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This article discusses the case of a 5-year-old black girl who was found to have high blood pressure during a routine medical examination. Further tests showed that she had hypokalemia, low blood levels of potassium, and alkalosis, low blood acidity associated with high bicarbonate levels. Levels of two compounds that regulate blood pressure and salt and water balance were also abnormal. Testing after hospitalization showed normal kidney function, but high levels of two adrenal cortex-derived steroids. Computed tomography (CT) scan showed no abnormalities in the adrenal glands. Medication lowered blood pressure somewhat. Repeat CT scans over the next year suggested a slight change in the left adrenal gland. Further tests showed excessive activity in the left adrenal, consistent with a tumor. Following adrenal gland removal, blood pressure normalized as did blood tests. The process used to establish the final diagnosis of adrenal hyperplasia (overgrowth), rather than adenoma is discussed, along with methods used to distinguish this disorder from other conditions, such as renal (kidney) artery stenosis (constriction), mineralocorticoid (steroids regulating salt balance) excess syndrome, or other diseases. (Consumer Summary produced by Reliance Medical Information, Inc.)

Patients receiving treatment by artificial kidney, or renal dialysis, have been considered at risk for toxicity as a result of increased aluminum intake. Signs of aluminum toxicity include dementia, bone fractures, bone pain and muscular weakness. Initial studies showed that to a great extent this problem of increased aluminum could be traced to the concentration of aluminum in the water used to make the dialysis fluid. Most centers subsequently changed to a pre-treated water source and the condition was greatly improved. Some patients continue to show the effect of aluminum toxicity on their central nervous systems. Some clinicians suspect that other sources of aluminum, including the compounds used to buffer or adjust the acidity of intravenous solutions used in these patients, may be responsible. This study surveys the level of aluminum-related disease in a population of dialysis patients seen between 1986 and 1987. Questionnaires covering 855 patients were collected from the dialysis staffs at a number of medical centers. Data collected indicated that signs and symptoms of aluminum-related conditions occur infrequently in dialysis patients, but when they do occur, they are likely to be associated with years on dialysis or with years of receiving oral aluminum gel. In 28 percent of the cases, aluminum levels were obtained which were found to correlate with the number of years of dialysis treatment. These data suggest that patients on long-term dialysis or those which receive aluminum gels are at increased risk for aluminum toxicity.

Over the years, aldosterone has been a favorite topic of renal physiologists given its role in the maintenance of body fluids. Investigators only recently are coming to appreciate a second proinflammatory and profibrotic role for this hormone. Mineralocorticoids such as aldosterone trigger a profibrotic process that in many respects mimics the early phase of wound healing. Depending on the type of cell involved, aldosterone may activate the profibrotic process through classic mineralocorticoid receptors, nonclassic membrane-associated mineralocorticoid receptors, and/or glucocorticoid receptors. In the kidney, the actions of aldosterone can be attenuated by 11-dehydro metabolites of endogenous glucocorticoids generated by isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD-1 and 11β-HSD-2). Thus, the renal 11β-HSD isoforms may have 2 functions: to block the improper activation of mineralocorticoid receptors by binding endogenous glucocorticoids and to synthesize agents that limit the actions of aldosterone. Although sodium in the diet has been implicated in aggravating aldosterone-induced renal fibrotic processes, preliminary findings are consistent with the view that aldosterone alone can initiate matrix production in renal tissue even in the absence of active sodium transport. Thus, there is a growing body of laboratory and clinical evidence supporting the use of inhibitors of aldosterone action in patients with both glomerular and tubular diseases.

