View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 34 (1988), pp. 278—287 NEPHROLOGY FORUM Uremic acidosis Principal discussant: DAVID G. WARNOCK San Francisco Veterans Administration Medical center, San Francisco, california mg/dl; and glucose, 145 mg/dl. Urinalysis revealed a specific gravity of 1.010; pH 6.0; trace protein; occasional white blood cells; and no red Editors blood cells, casts, or crystals. A 12-hour urine collection disclosed 638 JORDAN J. COHEN mg of creatinine and a creatinine clearance of 13 mI/mm. The patient had dialysis twice via a subclavian catheter, and an JOHN T. HARRINGTON arteriovenous fistula was constructed. All antihypertensive medications JEROME P. KA55IRER were discontinued and the patient was discharged on a regimen of NIcoLAos E. MADIA5 furosemide, aluminum hydroxide, and allopurinol. Despite discontinuation of calcitriol and calcium carbonate, the patient's serum calcium remained above 10 mg/dl. The serum PTH level Managing Editor was 4200 dEq/ml when the serum calcium was 10.3 mg/dl. Some CHERYL J. ZU5MAN suppression of the serum PTH level was obtained (to 2400 pJEq/ml) when the serum calcium was raised to 11 mg/dl, but this decrease was followed by rebound of the PTH to the previous level. Subperiosteal University of Chicago Pritzker School of Medicine resorption was not seen on radiographs of the hands, but a sonogram of the neck revealed 2 large (2 x 1.5 cm), solid, cystic parathyroid masses. and A subtotal parathyroidectomy (3.5 glands) therefore was performed. At Tufts University School of Medicine the time of surgery, arterial blood gas measurements revealed a pH of 7.38, PaCO2 of 35 mm Hg, and a plasma bicarbonate of 20.4 mEq/liter. Since surgery, the serum calcium level has remained below 10 mg/dl, and renal function has stabilized with a creatinine clearance of 18 mI/mm. The total co2 stabilized at 22 mEq/liter while the patient was taking furosemide, aluminum hydroxide, and allopurinol. Repeated Case presentation measurement of the PTH level was 800 lEq/ml. The most recent evaluation revealed a creatinine clearance of 14 ml/min; sodium, 144 A 62-year-old male with a 22-year history of albuminuria and pro- mEg/liter; potassium, 5.2 mEg/liter; chloride, 107 mEg/liter; carbon gressive renal insufficiency was admitted to the hospital for placement dioxide, 22 mEg/liter; anion gap, 15 mEg/liter; calcium, 9.0 mg/dl; of a vascular access preparatory to dialysis. The left kidney had been phosphate, 4.6 mg/dl; BUN, 74 mg/dl; and creatinine, 5.9 mg/dl. found to be hypoplastic when proteinuria was first noted. The causes of his renal failure were presumed to be chronic glomerulonephritis and hypertension. The patient complained of nocturnal pruritis at the time of admission but no other symptoms. Discussion The medical history was otherwise unremarkable except for several episodes of acute gout. Medications being taken prior to admission Da. DAVtD G. WARNOCK (Chief, Nephrology Section, San included minoxidil, furosemide, metoprolol, allopurinol, calcitriol, alu- Francisco Veterans Administration Medical Center, and Pro- minum hydroxide, and calcium carbonate. Physical examination revealed a blood pressure of 96/60 mm Hg; fessor of Medicine and Pharmacology, University of Califor- pulse, 98 beats/mm; respiratory rate, 20/mm; and oral temperature, nia, San Francisco, California): The patient presented today 94°F. The sclerae were pale and anicteric, and the pupils were equally has clearly established chronic renal insufficiency and surgically reactive. The fundi revealed arteriovenous nicking but no hemorrhages proved diffuse hyperparathyroidism. Although the exact cause or exudates. The chest was clear, cardiac examination revealed an S4 gallop but no murmurs or rubs. The jugular venous pressure was normal of renal insufficiency has not been documented, it is notable and peripheral edema was not present. The abdomen revealed nothat his course has stabilized since he had a subtotal parathy- organomegaly, tenderness, or masses. Guaiac test of the stool wasroidectomy 1.5 years ago. At the time of surgery, determina- negative, and the neurologic examination was unremarkable. Several tions of arterial blood gases documented a mild metabolic excoriated areas were present on the arms and back. Laboratory studies showed a hematocrit of 30.5%; white blood cell acidosis with appropriate respiratory adaptation, despite ad- count, 8900 mm3 with a normal differential; platelet count, 177,000 vanced renal insufficiency with a creatinine clearance of 13 mm3; BUN, 108 mg/dl; creatinine, 6.8 mg/dl; sodium, 141 mEq/liter; ml/min. For the purposes of our discussion of uremic acidosis, potassium, 3.0 mEq/liter; chloride, 106 mEq/liter; carbon dioxide, 24the questions we need to address include: (1) What is uremic mEg/liter; anion gap, 11 mEg/liter; calcium, 11.0 mg/dl; phosphate, 4,8acidosis? (2) What are the pathophysiologic processes that cause acidosis to develop in the setting of chronic renal insuf- Presentation of the Forum is made possible by grants from Pfizer;ficiency? (3) What are the renal and extrarenal adaptations to Incorporated; Merck Sharp & Dohme; Sandoz, Incorporated; and E. R. chronic renal insufficiency that defend acid-base homeostasis? Squibb & Sons, Incorporated. The case presentation is instructive, particularly if we ask why © 1988 by the International Society of Nephrology acidosis was so mild in this patient. 