Eric Langewisch, MD
John M. Barry, MD, FACS
BASICS
DESCRIPTION
• Chronic glomerulonephritis is the loss of renal function caused by damage to glomeruli
• Often mediated by inflammation and cellular proliferation
• Frequently associated with hematuria and proteinuria
• Many forms of glomerulonephritis (GN) present acutely. Progression from acute to chronic GN is variable
• IgA nephropathy is the most common type of GN
EPIDEMIOLOGY
Incidence
• 4/100,000 people in the United States (US)
• 20–50% of patients with acute GN will develop chronic GN
Prevalence
• GN is the 3rd leading cause of end-stage renal disease (ESRD) in the United States after diabetes mellitus and hypertension (1)
– Accounts for about 10% of dialysis patients
RISK FACTORS
• The cause of many forms of chronic GN is unknown
• Acute GN (focal segmental glomerulosclerosis, hemolytic uremic syndrome, IgA nephropathy, membranous GN)
• Autoimmune diseases (systemic lupus erythematosus (SLE), Goodpasture’s syndrome, systemic vasculitis)
• Infections (β-streptococci, human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C)
• Other systemic diseases (diabetes mellitus, multiple myeloma, amyloidosis, Henoch–Schönlein purpura, polyarteritis nodosa, Wegener’s granulomatosis)
• Family history of hereditary GN (Alport syndrome, thin basement membrane disease)
Genetics
Some cases of hereditary GN or nephritis (Alport syndrome caused by a mutation of COL4A5 gene, usually X-linked and more severe in men; thin basement membrane disease)
PATHOPHYSIOLOGY (2)
• Damage to glomeruli, often mediated through immune/inflammatory mediators, leads to decreased filtering surface and nephron mass
• Remaining glomeruli are subjected to increased filtering pressure. This results in hyperfiltering by remaining glomeruli.
• Increased glomerular pressure causes progressive sclerosis of glomeruli and interstitial fibrosis and progressive loss of functioning glomeruli
ASSOCIATED CONDITIONS
See Risk Factors
GENERAL PREVENTION
• Early nephrology consultation can improve outcomes
• Treat active GN, eg, immune suppressing/modulating agents for active lupus nephritis
• Control blood pressure
– Target <125/75 in patients with >1 g proteinuria
– Target <130/80 in patients with <1 g proteinuria
• Treat comorbid conditions
– Dyslipidemia
– Diabetes
– Infectious disease
– Malignancy
• Dietary protein restriction
– Must balance protein restriction with risk of malnutrition
• Avoid NSAIDs, aminoglycosides, and contrast media as they may further impact on the renal insufficiency
DIAGNOSIS
HISTORY
• Often asymptomatic
• Past acute kidney disease
• Symptoms of uremia
– Decreased energy
– Met allic taste in mouth
– Poor appetite
– Pruritus
– Slowed cognition
PHYSICAL EXAM
• May be unremarkable
• Weight loss
• Hypertension
• Volume overload
– Elevated jugular venous pressure, pulmonary rales, pedal edema
• Signs of uremia
– Asterixis
– Pericardial rub
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Elevated plasma creatinine from loss of renal function (3)
– Prior plasma creatinine values may help determine rate of renal function deterioration
• Serologies may help identify etiology
– Antistreptolysin O, antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), C3, C4, HIV, Hep B, Hep C
• Urinalysis
– Proteinuria
– RBC casts
Considered diagnostic for GN or vasculitis
– Dysmorphic RBC
Isomorphic RBCs appear similar to erythrocytes in the circulation (small, anucleated cells; biconcave discs)
Dysmorphic RBC criterion varies; membrane protrusions such as seen with peripheral acanthocytes are 1 described criterion
• Urine protein measurement
– 24-hr urine (normally <100 mg)
– Random urine microalbumin/ creatinine ratio (normally <20 μ/mg)
– Random urine protein/creatinine ratio (normally <0.2)
• With significant chronic kidney disease
– Anemia from decreased erythropoietin production
– Hyperkalemia from decreased potassium clearance
– Hyperphosphatemia from decreased phosphorous excretion
– Acidemia from decreased acid buffering
Imaging
• Renal ultrasound to assess kidney size and cortical volume
– Advanced disease is associated with decreased renal size, increased echogenicity, and cortical thinning
