7.2. Viabilidad tecnológica en la implementación de una red de internet con
7.3.2. CANVAS
Annual screening for DKD is indicated in all post-pubertal people with type 1 diabetes 5 years after diagnosis, and in all people with type 2 diabetes at the time of diagnosis and annually thereafter.7 Screening for CKD in people with diabetes should ideally be performed with the measurement of the albumin level in a first morning urine specimen and a serum creatinine measurement that is then converted into an eGFR and the result expressed as ACR8 (Figure II). When a first morning urine specimen is inconvenient, an untimed “spot” urine sample is acceptable.8 An abnormal screening test should be confirmed by repeat testing of the eGFR within three months, and two more urine ACR measurements performed during that interval.7,8 If either the eGFR remains low or at least two of the three random urine ACRs are abnormal, then a diagnosis of CKD is confirmed.8 The exception to this approach is when the random urine ACR indicates albuminuria in the severely increased albuminuria range, as this level of proteinuria rarely resolves spontaneously, so confirmatory testing is usually unnecessary.7
Once a diagnosis of CKD has been made, a urine sample for dipstick and microscopy should be ordered.7 In the absence of any significant abnormalities other than proteinuria, a presumptive diagnosis of kidney disease due to diabetes can be made. The presence of clinical or laboratory abnormalities suggesting nondiabetic kidney disease indicates the need for appropriate workup or referral.7
19.5 Prevention, treatment and follow up
19.5.1 Prevention
Tight blood sugar control in patients with type 1 diabetes reduces the risk of developing microvascular diabetes complications including DKD.15 Tight blood sugar control comes at the risk of hypoglycaemia and there is no firm evidence for specific blood glucose targets. There is a lack of evidence from RCTs on the effects of tight blood sugar control in older patient populations or patients with macrovascular disease. Although tight blood glucose control in patients with type 2 diabetes reduces the risk of developing albuminuria, evidence is lacking in terms of
a benefit for clinically important renal endpoints.16,17 A recent Cochrane review concluded that angiotensin-converting enzyme inhibitors (ACEi) reduce the risk of new onset moderate and severe albuminuria with similar benefits in people with and without hypertension.18 In this meta-analysis angiotensin receptor blocking agents (ARBs) were only of value in preventing kidney disease in high risk patients.
19.5.2 Treatment
Although intensive glycaemic control may slow down the progression of DKD in patients with type 2 diabetes,16,20 lowering blood pressure is the most effective strategy in preventing end-stage renal disease in patients with established DKD.21 Progression of DKD in patients with type 2 diabetes can be slowed down by the use of either an ACEi or an ARB.22 Since ACE inhibitors have been shown to reduce major CVD events in patients with diabetes, and since the risk of CVD is increased in patients with albuminuria, ACE inhibitors should remain first- line agents in the treatment of patients with diabetes who have established albuminuria.23
Combination treatment with an ACEi and an ARB to prevent progression of DKD is not recommended on the grounds of increased risk of hyperkalaemia, and renal dysfunction.24,25 A recent meta-analysis, however, showed that the most effective strategy to prevent end-stage kidney disease in patients with established DKD is by lowering blood pressure using dual treatment with an ARB and an ACEi,26 while monotherapy with an ARB was also effective but less so than dual therapy.21 Unfortunately, no blood pressure-lowering strategy prolonged survival in adults with diabetes and kidney disease.26 Any benefits of combined ACE inhibitor and ARB treatment need to be balanced against potential harms of hyperkalaemia and acute kidney injury.21,26 At this stage combination therapy with an ACE inhibitor plus an ARB should not be used in patients with DKD. Initiation of an ACEi in patients with diabetes and serum creatinine levels greater than 124 µmol/L is associated with acute increases in serum creatinine of up to 30% that stabilises within the first two months of ACEi therapy and long-term preservation of renal function.27 A significant increase in serum potassium and
Table V. Modifications of antidiabetic drugs in patients with type 2 diabetes mellitus
Dosing recommendation Dosing Class Drug stages 3 and 4 CKD or recommendation kidney transplant dialysis
Second-generation Glipizide, gliclazide Preferred sulfonylurea Preferred sulfonylurea Sulfonylureas No dose adjustment No dose adjustment Glibenclamide Avoid Avoid
Glimepiride Initiate at low dose, 1 mg/day Avoid Glucosidase inhibitors Acarbose Not recommended if serum Avoid creatinine >180 μmol/L
