scholarly journals Arylsulfatase A: An Important Metabolic Factor in Pathophysiology of Different Diseases

2015 ◽  
Vol 61 (3) ◽  
pp. 233-235 ◽  
Author(s):  
Kovacs Zsolt ◽  
Tripon Robert ◽  
Nemes Nagy Eniko ◽  
Balogh Samarghitan Victor ◽  
Tilinca Mariana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Lysosomal Enzyme ◽  
Autosomal Recessive Disorder ◽  
Arylsulfatase A ◽  
Parkinson Syndrome ◽  
Metachromatic Leucodystrophy ◽  
Enzyme Dosage ◽  
End Stage

Abstract Arylsulfatase A (ARSA) is a lysosomal enzyme that plays an important role in catalysis of degradation of cerebrosidesulphate. The deficiency of this lysosomal enzyme causes an autosomal recessive disorder, called metachromatic leucodystrophy. However, a low ARSA activity can be observed in clinically healthy people, called ARSA pseudodeficiency. In our study we investigated the possible linkage between ARSA activity and sulfatide deficiency causing characteristic aspects of degenerative diseases, such as end stage kidney disease, type 2 Diabetes mellitus, Parkinson syndrome, prostate cancer and HIV (Human Immunodeficiency Virus) infection. We used a spectrophotometric method to determine the activity of ARSA. This method of enzyme dosage is based on a 4 hour long hydrolysis of the ARSA enzyme on 4-nitrocatechol sulfate (p-NCS) substrate. The unit of this measurement is nmol/ml/4h. Our findings show significant values in type 2 diabetes, Parkinson syndrome and chronic kidney disease. The importance of sulfatide in these diseases is well-known, thus presumably the variation of the ARSA’s activity might play an important role in the pathophysiology of these diseases, involving a vicious cycle between sulfatide degradation andthese diseases.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

Type 2 diabetes in patients with end‐stage kidney disease: influence on cardiovascular disease‐related mortality risk

2018 ◽  
Vol 209 (10) ◽  
pp. 440-446 ◽  
Author(s):  
Wai H Lim ◽  
David W Johnson ◽  
Carmel Hawley ◽  
Charmaine Lok ◽  
Kevan R Polkinghorne ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Kidney Disease ◽  
Mortality Risk ◽  
End Stage Kidney Disease ◽  
End Stage ◽  
Related Mortality

scholarly journals Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the CARMELINA randomized trial

2020 ◽  
Author(s):  
Vlado Perkovic ◽  
Robert Toto ◽  
Mark E Cooper ◽  
Johannes FE Mann ◽  
Julio Rosenstock ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Secondary Analysis ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
First Occurrence ◽  
Outcome Trial ◽  
End Stage ◽  
Reduced Kidney Function

<b>Objective</b> <p>Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular and kidney outcomes across baseline eGFR categories (≥ 60, 45-<60, 30-<45 and < 30 ml/min/1.73 m<sup>2</sup>) in CARMELINA, a cardio-renal placebo-controlled outcome trial of the DPP-4 inhibitor linagliptin (NCT01897532).</p> <p><b>Research Design and Methods</b></p> <p>Participants with cardiovascular disease (CVD) and/or CKD were included. The primary outcome was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with a secondary outcome renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other endpoints included progression of albuminuria, change in HbA1c and adverse events (AEs) including hypoglycemia. </p> <p><b>Results</b></p> <p>6979 subjects (mean age 65.9 years, eGFR 54.6 ml/min/1.73m<sup>2</sup>, 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared to placebo did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction p-values > 0.05). Regardless of eGFR, albuminuria-progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced between groups overall and across eGFR categories. </p> <p><b>Conclusions </b></p> <p>Across all GFR categories, in participants with type 2 diabetes and CKD and/or CVD, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c, and no difference in AEs was observed.</p>

scholarly journals The Association Between Age of Onset of Type 2 Diabetes with Long-term Risk of End Stage Kidney Disease: A National Registry Study

2020 ◽  
Author(s):  
Jedidiah I Morton ◽  
Danny Liew ◽  
Stephen P McDonald ◽  
Jonathan E Shaw ◽  
Dianna J Magliano
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Cumulative Incidence ◽  
Age Of Onset ◽  
End Stage Kidney Disease ◽  
Onset Of Diabetes ◽  
End Stage ◽  
Effect Of Age

