular risk profile as compared to patients with normoalbuminuria. A subgroup of 582 patients was followed up over a 4-year period. One hundred and twenty five patients (21.5%) showed a loss of eGFR > 30%. The proportion of patients reaching the renal outcome was significantly higher among those with baseline albuminuria as compared to patients with normoalbuminuria (P < 0.0001). At the multivariate logistic analysis microalbuminuria, macroalbuminuria and proliferative retinopathy were the only parameters independently associated to eGFR reduction.ConclusionsThe proportion of T1DM patients with normoalbuminuria renal impairment is high (about 50%). These patients have a slower eGFR decline as compared to that observed in patients with albuminuria renal impairment.
| S-EPMC6069993 | biostudies-literature
Project description:The management of patients with type 2 diabetes and chronic kidney disease (CKD) encompasses lifestyle modifications, glycemic control with individualized HbA1c targets, and cardiovascular disease risk reduction. Metformin and sodium-glucose cotransporter-2 inhibitors are first-line agents. Glucagon-like peptide-1 receptor agonists are second-line agents. The use of other antidiabetic agents should consider patient preferences, comorbidities, drug costs, and the risk of hypoglycemia. Renin-angiotensin-aldosterone system inhibitors are strongly recommended for patients with diabetes, hypertension, and albuminuria. Non-steroidal mineralocorticoid receptor antagonists, which pose less risk of hyperkalemia than steroidal agents, are undergoing further evaluation among patients with diabetic kidney disease. Here, we discuss important advancements in the management of patients with type 2 diabetes and CKD.
| S-EPMC8314731 | biostudies-literature
Project description:BackgroundClinical practice guidelines recommend sodium-glucose co-transporter 2 inhibitors (SGLT2is) to mitigate adverse kidney and cardiovascular outcomes in patients with type 2 diabetes (T2D), including patients with comorbid chronic kidney disease (CKD), also referred to as diabetic kidney disease (DKD), who are at even higher risk. In this study, we sought to identify predictors of cardio-kidney events, cardio-kidney complications, and treatment failure (i.e., addition/initiation of a new T2D class, insulin, or discontinuation of SGLT2is) after new initiation of SGLT2is in patients with CKD and T2D (DKD).MethodsIn this retrospective cohort study, we identified adult patients with DKD who initiated SGLT2is between April 1, 2012, and June 30, 2019, in Optum claims data. Outcome rates per 1000 person-years (PY) are reported with 95% confidence intervals (CIs). Cox proportional hazards regression identified patient characteristics associated with each outcome.ResultsThe study population consisted of 6389 initiators of SGLT2is. The rate of CV hospitalization was 26.0 (95% CI 21.6, 30.4) per 1000 PY. Baseline characteristics associated with higher risk of CV hospitalization included age, atrial fibrillation, peripheral vascular disease (PVD), and cancer. The rate of kidney hospitalization was 12.0 (95% CI 9.0, 15.0) per 1000 PY. The risk increased significantly with baseline evidence of heart failure, hyperkalemia, respiratory failure, depression, and use of loop diuretics. In total, 55.0% of all SGLT2i initiators discontinued treatment during the follow-up period. The rate of treatment failure was 510.5 (95% CI 492.9, 528.1) per 1000 PY. Analysis of key time-dependent SGLT2i-associated adverse events showed that experiencing diabetic ketoacidosis and volume depletion were associated with risk of treatment failure.ConclusionsOur study demonstrated high rates of residual cardio-kidney outcomes and treatment failure in patients with DKD treated with SGLT2is. Patients with high baseline CV risk and the presence of certain conditions, such as atrial fibrillation, PVD, and heart failure, were at higher risk for cardio-kidney events. Further research is needed to assess the potential relationship between adverse events and SGLT2i treatment failure.
