An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria

Bartter syndrome (BS) I-IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.

Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C / 소아과

The calcium sensing receptor (CaSR) plays an important role in calcium homeostasis. Activating mutations of CaSR cause autosomal dominant hypocalcemia by affecting parathyroid hormone secretion in parathyroid gland and calcium resorption in kidney. They can also cause a type 5 Bartter syndrome by inhibiting the apical potassium channel in the thick ascending limb of the loop of Henle in the kidney. This study presents a patient who had autosomal dominant hypocalcemia with Bartter syndrome due to an activating mutation Y829C in the transmembrane domain of the CaSR. Symptoms of hypocalcemia occurred 12 days after birth and medication was started immediately. Medullary nephrocalcinosis and basal ganglia calcification were found at 7 years old and at 17 years old. Three hypercalcemic episodes occurred, one at 14 years old and two at 17 years old. The Bartter syndrome was not severe while the serum calcium concentration was controlled, but during hypercalcemic periods, the symptoms of Bartter syndrome were aggravated.

A Case of Adult onset Bartter Syndrome with Nephrocalcinosis / 고신대학교의과대학학술지

Bartter syndrome is a renal tubular defect in electrolyte transport characterized by hypokalemia, metabolic alkalosis, hyperreninemia, hyperaldosteronism, normal blood pressure, and other clinical symptoms. As a clinical and genetical heterogeneous disorder, this syndrome can be classified into two clinical variants, antenatal Bartter syndrome and classic Bartter syndrome according to the onset age. Nephrocalcinosis is common in antenatal Bartter syndrome, but is rare in classic Bartter syndrome. It can also be classified into five genetic subtypes by the underlying mutant gene, all of which are expressed in the tubular epithelial cells of the thick ascending limb of the loop of Henle. Patients with Bartter syndrome type 1, 2 and 4 present at a younger age than classic Bartter syndrome type 3. We have experienced a case of Bartter syndrome with nephrocalcinosis in a 42-year-old woman diagnosed by biochemical and radiologic studies. We had successful response with potassium chloride and spironolactone.

Expression of ciliary neurotrophic factor and its receptor in experimental obstructive nephropathy / 대한해부학회지

Ciliary neurotrophic factor (CNTF) is well known as a growth/survival factor of neuronal tissue. We investigated the expression of CNTF and its specific receptor alpha (CNTFRalpha) in a unilateral ureteral obstruction (UUO) model. Complete UUO was produced by left ureteral ligation in Sprague-Dawley rats. The animals were sacrificed on days 1, 3, 5, 7, 14, 21, and 28 after UUO. The kidneys were fixed, and processed for both immunohistochemistry and in situ hybridization. CNTF immunoreactivity in sham-operated kidneys was observed only in the descending thin limb (DTL) of the loop of Henle. In UUO kidneys, CNTF expression was induced in the S3 segment (S3s) of the proximal tubule from day 1, and progressively expanded into the entire S3s and a part of the convoluted proximal tubules, distal tubules (DT), and glomerular parietal epithelium up to day 7. Upregulated CNTF expression was maintained to day 28. From day 14, the inner medullary collecting duct showed weak CNTF immunoreactivity. The CNTFRalpha mRNA hybridization signal in sham-operated kidneys was weakly detected in the DTL, DT, medullary thick ascending limb, and in a few S3s cells. After UUO, CNTFRalpha mRNA expression increased progressively in both the renal cortex and the medulla up to day 7 and increased expression was maintained until day 28. The results suggest that the S3s may be the principal induction site for CNTF in response to renal injury, and that CNTF may play a role in chronic renal injury.

