Nephropathy

Assisting clients to successfully manage diabetes along with the complexities of chronic kidney disease is often voiced as one of the most challenging areas for diabetes educators.

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1. What is Chronic Kidney Disease (CKD) and Diabetic Nephropathy?

  • First of all, it may be helpful to review basic kidney function. Kidneys are vascular organs composed of about a million tiny units called nephrons. The nephron, magnified in picture below, is composed of a tiny filter called the glamorous and an attached tubule. As blood flows through the glomerulus the first stage of filtration occurs where larger molecules such as proteins are prevented from passing into the filtrate. The filtrate then passes through the tubule where electrolytes, glucose, and amino acids may be reabsorbed into the blood. The tubule is where SGLT-1 and SGLT-2 receptors function to drive glucose reabsorption. (Click here to learn more about SGLT inhibitor medications). Waste products such as urea, uric acid, creatinine and extra fluid remain in the filtrate that is sent to the collecting tubule as urine. Urine passes through the ureters to the bladder.

 nephron

Photo courtesy of: https://www.niddk.nih.gov/health-information/kidney-disease/kidneys-how-they-work

  • Along with removing waste and extra fluid from the blood, kidneys have an important role in keeping electrolytes such as sodium, potassium and phosphate levels stable. Additionally, the kidneys produce important hormones that help regulate blood pressure (through the enzyme renin), make red blood cells (erythropoietin) and maintain bone strength (calcitriol- Vitamin D).

Chronic Kidney Disease (CKD)

  • Chronic Kidney Disease (CKD) encompasses a variety of kidney diseases. People with diabetes can experience diabetic nephropathy, nephropathy secondary to vascular damage from hypertension, and other renal problems not related to diabetes such as polycystic kidney disease. Chronic Kidney Disease is defined as the following, according to http://www.ckdpathway.ca/aboutckd:
    • eGFR < 60 mL/min/1.73mthat is present for ≥ 3 months
    • - or –
    • Markers of kidney damage present for ≥ 3 months:
      • Albuminuria ≥ 3 mg/mmol
      • Urine sediment abnormalities
      • Structural or pathological abnormalities
  • Refer to table Diabetes Canada 2018 Guidelines for Stages of Chronic Kidney Disease:

CKD Stages

Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2018;42(Suppl 1):S1-S325. Accessed May 2018.

Diabetic Nephropathy 

  • Kidney damage caused by diabetes is a complex, multifaceted disease thought to be caused by both metabolic and genetic factors. Chronic hyperglycemia is linked to intraglomerular hypertension, glomerular damage and hypertrophy, altered permeability of glomerular membranes and atherosclerosis of glomerular vessels. We often simplify the explanation by stating that high blood sugars damage the filters in our kidneys so that they can no longer filter our blood properly. This causes beneficial proteins to leak into the urine and waste products to build up in the blood. Some clients relate to the following visual analogy:

 Kidney filters

Pictures courtesy of Clip Art (have to reference?) 

  • Or, alternatively some refer to the analogy of a coffee filter when teaching the concept of nephropathy to clients. For example, high glucose levels and/or high blood pressure levels could act to damage the filters in the kidneys the same as putting a coffee filter under a tap running at full water pressure. The end result would be theoretical “holes” causing items to leak through when the filter is used. The item leaking through would be albumin. This would be one of the first indicators of damage to the kidneys.

2. How is Diabetic Nephropathy Prevented, Screened for and Treated?

Primary Prevention

  • Glycemic Control: The Diabetes Complications and Control Trial (DCCT), landmark study in type 1 diabetes population, showed that intensive glycemic control (A1c less than 7.0%) reduced albuminuria by 34% in those with no complications at beginning of study. The United Kingdom Prospective Diabetes Study (UKPDS), landmark study in type 2 diabetes population, showed that intensive glycemic control (A1c less than 7.0%) also reduced albuminuria risk by 34%. The main message is to promote the best blood sugars possible soon after diagnosis.
  • Blood Pressure Control: According to 2018 Diabetes Canada CPG’s, optimal blood pressure likely helps to prevent diabetic nephropathy. However, blood pressure control is especially important in the prevention of other kidney diseases people with diabetes may be at risk of, in particular, ischemic damage secondary to vascular disease and hypertension. Target blood pressure is less than 130/80 mm Hg.
  • Blockade of the renin-angiotensin-aldosterone system (RAAS)- ACE (Angiotensin Converting Enzyme) inhibitor or ARB (angiotensin II receptor blocker) medications have been shown to prevent diabetic nephropathy in those with diabetes and hypertension.

