Diabetic nephropathy medical therapy: Difference between revisions

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==Overview==
==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 reduces glomerular hypertension, [[proteinuria]] levels, [[systemic hypertension]] and slows the progression of diabetic nephropathy.
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 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 [[angtiontensin converting enzyme inhibitor]] ([[ACEI]]) or an [[angiotensin receptor blocker]] ([[ARBs]]).<ref name="book">{{cite book |last= Kasper |first=Dennis |date=2015 |title=Harrison's Principles of Internal Medicine |url= |location= New York, New York |publisher= McGraw-Hill |page= |isbn=0071802150}}</ref><ref name="pmid26928912">{{cite journal |vauthors=Chamberlain JJ, Rhinehart AS, Shaefer CF, Neuman A |title=Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes |journal=Ann. Intern. Med. |volume=164 |issue=8 |pages=542–52 |year=2016 |pmid=26928912 |doi=10.7326/M15-3016 |url=}}</ref>
See [[Diabetic nephropathy secondary prevention]]


===Glycemic Control===
===Lifestyle Modifications===
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 drug|Anti-diabetic drugs]] and injectable [[insulin analog]]s 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.<ref name="pmid8487827">{{cite journal |vauthors=Nathan DM |title=Long-term complications of diabetes mellitus |journal=N. Engl. J. Med. |volume=328 |issue=23 |pages=1676–85 |year=1993 |pmid=8487827 |doi=10.1056/NEJM199306103282306 |url=}}</ref><ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref><br>
The management of diabetic nephropathy depends a lot on lifestyle and dietary modifications.These include:<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref>  
 
*[[Weight loss]]
Certain [[anti-diabetic drug|anti-diabetic drugs]] have additional benefits in addition to lowering blood [[glucose]] levels. These include:<ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref>
*Exercise
*PPAR-ɣ inhibitors, such as [[pioglitazone]] and [[rosiglitazone]] have anti-fibrotic and [[anti-inflammatory]] effects.
*[[Smoking cessation]]
*[[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.<ref name="pmid24843780">{{cite journal |vauthors=Mori H, Okada Y, Arao T, Tanaka Y |title=Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus |journal=J Diabetes Investig |volume=5 |issue=3 |pages=313–9 |year=2014 |pmid=24843780 |pmc=4020336 |doi=10.1111/jdi.12142 |url=}}</ref>
*Reduction of salt and alcohol intake
*SGLT-2 inhibitors decrease the rate of hyperfiltration by exerting an effect on [[tubuloglomerular feedback]].<ref name="pmid24334175">{{cite journal |vauthors=Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, Fagan NM, Woerle HJ, Johansen OE, Broedl UC, von Eynatten M |title=Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus |journal=Circulation |volume=129 |issue=5 |pages=587–97 |year=2014 |pmid=24334175 |doi=10.1161/CIRCULATIONAHA.113.005081 |url=}}</ref><br>
*Limiting protein intake to less than 0.8 g per kg per day
 
Drugs such as [[metformin]] and [[sulfonylureas]] are contraindicated in advanced renal insufficiency.<ref name="book">{{cite book |last= Kasper |first=Dennis |date=2015 |title=Harrison's Principles of Internal Medicine |url= |location= New York, New York |publisher= McGraw-Hill |page= |isbn=0071802150}}</ref>


===Blood Pressure Control===
===Blood Pressure Control===
[[Blood pressure]] in diabetic patients with [[nephropathy]] is aimed at levels of less than 130/80.<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid11403001">{{cite journal |vauthors= |title=American Diabetes Association Clinical Practice Recommendations 2001 |journal=Diabetes Care |volume=24 Suppl 1 |issue= |pages=S1–133 |year=2001 |pmid=11403001 |doi= |url=}}</ref><ref name="pmid9834731">{{cite journal |vauthors=Meltzer S, Leiter L, Daneman D, Gerstein HC, Lau D, Ludwig S, Yale JF, Zinman B, Lillie D |title=1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association |journal=CMAJ |volume=159 Suppl 8 |issue= |pages=S1–29 |year=1998 |pmid=9834731 |pmc=1255890 |doi= |url=}}</ref>
[[Blood pressure]] in diabetic patients with [[nephropathy]] is aimed at levels of less than 130/80.<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid11403001">{{cite journal |vauthors= |title=American Diabetes Association Clinical Practice Recommendations 2001 |journal=Diabetes Care |volume=24 Suppl 1 |issue= |pages=S1–133 |year=2001 |pmid=11403001 |doi= |url=}}</ref><ref name="pmid9834731">{{cite journal |vauthors=Meltzer S, Leiter L, Daneman D, Gerstein HC, Lau D, Ludwig S, Yale JF, Zinman B, Lillie D |title=1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association |journal=CMAJ |volume=159 Suppl 8 |issue= |pages=S1–29 |year=1998 |pmid=9834731 |pmc=1255890 |doi= |url=}}</ref>
*[[ACE inhibitors]] and [[ARB's]] are the drug of choice for controlling [[hypertension]] in diabetic nephropathy.<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref><ref name="pmid26928912">{{cite journal |vauthors=Chamberlain JJ, Rhinehart AS, Shaefer CF, Neuman A |title=Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes |journal=Ann. Intern. Med. |volume=164 |issue=8 |pages=542–52 |year=2016 |pmid=26928912 |doi=10.7326/M15-3016 |url=}}</ref> 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.[http://www.ksu.edu.sa/sites/Colleges/Medicine/Lists/Medical%20Subjects/Flat.aspx?RootFolder=http%3a%2f%2fwww%2eksu%2eedu%2esa%2fsites%2fColleges%2fMedicine%2fLists%2fMedical%20Subjects%2fDiabetes%20Mellitus%20and%20Angiotensin%20Converting%20Enzyme%20Inhibitors&FolderCTID=0x01200200CEDE56CEF8D11C46824F2F6116DF88AA]<br>


