Hypomagnesaemic hypocalcaemia with hypokalaemia caused by treatment with high dose gentamicin.

A 12-year-old boy developed renal wasting of magnesium, calcium, and potassium, with secondary hypomagnesaemia, hypocalcaemia, and hypokalaaemia (without hyperaldosteronism) after treatment with 14 400 mg gentamicin over 4 months. Gentamicin should not be given for prolonged courses if less toxic antibiotics are suitable. If it used, plasma magnesium, calcium, and potassium levels should be monitored during and after treatment.     

Cisplatin nephrotoxicity: symptomatic hypomagnesemia and renal failure

Cisplatin is an inorganic platinum compound used in the treatment of solid tumors. Clinical trials have proved its efficacy whilst recognising the nephrotoxicity of the drug. We report the case of a 14 1/2 year old female with an epidermoid carcinoma of the lung, who developed acute renal failure following two courses of Cisplatin. The predominant features were symptomatic hypomagnesaemia, hypocalcaemia and hypokalaemia which were corrected following the administration of intravenous magnesium. Renal failure persisted for several months and the patient died due to her primary disease. Electrolyte disturbances should be anticipated when high dose Cisplatin is used.     

External hydrocephalus in primary hypomagnesaemia: a new finding

This paper reports a new finding in two siblings with primary hypomagnesaemia as a result of renal magnesium wasting, namely, rapidly increasing head size. External hydrocephalus and brain shrinkage in primary hypomagnesaemia seen on computed tomography of the brain with reversibility after magnesium treatment has not been reported previously.     

External hydrocephalus in primary hypomagnesaemia: a new finding.

This paper reports a new finding in two siblings with primary hypomagnesaemia as a result of renal magnesium wasting, namely, rapidly increasing head size. External hydrocephalus and brain shrinkage in primary hypomagnesaemia seen on computed tomography of the brain with reversibility after magnesium treatment has not been reported previously.     

Clinical presentation and outcome in primary familial hypomagnesaemia

The clinical presentation and long term outcome (mean follow up eight years, range 0.25 to 21) of 15 patients with autosomal recessive primary familial hypomagnesaemia is described. The most common (67%) presenting events were generalised hypocalcaemic-hypomagnesaemic seizures at a mean (SD) age of 4.9 (2.5) weeks. Thirteen infants, treated soon after diagnosis with high dose enteral magnesium developed normally. Their serum calcium returned to normal concentrations but serum magnesium could not be maintained at normal concentrations (0.53 (0.12 SD) mmol/l; normal > 0.62). Delay in establishing a diagnosis led to a convulsive disorder with permanent neurological impairment in two infants. Reported complications of prolonged hypomagnesaemia such as renal stones, hypertension, arrhythmias, sudden death, or dyslipidaemia were not observed.     

Clinical presentation and outcome in primary familial hypomagnesaemia

The clinical presentation and long term outcome (mean follow up eight years, range 0.25 to 21) of 15 patients with autosomal recessive primary familial hypomagnesaemia is described. The most common (67%) presenting events were generalised hypocalcaemic-hypomagnesaemic seizures at a mean (SD) age of 4.9 (2.5) weeks. Thirteen infants, treated soon after diagnosis with high dose enteral magnesium developed normally. Their serum calcium returned to normal concentrations but serum magnesium could not be maintained at normal concentrations (0.53 (0.12 SD) mmol/l; normal >0.62). Delay in establishing a diagnosis led to a convulsive disorder with permanent neurological impairment in two infants. Reported complications of prolonged hypomagnesaemia such as renal stones, hypertension, arrhythmias, sudden death, or dyslipidaemia were not observed.

     

Successful management of primary hypomagnesaemia with high-dose oral magnesium citrate: a case report

We report a 40-d-old female infant who presented to our clinic with afebrile generalized convulsive episodes due to severe hypomagnesaemia with secondary hypocalcaemia. Laboratory investigations revealed mild hypoparathyroidism, which was to return normal following magnesium (Mg) treatment, and normal fractional renal excretion of Mg (0.8%). After the diagnosis of primary hypomagnesaemia was established, the patient was discharged with oral Mg subcarbonate and intramuscular Mg sulphate. On regular follow-up until the age of 4 y, the child was asymptomatic. Mean serum calcium levels remained normal, while mean serum Mg levels remained subnormal. During this 4-y period, oral Mg dose was gradually increased while the doses and frequency of administration of parenteral Mg were decreased. Additionally, oral Mg subcarbonate was switched to Mg citrate because of its side effects. Finally, parenteral Mg was discontinued as the dosage of oral Mg supplementation reached a level of 90 mg/kg/d elemental Mg citrate, without any gastrointestinal side effects. Some screening tests were performed to evaluate the complications of chronic hypomagnesaemia. Bone age, bone densitometry, ECG and renal sonography were all normal. Our patient is now 5 y old and symptom free. CONCLUSION: Treatment with high doses of oral Mg was successful in keeping our patient symptom free and normocalcaemic, but cannot fully normalize serum Mg concentrations. Thus, during the regular follow-up of patients with primary hypomagnesaemia, the main target must be to increase oral Mg supplementation to a dosage which can maintain normocalcaemia rather than normomagnesaemia.     

