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RENAL TUBULAR ACIDOSIS
1364 RENAL TUBULAR ACIDOSIS SIR,—I was interested to read the papers of Dr. Richards and his colleagues (Nov. 11, p. 994) and Dr. Richards and Professor Wrong (Nov. 11, p. 998) on this subject. The statement of Dr. Richards and Professor Wrong that their case " is the third family in which inheritance of renal tubular acidosis as an autosomal mendelian dominant seems thoroughly established, the others being those described by Pitts, Randall, and colleagues and by Gyory and Edwards " is surprising. I have described, in a family study of 27 cases, 18 affected members with renal tubular acidosis (R.T.A.).1-5 11 of the 18 affected cases were females, which supports the contention that there is greater expressivity in females with R.T.A.
SIR,—We read with interest that the family reported by Dr. Richards and Professor Wrong was the third such family to appear in the literature with clearly established
dominantly inherited distal renal tubular acidosis. We have investigated the following pedigree demonstrating this disorder in at least 15 of 31 family members:e
The conclusions which were drawn from 22 patients with R.T.A. and which were recorded in my thesisare worth mentioning; this series represents the largest individual collection of cases.
(1) R.T.A. may represent in some cases a mendelian autosomal dominant condition with greater expressivity in the female. (2) (a) Nephrocalcinosis is not a cause of R.T.A. ; (b) the low citrate excretion in the urine may account for the nephrocalcinosis. (3) Pyelonephritis is unlikely to be a cause of R.T.A., though this cannot be entirely excluded. (4) R.T.A. is a disease with different enzymatic faults giving rise to varying biochemical changes, and this accounts for the fact that rickets, nephrocalcinosis, hypokalxmia, complete " R.T.A., and " incomplete " R.T.A. can occur in one family. "
(5) It is possible that an autoimmune form of R.T.A. may result and that this should be searched for to further elucidate R.T.A. and the nature of autoimmune disease as a whole. (6) In one patient in my series treatment with alkalis cured the osteomalacia in R.T.A. without the addition of vitamin D. I feel that alkalis initiate and promote the healing of rickets in R.T.A., vitamin D being necessary only to expedite the healing biochemically. (7) The radiological changes of subperiosteal reabsorption of the hands denoting secondary hyperparathyroidism were described in 2 cases. This supported the view that secondary hyperparathyroidism did play a part in R.T.A. (8) All my patients with nephrocalcinosis had a fixed urinary specific gravity, whereas all my other patients with R.T.A. but no nephrocalcinosis had normal specific gravities of the urine. These findings suggest that loss of the ability to concentrate urine is related to the nephrocalcinosis and not to the defect in the ability to acidify urine. (9) Hyperchloræmia which does occur in most patients with R.T.A. is not essential for the diagnosis of R.T.A. (10) There was no gross deficiency in the acid-secreting mechanism of the stomach, but it did not rule out a rate limitation in the secretion of acid by the gastric glands. (11) Beside the hazards of labour in a woman with a pelvis deformed by osteomalacic changes or increased susceptibility to pyelonephritis, patients with R.T.A. are usually able to have normal pregnancies. (12) Patients with R.T.A. usually have a normal serum-protein. It may be raised in states of dehydration, and if this can be excluded one should suspect autoimmunity, particularly if the serum y-globulin is raised. (13) Latent cases of R.T.A. are probably more common than previously recognised. The majority of patients with R.T.A. are usually asymptomatic. Department of Medicine, University of Natal, P.O. Box 39, Congella, Durban, South Africa.