Biguanides Metformin See text Avoid Meglitinides Repaglinide No dose adjustment Avoid Nateglinide Initiate at low dose (60 mg before each meal) Avoid
Thiazolidinediones Pioglitazone No dose adjustment No dose adjustment Adapted from the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines).3
Journal of Endocrinology, Metabolism and Diabetes of South Africa 2017 ; 22(1) S92
serum creatinine levels have been described in patients with bilateral renal artery stenosis within two weeks of initiation of a RAAS blocker.28 For these reasons, the serum creatinine and potassium should be checked between one and two weeks after initiation or titration of a RAAS blocker.7 For patients in whom a significant change in creatinine or potassium is seen, further testing should be performed to ensure that these results have stabilised.7
Any degree of albuminuria increases the risk of cardiovascular events in diabetic as well as in non-diabetic individuals.29 Cardiovascular risk factors must be treated in all patients with CKD to address this risk. An intensified long-term intervention aimed at multiple risk factors in patients with type 2 diabetes and moderate albuminuria reduces the risk of cardiovascular and microvascular events by 50 percent.30
There are no randomised controlled trials of blood pressure levels in diabetes that have examined CKD events as outcomes. Blood pressure levels below 140/90 mmHg in diabetes are recommended to reduce CVD mortality and slow CKD progression (KDIGO, 2012). In individuals with albuminuria, consider lower blood pressure targets of < 130/80 mmHg.20,21 People with diabetes should be referred to a nephrologist or specialist physician with an expertise in CKD in the following situations:
a. Chronic, progressive loss of kidney function b. ACR persistently >60 mg/mmol
c. eGFR<30 mL/min
d. Unable to remain on renal-protective therapies due to adverse effects such as hyperkalaemia or >30% increase in serum creatinine within 3 months of starting an ACE inhibitor or ARB
e. Unable to achieve target BP (could be referred to any specialist in hypertension).
19.6 Sick day rules
If patients become ill and are unable to maintain adequate fluid intake, or have an acute decline in renal function (e.g. due to gastrointestinal upset or dehydration), they should be instructed to withhold medications which will increase the risk for decline in kidney function or have reduced clearance and increased risk of adverse effects (Table IV).7 Patients should be instructed that increased frequency of self-monitoring of blood glucose will be required and adjustments to their doses of insulin or oral anti- hyperglycaemic agents may be necessary.
Table IV. Medications that should be withheld or dose reduced during acute illness7
Analgesics
19.7 Modifications of antidiabetic drugs in patients
with type 2 diabetes mellitus
3Patients with stages 3-5 kidney disease are at increased risk of hypoglycaemia due to decreased renal clearance of insulin and sulfonylureas and also due to reduced gluconeogenesis. This has the following implications:
• In patients with type 1 diabetes, insulin needs may change with decreasing renal function, as CKD is associated with insulin resistance and there is decreased renal clearance of insulin with advancing CKD.
• Metformin should be used with caution in patients with stages 4 and 5 CKD. Its use in CKD carries a small risk of severe lactic acidosis; the risk increases with decreasing glomerular filtration rate (GFR) and the dose should be adjusted. The use of metformin should be reviewed when the patient reaches stage 3 CKD and its use is contraindicated in stages 4 and 5 CKD.
• Sulfonylureas: First-generation sulfonylureas should be avoided. Second-generation sulfonylureas may be used in patients who have learnt to avoid hypoglycaemic episodes, as long as their diabetes is controlled and nutritional status is satisfactory.
• Thiazolidinediones: These may be used in patients without heart failure. Caution is advised in patients with ischaemic heart disease.
• Insulin: When insulin therapy is used, care should be taken to avoid hypoglycaemic episodes, as the renal clearance of insulin declines with advancing renal impairment.
• DPP-4 antagonists (vildagliptin, saxagliptin) can be used with dose adjustments (sitagliptin – caution). Avoid combination drugs that also contain metformin.
• GLP-1 receptor agonists (exenatide, liraglutide): These should not be used in moderate renal function impairment (creatinine clearance <30 mL/min).
Author: Willie Mollentze Editor: Nazeer A Mohamed
References
1. Rosenberg M, Curhan GC, Sheridan AM. Overview of the management of chronic kidney disease in adults. UpToDate. 2016.
2. Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic Kidney Disease: A Report From an ADA Consensus Conference. Diabetes Care 2014;37:2864–2883.