Technical report: precautions regarding the use of aerosolized antibiotics. Committee on Infectious Diseases and Committee on Drugs

In 1998, the Food and Drug Administration (FDA) approved the licensure of tobramycin solution for inhalation (TOBI). Although a number of additional antibiotics, including other aminoglycosides, beta-lactams, antibiotics in the polymyxin class, and vancomycin, have been administered as aerosols for many years, none are approved by the FDA for administration by inhalation. TOBI was approved by the FDA for the maintenance therapy of patients 6 years or older with cystic fibrosis (CF) who have between 25% and 75% of predicted forced expiratory volume in 1 second (FEV(1)), are colonized with Pseudomonas aeruginosa, and are able to comply with the prescribed medical regimen. TOBI was not approved for the therapy of acute pulmonary exacerbations in patients with CF nor was it approved for use in patients without CF. Currently, no other antibiotics are approved for administration by inhalation to patients with or without CF. The purpose of this statement is to briefly summarize the data that supported approval for licensure of TOBI and to provide recommendations for its safe use. The pharmacokinetics of inhaled aminoglycosides and problems associated with aerosolized antibiotic treatment, including environmental contamination, selection of resistant microbes, and airway exposure to excipients in intravenous formulations, will be discussed.     

Are measurements of urine enzymes useful during aminoglycoside therapy?

We prospectively evaluated concentrations of beta-D-galactosidase, alpha-L-fucosidase, beta-D-N-acetylglucosaminidase, and lysozyme in urine from normal subjects, ambulatory patients with cystic fibrosis (CF), and CF patients with previously normal renal function who were receiving intravenous aminoglycoside (AG) therapy. Enzyme activities were generally low or negligible in subjects not receiving AG. Enzymuria was documented during 12 of 13 AG treatment courses and most frequently involved beta-D-N-acetylglucosaminidase excretion. In nine courses, enzymuria occurred in the absence of proteinuria or elevations of blood urea nitrogen and serum creatinine. In three courses attended by enzymuria and evidence of nephrotoxicity, neither the time of appearance nor the magnitude of enzymuria was different from that of nonnephrotoxic patients. In two of these three treatment courses, enzymuria preceded clinical evidence of nephrotoxicity of 16 and 5 days, and in the third course enzymuria and elevation of blood urea nitrogen and serum creatinine occurred simultaneously. We conclude that enzymuria is not a reliable predictor of nephrotoxicity due to AG in CF patients and is not an indication of discontinue AG therapy.     

Renal clearance of gentamicin in cystic fibrosis

This study was designed to corroborate previous observations of low serum concentrations of aminoglycosides after usual doses in patients with cystic fibrosis and to investigate possible mechanisms for this change. We studied gentamicin clearance after single and multiple intravenously administered doses in 10 non-acutely ill patients with mild to moderate CF. The data could best be described by a two-compartment model for drug elimination. The mean 1-hour serum concentration, mean volume of distribution, and mean total plasma clearance of gentamicin were not different from those reported for patients without CF. The similarity of the plasma and the renal gentamicin clearances, supported by the observations that greater than 80% of administered drug was excreted in the urine by 4 hours and that negligible amounts were detected in sweat, saliva, or sputum, implies that the kidney is the major route of elimination in patients with mild CF. The correlation of increased plasma gentamicin clearance as NIH score decreases supports the hypothesis that aminoglycoside pharmacokinetics are changed as the severity of disease increases. For patients with mild CF, standard doses of gentamicin (60 mg/m2) will give safe and therapeutic concentrations.     

