- Email: [email protected]
TRIAMTERENE-INDUCED ACUTE INTERSTITIAL NEPHRITIS
226
previous findings (low OKT8% in peripheral blood)’and with the data of Janossy et awl.,who found a marked decrease of OKTS cells in lymphoid aggregates in the synovial membrane of + patients with active rheumatoid arthritis, HLA-DR cells of with a number interdigitating forming close contacts large OKT4 T cells. It remains to be determined whether the OKT8’ cells in synovial fluid are playing an active pathogenetic role or whether they migrate there because of a failure of mechanisms regulating their presence in blood and lymphoid aggregates.
SUBCUTANEOUS INFUSION OF GAMMAGLOBULINS IN MANAGEMENT OF AGAMMAGLOBULINAEMIA
our
Department of Rheumatology, University of Ghent, B-9000 Ghent, Belgium
E. M. VEYS P. HERMANNS G. VERBRUGGEN
Immunobiology Division, Ortho Pharmaceutical Corporation, Raritan, New Jersey, U.S A.
J. SCHINDLER G. GOLDSTEIN
TRIAMTERENE-INDUCED ACUTE INTERSTITIAL NEPHRITIS
SIR,-We have seen a patient with acute interstitial nephritis after the administration of triamterene. The manufacturers are unaware of any previous reports of this complication after triamterene therapy alone. A 52-year-old woman with hypertension had taken frusemide 40 mg daily and prinadolol 5 mg 8-hourly for 7 years. Her only other medication was doxepin 50 mg at night. 4 years previously she had had a mastectomy for carcinoma of the breast. The frusemide was replaced by triamterene 100 mg every morning. Almost immediately she had increasing malaise, lassitude, nausea and weight loss. Over the next 51a weeks she lost 7 kg in weight and oedema increased. When she had taken triamterene for 25 days her plasma urea was 7 -mmol/1 and creatinine 190 mol/1, and after 36 days the respective values were 12 -8 and 310. 4 days later triamterene was discontinued. Serial urine specimens showed no proteinuria or microscopic haematuria. Percutaneous renal biopsy revealed no immunoglobulin deposition in the glomeruli or tubules on immunofluorescence. On light microscopy there were _ thirty normal glomeruli. There was a heavy interstitial infiltrate of lymphocytes, plasma cells, and eosinophils and considerable interstitial oedema consistent with a drug-induced acute interstitial nephritis. 7 days after the triamterene was discontinued the patient’s renal function began to improve. 18 days after stopping triamterene the plasma urea was 10-1 mmol/1 and creatinine 120 mol/1 and the patient was symptomatically improved. Extensive investigations showed no evidence of metastatic cancer. Magil et al. reported three elderly patients with no history of renal disease in whom non-specific symptoms and renal insufficiency developed insidiously after starting ’Dyazide’ (a combination of hydrochlorothiazide 25 mg and triamterene 50 mg) for the treatment of hypertension. All three had normal renal function before therapy and showed acute interstitial nephritis on biopsy. Although these workers considered that the thiazide was probably the drug responsible for the reaction they suspected a possible potentiating role for triamterene. This uncommon reaction should be differentiated from the more common problems seen when potassium-sparing diuretics are administered to patients with renal insufficiency/hyperkalaemia and a further deterioration in renal function.4 ’
SIR,-Long-term treatment of primary agammaglobulinaemia is hampered by the need for painful intramuscular injection of large amounts of human standard globulin (HSG).1 Non-compliance is frequent, especially in adolescents. Furthermore, because of problems in injecting volumes large enough to achieve high serum IgG concentrations, levels 30-50% of age-normal values are usually accepted as sufficient,2 but may explain, at least in part, the high frequency of minor chronic infections developing even in welltreated patients. The introduction of HSG suitable for intravenous use3circumvents these problems but requires hospital admission for a day every 15-20 days, and HSG for i.v. use is expensive. Over the past 3 months we have treated ten children with primary agammaglobulinaemia, who had previously been treated with i.m. HSG, with HSG (available for i.m. use) injected subcutaneously by syringe driver type MS 16 (Pye dynamics). After a loading dose of 100 mg/kg daily for 5-10 days, 100 mg/kg has been given once a week over 6-8 h to maintain stable serum IgG levels (see figure). In all patients the loading dose resulted in a dramatic increase of serum IgG always accompanied by a parallel increase in "natural" and antibacterial antibodies, indicating the absorption of intact IgG molecules. All children are clinically well and have not had significant infections during the trial: treatment has been given at home while the child was sleeping or playing and is much better tolerated than the i.m. regimen, especially since there is very little or no pain. Similar results have been reported in adults with
agammaglobulinaemia.44
Whether the attainment of normal serum IgG levels will result in better long-term prognosis, remains to be evaluated by controlled clinical trials now in progress. A. G. UGAZIO M. DUSE R. RE Department of Paediatrics, G. MANGILI of Pavia, University G. R. BURGI0 27100 Pavia, Italy a
1. WHO Scientific
Group on Immunodeficiency. Immunodeficiency. Clin Immunol Immunopathol 1979; 13: 296-359. 2. Janeway CA, Rosen FS, Merler E, Alper CA. The gamma globulins. Boston: 1967, Little, Brown: 103-04.