Alterations of Aquaporin mRNA and Protein Expression in Hypokalemic Rat Kidney / 대한해부학회지

There has been a general agreement that potassium depletion causes metabolic alkalosis and substantial morphological changes in kidney structure, and is associated with renal functional abnormalities, including a decrease in urinary concentrating ability. The present study was to examine the alterations of expression and distribution of AQP-1, 2, 3 and 4 mRNAs and proteins in the kidneys of normal and K-depleted rats using RT-PCR, Western blot analysis, and immunohistochemistry. Predicted size of AQP-1, 2, 3, and 4 mRNAs was 119, 822, 539, and 642 bp, respectively. AQP-1 mRNA expression was gradually decreased in K-depleted rats, particularly LK 2W. AQP-2, 3 mRNAs were markedly decreased in K-depleted rats. AQP-4 mRNA expression was markedly increased in K-depleted rats, particularly LK 2W. Western blot analysis demonstrated that AQP-1 protein expression was only decreased in LK 3D and others were comparable with normal rat. AQP-2, 3 proteins expression was markedly decreased in K-depleted rats, compared with normal rat. But, AQP-4 protein expression was markedly increased in K-depleted rats, particularly LK 3W. In immunohistochemistry, AQP-1 was detected in the apical membranes of proximal tubules and thin limb of Henle loop. In potassium-depleted kidney, the pattern of cellular labeling and signal intensity of AQP-1 protein is identical to that of normal rat. AQP-2 was detected in apical region and cytoplasm of the principal cells of entire collecting duct. In potassium-depleted kidney, the pattern of cellular labeling of AQP-2 protein is identical to that of normal rat, but signal intensity is markedly decreased. AQP-3 was detected in the bosolateral plasma membrane of principal cells of entire collecting duct. In potassium-depleted kidney, the pattern of cellular labeling of AQP-3 protein is identical to that of normal rat, but signal intensity is markedly decreased. AQP-4 was detected in the bosolateral plasma membrane of principal cells of entire collecting duct. In potassium-depleted kidney, the pattern of cellular labeling of AQP-4 protein is identical to that of normal rat, but signal intensity is markedly increased in outer and inner medullary collecting ducts. In summary, these results demonstrate that chronic hypokalemia shows the different expression pattern of AQP-1, 2, 3, and 4 mRNAs and proteins. These results suggest that a decrease in urinary concentrating ability is a major factor in the decreased AQP-2, 3 expression, and that is partly compensated by increased expression of AQP-4.

Expression of Occludin in Porcine Renal Epithelial Cells / 대한해부학회지

Occludin is a cell adhesion molecule that is abundantly expressed in the kidney. However, the expression pattern in various renal epithelial cells is not well established. The purpose of this study was to determine the cellular localization along the tubular epithelial cells in the kidney. Kidneys from adult pigs crossbred of Yorkshire, Landrace and Duroc (three breeds) were processed for immunohistochemistry. Thiazide sensitive sodium chloride cotransporter (TSC), Na+-KATPase bat1, calbindinD28k, and H+-ATPase were used to identify the thick ascending limb, distal convoluted tubule, connecting tubule, and collecting duct, respectively. In the pig kidney, occludin was expressed in the apical domain of the tubular epithelial cells. The immunoreactivity of occludin was strongest in the collecting duct, and then gradually decreased in the connecting tubule, distal convoluted tubule, and thick ascending limb. Occludin expression was weak in the thin limbs of the loop of henle and in the proximal tubule in the pig kidney. These results suggest that occludin may be a major adhesion molecule in distal tubular epithelial cells and play a critical role in maintaining epithelial polarity of these nephron segments.

Renal Handling of Ammonium and Acid Base Regulation

Renal ammonium metabolism is the primary component of net acid excretion and thereby is critical for acid - base homeostasis. Briefly, ammonium is produced from glutamine in the proximal tubule in a series of biochemical reactions that result in equimolar bicarbonate. Ammonium is predominantly secreted into the luminal fluid via the apical Na++xchanger, NHE3. The thick ascending limb of the loop of Henle reabsorbs luminal ammonium, predominantly by transport of NH4+y the apical Na++Cl - cotransporter, BSC1/NKCC2. This process results in renal interstitial ammonium accumulation. Finally, the collecting duct secretes ammonium from the renal interstitium into the luminal fluid. Although in past ammonium was believed to move across epithelia entirely by passive diffusion, an increasing number of studies demonstrated that specific proteins contribute to renal ammonium transport. Recent studies have yielded important new insights into the mechanisms of renal ammonium transport. In this review, we will discuss renal handling of ammonium, with particular emphasis on the transporters involved in this process.