Hypercalciuria and nephrocalcinosis in cystic fibrosis patients

The objective of this study was to determine the frequency of nephrocalcinosis and hypercalciuria in cystic fibrosis (CF) patients, and to search possible causes of this phenomenon. Forty-three CF children (24 boys, 19 girls; mean age 64.9 months, range 5 months-18 years) were included in this study. Plasma sodium, potassium, chloride, BUN, creatinine, calcium, phosphorus, magnesium, alkaline phosphatase; spot urine sodium, potassium, chloride, creatinine, calcium, magnesium; and serum 25-hydroxyvitamin-D levels were measured in all patients. Urine samples were examined for microscopic hematuria. Fractional sodium, potassium, chloride excretion and estimated glomerular filtration rate (GFR) were calculated. All patients underwent renal ultrasonography. Hypercalciuria, nephrocalcinosis and microscopic hematuria were detected in 15 patients (34.2%), 10 patients (23.2%) and two patients (5%), respectively. There was no significant but borderline correlation between 25-hydroxyvitamin-D levels and hypercalciuria (r: 0.308, p:0.05). There were no correlations between Shwachman clinical scoring system results and hypercalciuria (r: 0.221, p: 0.148) and age and hypercalciuria (r: -0.229, p: 0.135). Patients with chronic Pseudomonas colonization showed no hypercalciuria or nephrocalcinosis. There was no difference for plasma biochemical results, renal function tests, hypercalciuria and nephrocalcinosis between CF patients who had or had not experienced pseudo Bartter's syndrome (PBS) before. There was no relation between detected CF mutations of the patients and hypercalciuria and nephrocalcinosis. These results suggested that it is a primary abnormality of calcium metabolism in the kidney.     

原发肾小管性低钾碱中毒的临床特点

目的 探讨原发肾小管性低钾碱中毒的临床特点.方法 收集在天津市儿童医院住院治疗的原发肾小管性低钾碱中毒患儿8例,其中Bartter综合征(BS)、Gitelman综合征(GS)各4例.回顾性分析其临床表现、实验室检查、治疗方法及转归情况.结果 4例BS均婴幼儿期起病,临床表现为间断呕吐、腹泻、脱水、生长发育迟缓.4例GS发病年龄为10～15岁,临床表现为肢体无力、四肢麻木及间断手足搐搦.8例患儿血压均正常.实验室检查均表现为低血钾、代谢性碱中毒、尿钾、尿氯排出增加;4例BS息儿血浆肾素、血管紧张素、醛固酮明显升高;4例GS患儿血管紧张素均升高,血浆肾素升高3例、醛固酮明显升高2例;BS患儿尿钙肌酐比>0.2,GS患儿伴低血镁、尿钙肌酐比<0.2.2例BS患儿B超示双肾回声均匀增强,其中1例左肾盂扩张.单纯补钾或联合补镁、吲哚美辛、螺内酯和卡托普利后症状缓解.结论 原发肾小管性低钾碱中毒主要表现为低血钾、代谢性碱中毒、血压正常.检查其血镁、尿钾、尿氯、尿钙肌酐比和血浆肾素、血管紧张素、醛固酮水平可帮助诊断.BS和GS的发病机制、临床表现、治疗及预后均有不同.     

Primary hypomagnesaemia: Case report

ABSTRACT. A patient with primary hypomagnesaemia is presented. The condition is associated with abnormal magnesium absorption from the small bowel.
The duodenal mucosal magnesium content in this patient was estimated and was normal. This has implications about the pathophysiological basis of the defect which are discussed.     

Renal calcium handling in cystic fibrosis: lack of evidence for a primary renal defect.

Because cystic fibrosis (CF) epithelia have ion transport abnormalities that may in part be regulated by intracellular calcium metabolism, and the kidney is actively involved in both ion transport and calcium homeostasis, we have investigated renal calcium handling in CF. Twenty-four-hour urine collections were analyzed in 34 CF patients (age 5 to 35 years) and kidney ultrasound studies were performed in 17 CF patients (age 6 months to 23 years). Renal histologic findings at postmortem examination of 14 CF patients (age 4 months to 23 years) were compared with those of 12 patients (age 11 months to 17 years) with other chronic illnesses (6 congenital heart disease, 6 malignancy). In 30 of the 34 CF patients urinary calcium excretion was normal (less than 4 mg (0.1 mmol)/kg/24 hr). Four CF patients had hypercalciuria (calcium excretion 4.4 to 8.8 mg (0.11 to 0.22 mmol)/kg/24 hr). However, these patients had other possible explanations for hypercalciuria, such as immobilization (n = 2), increased dietary sodium load (n = 1), and glucocorticoid therapy (n = 1). None of the 17 patients examined by renal ultrasonography had nephrocalcinosis. Five CF patients had histologic evidence of sparse nephrocalcinosis at autopsy. However, 6 of 12 autopsy kidney specimens from patients with other chronic illnesses and similar preterminal events also showed nephrocalcinosis. The hypercalciuria and nephrocalcinosis in CF and other chronic debilitating diseases may be explained by factors known to affect calcium handling. Our evidence does not support a primary renal defect as the basis of hypercalciuria and nephrocalcinosis in CF.     