Ig-"
Renal Tubular
? Not examined
or
Acidosis
Renal Tubular Acidosis with
insufficient information
Nephrocalcinosis
Expired
Still born at 8 months
Clinical manifestations in this family of French extraction have been limited to short stature, recurrent hæmaturia, abdominal pain, and urolithiasis, but for the propositus (see arrow in pedigree), who presented at age 16 with nephrocalcinosis and symptomatic hypokalxmia. This 43-year-old woman has a history of polyuria, polydipsia, recurrent urinary-tract infections, hsematuria, and urolithiasis resulting in progressive renal insufficiency. Although she had hyperchloraemic acidosis, no glycosuria or aminoaciduria was present. At age 24 a subtotal parathyroidectomy was performed for suspected hyperparathyroidism, following which she experienced many episodes of hypocalcæmia. Subsequently she has undergone successful renal transplantation and has a functioning cadaveric renal graft that acidifies normally. Her affected identical twin sister has minimally reduced renal function and nephrocalcinosis. Carbonicanhydrase isoenzyme analysis of red cells and renal tissue from this twin were normal. The affected 8-year-old son of the propositus had his first episode of hæmaturia and urolithiasis at age 2 years. He is of short stature, has nephrocalcinosis and urolithiasis, and has never demonstrated the ability to concentrate his urine above specific gravity 1-012 after 12 hours of water deprivation. His 11-year-old sister is unable to acidify her urine below pH 6-0 after ammoniumchloride loading, but she is able to concentrate to a specific gravity greater than 1-020, is of normal stature for her age, and has no radiographically demonstrable nephrocalcinosis.
It
that morbidity in this family, but for the index is limited to that related to recurrent urolithiasis and case, short stature, with little or no reduction in longevity. Our observations concur with those of Dr. Richards and Professor Wrong that defective concentrating ability is not necessarily an intrinsic feature of distal renal tubular acidosis. JAMES E. MUSGRAVE Department of Pediatrics, WILLIAM M. BENNETT University of Oregon ROBERT A. CAMPBELL Medical School, CARL S. EISENBERG Portland, Oregon 97201, U.S.A. seems
ACUTE RENAL FAILURE AFTER RIFAMPICIN Y. K. SEEDAT.
were interested in the report by Kleinknecht al.1 of acute renal failure after rifampicin. In 1970, we observed a very similar situation in two women aged 20 and 25.
SIR,—We
et 1. 2. 3. 4. 5.
D.M.
thesis. National University of Ireland. January, 1967. K. S. Afr. med. J. 1964, 38, 606. K. ibid. 1967, 41, 1007. K. Excerpta med. Sect. VI, 1965, 19, abstract 2809. K. Ann. intern. Med. 1968, 69, 1329.
Seedat, Y. Seedat, Y. Seedat, Y. Seedat, Y.
1.
Kleinknecht, D., Homberg, J. C., Decroix,
G. Lancet,
1972, i, 1238.
SIR,—We read with interest that the family reported by Dr. Richards and Professor Wrong was the third such family to appear in the literature with clearly established
dominantly inherited distal renal tubular acidosis. We have investigated the following pedigree demonstrating this disorder in at least 15 of 31 family members:e
The conclusions which were drawn from 22 patients with R.T.A. and which were recorded in my thesisare worth mentioning; this series represents the largest individual collection of cases.
(1) R.T.A. may represent in some cases a mendelian autosomal dominant condition with greater expressivity in the female. (2) (a) Nephrocalcinosis is not a cause of R.T.A. ; (b) the low citrate excretion in the urine may account for the nephrocalcinosis. (3) Pyelonephritis is unlikely to be a cause of R.T.A., though this cannot be entirely excluded. (4) R.T.A. is a disease with different enzymatic faults giving rise to varying biochemical changes, and this accounts for the fact that rickets, nephrocalcinosis, hypokalxmia, complete " R.T.A., and " incomplete " R.T.A. can occur in one family. "
(5) It is possible that an autoimmune form of R.T.A. may result and that this should be searched for to further elucidate R.T.A. and the nature of autoimmune disease as a whole. (6) In one patient in my series treatment with alkalis cured the osteomalacia in R.T.A. without the addition of vitamin D. I feel that alkalis initiate and promote the healing of rickets in R.T.A., vitamin D being necessary only to expedite the healing biochemically. (7) The radiological changes of subperiosteal reabsorption of the hands denoting secondary hyperparathyroidism were described in 2 cases. This supported the view that secondary hyperparathyroidism did play a part in R.T.A. (8) All my patients with nephrocalcinosis had a fixed urinary specific gravity, whereas all my other patients with R.T.A. but no nephrocalcinosis had normal specific gravities of the urine. These findings suggest that loss of the ability to concentrate urine is related to the nephrocalcinosis and not to the defect in the ability to acidify urine. (9) Hyperchloræmia which does occur in most patients with R.T.A. is not essential for the diagnosis of R.T.A. (10) There was no gross deficiency in the acid-secreting mechanism of the stomach, but it did not rule out a rate limitation in the secretion of acid by the gastric glands. (11) Beside the hazards of labour in a woman with a pelvis deformed by osteomalacic changes or increased susceptibility to pyelonephritis, patients with R.T.A. are usually able to have normal pregnancies. (12) Patients with R.T.A. usually have a normal serum-protein. It may be raised in states of dehydration, and if this can be excluded one should suspect autoimmunity, particularly if the serum y-globulin is raised. (13) Latent cases of R.T.A. are probably more common than previously recognised. The majority of patients with R.T.A. are usually asymptomatic. Department of Medicine, University of Natal, P.O. Box 39, Congella, Durban, South Africa.
