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They diswase promote and support healthy blood glucose levels. These drugs are "game-changing therapies," said Dr. Janani Rangaswami, who led the writing group for an AHA scientific statement on the drugs, published in September in Circulation. Not only do the medicines dramatically cut deaths from kidney disease, studies show they can reduce rates of heart failure, stroke and death from cardiovascular causes.
She is associate chair of research in the department of medicine at Einstein Medical Center and associate clinical professor at the Sidney Kimmel College of Thomas Jefferson University, both in Philadelphia. Bhalla, who also helped write the scientific statement, acknowledged the drugs come with side effects.
But he shared Rangaswami's enthusiasm. The drugs' effects on multiple systems in the body might be slowing their adoption, he said, because specialists might be waiting for multiple members of a patient's care team to weigh in.
Jane DeMeis, who developed kidney disease and diabetes after a bad reaction to arthritis treatment, said her current group of doctors does a good job of talking. But it hasn't always been that way. DeMeis, 66, of Fairport, New York, has had to sort out conflicts on medical advice — what's best for someone with one condition can be problematic for someone with another.
She said she had to part ways with one doctor. Bhalla suggests patients "pick one physician as their main advocate. And let the physician be the one that's doing the juggling.
It can reduce your blood pressure. It can reduce your risk of kidney disease. It's not easy to achieve but is possible and is the silver bullet in this scenario of these three conditions. If you have questions or comments about this story, please email [email protected]. American Heart Association News covers heart disease, stroke and related health issues.
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Much of that cycle goes on invisibly, Bhalla said. A new generation of diabetes drugs could radically improve that. Rangaswami said that highlights the need for doctors to better communicate with one another.
Jane DeMeis, who has diabetes and kidney disease, stresses the importance of communication among a patient's health care providers. Photo courtesy of Jane DeMeis DeMeis, 66, of Fairport, New York, has had to sort out conflicts on medical advice — what's best for someone with one condition can be problematic for someone with another.
American Heart Association News Stories American Heart Association News covers heart disease, stroke and related health issues.
: Hyperglycemia and kidney disease| The connection between diabetes, kidney disease and high blood pressure | Finerenone reduces the progression of kidney function impairment and cardiovascular events in patients with type 2 diabetes and DKD, while not substantially impacting blood pressure and only slightly increasing serum potassium levels. Finerenone has been studied in patients taking maximally tolerated doses of ACE inhibitors or ARBs but has not been studied extensively in patients taking SGLT2 inhibitors plus maximally tolerated doses of ACE inhibitors or ARBs. Aside from SGLT2 inhibitors, the glucose-lowering drugs with the strongest evidence of benefit on cardiovascular and kidney outcomes in patients with preexisting cardiovascular or kidney disease are the GLP-1 receptor agonists [ 31 ]. Thus, in patients with type 2 diabetes and DKD who have not achieved glycemic control despite initial glucose-lowering therapy which is typically metformin and an SGLT2 inhibitor, a GLP-1 receptor agonist can improve glycemic control and may provide additional benefit [ ]. GLP-1 receptor agonists are discussed below and in other topics. See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus" and "Management of persistent hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus". Our recommendations outlined above are consistent with guidelines from the American Diabetes Association ADA and the Kidney Disease Improving Global Outcomes KDIGO on the treatment of patients with DKD [ 37,38 ]. The glycosuria is dependent upon kidney function, and therefore the magnitude of glycosuria and lowering of blood glucose is smaller among individuals with reduced kidney function. SGLT2 inhibitors have additional effects on the kidney, and, given their weak glucose-lowering effect, these effects are likely independent of glycemic control. By blocking the cotransporter, they reduce sodium reabsorption, which is usually increased in patients with diabetes due to the excess tubular glucose load. The resulting natriuresis reduces intravascular volume and blood pressure, but it also increases the delivery of sodium to the macula densa. Increased sodium delivery to the macula densa normalizes tubuloglomerular feedback and thereby reduces intraglomerular pressure ie, reduces glomerular hyperfiltration through constriction of the abnormally dilated afferent arteriole [ 39 ]. This decrease in glomerular hyperfiltration can, hypothetically, slow the rate of progression of kidney disease see "Diabetic kidney disease: Pathogenesis and epidemiology", section on 'Glomerular hyperfiltration'. A range of additional mechanisms may explain the benefits of SGLT2 inhibitors on kidney disease progression [ 40 ]. SGLT2 inhibitors reduce the risk of kidney disease progression among patients with DKD who are already taking ACE inhibitors or ARBs [ 33, ], as well as the incidence of cardiovascular disease [ 33 ]. Among patients with DKD and severely increased albuminuria, the best data come from three large trials:. Approximately two-thirds of enrolled patients had type 2 diabetes; 98 percent were taking an ACE inhibitor or ARB. The beneficial effect of dapagliflozin was similar in patients with DKD and in patients with other forms of kidney disease, reinforcing the concept that beneficial effects are independent of glycemic control. There were no differences between the treatment groups with respect to major adverse effects. Less than half 46 percent of participants had diabetes. At two years, empagliflozin reduced the incidence of ESKD 3. The risks of all-cause mortality 4. Effects were similar in patients with and without diabetes and regardless of the eGFR at the start of the study. Numerous other large trials of SGLT2 inhibitors in patients with type 2 diabetes enrolled subsets of patients with mostly nonalbuminuric DKD [ 45, ]. Compared with placebo, SGLT2 inhibitors reduced the rate of kidney disease progression among patients with diabetes regardless of preexisting DKD 1. The relative benefits from SGLT2 inhibitors were similar among patients with different baseline levels of albumin excretion. However, given that the rate of kidney disease progression is substantially higher in patients with severely increased albuminuria, the absolute benefits of SGLT2 inhibitor therapy are greater among those with higher levels of albuminuria, despite similar relative risks. SLGT2 inhibitors also reduced the rates of major cardiovascular events among patients with established atherosclerotic cardiovascular disease regardless of whether patients had DKD [ 31,33,45,51,56,59 ]. These drugs also prevent heart failure hospitalization and death in patients who have heart failure with reduced ejection fraction. