Diabetic nephropathy research -
Diabetic nephropathy is a progressive kidney disease associated with diabetes mellitus — type 1 and type 2 — affecting kidney glomeruli, arterioles, tubules and the interstitium.
Clinical features include macroalbuminuria and a reduction in glomerular filtration rate that may lead to end-stage renal disease, requiring dialysis or kidney transplantation.
To mark this event, Nature Reviews Nephrology invited five researchers from different geographical regions worldwide to discuss the impact of new and emerging therapies for diabetic kidney disease on patient care as well as the barriers that must be overcome to ensure equitable access to these therapies.
Poor renal distribution of antibody-based drugs limits the treatment efficiency for diabetic nephropathy and causes side effects. In this Review, the authors provide an overview of the roles of miRNAs in the development of chronic kidney disease, acute kidney injury and allograft injury.
They also discuss the utilization of miRNAs as biomarkers and their potential as therapeutic targets in kidney disease. New clinical studies suggest that mesenchymal stem cell MSC therapy can have positive clinical effects, potentially via immunomodulation, in patients with diabetic nephropathy or nephrotic syndrome.
These trials suggest that the therapy is safe, but adverse reactions highlight the need to examine the source and functional attributes of MSCs closely. Skip to main content Thank you for visiting nature. nature subjects diabetic nephropathy. Diabetic nephropathy articles from across Nature Portfolio Atom RSS Feed Definition Diabetic nephropathy is a progressive kidney disease associated with diabetes mellitus — type 1 and type 2 — affecting kidney glomeruli, arterioles, tubules and the interstitium.
Reviews 02 Jan Nature Reviews Nephrology P: Research Open Access 13 Dec Nature Communications Volume: 14, P: The crosstalk between glomerular endothelial cells and podocytes controls their responses to metabolic stimuli in diabetic nephropathy Michael Albrecht Carsten Sticht Boyan K.
Research Open Access 20 Oct Scientific Reports Volume: 13, P: Prognostic significance of albuminuria in elderly of various ages with diabetes Subin Hwang Kyungho Lee Jung Eun Lee.
Research Open Access 01 May Scientific Reports Volume: 13, P: Long noncoding RNA ENST promotes podocyte injury in diabetic kidney disease by facilitating the association of PTBP1 with RAB3B Jinxiu Hu Qimeng Wang Zhimei Lv. MicroRNAs in kidney injury and disease In this Review, the authors provide an overview of the roles of miRNAs in the development of chronic kidney disease, acute kidney injury and allograft injury.
Nonetheless, there is an important overlap in mesangial expansion and glomerular basement membrane thickening among normoalbuminuric, microalbuminuric, and proteinuric type 1 and type 2 diabetic patients 73 , 74 , with no clear cutoff to distinguish the groups.
After the diagnosis of micro- or macroalbuminuria is confirmed, patients should undergo a complete evaluation, including a work-up for other etiologies and an assessment of renal function and the presence of other comorbid associations. Differential diagnosis is usually based on the history, physical examination, laboratory evaluation, and imaging of the kidneys.
Renal biopsy is only recommended in special situations. Typical diabetic nephropathy is also likely to be present in proteinuric type 2 diabetic patients with retinopathy. The presence of symptoms during urination suggests urinary tract disorders such as obstruction, infection, or stones.
Skin rash or arthritis may indicate systemic lupus erythematosus or cryoglobulinemia. Presence of risk factors for parenterally transmitted disease may raise the suspicion of kidney disease associated with HIV, hepatitis C, or hepatitis B.
Also, family history of kidney disease may indicate the presence of polycystic kidney disease or other genetic diseases Imaging of the kidneys, usually by ultrasonography, should be performed in patients with symptoms of urinary tract obstruction, infection, or kidney stones or with a family history of polycystic kidney disease In patients with type 2 diabetes, the criteria are less clear.
The proportion of nondiabetic renal lesions in proteinuric type 2 diabetic patients seems to vary according to the criteria used to perform the biopsy and to the ethnic background of the patient.
Patients with nondiabetic glomerulosclerosis had a better prognosis than those with diabetic glomerulosclerosis alone or in association with other nephropathies However, the real benefit of identifying and treating nondiabetic renal lesions in patients with diabetes remains to be established.