<b>Objective</b>: The long-term risk of end-stage kidney disease (ESKD) in type 2 diabetes is poorly described, as is the effect that younger age of diabetes onset has on this risk. Therefore, we aimed to estimate the effect of age of onset on the cumulative incidence of ESKD from onset of type 2 diabetes. <p><b>Research Design and Methods: </b>This study included 1,113,201 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2002 until 2013. The NDSS was linked to the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index. </p> <p><b>Results: </b>Between 2002 and 2013,<b> </b>there were 7,592 incident cases of ESKD during 7,839,075 person-years of follow up. In the first 10-15 years following onset of diabetes, the incidence of ESKD was highest in those with an older age of onset of diabetes, whereas over longer durations of diabetes the incidence of ESKD became higher in those with younger-onset diabetes. After 40 years of diabetes, the cumulative incidence of ESKD was 11.8% and 9.3% in those diagnosed with diabetes aged 10-29 and 30-39 years, respectively. When death from ESKD without renal replacement therapy was included, incidence of ESKD remained higher in older onset diabetes for the initial 20 years, with no clear effect of age thereafter.</p> <p><b>Conclusions: </b>The long-term risk of ESKD in type 2 diabetes is high, which disproportionately affects those with younger-onset of diabetes as they are more likely to survive to longer diabetes durations.</p>

scholarly journals Retinopathy progression and the risk of end-stage kidney disease: results from a longitudinal Japanese cohort of 232 patients with type 2 diabetes and biopsy-proven diabetic kidney disease

2019 ◽  
Vol 7 (1) ◽  
pp. e000726 ◽  
Author(s):  
Masayuki Yamanouchi ◽  
Mikiro Mori ◽  
Junichi Hoshino ◽  
Keiichi Kinowaki ◽  
Takeshi Fujii ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
End Stage Kidney Disease ◽  
Diabetic Kidney ◽  
Clinical Model ◽  
Renal Lesions ◽  
End Stage

ObjectiveThe predictive value of diabetic retinopathy on end-stage kidney disease (ESKD) has not been fully addressed in patients with type 2 diabetes and diabetic kidney disease.Research design and methodsWe studied 232 patients with type 2 diabetes and biopsy-proven diabetic kidney disease who were screened for diabetic retinopathy during the 1 month of kidney biopsy. We examined the association between retinopathy progression and renal lesions. We used Cox regression analyses to explore the risk of ESKD adjusting for known risk demographic and clinical variables. We assessed the incremental prognostic value of ESKD by adding diabetic retinopathy to the clinical variables.ResultsThe diabetic retinopathy progression positively correlated with all scores of renal lesions, especially with the glomerular-based classification (r=0.41), scores of interstitial fibrosis (r=0.41) and diffuse lesion (r=0.48). During a median follow-up of 5.7 years, 114 patients developed ESKD. Adjusting for known risk factors of ESKD, the HR for ESKD (patients with no apparent retinopathy as a reference) were 1.96 (95% CI 0.62 to 6.17) for patients with mild non-proliferative diabetic retinopathy (NPDR), 3.10 (95% CI 1.45 to 6.65) for patients with moderate NPDR, 3.03 (95% CI 1.44 to 6.37) for patients with severe NPDR, and 3.43 (95% CI 1.68 to 7.03) for patients with proliferative diabetic retinopathy, respectively. Addition of the retinopathy grading to the clinical model alone improved the prognostic value (the global χ2 statistic increased from 155.2 to 164.5; p<0.001), which is an improvement equivalent to the addition of the renal lesion grading to the clinical model.ConclusionsRetinopathy progression appeared to be associated with renal lesions and the development of ESKD. Our findings suggest that diabetic retinopathy and kidney disease share the same magnitude of disease progression, and therefore diabetic retinopathy may be useful for prognosticating the clinical course for diabetic kidney disease.

scholarly journals The ras responsive transcription factor RREB1 is a novel candidate gene for type 2 diabetes associated end-stage kidney disease

2014 ◽  
Vol 23 (24) ◽  
pp. 6441-6447 ◽  
Author(s):  
J. A. Bonomo ◽  
M. Guan ◽  
M. C. Y. Ng ◽  
N. D. Palmer ◽  
P. J. Hicks ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Candidate Gene ◽  
End Stage Kidney Disease ◽  
End Stage

scholarly journals An Exome-wide Association Study for Type 2 Diabetes–Attributed End-Stage Kidney Disease in African Americans

2018 ◽  
Vol 3 (4) ◽  
pp. 867-878 ◽  
Author(s):  
Meijian Guan ◽  
Jacob M. Keaton ◽  
Latchezar Dimitrov ◽  
Pamela J. Hicks ◽  
Jianzhao Xu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
African Americans ◽  
Kidney Disease ◽  
Association Study ◽  
End Stage Kidney Disease ◽  
End Stage

scholarly journals Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial

2021 ◽  
Author(s):  
Frederik Persson ◽  
Peter Rossing ◽  
Priya Vart ◽  
Glenn M. Chertow ◽  
Fan Fan Hou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Glycemic Status ◽  
End Stage ◽  
Design And Methods ◽  
Egfr Decline

<b>Objective </b> <p>DAPA-CKD demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. </p> <p><b>Research Design and Methods </b></p> <p>We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) <br> 25–75ml/min/1.73m<sup>2 </sup>and urinary albumin-to-creatinine ratio 200–5000mg/g. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. </p> <p><b>Results </b></p> <p>Of 4304 participants, 738 had normoglycemia, 660 pre-diabetes, and 2906 type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (p-interaction=0.19) in normoglycemia (HR [95%CI] 0.62 [0.39–1.01]), pre-diabetes (HR 0.37 [0.21–0.66]) and type 2 diabetes (HR 0.64 [0.52–0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or pre-diabetes. </p> <p><b>Conclusions</b></p> <p>Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status. </p>

scholarly journals Cardiorenal outcomes with sodium/glucose cotransporter-2 inhibitors in patients with type 2 diabetes and low kidney risk: real world evidence