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Clinical outcomes'. SGLT2 inhibitors increase the risk of genital infections by two- to fourfold; such infections primarily include vulvovaginal candidiasis, which occur in 10 to 15 percent of women taking these drugs. SGLT2 inhibitors are also associated with Fournier's gangrene in rare cases [ 62 ]. In addition, SGLT2 inhibitors can produce "euglycemic" diabetic ketoacidosis in type 1 diabetes and more rarely in type 2 diabetes. Thus, patients with a prior history of or risk factors for genital infections may reasonably choose to not take an SGLT2 inhibitor. In patients with DKD who have a lower absolute risk for progression of kidney disease, and who also do not have established atherosclerotic cardiovascular disease or heart failure, the benefits and harms of taking an SGLT2 inhibitor may be more closely balanced. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Adverse effects'. Activation of the mineralocorticoid receptor is associated with cardiovascular and kidney disease, putatively by stimulating inflammatory and fibrotic cascades [ 63 ]. Steroidal MRAs, such as spironolactone , reduce albuminuria in patients with DKD but often cause hyperkalemia in patients with reduced eGFR, particularly when ACE inhibitors or ARBs are also used. The nonsteroidal MRA finerenone also reduces albuminuria and has a smaller effect on the serum potassium [ 64,65 ]. The effects of finerenone on kidney disease progression were examined in two large trials:. All patients were taking a maximal, or maximally tolerated, dose of an ACE inhibitor or ARB at baseline. Hyperkalemia occurred more frequently with finerenone Compared with placebo, finerenone reduced the risk of heart failure hospitalization 3. Hyperkalemia was more common with finerenone In a pooled analysis of these two trials, finerenone lowered the risk of kidney failure 3. The great majority of patients enrolled in these two trials were not simultaneously treated with an SGLT2 inhibitor, and the subgroup of patients who were was too small to determine with certainty whether or not finerenone provided additional benefit. Another nonsteroidal MRA, esaxerenone, also reduces albuminuria in patients with DKD [ 69 ]. However, trials of esaxerenone report higher rates of hyperkalemia than those examining finerenone [ ], and the effects of esaxerenone on mortality and ESKD are unknown. However, the effect was predominantly due to a reduction in new-onset albuminuria. Similarly, another GLP-1 receptor agonist dulaglutide slowed the rate of decline in eGFR and prevented worsening of albuminuria in trials of patients with type 2 diabetes with and without CKD [ 73,74 ]. Thus, if additional glucose-lowering therapy is required in a patient with DKD despite initial glucose-lowering therapy and an SGLT2 inhibitor, then we would prefer starting a GLP-1 receptor agonist. GLP-1 receptor agonists also reduce the rates of cardiovascular disease [ 31 ]. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'. By inhibiting dipeptidyl peptidase DPP 4, DPP-4 inhibitors prevent the deactivation of a variety of bioactive peptides, including GLP-1, thereby modestly increasing GLP-1 levels. However, unlike GLP-1 receptor agonists, DPP-4 inhibitors have not prevented the development or progression of kidney disease in patients with diabetes, nor do they have any cardiovascular benefits [ 75,76 ]. The use of DPP-4 inhibitors in patients with type 2 diabetes, including their safety and need for dose adjustments in the setting of CKD, is discussed separately. See "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus". A large trial of more than individuals with type 2 diabetes treated with metformin monotherapy directly compared the kidney effects of the GLP-1 receptor agonist liraglutide with a DDP-4 inhibitor, insulin, and glimepiride [ 77 ]. There were no significant differences among the groups at five years in terms of eGFR decline or development of CKD in this low-risk group. The patients enrolled had normal kidney function and well controlled blood pressure at baseline, and the number of events was small. This study does not support the use of expensive GLP-1 receptor agonists for kidney protection in patients at low risk. Therapies of limited use — Various other approaches have been studied as methods to slow the progression of DKD. However, there are insufficient data to advocate their use:. Data are conflicting as to whether protein restriction can slow the progression of kidney disease [ ]. In addition, it is uncertain whether a low-protein diet is significantly additive to other measures aimed at preserving kidney function, such as ACE inhibition and aggressive control of blood pressure and blood glucose [ 78 ]. Other aspects of monitoring should be based upon the clinical situation. See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers". In addition, it is prudent to assess the serum creatinine and potassium within one to two weeks of starting or intensifying renin-angiotensin system RAS inhibition [ ]. Blood pressure should be assessed within one to two weeks of initiating or intensifying these agents. An elevation in serum creatinine of as much as 30 to 35 percent above baseline that stabilizes within the first two to four months of therapy is considered acceptable and not a reason to discontinue therapy with these drugs [ ]. Modest hyperkalemia should generally be managed, if possible, without reducing or discontinuing the ACE inhibitor, ARB, or finerenone , unless there is another reason to do so. If discontinued for hyperkalemia, the ACE inhibitor or ARB should be resumed as soon as it is safe to do so. See "Treatment and prevention of hyperkalemia in adults", section on 'Patients who can have the serum potassium lowered slowly'. Similarly, the serum creatinine, serum potassium, and blood pressure, plus the patient's volume status, should generally be ascertained within a few weeks of commencing a sodium-glucose cotransporter 2 SGLT2 inhibitor. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Hypotension'. Both RAS inhibition and SGLT2 inhibitors may increase the risk of symptomatic hypotension, and other antihypertensive therapies should be withdrawn first if possible before considering cessation of these evidence-based therapies. Similarly, SGLT2 inhibitors may cause volume depletion, and withdrawal or reduction of thiazide or loop diuretics should be attempted before discontinuing the SGLT2 inhibitor. See "Definition and staging of chronic kidney disease in adults", section on 'Referral to a specialist'. PROGNOSIS — A substantial proportion of people with diabetic kidney disease DKD will have progressive loss of kidney function and will develop end-stage kidney disease ESKD. The strongest risk factor for risk of progression is the presence of increased albuminuria, while people with reduced estimated glomerular filtration rate eGFR or anemia are also at increased risk. With available protective therapies, a dramatic stabilization of kidney function is likely to be achievable. See "Diabetic kidney disease: Manifestations, evaluation, and diagnosis", section on 'Natural history'. Of note, people with DKD are at particularly high risk of cardiovascular events, and most have a higher risk of death mostly cardiovascular than developing kidney failure. Cardiovascular protective therapies are therefore also critical. See "Overview of general medical care in nonpregnant adults with diabetes mellitus", section on 'Reducing the risk of macrovascular disease'. SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. See "Society guideline links: Glomerular disease in adults" and "Society guideline links: Chronic kidney disease in adults" and "Society guideline links: Diabetic kidney disease". These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest. The evidence supporting our recommendation is presented separately. See "Goal blood pressure in adults with hypertension", section on 'Patients with chronic kidney disease' and "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus' and 