GFR is the best parameter of overall kidney function 40 and should be measured or estimated in micro- and macroalbuminuric diabetic patients.
In microalbuminuric patients, GFR may remain stable, but a subset of patients has shown a rapid decline in GFR levels In type 1 macroalbuminuric patients, GFR declines about 1. In patients with type 2 diabetes, GFR decline is more variable. Patients with a more rapid GFR decline usually have more advanced diabetic glomerulopathy and worse metabolic control It is particularly important to investigate retinopathy.
Ideally, this should be done by an experienced ophthalmologist, since retinopathy is frequent in the presence of diabetic nephropathy and is a clue for its diagnosis.
Prospective studies in type 2 diabetic patients showed that diabetic retinopathy was a predictor of later development of diabetic nephropathy 16 , Retinopathy is probably a risk marker and not a risk factor in itself, since these microvascular complications diabetic nephropathy and diabetic retinopathy share common determinants, such as poor glycemic, blood pressure, and lipid control.
Other complications of diabetes, such as peripheral and autonomic neuropathy, should also be evaluated, since they are seen more frequently in patients with diabetic nephropathy 86 , 87 and are associated with increased morbidity and mortality. Patients with diabetic nephropathy, due to their high cardiovascular risk, should be routinely evaluated for the presence of coronary heart disease, independently of the presence of cardiac symptoms.
Other atherosclerotic complications, such as carotid disease, peripheral artery disease, and atherosclerotic renal-artery stenosis should also be assessed. This can be prevented by prior hydration and administration of an iso-osmolar contrast media Acetylcysteine, a free-radical scavenger, has also been shown to be renoprotective in some studies 90 , but this was not confirmed in a recent study In these patients, the use of ACE inhibitors or angiotensin II type 1 receptor blockers ARBs could reduce transcapillary filtration pressure, leading to acute or chronic renal insufficiency, especially if renal-artery stenosis affects both kidneys or the sole functioning kidney.
Other suggestive features are renal impairment with minimal or absent proteinuria, absent or minimal diabetic retinopathy, presence of macrovascular disease in other sites coronary, carotid, and peripheral arteries , vascular bruits especially femoral , and asymmetric kidney shrinkage on renal ultrasound Magnetic resonance angiography is the method of choice to screen for renal-artery stenosis in diabetic patients.
Other options, even though with lower sensitivity, are captopril renal scintigraphy and duplex Doppler ultrasonography imaging of the renal arteries. Rarely does renal revascularization cure hypertension, but it may improve or stabilize renal function in patients with chronic kidney disease The basis for the prevention of diabetic nephropathy is the treatment of its known risk factors: hypertension, hyperglycemia, smoking, and dyslipidemia.
These are also risk factors for cardiovascular disease and should be vigorously treated. Moreover, in the Kumamoto Study, intensive glycemic control also reduced the rate of development of micro- and macroalbuminuria Treatment of hypertension dramatically reduces the risk of cardiovascular and microvascular events in patients with diabetes.
Hypertension is common in diabetic patients, even when renal involvement is not present. The role of ACE inhibitors in the prevention of diabetic nephropathy in patients with type 1 diabetes has not been defined.
The use of perindopril during 3 years in normotensive normoalbuminuric type 1 diabetic patients delayed the increase in albuminuria In patients with type 2 diabetes, ACE inhibitors and ARBs both diminish the risk for diabetic nephropathy , and reduce the occurrence of cardiovascular events Moreover, ramipril reduced UAE at 1 year and at the end of the study Therefore, ACE inhibitors have been shown to be beneficial for reno- and cardioprotection in patients with type 2 diabetes.
The goal of treatment is to prevent the progression from micro- to macroalbuminuria, the decline of renal function in patients with macroalbuminuria, and the occurrence of cardiovascular events.
The treatment principles are the same as those adopted for the prevention of diabetic nephropathy, although in this case multiple and more intensive strategies must be used.
The strategies and goals are described in Table 2. The effect of strict glycemic control on the progression from micro- to macroalbuminuria and on the rate of renal function decline in macroalbuminuric patients is still controversial.
