117 5 patients aged 36-49 (3 males, 2 females) were admitted because of sudden onset of muscle weakness and hypokalaemia late at night or in the early morning. In 2 patients serum and erythrocyte potassium levels were very low (1-5, 20 and 84, 99 mmol/1, respectively). Ventricular bigeminy was observed in 2, and U waves were seen in 3 patients. 2 patients had respiratory failure and required intubation. All patients survived thanks to prompt medical treatment; had that not been available all might have died, and the pattern of deaths might then have been attributed to SUND. We also found that urine potassium excretion in 59 villages in Khon Kaen was much lower than it was in 35 adults in Bangkok (16-3 [SE 1 -0] vs 37-4 [2.5] mmol per day). The potassium content of the diet of the indigenous population is low (males 0-8 [SD 0’1], females 1-3 [0’4] g per day), as against a recommended dietary allowance of 1 -4-5-6g; Puwastien P, Institute of Nutrition, Mahidol University, personal communication). There is also a high possibility of excess loss of potassium through sweating in a persistently hot climate in which, in summer, temperatures may reach 41°C. These features and the lack of evidence of gastrointestinal loss of potassium suggest a state of chronic potassium deficiency in this population. Potassium deficiency, if severe, can lead to general paralysis and life-threatening respiratory failure and cardiac arrhythmia. In chronic deficiency, renal tubulointerstitial damage had been described.2 Potassium deficiency could therefore be one of the prime factors responsible for the high prevalence of distal renal tubular acidosis and periodic paralysis in the area. Renal Unit,
Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 10700 Thailand, and Ubolrajathani and Khonkaen Hospitals
SUMALEE NIMMANNIT PRIDA MALASIT VIPADA CHAOVAKUL WATTANACHAI SUSAENGRAT SANGA NILWARANGKUR
Nilwarangkur S, Nimmannit S, Chaovakul V, et al Endemic primary distal renal tubular acidosis in Thailand. Q J Med 1990; 74: 289-301. 2. Muehrcke RC, Rosen S. Hypokalemic nephropathy m rat and man. Lab Invest 1964; 1.
13: 1359-73.
Dangers of dietary germanium supplements use of "natural" remedies is a reason for because of the lack of scientific evidence of efficacy and the toxicity of some of these products (eg, comfrey). Several reports have come from Japan of renal damage attributed to germaniumcontaining products’ but we know of no similar published cases from western countries. A 57-year-old woman with a diagnosis of breast cancer in 1984 had been successfully treated since 1986 with 30 mg tamoxifen daily because of bone and lung metastases. She did not use other prescribed drugs. At that time renal and hepatic function were normal. Since early 1986 she had been taking 66 mg germanium lactate citrate (12 mg germanium) and 0-2 mg selenium daily because she thought that this would improve her medical condition. In October, 1988, she was admitted to hospital with deteriorating renal function (figure). She did not have fever, nausea, malaise, myalgia, jaundice, or signs of chronic liver disease. At that time she had ingested about 10g germanium and 180 mg selenium over 2 years. She had a raised erythrocyte sedimentation rate, reduced haemoglobin and erythrocyte count, raised serum creatinine (402 pmol/1), and abnormal creatinine clearance (10 ml/min). Other laboratory abnormalities were hypokalaemia (3-2 mmol/1), and increased aminotransferases (ALAT 435 and ASAT 315 U/1), lactate dehydrogenase (829 U/1), and creatine kinase (309 U/1). Tests for hepatitis A and B were negative. Urinalysis showed many leucocytes and bacteria (Escherichia colt) but no erythrocytes, protein, or renal casts. Blood cultures were negative. Ultrasonography revealed a cyst in the lower pole of the right kidney and a distended gallbladder. On renal biopsy the glomeruli were normal and there were no signs of interstitial inflammation. However, the epithelial cells of the renal tubuli had a strikingly vacuolated cytoplasm without tubular degeneration. A liver biopsy revealed slight portal infiltration and moderate steatosis.
SiR,—The increasing
concern
Serum creatinine levels before, during, and after
germanium
use.