| S-EPMC8744296 | biostudies-literature
Project description:BackgroundGlomerular hyperfiltration, initiating development of obesity-related glomerulopathy, results in an enlargement of the glomeruli and unsealing of the filtration barrier. It can be followed by adaptive focal segmental glomerulosclerosis and chronic kidney disease (CKD). The aim of the study was to determine the expression pattern of lipid metabolism and selected kidney damage markers in obese adolescents and to identify potential factors which can predict CKD.MethodsThe study group consisted of 142 adolescents with a BMI z-score > 2. Sixty-two healthy and normal-weight individuals served as controls. The factors associated with the rate of glomerular filtration in obese adolescents were assessed by linear regression methods using univariate and multivariate analyses. The risk of developing CKD was estimated using the Fisher's exact test.ResultsThe study group was divided into "elevated," "normal," and "decreased" glomerular filtration rate (GFR) patients. Increased urine galectin-3 (Gal-3) concentration was diagnosed in all patients. "Decreased GFR" subjects expressed increased urine concentration of neutrophil gelatinase-associated lipocalin (NGAL) and daily megalin excretion. Thirty-nine study participants developed CKD. Increased uric acid (UA) concentration was associated with CKD development both in "normal" and "decreased GFR" patients. Additionally, in "normal" GFR patients, increased concentrations of cholesterol (Ch), triglycerides (TG), and NGAL were associated with CKD.ConclusionsIncreased serum concentrations of Ch, TG, and UA and increased urine concentration of NGAL might predict CKD development in obese adolescents with normal and decreased GFR. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Project description:Background and objectivesThe glucagon-like peptide-1 receptor agonist liraglutide demonstrated cardiovascular and kidney benefits in the LEADER trial, particularly in participants with CKD.Design, setting, participants, & measurementsThis post hoc analysis evaluated the safety of liraglutide treatment in patients with CKD in LEADER. Overall, 9340 patients were randomized to liraglutide or placebo, both in addition to standard of care. Of those, 2158 patients had CKD versus 7182 without CKD (defined as eGFR <60 versus ≥60 ml/min per 1.73 m2, respectively); 966 patients had macroalbuminuria and 2456 had microalbuminuria (urine albumin-creatinine ratio >300 mg/g and ≥30 to ≤300 mg/g, respectively). At baseline, the mean eGFR in patients with CKD was 46±11 ml/min per 1.73 m2 versus 91±22 ml/min per 1.73 m2 in those without CKD. Time to first event within event groups was analyzed using Cox regression with treatment group, baseline eGFR group, or baseline albuminuria group as fixed factors.ResultsOverall, serious adverse events were more frequently recorded in patients with CKD compared with those without CKD (59% versus 50%; interaction P=0.11); however, they occurred to the same extent in those on liraglutide versus placebo. Similarly, no interaction of adverse events with randomized therapy was observed in patients with micro- or macro- versus normoalbuminuria (interaction P=0.11). Risk of severe hypoglycemia was significantly reduced with liraglutide versus placebo in patients with CKD or with micro- or macroalbuminuria (hazard ratio, 0.63 [95% CI, 0.43 to 0.91] and 0.57 [95% CI, 0.40 to 0.82], respectively).ConclusionsIn LEADER, the use of liraglutide in those with CKD was safe, with no difference between patients with and without CKD.Clinical trial registry name and registration numberClinicalTrials.gov; NCT01179048 (https://clinicaltrials.gov/ct2/show/NCT01179048).
| S-EPMC7133133 | biostudies-literature
Project description:BACKGROUND: In patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD. METHODS: Type 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12?months prior to enrolment) on the risk of death. RESULTS: In this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66?years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values?<?0.05). CONCLUSIONS: Severe hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.
| S-EPMC4151079 | biostudies-other
Project description:Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown.We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m(2) of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes.The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group.Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. (Funded by Reata Pharmaceuticals; BEACON ClinicalTrials.gov number, NCT01351675.).
| S-EPMC4496027 | biostudies-literature
Project description:PurposeTo explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).MethodsThis was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73 m2 and/or urine albumin to creatinine ratio (UACR) ?30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.ResultsCKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4-1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ?10 mg/g, and increased considerably with UACR values ?300 mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6-2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73 m2 [OR], 95% confidence interval [CI], 1.3 (1.1-1.6).ConclusionsThese results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.
| S-EPMC4757564 | biostudies-literature