3. Alving BM, Finlayson JJ (eds). Immunoglobulins: Characteristics and uses of intravenous preparations U.S. Department of Health, and Human Services DHHS publication no (FDA)-80-9005, 1980. 4. van Furth R. Communication to meeting on Haemotherapy (Interlaken, Aug. 24-26, 1981).
ROSS R. BAILEY KELVIN L. LYNN
Christchurch
Department of Nephrology, Hospital,
C. J. DRENNAN
Christchurch, New Zealand
G. A. L. TURNER
IgG levels in ten patients with agammaglobulinaemia on replacement therapy with human standard globulins subcutaneously.
Serum
2. Janossy G, Duke O, Panayi G, et al. Rheumatoid arthritis: a disease of T lymphocyte/macrophage immunoregulation. Lancet 1981; ii. 839-44. 3. Magil AB, Ballon HS, Cameron EC, Rae A. Acute interstitial nephritis associated with thiazide diuretics: Clinical and pathologic observations in three cases Am J Med 1980, 69: 939-43. 4. Neale
TJ, Lynn KL, Bailey RR. Spironolactone-associated aggravation of renal functional impairment NZ Med J 1976; 83: 147-49.
On the ordinate, values are expressed as percent of the lower limit of the agenormal range (broken horizontal line); values at - I (abscissa).indicate the last level monitored during conventional intramuscular HSG and those at 0 weeks the levels just before beginning subcutaneous replacement. -
previous findings (low OKT8% in peripheral blood)’and with the data of Janossy et awl.,who found a marked decrease of OKTS cells in lymphoid aggregates in the synovial membrane of + patients with active rheumatoid arthritis, HLA-DR cells of with a number interdigitating forming close contacts large OKT4 T cells. It remains to be determined whether the OKT8’ cells in synovial fluid are playing an active pathogenetic role or whether they migrate there because of a failure of mechanisms regulating their presence in blood and lymphoid aggregates.
SUBCUTANEOUS INFUSION OF GAMMAGLOBULINS IN MANAGEMENT OF AGAMMAGLOBULINAEMIA
our
Department of Rheumatology, University of Ghent, B-9000 Ghent, Belgium
E. M. VEYS P. HERMANNS G. VERBRUGGEN
Immunobiology Division, Ortho Pharmaceutical Corporation, Raritan, New Jersey, U.S A.
