Melissa A Cadnapaphornchai

Children's Hospital Colorado, Aurora, Colorado, United States

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Publications (39)155.16 Total impact

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    ABSTRACT: Autosomal dominant polycystic kidney disease is a genetic disorder associated with substantial variability in its natural course within and between affected families. Understanding predictors for rapid progression of this disease has become increasingly important with the emergence of potential new treatments. This systematic review of the literature since 1988 evaluates factors that may predict and/or effect autosomal dominant polycystic kidney disease progression. Predicting factors associated with early adverse structural and/or functional outcomes are considered. These factors include PKD1 mutation (particularly truncating mutation), men, early onset of hypertension, early and frequent gross hematuria, and among women, three or more pregnancies. Increases in total kidney volume and decreases in GFR and renal blood flow greater than expected for a given age also signify rapid disease progression. Concerning laboratory markers include overt proteinuria, macroalbuminuria, and perhaps, elevated serum copeptin levels in affected adults. These factors and others may help to identify patients with autosomal dominant polycystic kidney disease who are most likely to benefit from early intervention with novel treatments.
    Journal of the American Society of Nephrology : JASN. 06/2014;
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    ABSTRACT: In autosomal dominant polycystic kidney disease (ADPKD), progressive kidney cyst formation commonly leads to ESRD. Because important manifestations of ADPKD may be evident in childhood, early intervention may have the largest effect on long-term outcome. Statins are known to slow progressive nephropathy in animal models of ADPKD. This randomized double-blind placebo-controlled phase III clinical trial was conducted from 2007 to 2012 to assess the effect of pravastatin on height-corrected total kidney volume (HtTKV) and left ventricular mass index (LVMI) by magnetic resonance imaging (MRI) and urine microalbumin excretion (UAE) in children and young adults with ADPKD. There were 110 pediatric participants with ADPKD and normal kidney function receiving lisinopril who were randomized to treatment with pravastatin or placebo for a 3-year period with evaluation at 0, 18, and 36 months. The primary outcome variable was a ≥20% change in HtTKV, LVMI, or UAE over the study period. Ninety-one participants completed the 3-year study (83%). Fewer participants receiving pravastatin achieved the primary endpoint compared with participants receiving placebo (69% versus 88%; P=0.03). This was due primarily to a lower proportion reaching the increase in HtTKV (46% versus 68%; P=0.03), with similar findings observed between study groups for LVMI (25% versus 38%; P=0.18) and UAE (47% versus 39%; P=0.50). The percent change in HtTKV adjusted for age, sex, and hypertension status over the 3-year period was significantly decreased with pravastatin (23%±3% versus 31%±3%; P=0.02). Pravastatin is an effective agent to slow progression of structural kidney disease in children and young adults with ADPKD. These findings support a role for early intervention with pravastatin in this condition.
    Clinical Journal of the American Society of Nephrology 04/2014; · 5.07 Impact Factor
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    ABSTRACT: Inflammatory activity is evident in patients with chronic kidney disease with limited data available in ADPKD. We hypothesized that inflammation is an upstream event in the pathogenesis of ADPKD and may be a contributing factor in the disease severity and progression. Serum samples from 61 HALT study A group patients (early disease group with eGFR>60mL/min/1.73m2) were compared with samples from 49 patients from HALT study B group with moderately advanced disease (eGFR 25-60mL/min/1.73m2). Targeted mass spectrometry analysis of bioactive lipid mediators as markers of inflammation was performed and correlated with eGFR and total kidney volume (TKV) normalized to the body surface area (BSA) to assess if these markers are predictive of ADPKD severity. ADPKD patients with eGFR >60mL/min/1.73m2 showed higher levels of 5- and 12/15-lipoxygenase (LOX) and cycloxygenase (COX) generated hydroxy-octadecadienoic acids 9-HODE and 13-HODE and hydroxy-eicosatetraenoic acids 8-HETE, 11-HETE, 12-HETE and 15-HETE as compared to healthy subjects. Linear regression of 9-HODE and 13-HODE revealed significant relationship with eGFR and TKV, while 15-HETE significantly correlated with TKV/BSA. Production of 20-HETE, a P450-produced metabolite of arachidonic acid, was higher in ADPKD patients as compared to healthy subjects and significantly correlated with eGFR and TKV/BSA. Perturbation in fatty acid metabolism is evident early in ADPKD patients, even in those with preserved kidney function. Identified lipoxygenase pathways may be potential therapeutic targets for slowing down ADPKD progression.
