Clinical guidelines and hospital discharges of children with acute urinary tract infections

 In order to evaluate the effect of the introduction of recent similar guidelines on the treatment of acute urinary tract infection (UTI) in children, and possible changes in its epidemiology, we analyzed the records of hospital discharge for acute UTI under the age of 15 years in England and Wales between 1979 and 1993 and in Finland between 1978 and 1994. Cases were defined by the ICD9 diagnostic codes 590.1 (acute pyelonephritis) and 599.0 (UTI, site not specified) for males and females according to three age groups (0–4, 5–9, and 10–14 years). We also compared the registry data on kidney transplants due to end-stage renal disease caused by recurrent pyelonephritis in the United Kingdom and Finland. In England the rate of attack of symptomatic UTI per 1,000 girls under 15 years increased from 0.74 (95% confidence interval 0.71–0.76) in 1987 to 1.32 (1.29–1.35) in 1993 (P<0.001, test for trend). The respective figures for Finnish girls were 1.74 (1.62–1.86) in 1987 and 1.62 (1.51–1.74) in 1993 (P=0.72). In English boys, the increase in the attack rate was from 0.38 (0.36–0.40) in 1987 to 0.70 (0.68–0.73) in 1993 (P<0.001). In Finnish boys the respective figures were 0.74 (0.66–0.82) in 1987 and 0.88 (0.80–0.97) in 1993 (P<0.02). The observed increases in the attack rates of UTI most probably relate to increased referral of acute UTI patients to hospitals for the recommended imaging studies rather than changing occurrence. Publication of guidelines for treatment of UTI in children, consolidating more-general awareness, may have contributed to this. The mean annual numbers of kidney transplants in the United Kingdom and Finland during 1989–1995 due to end-stage renal disease caused by pyelonephritis were of similar magnitude, i.e., 1.9 (1.6–2.3) transplants per million inhabitants in the United Kingdom and 2.8 (1.5–4.7) transplants per million inhabitants in Finland. The decreasing trend in these figures in both countries, although statistically significant only in the United Kingdom (P<0.05, test for trend), suggests improved long-term outcome of these patients induced by better diagnosis and treatment of pyelonephritis and the diseases related to it, such as congenital malformations. According to our data, valid clinical guidelines are effective in changing clinical practice. Received: 1 September 1997 / Revised: 29 April 1998 / Accepted: 29 April 1998     

Influence of serum albumin on renal function in nephrotic syndrome

 Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), determined by the clearances of inulin and para-aminohippuric acid, were evaluated in 119 children with different types of nephrotic syndrome and in different stages: the nephrotic stage (serum albumin <25 g/l), recovery stage (25–35 g/l), and remission (>35 g/l). GFR in the nephrotic stage was significantly lower than in remission and in controls, and was lowest at onset of the disease (84±6, 111±4, and 119±2 ml/min per 1.73 m²). ERPF was higher in the nephrotic stage than in recovery, especially in children with histological lesions. Thus the filtration fraction (FF) was greatly decreased in the nephrotic stage. In patients investigated both in the nephrotic and the remission phase, GFR and FF increased significantly. There was a direct correlation between the serum albumin concentration and FF and an inverse correlation between mean arterial pressure (MAP) and GFR and FF in all patients, a direct correlation between the serum albumin concentration and GFR in minimal change nephrotic syndrome patients, and an inverse correlation between ERPF and serum albumin in children with histological lesions. In conclusion, GFR and FF were decreased and ERPF increased in the nephrotic stage, normalizing in remission. The low GFR in the nephrotic stage was thus not dependent on hypoperfusion. We suggest that the low GFR is dependent on a very low ultrafiltration coefficient. The direct correlation between GFR and serum albumin and the indirect correlation between GFR and MAP suggest compensatory mechanisms that increase the ultrafiltration pressure to counteract the severely reduced ultrafiltration coefficient. Received: 19 November 1997 / Revised: 11 April 1998 / Accepted: 14 April 1998     

Impact of a preceding striatal excitotoxic lesion and treatment with ciliary neurotrophic factor on striatal graft survival

The survival of grafted embryonic striatal tissue, dissected from the lateral ganglionic eminence, depends on the status of the host striatum. We found significantly larger volumes of surviving graft tissue and of striatal-like tissue (P-zone) within the graft, when the host striatum had been subjected to an excitotoxic lesion prior to transplantation surgery. Concomitantly the numbers of surviving grafted cells, assessed in both cresyl violet-stained sections and in sections stained with an immunohistochemical marker for striatal neurons, increased as compared to when graft tissue was placed in an intact unlesioned striatum. Finally, we examined the impact of treatment of the donor tissue with ciliary neurotrophic factor (CNTF) on graft survival. CNTF has previously been shown to protect striatal neurons against excitotoxic insults both in vitro and in vivo, but it did not improve striatal graft survival when added to the cell suspension prior to implantation.     