Localization of E-cadherin Along the Nephron Segments in the Rat Kidney / 대한해부학회지

E-cadherin is a cell adhesion molecule that is expressed abundantly in the kidney. However, the expression pattern in various renal epithelial cells is not well established. The purpose of this study was to determine the cellular localization along the nephron segments in the rat kidney. Kidneys from adult Sprague Dawley rats were fixed in 4% paraformaldehyde and processed for immunohistochemistry. Bumetanide-sensitive Na+/K+/2Cl- cotransporter (BSC1), thiazide-sensitive Na+/Cl- cotransporter (TSC), calbindin D28k, and H+-ATPase were used to identify the thick ascending, distal convoluted stubule, connecting tubule, and collecting duct, respectively. In the rat kidney, Ecadherin was expressed mainly in the basolateral domain of the collecting duct and papillary surface epithelial cells. The expression level of E-cadherin changed gradually in the connecting tubule and became moderate in the distal convoluted tubule, thick ascending limb, and loop of Henle. The S1 and S2 segment of the proximal tubule showed weak immunoreactivity. However, E-cadherin was not expressed in the S3 segment of the proximal tubule in the rat kidney. These results suggest that E-cadherin is a major adhesion molecule in the collecting duct and papillary surface epithelium, and that E-cadherin may play a critical role in maintaining the epithelial polarity of these nephron segments.

Renal Effects of Prostaglandins and Cyclooxygenase-2 Inhibitors

Prostaglandins (PGs) with best-defined renal functions are PGE2 and prostacyclin (PGI2). These vasodilatory PGs increase renal blood flow and glomerular filtration rate under conditions associated with decreased actual or effective circulating volume, resulting in greater tubular flow and secretion of potassium. Under conditions of decreased renal perfusion, the production of renal PGs serves as an important compensatory mechanism. PGI2 (and possibly PGE2) increases potassium secretion mainly by stimulating secretion of renin and activating the renin-angiotensin system, which leads to increased secretion of aldosterone. In addition, PGE2 is involved in the regulation of sodium and water reabsorption and acts as a counterregulatory factor under conditions of increased sodium reabsorption. PGE2 decreases sodium reabsorption at the thick ascending limb of the loop of Henle probably via inhibition of the Na+-K+-2Cl-cotransporter type 2 (NKCC2). Cyclooxygenase inhibitors may enhance urinary concentrating ability in part through effects to upregulate NKCC2 in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct. Thus, they may be useful to treat Bartter's syndrome and nephrogenic diabetes insipidus.

Alterations of Aquaporin-1, 2, 3 Protein Expression in Pregnant Rat Kidney / 대한해부학회지

The pregnancy causes the marked change in maternal renal hemodynamic and volume homeostasis. During pregnancy, renal sodium and water retention result in an expansion of extracellular fluid and plamsma volume. Although many studies suggested that water balance or water balance disorder was associated with regulation of Aquaporin (AQP) expression, the studies were only limited to AQP-2 expression during the pregnancy. The present study was to examine altered expression and distribution of AQP-1, 2, and 3 proteins in the kidneys of non-pregnant (NP) and pregnant rats using Westhern blot analysis and immunohistochemistry. Pregnant Sprague-Dawley rats were evaluated on various time sets: days 10.5 (P10.5), 12.5 (P12.5), 17.5 (P17.5), and 19.5 (P19.5). In Westhern blot analysis, expression of AQP-1, 2 was peaked at P17.5 and AQP-3 at 19.5. Immunoreactivity of AQP-1 of NP rat was detected in the apical membranes of proximal tubules and thin limb of Henle loop. In pregnant rats, the pattern of cellular labeling of AQP-1 protein was identical to NP rat, but signal intensity was continuously increased from P10.5 and peaked at P17.5. In NP rat, immunoreactivity of AQP-2 was the most prominent in apical region and moderate in cytoplasm of the principal cells of entire collecting duct. In pregnant rats, the pattern of cellular labeling of AQP-2 protein was identical to NP rat, but signal intensity was moderately expressed in P10.5 and P12.5 and most prominent signal was observed in P19.5. In NP rat, immunoreactivity of AQP-3 was most prominent in the bosolateral plasma membrane of principal cells of entire collecting duct. In pregnant rats, the pattern of cellular labeling of AQP-3 protein was identical to NP rat, but signal intensity was continuously increased from P10.5 to P17.5 and peaked at P19.5. These results suggest that the expansion of extracellular fluid volume and water retention are regulated by AQP-1, 2, and 3 during the pregnancy, especially at late stage.