In the DCCT study, intensified glycemic control did not decrease the rate of progression to macroalbuminuria in patients with type 1 diabetes who were microalbuminuric at the beginning of the study 95 , The Microalbuminuria Collaborative Study Group reported similar findings However, these studies , were underpowered to detect an effect of intensified glycemic control on the progression from micro- to macroalbuminuria.
Moreover, improvement of glycemic control, especially if associated with lower blood pressure levels, reduced the renal function decline in proteinuric type 1 diabetic patients In patients with type 2 diabetes, very few studies analyzed the role of blood glucose control on the progression of diabetic nephropathy.
In the Kumamoto Study, a reduction in the conversion from micro- to macroalbuminuria was observed with intensive treatment Although the effects of strict glycemic control on the progression of diabetic nephropathy are not firmly established, it should be pursued in all these patients.
Some oral antihyperglycemic agents seem to be especially useful. Rosiglitazone, as compared with glyburide, has been shown to decrease UAE in patients with type 2 diabetes. This suggests a beneficial effect in the prevention of renal complications of type 2 diabetes Also, the use of antihyperglycemic agents in proteinuric type 2 diabetic patients should take renal function into account.
Sulfonylureas and their metabolites, except glimepiride, are eliminated via renal excretion and should not be used in patients with decreased renal function Repaglinide and nateglinide have a short duration of action, are excreted independently of renal function, and have a safety profile in patients with renal impairment.
However, at this point, sulfonylureas and insulin secretagogues are usually not very effective due to the low endogenous production of insulin resulting from the long duration of diabetes. Thus, most type 2 diabetic patients with diabetic nephropathy should be treated with insulin. In microalbuminuric type 1 and type 2 diabetic patients, numerous studies have demonstrated that treatment of hypertension, irrespective of the agent used, produced a beneficial effect on albuminuria Renin-angiotensin system RAS blockade with ACE inhibitors or ARBs confers an additional benefit on renal function.
This renoprotective effect is independent of blood pressure reduction , and may be related to decreased intraglomerular pressure and passage of proteins into the proximal tubule These drugs decrease UAE and the rate of progression from microalbuminuria to more advanced stages of diabetic nephropathy.
ARBs were also effective in reducing the development of macroalbuminuria in microalbuminuric type 2 diabetic patients.
It is also interesting to note that UAE was still reduced 1 month after the withdrawal of irbesartan These data reinforce the idea that the antiproteinuric effect of ARBs is blood pressure independent. Although there is no long-term study comparing the effects of ACE inhibitors and ARBs on the progression from microalbuminuria to overt diabetic nephropathy, both agents led to a similar reduction in albuminuria in a week study and a 1-year study Therefore, the use of either ACE inhibitors or ARBs is recommended as a first-line therapy for type 1 and type 2 diabetic patients with microalbuminuria, even if they are normotensive In proteinuric patients, Mogensen was the first to demonstrate, almost 30 years ago, that treatment of hypertension reduced albuminuria and the rate of GFR decline in type 1 diabetic patients.
Subsequently, other studies have clearly demonstrated that aggressive treatment of hypertension has a strong beneficial effect in reducing GFR decline in proteinuric type 1 diabetic patients This reduction in GFR decline was predicted by reduction in albuminuria According to the MDRD Modification of Diet in Renal Disease trial, the lower the blood pressure, the greater the preservation of renal function in nondiabetic patients Although this study included mainly nondiabetic patients, this goal also has been recommended for proteinuric diabetic patients Addition of ACE inhibitors in proteinuric type 1 diabetic patients or ARBs in macroalbuminuric type 2 diabetic patients , decreased proteinuria and renal function decline.
Although there was no difference in the cardiovascular event rate, a significantly lower incidence of congestive heart failure was observed among patients receiving ARBs The antiproteinuric effect of ARBs has certain characteristics. It occurs early within 7 days after treatment is started and persists stable thereafter , and it is independent of blood pressure reduction and has a dose-response effect beyond the doses needed to control blood pressure This raise in creatinine is associated with long-term preservation of renal function, and therefore ACE inhibitors should not be stopped Greater increases should raise the suspicion of renal-artery stenosis.