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Meir Schechter ◽  
Cheli Melzer-Cohen ◽  
Aliza Rozenberg ◽  
Ilan Yanuv ◽  
Gabriel Chodick ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Propensity Score ◽  
Lower Risk ◽  
Urinary Albumin ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Infraction ◽  
Specific Outcome ◽  
End Stage

Abstract Background Randomized controlled trials showed that sodium/glucose cotransporter-2 inhibitors (SGLT2i) protect the heart and kidney in an array of populations with type 2 diabetes (T2D) and increased cardiorenal risk. However, the extent of these benefits also in lower kidney-risk T2D populations needs further investigation. Methods Members of Maccabi Healthcare Systems listed in their T2D registry who initiated new glucose lowering agents (GLA), were divided into SGLT2i initiators and other GLAs (oGLAs). Groups were propensity score-matched by baseline demographic and medical characteristics. Two composite cardiovascular outcomes were defined: all-cause mortality (ACM) or hospitalization for heart failure (hHF); and ACM, myocardial infraction (MI) or stroke. The cardiorenal outcome was: ACM, new end-stage kidney disease (ESKD) or  ≥  40% reduction from baseline estimated glomerular filtration rate (eGFR). Renal-specific outcome was new ESKD or  ≥  40% eGFR reduction. Single components of cardiovascular and kidney outcomes were also assessed. Three subgroup definitions of low baseline kidney-risk were used: eGFR  >  90 ml/min/1.73 m2; urinary albumin below detectable levels; and low risk according to Kidney Disease: Improving Global Outcomes (KDIGO) classification. Analyses were performed utilizing an unadjusted model, and a model adjusted to baseline eGFR and urinary albumin-to-creatinine ratio. Results Between April 1, 2015 and June 30, 2018; 68,187 patients initiated new GLAs — 11,321 SGLT2i initiators and 42,077 oGLAs initiators were eligible. Propensity score-matching yielded two comparable cohorts; each included 9219 participants. Median follow-up was 1.7 years. Compared to oGLAs, SGLT2i initiators had lower incidence of ACM or hHF [HR95%CI  =  0.62(0.51–0.75)]; ACM, MI or stroke [0.67(0.57–0.80)]; the cardiorenal outcome [0.65(0.56–0.76)]; and the renal-specific outcome [0.70(0.57–0.85)]. SGLT2i initiators also had lower risk for ACM, hHF and  ≥  30%,  ≥  40%,  ≥  50%,  ≥  57% eGFR reduction. No difference between groups was observed for MI or stroke. In the low baseline kidney-risk subgroups, SGLT2i initiation was generally associated with lower risk of the cardiovascular and cardiorenal outcomes, driven mainly by lower ACM incidence. Conclusions Our findings in the general population of patients with T2D demonstrates lower risk of cardiorenal outcomes associated with initiation of SGLT2i compared with oGLAs, including specifically in patients with low baseline kidney-risk.

scholarly journals Effects of linagliptin on cardiovascular and kidney outcomes in people with normal and reduced kidney function: secondary analysis of the CARMELINA randomized trial

2020 ◽  
Author(s):  
Vlado Perkovic ◽  
Robert Toto ◽  
Mark E Cooper ◽  
Johannes FE Mann ◽  
Julio Rosenstock ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Secondary Analysis ◽  
Cardiovascular Death ◽  
Secondary Outcome ◽  
First Occurrence ◽  
Outcome Trial ◽  
End Stage ◽  
Reduced Kidney Function

<b>Objective</b> <p>Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular and kidney outcomes across baseline eGFR categories (≥ 60, 45-<60, 30-<45 and < 30 ml/min/1.73 m<sup>2</sup>) in CARMELINA, a cardio-renal placebo-controlled outcome trial of the DPP-4 inhibitor linagliptin (NCT01897532).</p> <p><b>Research Design and Methods</b></p> <p>Participants with cardiovascular disease (CVD) and/or CKD were included. The primary outcome was time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with a secondary outcome renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other endpoints included progression of albuminuria, change in HbA1c and adverse events (AEs) including hypoglycemia. </p> <p><b>Results</b></p> <p>6979 subjects (mean age 65.9 years, eGFR 54.6 ml/min/1.73m<sup>2</sup>, 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared to placebo did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction p-values > 0.05). Regardless of eGFR, albuminuria-progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced between groups overall and across eGFR categories. </p> <p><b>Conclusions </b></p> <p>Across all GFR categories, in participants with type 2 diabetes and CKD and/or CVD, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c, and no difference in AEs was observed.</p>

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