Proper Use of Diuretics

Diuretics are among the most commonly used drugs. They primarily block active reabsorption of sodium at different sites in the nephron, thereby increasing urinary losses of NaCl and H2O. This ability to induce a negative fluid balance has made these drugs particularly useful in the treatment of a variety of conditions, edematous: congestive heart failure, nephrotic syndrome, liver cirrhosis, chronic renal failure, idiopathic edema, and nonedematous states: hypertension, hypercalcemia, nephrolithiasis, and syndrome of inappropriate antidiuretic hormone secretion. The diuretics are generally divided into three major classes, which are distinguished by the sites at which they impair the sodium reabsorption: loop diuretics at the thick ascending limb of the loop of Henle, thiazide-type diuretics at the distal tubule, and potassium-sparing diuretics at the cortical collecting tubule. The loop diuretics that are generally the most potent are furosemide, torasemide, and ethacrynic acid. The thiazide-type diuretics include chlorothiazide and metolazone. Spironolactone and amiloride are potassium-sparing diuretics. Diuretics should be started at an effective single dose and given intermittently with a subsequent increase in dose or frequency of administration. As a general rule, the rate of diuresis in an edematous patient should not exceed 1 to 2kg weight loss per day. In renal failure patients, loop diuretics at a higher than normal dose are required to get the desired diuretic effect because the diuretic excretion is often limited, in part due to the retention of organic anions. The patients with liver cirrhosis are responsive to spironolactone. After the administration of diuretics, even if a net diuresis is induced, the response is short-lived as a new steady state is rapidly established because the diuretic-induced sodium losses are counterbalanced by neuro-humorally mediated increases in tubular reabsorption at nondiuretic sensitive sites. This process is called compensatory antidiuresis or diuretic tolerance. Therefore sodium restriction is important when a patient is taking loop diuretics, and the concurrent use of a thiazide diuretic can inhibit downstream NaCl reabsorption, resulting in an exaggeration of diuresis. The most common side-effects are those encountered in virtually all the effective drugs: hypovolemia, hypokalemia and potassium depletion, hyperuricemia, and metabolic alkalosis. Other side-effects include hyperglycemia, hyperlipidemia, hyperuricemia, ototoxicity and sexual dysfunction. In addition, diuretics have the potential to increase the toxicity of several other agents. Nonsteroidal antiinflammatory drugs may antagonize the natriuretic effects of diuretics. The combination of potassium-sparing diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may result in severe hyperkalemia.

Expression of H(+)-ATPase in Inner Medullary Collecting Duct Cells of Aquaporin-3-Deficient Mice / 대한해부학회지

