- Etiology
- Pathology
- Pathophysiology
- Epidemiology
- Management & Treatment
- Prevention
- Complications
- Prognosis
- Research Frontier
- Clinical Case Studies
- Study Questions
Left: Schema of the normal glomerular architecture. Right: Secondary glomerular changes associated with a reduction in nephron number, including enlargement of capillary lumens and focal adhesions, which are thought to occur consequent to compensatory hyperfiltration and hypertrophy in the remaining nephrons. (Modified from JR Ingelfinger: N Engl J Med 348:99, 2003.)
Chronic kidney disease (CKD) is long-standing, irreversible impairment of kidney function.
Updated classification, in which stages of CKD are stratified by both estimated GFR and the degree of albuminuria, in order to predict risk of progression of CKD. Previously, CKD had been staged solely by the GFR. However, the risk of worsening of kidney function is closely linked to the amount of albuminuria, and so it has been incorporated into the classification.Gradation of color from green to red corresponds to increasing risk and progression of CKD. GFR, glomerular filtration rate. (Reproduced with permission from Kidney Int Suppl 3:5-14, 2013.)
_______________________________________________
There is a spectrum of disease related to decrements in renal function; clinical and therapeutic issues differ greatly depending on whether the glomerular filtration rate (GFR) reduction is moderate (stage 3 CKD, 30–59 mL/min per 1.73 m2) .
THE CLASSIFICATION OF CHRONIC KIDNEY DISEASE (NATIONAL KIDNEY FOUNDATION GUIDELINES)
| Kidney Damage Stage | Description | eGFR (mL/min per 1.73 m2) |
|---|---|---|
| 0 | With risk factors for CKDa | >90 |
| 1 | With evidence of kidney damageb | >90 |
| 2 | Mild decrease in GFR | 60–89 |
| 3 | Moderate decrease in GFR | 30–59 |
| 4 | Severe decrease in GFR | 15–29 |
| 5 | Kidney failure | <15 |
severe (stage 4 CKD, 15–29 mL/min per 1.73 m2), or “end-stage renal disease” (stage 5 CKD, <15 mL/min per 1.73 m2). Dialysis is usually required once GFR <10 mL/min per 1.73 m2.
Common causes of CKD are outlined in Table 139-1.
TABLE 139-1COMMON CAUSES OF CHRONIC RENAL FAILURE
| Diabetic nephropathy |
| Hypertensive nephropathya |
| Glomerulonephritis |
| Renovascular disease (ischemic nephropathy) |
| Polycystic kidney disease |
| Reflux nephropathy and other congenital renal diseases |
| Interstitial nephritis, including analgesic nephropathy |
| HIV-associated nephropathy |
| Transplant allograft failure (“chronic rejection”) |
The pathophysiology of CKD involves two broad sets of mechanisms of damage: (1) initiating mechanisms specific to the underlying etiology (e.g., genetically determined abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium) and (2) a set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology. The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors. Eventually, these short-term adaptations of hypertrophy and hyperfiltration become maladaptive as the increased pressure and flow within the nephron predisposes to distortion of glomerular architecture, abnormal podocyte function, and disruption of the filtration barrier leading to sclerosis and dropout of the remaining nephrons (Fig. 335-2). Increased intrarenal activity of the renin-angiotensin system (RAS) appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis. This process explains why a reduction in renal mass from an isolated insult may lead to a progressive decline in renal function over many years (Fig. 335-3).
Case: A 63-year-old woman with stage 4 CKD presents with fatigue and is noted to have a hemoglobin of 8.5 mg/dL. You are considering starting erythropoietin therapy.
-
How does chronic kidney disease (CKD) lead to anemia?1
— Decreased production of erythropoietin (stimulus for red blood cell production) by diseased kidneys → normocytic, normochromic anemia
-
What labs must be checked prior to the initiation of erythropoietin?1
— Baseline iron studies (serum iron, transferrin, and ferritin levels)
-
If iron deficient, need to pursue potential cause of iron-deficiency (e.g., GI blood loss) and replete iron stores prior to initiating erythropoietin
-
-
How can iron be administered to patients with CKD and iron-deficiency?1
— IV iron formulations are preferred (more rapid repletion and better patient adherence compared to PO ferrous sulfate)
-
1 g of iron will improve Hct by 10% over 3 months
-
IV iron gluconate (Ferrlecit) + iron sucrose (Venofer) are preferred due to reduced risk of anaphylaxis compared to IV iron dextran
-
-
Is a higher hemoglobin target preferred in CKD?2
— CHOIR trial: RCT of 1,432 patients with predialysis CKD comparing erythropoietin titrated to a hemoglobin target of 13.5 vs. 11.3 g/dL
-
Risk of primary outcome: composite end-point (death, myocardial infarction, hospitalization for CHF, and/or stroke) increased in high-hemoglobin target group vs. low target (hazard ratio of 1.34)
-
Quality of life improvement was not significantly different between the two groups (based on three different scoring systems including the Linear Analogue Self-Assessment score)
-
-
What hemoglobin target do the guidelines recommend for CKD?3
— 2012 KDIGO guidelines recommend a hemoglobin target of 10–11.5 g/dL
-
What are the possible reasons for failure to respond to erythropoietin treatment?1
— Iron deficiency, chronic inflammation, severe hyperparathyroidism (can lead to bone marrow fibrosis), hemoglobinopathies, B12/folate deficiencies
Outcomes of high-versus low-hemoglobin treatment targets for erythropoietin in chronic kidney disease: data from the CHOIR trial.