    The Journal of Lipid Research 12/2013; · 4.39 Impact Factor
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    ABSTRACT: Nephrotic syndrome is an important clinical condition affecting both children and adults. Studies suggest that the pathogenesis of edema in individual patients may occur via widely variable mechanisms, i.e., intravascular volume underfilling versus overfilling. Managing edema should therefore be directed to the underlying pathophysiology. Nephrotic syndrome is also associated with clinically important complications related to urinary loss of proteins other than albumin. This educational review focuses on the pathophysiology and management of edema and secondary complications in patients with nephrotic syndrome.
    Pediatric Nephrology 08/2013; · 2.94 Impact Factor
  • Melissa A Cadnapaphornchai, Isaac Teitelbaum
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    ABSTRACT: In adults with end-stage renal disease (ESRD), the preservation of residual renal function (RRF) has been shown to be associated with decreased mortality and improved control of complications of chronic kidney disease. However, less is known on the benefits of RRF in the pediatric dialysis population. The purpose of this article is to review the clinical significance of RRF and to discuss strategies for the preservation of RRF in children with ESRD.
    Pediatric Nephrology 07/2013; · 2.94 Impact Factor
  • Melissa A Cadnapaphornchai
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting 1 in 1000 individuals. Previously termed "adult polycystic kidney disease", ADPKD is now known to have important clinical manifestations beginning early in life and even in utero. Hypertension is an important risk factor for progressive renal and cardiovascular disease in children with ADPKD and may signify irremediable organ injury. The purpose of this article is to review current knowledge and treatment strategies in hypertension associated with pediatric ADPKD.
    Current Hypertension Reviews 02/2013; 9(1):21-6.
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    ABSTRACT: Hemolytic uremic syndrome is a thrombotic microangiopathy. Clopidogrel, a recently developed platelet aggregation inhibitor, has not been previously reported as a treatment for this illness. Our study's objective was to explore the efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome. We performed a retrospective chart review of all children (≤ 18 years) hospitalized with diarrhea associated hemolytic uremic syndrome. Outcomes in clopidogrel treated children were described. In subgroup analysis, outcomes were compared to those untreated with platelet aggregation inhibitors. Of 72 children with diarrhea associated hemolytic uremic syndrome, 88% were treated with platelet aggregation inhibitors (clopidogrel 56%, sulfinpyrazone 19%, dipyridamole 13%). The median age of clopidogrel treated children was 5 years; 40% were male. Initial median hemoglobin, platelet count, and serum creatinine were 10.1g/dL, 53 × 10(3)/μL, and 2.3mg/dL respectively. Clopidogrel (median dose 1mg/kg/d) was given for a median of 4 days (range 1-15). Other therapies included erythropoietin (98%), red blood cell transfusions (80%), diuretics (58%), anti-hypertensive agents (45%), and dialysis (33%). The median hospital length of stay was 9 days (range 3-26). Three children had bleeding complications (epistaxis/hematemesis). The risk of chronic kidney disease was 5% and death 2.5%. In subgroup analysis, median duration of dialysis was 11 days in thirteen clopidogrel treated children compared to 21 days in five untreated patients (P=0.04). Children with diarrhea associated hemolytic uremic syndrome treated with clopidogrel have outcomes comparable to untreated patients. Bleeding complications may occur.
