Hyperkalemia Suppresses the Renal Adaptation to Chronic Respiratory Acidosis

VIGNETTES IN CLINICAL PATHOPHYSIOLOGY

Hyperkalemia Suppresses the Renal Adaptation to Chronic Respiratory Acidosis Reto Krapf, MD, and Martin G. Cogan, MD INDEX WORDS: Hyperkalemia; ammoniagenesis; respiratory acidosis.

T

HE RENAL RESPONSE to chronic respiratory acidosis involves an initial stimulation of ammoniagenesis and ammonium excretion and a sustained increase in proximal tubule bicarbonate reabsorption. The following case illustrates a reversible case of impaired renal response to chronic respiratory acidosis. CASE REPORT A 48-year-old Hispanic man was admitted for resection of a squamous cell cancer of the lung. He had been known to have moderate chronic renal insufficiency for about 3 years, with stable serum creatinine levels (265 I'mollL [-3 mg/dL)). On admission he had a hyperchloremic, hyperkalemic metabolic acidosis without hypercapnia and a positive urine anion gap (UNa + UK - U CI ) of 51 (Table 1). Creatinine clearance was 21 mLimin. The urine sediment showed three to five RBCs per high-power field and a few tubular cells but no cellular casts. Renal ultrasound revealed normal-sized kidneys without evidence of hydronephrosis. Medication on admission included trimethoprim/sulfamethoxazole, acetaminophen, and diphenylhydantoin, of which only the latter was continued for a seizure disorder attributed to alcohol abuse. The preoperative cortisol levels were normal, 11 ng/dL in the morning and 22 ng/dL shortly after noon. The plasma renin activity was 1.6 ng/ mLih (normal, 1 to 3.0) and the plasma aldosterone was 4 ng/ dL (normal, 4 to 20), when the serum potassium was 5.8 mmol/L. Therefore, a diagnosis of type IV, generalized distal renal tubular acidosis (RTA) was made. No further work-Up of the cause of the renal insufficiency was performed preoperatively. The patient underwent tumor removal with resection of the right middle and lower lobes. His postoperative course was complicated by sustained hypercapnia and acidemia in addition to persistent hyperkalemia (Fig 1; Table 1). He remained euvolemic and his BP (150/90) and pulse rate (80 beats/min) were stable. Throughout the preoperative and postoperative course the patient received parenteral nutrition. He was always euglycemic and ketones in urine and blood remained negative. After more than three days of hypercapnia (postoperative day 4), plasma total CO 2 did not increase, suggesting inadequate renal

From the Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco. Address reprint requests to Reto Krapf, MD, Department of Medicine, Insel University Hospital, CH-30JO Berne, Switzerland. © 1989 by the National Kidney Foundation, Inc. 0272-6386/89/1402-0012$3.00/0 158

bicarbonate generation in response to acidemia. For persistence of severe acidemia (pH 7.18), the patient was intubated and ventilated. Also on postoperative day 4 the patient began receiving kayexalate (25 g twice daily for one day, then 25g/d or as needed to keep serum potassium <4.5 mmol/L). As shown in Table 1 and Fig 1, the total CO 2 and pH increased subsequently until nearly perfect renal compensation of the respiratory acidosis was achieved. This response occurred despite persistence of low plasma renin activity (1.3 ng/mL/h) and plasma aldosterone (3 ng/dL, postoperative day 10) and stable serum creatinine levels.

Questions 1. Why were this patient's kidneys unable to respond appropriately to chronic respiratory acidosis (postoperative days 1 through 4)? 2. What might have been the mechanisms involved that allowed renal compensation beginning on postoperative day 5? DISCUSSION

The detailed renal response to chronic respiratory acidosis has not been characterized in humans, but animal studies in different species show that a sustained increase in Peo 2 stimulates ammoniagenesis and rapidly increases ammonium excretion. 1 Consequently, plasma bicarbonate increases and blood pH increases toward normal. The increase in ammonium excretion is transient and the high serum bicarbonate concentration in the chronic phase of respiratory acidosis is maintained by increased bicarbonate reabsorption in the proximal tubule. 2.3 In general, the renal response to respiratory acidosis is complete by the third day of increased Peo2' Potassium is also known to influence ammoniagenesis. Specifically, hyperkalemia decreases renal ammoniagenesis and ammonium excretion. 4 Plasma bicarbonate and pH decrease secondarily, as illustrated by the preoperative laboratory values in our patient with type IV, generalized distal RTA.5 Ammonium excretion was evaluated with the aid of the urine anion gap, which is defined as: (UNa + UK) - (U Cl). To maintain the electroneutrality of urine, the sum of cationic charges (NH4

American Journal of Kidney Diseases, Vol XIV, No 2 (August), 1989: pp 158-160

159

HYPERKALEMIA IN RESPIRATORY ACIDOSIS

Table 1.

