Renal Tubular Acidosis in a Patient with Recurrent Metabolic Alkalosis

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Renal

Tubular

Acidosis

in a Patient

with

Recurrent

Metabolic

Alkalosis

Leonard

C.

Hymes,

MD, and

Barry

L. Warshaw,

MD

From the Department of Pediatrics, Division of Nephrology, Emory University School of Medicine, Atlanta

ABSTRACT. A 7-month-old infant with failure to thrive

and recurrent episodes of vomiting and metabolic alka-losis was evaluated. Urine pH, serum bicarbonate, and

urine Pco2-blood Pco2 studies were consistent with the diagnosis of distal renal tubular acidosis (RTA-type I).

Analysis of serum potassium and chloride levels during

periods of alkalosis and acidosis revealed that potassium

depletion and hypochloremic volume contraction served

to maintain the alkalotic state despite the presence of an underlying chronic acidosis. This case represents an un-usual presentation forrenal tubular acidosis and suggests that, under certain conditins, renal tubular acidosis may predispose to the maintenance of a metabolic alkalosis.

Pediatrics 1983;72:207-210; renal tubular acidosis,

rneta-bolic alkalosis.

Renal tubular acidosis (RTA) in childhood is characterized by impaired urinary acidification, hy-perchloremic acidosis, and failure to thnive.’3

Ad-ditionally, other metabolic disturbances and their

sequelae may be associated with RTA. These in-dude Fanconi syndrome, osteomalacia,

nephnocal-cinosis, hypokalemia, and hypemaldosteronism.3

Acute metabolic alkalosis, however, is a rare and unexpected presentation for this clinical syn-drome.4’5 This report describes an infant with

pni-many distal RTA (type I) who was seen with recur-rent episodes of vomiting and severe metabolic alkalosis. Analysis of urine bicarbonate excretions,

urine pH, and serum potassium and chloride con-centrations during alkalosis and acidosis suggests that, under certain conditions, RTA may predispose

to the maintenance of a metabolic alkalosis.

Received for publication Aug 30, 1982; accepted Nov 4, 1982. Reprint requests to (L.C.H.) Emory University School of Med-icine, Department of Pediatrics, Division of Nephrology, 2040 Ridgewood Dr, NE, Atlanta, GA 30322.

PEDIATRICS (ISSN 0031 4005). Copyright © 1983 by the American Academy of Pediatrics.

CASE REPORT

The patient, a 7-month-old male infant, birth weight 3.7 kg, was admitted to Grady Memorial Hospital follow-ing a four-day history of persistent vomiting. Two

epi-sodes of vomiting and severe metabolic alkalosis (serum bicarbonate >40 mEqJL) had occurred previously at 2 and at 5 months of age. In both instances, alkalosis resolved with intravenous fluid therapy received at

an-other hospital. The patient’s current diet consisted of

Isomil infant formula (Ross Laboratories). Previous

for-mulas included Similac (Ross Laboratories) and

Proges-timil (Mead Johnson), with episodes of vomiting and

alkalosis occurring with each. The remainder of the his-tory was negative for diarrhea, edema, or the use of diuretics.

On physical examination, the infant’s weight was 6.1

kg and length 64 cm, both less than the fifth percentile for age. Blood pressure was 70/44 mm Hg. Mucous mem-branes were dry, eyes were sunken, and tenting of the

skin was present. The remainder of the examination was

unremarkable. Laboratory values revealed: serum so-dium, 127 mEcijL; potassium, 2.5 mEqJL; chloride, 69

mEqJL; and bicarbonate, 38 mEqJL. Urine electrolytes

revealed: sodium, 19 mEqJL; chloride, 15 mEqJL; and potassium, 49 mEciJL. Urine pH was 6.1. The complete blood count (CBC) was normal, serum creatinine was 0.9 mg/dL, and BUN was 17 mg/dL. Peripheralplasma renin

activity was elevated to 77.49 ng/mL/h (normal: 0 to 9 ng/mL/h), and serum aldosterone was >90 ng/mL

(nor-mal: 2 to 36 ng/mL). Urine culture was negative, and no abnormal urinary excretion of amino acids or reducing

substances was detected. Roentgenographic studies, in-cluding upper gastrointestinal tract series, barium enema, and intravenous pyelogram were normal.

The patient was treated with intravenous sodium and

potassium chloride. Dehydration, alkalosis, and

hypoka-lemia rapidly resolved and serum creatinine decreased from 0.9 to 0.4 mg/dL with a corresponding decrease in

BUN from 17 to 7 mg/dL. Creatinine clearance,

calcu-lated from a 24-hour urine collection, was 90 mL/min/

1.73 m’.

