Minimal Change Disease I.
Clinical manifestations. Minimal change disease is responsible for idiopathic nephrotic syndrome in 15% of cases in adults and 75% of cases in children. The peak age at onset is 2-6 years. A recent history of viral upper respiratory infection is often present. The clinical presentation is usually that of the nephrotic syndrome. The blood pressure, GFR, and serum complement levels are usually normal. Urinalysis is not remarkable except for heavy proteinuria. In adults, this syndrome may be seen in association with lymphoma, particularly Hodgkin’s disease. II. Treatment and prognosis. The course is characterized by remissions and re-lapses. Corticosteroid therapy is usually effective, and the prognosis is good. A. Initial treatment in adults is with oral prednisone or prednosolone, 1-1.5 mg/kg/d (usually not to exceed 80 mg/d) in divided doses for 4 weeks. About 90% of patients will respond to this regimen with resolution of abnormal proteinuria. The dose of prednisone is then decreased to 0.9 mg/kg given as a single dose on alternate days for an additional 4 weeks. Treatment is usually continued in this ways for 4 weeks after remission, and the drug is then tapered and discontinued. The same regimen is used for treatment of relapses. B. Patients who do not respond to the above regimen can be treated with a longer course of steroid therapy or a 4- to 8-week trial of cyclophosphamide, 3mg/kg/d, or chlorambucil, 0.2 mg/kg/d. Focal Glomerulosclerosis I. Clinical manifestations. Focal glomerulosclerossis occurs in 15-20% of adults with idiopathic nephrotic syndrome. It occurs more frequently in males, with a mean age at onset of 20 years. The clinical presentation is similar to that of minimal change disease except that hypertension, hematuria, and progressive renal functional decline are more common. This disease is often confused with minimal change disease, and cases of treatment-resistant minimal change disease may actually be diagnosied later as focal glomeruloscierosis. This histologic lesion can also be seen with the nephropathies associated with analgesic abuse, ureteral reflux, heroin abuse, sickle cell disease, sarcoidosis, and some types of cancer. occasionally occurs with ascites and pleural effusions. Edema is usually “dependent,” with lower extremity edema at the end of the day and periorbital and finger edema upon awakening. D. Acute glomerulonephrities. Edema can occur with any form of acute glomerulonephritis. It is usually of mild to moderate degree. E. Idiopathic recurrent edema. This syndrome of unknown cause occurs chiefly in women and is characterized by recurrent edema, irritability and headaches. Edema may be cyclic or persistent and most often occurs in the lower extremities. F. Drugs. Edema may occur as a side effect of estrogen-containing drugs or vasodilator drugs such as minoxidil. G. Pregnancy. Preeclampsia-eclampsia is characterized by edema, hypertension and proteinuria. Some degree of lower extremity edema can be detected in most uncomplicated pregnancies as well. II. General treatment. Treatment of edema as such consists mainly of dietary sodium restriction and diuretic therapy. A. Dietary sodium restriction. In the USA, the average daily diet contains 3-6g of sodium. (For reference, 1 g of salt contains 17 meq of sodium, and there are about 44 meq of sodium in 1 g of sodium.) Dietary sodium restriction of 1-3 g/d is prescribed depending on the severity of the underlying disease. Diets containing less than 1 g of sodium may be prescribed but are extremely unpalatable. In patients receiving diuretic therapy and a salt-restricted diet, fluid restriction to 1500 mL/d may be necessary to prevent hyponatremia. B. Diuretics. Diuretics are useful for their natriuretic effect, with subsequent increased renal fractional excretion of salt and water. Diuretics are potent drugs and should be used with caution. Except in the case of acute pulmonary edema, diuresis should be done gradually, with daily weight losses of no more than 0.5-1 kg/d. Rapid diuresis or overdiuresis results in intravascular volume depletion and findings of weakness, dizziness, orthostatic hypotension and an elevated BUN and serum creatinine. 1. Carbonic anhydrase inhibitors. These drugs inhibit carbonic anhydrase and subsequently Na+/H+ exchange, primarily in the proximal tubule. They are weak natriuretic agents that result in excretion of an alkaline urine and mild metabolic acidosis. The main drug in this category is acetazolamide. An initial dose of 250-375 mg daily is given until a response is seen. The dosing interval is then changed to every other day. Acetazolamide may be used to alkalinize the urine in patents with uric acid nephrolithiasis. It is generally not useful in the treatment of edema.