Inhibition of the RAS, especially with ACE inhibitors, might raise serum potassium levels, particularly in patients with renal insufficiency For these reasons, albuminuria, serum creatinine, and potassium should be checked monthly during the first 2—3 months after starting treatment with ACE inhibitors or ARBs.
Recently, Mogensen et al. ACE inhibitors and ARBs interrupt the RAS at different levels, and the combination of these classes of drugs may have an additive effect on renoprotection. Other studies have also demonstrated that the combination of ACE inhibitors and ARBs had a synergistic effect in blood pressure and UAE reduction in patients with type 1 and type 2 diabetes with diabetic nephropathy.
RAS dual blockade is more effective in reducing UAE than maximal recommended doses of ACE inhibitors alone Even though no long-term trials analyzing the benefit of RAS dual blockade in diabetic nephropathy are available, in nondiabetic proteinuric patients the COOPERATE Combination Treatment of Angiotensin-II Receptor Blocker and Angiotensin-Converting-Enzyme Inhibitor in Nondiabetic Renal Disease trial has shown that dual therapy was superior to monotherapy at its maximal doses in retarding the progression of renal disease in a 3-year follow-up The combination of spironolactone, an aldosterone antagonist, with an ACE inhibitor was also more effective in reducing UAE and blood pressure in micro- and macroalbuminuric type 2 diabetic patients than the ACE inhibitor alone A detailed discussion of the agents used to treat hypertension in patients with diabetic nephropathy is beyond the scope of this article, and recent guidelines , and reviews on this subject are available , , Therefore, only general guidelines will be discussed here, taking into account the special characteristics of these patients.
It is more important to reach the blood pressure goals than to use a particular agent, since most patients will require several agents.
However, due to the known renoprotective effect of ACE inhibitors and ARBs, treatment should start with either of these agents. Patients with systolic blood pressure 20 mmHg or diastolic blood pressure 10 mmHg above the goal should start treatment with two agents.
An ACE inhibitor or ARB and a low-dose thiazide diuretic ARBs and ACE inhibitors can be combined if there is no reduction in albuminuria or if blood pressure target levels are not reached, even before maximizing the dose of each agent. Additional agents should be added as needed.
Calcium channel blockers have an additional effect on reducing blood pressure levels. These agents should only be used in combination with an ACE inhibitor and should not be used in patients with a recent coronary event.
Possibly, a metabolic neutral compound, carvedilol, should be used. The combination of β-blockers and nondihydropyridine calcium channel blockers should be used with caution, since both agents have negative chronotropic effects. Blood pressure treatment could be assessed by h ambulatory monitoring in the following situations: in patients with treatment-resistant hypertension, when there is a suspicion of white coat hypertension, or to detect drug-induced or autonomic neuropathy—related hypotensive episodes This was probably related to the lower amount of saturated fat and the higher proportion of polyunsaturated fatty acids found in chicken meat than in red meat.
The beneficial effect of polyunsaturated fatty acids on endothelial function could also reduce UAE. A normal protein diet with chicken as the only source of meat may represent an additive strategy for the treatment of microalbuminuric type 2 diabetic patients.
However, long-term studies are necessary. According to a meta-analysis of five studies including a total of patients, dietary protein restriction slowed the progression of diabetic nephropathy in patients with type 1 diabetes.
More recently, a 4-year randomized controlled trial in 82 patients with type 1 diabetes with progressive diabetic nephropathy showed that a moderately low—protein diet 0. The effect of lipid reduction by antilipemic agents on progression of diabetic nephropathy is still unknown.
So far, there have been no large trials analyzing whether the treatment of dyslipidemia could prevent the development of diabetic nephropathy or the decline of renal function.
However, there is some evidence that lipid reduction by antilipemic agents might preserve GFR and decrease proteinuria in diabetic patients Moreover, the results of the recently presented CARDS Collaborative Atorvastatin Diabetes Study , which showed a marked reduction of cardiovascular events in patients with diabetes and at least one additional risk factor for coronary artery disease, suggest that all diabetic patients should be taking statins www.
Furthermore, anemia has been considered a risk factor for progression of renal disease and retinopathy Low-dose aspirin has been recommended for primary and secondary prevention of cardiovascular events in adults with diabetes.