Secondary Prevention 

  • Glycemic Control: The DCCT showed that intensive glycemic control lowered albuminuria by 43% and proteinuria by 56% in those with pre-existing kidney complications.
  • Blood Pressure Control: The 2018 Diabetes Canada CPG’s state renal damage can be slowed by optimization of blood pressure. Target blood pressure is less than 130/80 mm Hg.
  • Blockade of RAAS – ACE inhibitor and ARB medications can slow progression of diabetic nephropathy independent of blood pressure level. This means that even without diagnosis of hypertension, if albuminuria is present, blockade of RAAS has been shown to slow kidney damage. 

Screening

Screening for CKD should begin upon diagnosis and then annually in type 2 diabetes. Screening can be delayed for 5 years after diagnosis in type 1 diabetes, and then annually thereafter.

  • Random Urine ACR (Albumin to Creatinine Ratio): As explained by http://www.ckdpathway.ca/aboutckd, random urine ACR is preferred to detect proteinuria as it has greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria. Excess amounts of protein in urine are a marker of kidney damage. If the random ACR is abnormal (greater than 2.0 mg/mmol), 2 more repeat tests should be completed in next 3 months. If 2/3 ACR’S are greater than 2.0 mg/mmol, CKD is diagnosed. The exception to this, would be in the case of ‘overt nephropathy’ in that the random urine ACR is greater than 20 mg/mmol and CKD diagnosed immediately.As listed in the 2018 CPG’s, albuminuria can be temporarily increased in the following situations:
    • Recent major exercise
    • Urinary tract infection
    • Febrile illness
    • Decompensated congestive heart failure
    • Menstruation
    • Acute severe elevation in blood glucose
    • Acute severe elevation in blood pressure
  • Creatinine for eGFR: As explained by http://www.ckdpathway.ca/aboutwhoandhowtotest, eGFR is the best measure of kidney function. eGFR <60mL/min/1.73m2 for ≥ 3 months is diagnostic for CKD.