Pseudomonas cepacia colonization in patients with cystic fibrosis: risk factors and clinical outcome

During the period of 1979 to 1983, 38 patients with cystic fibrosis (CF) at the CF center of St. Christopher's Hospital for Children in Pennsylvania developed respiratory tract colonization with Pseudomonas cepacia. Seventeen (45%) of the patients with colonization died. Yearly incidence rates of P. cepacia colonization fluctuated between 1.3% and 6.1%, suggesting an endemic phenomenon. Case-control studies showed that severe underlying CF, use of aminoglycosides, and having a sibling with CF and P. cepacia colonization were significant risk factors for P. cepacia colonization. Once colonized with P. cepacia, patients with CF were likely to be hospitalized longer (P = 0.008) and to die sooner (P = 0.0001) than control patients with CF. Environmental and microbiologic studies did not identify a common source or mode of transmission of P. cepacia among patients. The results of this investigation suggest that P. cepacia colonization of patients with CF was endemic in the hospital, occurred more frequently in those with severe disease, and was associated with adverse clinical outcome.     

Ear disease is not a common complication in cystic fibrosis

Although upper respiratory tract involvement is a common finding in cystic fibrosis (CF), there is no agreement on whether hearing is affected in these patients. We studied 75 CF subjects and 50 healthy agematched children with the same audiological protocol. An original scoring system was used to quantify the degree of hearing involvement (normal, mild, moderate and severe) in each subject. Prevalence of ear involvement in children with CF was similar to that in agematched control subjects (25.4% and 18% respectively,P>0.05). Ear disease in CF was not related to pulmonary disease, radiological sinusitis, nasal polyposis, or use of parenteral aminoglycosides. These data showed that the risk of ear disease in CF was not increased even if patients with severe audiological involvement were described only in the CF group.     

Serum magnesium in health and disease

Summary Serum magnesium levels were determined in 500 children—100 normal controls and 400 patients with various clinical disorders. A wide range of values was obtained. The clinical features of hypomagnesaemia and its treatment are discussed. From the Department of Pediatrics, V, J. Hospital and Medical College, Amritsar.     

Hypo- and hypermagnesemia in an Indian Pediatric Intensive Care Unit

Data on magnesium disturbances in critically ill children admitted to a Paediatric Intensive Care Unit (PICU) are scarce, especially from developing countries. We have studied occurrence and incidence of hypo- and hypermagnesaemia in children admitted to a PICU and the correlation between such disturbances and the outcome of illness. A total of 100 children (68 boys, 32 girls) aged 6 months to 12 years (mean +/- SD 4.9 + 3.5 years) admitted consecutively to a PICU were studied. At admission and on every alternate day venous blood was obtained for the estimation of serum and RBC-magnesium, serum calcium, sodium, and potassium, and arterial blood for ionized calcium and pH. This was done after ethical approval and informed consent. Hypomagnesaemia and hypermagnesaemia occurred in 60 per cent and 4 per cent of patients, respectively. The incidence of hypomagnesaemia was 30.1, and hypermagnesaemia was two episodes per 100 patient days. The incidence of low RBC-Mg was 17.3 episodes per 100 patient days. Hypomagnesaemia was most common in patients with raised intracranial pressure (63 episodes per 100 patients days). Mortality was nine-fold higher in hypomagnesaemic (30 per cent, 19 of 63) compared with normomagnaesemic (3.3 per cent, one of 30) patients. If Mg and Ca both were low, the mortality rate was 33 per cent (15 of 45 patients) in contrast to nil if both were normal (p < 0.05). We conclude that hypomagnesaemia and low RBC-Mg are a common occurrence in PICU patients and are associated with higher mortality.     

Distal renal tubular acidosis with severe hypokalaemia, probably caused by colonic H(+)-K(+)-ATPase deficiency.

We describe a 21 month old male infant who presented with failure to thrive associated with severe hypokalaemia and metabolic acidosis, together with hypomagnesaemia. Evaluation revealed marked renal and probable faecal potassium wasting, distal renal tubular acidosis, mild urinary magnesium wasting, and a normal gastric pH (gastric H(+)-K(+)-ATPase). Hypokalaemic forms of metabolic acidosis, such as diabetic ketoacidosis and proximal renal tubular acidosis were ruled out from the clinical picture. The hypokalaemia of distal renal tubular acidosis usually improves with alkali therapy, but this was not observed: despite correction of acidosis with 5 mmol/kg potassium citrate per day, an additional 5 mmol/kg potassium chloride was required to bring serum potassium to 3.5 mmol/l. At 3 years of age potassium was provided in the absence of potential alkali and acidosis ensued; serum bicarbonate fell to 10 mmol/l. Although a specific genetic analysis is not yet possible, the abnormalities are consistent with a novel form of distal renal tubular acidosis. The pathophysiology probably does not stem from defects in the vacuolar H(+)-ATPase but more likely from deficient activity of the colonic isoform of H(+)-K(+)-ATPase that is resident in the medullary collecting duct and mediates potassium absorption and proton secretion.