When our bodies digest the protein we eat, the process creates waste products. In the kidneys, millions of tiny blood vessels capillaries with even tinier holes in them act as filters. As blood flows through the blood vessels, small molecules such as waste products squeeze through the holes.
Diabetes can damage this system. All this extra work is hard on the filters. After many years, they start to leak and useful protein is lost in the urine. When kidney disease is diagnosed early, during microalbuminuria, several treatments may keep kidney disease from getting worse. Having larger amounts of protein in the urine is called macroalbuminuria.
In time, the stress of overwork causes the kidneys to lose their filtering ability. Waste products then start to build up in the blood. Finally, the kidneys fail. This failure, ESRD, is very serious. A person with ESRD needs to have a kidney transplant or to have the blood filtered by machine dialysis. Not everyone with diabetes develops kidney disease.
The better a person keeps diabetes and blood pressure under control, the lower the 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. Research has shown that tight blood glucose control 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 control can reverse microalbuminuria. Important treatments for kidney disease are tight control 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 losing weight, eating less salt, avoiding alcohol and tobacco, and getting regular exercise.
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When these methods fail, certain medicines may be able to lower blood pressure. The rapid-acting insulin analogs aspart Novolog , lispro Humalog, U and U and glulisine Apidra are absorbed the quickest and are ideal for quick correction of elevated blood sugars or for prandial insulin needs.
These insulins have an onset of action at 5 to 15 minutes, peak action at minutes and an average duration of about 5 hours. Some studies have shown the duration of action of glulisine to be slightly longer than the other two rapid-acting insulins. These insulins should be given at most 15 minutes prior to a meal. Patients with Stage CKD and those on dialysis often have some degree of 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 ahead of time how much they will be able to 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 as well. The only short-acting insulin available is regular crystalline insulin, which has an onset of action at 30 to 60 minutes, peak action at 2 to 3 hours and duration up to 5 to 8 hours.
Regular insulin should ideally be given about 30 minutes prior to a meal. The available intermediate-acting insulin is isophane, or NPH neutral protamine Hagedorn. It has an onset of action at 2 to 4 hours, peak concentration at 4 to 10 hours and duration up to 10 to 18 hours. In order to achieve adequate basal coverage, it is typically dosed twice daily.
Are there different types of diabetes?
Its use can be limited by its highly variable absorption. In patients getting overnight peritoneal dialysis using a cycler, sometimes the time duration of NPH or premixed insulins see below may be useful to cover the glucose absorption that occurs from the dialysis fluid.
The long-acting insulin analogs glargine Lantus, Basaglar; U and detemir Levemir are readily available. Glargine has an onset of action at 2 to 4 hours, with minimal peak and lasts approximately 20 to 24 hours. It is usually dosed once daily. Detemir has an onset of action at 1 to 3 hours, with a small peak at 6 to 8 hours and approximate duration of action of 18 to 22 hours.
Detemir is typically dosed twice daily to give adequate basal coverage in those with type 1 diabetes; in type 2 diabetes, it can often be dosed only once daily. Recently, a more concentrated version of glargine U Toujeo has become available, in pen-form only; it has an even smaller peak and less day-to-day variability.
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Degludec Tresiba is a newly available very long-acting insulin that is available in U and U pen forms. It has a half-life of about 25 hours, a minimal peak, and low day-to-day variability. There are various premixed preparations of insulin available that include a fixed percentage of an intermediate-acting insulin and a rapid- or short-acting insulin.
Because they contain a combination of 2 different insulin types, they have two separate peaks in insulin.
These preparations can offer convenience for the patient with twice daily dosing but offer less flexibility and restrictions in ability to titrate insulin doses. The insulin must be taken at fixed times and the patient must have regular meal times and size.
Diabetic Kidney Disease: Diagnosis, Treatment, and Prevention
As noted above, sometimes these premixed insulins are useful to cover the glucose absorption that occurs with overnight peritoneal dialysis. The majority of insulin is U, defined as units of insulin per 1 mL. U contains units per 1 mL and is available only as regular insulin. The high concentration of U alters its kinetics, making it act more like NPH insulin when used subcutaneously. U, the U form of Glargine Toujeo , and the U form of degludec are concentrated forms of insulin useful for patients with severe insulin resistance who require large doses of insulin as well as patients with minimal fat depots.