Germanium and selenium were discontinued on admission, tamoxifen being continued. Transaminases and creatine kinase returned to normal within 2 months but recovery of renal function over the next 2 years was slow and incomplete (figure). In February, 1990, the patient felt well despite a serum creatinine of 206 Nznol/1. There were no signs of metastases. Biopsies were not repeated because the patient was reluctant to undergo further investigation. Germanium was probably the cause of the renal damage in this woman. This agent has been associated with renal damage after intake of a cumulative dose of 16-328 g over 4-36 months Bacteria were present in our patient’s urine but there was no fever and histological findings were not consistent with pyelonephritisindeed vacuolar degeneration in renal tubular epithelial cells in the absence of significant glomerular changes has been noted in previous germanium-associated cases.2-ó Moreover, there was no history of urinary tract infection. A combination of renal and muscular damage was noted in several Japanese patients who had ingested germanium for long periods.2,5 Although liver enzymes have usually been normal or only slightly raised, necropsy in one fatal case revealed severe hepatic steatosis.2 Although we cannot rule out selenium (or its combination with germanium) as the cause we know of no published cases of combined renal, hepatic, and muscle damage due to selenium, and the daily intake of 02 mg was in the normal ranged We conclude that the irreversible renal damage in this patient was caused by germanium and would endorse the warning issued by the Department of Health in the UK.8 Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam
J. I. VAN
Netherlands Centre for Monitoring of Adverse Reactions to Drugs, 2280 HK Rijswijk, Netherlands
B. H. CH. STRICKER
Departments of Internal Medicine and Pathology, Onze Lieve Vrouwe Gasthuis
DER
SPOEL
M. R. ESSEVELD M. E. I. SCHIPPER
1. Anon. Germanium dangers. Lancet 1989; ii: 755. 2. Nagata N, Yoneyama T, Yanagida K, et al. Accumulation of germanium in the tissues of a long-term user of germanium preparation who died of acute renal failure. J Toxicol Sci 1985; 10: 333-41. 3. Omata M, Kikuchi M, Higuchi C, Sanaka S, Takuma T, Sugino N. Drug-induced nephropathy: our recent clinical experience. In: Tanabe T, Hook JB, Endou H, ed. Nephrotoxicity of antibiotics and immunosuppressants. Amsterdam: Elsevier, 1986: 15-20. 4. Okuda S, Kiyama S, Oh Y, et al. Persistent renal dysfunction induced by chronic intake of germanium-containing compounds. Curr Ther Res 1987; 41: 265-75. 5. Matsusaka T, Fujii M, Nakano T, et al. Germanium-induced nephropathy: report of two cases and review of the literature. Clin Nephrol 1988; 30: 341-45. 6. Okada K, Okagawa K, Kawakami K, et al. Renal failure casused by long-term use of a germanium preparation as an elixir. Chn Nephrol 1989; 31: 219-24. 7. Marcus R, Coulston AM. The vitamins: introduction. In: Gilman A, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman’s pharmacological basis of
therapeutics, 7th ed. New York: Macmillan, 1985: 1544-51. Pharm J 1989; 242: 475.
8. Anon
Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, 10700 Thailand, and Ubolrajathani and Khonkaen Hospitals
SUMALEE NIMMANNIT PRIDA MALASIT VIPADA CHAOVAKUL WATTANACHAI SUSAENGRAT SANGA NILWARANGKUR
Nilwarangkur S, Nimmannit S, Chaovakul V, et al Endemic primary distal renal tubular acidosis in Thailand. Q J Med 1990; 74: 289-301. 2. Muehrcke RC, Rosen S. Hypokalemic nephropathy m rat and man. Lab Invest 1964; 1.
13: 1359-73.
