eMedicine Specialties > Nephrology > Glomerular Diseases
Glomerulonephritis, Chronic
Updated: Jul 20, 2007
Introduction
Background
Nearly all forms of acute glomerulonephritis have a tendency to progress to chronic glomerulonephritis. The condition is characterized by irreversible and progressive glomerular and tubulointerstitial fibrosis, ultimately leading to a reduction in the glomerular filtration rate (GFR) and retention of uremic toxins. If disease progression is not halted with therapy, the net result is chronic kidney disease (CKD), end-stage renal disease (ESRD), and cardiovascular disease. The diagnosis of CKD can be made without knowledge of the specific cause.
The National Kidney Foundation defines CKD as (1) evidence of kidney damage based on abnormal urinalysis results (eg, proteinuria, hematuria) or structural abnormalities observed on ultrasound images or (2) a GFR of less than 60 mL/min for 3 or more months. Based on this definition, the National Kidney Foundation developed guidelines that classify the progression of renal disease into 5 stages, from kidney disease with a preserved GFR to end-stage kidney failure. This classification includes treatment strategies for each progressive level, as follows:
- Stage 1: This stage is characterized by kidney damage with a normal GFR (>90 mL/min). The action plan is diagnosis and treatment, treatment of comorbid conditions, slowing of the progressing of kidney disease, and reduction of cardiovascular disease risks.
- Stage 2: This stage is characterized by kidney damage with a mild decrease in the GFR (60-90 mL/min). The action plan is estimation of the progression of kidney disease.
- Stage 3: This stage is characterized by a moderately decreased GFR (30-59 mL/min). The action plan is evaluation and treatment of complications.
- Stage 4: This stage is characterized by a severe decrease in the GFR (15-29 mL/min). The action plan is preparation for renal replacement therapy.
- Stage 5: This stage is characterized by kidney failure. The action plan is kidney replacement if the patient is uremic.
At the later stages of glomerular injury, biopsy results cannot help distinguish the primary disease. Histology and clues to the etiology are often derived from other systemic diseases, if present. Considerable cause-specific variability is observed in the rate at which acute glomerulonephritis progresses to chronic glomerulonephritis.
Pathophysiology
Reduction in nephron mass from the initial injury reduces the GFR. This reduction leads to hypertrophy and hyperfiltration of the remaining nephrons and to the initiation of intraglomerular hypertension. These changes occur in order to increase the GFR of the remaining nephrons, thus minimizing the functional consequences of nephron loss. The changes, however, are ultimately detrimental because they lead to glomerulosclerosis and further nephron loss.
In early renal disease (stages 1-3), a substantial decline in the GFR may lead to only slight increases in serum creatinine levels. Azotemia (ie, a rise in BUN and serum creatinine levels) is apparent when the GFR decreases to less than 60-70 mL/min. In addition to a rise in BUN and creatinine levels, the substantial reduction in the GFR results in decreased production of (1) erythropoietin, thus resulting in anemia; (2) decreased production of vitamin D, resulting in hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, and renal osteodystrophy; (3) reduction in acid, potassium, salt, and water excretion, resulting in acidosis, hyperkalemia, hypertension, and edema; and (4) platelet dysfunction, leading to increased bleeding tendencies.
Accumulation of toxic waste products (uremic toxins) affects virtually all organ systems. Azotemia occurring with the signs and symptoms listed above is known as uremia. Uremia occurs at a GFR of approximately 10 mL/min. Some of these toxins (eg, BUN, creatinine, phenols, guanidines) have been identified, but none has been found to be responsible for all the symptoms.
Frequency
United States
Chronic glomerulonephritis is the third leading cause of ESRD and accounts for 10% of patients on dialysis in the United States.
International
Chronic glomerulonephritis accounted for up to 40% of patients on dialysis in Japan and some Asian countries. However, more recent data suggest that, in Japan, for instance, the rate of chronic glomerulonephritis in patients on dialysis is 28%. The cause of this declining rate is not known. Concurrent with the decline in chronic glomerulonephritis in these countries is an increase in diabetic nephropathy in up to 40% of patients on dialysis.
Mortality/Morbidity
ESRD and death are common outcomes unless renal replacement therapy is instituted.