3. Moosa RM, van der Walt I, Naicker S, Meyers AM. Important causes of chronic kidney disease in South Africa. S Afr Med J 2015;105(4):320.
4. Noubiap JJ, Naidoo J, Kengne AP. Diabetic nephropathy in Africa: A systematic review. World J Diabetes. 2015 Jun 10;6(5):759-73. doi: 10.4239/wjd.v6.i5.759. 5. Naicker S. End-stage renal disease in sub-Saharan Africa. Ethn Dis. 2009
Spring;19(1 Suppl 1):S1-13-5.
6. MR Davids, N Marais, JC Jacobs. South African Renal Registry. Annual Report 2012. South African Renal Society, Cape Town 2014.
Chapter 19: Diabetic Kidney Disease S93
10. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS. Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285–2293
11. Zandbergen AA, Baggen MG, Lamberts SW, Bootsma AH, de Zeeuw D, Ouwendijk RJ. Effect of losartan on microalbuminuria in normotensive patients with type 2 diabetes mellitus. A randomized clinical trial. Ann Intern Med. 2003 Jul 15;139(2):90-6.
12. Holtkamp FA, de Zeeuw D, de Graeff PA, Laverman GD, Berl T, Remuzzi G, Packham D, Lewis JB, Parving HH, Lambers Heerspink HJ. Albuminuria and blood pressure, independent targets for cardioprotective therapy in patients with diabetes and nephropathy: a post hoc analysis of the combined RENAAL and IDNT trials. Eur Heart J. 2011 Jun;32(12):1493-9.
13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. 14. Mazzucco G, Bertani T, Fortunato M, Bernardi M, Leutner M, Boldorini R, Monga
G. Different patterns of renal damage in type 2 diabetes mellitus: a multicentric study on 393 biopsies. Am J Kidney Dis. 2002 Apr;39(4):713-20.
15. Fullerton B, Jeitler K, Seitz M, Horvath K, Berghold A, Siebenhofer A. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2014 Feb 14;2:CD009122. 16. Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR. Role of
intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in type 2 diabetes. Arch Intern Med. 2012 May 28;172(10):761-9.
17. Buehler AM, Cavalcanti AB, Berwanger O, Figueiro M, Laranjeira LN, Zazula AD, Kioshi B, Bugano DG, Santucci E, Sbruzzi G, Guimaraes HP, Carvalho VO,Bordin SA. Effect of tight blood glucose control versus conventional control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. Cardiovasc Ther. 2013 Jun;31(3):147-60.
18. Lv J, Perkovic V, Foote CV, Craig ME, Craig JC, Strippoli GF. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004136.
19. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet. 1993 May 22;341(8856):1306-9.
20. Buehler AM, Cavalcanti AB, Berwanger O, Figueiro M, Laranjeira LN, Zazula AD, Kioshi B, Bugano DG, Santucci E, Sbruzzi G, Guimaraes HP, Carvalho VO,Bordin SA. Effect of tight blood glucose control versus conventional
control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials. Cardiovasc Ther. 2013 Jun;31(3):147-60.
21. Palmer SC, Mavridis D, Navarese E, Craig JC, Tonelli M, Salanti G, Wiebe N, Ruospo M, Wheeler DC, Strippoli GF. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet. 2015 May 23;385(9982):2047-56.
22. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J; Diabetics Exposed to Telmisartan and Enalapril Study Group. Angiotensin- receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004 Nov 4;351(19):1952-61.
23. Anonymous. Effects of Ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE and MICRO-HOPE sub-study. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000 Jan 22;355(9200):253-9.
24. Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008 Apr 10;358(15):1547-59.
25. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, Leehey DJ, McCullough PA, O'Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P; VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013 Nov 14;369(20):1892-903.
26. Ren F, Tang L, Cai Y, Yuan X, Huang W, Luo L, Zhou J, Zheng Y. Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy. Ren Fail. 2015 May;37(4):548-61.
27. Bakris GL1, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000 Mar 13;160(5):685-93.
28. Miyamori I, Yasuhara S, Takeda Y, Koshida H, Ikeda M, Nagai K, Okamoto H, Morise T, Takeda R, Aburano T. Effects of converting enzyme inhibition on split renal function in renovascular hypertension. Hypertension. 1986 May;8(5):415-21.
29. Gerstein HC1, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Hallé JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S; HOPE Study Investigators. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6.