* [[ACEI]] and [[ARBs]] should not be combined due to increased risk of [[hyperkalemia]] and [[acute kidney injury]] ([[AKI]]).<ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref><ref name="pmid26928912">{{cite journal |vauthors=Chamberlain JJ, Rhinehart AS, Shaefer CF, Neuman A |title=Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes |journal=Ann. Intern. Med. |volume=164 |issue=8 |pages=542–52 |year=2016 |pmid=26928912 |doi=10.7326/M15-3016 |url=}}</ref>


**[[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]].<ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref>
**Other drugs, such as [[beta blockers]], [[calcium channel blockers]] and [[diuretics]] may be added if [[blood pressure]] is not well controlled.<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid26928912">{{cite journal |vauthors=Chamberlain JJ, Rhinehart AS, Shaefer CF, Neuman A |title=Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes |journal=Ann. Intern. Med. |volume=164 |issue=8 |pages=542–52 |year=2016 |pmid=26928912 |doi=10.7326/M15-3016 |url=}}</ref>


===Lipid Therapy===
* The use of [[statins]] decreases the risk of [[cardiovascular disease]] and slows the loss of renal function.<ref name="pmid11948275">{{cite journal |vauthors=Remuzzi G, Schieppati A, Ruggenenti P |title=Clinical practice. Nephropathy in patients with type 2 diabetes |journal=N. Engl. J. Med. |volume=346 |issue=15 |pages=1145–51 |year=2002 |pmid=11948275 |doi=10.1056/NEJMcp011773 |url=}}</ref><ref name="pmid9742977">{{cite journal |vauthors= |title=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 |journal=Lancet |volume=352 |issue=9131 |pages=854–65 |year=1998 |pmid=9742977 |doi= |url=}}</ref>
* For diabetic patients over the age of 40 with diabetic nephropathy, [[statins]] are recommended regardless of baseline [[lipid]] levels.<ref name="pmid25342915">{{cite journal |vauthors=Lim AKh |title=Diabetic nephropathy - complications and treatment |journal=Int J Nephrol Renovasc Dis |volume=7 |issue= |pages=361–81 |year=2014 |pmid=25342915 |pmc=4206379 |doi=10.2147/IJNRD.S40172 |url=}}</ref><ref name="pmid11466120">{{cite journal |vauthors=Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S |title=Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals |journal=JAMA |volume=286 |issue=4 |pages=421–6 |year=2001 |pmid=11466120 |doi= |url=}}</ref>


 
===Dialysis===
 
* [[Dialysis]] may be necessary once end-stage renal disease develops.
* [[ACE inhibitors]] and [[ARB's]] are the drug of choice for controlling [[hypertension]] in diabetic nephropathy. 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.[http://www.ksu.edu.sa/sites/Colleges/Medicine/Lists/Medical%20Subjects/Flat.aspx?RootFolder=http%3a%2f%2fwww%2eksu%2eedu%2esa%2fsites%2fColleges%2fMedicine%2fLists%2fMedical%20Subjects%2fDiabetes%20Mellitus%20and%20Angiotensin%20Converting%20Enzyme%20Inhibitors&FolderCTID=0x01200200CEDE56CEF8D11C46824F2F6116DF88AA]
** [[ACE inhibitors]] and [[ARB's]] slow the progression of renal damage from [[diabetes]] to overt renal failure. It is recommended that all patients with [[type I diabetes mellitus|type I]] and [[type II diabetes mellitus]] with [[microalbuminuria]] on routine urine screening should be on [[ACE inhibitors]].
* [[Urinary tract]] and other [[infections]] are common and can be treated with appropriate [[antibiotics]].
* [[Dialysis]] may be necessary once end-stage renal disease develops. At this stage, a [[kidney transplantation]] must be considered. Another option for type 1 diabetes patients is a combined kidney-pancreas transplant, which is the preferred mode of renal replacement therapy in otherwise stable patients..
 
===Drug interaction===
Patients with diabetic nephropathy should avoid taking the following drugs:
* Contrast agents containing [[iodine]]
* Commonly used non-steroidal anti-inflammatory drugs ([[NSAID]]s) like [[ibuprofen]] and [[naproxen]], or [[COX-2]] inhibitors like [[Celebrex]], because they may injure the weakened kidney.


==References==
==References==

Latest revision as of 13:04, 16 June 2022

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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

See Diabetic nephropathy secondary prevention

Lifestyle Modifications

The management of diabetic nephropathy depends a lot on lifestyle and dietary modifications.These include:[1]

Blood Pressure Control

Blood pressure in diabetic patients with nephropathy is aimed at levels of less than 130/80.[1][2][3]

Lipid Therapy

Dialysis

  • Dialysis may be necessary once end-stage renal disease develops.

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 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.
  2. ↑ "American Diabetes Association Clinical Practice Recommendations 2001". Diabetes Care. 24 Suppl 1: S1–133. 2001. PMID 11403001.
  3. ↑ 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.
  4. ↑ 4.0 4.1 4.2 4.3 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)
  5. ↑ 5.0 5.1 5.2 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.
  6. ↑ "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.
  7. ↑ 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.


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