    Thrombosis Research 06/2012; 130(3):e26-30. · 3.13 Impact Factor
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    ABSTRACT: Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) is a novel disease caused by a gain-of-function mutation in the V2 vasopressin receptor (V2R), which results in water overload and hyponatremia. We report the effect of water loading in a 3-year old boy with NSIAD, diagnosed in infancy, to assess urine aquaporin-2 (AQP2) excretion as a marker for V2R activation, and to evaluate the progression of the disease since diagnosis. The patient is one of the first known NSIAD patients and the only patient with a R137L mutation. Patient underwent a standard water loading test in which serum and urine sodium and osmolality, serum AVP, and urine AQP2 excretion were measured. The patient was also evaluated for ad lib fluid intake before and after the test. This patient demonstrated persistent inability to excrete free water. Only 39% of the water load (20 ml/kg) was excreted during a 4-hour period (normal ≥ 80-90%). Concurrently, the patient developed hyponatremia and serum hypoosmolality. Serum AVP levels were detectable at baseline and decreased one hour after water loading; however, urine AQP2 levels were elevated and did not suppress normally during the water load. The patient remained eunatremic but relatively hypodipsic during ad lib intake. In conclusion, this is the first demonstration in a patient with NSIAD caused by a R137L mutation in the V2R that urine AQP2 excretion is inappropriately elevated and does not suppress normally with water loading. In addition, this is the first longitudinal report of a pediatric patient with NSIAD diagnosed in infancy who demonstrates the ability to maintain eunatremia during ad lib dietary intake.
    International Journal of Pediatric Endocrinology 02/2012; 2012(1):3.
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    ABSTRACT: The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children. One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance ≥140 ml/min per 1.73 m(2). Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm(3)/year) over 5 years compared with those without GH at baseline (β = -4.3 ± 7.7 cm(3)/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = -5.0 ± 0.8 ml/min per 1.73 m(2) per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m(2) per year), P < 0.0001. This study revealed that occurrence of GH in ADPKD children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.
    Clinical Journal of the American Society of Nephrology 09/2011; 6(10):2439-43. · 5.07 Impact Factor
  • Melissa A Cadnapaphornchai, Amirali Masoumi, John D Strain, Kim McFann, Robert W Schrier
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and has important clinical manifestations in childhood. Numerous studies have documented the superiority of magnetic resonance imaging (MRI) for serial monitoring of kidney and cyst volume in this condition in adults. However, no studies have examined the utility of MRI for serial assessment of kidney and cyst volume in children with ADPKD. Subjects 4 to 21 years of age with ADPKD underwent abdominal MRI on an annual basis for 5 years. Subjects were grouped according to BP as hypertensive (HBP; BP≥95th percentile for age, height, and gender) or as normotensive (NBP; BP<95th percentile). Total kidney volume (TKV), cyst volume, and cyst number were assessed by stereology. MRI studies (n=302) were obtained in 77 children with ADPKD. TKV and cyst volume were significantly increased in HBP versus NBP subjects. HBP subjects demonstrated a greater increase in fractional cyst volume over time versus NBP subjects. Cyst number increased more rapidly in HBP ADPKD children. This is the first large-scale clinical study examining the utility of MRI for serial assessment of TKV, cyst volume, and cyst number in children with ADPKD. These results demonstrate that MRI is an acceptable means to follow these parameters in children with ADPKD. Because of the embryonic occurrence of cysts, interventional trials are needed in ADPKD children and MRI may be the preferred renal imaging approach.
    Clinical Journal of the American Society of Nephrology 02/2011; 6(2):369-76. · 5.07 Impact Factor
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney condition and is associated with important renal and cardiovascular manifestations in childhood. Renal cystic disease can be documented in some cases as early as in utero. Early intervention is critical if the long-term complications of this condition, including end-stage renal disease, are to be ameliorated. Here we describe our ongoing randomized double-blind placebo-controlled phase III clinical trial to assess the effect of pravastatin treatment on renal and cardiovascular disease progression in 107 children and young adults age 8-22 years with ADPKD who are receiving the angiotensin converting enzyme inhibitor lisinopril. Baseline demographic and laboratory data are provided. Results of this study could markedly impact the standard of care for evaluation and treatment of ADPKD in this population.
    Contemporary clinical trials 01/2011; 32(3):437-45. · 1.51 Impact Factor
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    ABSTRACT: Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD.