Aldosterone (Aldo) can be a profibrotic factor in cardiovascular and renal tissues. This study tests the hypothesis that prolonged Aldo exposure is able to directly induce fibrotic changes in the kidney of a normal nonhypertensive animal. Immortalized rat proximal tubule cells (IRPTC) containing 11β-hydroxysteroid dehydrogenase (11β-HSD1) but no mineralocorticoid receptors (MR) and mouse inner medullary collecting duct cells (IMCD) containing 11β-HSD2 and MR were examined. IRPTC exposed to Aldo or corticosterone (10 nM) for 48 h demonstrated no change in collagen production as assessed by Sirius red staining. In contrast, IMCD treated with Aldo exhibited a marked increase in the expression of collagen, fibronectin, and connective tissue growth factor (CTGF), whereas corticosterone alone had no effect. The Aldo-induced overexperession of collagen, fibronectin, and CTGF was substantially attenuated by the MR antagonist RU-318 and by the 11β-HSD end product 11-dehydrocorticosterone, but not by the glucocorticoid receptor antagonist RU-486. In vivo, early fibrotic changes with elevated collagen, fibronectin, and CTGF expression were observed in kidneys isolated from normotensive adrenalectomized mice receiving a continuous infusion of Aldo (8 μg·kg−1·day−1) for 1 wk. These changes were not present in corticosterone-treated mice. Aldo-induced changes were attenuated in adrenally intact mice and in mice treated with RU-318 or 11-dehydrocorticosterone. Thus, extended Aldo exposure produces fibrotic changes in cells containing MR and in normal kidneys. MR antagonists and the end products of 11β-HSD attenuate these fibrogenic effects.

The association between excess glucocorticoids and hypertension has been much discussed but poorly understood. From both clinical observations and laboratory studies, it is clear that glucocorticoids exert their effects at many different sites responsible for blood pressure regulation. Isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD), located in steroid-responsive tissues, metabolize endogenously produced glucocorticoids. These enzymes limit steroid access to mineralocorticoid and/or glucocorticoid receptors. In the kidney, synthetic and endogenous glucocorticoids are capable of enhancing transepithelial sodium transport in the presence of 11β-HSD inhibition. Proximal tubule reabsorption of sodium can be indirectly augmented after chronic exposure to glucocorticoids. In this segment, steroids have a permissive effect, increasing the expression of both Na+, K+adenosine triphosphatase along the basolateral membrane and Na+-H+exchanger along the apical membrane of epithelial cells. Although glucocorticoids themselves produce no increase in sodium reabsorption in this segment, angiotensin II-stimulated sodium transport is significantly greater in proximal tubular cells pretreated with glucocorticoids. The increased transport in distal renal segments is more direct and stems in part from glucocorticoid cross-over binding to mineralocorticoid receptors. In vascular tissue, synthetic and endogenous glucocorticoids, after inhibition of the dehydrogenase reaction, magnify the response to circulating vasoconstrictors. The effects of glucocorticoids in vascular tissue is indirect, upregulating the expression of receptors to many vasoconstrictors and downregulating the effects of potential vasodilators. Thus, glucocorticoids have the potential to alter both circulating volume and vascular resistance.

Network 1 (New England) initiated the Clinical Indicator Project to survey dialysis adequacy (Kt/V), nutrition (serum albumin level), and anemia management in patients maintained on chronic dialysis. Because little information is available in children, data were specifically recorded covering these variables in patients (age, 1 to 18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD). During the 18 months of data collection, 29 observations were recorded on 23 HD patients (age, 14.3 ± 3.6 years), and 43 observations were made on 30 PD patients (age,10.6 ± 4.7 years). Kt/V correlated inversely with the age of the patient (HD, P< 0.004; PD, P< 0.0007). Although serum albumin level was not associated with dialysis adequacy in HD patients, there was a strong inverse relationship between albumin level and Kt/V in PD patients (P< 0.002). Hematocrit values were not significantly different in the two groups (HD, 31.0% ± 5.5% versus PD, 32.9% ± 4.8%) and could not be correlated with weekly erythropoietin dose. Weekly erythropoietin dose was directly related to patient age in both groups (HD, P< 0.05; PD, P< 0.02). The weekly erythropoietin dosage needed to maintain the hematocrit was greater in HD patients (HD, 11,211 ± 7,484 U versus PD, 3,790 ± 1,968 U; P< 0.0001). We conclude that (1) smaller children in both groups tend to have a greater Kt/V, (2) Kt/V greater than 2.75 in PD patients may not improve nutrition per se and could result in increased albumin losses, and (3) erythropoietin dosing appears to correlate best with patient size (age) rather than degree of anemia.