'Blood pressure control' above. However, glycemic targets in type 1 diabetes have not been well studied in patients with advanced chronic kidney disease CKD. The approach to target an A1C of 7 percent or less, if tolerated is similar in patients with type 2 diabetes, although fewer supportive data are available than for type 1 diabetes. The evidence for these approaches is presented elsewhere. See "Glycemic control and vascular complications in type 1 diabetes mellitus" and "Glycemic control and vascular complications in type 2 diabetes mellitus" and 'Glycemic control' above. See 'Other' above. However, while these drugs are more beneficial than other antihypertensive agents in patients with albuminuric DKD, they do not have clear advantages over calcium channel blockers or diuretics among those without albuminuria. See 'Severely increased albuminuria: Treat with angiotensin inhibition' above. We also suggest use of an SGLT2 inhibitor in patients with DKD who have lower levels of urine albumin excretion Grade 2B. The SGLT2 inhibitor is typically added to the patient's existing glucose-lowering regimen since these drugs have weak glucose-lowering effects in patients with reduced kidney function. See 'Type 2 diabetes: Treat with additional kidney-protective therapy' above. SGLT2 inhibitors increase the risk of genital infections by two- to fourfold primarily vulvovaginal candidiasis and have been associated with Fournier's gangrene in rare cases. SGLT2 inhibitors are not appropriate for use in patients with type 1 diabetes and kidney disease. See 'Monitoring during therapy' above. Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you. Select the option that best describes you. View Topic. Font Size Small Normal Large. Treatment of diabetic kidney disease. Formulary drug information for this topic. No drug references linked in this topic. Find in topic Formulary Print Share. View in. Language Chinese English. Authors: Vlado Perkovic, MBBS, PhD Sunil V Badve, MD, PhD George L Bakris, MD Section Editors: Richard J Glassock, MD, MACP David M Nathan, MD Deputy Editor: John P Forman, MD, MSc Contributor Disclosures. All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jan This topic last updated: Jul 17, aspx Accessed on March 05, Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med ; Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. Fullerton B, Jeitler K, Seitz M, et al. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev ; :CD Fioretto P, Steffes MW, Sutherland DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. The Diabetes Control and Complications DCCT Research Group. Kidney Int ; Hemmingsen B, Lund SS, Gluud C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Amod A, Buse JB, McGuire DK, et al. Glomerular Filtration Rate and Associated Risks of Cardiovascular Events, Mortality, and Severe Hypoglycemia in Patients with Type 2 Diabetes: Secondary Analysis DEVOTE Diabetes Ther ; Davis TM, Brown SG, Jacobs IG, et al. Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. J Clin Endocrinol Metab ; Alsahli M, Gerich JE. Hypoglycemia, chronic kidney disease, and diabetes mellitus. Mayo Clin Proc ; Flynn C, Bakris GL. Noninsulin glucose-lowering agents for the treatment of patients on dialysis. Nat Rev Nephrol ; Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. Hebert LA, Bain RP, Verme D, et al. Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group. Kasiske BL, Kalil RS, Ma JZ, et al. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med ; Parving HH, Hommel E, Jensen BR, Hansen HP. Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Berl T, Hunsicker LG, Lewis JB, et al. Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial. J Am Soc Nephrol ; Pohl MA, Blumenthal S, Cordonnier DJ, et al. Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. Parving HH, Lehnert H, Bröchner-Mortensen J, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. Patel A, ADVANCE Collaborative Group, MacMahon S, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus the ADVANCE trial : a randomised controlled trial. Lancet ; Kaplan NM. Vascular outcome in type 2 diabetes: an ADVANCE? Bakris GL, Berkwits M. Trials that matter: the effect of a fixed-dose combination of an Angiotensin-converting enzyme inhibitor and a diuretic on the complications of type 2 diabetes. Barnett AH, Bain SC, Bouter P, et al. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. ONTARGET Investigators, Yusuf S, Teo KK, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk the ONTARGET study : a multicentre, randomised, double-blind, controlled trial. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. Mann JF, Anderson C, Gao P, et al. Dual inhibition of the renin-angiotensin system in high-risk diabetes and risk for stroke and other outcomes: results of the ONTARGET trial. J Hypertens ; Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. American Diabetes Association. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes Diabetes Care ; S Palmer SC, Tendal B, Mustafa RA, et al. Sodium-glucose cotransporter protein-2 SGLT-2 inhibitors and glucagon-like peptide-1 GLP-1 receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ ; m Dekkers CCJ, Wheeler DC, Sjöström CD, et al. Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease. Nephrol Dial Transplant ; Salah HM, Al'Aref SJ, Khan MS, et al. Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials. Am Heart J ; Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes. Dave CV, Kim SC, Goldfine AB, et al. Risk of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Addition of SGLT2 Inhibitors Versus Sulfonylureas to Baseline GLP-1RA Therapy. Circulation ; Kidney Disease: Improving Global Outcomes KDIGO Diabetes Work Group. KDIGO Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int ; S1. de Boer IH, Khunti K, Sadusky T, et al. Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association ADA and Kidney Disease: Improving Global Outcomes KDIGO. Rossing P, Caramori ML, Chan JCN, et al. Executive summary of the KDIGO Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence. Heerspink HJ, Perkins BA, Fitchett DH, et al. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Heerspink HJL, Kosiborod M, Inzucchi SE, Cherney DZI. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol ; Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. It reduces A1c by 1. The most common side effects are diarrhea, bloating and cramping. Vitamin B12 deficiency has been reported with extended use [ 29 ]. Because metformin is renally cleared, this recommendation is in place to reduce the risk of lactic acidosis in individuals with even modest renal impairment [ 30 ]. The overall incidence of lactic acidosis with metformin use, however, appears to be rare. A Cochrane database review of prospective trials and observational cohort studies showed no cases of fatal or non fatal lactic acidosis in 70, patient-years of metformin users or in 55, patient-years of users of other anti-hyperglycemic agents [ 31 ]. In a study evaluating metformin-associated lactic acidosis in 14 patients, other causes of lactic acidosis including clinical shock or tissue hypoxia were noted and seemed to be the driving cause and not specifically metformin; 10 of these patients did have metformin accumulation related to elevated serum creatinine range 3. Given the differences in translation of creatinine into creatinine clearance based on age, weight and race, it is reasonable to consider use of a GFR-based guideline such as outlined here rather than one based on creatinine alone. This approach has been accepted by various societies including KDIGO and confirmed in additional studies [ 35 ] [ 36 ]. The KDIGO