278 Nephrology Forum: Uremic acidosis 279 Clinical features of uremnic acidosis ganic-acid anions that have not been completely oxidized) with their daily production, just as they are not able to excrete the Chronic progressive renal disease usually results in somedaily endogenous acid load [2]; the retention of these acid degree of systemic acidosis when the glomerular filtration rateanions and hydrogen ions generates the so-called anion-gap is reduced to 25 mllmin or less [1]. Metabolic acid productionmetabolic acidosis characteristic of uremia [10]. generally is not increased in patients with chronic renal insuf- ficiency [2]; therefore the development of acidosis reflects an Patho genesis of uremic acidosis impairment in the renal acidification mechanisms [3] as well as If serum bicarbonate levels in uremic patients are raised some limitations in the renal homeostatic responses to acidosis.towards normal, the urine pH rises and the already reduced Reduced bicarbonate reabsorption [4] and impaired ammoniarenal net acid excretion falls further. At times, overt production [5] are thought to be the underlying disturbances inbicarbonaturia occurs [4]. In the absence of bicarbonate sup- the renal acidification process characteristic of uremic acidosis.plementation, however, the urine pH usually is less than 5.4. Hyperchloremic metabolic acidosis can develop early in theThis finding suggests that the ability of the distal nephron to course of renal disease but the acidosis "converts" to anacidify the urine (that is, maintain a normal pH gradient) is anion-gap form when the glomerular filtration rate falls below 20intact in chronic renal failure. Furthermore, the capacity of the mLfmin [6]. Hyperchloremic metabolic acidosis, well describeddistal nephron's proton secretory systems to respond to an in patients with tubulointerstitial disease [3, 6], also has beenincrease in buffer delivery (such as that following administra- seen in patients with primary glomerular disease [7]. One of thetion of a phosphate load) is also well maintained (reviewed in classic studies analyzing metabolic acidosis in patients withRef. 11). There is an important distinction, however, between chronic renal insufficiency was done here at the New Englandsimple acidification of the urine and renal net acid excretion Medical Center. In a retrospective analysis of 138 ambulatory(defined as the sum of ammonium excretion and titratable acid patients with stable renal function, Widmer, Gerhardt, Har-minus the excretion of bicarbonate). Unlike patients with distal rington, and Cohen examined the relationships between serumrenal tubular acidosis, in whom the primary acidification defect electrolytes and renal function, as assessed by serum creatinineresides in the distal proton secretory mechanisms, patients with measurements [7]. The study excluded patients with vomiting,chronic renal insufficiency appear to have impaired renal net diarrhea, or volume depletion and those who had receivedacid excretion because of inadequate or inappropriate delivery diuretics, alkali, steroids, potassium-exchange resins, or antac-of buffer to the distal nephron acidification sites. I will now ids. Patients also were excluded who had multiple myeloma, oraddress the defects in the renal excretion of ammonium and who had undergone adrenalectomy or parathyroidectomy. Ob-reabsorption of bicarbonate, which are the central factors viously these patients were highly selected; many of the pa-responsible for the development of acidosis in chronic renal tients in a typical renal clinic would not meet these criteria, butinsufficiency. the goal of the investigators was to determine the relationship Ammonium excretion. A major factor in the limitation of between the various serum electrolytes and renal function in therenal net acid excretion in chronic renal insufficiency is inade- steady state. The final analysis included 41 patients who werequate renal ammonium excretion. Although there is an adaptive 16 to 73 years old. There were 25 men