It has been reported that the decrease in urinary pH observed in AQP1 null mice with a urinary concentrating defect is due to upregulation of H(+)-ATPase in the IMCD. This is thought to be caused by the chronically low interstitial osmolality in these animals. To explore whether increase of H(+)-ATPase expression in the IMCD is associated with changes in the prolonged decrease of interstitial osmolality, we examined the expression of H(+)-ATPase and Na(+)-H(+) exchanger (NHE3) using light and electron microscopic immunocytochemistry in the kidneys of AQP3 null mice which are polyuric and manifest a urinary concentrating defect because of an inability to create a hypertonic medullary interstitium. In both AQP3 (-/-) and AQP1 (-/-) mouse kidneys, type A intercalated cells in cortical and medullary collecting ducts are slightly activated, and strong H(+)-ATPase immunostaining was present in the apical plasma membrane of IMCD cells, whereas no H(+)-ATPase labeling was observed in IMCD cells in wild type mice. No differences of the immunoreactivity for NHE3 in the proximal tubule and thick ascending limb of loop of Henle were observed between AQP3 or AQP1 (-/-) mice and AQP3 (+/+) mouse. These results suggest that the induction of H(+)-ATPase expression in IMCD cells of AQP3 null mice, as well as AQP1 null mice, may be related to their chronically low interstitial osmolality.

Effects of Bilateral Ureteral Obstruction on Renal Aquaporin Expression / 대한신장학회잡지

BACKGROUND: Obstruction of urinary tract is common cause of renal disfunction. Recent discovery of aquaporin water channels expressed in the kidney and various organs has faciliated our understanding of water transport across the permeable epithelial cell membrane. This study was performed to investigate the effects of bilateral ureteral obstruction on renal expression and cellular distribution of these water channels in rat kidney. METHODS: Male Sprague-Dawley rats were divided two groups. The abdominal cavity was opened and 2-0 silk ligatures were proximally placed on both ureters in experimental group. Sham-operated group was treated in the same procedures except ligation. After closure of the abdomen, the animals were maintained for 48 hr while being given food and water ad libitum. Kidney sections of both groups were processed for immunohistochemistry using antibodies to aquaporin-1, 2, 3, and 4. RESULTS: Immunoreactivity for aquaporin-1 of sham-operated kidney was detected in the apical and basolateral plasma membrane of proximal tubules and thin limb of Henle loop. That of bilateral ureteral obstructed kidney was decreased in the both tubules, especially in the proximal tubules and thin limb of Henle loop of inner medulla. Immunoreactivity for aquaporin-2 of sham-operated kidney was the most prominent in apical region and moderate in cytoplasm of the principal cells of entire collecting ducts. That of obstructed kidney was markedly decreased in entire collecting duct, especially inner medulla except inner stripe of outer medulla. The decrease was in parallel between the apical region and cytoplasm. Immunoreactivity for aquaporin-3 of sham-operated kidney was the most prominent in the basolateral plasma membrane of principal cells of entire collecting duct. That of obstructed kidney was decreased in entire collecting duct. Papillary epithelium was stained in obstructed kidney. Immunoreactivity for aquaporin-4 of sham-operated kidney was moderate in the basolateral plasma membrane of principal cells of collecting ducts of inner stripe of outer medulla and inner medulla. In obstructed kidney, immunoreactivity was detected in cortical and outer stripe of outer medullary collecting duct, and decreased in inner stripe of outer medulla and inner medulla. A marked heterogeneity was observed in inner medullary collecting duct. CONCLUSION: These results indicate that alterations of expression of aquaporin proteins after bilateral ureteral obstruction may lead to change in renal functions, such as urine concentrating ability.

Two Cases of Gitelman's Syndrome Diagnosed by Renal Clearance Study / 대한신장학회잡지

We have experienced two patients who had hypokalemic metabolic alkalosis as well as hypomagnesemia and hypocalciuria with elevated plasma renin activity. We have performed renal clearance study after water loading, administration of furosemide and thiazide in two patients and two normal controls. Maximal free water clearance per 100 mL glomerular filtration rate(CH2O) and distal fractional chloride reabsorption[CH2O/(CH2O+CCl)] in our patients were reduced than the controls. Chloride clearance(CCl) was increased after furosemide administration but not after thiazide administration. Distal fractional chloride reabsorption[CH2O/(CH2O+CCl)] was dramatically decreased by furosemide administration in our patients, whereas thiazide had little effect on it. Fractional excretion of sodium, chloride, magnesium, calcium was increased by furosemide administration, whereas thiazide administration had little effect on this parameters. These findings suggested the presence of a defect in the distal convoluted tubule rather than in the thick ascending loop of Henle. Herein, we report two cases of Gitelman's syndrome diagnosed by renal clearace study after water loading, administration of furosemide and thiazide.