Controversies Conference proposed a change to the FDA guidelines [ 16 ]. Sulfonylureas bind to the sulfonylurea receptor on the pancreatic beta-cells and lead to increased insulin secretion. They typically lower A1c by 1. The first-generation sulfonylureas are rarely prescribed. The second-generation sulfonylureas, which include glipizide, glimepiride, glyburide, and gliclazide the latter is not available in the U. Sulfonylureas and their metabolites are renally cleared, leading to an increased risk of hypoglycemia as GFR declines. They have a shorter half-life compared to the sulfonylureas. They result in a rapid and short duration of insulin release and should be taken prior to meals. They also can cause hypoglycemia [ 41 ]. The glinides reduce A1c on average by 0. The active metabolite is cleared, however, by hemodialysis so nateglinide can be used in those undergoing dialysis [ 42 ]. Conversely, repaglinide appears safe to use in individuals with CKD [ 43 ]. Thiazolidinediones pioglitazone, rosiglitazone increase insulin sensitivity by acting as PPARγ agonists. They do not cause hypoglycaemia and they lead to an A1c decrease of 0. They are metabolized by the liver and can be used in CKD. However, fluid retention is a major limiting side effect and they should not be used in advanced heart failure. This also makes their use in CKD, particularly patients on dialysis, limiting. They have been linked with increased fracture rates and bone loss, thus use in patients with underlying bone disease such as renal osteodystrophy needs to be considered. No dose adjustment is indicated with either in CKD. In September , the FDA restricted use of rosiglitazone based on studies linking it to increased cardiovascular events. Upon further review, these restrictions were lifted in An association between pioglitazone and bladder cancer has been raised but further analysis and investigation into the data shows that this association is not clearly supported [ 44 ]. A recent pooled multi-population analysis also showed no association between the thiazolidinediones and bladder cancer [ 45 ]. Alpha-glucosidase inhibitors acarbose, miglitol decrease the breakdown of oligo-and disaccharides in the small intestine, slowing ingestion of carbohydrates and delaying absorption of glucose after a meal. The major side effects are bloating, flatulence, and abdominal cramping. They typically lower A1c by 0. With reduced renal function, serum levels of acarbose and metabolites are significantly higher. Dipeptidyl peptidase 4 DPP 4 inhibitors decrease the breakdown of incretin hormones such as GLP-1 and include sitagliptin, saxagliptin, linagliptin, and alogliptin. This class of medication is weight-neutral and decreases A1c by 0. Only a small amount of linagliptin is cleared renally; thus, no dose adjustment is indicated with a reduced GFR [ 48 ]. Alogliptin also needs a dose reduction from the baseline dose of 25 mg daily to SGLT2 inhibitors reduce glucose absorption from the kidney, leading to an increase in glucose excretion and a reduction in A1c of about 0. The increase in urine glucose can result in a weight loss of up to 5 kg in one year. Exenatide regular and extended-release and liraglutide are injectable medications that mimic gut hormones known as incretins, leading to insulin release, delayed glucagon secretion and delayed gastric emptying. They contribute to central satiety leading to a reduction in appetite and often weight loss. The average expected A1c decrease is 0. Both agents have been associated with pancreatitis, and nausea is a common side effect that can limit its use. In addition, liraglutide has been associated with the development of thyroid C-cell tumors in animal studies and thus should not be given to patients with or at risk for medullary thyroid cancer. Exenatide is given twice daily and liraglutide is given once daily; exenatide extended-release is dosed once weekly. Albiglutide and dulaglutide are other GLP-1 receptor agonists that can also be dosed once weekly. Clearance of exenatide decreases with declines in GFR [ 50 ]. Additionally, in a case report of a patient with renal impairment and CKD, use of exenatide led to a rise in serum creatinine that resolved when the medication was stopped [ 51 ]. Liraglutide is not metabolized primarily by the kidney; no dose adjustment is indicated in those with renal impairment, including ESRD, although data in this population are limited [ 53 ]. No dosage restrictions are needed for albiglutide or dulaglutide with decreasing GFR [ 54 , 55 ]. The manufacturer has reported cases of renal failure and worsening of chronic renal impairment with its use and advises caution with initiating or increasing the dose in those with nephropathy. Pramlintide is also an injectable medication that is used with meals as an adjunct to insulin therapy in both type 1 and type 2 diabetes. Amylin is secreted along with insulin by pancreatic beta-cells and levels are low in patients with diabetes. It typically reduces A1c by 0. No dose adjustment appears necessary for CKD; it has not been studied in ESRD. The primary goal of optimizing glycemic control to reduce the development of microvascular and macrovascular complications is universal. The medication regimen is based on the comfort of the patient and physician and should be individualized, especially as renal function changes. For those who need insulin, MDI with an average of 4 daily injections is common. The closest approximation of physiologic insulin secretion can be achieved with an insulin pump delivering a continuous subcutaneous infusion. A single type of insulin is used in the pump such as a rapid-acting analog that serves as the basal, bolus and correction insulin. Insulin pumps require vigilance on the part of the patient and their use should be overseen by endocrinologists and experienced diabetes educators. Continuous Glucose Monitoring Systems CGMS are available that can continually measure glucose levels. A small plastic catheter is inserted subcutaneously and measures glucose every 5 min. Patients can view this in real-time and detect upward and downward trends in glucose. The added benefit is that alarms for high and low readings can be set. In addition to glucose control, a comprehensive approach to care is encouraged. Behavioral modification and lifestyle changes are important to control weight, improve nutrition, modify dietary intake and monitor glucose levels. Appropriate medication should be used for treatment of nephropathy, in conjunction with a nephrologist as appropriate. Close attention should also be paid to blood pressure control. Diabetes in itself is a major cause of cardiovascular disease and individuals with CKD often die of CVD; it is the major cause of death in this population. The presence of microalbuminuria, albuminuria and declining GFR are all known predictors of CVD. The combination of diabetes and CKD is particularly powerful in regards to CVD risk, necessitating aggressive control of risk factors [ 56 ]. In addition to hypertension, dyslipidemia and weight control should be addressed. Nutrition plays an important role in individuals with diabetic kidney disease as a balance of multiple dietary factors including sodium, potassium, phosphorus, and protein intake must be followed as well as intake of carbohydrates and unhealthy fats. Reduction in weight in patients who are overweight or obese and increases in exercise are generally recommended, keeping in mind the need for cardiac stress testing. It is helpful to use an experienced dietician and certified diabetes educator to safely attain dietary, exercise and weight loss goals. The KDIGO Controversies Conference addresses some of the issues