Diabetic nephropathy medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
Overview
The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment, once proteinuria is established, is ACE inhibitor drugs, which usually reduce glomerular hypertension, proteinuria levels, systemic hypertension and slow the progression of diabetic nephropathy.
Medical Therapy
Medical treatment in diabetic nephropathy is aimed at slowing the progression of albuminuria. Interventions include improved glycemic control, a strict control of blood pressure, treatment of dyslipidemia, as well as administration of an angtiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARBs).[1][2]
Lifestyle Modifications
The management of diabetic nephropathy depends a lot on lifestyle and dietary modifications. These include:[3]
- Weight loss
- Exercise
- Smoking cessation
- Reduction of salt and alcohol intake
- Limiting protein intake to less than 0.8 g per kg per day
Glycemic Control
- Glycemic control is effective in reducing the microvascular complications of diabetes mellitus, as well as lowering the incidence of microalbuminuria and macroalbuminuria. In general, an HbA1c of less than 7.0% is considered adequate glycemic control.
- However, very tight glycemic control (i.e: HbA1c levels of less than 6.0% is associated with an increased mortality and cardiovascular disease. Anti-diabetic drugs and injectable insulin analogs should be used to maintain normoglycemia.
- While a strict glycemic control reduces the rate at which microalbuminura appears and progress in patients with both type I and type II diabetes mellitus, it is debatable as to whether or not an improved blood glucose control halts the progression of renal disease once microalbuminuria is present.[4][3][5]
Certain anti-diabetic drugs have additional benefits in addition to lowering blood glucose levels. These include:[5]
- PPAR-ɣ inhibitors, such as pioglitazone and rosiglitazone have anti-fibrotic and anti-inflammatory effects.
- DPP-4 inhibitors, such as sitagliptin has anti-inflammatory and anti-apoptotic properties. When sitagliptin is used for 6 months in patients with type II DM, it reduces the rate of albuminuria in these patients.[6]
- SGLT-2 inhibitors decrease the rate of hyperfiltration by exerting an effect on tubuloglomerular feedback.[7][8]
- Drugs such as metformin and sulfonylureas are contraindicated in advanced renal insufficiency.[1]
Blood Pressure Control
Blood pressure in diabetic patients with nephropathy is aimed at levels of less than 130/80.[3][9][10]
- ACE inhibitors and ARB's are the drug of choice for controlling hypertension in diabetic nephropathy.[3][5][2] Aggressive treatment of hypertension is found to retard the progression of damage to nephrons secondary to diabetes. Some advantages include:
- Lowering systemic hypertension.
- Lowering glomerular hypertension.
- Dilatation of systemic and renal arterioles, increasing renal blood flow.
- Rise in kinins which is also responsible for some of the side effects such as dry cough.[3]
- ACEI and ARBs should not be combined due to increased risk of hyperkalemia and acute kidney injury (AKI).[5][2]
- Aldosterone antagonists: found to decrease blood pressure as well as proteinuria, whether used alone or in combination with an ACEI/ARB. However, when used in combination with the other drugs, patients should be monitored for hyperkalemia.[5]
- Other drugs, such as beta blockers, calcium channel blockers and diuretics may be added if blood pressure is not well controlled.[3][2]
Lipid Therapy
- The use of statins decreases the risk of cardiovascular disease and slows the loss of renal function.[3][11]
- For diabetic patients over the age of 40 with diabetic nephropathy, statins are recommended regardless of baseline lipid levels.[5][12]
Dialysis
- Dialysis may be necessary once end-stage renal disease develops.
References
- ↑ 1.0 1.1 Kasper, Dennis (2015). Harrison's Principles of Internal Medicine. New York, New York: McGraw-Hill. ISBN 0071802150.
- ↑ 2.0 2.1 2.2 2.3 Chamberlain JJ, Rhinehart AS, Shaefer CF, Neuman A (2016). "Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes". Ann. Intern. Med. 164 (8): 542–52. doi:10.7326/M15-3016. PMID 26928912.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Remuzzi G, Schieppati A, Ruggenenti P (2002). "Clinical practice. Nephropathy in patients with type 2 diabetes". N. Engl. J. Med. 346 (15): 1145–51. doi:10.1056/NEJMcp011773. PMID 11948275.
- ↑ Nathan DM (1993). "Long-term complications of diabetes mellitus". N. Engl. J. Med. 328 (23): 1676–85. doi:10.1056/NEJM199306103282306. PMID 8487827.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Lim A (2014). "Diabetic nephropathy - complications and treatment". Int J Nephrol Renovasc Dis. 7: 361–81. doi:10.2147/IJNRD.S40172. PMC 4206379. PMID 25342915. Vancouver style error: initials (help)
- ↑ Mori H, Okada Y, Arao T, Tanaka Y (2014). "Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus". J Diabetes Investig. 5 (3): 313–9. doi:10.1111/jdi.12142. PMC 4020336. PMID 24843780.
- ↑ Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M (2014). "Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus". Circulation. 129 (5): 587–97. doi:10.1161/CIRCULATIONAHA.113.005081. PMID 24334175.
- ↑ Anders, Hans‐Joachim; Davis, John M.; Thurau, Klaus (2016). "Nephron Protection in Diabetic Kidney Disease". The New England Journal of Medicine. 375 (21): 2096–2098. doi:10.1056/NEJMcibr1608564.
- ↑ "American Diabetes Association Clinical Practice Recommendations 2001". Diabetes Care. 24 Suppl 1: S1–133. 2001. PMID 11403001.
- ↑ Meltzer S, Leiter L, Daneman D, Gerstein HC, Lau D, Ludwig S, Yale JF, Zinman B, Lillie D (1998). "1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association". CMAJ. 159 Suppl 8: S1–29. PMC 1255890. PMID 9834731.
- ↑ "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group". Lancet. 352 (9131): 854–65. 1998. PMID 9742977.
- ↑ Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S (2001). "Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals". JAMA. 286 (4): 421–6. PMID 11466120.