Ig-"
Renal Tubular
? Not examined
or
Acidosis
Renal Tubular Acidosis with
insufficient information
Nephrocalcinosis
Expired
Still born at 8 months
Clinical manifestations in this family of French extraction have been limited to short stature, recurrent hæmaturia, abdominal pain, and urolithiasis, but for the propositus (see arrow in pedigree), who presented at age 16 with nephrocalcinosis and symptomatic hypokalxmia. This 43-year-old woman has a history of polyuria, polydipsia, recurrent urinary-tract infections, hsematuria, and urolithiasis resulting in progressive renal insufficiency. Although she had hyperchloraemic acidosis, no glycosuria or aminoaciduria was present. At age 24 a subtotal parathyroidectomy was performed for suspected hyperparathyroidism, following which she experienced many episodes of hypocalcæmia. Subsequently she has undergone successful renal transplantation and has a functioning cadaveric renal graft that acidifies normally. Her affected identical twin sister has minimally reduced renal function and nephrocalcinosis. Carbonicanhydrase isoenzyme analysis of red cells and renal tissue from this twin were normal. The affected 8-year-old son of the propositus had his first episode of hæmaturia and urolithiasis at age 2 years. He is of short stature, has nephrocalcinosis and urolithiasis, and has never demonstrated the ability to concentrate his urine above specific gravity 1-012 after 12 hours of water deprivation. His 11-year-old sister is unable to acidify her urine below pH 6-0 after ammoniumchloride loading, but she is able to concentrate to a specific gravity greater than 1-020, is of normal stature for her age, and has no radiographically demonstrable nephrocalcinosis.
It
that morbidity in this family, but for the index is limited to that related to recurrent urolithiasis and case, short stature, with little or no reduction in longevity. Our observations concur with those of Dr. Richards and Professor Wrong that defective concentrating ability is not necessarily an intrinsic feature of distal renal tubular acidosis. JAMES E. MUSGRAVE Department of Pediatrics, WILLIAM M. BENNETT University of Oregon ROBERT A. CAMPBELL Medical School, CARL S. EISENBERG Portland, Oregon 97201, U.S.A. seems
ACUTE RENAL FAILURE AFTER RIFAMPICIN Y. K. SEEDAT.
were interested in the report by Kleinknecht al.1 of acute renal failure after rifampicin. In 1970, we observed a very similar situation in two women aged 20 and 25.
SIR,—We
et 1. 2. 3. 4. 5.
D.M.
thesis. National University of Ireland. January, 1967. K. S. Afr. med. J. 1964, 38, 606. K. ibid. 1967, 41, 1007. K. Excerpta med. Sect. VI, 1965, 19, abstract 2809. K. Ann. intern. Med. 1968, 69, 1329.
Seedat, Y. Seedat, Y. Seedat, Y. Seedat, Y.
1.
Kleinknecht, D., Homberg, J. C., Decroix,
G. Lancet,
1972, i, 1238.