Treatment Considerations 

  • Manage Cardiovascular Risk Factors: Important to concurrently manage other risk factors for cardiovascular events: target BP less than 130/80 mm Hg, optimize blood glucose, treat dyslipidemia, and lifestyle factors such as smoking, obesity, sedentary lifestyle, diet and alcohol consumption. See Vascular Risk Reduction page for more details. 
  • Sick Day medication List: Educators are advised to consult physicians when they suspect a client with or without chronic kidney disease is dehydrated from an acute illness, so as to learn which, if any, medications should be held. The holding of these medications (diabetes and non-diabetes medications) should be ordered and subsequently assessed by the physician. See Medication resources on Topics Catalogue page for handout. 
  • Women of Childbearing Age: Special consideration needs to be paid to women of childbearing age on ACE or ARB medications as there is risk to a developing fetus of congenital malformations.
  • Referral to Kidney Specialist: Refer to the online pathway www.ckdpathway.ca to understand when a patient should be referred to a nephrologist.
  • Dialysis: 
    • Peritoneal Dialysis (PD): 
      • CAPD (Continuous Ambulatory Peritoneal Dialysis): Involves 3 – 4 daytime exchanges with varied glucose solutions and one overnight exchange with Extraneal® (no glucose dialysate). Clients are exposed to a hyperglycemic environment for approximately 16 hours daily.
      • CCPD (Continuous Cycler Peritoneal Dialysis): Either a dialysis solution is used during the day or no solution is used (the client is ‘dry’). At night, the PD catheter is connected to a dialysis machine called a cycler, which loads various PD dialysis fluids during the night. These clients are exposed to a hyperglycemic environment for approximately for 8 – 9 hours daily.
      • Dialysates for PD contain glucose, which can affect blood glucose levels or alternatively, modified starch or amino acids, which do not affect glucose levels. Extraneal® is an example of the latter. Extraneal is not normally used as the sole type of dialysate. It may be used for one of the 3-4 bags during the day.
      • Recent changes to concentrations of glucose in dialysate solutions can affect blood glucose. Asking if the percentage glucose in the client’s solutions has changed can help problem-solve blood glucose logbooks.
      • If Extraneal dialysate is used in the evening, clients may require a bedtime snack.
      • Bolus insulin (rapid or regular) is usually used to adjust for glucose containing dialysis solutions. In some centres, insulin is added to the PD glucose solution, although not typically in Calgary. In type 2 diabetes, repaglinide may be used with meals or with TID dialysate exchanges, by some physicians.
      • Blood glucose levels can alter with peritonitis (infection or inflammation) and with obstructed drainage of dialysate. Constipation can impair drainage of dialysate.
      • With CCPD, the client may require basal insulin 2 – 3 hours before starting the cycler (usually at night). This allows for onset of insulin action close to the time that the cycler starts. Long acting insulin may continue to work after the cycler (and the glucose infusion) stops. Hypoglycemia may be avoided by directing the individual to have small amount of apple juice before rising and becoming more active.
      • Meals and carb intake may vary due to less hunger from volume of fluid in abdomen, increased caloric intake from dialysate and, early on, due to lingering symptoms of uremia.
      • Obesity, dyslipidemia and low muscle mass are common in CKD. Glucose calories supplied by the dialysis solution are usually about 400kcal per day. Dietary carbohydrate is usually subtracted from the diet to compensate and to help prevent obesity. Further reduction in carbohydrate intake may be recommended for hypertriglyceridemia. Intake of protein is liberalized to 1.2 g/kg daily and monitored carefully due to renal protein losses and in dialysis fluids Source: American Journal of Kidney Diseases. Feb 2007. Vol 49(2) suppl 2, pages S1-179 
    • Hemodialysis (HD): 
      • Clients often have poor appetites and intake before the HD run due to uremia, and significantly improved appetites after the run. SARP nurses monitor blood glucose levels carefully before, during and after runs and usually suggest snacks. Snacks are often necessary after HD run as more likely to have dropping glucose levels after dialysis ends (no glucose from dialysate transferring in). Clients are advised to carry food and treatment for hypoglycemia with them on the handibus or car. Many clients eat large meals after the HD run, as they are feeling better. Rapid or short acting hypoglycemic medications may need to be increased for that larger meal.

3. How can CKD Affect Diabetes Management? 

  • Hypoglycemia: Individuals with advanced renal disease are at increased risk of hypoglycemia, particularly overnight and in the fasting state. Some clients requiring insulin may not require evening basal insulin. Some clients may experience significant drops in overnight blood glucose readings without evening insulin injections (e.g. of up to 8 mmol/L) Contributing factors:
    • Reduced clearance of medications/insulin
    • Impaired renal gluconeogenesis (decline in renal mass)
    • Dietary factors: uremia increases anorexia/nausea/vomiting; suboptimal nutrition due to reduced clearance
    • Additional factors: gastroparesis, hypoglycemia unawareness secondary to autonomic neuropathy
  • Targets: Should be individualized. See Targets and Priorities page
  • A1c: Rely on blood glucose monitoring as A1c may not be reliable marker of glycemia in CKD. A1c can be falsely increased with altered glycation or iron deficiency. A1c can be falsely decreased with decreased RBC lifespan seen in CKD and use of (erythropoetin) EPO, iron supplement. See A1c page for more details. 
  • Diabetes Medications: Medications should be prescribed and adjusted to suit individual client glucose patterns and lifestyles. More antihyperglycemic medication options are emerging that can be used in renal impairment. See Topics Catalogue, Renal Disease for Therapeutic Considerations for Renal Impairment
    • Insulin: 
      • Starting insulin doses are usually less in stage 4-5 compared to stage 1-3 (which is similar to the population of people with diabetes and no kidney disease).
      • Some insulin-requiring clients may require morning basal insulin only, with no evening dose. Morning basal insulin may be increased to address elevated fasting readings.
      • Meal bolus insulin should be matched to the client’s rate of digestion. In the case of delayed emptying due to neuropathy, rapid insulin may be given post meal or regular insulin may given with the meal, depending on the degree of delayed digestion.
    • Nutrition: 
      • Bedtime snack is often recommended in insulin users for the prevention of hypoglycemia.
      • Some foods or supplements may be limited due to sodium, potassium, phosphorus, fluid or protein content and individual client lab results.
      • Glucose from dialysate, not just food, can impact blood glucose levels.

4. Supplemental notes, learning activities