Unexpectedly, a persistent hyperchioremic metabolic

alkalosis developed after the third day of hospitalization:

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9 8 7 6 5 I 0. LU z

13 14 15 16 17 18 19 20

208

RENAL TUBULAR ACIDOSIS AND RECURRENT ALKALOSIS

SERUM BICARBONATE mEq/L

Fig 1. Urine pH v serum bicarbonate levels during

aci-dosis.

114 mEciJL; serum bicarbonate, 14 to 19 mEaJL; and

anion gap, 9to 15. Urine pH ranged from 6.3 to 8.1 (Fig 1). Alkali supplements were started and eventually 5 mEqJkg/d of oral sodium bicarbonate was required for sustained correction of acidosis. With this therapy, plasma renin activity decreased from the initial level of 77.49 ng/mL/h to 1.11 ng/mL/h and serum potassium

remained above 4.0 mEqJL.

The patient experienced accelerated growth velocity with sustained alkali supplements, attaining a height and weight at the 50th percentile for age by the first year of life (height 74 cm, weight 11.1 kg). Two further episodes of vomiting and alkalosis occurred at 13 months and at 17 months of age. Hyperchloremic acidosis again devel-oped when the patient was rehydrated, and sodium bicar-bonate supplements were resumed after each episode. At 29 months of age, the child continues to grow normally with sustained alkali therapy (height 90 cm, weight 14.0 kg), without further episodes of vomiting and alkalosis.

METHODS

AND SPECIAL

STUDIES

In order to delineate possible mechanisms to

account for the progression of metabolic alkalosis to acidosis, the following data were evaluated during

the patient’s hospital course: (1) Assessment of distal tubular acid excretion was obtained by ana-lyzing the urine pH over a range of serum

bicarbon-ate levels and by evaluating the urine PCO2-blood

PC02 gradient, as described by Halpenin et al.6 (2)

Assessment of renal acidification in response to alkalosis, acidosis, hypokalemia, and

hypochlo-remic dehydration was obtained by evaluating

si-multaneous serum potassium, chloride, and

bicam-bonate concentrations; urine PH; and the percent

of filtered bicarbonate excreted in the urine.

Urine for PC02 and pH were freshly voided,

bagged specimens collected under oil. Urine pH was measured by pH meter and urine PC02 by blood gas autoanalyzer. Urine bicarbonate concentrations were calculated from urine pH and urine Pco2 using the Henderson-Hasselbalch equation. The percent

of filtered bicarbonate excreted was derived from the following equation: % = [(urine HCO3 x serum

cmeatinine)/(serum HCO3 x urine creatinine)] x

100. For evaluation of the urine PCO2-blood PC02

difference, capillary blood pH and PC02 were ob-tamed by blood gas autoanalyzer and compared with simultaneous urine pH and PC02 values when urine pH was greaten than blood pH (sodium bicar-bonate loading was found to be unnecessary in

achieving this requirement).

Serum and urine creatinine and electrolytes were obtained by standard clinical laboratory technique.

Plasma renin activity was measured by radioim-munoassay of angiotensin I generated at 37#{176}Cfor

one hour.7 Serum aldosterone was measured by 125I madioimmunoassay.8

RESULTS

Simultaneous urine pH and serum bicarbonate values are depicted in Fig 1. The lowest urine pH recorded during acidosis was 6.3 corresponding to

a serum bicarbonate level of 14 mEciJL. Evaluation

of the urine-blood Pco2 difference was also

consist-ent with impaired distal nephron excretion of

hy-drogen ions: urine pH, 8.1; urine PC02, 26; blood pH, 7.38; blood PC02 was 33; urine PCO2-blood PC02, -7 (normal: >20).6

Simultaneous serum potassium, chloride, and

bi-carbonate concentrations, and urine pH values are

shown in Fig 2. During alkalosis, hypokalemia, and

hypochioremia, the initial urine pH was 6.1; as

serum potassium and chloride concentrations

in-creased, urine pH became more alkaline and serum

bicarbonate progressively decreased to subnormal

levels. Correspondingly, the percent of excretion of filtered bicarbonate also increased from 0.05% dur-ing alkalosis to 4% with development of metabolic acidosis and normalization of serum potassium and chloride concentrations (Table).

DISCUSSION

The pathophysiology of distal RTA (type I) is

characterized by a reduced rate of renal acid

excre-tion relative to the mate of endogenous acid produc-tion.9”#{176}In contrast to adults with this disorder,

distal RTA of childhood may also be associated with renal tubular bicarbonate wasting.3’5’9 The findings in this patient were consistent with the

diagnosis of distal RTA as evidenced by a urine pH

>5.5,10 and fractional excretion of filtered

bicanbon-ate of 4% during acidosis.3’9 The reduced urine Pco2-blood PC02 gradient further supports the

in-ability of the distal tubule to secrete hydrogen ions.