surrounding diabetic kidney disease management including management of dyslipidemia and blood pressure control [ 16 ]. The American Diabetes Association also has recommendations on management of blood pressure and dyslipidemia [ 57 ]. There are a few oral agents that can be used safely in patients on dialysis, particularly if the diabetes is fairly mild. Most others, however, will need insulin for glycemic control. Patients receiving hemodialysis HD can have different clearance rates of insulin that may be affected by the timing of dialysis. Patients who are on peritoneal dialysis PD have exposure to large amounts of glucose in the dialysate that can lead to uncontrolled hyperglycemia. The nephrologist prescribing the PD will often change the glucose concentration of the dialysate because of the need for more or less fluid removal and such changes need to be discussed with the endocrinologist so that the insulin doses may be appropriately changed. In the immediate post-transplant period, glycemic control can acutely decline. This is due to the initiation of anti-rejection therapies including glucocorticoids, calcineurin inhibitors and sirolimus, and an increase in insulin resistance. In addition, patients may experience other fluctuations in their daily routines including adjustments in diet, activity and medications. Because many variables are present, glycemic control can fluctuate quite a bit, and close monitoring of blood glucose levels and adjustments of medications are needed. The management of patients with diabetes and nephropathy necessitates attention to several aspects of care. Importantly, glycemic control should be optimized for the patient, attaining the necessary control to reduce complications but done in a safe, monitored manner. Screening for development of nephropathy should be performed on a regular basis to identify microalbuminuria or reductions in GFR and if identified, the diabetes regimen should be tailored accordingly. 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| Diabetic Kidney Disease | This metabolic disorder changes the way the body produces or uses insulin. Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, et al. Dose adjustment for these agents should be gradual, with periodic assessment of renal function and potassium levels, since there is a risk for creatinine level elevation and hyperkalemia. In addition to glucose control, a comprehensive approach to care is encouraged. Comprehensive Clinical Nephrology. International Patients. Diabetic kidney disease can lead to kidney failure. |
| The Surprising Link Between Chronic Kidney Disease, Diabetes, and Heart Disease | The better a person keeps diabetes and blood pressure well-managed, the lower their chance of getting kidney disease. The kidneys work hard to make up for the failing capillaries, so kidney disease produces no symptoms until almost all function is gone. Also, the symptoms of kidney disease are not specific. The first symptom of kidney disease is often fluid buildup. Other symptoms of kidney disease include loss of sleep, poor appetite, upset stomach, weakness, and difficulty concentrating. It is vital to see a doctor regularly. The doctor can check blood pressure, urine for protein , blood for waste products , and organs for other complications of diabetes. Diabetes-related kidney disease can be prevented by keeping blood glucose in your target range. Research has shown that tight blood glucose management reduces the risk of microalbuminuria by one third. In people who already had microalbuminuria, the risk of progressing to macroalbuminuria was cut in half. Other studies have suggested that tight management can reverse microalbuminuria. Important treatments for kidney disease are management of blood glucose and blood pressure. Blood pressure has a dramatic effect on the rate at which the disease progresses. Even a mild rise in blood pressure can quickly make kidney disease worsen. Four ways to lower your blood pressure are:. In addition to these steps and your diabetes medication, certain medications lower blood pressure. There are several kinds of blood pressure drugs. Work with your health care team about other medications that may be helpful for you to lower your risk of kidney disease. You can plan a kidney-friendly meal by eating a balanced diet with a variety of whole, minimally processed foods and by following these general meal planning tips:. Talk to your health care provider about limiting fluid intake and to your registered dietician nutritionist RDN about other nutrition considerations. You may need to limit certain nutrients like sodium, potassium, and phosphorus in your eating plan. Your nutrition care plan might change over time depending on the status of your condition. Your RDN or health care provider will tell you if changes are needed based on your blood test results. Once kidneys fail, dialysis is necessary. The person must choose whether to continue with dialysis or to get a kidney transplant. This choice should be made as a team effort. Abe M, Kalantar-Zadeh K. Hemodialysis induced hypoglycemia and glucose disarrays. Nat Rev Nephrol. Renal Data System. Incidence, prevalence, patient characteristics and treatment modalities. National Institutes of Health, National Institute of Diabetes and Kidney Diseases. In: USRDS Annual data report. Bethesda; UK Prospective Diabetes Study Group. 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Urata H, Mori K, Emoto M, Yamazaki Y, Motoyama K, Morioka T, et al. Advantage of insulin glulisine over regular insulin in patients with type 2 diabetes and severe renal insufficiency. J Ren Nutr. Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol. Lubowsky ND, Siegel R, Pittas AG. Management of glycemia in patients with diabetes mellitus and CKD. Cefalu WT. Article PubMed Central Google Scholar. Ramirez SPB, McCullough KP, Thumma JR, Nelson RG, Morgenstern H, Gillespie BW, et al. Hemoglobin A 1c levels and mortality in the diabetic hemodialysis population: findings from the Dialysis Outcomes and practice patterns study DOPPS. Rhee CM, Leung AM, Kovesdy CP, Lynch KE, Brent GA, Kalantar-Zadeh K. Updates on the management of diabetes in dialysis patients. Download references. All authors contributed reviewing the literature and writing the manuscript. RPF and SV did the final review and editing. All authors made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; had been involved in drafting the manuscript or revising it critically for important intellectual content and had given final approval of the version to be published. All the authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript. The authors would like to thank Editage www. br for English language editing. The authors would also like to thank Maria Kamimura for all her assistance during the discussions and preparation of the manuscript. Our workgroup formed by nephrologists, endocrinologists and diabetologists worked between and discussing issues related to diabetes and the kidney were sponsored by Novartis in a complete independent educational program. School of Medicine, Pontificia Universidade Católica do Paraná, Imaculada Conceição, , Curitiba, PR, , Brazil. School of Medicine, University of São Paulo, São Paulo, Brazil. Hospital Regional de Presidente Prudente, Universidade do Oeste Paulista, Presidente Prudente, São Paulo, Brazil. Erika B. Institute of Pharmaceutical Sciences, Goiania, Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Roberto Pecoits-Filho. Open Access This article is distributed under the terms of the Creative Commons Attribution 4. Reprints and permissions. Pecoits-Filho, R. et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr 8 , 50 Download