The association between excess glucocorticoids and hypertension has been much discussed but poorly understood. From both clinical observations and laboratory studies, it is clear that glucocorticoids exert their effects at many different sites responsible for blood pressure regulation. Isoforms of the enzyme 11ß-hydroxysteroid dehydrogenase (11ß-HSD), located in steroid-responsive tissues, metabolize endogenously produced glucocorticoids. These enzymes limit steroid access to mineralocorticoid and/or glucocorticoid receptors. In the kidney, synthetic and endogenous glucocorticoids are capable of enhancing transepithelial sodium transport in the presence of 11ß-HSD inhibition. Proximal tubule reabsorption of sodium can be indirectly augmented after chronic exposure to glucocorticoids. In this segment, steroids have a permissive effect, increasing the expression of both Na+, K+adenosine triphosphatase along the basolateral membrane and Na+-H+exchanger along the apical membrane of epithelial cells. Although glucocorticoids themselves produce no increase in sodium reabsorption in this segment, angiotensin II-stimulated sodium transport is significantly greater in proximal tubular cells pretreated with glucocorticoids. The increased transport in distal renal segments is more direct and stems in part from glucocorticoid cross-over binding to mineralocorticoid receptors. In vascular tissue, synthetic and endogenous glucocorticoids, after inhibition of the dehydrogenase reaction, magnify the response to circulating vasoconstrictors. The effects of glucocorticoids in vascular tissue is indirect, upregulating the expression of receptors to many vasoconstrictors and downregulating the effects of potential vasodilators. Thus, glucocorticoids have the potential to alter both circulating volume and vascular resistance.

The hormonal interactions that regulate electrolyte transport in the proximal tubule are complex and incompletely understood. Since endogenous glucocorticoids and angiotensin II each can affect electrolyte transport in this renal segment, we hypothesized that local metabolism of glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) might alter the response to angiotensin II. Studies were conducted in cultured origin defective SV-40 transformed immortalized renal proximal tubule cells (IRPTC) derived from weanling Wistar rat kidney. The 11β-HSD contained in these cells uses NADP+, has an apparent Kmfor corticosterone of 1.6 μM, but functions only as a dehydrogenase (corticosterone → 11-dehydro-corticosterone). When mounted in modified Ussing chambers, IRPTC generate a transmembrane current, and angiotensin II (10 pMto 10 μM) increases this sodium-dependent current. Cells incubated with corticosterone (100 nM) and the 11β-HSD inhibitor carbenoxolone (CBX) (1 μM) for 24 hr and then acutely stimulated with angiotensin (10 nM) show a greater rise in current than do cells exposed to corticosterone alone and stimulated with angiotensin (corticosterone + CBX: 64.2% ± 20.5% vs. corticosterone: 18.8% ± 5.9%; P> 0.02 at 180 min)[mean ± SE percentage above baseline, n= 8/group]. Cells exposed to corticosterone (100 nM) or CBX (1 μM) alone for 24 hr and then stimulated with angiotensin II (10 nM) had responses similar to controls. Thus glucocorticoids can enhance angiotensin II-induced electrolyte transport in proximal tubule epithelial cells when local 11β-HSD is inhibited.

