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The New England Journal of Medicine Nov 1993Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Renal function declines progressively in patients who have diabetic nephropathy, and the decline may be slowed by antihypertensive drugs. The purpose of this study was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy.
METHODS
We performed a randomized, controlled trial comparing captopril with placebo in patients with insulin-dependent diabetes mellitus in whom urinary protein excretion was > or = 500 mg per day and the serum creatinine concentration was < or = 2.5 mg per deciliter (221 mumol per liter). Blood-pressure goals were defined to achieve control during a median follow-up of three years. The primary end point was a doubling of the base-line serum creatinine concentration.
RESULTS
Two hundred seven patients received captopril, and 202 placebo. Serum creatinine concentrations doubled in 25 patients in the captopril group, as compared with 43 patients in the placebo group (P = 0.007). The associated reductions in risk of a doubling of the serum creatinine concentration were 48 percent in the captopril group as a whole, 76 percent in the subgroup with a baseline serum creatinine concentration of 2.0 mg per deciliter (177 mumol per liter), 55 percent in the subgroup with a concentration of 1.5 mg per deciliter (133 mumol per liter), and 17 percent in the subgroup with a concentration of 1.0 mg per deciliter (88.4 mumol per liter). The mean (+/- SD) rate of decline in creatinine clearance was 11 +/- 21 percent per year in the captopril group and 17 +/- 20 percent per year in the placebo group (P = 0.03). Among the patients whose base-line serum creatinine concentration was > or = 1.5 mg per deciliter, creatinine clearance declined at a rate of 23 +/- 25 percent per year in the captopril group and at a rate of 37 +/- 25 percent per year in the placebo group (P = 0.01). Captopril treatment was associated with a 50 percent reduction in the risk of the combined end points of death, dialysis, and transplantation that was independent of the small disparity in blood pressure between the groups.
CONCLUSIONS
Captopril protects against deterioration in renal function in insulin-dependent diabetic nephropathy and is significantly more effective than blood-pressure control alone.
Topics: Adult; Captopril; Creatinine; Diabetic Nephropathies; Double-Blind Method; Female; Follow-Up Studies; Humans; Kidney; Male; Middle Aged; Patient Compliance; Prospective Studies
PubMed: 8413456
DOI: 10.1056/NEJM199311113292004 -
Disease-a-month : DM May 1998Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) and accounts for 35% of the ESRD population in the United States. It results in... (Review)
Review
Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) and accounts for 35% of the ESRD population in the United States. It results in considerable morbidity, mortality, and expense. The average cost of managing one diabetic patient with ESRD is approximately $50,000 a year. Over the last decade, several advances in the management of diabetic nephropathy have allowed physicians to intervene and retard the progression of renal failure in patients with diabetic nephropathy. Stalling the progression of renal failure allows patients to maintain a superior quality of life and saves society millions of dollars that can be allocated to other aspects of health care. The prevalence of diabetes mellitus continues to increase. With the continued advances in medical technology and care, persons with this disease will live longer, and the incidence of diabetic nephropathy will increase. Primary care physicians will have the most frequent contact with these patients and therefore will have the greatest potential to favorably affect their clinical course. This review focuses on the therapeutic interventions available to delay the progression of diabetic nephropathy. Clinicians should strive to secure euglycemia and obtain optimal blood pressure control in their patients. The unique renal-protective effects of angiotensin-converting enzyme inhibitors will be reviewed, as will the salutary effects of a low-protein diet, normalizing serum cholesterol, and the cessation of smoking. The optimal timing of dialysis access placement and the initiation of dialysis and transplantation will also be discussed.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Disease Susceptibility; Hemodynamics; Humans; Hyperglycemia; Kidney; Kidney Failure, Chronic; Risk Factors
PubMed: 9656970
DOI: 10.1016/s0011-5029(98)90022-0 -
Journal of Internal Medicine Jan 2017Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney... (Review)
Review
Kidney disease is a serious development in diabetes mellitus and poses an increasing clinical problem. Despite increasing incidence and prevalence of diabetic kidney disease, there have been no new therapies for this condition in the last 20 years. Mounting evidence supports a biological role for C-peptide, and findings from multiple studies now suggest that C-peptide may beneficially affect the disturbed metabolic and pathophysiological pathways leading to the development of diabetic nephropathy. Studies of C-peptide in animal models and in humans with type 1 diabetes all suggest a renoprotective effect for this peptide. In diabetic rodents, C-peptide reduces glomerular hyperfiltration and albuminuria. Cohort studies of diabetic patients with combined islet and kidney transplants suggest that maintained C-peptide secretion is protective of renal graft function. Further, in short-term studies of patients with type 1 diabetes, administration of C-peptide is also associated with a lowered hyperfiltration rate and reduced microalbuminuria. Thus, the available information suggests that type 1 diabetes should be regarded as a dual hormone deficiency disease and that clinical trials of C-peptide in diabetic nephropathy are both justified and urgently required.