citation. Received : 09 May Accepted : 10 July Published : 28 July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Review Open access Published: 28 July Interactions between kidney disease and diabetes: dangerous liaisons Roberto Pecoits-Filho 1 , Hugo Abensur 2 , Carolina C. Betônico 3 , Alisson Diego Machado 2 , Erika B. Methods In this review article, based on a report of discussions from an interdisciplinary group of experts in the areas of endocrinology, diabetology and nephrology, we detail the relationship between diabetes and kidney disease, addressing the care in the diagnosis, the difficulties in achieving glycemic control and possible treatments that can be applied according to the different degrees of impairment. Discussion Glucose homeostasis is extremely altered in patients with DKD, who are exposed to a high risk of both hyperglycemia and hypoglycemia. From kidney disease basics to treatment options and patient stories, watch videos that will help you learn more about kidney disease. Kidney Health Education Kidney Disease Risk Factors High Blood Sugar and Chronic Kidney Disease. Take control of your kidney health. Attend a no-cost virtual class online or via telephone from the comfort of home , or find an in-person class where available. FIND A CLASS. Provided by DaVita® Dietitians Diabetes is the most common cause of kidney failure in the United States. Symptoms of hyperglycemia If you have diabetes you are likely to have had experience with hyperglycemia. Symptoms of hyperglycemia include the following: Dry skin Hunger Drowsiness Nausea Thirst Blurry vision Causes of high blood sugar There are many causes of high blood sugar, including: Eating too many carbohydrates such as starch, fruits and sweets Not getting enough insulin Not taking the adequate amount of diabetes medications Illness, fractures and infections Stress Recent surgery or injury Not exercising enough Ways to prevent hyperglycemia Although people with diabetes are at risk for hyperglycemia, the good news is there are steps you can take to help prevent it: Always take your medicine as prescribed by your healthcare team. Every day, eat three balanced meals that include protein , carbohydrate and fat, plus an evening snack if your dietitian recommends it. Have your renal dietitian teach you exactly how many carbohydrate servings you can eat in one day and how to balance your meals. Eat more high-fiber , low-sugar foods. Keep track of your blood sugar, and when it is high, share this information with your doctor. Check your blood sugar at least daily or as often as recommended. |
Hyperglycemia and kidney disease -
There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events.
Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed. Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease CKD and kidney failure.
Screening for diabetic nephropathy along with early intervention is fundamental to delaying its progression in conjunction with providing proper glycemic control.
Given the growing population that is now affected by diabetes and thus, nephropathy, knowledge regarding the safe use of various anti-hyperglycemic agents in those with nephropathy is of importance. In addition, attention to modification of cardiovascular disease CVD risk factors is essential.
Altogether, knowledge regarding the prevention and management of diabetic nephropathy, along with other aspects of diabetes care, is part of the comprehensive care of any patient with diabetes.
Patients with diabetes should be screened on an annual basis for nephropathy. In individuals with type 1 diabetes, screening for nephropathy should start 5 years after diagnosis of diabetes since the onset of diabetes itself is usually known.
It typically takes about 5 years for microvascular complications to develop. In patients with type 2 diabetes, screening should begin at initial diagnosis since the exact onset of diabetes is often unknown [ 1 ]. Diabetic nephropathy can be detected by the measurement of urine albumin or serum creatinine, and both tests should be performed at minimum annually [ 1 ]; those with abnormal levels should have repeat tests done sooner.
The first stage of nephropathy is usually the onset of elevated urine albumin which predicts the development of CKD and a gradual decline in glomerular filtration rate GFR. Some individuals with CKD, however, do not develop elevated urine albumin initially.
It is therefore important that individuals have both blood and urine screening tests performed. Using both modalities allows for identification of more cases of nephropathy than using either test alone.
The urine albumin to creatinine ratio can be measured on a spot or timed urine collection such as 4 or 24 h. An abnormal value should be confirmed on at least one additional urine specimen over a 6 month period.
Increased albumin excretion is not only a marker for early diabetic kidney disease but also for increased risk for macrovascular disease [ 1 ].
Other causes of elevated urine protein should be considered and avoided such as infection, strenuous exercise, hypertension, heart failure and hematuria. The serum creatinine should be used to estimate GFR and thus, the level of CKD.
One must also consider that the development of nephropathy may not be related to the diabetes itself. In patients with type 1 diabetes, the onset of retinopathy usually precedes the development of nephropathy. An individual who present with nephropathy but no retinopathy should have an evaluation for other causes.
Referral to a nephrologist should be utilized to establish the cause of nephropathy when this is uncertain. Nephrologists are also vital to assist management of complications of advancing kidney disease, such as difficult to control hypertension, hyperkalemia and rapid progression [ 1 , 2 ]. Glycemic control is essential to delay the onset of complications from diabetes, and it can be challenging for even the most experienced physician.
Blood sugar control in those with CKD adds another level of complexity. It requires detailed knowledge of which medications can be safely used and how kidney disease affects metabolism of these medications.
In addition, the glycemic target needs to be individualized for each patient, acknowledging that our ability to interpret the data can be altered in the setting of kidney disease. Glycemic control is essential to delay or possibly prevent nephropathy.
In type 1 diabetes, a number of studies show the development of microalbuminuria is associated with poorer glycemic control. In the DCCT, intensive therapy in patients with type 1 diabetes mean A1c 9. To assess whether risk reduction of diabetic nephropathy persists long-term, the EDIC Study demonstrated there were fewer cases of new microalbuminuria and progression to albuminuria in the original intensive group.
In patients with type 2 diabetes, the Kumamoto study, UKPDS and Veterans Affairs Cooperative studies showed reduction of new onset nephropathy and progression of nephropathy with intensive glycemic control [ 9 — 11 ].
A systematic review and meta-analysis of 7 trials evaluating intensive glucose control on kidney-related end points in patients with type 2 diabetes showed lower risk of developing microalbuminuria and macroalbuminuria. The intensive control groups had a median A1c ranging from 6.
The A1c difference in the intensive groups compared to the control groups ranged from 0. The analysis also found there was no benefit in regards to doubling of serum creatinine, development of ESRD or death related to kidney disease [ 12 ]. The ACCORD study showed higher risk of hypoglycemia and mortality in patients with type 2 diabetes treated with intensive glucose control mean A1c 6.