Dangers of dietary germanium supplements use of "natural" remedies is a reason for because of the lack of scientific evidence of efficacy and the toxicity of some of these products (eg, comfrey). Several reports have come from Japan of renal damage attributed to germaniumcontaining products’ but we know of no similar published cases from western countries. A 57-year-old woman with a diagnosis of breast cancer in 1984 had been successfully treated since 1986 with 30 mg tamoxifen daily because of bone and lung metastases. She did not use other prescribed drugs. At that time renal and hepatic function were normal. Since early 1986 she had been taking 66 mg germanium lactate citrate (12 mg germanium) and 0-2 mg selenium daily because she thought that this would improve her medical condition. In October, 1988, she was admitted to hospital with deteriorating renal function (figure). She did not have fever, nausea, malaise, myalgia, jaundice, or signs of chronic liver disease. At that time she had ingested about 10g germanium and 180 mg selenium over 2 years. She had a raised erythrocyte sedimentation rate, reduced haemoglobin and erythrocyte count, raised serum creatinine (402 pmol/1), and abnormal creatinine clearance (10 ml/min). Other laboratory abnormalities were hypokalaemia (3-2 mmol/1), and increased aminotransferases (ALAT 435 and ASAT 315 U/1), lactate dehydrogenase (829 U/1), and creatine kinase (309 U/1). Tests for hepatitis A and B were negative. Urinalysis showed many leucocytes and bacteria (Escherichia colt) but no erythrocytes, protein, or renal casts. Blood cultures were negative. Ultrasonography revealed a cyst in the lower pole of the right kidney and a distended gallbladder. On renal biopsy the glomeruli were normal and there were no signs of interstitial inflammation. However, the epithelial cells of the renal tubuli had a strikingly vacuolated cytoplasm without tubular degeneration. A liver biopsy revealed slight portal infiltration and moderate steatosis.
SiR,—The increasing
concern
Serum creatinine levels before, during, and after
germanium
use.
Germanium and selenium were discontinued on admission, tamoxifen being continued. Transaminases and creatine kinase returned to normal within 2 months but recovery of renal function over the next 2 years was slow and incomplete (figure). In February, 1990, the patient felt well despite a serum creatinine of 206 Nznol/1. There were no signs of metastases. Biopsies were not repeated because the patient was reluctant to undergo further investigation. Germanium was probably the cause of the renal damage in this woman. This agent has been associated with renal damage after intake of a cumulative dose of 16-328 g over 4-36 months Bacteria were present in our patient’s urine but there was no fever and histological findings were not consistent with pyelonephritisindeed vacuolar degeneration in renal tubular epithelial cells in the absence of significant glomerular changes has been noted in previous germanium-associated cases.2-ó Moreover, there was no history of urinary tract infection. A combination of renal and muscular damage was noted in several Japanese patients who had ingested germanium for long periods.2,5 Although liver enzymes have usually been normal or only slightly raised, necropsy in one fatal case revealed severe hepatic steatosis.2 Although we cannot rule out selenium (or its combination with germanium) as the cause we know of no published cases of combined renal, hepatic, and muscle damage due to selenium, and the daily intake of 02 mg was in the normal ranged We conclude that the irreversible renal damage in this patient was caused by germanium and would endorse the warning issued by the Department of Health in the UK.8 Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam
J. I. VAN
Netherlands Centre for Monitoring of Adverse Reactions to Drugs, 2280 HK Rijswijk, Netherlands
B. H. CH. STRICKER
Departments of Internal Medicine and Pathology, Onze Lieve Vrouwe Gasthuis
DER
SPOEL
M. R. ESSEVELD M. E. I. SCHIPPER
1. Anon. Germanium dangers. Lancet 1989; ii: 755. 2. Nagata N, Yoneyama T, Yanagida K, et al. Accumulation of germanium in the tissues of a long-term user of germanium preparation who died of acute renal failure. J Toxicol Sci 1985; 10: 333-41. 3. Omata M, Kikuchi M, Higuchi C, Sanaka S, Takuma T, Sugino N. Drug-induced nephropathy: our recent clinical experience. In: Tanabe T, Hook JB, Endou H, ed. Nephrotoxicity of antibiotics and immunosuppressants. Amsterdam: Elsevier, 1986: 15-20. 4. Okuda S, Kiyama S, Oh Y, et al. Persistent renal dysfunction induced by chronic intake of germanium-containing compounds. Curr Ther Res 1987; 41: 265-75. 5. Matsusaka T, Fujii M, Nakano T, et al. Germanium-induced nephropathy: report of two cases and review of the literature. Clin Nephrol 1988; 30: 341-45. 6. Okada K, Okagawa K, Kawakami K, et al. Renal failure casused by long-term use of a germanium preparation as an elixir. Chn Nephrol 1989; 31: 219-24. 7. Marcus R, Coulston AM. The vitamins: introduction. In: Gilman A, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman’s pharmacological basis of
therapeutics, 7th ed. New York: Macmillan, 1985: 1544-51. Pharm J 1989; 242: 475.
8. Anon