Topics: Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Models, Animal; Humans
PubMed: 27640884
DOI: 10.1111/joim.12548 -
Frontiers in Endocrinology 2024Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship...
CONTEXT
Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear.
OBJECTIVE
To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM).
METHODS
Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored.
RESULTS
DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN.
CONCLUSION
DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR.
TRIAL REGISTRATION
ClinicalTrails.gov, NCT03865914.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Risk Factors; Hemoglobins
PubMed: 38344659
DOI: 10.3389/fendo.2024.1292412 -
PloS One 2022Studies suggested that the association between depression and diabetic nephropathy may be bi-directional, but this hypothesis remains investigating. In this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies suggested that the association between depression and diabetic nephropathy may be bi-directional, but this hypothesis remains investigating. In this meta-analysis, the bi-directional relationship between depression and diabetic nephropathy was investigated.
METHODS
A search for the publications on depression and diabetic nephropathy in the databases of PubMed, Web of science, and Embase from the earliest available to August 2022 was conducted. Two sets of pooled risk estimates were calculated using random effects models: diabetic nephropathy predicting depression and depression predicting diabetic nephropathy. Cross-sectional studies were assessed using Agency for Healthcare Research and Quality (AHRQ), cohort and case-control studies were assessed using Newcastle-Ottawa Scale (NOS).
RESULT
Of the 974,121 patients in 30 clinical studies, 24 studies met eligibility for diabetic nephropathy predicting onset of depression, representing 28,438 incident cases. The other 6 studies met criteria for depression predicting onset of diabetic nephropathy, representing 945,683 incident cases. The pooled odds ratio (OR) of diabetic nephropathy predicting depression was 1.46 (95% CI 1.27-1.67). The OR of depression predicting diabetic nephropathy was 1.22 (95% CI 1.13-1.31).
CONCLUSION
This meta-analysis shows that the relationship between depression and diabetic nephropathy may be bidirectional. Diabetic nephropathy may be a predictor of depression, and depression may also be an indicator of diabetic nephropathy. The mechanisms underlying the bidirectional relationship need to be further investigated and interventions of the comorbidity of depression and diabetic nephropathy need be studied in clinical practice.
Topics: Humans; Diabetic Nephropathies; Depression; Cross-Sectional Studies; Comorbidity; Odds Ratio; Diabetes Mellitus
PubMed: 36538528
DOI: 10.1371/journal.pone.0278489 -
Nature Reviews. Nephrology Sep 2014Diabetic nephropathy (DN), a severe microvascular complication frequently associated with both type 1 and type 2 diabetes mellitus, is a leading cause of renal failure.... (Review)
Review
Diabetic nephropathy (DN), a severe microvascular complication frequently associated with both type 1 and type 2 diabetes mellitus, is a leading cause of renal failure. The condition can also lead to accelerated cardiovascular disease and macrovascular complications. Currently available therapies have not been fully efficacious in the treatment of DN, suggesting that further understanding of the molecular mechanisms underlying the pathogenesis of DN is necessary for the improved management of this disease. Although key signal transduction and gene regulation mechanisms have been identified, especially those related to the effects of hyperglycaemia, transforming growth factor β1 and angiotensin II, progress in functional genomics, high-throughput sequencing technology, epigenetics and systems biology approaches have greatly expanded our knowledge and uncovered new molecular mechanisms and factors involved in DN. These mechanisms include DNA methylation, chromatin histone modifications, novel transcripts and functional noncoding RNAs, such as microRNAs and long noncoding RNAs. In this Review, we discuss the significance of these emerging mechanisms, how they mediate the actions of growth factors to augment the expression of extracellular matrix and inflammatory genes associated with DN and their potential usefulness as diagnostic biomarkers or novel therapeutic targets for DN.