The increased mortality could not be attributed to hypoglycemia [ 13 ]. In the ADVANCE trial, more intensive glycemic control A1c 6. The VADT study intensive group with A1c 6.
The data clearly show that lowering A1c leads to benefit in regards to nephropathy. Benefits in A1c reduction are also seen on rates of retinopathy and neuropathy.
However, the effect of lowering A1c is much less in regards to macrovascular disease. Thus, it is reasonable that a target A1c ~7. Lower A1c levels are associated with higher risk of hypoglycemia which necessitates tailored A1c targets for different individuals.
Consequences of hypoglycemia, which in turn can cause injury, myocardial infarction, seizure, stroke or death, are greatest in those who are frail and elderly, with erratic eating habits, on insulin and sulfonylureas, and with CKD.
Higher A1c targets should be considered for those with shortened life expectancies, a known history of severe hypoglycemia or hypoglycemia unawareness, CKD, as well as in children.
The Controversies Conference on Diabetic Kidney Disease DKD held by KDIGO addressed a number of issues surrounding DKD, including appropriate glycemic control targets [ 16 ].
There are insufficient data and trials regarding the ideal glucose target in patients with CKD stage 3 or worse. The hemoglobin A1c can be inaccurate in some patients with kidney disease. Contributing factors include anemia from reduced lifespan of the red blood cell, hemolysis and iron deficiency; falsely increased levels can occur from carbamylation of hemoglobin and the presence of acidosis.
Fructosamine and glycated albumin are alternative measures available to estimate glycemic control. Fructosamine reflects the glycation of multiple serum proteins whereas glycated albumin reflects glycation of only albumin; both provide an estimate of control over the past 2 weeks.
It is unclear if they offer superior measures of glucose control compared to A1c in patients with CKD. Some studies suggest glycated albumin is superior to A1c in dialysis patients since A1c tends to underestimate glycemic control in those with ESRD, but others argue that A1c remains the gold standard in these patients [ 21 — 23 ].
Medical therapy for diabetes is continually changing as new therapies become available for use and new updates are available that add to our knowledge of the safety profile of available medications. Please refer to Table 1 for adjustments in dosing for diabetes medications used in CKD.
Patients with progression of kidney disease are at increased risk of hypoglycemia due to decreased clearance of insulin and some medications used to treat diabetes as well as impairment of renal gluconeogenesis from lower kidney mass.
All available insulin preparations can be used in patients with CKD, and there is no specified advised reduction in dosing for patients on insulin. The insulin type, dose and administration must be tailored to each patient to achieve goal glycemic levels but limit hypoglycemia.
The rapid-acting insulin analogs aspart, lispro and glulisine are the quickest absorbed and are ideal for rapid correction of elevated blood sugars or for prandial insulin needs; they most resemble physiologic insulin secretion.
They have an onset of action at 5—15 min, peak action at 30—90 min and an average duration of 5 h. Some studies have shown glulisine has a slightly longer duration of action than the other two rapid-acting insulins. These insulins can be given up to 15 min prior to eating. Patients with Stage 4—5 CKD and those on dialysis often have some delayed gastric emptying; giving rapid-acting insulin after the meal may be helpful for matching the insulin peak with the time of the postprandial blood glucose peak.
In patients with nausea who may not know how much they will eat, postprandial rapid-acting insulin dosing may be worth trying.
Similarly, patients on peritoneal dialysis obtain large amounts of calories from their dialysis fluid and often eat less than they might expect so that postprandial dosing may be helpful for them also.
The short-acting insulin available is regular crystalline insulin, which has an onset of action at 30—60 min, peak action at 2—3 h and duration up to 5—8 h. Regular insulin should ideally be given 30 min prior to a meal. The main advantage of regular insulin is its substantially lower cost compared to the rapid-acting analogs.
The available intermediate-acting insulin is isophane, or NPH. It has an onset of action at 2—4 h, peak concentration at 4—10 h and duration up to 10—18 h. In order to achieve adequate basal coverage, it is dosed twice daily.
Its use can be limited by its highly variable absorption. Its cost is similar to that of Regular insulin. The long-acting insulin analogs are glargine and detemir. Glargine has an onset of action at 2—4 h, with minimal peak and duration of 20—24 h; it is usually dosed once daily. A unique property of glargine is that it does not have a clear peak.
Detemir has an onset of action at 1—3 h, with a small peak at 6—8 h and duration of action of 18—22 h. Detemir is dosed twice daily to give adequate basal coverage in type 1 diabetes; in type 2 diabetes, once daily dosing sometimes is sufficient.
There are various premixed preparation of insulin that have a fixed percentage of an intermediate-acting and a rapid-or short-acting insulin. Because they contain a combination of 2 insulins, they have two separate peaks.
These preparations offer convenience for the patient with twice daily dosing but offer less flexibility and more restrictions in titration of the insulin. It must be taken at fixed times and the patient must have consistent meals.
The high concentration of U insulin alters the properties of regular insulin so its pharmacokinetics are different. It has a similar onset of action, near 30 min, but the peak is at 4—8 h and duration is 14—15 h.
It can be given up to 30 min prior to meals and is typically given two to three times daily, without the use of a basal insulin [ 27 ].
It is generally used in patients who are severely insulin resistant and can be used as a subcutaneous injection or in a pump. Metformin increases insulin sensitivity and decreases hepatic gluconeogenesis; it does not cause hypoglycemia and may lead to weight loss in some patients.
It reduces A1c by 1. The most common side effects are diarrhea, bloating and cramping. Vitamin B12 deficiency has been reported with extended use [ 29 ]. Because metformin is renally cleared, this recommendation is in place to reduce the risk of lactic acidosis in individuals with even modest renal impairment [ 30 ].
The overall incidence of lactic acidosis with metformin use, however, appears to be rare. A Cochrane database review of prospective trials and observational cohort studies showed no cases of fatal or non fatal lactic acidosis in 70, patient-years of metformin users or in 55, patient-years of users of other anti-hyperglycemic agents [ 31 ].
In a study evaluating metformin-associated lactic acidosis in 14 patients, other causes of lactic acidosis including clinical shock or tissue hypoxia were noted and seemed to be the driving cause and not specifically metformin; 10 of these patients did have metformin accumulation related to elevated serum creatinine range 3.
Given the differences in translation of creatinine into creatinine clearance based on age, weight and race, it is reasonable to consider use of a GFR-based guideline such as outlined here rather than one based on creatinine alone.