    Kidney International 09/2010; 79(1):128-34. · 8.52 Impact Factor
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    ABSTRACT: To date, there are no criteria for diagnosing autosomal dominant polycystic kidney disease (ADPKD) in at-risk children 15 years or younger. Longitudinal (retrospective cohort study). 420 children (mean age, 8.3 +/- 4.2 years) with a family history of ADPKD were studied. Renal ultrasonography was performed for cyst detection. Urine protein was measured using two 24-hour urine collections. Glomerular filtration rate was calculated using the Schwartz formula. Blood pressure measurements were performed in the arm with the highest blood pressure, using an appropriate cuff size. Standard 2-dimensional and Doppler echocardiography was performed for measuring left ventricular mass index. None. Presence of renal cysts. Renal cysts were detected in 193 children and no cysts were detected in 227 children. In children with renal cysts, 150 had bilateral and 43 had unilateral cysts. Children with bilateral cysts had larger kidneys and more hypertension than children with unilateral or no cysts. Follow-up in 77 children 15 years or younger showed bilateral cysts in 14 and unilateral cysts in 4 of the children who had no detectable renal cysts using ultrasonography at baseline. Similar follow-up of 26 children 15 years or younger with unilateral cysts detected at baseline showed bilateral cysts in 17 children using ultrasonography. By 15 years of age, 181 patients in the total group of 420 showed bilateral cysts. Overall, 193 of 304 children (63.4%) who had follow-up at any age developed bilateral cysts detected using ultrasonography. Follow-up unavailable for all participants. The present results in 420 at-risk children with ADPKD 15 years or younger detected bilateral renal cysts using ultrasonography in 181 of the children who had a family history of this genetic disease.
    American Journal of Kidney Diseases 05/2010; 56(1):50-6. · 5.29 Impact Factor
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    ABSTRACT: In autosomal dominant polycystic kidney disease, cysts derived from tubules are detected at birth by ultrasound (threshold for detection >7.0 mm); thus, fetal cyst growth rates must exceed 2300%/yr. In adults, the combined renal cyst component enlarges at approximately 12%/yr by growth of individual cysts. To explore this discrepancy, the growth rates of individual cysts were determined in adult polycystic kidneys. Diameter, volume, and growth rates of individual cysts were measured by magnetic resonance in 30 individual cysts in three adult patients over a span of 3 years. Results were confirmed in 22 cysts measured in five patients by computed tomography over a span of 11 years. Mean cyst diameters were 20.4 +/- 9.9 mm (range 7.1 to 40.5 mm) at baseline and 25.8 +/- 15.6 mm (range 7.8 to 49.6 mm) after 3 years. Mean cyst volumes, determined by manual segmentation and summation of magnetic resonance cross sections, were 8.7 +/- 12.9 cm(3) (0.3 to 43.3 cm(3)) and 24.2 +/- 66.3 cm(3) (0.3 to 364.8 cm(3)) after 3 years. Mean cyst growth rates ranged from 6.9 to 23.9%/yr; the maximum growth rate was 71.1%/yr, far less than required to develop a 7-mm diameter cyst in utero. Results were similar in 22 cysts examined by computed tomography. It was concluded that renal cysts detected by ultrasound in newborns must have grown at exuberant rates in utero; thereafter, expansion appears to proceed at much slower rates.
    Clinical Journal of the American Society of Nephrology 04/2010; 5(5):889-96. · 5.07 Impact Factor
  • Bahareh Schweiger, Margaret W Moriarty, Melissa A Cadnapaphornchai
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    ABSTRACT: Hyponatremia and hyperkalemia in infancy can represent a variety of renal and genetic disorders with significant long-term health implications. We report a newborn with severe hyperkalemia and hyponatremia from autosomal recessive pseudohypoaldosteronism type 1 requiring aggressive therapy. The evaluation and treatment of children with disorders of mineralocorticoid action are discussed.
