Harrison’s Manual of Medicine



Acute Glomerulonephritis (GN)
Rapidly Progressive Glomerulonephritis
Nephrotic Syndrome (NS)
Asymptomatic Urinary Abnormalities

Acute Glomerulonephritis (GN)
Characterized by development, over days, of azotemia, hypertension, edema, hematuria, proteinuria, and sometimes oliguria. Salt and water retention are due to reduced GFR and may result in circulatory congestion. RBC casts on UA confirm Dx. Proteinuria usually ❤ g/d. Most forms of acute GN are mediated by humoral immune mechanisms. Clinical course depends on underlying lesion (Table 142-1).

Table 142-1 Causes of Acute Glomerulonephritis

ACUTE POSTSTREPTOCOCCAL GN   The prototype and most common cause in childhood. Nephritis develops 1–3 weeks after pharyngeal or cutaneous infection with “nephritogenic” strains of group A b-hemolytic streptococci. Dx depends on a positive pharyngeal or skin culture, rising antibody titers, and hypocomplementemia. Renal biopsy reveals diffuse proliferative GN. Treatment consists of correction of fluid and electrolyte imbalance. In most cases the disease is self-limited, although the prognosis is less favorable and urinary abnormalities are more likely to persist in adults.
POSTINFECTIOUS GN   May follow other bacterial, viral, and parasitic infections. Examples are bacterial endocarditis, sepsis, hepatitis B, and pneumococcal pneumonia. Features are milder than with poststreptococcal GN. Control of primary infection usually produces resolution of GN.
SLE (LUPUS)   Renal involvement is due to deposition of circulating immune complexes. Clinical features of SLE with or without renal involvement include arthralgias, “butterfly” skin rash, serositis, alopecia (hair loss), and CNS disease. Nephrotic syndrome with renal insufficiency is common. Renal biopsy reveals mesangial, focal, or diffuse GN and/or membranous nephropathy. Diffuse GN, the most common finding, is characterized by an active sediment, severe proteinuria, and progressive renal insufficiency and may have an ominous prognosis. Pts have a positive ANA, anti-dsDNA, and complement. Treatment includes glucocorticoids and cytotoxic agents. Oral or IV monthly cyclophosphamide is most commonly employed. Mycophenolate mofetil or azathioprine may be of benefit in some pts, especially those unable to be easily tapered off prednisone.
GOODPASTURE’S SYNDROME   Characterized by lung hemorrhage, GN, and circulating antibody to basement membrane, usually in young men. Hemoptysis may precede nephritis. Rapidly progressive renal failure is typical. Circulating antiglomerular basement membrane (GBM) antibody and linear immunofluorescence on renal biopsy establish Dx. Linear IgG is also present on lung biopsy. Plasma exchange may produce remission. Severe lung hemorrhage is treated with IV glucocorticoids (e.g., 1 g/d × 3 d). Disease isolated to the kidney (“anti-GBM disease”) may also occur.
HENOCH-SCHÖNLEIN PURPURA   A generalized vasculitis causing GN, purpura, arthralgias, and abdominal pain; occurs mainly in children. Renal involvement is manifested by hematuria and proteinuria. Serum IgA is increased in half of pts. Renal biopsy is useful for prognosis. Treatment is symptomatic.
VASCULITIS   Polyarteritis nodosa causes hypertension, arthralgias, neuropathy, and renal failure. Similar features plus palpable purpura and asthma are common in hypersensitivity angiitis. Wegener’s granulomatosis involves upper respiratory tract and kidney and responds well to IV or oral cyclophosphamide.
Rapidly Progressive Glomerulonephritis
Characterized by gradual onset of hematuria, proteinuria, and renal failure, which progresses over a period of weeks to months. Crescentic GN is usually found on renal biopsy. The causes are outlined in Table 142-2. Prognosis for preservation of renal function is poor. Some 50% of pts require dialysis within 6 months of diagnosis. Combinations of glucocorticoids in pulsed doses, cyclophosphamide, and intensive plasma exchange may be useful, although few prospective clinical trial data are available.