This approach has been accepted by various societies including KDIGO and confirmed in additional studies [ 35 ] [ 36 ]. The KDIGO Controversies Conference proposed a change to the FDA guidelines [ 16 ].
Sulfonylureas bind to the sulfonylurea receptor on the pancreatic beta-cells and lead to increased insulin secretion. They typically lower A1c by 1. The first-generation sulfonylureas are rarely prescribed. The second-generation sulfonylureas, which include glipizide, glimepiride, glyburide, and gliclazide the latter is not available in the U.
Sulfonylureas and their metabolites are renally cleared, leading to an increased risk of hypoglycemia as GFR declines. They have a shorter half-life compared to the sulfonylureas.
They result in a rapid and short duration of insulin release and should be taken prior to meals. They also can cause hypoglycemia [ 41 ]. The glinides reduce A1c on average by 0.
The active metabolite is cleared, however, by hemodialysis so nateglinide can be used in those undergoing dialysis [ 42 ].
Conversely, repaglinide appears safe to use in individuals with CKD [ 43 ]. Thiazolidinediones pioglitazone, rosiglitazone increase insulin sensitivity by acting as PPARγ agonists. They do not cause hypoglycaemia and they lead to an A1c decrease of 0.
They are metabolized by the liver and can be used in CKD. However, fluid retention is a major limiting side effect and they should not be used in advanced heart failure. This also makes their use in CKD, particularly patients on dialysis, limiting.
They have been linked with increased fracture rates and bone loss, thus use in patients with underlying bone disease such as renal osteodystrophy needs to be considered.
No dose adjustment is indicated with either in CKD. In September , the FDA restricted use of rosiglitazone based on studies linking it to increased cardiovascular events.
Upon further review, these restrictions were lifted in An association between pioglitazone and bladder cancer has been raised but further analysis and investigation into the data shows that this association is not clearly supported [ 44 ].
A recent pooled multi-population analysis also showed no association between the thiazolidinediones and bladder cancer [ 45 ]. Alpha-glucosidase inhibitors acarbose, miglitol decrease the breakdown of oligo-and disaccharides in the small intestine, slowing ingestion of carbohydrates and delaying absorption of glucose after a meal.
The major side effects are bloating, flatulence, and abdominal cramping. They typically lower A1c by 0. With reduced renal function, serum levels of acarbose and metabolites are significantly higher.
Dipeptidyl peptidase 4 DPP 4 inhibitors decrease the breakdown of incretin hormones such as GLP-1 and include sitagliptin, saxagliptin, linagliptin, and alogliptin. This class of medication is weight-neutral and decreases A1c by 0. Only a small amount of linagliptin is cleared renally; thus, no dose adjustment is indicated with a reduced GFR [ 48 ].
Alogliptin also needs a dose reduction from the baseline dose of 25 mg daily to SGLT2 inhibitors reduce glucose absorption from the kidney, leading to an increase in glucose excretion and a reduction in A1c of about 0.
The increase in urine glucose can result in a weight loss of up to 5 kg in one year. Exenatide regular and extended-release and liraglutide are injectable medications that mimic gut hormones known as incretins, leading to insulin release, delayed glucagon secretion and delayed gastric emptying.
They contribute to central satiety leading to a reduction in appetite and often weight loss. The average expected A1c decrease is 0. Both agents have been associated with pancreatitis, and nausea is a common side effect that can limit its use. In addition, liraglutide has been associated with the development of thyroid C-cell tumors in animal studies and thus should not be given to patients with or at risk for medullary thyroid cancer.
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Find in topic Formulary Print Share. View in. Language Chinese English. Authors: Vlado Perkovic, MBBS, PhD Sunil V Badve, MD, PhD George L Bakris, MD Section Editors: Richard J Glassock, MD, MACP David M Nathan, MD Deputy Editor: John P Forman, MD, MSc Contributor Disclosures.
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About 1 out of 3 adults with diabetes has kidney disease. The main job of the kidneys is to filter wastes and extra water out of your blood to make urine. Your kidneys also help control blood pressure and make hormones that your body needs to stay healthy. Kidney damage can also cause other health problems.
Kidney damage caused by diabetes usually occurs slowly, over many years. You can take steps to protect your kidneys and to prevent or delay kidney damage.
Diabetic kidney disease is also called DKD, chronic kidney disease, CKD, kidney disease of diabetes, or diabetic nephropathy. High blood glucose , also called blood sugar, can damage the blood vessels in your kidneys.
Many people with diabetes also develop high blood pressure , which can also damage your kidneys. Learn more about high blood pressure and kidney disease. Having diabetes for a longer time increases the chances that you will have kidney damage. If you have diabetes, you are more likely to develop kidney disease if your.
Most people with diabetic kidney disease do not have symptoms. The only way to know if you have diabetic kidney disease is to get your kidneys checked. Health care professionals use blood and urine tests to check for diabetic kidney disease. Your health care professional will check your urine for albumin and will also do a blood test to see how well your kidneys are filtering your blood.
The best way to slow or prevent diabetes-related kidney disease is to try to reach your blood glucose and blood pressure goals. Healthy lifestyle habits and taking your medicines as prescribed can help you achieve these goals and improve your health overall.
Your health care professional will test your A1C. The A1C is a blood test that shows your average blood glucose level over the past 3 months. This is different from the blood glucose checks that you may do yourself.
The higher your A1C number, the higher your blood glucose levels have been during the past 3 months. The A1C goal for many people with diabetes is below 7 percent. Ask your health care team what your goal should be. Reaching your goal numbers will help you protect your kidneys.
To reach your A1C goal, your health care professional may ask you to check your blood glucose levels. Work with your health care team to use the results to guide decisions about food, physical activity, and medicines.
Ask your health care team how often you should check your blood glucose level.
Diabetic nephropathy is a serious complication Hjperglycemia Improving athletic performance 1 diabetes Hyperglycemiia type 2 diabetes. It's also Muscle repair food diabetic kidney disease. In the Disaese States, about 1 Muscle repair food 3 people living with diabetes have diabetic nephropathy. Diabetic nephropathy affects the kidneys' usual work of removing waste products and extra fluid from the body. The best way to prevent or delay diabetic nephropathy is by living a healthy lifestyle and keeping diabetes and high blood pressure managed. Over years, diabetic nephropathy slowly damages the kidneys' filtering system.
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