View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 3 (1973), p. 251—257 Short stature, hyperkalemia and acidosis: A defect in renal transport of potassium ADRIAN SPITZER and CHESTER M. EDELMANN JR with LEE D. GOLDBERG and PHELIP H. HENNEMAN Departments of Pediatrics and Medicine and The Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, New York Short stature, hyperkalemia, and acidosis: A defect in renal jusqu'à des valeurs normales. Pendant une charge en bicarbonate transport of potassium. An eleven-year-old boy presented with les debits d'excretion du potassium dans les urines ont été short stature, hyperkalemia, and metabolic acidosis. No endo- nettement inferieurs a ceux obtenus ehez des sujets témoins. Ii crine cause for a short stature could be demonstrated. Renal apparait donc que le malade a une anomalie primitive de l'ex- function, as assessed by inulin and PAH clearances, concen- crétion de potassium. L'hyperkaliémie qui en est la consequence trating and diluting capacity, and ability to acidify the urine and a déterminé une perte de bicarbonate dans les urines et une to excrete net acid, was normal. No defect was detected in adrenal acidose systémique. La correction de l'acidose et de l'hyper- secretion of, or renal responsiveness to, aldosterone. A low renal kaliémie par l'administration permanente de Chlorothiazide et threshold for bicarbonate was documented which apparently de bicarbonate de sodium a eu pour résultat une reprise de Ia explained the acidosis. However, correction of the acidosis by croissance normale. administration of sodium bicarbonate did not influence the hyperkalemia, making it unlikely that an abnormality in bicar- bonate reabsorption was the primary defect. Chlorothiazide A relationship between renal tubular transport of po- induced a fall in serum potassium and a rise in serum bicarbonate tassium and bicarbonate has been documented in both to normal levels. During bicarbonate loading the rates of ex- animal and human experiments. Acute and chronic ad- cretion of potassium in urine were consistently below those ob- ministration of potassium chloride has been shown to cause served in control subjects. It appeared, therefore, that the patient had a primary abnormality in potassium excretion. The resulting alkalinization of the urine, with urinary loss of bicarbonate, hyperkalemia caused urinary loss of bicarbonate and systemic and a consequent fall in the concentration of bicarbonate in acidosis. Correction of both the acidosis and hyperkalemia by plasma. Despite this metabolic acidosis, the urine remains chronic administration of chlorothiazide and sodium bicarbonate alkaline. These findings are considered to account in part has resulted in resumption of normal growth. for the acidosis of chronic renal insufficiency. There is only Retard de croissance, hyperkalléme et acidose: Un deficit du one previous report [1], however, of a patient in whom transport renal dii potassium. Un enfant de 11 ans avait un retard hyperkalemia, causative of acidosis, was not the result of de croissance, une hyperkaliémie et une acidose métabolique. decreased glomerular filtration rate, but rather of a primary Aucune cause endocrine du retard de croissance n'a étb trouvée. La fonction rénale, estimée par les clearances de l'inuline et du renal defect in the transport of potassium. The present re- PAH, Ia capacité de concentration et de dilution et Ia capacité port describes an 11-year-old boy who presented with short d'acidifier l'urine, était normales. Aucun deficit de Ia secretion stature and was found to have hyperkalemia and proximal d'aldostérone ou de Ia réponse rénale a l'aldostérone n'a été renal tubular acidosis. A defect in renal transport of potas- mis en evidence. Un seuil renal bas des bicarbonates a été dé- sium at the level of the distal tubule was demonstrated and couvert, qui explique apparemment l'acidose. Cependant Ia correction de l'acidose par l'administration de bicarbonate de was considered to be causative of the acidosis. Therapy with sodium n'a pas influence l'hyperkaliémie, ce qui rend peu pro- chlorothiazide and sodium bicarbonate corrected the hyper- bable que le deficit de la reabsorption de bicarbonate soit la kalemia and acidosis and resulted in "catch-up" growth. cause de l'ensemble. Le Chlorothiazide a determine une baisse de Ia kaliéme et unc augmentation du bicarbonate plasmatique Clinical description Received for publication June 21, 1972; accepted in revised form November 27, 1972. M. C., an 11-year-old white boy, was admitted to the ©1973,by the International Society of Nephrology. Hospital of the Albert Einstein College of Medicine on 251 252 Spitzer et al November 1!, 1968, for evaluation of short stature. The 0.051 - 0 0 patient was the product of a 31 week uncomplicated ges- - tation. At birth his length was 47 cm and his weight 2.5 kg. 0.045 a 0a a His failure to grow was first noticed by his parents at the 0.039- 0 a age of 5 years. The past history included herniorrhaphies in a a 1958, scarlet fever in 1965, and two fractures of the clavicle. 