Efeito do antimalático, artesunato de sódio, sobre a funçäo renal / The effects on renal function of sodium artesunate

Introdução. O artesunato de sódio é usado atualmente no tratamento da malária. Os efeitos adversos desta droga não foram descritos, provavelmente porque não podem ser diferenciados dos efeitos relacionados com a malária. Materiais e Métodos. Os efeitos da infusão aguda de artesunato de sódio ( 12 mglkg de peso) sobre a função renal foram estudados em ratos com as técnicas de ciearance. Nós avaliamos também o efeito do artesunato de sódio no fluxo de lúmen-banho de cloreto na porção espessa da alça de Henle (Æb), isolada e perfundida "in vitro". Resultados. A infusão aguda de artesunato ao rato diminuiu o clearance de insulina, apesar de um aumento no fluxo sanguíneo renal. Estes efeitos foram associados com um aumento na excreção urinária de sódio, cloreto, potássio e dos metabólitos do óxido nítrico (NO2/NO3). Nos animais submetidos à sobrecarga de água, o artesunato aumentou o aporte distal de sódio e de água e diminuiu o CH2O corrigido pelo aporte distal de sódio e água. Após uma infusão hipertônica de NaCl, o artesunato diminuiu o TcH2O Corrigido pelo Cosm. Nos experimentos in vitro, o artesunato adicionado à solução do banho de microperfusão nas doses de 10-6 M a 10-3 M diminuiu o fluxo lúmen-banho de cloreto na porção espessa ascendente da alça de Henle do coelho Esta inibição da reabsorção de cloro foi dose dependente, com saturação na dose de 10-4M. Este efeito foi bloqueado completamente por L-NAME 5mM no banho. Quando o artesunato 10-4 M foi adicionado à solução de perfusão não ocorreu alteração do fluxo lúmen-banho de cloreto. Conclusão. Estes resultados sugerem que o artesunato diminui o RFG, aumenta o FSR e a excreção urinaria de Na, C[ e K. Estes achados são devidos, pelo menos em parte, à inibição do transporte de CI através de porção espessa ascendente da alça de Henle corticai e medular. Este efeito é mediado pela produção local do óxido nítrico, uma vez que está associado ao aumento na excreção urinária NO2/NO3 e é bloqueado pelo L-NAME in vitro

Regulation of salt and volume transport along the nephron during acute systolic hypertension

DISCUSSION Acute regulation of sodium pump activity There is a burgeoning literature on mechanisms responsible for short term regulation of Na,K-ATPase activity (Aperia et al, 1996, 1994; Boron et al, 1997; Bertorello & Katz, 1993). Pathways linked to both generation of protein kinase C (PKC) and/or cyclic-AMP dependent protein kinase A are postulated to regulate Na,K-ATPase activity by changing the alpha catalytic subunit phosphorylation status. However, phosphorylation has been associated with both decreased activity (Aperia et al, 1994; Chibalin et al, 1995; Middleton et al, 1993; Satoh et al, 1993a, 1993b), and increased activity (Carranza et al, 1996a, 1996b), and no change in activity (Boron et al, 1997). There is also evidence that PKC causes a withdrawal of sodiuln pumps from the basolateral membranes even if there is mutation of the phosphorylation site (Boron et al, 1997). Proximal tubule Na,K-ATPase activity is also inhibited (whether directly or indirectly is not known) by activation of phospholipase A2 which stimulates production of arachidonate metabolites of cytochrome P-450 such as 20-HETE (Aperia et al, 1996; Nowicki et al, 1997; Ominato et al, 1996). Although the precise signaling mechanisms re main to be elucidated for the responses to altered blood pressure, our results indicate that the inhibition of the sodium pump activity in PT is due to structural modification of the pump itself or an associated regulator, rather than solely mediated by trafficking of active pumps to a new location, because the data demonstrate. significant changes in total ATPase activity that persist through membrane fractionation and phase partitioning, and our results implicate a role of cat P45O aa metabolism to 20-HETE in the response(Zhang et al, 1998) Altered natriuretic responses in hypertension As discussed in the introduction, an altered natriuretic response to an elevation in blood pressure is the hallmark of hypertension. The Spontaneously Hypertensive Rat (SHR)has numerous renal defects that could account for the development of hypertension. In regards to this project, the PT of SHR fail to respond normally to the natriuretic hormone dopamine (Kinoshita et al, 1989), and they have enhanced tubuloglomerular feedback (TGF) response (reviewed in Cowley & Roman, 1997). Our results indicate a distribution of apical sodium transportes in SHR is the same as in acutely hypertensive SD (Magyar et al, 1997), In summary, our findings to date suggest that the dynamic regulation of proximal tubule and loop of Henle sodium transport by fluctuations in blood pressure may be mediated by changes in sodium transporter characteristics at both the apical and basolateral membranes: 1) by reversible inhibition of basolateral Na,K-ATPase activity in the PT and activation in the TALH, and 2) relocation of a set of apical proteins, including NHE-3 and NaPi, consistent with redistribution to intermicrovillar cleft region and/or internalization to endosomal pools in the PT. The reciprocal modulation of Na,K-ATPase activity in PT and TALH contributes the driving force for activating TGF, while minimizing changes in delivery of salt and water to the hormone sensitive distal nephron.