Table 142-2 Causes of Rapidly Progressive Glomerulonephritis

Nephrotic Syndrome (NS)
Characterized by albuminuria (>3.5 g/d) and hypoalbuminemia (<30 g/L) and accompanied by edema, hyperlipidemia, and lipiduria. Complications include renal vein thrombosis and other thromboembolic events, infection, vitamin D deficiency, protein malnutrition, and drug toxicities due to decreased protein binding.
In adults, a minority of cases are secondary to diabetes mellitus, SLE, amyloidosis, drugs, neoplasia, or other disorders (Table 142-3). By exclusion, the remainder are idiopathic. Renal biopsy is required to make the diagnosis and determine therapy in idiopathic NS.

Table 142-3 Causes of Nephrotic Syndrome (NS)

MINIMAL CHANGE DISEASE   Causes about 10–15% of idiopathic NS in adults. Blood pressure is normal; GFR is normal or slightly reduced; urinary sediment is benign or may show few RBCs. Protein selectivity is variable in adults. Recent URI, allergies, or immunizations are present in some cases. ARF may rarely occur, particularly among elderly persons. Renal biopsy shows only foot process fusion on electron microscopy. Remission of proteinuria with glucocorticoids carries a good prognosis; cytotoxic therapy may be required for relapse. Progression to renal failure is uncommon. Focal sclerosis has been suspected in some cases refractory to steroid therapy.
MEMBRANOUS GN   Characterized by subepithelial IgG deposits; accounts for ~ 45% of adult NS. Pts present with edema and nephrotic proteinuria. Blood pressure, GFR, and urine sediment are usually normal at initial presentation. Hypertension, mild renal insufficiency, and abnormal urine sediment develop later. Renal vein thrombosis is relatively common, more so than with other forms of nephrotic syndrome. Underlying diseases such as SLE, hepatitis B, and solid tumors and exposure to such drugs as high-dose captopril or penicillamine should be sought. Some pts progress to end-stage renal disease (ESRD); men and persons with very heavy proteinuria are at highest risk— glucocorticoids are frequently prescribed but are rarely effective. Cytotoxic agents (chlorambucil or cyclophosphamide) may promote complete or partial remission in some pts. There is less experience, but some positive reports, using cyclosporine.
FOCAL GLOMERULOSCLEROSIS (FGS)   Can be primary or secondary. Primary tends to be more acute, similar to minimal change disease in abruptness of nephrotic syndrome, but with added features of hypertension, renal insufficiency, and hematuria. Involves fibrosis of portions of some (primarily juxtamedullary) glomeruli and is found in 15% of pts with NS. African-Americans are disproportionately affected. HIV-associated nephropathy and collapsing nephropathy have similar pathologic features; both tend to be more rapidly progressive than typical cases. Fewer than half of pts with primary FGS undergo remission with glucocorticoids; half progress to renal failure in 10 years. FGS may recur in a renal transplant. Presence of azotemia or hypertension reflects poor prognosis.
Secondary FGS can occur in the late stages of any form of kidney disease associated with nephron loss (e.g., remote GN, pyelonephritis, vesicoureteral reflux). Typically responds to ACE inhibition and blood pressure control. No benefit of glucocorticoids in secondary FGS. Clinical history, kidney size, and associated conditions usually allow differentiation of primary vs. secondary causes.
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)   Mesangial expansion and proliferation extend into the capillary loop. Two ultrastructural variants exist. In MPGN I, subendothelial electron-dense deposits are present, C3 is deposited in a granular pattern indicative of immune-complex pathogenesis, and IgG and the early components of complement may or may not be present. In MPGN II, the lamina densa of the GBM is transformed into an electron-dense character, as is the basement membrane in Bowman’s capsule and tubules. C3 is found irregularly in the GBM. Small amounts of Ig (usually IgM) are present, but early components of complement are absent. Serum complement levels are decreased. MPGN affects young adults. Blood pressure and GFR are abnormal, and the urine sediment is active. Some have acute nephritis or hematuria. Similar lesions occur in SLE and hemolytic-uremic syndrome. Infection with hepatitis C virus has been linked to MPGN. Treatment with interferon a and ribavirin has resulted in remission of renal disease in some cases, depending on HCV serotype. Glucocorticoids, cytotoxic agents, antiplatelet agents, and plasmapheresis have been used with limited success. MPGN may recur in allografts.
DIABETIC NEPHROPATHY   Common cause of NS. Pathologic changes include diffuse and/or nodular glomerulosclerosis, nephrosclerosis, chronic pyelonephritis, and papillary necrosis. Clinical features include proteinuria, hypertension, azotemia, and bacteriuria. Although prior duration of diabetes mellitus (DM) is variable, proteinuria may develop 10–15 years after onset, progress to NS, and then lead to renal failure over 3–5 years. Other complications of DM are common; retinopathy is nearly universal. Treatment with ACE inhibitors delays the onset of nephropathy and should be instituted in all pts tolerant to that class of drug.
If a cough develops in a pt treated with an ACE inhibitor, an angiotensin (AII) receptor antagonist is the next best choice. If hyperkalemia develops and cannot be controlled with (1) optimizing glucose control, (2) loop diuretics, or (3) occasional polystyrene sulfonate (Kayexalate), then tight control of blood pressure with alternative agents is warranted. The combination of ACE inhibitor and AII receptor antagonist may be more effective than either agent alone, especially if there is an additive effect on blood pressure. Modest restriction of dietary protein may also slow decline of renal function.
Evaluation of NS is shown in Table 142-4.