30. Gaede P1, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003 Jan 30;348(5):383-93.
JEMDSA
ISSN 1608-9677 EISSN 2220-1009 © 2017 The Author(s)
SEMDSA GUIDELINES
20.1 Introduction
Diabetic eye disease is a leading cause of visual impairment in the developing world,1 and is mainly comprised of diabetic
retinopathy (DR), which includes diabetic macular oedema (DMO), and cataract formation. It is estimated that a third of people living with diabetes will develop diabetic retinopathy.2
Diabetic retinopathy is by and large preventable and/or treatable, while cataract surgery can now successfully be performed on a large scale. It is thus imperative that patients are appropriately screened and referred to an ophthalmologist to detect diabetic eye disease. Vision loss is disabling as it results in a loss of independence and an increased risk of falls. In patients with diabetes this is compounded by their difficulty with administering therapies such as insulin as well as self-monitoring of blood glucose levels.
20.2 Prevalence of diabetic eyes disease
It is estimated that approximately 34.6% of people with diabetes or 93 million people worldwide have some form of DR with 10.2% having vision-threatening diabetic retinopathy (VTDR).2
Screening studies of DR have often detected a high prevalence of cataracts, even in excess of the prevalence of DR3,4 and thus
cataracts remain a common cause of vision loss in patients with diabetes.
20.3 Risk factors for diabetic eye disease
develops in 2% of those with diabetes for under 5 years but is present in 25% of those with diabetes for 25 years.5
The most important modifiable risk factor is glycaemic control. Poor glucose control is associated with both the development and progression of DR.6-8 There is evidence that tight glycaemic
control will lower these risks and should be the target, if this can be attained safely. Blood pressure and lipid control also decrease the risk of DR.9 However there is no evidence to support intensive
blood pressure control (systolic BP < 120mmHG) to reduce DR.10
There is evidence that fenofibrate may reduce the progression of DR.10 Patients who develop diabetic kidney disease are at high
risk of also having DR..
20.4 Screening
Patients with significant DR may be asymptomatic and hence screening is important to detect patients in whom intervention may prevent vision loss. Patients and their family members must be educated that they may have significant eye disease that requires treatment even in the absence of symptoms. Since patients with type 2 diabetes may have had many years of undiagnosed diabetes, it is recommended that all such patients should be screened at diagnosis for DR. Ideally this should be done by an ophthalmologist or an optometrist who is trained in detecting DR. This, however, is not always possible in resource limited settings. All screening encounters should begin with a clinical evaluation with emphasis on glycaemic control;
SEMDSA 2017 Recommendations
Diabetic eye disease is a leading cause of visual impairment and screening for diabetic retinopathy is indicated in all patients with type 2 diabetes.
A Aim to optimise glucose, blood pressure and lipid control to reduce the risk and progression of diabetic retinopathy. A
Screening should begin at diagnosis of type 2 diabetes. B
Patients without retinopathy or diminished visual acuity should be screened again every 1 to 2 years. B
Patients should have their visual acuity assessed. C
The preferred screening method for diabetic retinopathy is either fundal photography or dilated indirect ophthalmoscopy.
C Urgent referral to an ophthalmologist is indicated if there is sudden severe vision loss; retinal tear and/or detachment;
proliferative diabetic retinopathy or severe diabetic macular oedema.
C Pregnancy may be associated with worsening of retinopathy. Patients should be counselled and screened for diabetic
retinopathy prior to pregnancy, or in the first trimester of pregnancy.
B Journal of Endocrinology, Metabolism and Diabetes of South Africa 2017 ; 22(1)
http://dx.doi.org/10.1080/16089677.2015.1056468 Open Access article distributed under the terms of the Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0
Chapter 20: Diabetic eye disease
SEMDSA 2017 Type 2 Diabetes Guidelines Expert CommitteeChapter 20: Diabetic eye disease S95
screening is not done by an ophthalmologist.11,15,18 Screening
should therefore be divided into 2 components: visual acuity and retinal examination.
20.4.1 Visual acuity
Visual acuity can be assessed by trained healthcare providers (HCP) in any of the following ways, depending on resources: • Refracted visual acuity examination using a 3- or 4-meter
visual acuity lane and a high contrast visual acuity chart.15
• Presenting visual acuity examination using a near or distance eye chart and a pin-hole option if visual acuity is reduced.15
• Presenting visual acuity examination using a 6/12 (20/40) equivalent handheld chart consisting of at least 5 standard