– Kidneys usually normal sized with diabetic nephropathy
Diagnostic Procedures/Surgery
• Renal biopsy can potentially diagnose different glomerular diseases
– Biopsy may not be helpful in advanced disease
Pathologic Findings
• Renal biopsy may determine type of glomerular disease by pattern of injury and immune complex staining
– With advanced disease and small kidneys on ultrasound, biopsy frequently shows advanced sclerosis/scarring and may not be able to determine etiology
DIFFERENTIAL DIAGNOSIS
• Aristocholic acid (for weight control)
• Chronic interstitial nephritis
• Diabetic nephrosclerosis
• Diuretic abuse
• Hypertensive nephrosclerosis
• Nephrotoxin exposure
• Obstructive uropathy
• Prerenal disease
• Renal artery stenosis
TREATMENT
GENERAL MEASURES
• See GENERAL PREVENTION
• Referral to nephrology
• Treat specific glomerular disease (eg, prednisone or other immunosuppressive agents)
• Control blood pressure (4)
• Renal replacement therapy may be necessary long term
MEDICATION
First Line
• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) slow the decline of the glomerular filtration rate (GFR) in patients with diabetic and nondiabetic proteinuric nephropathies
– ACEIs: Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, others
– ARB: Candesartan, eprosartan, irbesartan, losartan, telmisartan, valsartan
– Use may be limited by drug-induced hyperkalemia, increased plasma creatinine due to decreased glomerular pressure, or anemia
Second Line
• Diuretics to treat volume overload
• Additional antihypertensive agents to reach blood pressure goals
– β-Blockers, calcium channel blockers, central α2-agonists (eg, clonidine), α1-antagonists, and direct vasodilators
SURGERY/OTHER PROCEDURES
• Access for dialysis
– AV fistula or graft
– Hemodialysis access or peritoneal dialysis catheter
• Renal transplantation
– Preemptive transplantation before dialysis results in better survival than transplantation after the initiation of dialysis
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Oral calcium supplements (1 g/d) and vitamin D (400–800 IU/d) for prophylaxis against osteoporosis.
• Sodium bicarbonate has been shown to slow progressive kidney damage.
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Progression of glomerular disease to ESRD is variable and dependent upon cause and response to treatment
• Prognosis has negative correlation with higher blood pressure and degree of proteinuria
COMPLICATIONS
• ESRD
– Uremia
– Volume overload
– Hyperkalemia
– Anemia
– Acidosis
• Increased risk of cardiovascular disease
• Increased risk of mortality
FOLLOW-UP
Patient Monitoring
• Lab monitoring
– Estimate glomerular filtration rate (eGFR): BUN, plasma creatinine
– Basic metabolic panel + phosphorous
– Random urine protein/creatinine ratio
– 24-hr urine protein
• Blood pressure
• Signs or symptoms of uremia
Patient Resources
www.kidney.org/patients
REFERENCES
1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2 suppl 1):S1–S266.
2. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med. 1998;339(20):1448–1456.
3. Appel GB. Glomerular disorders and nephrotic syndromes. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, PA: Saunders Elsevier; 2007; Chapter 122.
4. Peterson JC, Adler S, Burkart JM, et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123(10):754–762.
ADDITIONAL READING
Kopp JB. Glomerular disease in 2012: More mechanistic insights, but translational progress is slow. Nat Rev Nephrol. 2013;9(2):67–68.
See Also (Topic, Algorithm, Media)
Glomerulonephritis, Acute
CODES
ICD9
• 582.1 Chronic glomerulonephritis with lesion of membranous glomerulonephritis
• 582.89 Chronic glomerulonephritis with other specified pathological lesion in kidney
• 582.9 Chronic glomerulonephritis with unspecified pathological lesion in kidney
ICD10
• N03.2 Chronic nephritic syndrome w diffuse membranous glomrlneph
• N03.9 Chronic nephritic syndrome with unsp morphologic changes
• N11.9 Chronic tubulo-interstitial nephritis, unspecified
CLINICAL/SURGICAL PEARLS
• Many cases of acute GN can progress to chronic GN.
• ACEIs and ARB can slow the decline of the GFR in patients with proteinuric nephropathies.