Table 142-4 Evaluation of Nephrotic Syndrome

Asymptomatic Urinary Abnormalities
Proteinuria in the nonnephrotic range and/or hematuria unaccompanied by edema, reduced GFR, or hypertension can be due to multiple causes (Table 142-5).

Table 142-5 Glomerular Causes of Asymptomatic Urinary Abnormalities

BERGER’S DISEASE, IGA NEPHROPATHY   The most common cause of recurrent hematuria of glomerular origin; is most frequent in young men. Episodes of macroscropic hematuria are present with flulike symptoms, without skin rash, abdominal pain, or arthritis. Renal biopsy shows diffuse mesangial deposition of IgA, often with lesser amounts of IgG, nearly always by C3 and properdin but not by C1q or C4. Prognosis is variable; 50% develop ESRD within 25 years; men with hypertension and heavy proteinuria are at highest risk. Glucocorticoids and other immunosuppressive agents have not proved successful. A randomized clinical trial of fish oil supplementation suggested a modest therapeutic benefit. Rarely recurs in allografts.
CHRONIC GLOMERULONEPHRITIS   Characterized by persistent urinary abnormalities, slow progressive impairment of renal function, symmetrically contracted kidneys, moderate to heavy proteinuria, abnormal urinary sediment (especially RBC casts), and x-ray evidence of normal pyelocalyceal systems. The time to progression to ESRD is variable, hastened by uncontrolled hypertension and infections. Control of blood pressure is of paramount importance and is the most important factor influencing the pace of progression. While ACE inhibitors may be the most effective agents, additional agents should be added to ACE inhibitors if blood pressure is not optimally controlled with ACE inhibitors alone. Diuretics, non-dihydropyridine calcium antagonists, and b- adrenergic blockers have been successfully used in a variety of clinical settings.

Table 142-6 Serologic Findings in Selected Multisystem Diseases Causing Glomerular Disease


For a more detailed discussion, see Brady HR, O’Meara YM, Brenner BM: The Major Glomerulopathies, Chap. 274, p. 1580; and O’Meara YM, Brady HR, Brenner BM: Glomerulopathies Associated with Multisystem Diseases, Chap. 275, p. 1590, in HPIM-15.


3 comments on “142 GLOMERULAR DISEASES

  1. c) Doppler US and anticoagulation for renal vein thrombosis that pts with proteinuria are at risk for.—>Dont give Acei to patients with AKI—>UA is not consistent with UTI ___________________”Dream as if you will live forever, live as if you only have today”. Internal Medicine PGY-2.

  2. Acute kidney injury (acute renal failure) in minimal change disease and other forms of nephrotic syndrome Causes and diagnosis of membranous nephropathy Diagnostic approach to the patient with acute or chronic kidney disease Differential diagnosis and evaluation of glomerular disease Evaluation of isolated proteinuria in adults Lipid abnormalities in nephrotic syndrome Pathophysiology and treatment of edema in patients with the nephrotic syndrome Overview of heavy proteinuria and the nephrotic syndrome Renal vein thrombosis and hypercoagulable state in nephrotic syndrome Urinalysis in the diagnosis of renal disease Etiology, clinical features, and diagnosis of minimal change disease in adults Treatment of minimal change disease in adults Treatment of idiopathic membranous nephropathy The following organizations also provide reliable health information.

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