History Of Diabetic Nephropathy Research Articles

Use of angiotensin-converting enzyme inhibitors in patients with diabetic nephropathy

Diabetic nephropathy is the most common cause of end-stage renal failure in the Western world. It accounts for 15–25% of all renal failure in patients requiring chronic dialysis. About 20%of patients with insulin-dependent diabetes and less than 15% of patients with non-insulin-dependent diabetes develop clinically significant nephropathy. The prevalence of diabetic nephropathy inpregnant patients with insulin-dependent diabetes is estimated to be 6%. Angiotensin converting enzyme (ACE) inhibitors are the drug of choice in treating women with diabetic nephropathy. In addition,many of these drugs may be started before conception. Unfortunately, these agents might be fetotoxic when taken during pregnancy. This article reviews the epidemiology and natural history of diabetic nephropathy,discusses the renoprotective effect of ACE inhibitors, reviews the effect of ACE inhibitors on fetomaternal outcome when used prior to and during pregnancy in women with diabetic nephropathy and discussesthe new class of drugs, angiotensin II receptor antagonists, in the management of diabetics who have or are prone to developing diabetic nephropathy.

Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy.

The potential contribution of maturity-onset diabetes of the young (MODY) genes to NIDDM susceptibility in African-American and Caucasian NIDDM-affected sibling pairs with a history of adult-onset diabetic nephropathy has been evaluated. Evidence for linkage to NIDDM was found with polymorphic loci that map to the long arms of human chromosomes 20 and 12 in regions containing the MODY1 and MODY3 genes. Nonparametric analysis of chromosome 20 inheritance data collected with the MODY1-linked marker D20S197 provides evidence for linkage to NIDDM with a P value of 0.005 in Caucasian sib pairs using affected sibpair (ASP) analyses. Non-parametric analysis of chromosome 12 inheritance data collected with the MODY3-linked markers D12S349 and D12S86 provides evidence for linkage to NIDDM with P values of 0.04 and 0.006, respectively, in Caucasian sib pairs using similar analyses. No evidence for linkage of MODY1 and MODY3 markers to NIDDM in African-American sib pairs was observed. In addition, no evidence for linkage to MODY2 (glucokinase-associated MODY) was observed with either study population. Results of multipoint maximum logarithm of odds (LOD) score analysis were consistent with the ASP results. A maximum LOD score of 1.48 was calculated for linkage to MODY1-linked loci and 1.45 to MODY3-linked loci in Caucasian sib pairs. Tabulation of allele sharing in affected sib pairs with D20S197 and D12S349 suggests that affected sibling pairs may inherit susceptibility genes simultaneously from chromosome 20 and chromosome 12. The results suggest that genes contributing to NIDDM in the general Caucasian population are located in the regions containing the MODY1 and MODY3 genes.

Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy

Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy

ACE inhibition in diabetic patients. Economic implications.

Diabetic nephropathy is the inevitable long term complication of prolonged hyperglycaemia for up to 40% of patients with diabetes mellitus. Most patients with renal involvement have a number of comorbid conditions including hypertension, coronary artery disease. peripheral vascular disease and retinopathy. These complications utilise considerable healthcare expenditures. In addition, end-stage renal disease (ESRD) therapies are extremely expensive (>$US40 000 per patient per year in the US»)II However, ESRD is associated with an accelerated course to death (5-year survival <209C). thereby limiting the length that these expenditures are required. Diabetes mellitus is the number one cause of ESRD in the developed world where dialysis is usually available. and in many of the Third World countries where dialysis is often unavailable. It is estimated that there are over 100 million patients with diabetes mellitus worldwide (American Diabetes Association). In the US. diabetes mellitus is responsible for one-third of all newly diagnosed cases of ESRD. and as a cause of ESRD it is increasing at a rate that exceeds all other causes of ESRD. Total US expenditures for ESRD exceed $US7 billion yearly and the ESRD programme has been increasing by 10% per year. I II Thus, it is easily appreciated that any treatment that affects the natural history of diabetic nephropathy has the potential to markedly affect the economics of this disease. ACE inhibitors have been demonstrated to slow the progression of diabetic nephropathy to ESRDI21 and therefore may greatly influence healthcare expenditures. The purpose of this article is to explore this topic and to project the economic impact that this class of antihypertensive agents may have on this dreaded complication of diabetes mellitus.

Epidemiology and prevention of diabetic nephropathy.

Diabetes mellitus is the leading underlying cause of end-stage renal disease in the USA. To develop preventive strategies aimed at combatting diabetic end-stage renal disease, three steps are required: first, the delineation of the natural history of diabetic nephropathy; second, the identification of modifiable risk factors for the development and progression of diabetic nephropathy; and third, the demonstration that manipulation of these factors does indeed reduce risk. A review of the literature regarding the epidemiology and prevention of diabetic renal disease in humans published during the past year revealed a wealth of data which may guide preventive efforts. Prospective cohort studies confirmed that microalbuminuria is a strong predictor of nephropathy and that blood pressure is an important modifiable risk factor for the progression of diabetic renal disease. In addition, observational studies identified several novel factors which might also increase risk. Randomized controlled trials provided convincing evidence that strict glycemic control reduces the risk of progression to diabetic nephropathy by 50%. Data from trials also demonstrated that angiotensin-converting enzyme inhibitors slow the progression of renal disease beyond their effect on blood pressure alone. Future research should further evaluate novel modifiable risk factors, define optimal treatment strategies for the use of angiotensin-converting enzyme inhibitors and antihypertensive agents, and develop methods to translate these findings into practice for the general population.