Clinical
History
The history should focus on cause-specific symptoms to determine the causes of CKD (if unknown) and on symptoms related to uremia to determine if renal replacement therapy is needed.
- Cause-specific history: Obtain a cause-specific history so that further workup and management of the disease (if systemic) can be planned.
- Uremia-specific history
- The following symptoms suggest uremia:
- Weakness and fatigue
- Loss of energy, appetite, and weight
- Pruritus
- Early morning nausea and vomiting
- Change in taste sensation
- Reversal in sleep pattern (ie, sleepiness in daytime, wakefulness at night)
- Peripheral neuropathy
- Seizures
- Tremors
- The presence of edema and hypertension suggests volume retention.
- Dyspnea or chest pain that varies with position suggests fluid overload and pericarditis, respectively.
- Leg cramps may suggest hypocalcemia or other electrolyte abnormalities.
- Weakness, lethargy, and fatigue may be due to anemia.
- The following symptoms suggest uremia:
Physical
Cause-specific physical examination findings are discussed in articles on the specific causes. See Causes for links to such articles.
- Uremia-specific findings
- Hypertension
- Jugular venous distension (if severe volume overload is present)
- Pulmonary rales (if pulmonary edema is present)
- Pericardial friction rub in pericarditis
- Tenderness in the epigastric region or blood in the stool (possible indicators for uremic gastritis or enteropathy)
- Decreased sensation and asterixis (indicators for advanced uremia)
Causes
The progression from acute glomerulonephritis to chronic glomerulonephritis is variable. Whereas complete recovery of renal function is the rule for patients with poststreptococcal glomerulonephritis, several other glomerulonephritides, such as immunoglobulin A (IgA) nephropathy, often have a relatively benign course and many do not progress to ESRD.
- Rapidly progressive glomerulonephritis or crescentic glomerulonephritis: Approximately 90% of patients progress to ESRD within weeks or months. See Glomerulonephritis, Rapidly Progressive and Glomerulonephritis, Crescentic.
- Focal segmental glomerulosclerosis: Approximately 80% of patients progress to ESRD in 10 years. Patients with the collapsing variant, which is termed malignant focal segmental glomerulosclerosis, have a more rapid progression. This form may be idiopathic or related to HIV infection.
- Membranous nephropathy: Approximately 20-30% of patients with membranous nephropathy progress to chronic renal failure (CRF) and ESRD in 10 years.
- Membranoproliferative glomerulonephritis: Approximately 40% of patients with membranoproliferative glomerulonephritis progress to CRF and ESRD in 10 years. See Glomerulonephritis, Membranoproliferative.
- IgA nephropathy: Approximately 10% of patients with IgA nephropathy progress to CRF and ESRD in 10 years.
- Poststreptococcal glomerulonephritis: Approximately 1-2% of patients with poststreptococcal glomerulonephritis progress to CRF and ESRD. Older children who present with crescentic glomerulonephritis are at greatest risk. See Glomerulonephritis, Poststreptococcal.
- Lupus nephritis: Overall, approximately 20% of patients with lupus nephritis progress to CRF and ESRD in 10 years; however, patients with certain histologic variants (eg, class IV) may have a more rapid decline. See Nephritis, Lupus.
More on Glomerulonephritis, Chronic |
 Overview: Glomerulonephritis, Chronic |
| Differential Diagnoses & Workup: Glomerulonephritis, Chronic |
| Treatment & Medication: Glomerulonephritis, Chronic |
| Follow-up: Glomerulonephritis, Chronic |
| References |
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Further Reading
Keywords
glomerulosclerosis, chronic renal failure, chronic kidney failure, CRF, end-stage renal disease, ESRD, end-stage kidney disease, ESKD, nephropathy, rapidly progressive glomerulonephritis, RPGN, focal segmental glomerulosclerosis, FSGS, glomerular fibrosis, tubulointerstitial fibrosis, lupus nephritis, azotemia, uremia, dialysis, renal replacement therapy, renal replacement, renal transplant, renal transplantation, kidney transplant, kidney replacement, kidney transplantation, renal dialysis, kidney dialysis, dialysis, hemodialysis, peritoneal dialysis