Topics: Diabetic Nephropathies; Epigenesis, Genetic; Gene Expression Regulation; Genetic Markers; Genetic Predisposition to Disease; Humans
PubMed: 25003613
DOI: 10.1038/nrneph.2014.116 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and... (Review)
Review
Diabetic nephropathy (DN) is a serious microvascular consequence of diabetes mellitus (DM), posing an encumbrance to public health worldwide. Control over the onset and progress of DN depend heavily on early detection and effective treatment. DN is a major contributor to end-stage renal disease, and a complete cure is yet to be achieved with currently available options. Though some therapeutic molecules have exhibited promise in treating DN complications, their poor solubility profile, low bioavailability, poor permeation, high therapeutic dose and associated toxicity, and low patient compliance apprehend their clinical usefulness. Recent research has indicated nano-systems as potential theranostic platforms displaying futuristic promise in the diagnosis and treatment of DN. Early and accurate diagnosis, site-specific delivery and retention by virtue of ligand conjugation, and improved pharmacokinetic profile are amongst the major advantages of nano-platforms, defining their superiority. Thus, the emergence of nanoparticles has offered fresh approaches to the possible diagnostic and therapeutic strategies regarding DN. The present review corroborates an updated overview of different types of nanocarriers regarding potential approaches for the diagnosis and therapy of DN.
Topics: Humans; Diabetic Nephropathies; Nanomedicine; Kidney Failure, Chronic; Glomerular Filtration Rate; Precision Medicine; Diabetes Mellitus
PubMed: 38027185
DOI: 10.3389/fendo.2023.1236686 -
Frontiers in Endocrinology 2023
Topics: Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Diabetes Mellitus, Type 2
PubMed: 36742398
DOI: 10.3389/fendo.2023.1142285 -
Experimental and Clinical... Apr 2019Diabetic nephropathy is one of the main long-term diabetic microangiopathies that can complicate type 1 and 2 and other secondary forms of diabetes mellitus, including... (Review)
Review
Diabetic nephropathy is one of the main long-term diabetic microangiopathies that can complicate type 1 and 2 and other secondary forms of diabetes mellitus, including posttransplant diabetes mellitus. Posttransplant diabetes mellitus was initially reported in the 1960s, with case reports of recurrent and de novo diabetic nephropathy after kidney transplant reported in the early 2000s, mostly as a result of same-risk and precipitating factors of diabetic nephropathy as in native kidneys. The disease may appear early in view of the hyperfiltration risk of being a single grafted kidney. Here, we discuss risk factors, early serologic and genetic biomarkers for early detection, and strategies to avoid and delay the progression of diabetic nephropathy after posttransplant diabetes mellitus. In this overview of published literatures, we searched PubMed and MEDLINE for all articles published in English language between January 1994 and July 2018. Included studies reported on the prevalence, incidence, or determinants of post-transplant diabetes among renal transplant recipients and studies reporting diabetic nephropathy in their cohorts. Our review showed that avoidance or good control of posttransplant diabetes is the cornerstone in management of posttransplant diabetes mellitus and hence diabetic nephropathy. Control and avoidance can be commenced in the preparatory stage before transplant using validated genetic markers that can predict posttransplant diabetes mellitus. The use of well-matched donors with tailored immunosuppression (using less diabetogenic agents and possibly steroid-free regimens) and lifestyle modifications are the best preventative strategies. Tight glycemic control, early introduction of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and possibly conversion to less diabetogenic regimens can help to delay progression of diabetic nephropathy.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Disease Progression; Early Diagnosis; Humans; Immunosuppressive Agents; Kidney Transplantation; Protective Factors; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 30945628
DOI: 10.6002/ect.2018.0157 -
Journal of Postgraduate Medicine 2018
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Vitamin D; Vitamin D Deficiency; Vitamins
PubMed: 29386411
DOI: 10.4103/jpgm.JPGM_311_17