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|Classification and external resources|
Photomicrography of nodular glomerulosclerosis in Kimmelstein-Wilson syndrome. Source: CDC
|ICD-10||E10.2, E11.2, E12.2, E13.2, E14.2|
Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime indication for dialysis in many Western countries.
The syndrome can be seen in patients with chronic diabetes (usually less than 15 years after onset) after about 5 years in type 1 diabetes. Clinical nephropathy secondary to glomerular disease usually manifests 15–25 years after diagnosis of diabetes and affects 25-35% of patients under the age of 30 years. It is the leading cause of premature death in young diabetic patients (between 50 and 70 years old). The disease is progressive and may cause death two or three years after the initial lesions, and is more frequent in men. Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States. People with both type 1 and type 2 diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. Furthermore, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure. Also people with high cholesterol level in their blood have much more risk than others.
The word diabetes means "passing through", referring to the polyuria (abnormal increase of urine production), a symptom historically present on those affected by the disease. When the level of blood glucose rises beyond the kidney's capacity to reabsorb glucose from the renal ultrafiltrate, glucose remains diluted in the fluid, raising its osmotic pressure and causing more water to be carried out, thus, increasing the excreted urine volume. The increased volume dilutes the sodium chloride in the urine, signalling the macula densa to release more renin, causing vasoconstriction, a survival mechanism to retain water by passing less blood through the kidneys. Because the kidney is nurtured exclusively by the blood it filtrates, the vasoconstriction also reduces the nutrients supplied to it, causing infarct of its tissues and reduction of renal function.
The earliest detectable change in the course of diabetic nephropathy is a thickening in the glomerulus. At this stage, the kidney may leak more serum albumin (plasma protein) than normal in the urine (albuminuria), and this can be detected by sensitive medical tests for albumin. This stage is called "microalbuminuria". As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed by progressive nodular glomerulosclerosis. Consequently, urine albumin increases to the point that it may be detected by ordinary urinalysis techniques. At this stage, a kidney biopsy generally clearly shows diabetic nephropathy.
The Armanni-Ebstein change (or Armanni-Ebstein cells) consists of deposits of glycogen in the tubular epithelial cells (pars straight of proximal convoluted tubule and loop of Henle). Because most diabetics are treated before this stage, it is very rare to see it at the present time. It appears in decompensated diabetics with glycemia higher than 500 mg/dL and in the presence of severe glycosuria; it is a reversible alteration without functional manifestations. The interstitium shows nonspecific chronic changes.
Signs and symptoms 
Kidney failure provoked by glomerulosclerosis leads to fluid filtration deficits and other disorders of kidney function. There is an increase in blood pressure (hypertension) and fluid retention in the body plus a reduced plasma oncotic pressure causes edema. Other complications may be arteriosclerosis of the renal artery and proteinuria.
Throughout its early course, diabetic nephropathy has no symptoms. They develop in late stages and may be a result of excretion of high amounts of protein in the urine or due to renal failure:
- edema: swelling, usually around the eyes in the mornings; later, general body swelling may result, such as swelling of the legs
- foamy appearance or excessive frothing of the urine (caused by the proteinuria)
- unintentional weight gain (from fluid accumulation)
- anorexia (poor appetite)
- nausea and vomiting
- malaise (general ill feeling)
- frequent hiccups
The first laboratory abnormality is a positive microalbuminuria test. Most often, the diagnosis is suspected when a routine urinalysis of a person with diabetes shows too much protein in the urine (proteinuria). The urinalysis may also show glucose in the urine, especially if blood glucose is poorly controlled. Serum creatinine and BUN may increase as kidney damage progresses.
A kidney biopsy confirms the diagnosis, although it is not always necessary if the case is straightforward, with a documented progression of proteinuria over time and presence of diabetic retinopathy on examination of the retina of the eyes.
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 proteinuria levels and slows the progression of diabetic nephropathy. Several effects of the ACEIs that may contribute to renal protection have been related to the association of rise in Kinins which is also responsible for some of the side effects associated with ACEIs therapy such as dry cough. The renal protection effect is related to the antihypertensive effects in normal and hypertensive patients, renal vasodilatation resulting in increased renal blood flow and dilatation of the efferent arterioles. Many studies have shown that related drugs, angiotensin receptor blockers (ARBs), have a similar benefit. However, combination therapy, according to the ONTARGET study, is known to worsen major renal outcomes, such as increasing serum creatinine and causing a greater decline in estimated glomerular filtration rate (eGFR).
Blood-glucose levels should be closely monitored and controlled. This may slow the progression of the disorder, especially in the very early ("microalbuminuria") stages. Medications to manage diabetes include oral hypoglycemic agents and insulin injections. As kidney failure progresses, less insulin is excreted, so lesser doses may be needed to control glucose levels.
High blood pressure should be aggressively treated with antihypertensive medications, in order to reduce the risks of kidney, eye, and blood vessel damage in the body. It is also very important to control lipid levels, maintain a healthy weight, and engage in regular physical activity.
Patients with diabetic nephropathy should avoid taking the following drugs:
- Contrast agents containing iodine
- Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, or COX-2 inhibitors like celecoxib, because they may injure the weakened kidney.
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.
Diabetic nephropathy continues to get gradually worse. Complications of chronic kidney failure are more likely to occur earlier, and progress more rapidly, when it is caused by diabetes than other causes. Even after initiation of dialysis or after transplantation, people with diabetes tend to do worse than those without diabetes.
Possible complications include:
- hypoglycemia (due to decreased renal clearance of insulin)
- rapidly progressing chronic kidney failure
- end-stage kidney disease
- severe hypertension
- complications of hemodialysis
- complications of kidney transplant
- coexistence of other diabetes complications
- peritonitis (if peritoneal dialysis used)
- increased infections
See also 
Additional images 
- Berkman, James; Rifkin, Harold (1973). "Unilateral nodular diabetic glomerulosclerosis (Kimmelstiel-Wilson): Report of a case". Metabolism (Elsevier Inc.) 22 (5): 715–722. doi:10.1016/0026-0495(73)90243-6. PMID 4704716.
- Kimmelstiel P, Wilson C. Benign and malignant hypertension and nephrosclerosis. A clinical and pathological study. Am J Pathol 1936;12:45-48.
- Diabetes Mellitus and Angiotensin Converting Enzyme Inhibitors
- The ONTARGET Investigators; Yusuf, S; Teo, KK; Pogue, J; Dyal, L; Copland, I; Schumacher, H; Dagenais, G et al. (2008). "Telmisartan, Ramipril, or Both in Patients at High Risk for Vascular Events". New England Journal of Medicine 358 (15): 1547–59. doi:10.1056/NEJMoa0801317. PMID 18378520.
- Wahren J, Ekberg K, Jörnvall H (2007). "C-peptide is a bioactive peptide". Diabetologia 50 (3): 503–9. doi:10.1007/s00125-006-0559-y. PMID 17235526.
- Diabetic nephropathy. HealthCentral.
- Diabetic nephropathy. MedlinePlus Medical Encyclopedia. Text from this public domain article was partially used here.
- Texas University Classification