Increased calcium-activated potassium channel (KCa) activity in vascular smooth muscle (VSM) cells leads to a relaxation response counteracting the effects of high blood pressure. Since chronic exposure to glucocorticoids (GC) can be associated with an increase in blood pressure, we reasoned that GCs might modify the expression ofKCachannels resulting in a net rise in vascular tone. To test this hypothesis, primary cultures of rat VSM cells were exposed to (a) RU 28362 (a pure glucocorticoid receptor agonist), 1 μM; (b) corticosterone 10 nM + carbenoxolone (an inhibitor of bidirectional VSM 11β-OH steroid dehydrogenase), 1 μM; (c) 11-dehydrocorticosterone (a biologically inactive metabolite), 10 nM + carbenoxolone; (d) carbenoxolone alone; or (e) aldosterone 10 nM for periods of up to 72 h. Proteins were then extracted and Western blots prepared. Gels were probed with a rabbit-derived polyclonal antibody directed againstKCachannel protein. The experimental procedure was repeated on separate sets of VSM cells to ensure reproducibility. Expression ofKCachannel protein was diminished in VSM cells incubated with corticosterone + carbenoxolone and with RU 28362 after 24 h and remained low at 72 h. Expression ofKCaprotein in cells exposed to 11-dehydrocorticosterone + carbenoxolone, carbenoxolone alone, and aldosterone was either similar to controls or mildly increased over the 72 h. These data are consistent with the hypothesis that GCs diminish the expression ofKCaprotein. DiminishedKCaexpression could contribute to the observed increase in vascular tone following chronic GC exposure.

An approach to the study of infants with hematuria and proteinuria is offered so that renal impairment can be effectively recognized and treated.

We describe three patients with Lowe (oculocerebrorenal) syndrome, emphasizing primarily the central nervous system and renal pathology. Using magnetic resonance imaging, we noted diffuse high T2 signals periventricularly, indicating significant white matter destruction, which may be responsible in part for the mental retardation, seizure disorder, hypotonia, and areflexia observed in the patients. In contrast to previously published reports, there was minimal renal tubular dysfunction; however, proteinuria was significantly increased in all patients. We believe that the observed proteinuria is primarily the result of glomerular pathology rather than renal tubular dysfunction and may represent a net loss of negative charges within the glomerular filter. This loss of charge may be linked to the increased excretion of glycosaminoglycans in the urine.

A relative cardiac hypertrophy has been observed in newborns chronically treated with dexamethasone. To test the hypothesis—that dexamethasone might alter steroid metabolism within the heart—rat pups were injected with vehicle, corticosterone (dosages 20 or 200 μg/pup/injection, or 1 mg/pup/injection) or dexamethasone (5 μg/pup/injection) on Day 2-6 and sacrificed on Day 7-8. Injections with dexamethasone in this dosage have induced the cardiac changes in this rat model. 11β-Hydroxysteroid dehydrogenase (11β-OHSD) activity was assessed in hearts from these adrenally intact rat pups by incubating tissues with 3H-corticosterone 10-8Mfor 60 min. On Day 7-8, controls transformed 10.3% ± 1.1% (mean ± SE) of the cortico-sterone (Compound B) to 11-dehydrocorticosterone (Compound A) generating 1.25 ± 0.35 × 10-12moles A/mg protein (n= 8). Tissues from pups pretreated with cortico-sterone at all three dosages were not different from controls in percent metabolized and moles A/mg generated. In contrast, hearts from dexamethasone treated pups transformed only 4.5% ± 1.0% of the corticosterone to A generating 3.19 ± 0.05 × 10-13moles A/mg protein (n= 10) (P<0.05 versus control in moles/mg protein metabolized). Cultured cardiomyocytes exposed to dexamethasone for 4 days in vitro also decreased their expression of 11β-OHSD mRNA. Readily metabolized endogenous glucocorticoids produced little or no effect on developing heart muscle while treatment with dexamethasone, a potent synthetic glucocorticoid, induced relative cardiac hypertrophy and downregulated 11β-OHSD mRNA expression and enzyme activity.