Estudio clínico, evolutivo y terapéutico de un caso de sindrome de Bartter a lo largo de 8 años / Clinic, evolution and therapeutics of a case of Bartter syndrome for 8 years long

Se presenta el caso de un niño de 2 años y 5 meses ingresado por un cuadro de vómitos, diarrea y deshidratación. Llamaba la atención un hipocrecimiento marcado: talla de 69 cm, peso 5320 g. y un perímetro caraneano de 42 cm. Tenía una historia de poliuria y polidipsia desde los 4 meses cuya causa no había sido aclarada. En los exámenes humorales del ingreso se destacaba una alcalosis hipopotasémica y una hiponatremia. Lograda su hidratación en la Unidad de Cuidados Intensivos y descartada la diabetes insípida hipofisaria por la prueba de la vasopresina, se planteó la posibilidad de un Síndrome de Bartter. Esto fue confirmado ya que presentaba cifras exageradas de renina y aldosterona con presión arterial normal. El tratamiento inicial con cloruro de potasio, hidroclorotiazida e indometacina, fue espectacular, mejorando la sintomatología y retornando un crecimiento y desarrollo acelerados. Posteriormente y por razones sociales, hubo dificultades en el control del niño ya que la madre no lo traía a la consulta. Más adelante, al encargarse los abuelos del cuidado del niño, fue posible ajustar las dosis de los fármacos lo que llevó a que mejoraran su peso y talla. Los controles actuales, a los 10 años de edad revelaron: buena escolaridad, EEG normal, normotensión arterial y en lo humoral azoemia y creatininemia normales. El estudio del ionograma en sangre mostró: un sodio de 139 mEq/1 (normal), potasio de 2,6 mEq/1 (bajo), calcio ionizado de 1,18 mmol/1 (normal) y un cloro de 86 mEq/1 (discretamente bajo). El magnesio es normal. En orina el sodio es normal 254 mEq/24 horas, el potasio es alto (124 mEq/24 h.) y un cloro bajo de 154 mEq/24 h. Así pues mantiene un potasio bajo en sangre y aumentado en la orina a pesar de la medicación correcta y continuada. El Síndrome de Bartter, enfermedad genética autosómica recesiva, es provocada por una tubulopatía topografiada a nivel de la rama gruesa del asa de Henle que causa un defecto en la reabsorción del cloro. Aunque poco frecuente (1,2 casos por millon de habitantes) mejora en muchos de sus aspectos como en nuestro caso, con los inhibidores de las prostaglandinas, diuréticos y suplementos de potasio, permitiendo una vida normal