Under normal circumstances hydrogen ions

se-creted into the distal nephmon will combine with

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Fr -

-sium was 2.0 mEciJL, chloride 77 mEqJL, and total

CO2 content 46 mEcijL. After six days of potassium chloride supplementation, total CO2 content de-creased to 12 mEJL.

The development of severe metabolic alkalosis in children with RTA appears related to the patho-physiologic effects of vomiting, extracellulan vol-ume contraction, and hypokalemia. Gastric losses of fluid, hydrochloric acid, potassium, and sodium chloride can generate an alkalosis associated with volume depletion and activation of the renin-angi-otensin-aldosterone system.” Under these condi-tions, hypokalemia is aggravated and maintained by urinary losses of potassium mediated by miner-alocorticoid excess.

In this report, the patient’s urine pH was rela-tively acidic (6.1) and bicarbonate excretion was minimal during the period of alkalosis,

hypokale-40 mia, and hypochloremic dehydration. These

find-%%% ings convey the picture of “alkalosis equilibrium”

% 35 as described by Seldin and Rector.’2 According to

30 this model, a metabolic alkalosis is generated by

a

25 gastric losses of hydrogen chloride and maintained by potassium deficiency and mineralocorticoid

ex-20 cess induced by hypochloremic volume contraction. 15 Evidence suggests that potassium depletion and

, I , aldosterone augment bicarbonate reabsorption in

2.0 3.0 4.0 5.0 6.0 the proximal renal tubule and enhance hydrogen

ion excretion in the distal nephron.”2 Correspond-ingly, urine pH is relatively low and contains neg-ligible amounts of bicarbonate. Thus, a metabolic

alkalosis is generated by gastric losses of hydrogen

40 ions and maintained by the response of the renal

35 - tubule to hypokalemia and volume contraction.

I- As demonstrated in this report, the patient’s 30 urine pH and bicarbonate excretion increased with

25 correction of potassium deficits and expansion of

20 extracellular volume. Eventually, hyperchloremic

15 acidosis evolved, with findings consistent with

dis-__________________ tal RTA of childhood, ie, diminished hydrogen ion

excretion and bicarbonatunia. This analysis

sug-gests that potassium depletion and volume

contrac-tion served to maintain the metabolic alkalosis, despite the presence of an underlying chronic

aci-dosis due to impaired distal nephron acid excretion

and urinary bicarbonate wasting.

9

8

7

6

9

8

7

6

I

0. LU z

SERUM POTASSIUM mEq/L

D--CS.funl CMoiile vs Umis pH .-#{149}SiiumChotide vs Simm BabOAMe

70 0 90 100 110

SERUM CHLORIDE mEq/L

Fig 2. Serum potassium and chloride concentrations v

urine pH and serum bicarbonate levels during alkalosis and acidosis.

excess bicarbonate present in alkaline urine to gen-emate carbonic acid, which, in turn, disassociates to

form CO2.6”#{176}

Severe alkalosis associated with RTA has been previously reported. Houston et al4 described a 4#{189}-year-old child with proximal RTA (type II) with

hypochloremia, hypokalemia, and metabolic alka-losis despite a low proximal renal tubular threshold

for bicarbonate. Alkalosis was corrected when salt

losses were balanced by large dietary supplements. In a report by McShemry,5 distal RTA in a 4-month-old infant was initially misdiagnosed as nephno-genic diabetes insipidus and treated with a pheno-thiazine-demivative diuretic. Within several weeks vomiting and dehydration developed. Serum

potas-o--.oS,rum Potassium vs. Un,,. pH

.-Sum Potassium v Stum Bicaibonats

TABLE. Percent of Excretion of Filtered Bicarbonate During Alkalosis and Acidosis*

Serum Urine % HCO3

Excreted

HCO3 .

Potassium .

Chloride . .

Creatmme pH Pco2 HCO3 . .

Creatinine

(m&iJL) (m&iJL) (mEqJL) (mg/dL) (mEqJL) (mg/dL)

Alkalosis 38 2.5 69 0.9 6.1 52 1.6 75 0.05

Acidosis 19 5.1 109 0.4 8.1 26 78.0 37 4.00

* Percent of filtered bicarbonate is derived as follows: % = [(urine HCO3 x serum creatinine)/(serum HCO3 x urine

