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.
Adult* ; Atrophy ; Bartter Syndrome* ; Biopsy ; Diagnosis ; Extremities ; Female ; Fibrosis ; Glomerulonephritis, IGA ; Humans ; Hyperplasia ; Hypokalemia ; Loop of Henle ; Mesangial Cells ; Parents ; Proteinuria* ; Young Adult

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.
Bartter Syndrome* ; Basal Ganglia ; Calcium ; Extremities ; Homeostasis ; Humans ; Hypocalcemia* ; Kidney ; Loop of Henle ; Nephrocalcinosis ; Parathyroid Glands ; Parathyroid Hormone ; Parturition ; Potassium Channels ; Receptors, Calcium-Sensing*

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.
Adult* ; Age of Onset ; Alkalosis ; Bartter Syndrome* ; Blood Pressure ; Epithelial Cells ; Extremities ; Female ; Humans ; Hyperaldosteronism ; Hypokalemia ; Loop of Henle ; Nephrocalcinosis* ; Potassium Chloride ; Spironolactone

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.
Animals ; Chimera ; Ciliary Neurotrophic Factor ; Ciliary Neurotrophic Factor Receptor alpha Subunit ; Epithelium ; Extremities ; Immunohistochemistry ; In Situ Hybridization ; Kidney ; Ligation ; Loop of Henle ; Neurons ; Rats, Sprague-Dawley ; RNA, Messenger ; Ureter ; Ureteral Obstruction

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.
Ammonia ; Diffusion ; Extremities ; Glutamine ; Handling (Psychology) ; Homeostasis ; Kidney ; Kidney Tubules, Collecting ; Loop of Henle ; Phenobarbital ; Proteins ; Quaternary Ammonium Compounds

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.
Adult ; Cell Adhesion ; Epithelial Cells ; Extremities ; Humans ; Immunohistochemistry ; Kidney ; Loop of Henle ; Nephrons ; Occludin ; Sodium Chloride Symporters ; Swine

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.
Alkalosis ; Animals ; Aquaporins ; Blotting, Western ; Cell Membrane ; Cytoplasm ; Extremities ; Hypokalemia ; Immunohistochemistry ; Kidney ; Loop of Henle ; Membranes ; Potassium ; Proteins ; Rats ; RNA, Messenger

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.
Aldosterone ; Aquaporin 2 ; Bartter Syndrome ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Diabetes Insipidus, Nephrogenic ; Dinoprostone ; Epoprostenol ; Extremities ; Glomerular Filtration Rate ; Kidney ; Kidney Concentrating Ability ; Loop of Henle ; Perfusion ; Potassium ; Prostaglandins ; Renal Circulation ; Renin ; Renin-Angiotensin System ; Sodium ; Water

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.
Animals ; Cell Membrane ; Cytoplasm ; Extracellular Fluid ; Extremities ; Hemodynamics ; Homeostasis ; Immunohistochemistry ; Kidney ; Loop of Henle ; Membranes ; Pregnancy ; Proteins ; Rats ; Rats, Sprague-Dawley ; Retention (Psychology) ; Sodium

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.
Adult ; Animals ; Cadherins ; Calcium-Binding Protein, Vitamin D-Dependent ; Cell Adhesion ; Epithelial Cells ; Epithelium ; Extremities ; Formaldehyde ; Humans ; Immunohistochemistry ; Kidney ; Loop of Henle ; Nephrons ; Polymers ; Rats ; Rats, Sprague-Dawley