Psychosocial character traits and coping skills were examined in 12 children with end-stage renal failure. Six of the children were maintained on in-center hemodialysis and 6 were treated with home peritoneal dialysis. All of the patients felt a lack of ability to control their lives. The incidence of anxiety, depression, and hostility did not appear to vary from a population of healthy adolescents. Personal and social adjustment scores were, on average, on the 20th percentile. Coping skills appeared to be most influenced by the mode of dialysis treatment. Home peritoneal dialysis patients utilized self-reliance as a coping process more often than their counterparts on hemodialysis. We conclude that children maintained on chronic dialysis therapy demonstrate reasonable psychological adjustment with some differences in social and emotional functioning when compared with healthy children, and that the type of treatment chosen may influence the development of certain coping skills.

Disorders of potassium balance occur often in clinical practice. Significant acute changes in extracellular potassium concentration influence “biologic electricity,” the ability for excitable cells in the body to conduct impulses or signals. Ileus, muscle weakness, and myocardial irritability can be signs and symptoms associated with altered biologic electricity and potassium imbalance. Most therapeutic interventions are directed to restoring a normal extracellular potassium concentration and “bioelectric conduction.”

Endogenous glucocorticoids are converted to their biologically inert 11-dehydroderivatives by isoforms of the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD). The low-Km, NAD+-dependent renal isoform (Type 2) identified in the distal nephron protects mineralocorticoid receptors from activation by endogenous glucocorticoids. The function of high-Km, NADP+-dependent renal isoform (Type 1) is less well understood. Since glucocorticoids may modulate sodium transport in renal proximal tubules (PT), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na+. 11β-HSD activity was assessed in homogenates of canine PT by the conversion of cortisol to cortisone in the presence of NADP+200 μM. A high-Na+diet for 4 days increased the Vmax4-fold, with no change in the Type 1 Km(40 mEq/day Na+diet: Km0.959 μM, Vmax3.40 pmoles/min/mg protein versus 150 mEq/day Na+diet: Km0.962 μM, Vmax14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+diet produced no detectable change in the Type 2 isoform enzyme kinetics and mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11β-HSD can be regulated by dietary Na+independent of changes in the renal Type 2 isoform.

A 6-year-old girl presented with acute hypertension and urinary tract infection. Evaluation revealed congenital absence of the inferior vena cava associated with an atrophic right kidney. A possible embryologic mechanism is proposed in an effort to relate the renal findings and vascular anomaly. In addition, any possible relationships among the urinary tract infection, the hypertension and the renal abnormality are discussed.

Lymphomatous involvement of the kidneys is a common manifestation of systemic nonHodgkin’s lymphoma but associated renal dysfunction is uncommon. In contrast, lymphoma originating within the kidneys is a rare event. We report a case of primary renal lymphoma presenting with renal insufficiency and hypertension in a 10-year-old boy.

A 9-year-old girl with meningomyelocele, an ileal conduit and a living related kidney transplant presented with a progressive gait disturbance. Radiographic evaluation included a computerized tomography scan that disclosed a large right psoas muscle abscess. The abscess cavity was drained percutaneously and culture of its contents yielded Pasteurella multocida. This case illustrates an unusual presentation of a psoas muscle abscess caused by an uncommon organism that was diagnosed and treated by nonoperative methods.

A seven week old previously healthy infant presented with tonic posturing and central nervous system irritability after concentrated tea ingestion. Using a gas chromatographic analysis technique, a sample of similarly prepared tea was examined for levels of caffeine, theophylline, and theobromine. Caffeine was the only xanthine found in the tea. A simulation of caffeine absorption and elimination was performed on a computer utilizing Euler's method on a three compartment model consisting of caffeine in the gut, in the body water, and caffeine excreted. Convulsions after caffeine administration have been reported at doses of 7 mg/kg. In our patient, the total estimated ingested dose of caffeine was 75 mg or 14.7 mg/kg with a maximum predicted blood level at 3 2/3 hours. A xanthine blood level from the infant at 5 hours was 1.1 mg/100 ml compared to a computer predicted value of 1.3 mg/100 ml. Computer simulation may be utilized to predict the pharmacologic course and distribution of ingested agents.