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210

RENAL

TUBULAR ACIDOSIS AND RECURRENT ALKALOSIS

Other causes of hypochloremic, hypokalemic, and metabolic alkalosis appear unlikely in this patient. It is improbable that a chloride-deficient diet was

responsible insofar as episodes of alkalosis occurred with three different infant formulas (Similac, Pro-gestimil, and Isomil). Bartter’s syndrome was also

considered, but this diagnosis was eliminated when

serum potassium concentrations normalized and

plasma renin activity was effectively suppressed with sodium bicarbonate and volume expansion.13 Also, the diagnosis of Liddle syndrome (pseudoal-dosteronism) was excluded, given the findings of hypemreninemia, elevated level of serum aldoster-one, and normal blood pressure.’4

More than likely, RTA predisposed this patient

to metabolic alkalosis. Gastrointestinal symptoms frequently occur with RTA,15’16 and chronic acidosis per se may have been the cause of recurrent

vom-iting. Furthermore, both distal and proximal RTA

are associated with polyunia,’5”6 increased aldoster-one secretion, hyperkaliuria, and intracellular po-tassium depletion.3”6’17 Because of this

predisposi-tion for volume contraction and hypokalemia,

chil-dren with these types of RTA are at risk for

gen-erating and maintaining a metabolic alkalosis. An underlying RTA should be considered in patients with metabolic alkalosis who develop acidosis

dun-ing treatment.

REFERENCES

1. Nash MA, Torrado AD, Greifer I, et al: Renal tubular acidosis in infants and children. J Pediatr 1972;80:738

2. Chan JCM: Acid-base and mineral disorders in children: A review.

mt

j Pediatr Nephrol 1980;1:54

3. McSherry E: Disorders of acid-base equilibrium. Pediatr Ann 1981;10:302

4. Houston IA, Boichis H, Edelmann CM: Fanconi syndrome with renal sodium wasting and metabolic alkalosis. Am J Med 1968;44:638

5. McSherry E: Renal tubular acidoses in childhood. Kidney

Int 1981;20:799

6. Halperin ML, Goldstein MB, Haig A, et al: Studies in the pathogenesis of type I (distal) renal tabular acidosis as revealed by the urinary Pco2 tensions. J Clin Invest

1979;53:669

7. Haber E, Koerner T, Page LB, et al: Application of a radioimmunoassay for angiotensin for the physiologic meas-urement of plasma renin activity in normal human subjects.

J Gun Endocrinol Metab 1969;29:1349

8. Ogihara T, linuma K, Nishi K, et al: A nonchromatographic nonextraction radioimmunoassay for serum aldosterone. J Clin Endocrinol Metab 1977;45:726

9. McSherry E, Morris RC: Attainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis. J Gun Invest 1978;61:509 10. Rector FC, Cogan MG: The renal acidoses. Hosp Pract

1980;15:99

11. Cogan MG, Rector FC, Seldin DW: Acid-base disorders, in Brenner BM, Rector FC (eds): The Kidney. Philadelphia, WB Saunders Co, 1981 p 885

12. eldin DW, Rector FC: The generation and maintenance of mettbo1ic alkalosi#{176}.Kidney

mt

1972;1:306

13. Schwartz H, Cornfield D: Bartter’s syndrome: Clinical study of its treatment with salt loading and propranolol. Clin Nephrol 1974;4:45

14. Aarshog D, Sota KF, Thorsen T, et al: Hypertension and hypokalemic alkalosis associated with underproduction of aldosterone. Pediatrics 1970;39:884

15. Hirschman GH, Rao OD, Oyemade 0: Renal tubular aci-dosis: Practical guides to diagnosis and treatment. Clin Pediatr 1976;15:645

16. Chan JCM: Acid-base, calcium, potassium and aldosterone metabolism in renal tubular acidosis. Nephron 1979;23:152 17. Sebastian A, Morris RC: Renal tubular acidosis. Clin

Ne-phrol 1973;7:216

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1983;72;207

Pediatrics

Leonard C. Hymes and Barry L. Warshaw

Renal Tubular Acidosis in a Patient with Recurrent Metabolic Alkalosis

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Leonard C. Hymes and Barry L. Warshaw

Renal Tubular Acidosis in a Patient with Recurrent Metabolic Alkalosis

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Figure

Fig 1.UrinepHv serumbicarbonatelevelsduringaci-dosis.

Fig 1.UrinepHv

serumbicarbonatelevelsduringaci-dosis. p.2
TABLE.Percentof Excretionof FilteredBicarbonateDuringAlkalosisandAcidosis*
TABLE.Percentof Excretionof FilteredBicarbonateDuringAlkalosisandAcidosis* p.3
Fig 2.SerumurinepotassiumandchlorideconcentrationsvpHandserumbicarbonatelevelsduringalkalosisandacidosis.

Fig 2.SerumurinepotassiumandchlorideconcentrationsvpHandserumbicarbonatelevelsduringalkalosisandacidosis.

p.3

References