Blood and Urine Parameters

Plasma

Arterial Blood

Cr K CI Na tC02 (mmoI/L) (mmoI/L) (mmoI/L) (mmoI/L) (mg/dL)

Preoperative Postoperative day

1 2 3 4 5 6 7 8 9 10

6.1

115

20

3.4

7.34

36

142 144 145 146 152 148 148 149 152 149

5.6 5.5 5.6 5.8 3.8 3.9 4.0 3.9 4.4 4.0

113 113 116 116 119 121 118 118 116 111

20 21 22 20 20 20 23 28 26 27

2.9 2.9 3.0 4.2 4.5 4.4 4.2 3.9 3.7 3.2

7.24 7.22 7.23 7.18 7.30 7.33 7.34 7.35 7.34 7.36

54 55 54 61 50 46 48 44 51 50

(mmel/I)

6

6

4

54

5~11

3

40

3 ~------~----------------~

UAG 30

40 30 20

(mmol) 20

10

10

30

30

(mmel/I) 25

25

1C0 2

20

P

60

20 ~------~--------~------~

C02

50

(mm Hg) 50

40 pH

60

~------~------------~

~I

7.40 7.30 7.20

40 7.40 7.30 7.20

o

2

3

4

5

6

7

8

9

10

POSTOPERATIVE DAYS

Fig 1. Serial determination of plasma potassium (K), urine anion gap (UAG), plasma bicarbonate (tC02), arterial carbon dioxide tension (PC02), and arterial pH. On the fourth postoperative day (dotted line) the patient was intubated and kayexalate administration was started.

Urine

Urine Anion Gap UC1 PC02 UK UNa (mmHg) (mmoIlL) (mmoI/L) (mmoI/L) (UNa + U0 - (Ud

138

+ K+ + Na +) must equal the sum of anionic charges (SO/- + pO/- + Cn. Changes in the (unmeasured) ammonium (NH4 +) excretion will therefore affect the urine anion gap: low ammonium excretion is associated with a positive urine

K

pH (U)

89

43

81

+51

80 44 70 74 113 51 74

34 38 24 14 8 11 14

77

+37 +41 +31 +13 +7 +4 +8

41 63 75 114 58 80

anion gap while a high ammonium excretion leads to a negative urine anion gap. The excreted NH4 + , of course, obligates the presence of cr, which increases the excretion of measured anions while leaving measured cations unchanged. Indeed, simultaneous determinations of urinary ammonium concentration and of the urine anion gap have established a good negative correlation between ammonium excretion and the urine anion gap.6 Evaluation of the urine anion gap has been shown to be clinically very valuable in the diagnosis of hyperchloremic metabolic acidosis. 6 If, for example, a hyperchloremic metabolic acidosis is due to diarrhea, renal ammoniagenesis, and ammonium excretion increase, causing the urine anion gap to become negative. In type IV, generalized distal RTA, however, the urine anion gap is positive because renal ammoniagenesis and urine ammonium excretion are suppressed (Table 1, preoperative values). The serial observations in this patient (Fig 1; Table 1) enable us to define the pertinent aspects with regard to acid-base regulation: (1) the kidneys were unable to generate bicarbonate appropriately despite marked hypercapnia for more than three days in this hyperkalemic patient with type IV, generalized distal RTA; (2) normalization of serum potassium induced a temporally related decrease in the urinary anion gap and therefore, presumably, urinary ammonium excretion which then allowed an increase in plasma bicarbonate to occur; and (3) this adaptation occurred despite a less severe degree of hypercapnia, persistently low aldosterone levels, and stable serum creatinine levels (postoperative days 4 through 8).

160

KRAPF AND COGAN

The decrease in the urine anion gap in response to correction of hyperkalemia on the sixth to eighth postoperative days can be presumed to reflect an increase in ammonium excretion. Urine ketones, which can interfere with this analysis , 6 were not present in this patient. An increase in ammonium excretion generates new plasma bicarbonate. In this patient, subsequent to the decrease in the urine anion gap, plasma bicarbonate increased by 6 to 7 mmollL over two days, representing near normal renal compensation for respiratory acido-

sis and allowing return of pH toward normal (Fig 1; Table 1). This case thus illustrates that concomitant hyperkalemia may prevent the renal adaptation to respiratory acidosis, probably by suppressing or attenuating the initial stimulation of ammonia production and ammonium excretion. Awareness of this phenomenon is clinically important because this case shows that correction of hyperkalemia can restore normal bicarbonatemic compensation and thus ameliorate acidemia in respiratory acidosis.

REFERENCES 1. Carter Nw, Seldin DW, Teng HC: Tissue and renal response to chronic respiratory acidosis. J Clin Invest 38:949960, 1959 2. Cogan MG: Chronic hypercapnia stimulates proximal bicarbonate reabsorption in the rat. J Clin Invest 74:1942-1947, 1984 3. Krapf R: Mechanisms of adaptation to chronic respiratory acidosis in the proximal tubule. J Clin Invest 83:890-896, 1989

4. Tannen RL: Relationship of renal ammonia production and potassium homeostasis. Kidney Int 11:453-456, 1977 5. Sebastian A, Schambelan M, Lindenfeld S, et al: Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninernic hypoaldosteronism. N Engl J Med 297:576583, 1977 6. Goldstein MB, Baer R, Richardson RMA, et al: The urine anion gap: A clinically useful index of ammonium excretion. Am J Med Sci 292: 198-202, 1986