The U form of Humalog offers the advantage of the same amount of insulin delivered in a smaller volume. It is also useful for those with high insulin requirement and will allow the pens to last longer each pen contains units per pen instead of the standard units. Metformin a biguanide increases insulin sensitivity and decreases hepatic gluconeogenesis.
Metformin does not cause hypoglycemia when used by itself. B12 deficiency has been reported with long-term use. Lactic acidosis is a rare and serious side effect of metformin use, which can occur when toxic levels of metformin accumulate. Metformin is cleared by the kidney, thus its use in CKD is restricted.
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Second-generation sulfonylureas glipizide, glyburide, glimepiride and gliclazide bind to a sulfonylurea receptor on pancreatic beta-cells and therefore increase insulin secretion. They can lead to hypoglycemia. Glipizide and gliclazide may be used in CKD stage 3 or worse. It is best to avoid the use of glyburide in CKD stage 3 since it has a long half-life and can cause hypoglycemia in patients with decreased GFR.
Glimepiride can be used starting at the lowest dose 1 mg and titrated with caution. Gliclazide is not available in the US. Glinides nateglinide, repaglinide work in a glucose-dependent mechanism and result in quick insulin release through an ATP-dependent potassium channel on beta-cells of the pancreas. Their ideal use is for control of post-prandial hyperglycemia; they can also lead to hypoglycemia. Repaglinide appears to be generally safe in those with CKD. Thiazolidinediones pioglitazone, rosiglitazone increase insulin sensitivity by acting as peroxisome proliferator-activated receptor gamma agonists.
They do not lead to hypoglycemia. They are metabolized by the liver and thus can be used in CKD. However, fluid retention is a major limiting side effect and they should not be used in advanced heart failure and other fluid-retaining states. This also makes their use in CKD, particularly patients on dialysis, limiting.
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They have been linked with increased fracture rates and bone loss, thus the appropriate use in patients with underlying bone disease such as renal osteodystrophy needs to be considered. Although there was a concern several years ago about an increased risk of ischemic heart disease with rosiglitazone, subsequent analyses did not support this conclusion and a prior warning from the FDA was lifted.
Alpha-glucosidase inhibitors acarbose, miglitol inhibit absorption of carbohydrates and thus slow glucose elevation post-prandially. These agents are not associated with hypoglycemia but side effects of bloating, flatulence and abdominal cramping can be limiting. Acarbose is only minimally absorbed, but with reduced renal function, serum levels of the drug and its metabolites increase significantly.
Miglitol has greater systemic absorption and undergoes renal excretion, and it should not be used in patients with decreased GFR.
Dipeptidyl peptidase 4 DPP 4 inhibitors decrease the breakdown of incretin hormones such as GLP-1 and include the oral medications sitagliptin Januvia , saxagliptin Onglyza , linagliptin Tradjenta , and alogliptin Nesina. They do not cause hypoglycemia. Linagliptin does not need to be adjusted in kidney disease since only a fraction is renally cleared.
The dose of alogliptin should be reduced from 25 mg to The EmpaReg study recently demonstrated significant benefits in reduction of cardiovascular outcomes and mortality and worsening of eGFR with empagliflozin use. A recent article CANVAS trials showed patients receiving canagliflozin also had a decreased risk of cardiovascular disease but also an increased risk of amputations. Glucagon-like peptide-1 GLP-1 receptor agonists exenatide [Byetta], exenatide extended-release [Bydureon], liraglutide [Victoza], albiglutide [Tanzeum], dulaglutide [Trulicity] and lixisenatide [Adlyxin] are injectable medications that mimic gut hormones known as incretins, leading to insulin release, delayed glucagon secretion, and delayed gastric emptying.
They are approved for use in type 2 diabetes along with sulfonyureas and metformin although, in practice, they are used with insulin as well. The GLP-1 receptor agonists also decrease appetite by increasing satiety, which leads to weight loss in many patients. 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.