J. SCHINDLER G. GOLDSTEIN
TRIAMTERENE-INDUCED ACUTE INTERSTITIAL NEPHRITIS
SIR,-We have seen a patient with acute interstitial nephritis after the administration of triamterene. The manufacturers are unaware of any previous reports of this complication after triamterene therapy alone. A 52-year-old woman with hypertension had taken frusemide 40 mg daily and prinadolol 5 mg 8-hourly for 7 years. Her only other medication was doxepin 50 mg at night. 4 years previously she had had a mastectomy for carcinoma of the breast. The frusemide was replaced by triamterene 100 mg every morning. Almost immediately she had increasing malaise, lassitude, nausea and weight loss. Over the next 51a weeks she lost 7 kg in weight and oedema increased. When she had taken triamterene for 25 days her plasma urea was 7 -mmol/1 and creatinine 190 mol/1, and after 36 days the respective values were 12 -8 and 310. 4 days later triamterene was discontinued. Serial urine specimens showed no proteinuria or microscopic haematuria. Percutaneous renal biopsy revealed no immunoglobulin deposition in the glomeruli or tubules on immunofluorescence. On light microscopy there were _ thirty normal glomeruli. There was a heavy interstitial infiltrate of lymphocytes, plasma cells, and eosinophils and considerable interstitial oedema consistent with a drug-induced acute interstitial nephritis. 7 days after the triamterene was discontinued the patient’s renal function began to improve. 18 days after stopping triamterene the plasma urea was 10-1 mmol/1 and creatinine 120 mol/1 and the patient was symptomatically improved. Extensive investigations showed no evidence of metastatic cancer. Magil et al. reported three elderly patients with no history of renal disease in whom non-specific symptoms and renal insufficiency developed insidiously after starting ’Dyazide’ (a combination of hydrochlorothiazide 25 mg and triamterene 50 mg) for the treatment of hypertension. All three had normal renal function before therapy and showed acute interstitial nephritis on biopsy. Although these workers considered that the thiazide was probably the drug responsible for the reaction they suspected a possible potentiating role for triamterene. This uncommon reaction should be differentiated from the more common problems seen when potassium-sparing diuretics are administered to patients with renal insufficiency/hyperkalaemia and a further deterioration in renal function.4 ’
SIR,-Long-term treatment of primary agammaglobulinaemia is hampered by the need for painful intramuscular injection of large amounts of human standard globulin (HSG).1 Non-compliance is frequent, especially in adolescents. Furthermore, because of problems in injecting volumes large enough to achieve high serum IgG concentrations, levels 30-50% of age-normal values are usually accepted as sufficient,2 but may explain, at least in part, the high frequency of minor chronic infections developing even in welltreated patients. The introduction of HSG suitable for intravenous use3circumvents these problems but requires hospital admission for a day every 15-20 days, and HSG for i.v. use is expensive. Over the past 3 months we have treated ten children with primary agammaglobulinaemia, who had previously been treated with i.m. HSG, with HSG (available for i.m. use) injected subcutaneously by syringe driver type MS 16 (Pye dynamics). After a loading dose of 100 mg/kg daily for 5-10 days, 100 mg/kg has been given once a week over 6-8 h to maintain stable serum IgG levels (see figure). In all patients the loading dose resulted in a dramatic increase of serum IgG always accompanied by a parallel increase in "natural" and antibacterial antibodies, indicating the absorption of intact IgG molecules. All children are clinically well and have not had significant infections during the trial: treatment has been given at home while the child was sleeping or playing and is much better tolerated than the i.m. regimen, especially since there is very little or no pain. Similar results have been reported in adults with
agammaglobulinaemia.44
Whether the attainment of normal serum IgG levels will result in better long-term prognosis, remains to be evaluated by controlled clinical trials now in progress. A. G. UGAZIO M. DUSE R. RE Department of Paediatrics, G. MANGILI of Pavia, University G. R. BURGI0 27100 Pavia, Italy a
1. WHO Scientific
Group on Immunodeficiency. Immunodeficiency. Clin Immunol Immunopathol 1979; 13: 296-359. 2. Janeway CA, Rosen FS, Merler E, Alper CA. The gamma globulins. Boston: 1967, Little, Brown: 103-04.
3. Alving BM, Finlayson JJ (eds). Immunoglobulins: Characteristics and uses of intravenous preparations U.S. Department of Health, and Human Services DHHS publication no (FDA)-80-9005, 1980. 4. van Furth R. Communication to meeting on Haemotherapy (Interlaken, Aug. 24-26, 1981).
ROSS R. BAILEY KELVIN L. LYNN
Christchurch
Department of Nephrology, Hospital,
C. J. DRENNAN
Christchurch, New Zealand
G. A. L. TURNER
IgG levels in ten patients with agammaglobulinaemia on replacement therapy with human standard globulins subcutaneously.
Serum
2. Janossy G, Duke O, Panayi G, et al. Rheumatoid arthritis: a disease of T lymphocyte/macrophage immunoregulation. Lancet 1981; ii. 839-44. 3. Magil AB, Ballon HS, Cameron EC, Rae A. Acute interstitial nephritis associated with thiazide diuretics: Clinical and pathologic observations in three cases Am J Med 1980, 69: 939-43. 4. Neale
TJ, Lynn KL, Bailey RR. Spironolactone-associated aggravation of renal functional impairment NZ Med J 1976; 83: 147-49.
On the ordinate, values are expressed as percent of the lower limit of the agenormal range (broken horizontal line); values at - I (abscissa).indicate the last level monitored during conventional intramuscular HSG and those at 0 weeks the levels just before beginning subcutaneous replacement. -