Perioperative blood transfusions after allogenic renal transplantation

Summary The requirement of blood transfusions was evaluated in a two compartment (retrospective/prospective) study in our renal transplantation program. Between July 1st, 1993 and December 31st, 1994 (observation period I) we retrospectively investigated 110 patients with end stage renal disease and anemia undergoing kidney transplantation. Between January 1st, 1995 and December 31st, 1996 (observation period II) the requirement of blood transfusions was followed prospectively in 134 patients after allogenic renal transplantation. The amount of blood drawn for preoperative diagnostic investigations was in observation period I significantly higher (280 ml) than in observation period II (150 ml) (p = 0.02). For postoperative diagnostic tests in observation period II significantly less blood (240 ml) was needed than in observation period I (510 ml) (p = 0.01). The intraoperative bloodloss was similar in both periods (170 ml vs. 190 ml; p = 0.6). The need for closer graft observation was the reason for significantly increased amount of blood transfusions in patients with delayed graft function. The number of blood transfusions was significant lower in patients with primary graft function (p = 0.0001). There was no correlation between blood transfusions and the use of ATG/OKT3, surgical complications and reoperations. With an improved management of blood drawing for diagnostic tests after allogenic kidney transplantation the number of perioperative blood transfusions can be reduced significantly.      

Effective treatment of acute hyperkalaemia in childhood by short-term infusion of salbutamol

Hyperkalaemia is a lifethreatening emergency and infusion of glucose with insulin has so far been regarded as the standard treatment of choice. Recently the -2 stimulatory drug salbutamol has been shown to be an effective agent to treat hyperkalaemia by inducing a shift of potassium into the intracellular compartment. We treated 15 children aged 0.1–14 (mean 5.2) years suffering from acute hyperkalaemia (mean level 6.6±0.54, range 5.9–7.7 mmol/l) with a single infusion of salbutamol (5 g/kg over 15 min). Serum potassium concentrations decreased significantly within 30 min to levels of 5.74±0.53 and 4.92±0.53 mmol/l after 120 min (P<0.001, respectively). No side-effects occurred other than a slight increase in heart rate in 3 patients.Conclusion A single intravenous infusion of salbutamol at a dose of 5 g/kg is a highly effective treatment for hyperkalaemia with minimal clinical side-effects. The effect lasts for at least 120 min and may reverse hyperkalaemia in some patients without further interventions so that salbutamol seems justified as the first choice treatment for this condition in childhood.     

Increased levels of urinary interleukin-6 in Kawasaki disease

Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels ofN-acetyl--d-glucosaminidase (NAG) and ₂-microglobulin (₂-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and ₂-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD.     

The effect of naringenin on the intestinal and renal transport of organic solutes

Summary Naringenin (4,5,7-trihydroxy-flavanone) inhibits the accumulation of glycine, -methyl-glucoside, p-amino-hippurate and N¹-methyl-nicotinamide in dog renal cortex slices. It also inhibits oxygen consumption by this tissue. Since the sensitivity of amino-acid uptake to the drug is less than the sensitivity of oxygen consumption, the inhibition of this transport might be secondary to an effect on intermediary metabolism. The inhibition of PAH uptake occurs at a lower concentration of the drug, and so naringenin may affect this process at the membrane level.Naringenin inhibits the transport of sugars and amino-acids by dog, guinea-pig and rat small intestine. Both steady-state accumulation and initial rates of entry are affected. Amino-acid uptake is depressed both in the presence or absence of sodium ions. The inhibition is reversible provided short contact times are employed. According to kinetic analysis, naringenin appeared to be a fully non-competitive inhibitor of phenylalanine influx. Examination of the unidirectional transmural fluxes of phenylalanine across guinea-pig intestine revealed that only the mucosal-serosal flux was affected, and then only if the flavanone was added to the solution bathing the mucosal face of the tissue. Naringenin does not inhibit mucosal Na⁺-K⁺-ATPase, but it does alter the intracellular ion concentrations.Although some of the results can be explained in terms of an effect of naringenin on metabolism, others can not. It is argued that naringenin has a direct action on cell membranes.Some of these results have been presented to the Physiological Society and a short report has appeared in their proceedings (Robinson, 1979)     

Changes in blood flow and vasculature of the dog kidney undergoing normothermic and hypothermic ischaemia

Summary In 11 mongrel dogs both kidneys have been subjected to a 2 h ischaemic period. One kidney was cooled by perfusing the renal artery at 4°C while the contralateral normothermic kidney was clamped for 2 h. Studying the renal blood flow using the Xenon wash out technique, sequential renal scanning and angiography, marked differences between hypo- and normothermic ischaemia kidneys were observed. One or two hours following hypothermic perfusion a marked decrease of blood flow in the first compartment and vasoconstriction was evident, while within this period following normothermic ischaemia an enhanced renal blood flow was observed. After 24 h renal blood flow and renal function tested by ¹³¹I-Hippuran clearance returned to normal values. Angiographic studies corresponded to the preoperative findings. In contrast, normothermic ischaemia kidneys showed a decreased renal blood flow, impairment of kidney function in isotope studies and pathological angiographic changes.Supported by Deutsche Forschungsgemeinschaft     

Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat

Summary The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml ·kg^–1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure.In healthy rats saralasin (6 g·kg^–1·min^–1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng·kg^–1·min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.Supported by Deutsche Forschungsgemeinschaft     

Delayed transient neurologic toxicity due to tacrolimus: CT and MRI

We report a case of transient neurologic toxicity secondary to tacrolimus. The clinical and imaging findings are reported and their subsequent regression after interruption of therapy in the patient following a bone-marrow transplant is also described. The etiology of the neurotoxicity and its analogy with other immunosuppressant agents are discussed. Received: 18 June 1999/Accepted: 14 December 1999