This therapy did not have a negative impact on renal function UAE or GFR in type 1 and type 2 diabetic patients with micro- or macroalbuminuria , Although this study was underpowered to analyze the effect on the development of cardiovascular events, these data raise the issue that diabetic patients could be less responsive to aspirin therapy aspirin resistance.
This phenomenon was associated with higher levels of A1c, lower concentration of HDL cholesterol, and higher concentration of total cholesterol Patients with microalbuminuria frequently have other cardiovascular risk factors, such as hypertension and dyslipidemia.
In the Steno-2 study, multifactorial intervention was compared with conventional treatment in microalbuminuric type 2 diabetic patients The multifactorial intervention consisted of a stepwise implementation of lifestyle changes and pharmacological therapy, including a low-fat diet, a three to five times a week light-to-moderate exercise program, a smoking cessation program, and prescription of ACE inhibitors or ARBs and aspirin.
The measures described above might not be effective in some patients with diabetes, and novel therapeutic strategies are warranted. High doses of thiamine and its derivate benfotiamine have been shown to retard the development of microalbuminuria in experimental diabetic nephropathy, probably due to decreased activation of protein kinase C, decreased protein glycation, and oxidative stress Treatment with ALT, a cross-link breaker of the advanced glycation end products, has been shown to result in a significant reduction in UAE, blood pressure, and renal lesions in experimental diabetes Treatment with a protein kinase C β inhibitor ruboxistaurin normalized GFR, decreased albumin excretion rate, and ameliorated glomerular lesions in diabetic rodents In a rat model of diabetes-induced glomerulosclerosis, administration of a modified heparin glycosaminoglycan prevented albuminuria, glomerular, and tubular matrix accumulation and transforming growth factor β1 mRNA overexpression Very few studies have been conducted in humans.
Sulodexide, a glycosaminoglycan, significantly reduced albuminuria in micro- or macroalbuminuric type 1 and type 2 diabetic patients Pimagedine, a second-generation inhibitor of advanced glycation end products, reduced urinary protein excretion and the decline in GFR in proteinuric type 1 diabetic patients in a randomized, placebo-controlled study In the last few years, we have witnessed enormous progress in the understanding of the risk factors and mechanisms of diabetic nephropathy, the stages of renal involvement in diabetes, and the treatment strategies to prevent or interrupt the progression of diabetic nephropathy.
Treatment of hypertension is a priority. Attention to these procedures will also ensure the reduction of cardiovascular mortality. In a 5-year prospective study, Barnett et al. Diabetic nephropathy stages: cutoff values of urine albumin for diagnosis and main clinical characteristics.
This study was partially supported by Projeto de Núcleos de Excelência do Ministério de Ciência e Tecnologia, Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq , and Hospital de Clínicas de Porto Alegre. A table elsewhere in this issue shows conventional and Système International SI units and conversion factors for many substances.
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Editroial on the Research Plant-based eating guide Advances Liquid multivitamin supplements the research nephropahy diabetic Diabetic nephropathy research volume II. In Reseadch past, renal nephropatyh due nsphropathy diabetes mellitus was predominantly a reswarch that was first preceded by Liquid multivitamin supplements and then nephgopathy by a decrease in eGFR Refillable art materials2. Recently, nepbropathy, a decrease in glomerular filtration rate GFR without obvious albuminuria has been observed. Therefore, the concept of diabetic kidney disease has been proposed as an umbrella concept for diabetic nephropathy 12. In recent years, improvements in renal prognosis with SGLT2 inhibitors and GLP-1 receptor agonists have been reported, and the effects of these drugs are actually felt in clinical practice 3but the pathogenesis of DKD still remains largely unexplored. Recently, the role of proximal renal tubule cells in the pathogenesis of diabetic kidney disease has been the focus of research 4. Diabetic Nephropathy, Liver healing herbs Diabetic nephropathy research Kidney Pomegranate syrup recipes, refers desearch the deterioration of kidney functioning in patients affected by type 1 and type researchh diabetes. Important Note : All contributions gesearch this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review. No records found. total views article views downloads topic views.
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