0.033- a a a A heart murmer was noted at 22 months of age. There was 0 0 0.027 a no history of episodes of muscular weakness. a S • The father is 178 cm tall and the mother 161 cm. There O 0.021 0 • C) 0 are four siblings in good health and of normal height. All 0 0.015 have normal levels of potassium and bicarbonate in serum. n 0• C) The patient was first investigated' for his failure to S O0.009 S Normal thrive at the age of ten. X-rays of the skull and an intra- S o 5controls venous urogram were normal. Serum potassium was found 0.003 • • MC. I I I I I I I to be 7.3 mhq/liter. The child was able to acidify (pH 5) 0.040.12 0.20 0.28 0.36 0.44 0.52 0.60 0.68 0.76 0.84 and to concentrate (sp. gr. 1.025) the urine. The electro- Uucor V, mmoles/1 00 ml GFR cardiogram revealed peaked T-waves, mainly in leads I and II. Urinary excretion of 17-ketosteroids was 2.2 mg/24 hr. Fig. 1. Relationship between urinary excretion of bicarbonate and Serum growth hormone was 2 jig/ml after an overnight the clearance of potassium during intravenous infusion of sodium bicarbonate. fast. Physical examination performed on admission to this hospital revealed an alert boy. Height (122.8 cm) and weight amount received by the patient at the time threshold was (23.7 kg) were both below the third percentile for age, and reached was 160 ml, or less than 1 per cent of body weight. would be average at age 71/2 years. The only other abnormal This minimizes the possibility that the threshold for finding was a grade 3/6 systolic murmur heard maximally bicarbonate was artificially depressed by extracellular at the upper left sternal border, which was interpreted as volume expansion. functional. Blood pressure was 110/70 mm Hg. The excretion of potassium during the bicarbonate in- X-rays of the chest, skull and abdomen were normal and fusion test increased from 0.028 mEq/100 ml glomerular f ii- epiphyseal maturation was that of a 7-year-old boy. trate, at a bicarbonate excretion rate of 0.02 mmoles/l00 ml Initial laboratory data included blood hematocrit 36%, glomerular filtrate, to 0.1 mhq, at a bicarbonate excretion hemoglobin 12 g/100 ml, WBC 8,800 per c. mm with a rate of 0.24. In normal adult subjects studied under similar normal differential count, reticulocyte count 2.8%, erytho- conditions of volume expansion, the excretion of potassium cyte sedimentation rate 18 mm at one hr. at comparable rates of bicarbonate excretion was con- Serum chemistries were Na 142, K 7.7 and Cl 114 mhq/ sistently greater, especially at low rates of bicarbonate liter, tCO216 mmoles/liter; Ca 9.5, P 5.2, BUN 12, creati- excretion when the difference was at least threefold. The nine 0.6, glucose 86 mg/100 ml; total protein 7, albumin relationship between the clearance of potassium and the 4 g/l00 ml; serum cholesterol 190, total bilirubin 0.4 mg/ excretion of bicarbonate is shown in Fig. 1. 100 ml; SOOT 68 and SOPT 16 SFU, alkaline phosphatase Indices of thyroid function were normal: serum thyroxine 16 KAU, LDH 220 U and CPK 6 BMU. Subsequent SOOT by column chromatography 3.9 jig/100 ml, T3 uptake 23 determinations were normal. percent, and 24-hour radio-iodine uptake 32 percent. Urinalysis revealed a pH of 5, a specific gravity of 1.025, Twenty-four hour excretion of 17-ketogenic steroids was and no protein, glucose, or ketone bodies. The sediment 5 mg under control conditions, increased to 17.7 mg follow- was normal. Absence of generalized renal disease was ing administration of metyrapone (0.5 g every 6 hr for further documented by normal inulin and PAH clearances, 2 days) and to 12 mg following administration of a single urinary concentration and dilution, and urinary acidification intramuscular dose of 40 U of ACTH gel. Fasting plasma and excretion of titratable acid and ammonium. A titration cortisol level was 8 jig/l00 ml. This value rose to 25 jig study revealed a renal threshold for bicarbonate of 18 within 4 hr after intravenous administration of 5 U of mmoles/liter, which was consistent with spontaneous serum ACTH. Twenty-four hour excretion of aldosterone was levels usually encountered in the patient.