Diabetic nephropathy in type 2 diabetes mellitus: animal models with emphasis on recently developed corpulent rat strains

Genetic background has recently been implicated as an important factor in the development of diabetic nephropathy in humans. Little is known about the natural history of renal disease in patients with type 2 (non-insulin-dependent) diabetes mellitus. Because toxins used in chemically induced models of diabetes may be associated with pathological renal changes, investigators have employed well-defined, genetically distinct animal models to study diabetic nephropathy. This review will focus on animal models of spontaneous type 2 diabetic nephropathy. No single animal model of diabetes corresponds exactly to the human disorder, nor develops renal changes identical to those seen in man. Rodents have been the most studied species with diabetic renal disease. The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat provides a unique model of obesity, type 2 diabetes and nephropathy. In addition, genetic controls for this rat, including the lean SHR/N-cp rat and the Wistar-Kyoto/NIH-corpulent (WKY/N-cp) rat, allow assessment of the role of hypertension and obesity in the pathogenesis of diabetic nephropathy. SHR/N-cp rats have abnormal glucose tolerance, hypertension, and develop a renal disease reminiscent of human diabetic nephropathy. WKY/N-cp rats are also obese and have hyperlipidaemia, but their glucose control is somewhat worse than that of the SHR/N-cp rat. In contrast, they do not have hypertension, the renal disease is less severe, and is less suggestive of the human pathology. Finally the LA/N-cp rat also carries the gene for obesity, and exhibits hyperlipidaemia. In contrast to the other two spontaneous models of obesity it does not exhibit hypertension or glucose intolerance. There is little evidence of renal disease in this model. The development of genetic models of obesity, hypertension and glucose intolerance provides a unique opportunity to make longitudinal observations on the natural history of diabetic nephropathy, and to test the various proposed mechanisms for the development of diabetic glomerulopathy, and the effects of various treatment modalities. Diversity in manifestations of diabetic renal disease in animals suggests the importance of genetic mechanisms in pathological outcomes.

Variable Mortality Rates among Dialysis Treatment Centers

To examine the variation in the risk for mortality among patients treated at renal dialysis facilities within a defined geographic area. All free-standing and hospital-based dialysis facilities in a single southeastern state reported to the registry. Cohort of dialysis patients followed for 1 year by an end-stage renal disease registry. Patients (n = 3612) aged 20 years and older receiving treatment at the dialysis facilities reporting to the registry during 1987. Demographic, comorbid, and severity of illness indicators were abstracted from patient records. Facility-specific risk estimates were derived from a Cox proportional hazards model. Facility-specific mortality rates ranged between 2.0 and 10.5 deaths per 10,000 patient days. Mortality rates were higher among older persons; whites; those with a history of diabetic nephropathy, angina, or congestive heart failure; and patients with either nutritional or functional status impairment. Facility-specific prevalence of each mortality risk factor varied widely. The unadjusted risk for death in a facility at the 75th percentile of risk was 1.3 times that of a facility at the median, whereas at the 25th percentile, it was 0.68 times as likely--a twofold range of risk. Controlling for differences in the prevalence of patient characteristics did not change the interquartile range in risks, and a facility's adjusted risk estimate showed a strong correlation with its unadjusted estimate (R2, 0.566; P less than 0.0001). Patient attributes associated with increased risk for mortality vary widely among dialysis facilities. Adjustment for these differences did not, however, substantially change either the degree of variation in mortality risks or the relative ranking of a facility's mortality.

Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus.

Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over one-quarter of all end-stage renal disease. Systemic/glomerular hypertension plays a role in the initiation and progression of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of glomerular hypertension may be the crucial factor involved. Human studies suggest that ACE inhibitors postpone the progression to clinical overt diabetic nephropathy in normotensive diabetic patients with persistent microalbuminuria. ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal insufficiency in hypertensive diabetics with overt nephropathy. No treatment modality other than antihypertensive treatment has yet been proven to be effective in protecting renal function in diabetic nephropathy. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate between 50 and 77% 10 years after the onset of proteinuria. Effective antihypertensive treatment has reduced the cumulative death rate to 15-20% 10 years after the onset of nephropathy.

The natural history of diabetic nephropathy.

Diabetic nephropathy is now the most common cause of ESRD in the US, and no other complication of diabetes is associated with more deaths. In addition to its impact on morbidity and mortality, it extracts a tremendous cost from the health-care economy. Prevention and better treatment of diabetic renal disease should be a high priority for both the health-care system and society at large. Ultimately, diabetic nephropathy should be preventable, but that goal can be accomplished only by the coordinated efforts between investigators, who work to uncover pathophysiologic processes and design new treatments, and clinicians, who take those findings to the patient's bedside.

Natural history of diabetic nephropathy in IDD

Natural history of diabetic nephropathy in IDD

P-7-24 Natural history of diabetic nephropathy in IDD

P-7-24 Natural history of diabetic nephropathy in IDD