Most people with pyelonephritis do not have complications if appropriately treated with bacteria-fighting medications called antibiotics.
In rare cases, pyelonephritis may cause permanent kidney scars, which can lead to chronic kidney disease, high blood pressure, and kidney failure. These problems usually occur in people with a structural problem in the urinary tract, kidney disease from other causes, or repeated episodes of pyelonephritis.
Infection in the kidneys may spread to the bloodstream—a serious condition called sepsis—though this is also uncommon.
Content 3
Content 13
Case: A 63-year-old woman with stage 4 CKD presents with fatigue and is noted to have a hemoglobin of 8.5 mg/dL. You are considering starting erythropoietin therapy.
-
How does chronic kidney disease (CKD) lead to anemia?1
— Decreased production of erythropoietin (stimulus for red blood cell production) by diseased kidneys → normocytic, normochromic anemia
-
What labs must be checked prior to the initiation of erythropoietin?1
— Baseline iron studies (serum iron, transferrin, and ferritin levels)
-
If iron deficient, need to pursue potential cause of iron-deficiency (e.g., GI blood loss) and replete iron stores prior to initiating erythropoietin
-
-
How can iron be administered to patients with CKD and iron-deficiency?1
— IV iron formulations are preferred (more rapid repletion and better patient adherence compared to PO ferrous sulfate)
-
1 g of iron will improve Hct by 10% over 3 months
-
IV iron gluconate (Ferrlecit) + iron sucrose (Venofer) are preferred due to reduced risk of anaphylaxis compared to IV iron dextran
-
-
Is a higher hemoglobin target preferred in CKD?2
— CHOIR trial: RCT of 1,432 patients with predialysis CKD comparing erythropoietin titrated to a hemoglobin target of 13.5 vs. 11.3 g/dL
-
Risk of primary outcome: composite end-point (death, myocardial infarction, hospitalization for CHF, and/or stroke) increased in high-hemoglobin target group vs. low target (hazard ratio of 1.34)
-
Quality of life improvement was not significantly different between the two groups (based on three different scoring systems including the Linear Analogue Self-Assessment score)
-
-
What hemoglobin target do the guidelines recommend for CKD?3
— 2012 KDIGO guidelines recommend a hemoglobin target of 10–11.5 g/dL
-
What are the possible reasons for failure to respond to erythropoietin treatment?1
— Iron deficiency, chronic inflammation, severe hyperparathyroidism (can lead to bone marrow fibrosis), hemoglobinopathies, B12/folate deficiencies
Content 2
Content 3
A
A 75-year-old triathlete complains of gradually worsening vision over the past year. It seems to be involving near and far vision. The patient has never required corrective lenses and has no significant medical history other than diet-controlled hypertension. He takes no regular medications. Physical examination is normal except for bilateral visual acuity of 20/100. There are no focal visual field defects and no redness of the eyes or eyelids. Which of the following is the most likely diagnosis?
The correct answer is A. You answered A.
Age-related macular degeneration is a major cause of painless, gradual bilateral central visual loss. It occurs as nonexudative (dry) or exudative (wet) forms. Recent genetic data have shown an association with the alternative complement pathway gene for complement factor H. The mechanism link for that association is unknown. The nonexudative form is associated with retinal drusen that leads to retinal atrophy. Treatment with vitamin C, vitamin E, beta-carotene, and zinc may retard the visual loss. Exudative macular degeneration, which is less common, is caused by neovascular proliferation and leakage of choroidal blood vessels. Acute visual loss may occur because of bleeding. Exudative macular degeneration may be treated with intraocular injection of a vascular endothelial growth factor antagonist (bevacizumab or ranibizumab). Blepharitis is inflammation of the eyelids usually related to acne rosacea, seborrheic dermatitis, or staphylococcal infection. Diabetic retinopathy, now a leading cause of blindness in the United States, causes gradual bilateral visual loss in patients with long-standing diabetes. Retinal detachment is usually unilateral and causes visual loss and an afferent pupillary defect.
Mr. Jenson is a 40-year-old man with a congenital bicuspid aortic valve who you have been seeing for more than a decade. You obtain an echocardiogram every other year to follow the progression of his disease knowing that bicuspid valves often develop stenosis or regurgitation requiring replacement in middle age. Given his specific congenital abnormality, what other anatomic structure is important to follow on his biannual echocardiograms?
The correct answer is A. You answered A.
The answer is A. (Chap. 282) Bicuspid aortic valve is among the most common of congenital heart cardiac abnormalities. Valvular function is often normal in early life and thus may escape detection. Due to abnormal flow dynamics through the bicuspid aortic valve, the valve leaflets can become rigid and fibrosed, leading to either stenosis or regurgitation. However, pathology in patients with bicuspid aortic valve is not limited to the valve alone. The ascending aorta is often dilated, misnamed “poststenotic” dilatation; this is due to histologic abnormalities of the aortic media and may result in aortic dissection. It is important to screen specifically for aortopathy because dissection is a common cause of sudden death in these patients.