    Current opinion in pediatrics 05/2009; 21(2):269-71. · 2.01 Impact Factor
  • Melissa A Cadnapaphornchai, Kim McFann, John D Strain, Amirali Masoumi, Robert W Schrier
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a progressive hereditary disorder affecting children and young adults. Early intervention may be necessary to significantly affect the long-term consequences of this disease. The authors conducted a 5-yr randomized clinical trial to assess the effect of BP control with angiotensin-converting enzyme inhibition (ACEI) on disease progression in 85 children and young adults with ADPKD. Study groups were determined by subject BP, including hypertension (BP >or= 95th percentile), borderline hypertension (BP 75 to 95th percentile), and severe ADPKD (BP <or=75th percentile with > 10 renal cysts). The primary outcome variable was renal volume by ultrasound, with secondary outcome variables including left ventricular mass index (LVMI) and microalbuminuria. In secondary analysis, the authors compared results between hypertensive and normotensive groups. The authors were not able to demonstrate a significant effect of ACEI on renal growth in young subjects with ADPKD. Hypertensive children were at particular risk for increases in renal volume and LVMI and decreased renal function as compared with the other study groups, and borderline hypertensive children were at high risk to develop hypertension over time. However, ACEI treatment was associated with stable renal function and LVMI in this group of children. Close monitoring of cardiovascular and renal status is indicated in ADPKD children with hypertension or borderline hypertension. In contrast to effects in hypertensive ADPKD children, ACEI treatment in normotensive or borderline hypertensive ADPKD children may prevent the development of increased LVMI and deterioration in renal function.
    Clinical Journal of the American Society of Nephrology 04/2009; 4(4):820-9. · 5.07 Impact Factor
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    Melissa A Cadnapaphornchai, Kim McFann, John D Strain, Amirali Masoumi, Robert W Schrier
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    ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary condition that may be diagnosed in utero. Our goal was to evaluate symptoms of ADPKD in children, including left ventricular mass index (LVMI), renal volume, renal function and microalbuminuria in relation to systolic and diastolic blood pressure. Eighty-five children were stratified by blood pressure into three cohorts: hypertensive (95th percentile and over), borderline hypertensive (75-95th percentile) and normotensive (75th percentile and below). There were no differences in gender, age, height, renal function, or microalbuminuria between the groups. Both the hypertensive and borderline hypertensive children had a significantly higher LVMI than normotensive children, with no significant difference between hypertensive and borderline hypertensive groups. There was a significant correlation between renal volume and both systolic and diastolic blood pressures in all subjects. Renal volume in hypertensive children was significantly larger than in the borderline hypertensive group, with no significant difference between normotensive and borderline hypertensive groups. These findings show that an increase in LVMI may be detected earlier than an increase in renal volume in children with ADPKD and borderline hypertension, suggesting that close monitoring of cardiac status is indicated in these children.
    Kidney International 09/2008; 74(9):1192-6. · 8.52 Impact Factor
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    ABSTRACT: There are considerable experimental results that indicate that arginine vasopressin (AVP)-independent factors are involved in urinary concentration. This study examined the role of hyperosmolality in vivo to modulate aquaporin 2 (AQP2) and Na-K-2Cl co-transporter (NKCC2), pivotal factors in urinary concentration, in AVP-deficient Brattleboro (BB) rats. Hyperglycemia with associated hyperosmolality occurred in diabetic BB rats (BBDM). Protein abundance of AQP2 increased and was reversed by insulin in the inner medulla (IM; control 100+/-5%; BBDM 146+/-8%; BBDM+Ins 122+/-9%; P<0.001) and inner stripe of outer medulla (ISOM; control 100+/-4%; BBDM 123+/-8%; BBDM+Ins 93+/-6%; P<0.05). These results were confirmed by immunohistochemistry studies. NKCC2 rose in the ISOM but was not reversed with insulin treatment. For investigation of the role of hyperosmolality in the absence of hyperglycemia on the regulation of the expression of renal AQP and NKCC2, studies were performed with hyperosmolality that was induced by 0.5% NaCl in drinking water in BB rats. Hyperosmolality that was induced by NaCl increased significantly the protein abundance of IM AQP2 (121+/-2 versus 100+/-5%; P<0.01), ISOM AQP2 (135+/-6 versus 100+/-5%; P<0.001), cortex plus outer stripe of outer medulla AQP2 (121+/-4 versus 100+/-1%; P<0.001), ISOM NKCC2 (133+/-1 versus 100+/-4%; P<0.05), and cortex plus outer stripe of outer medulla NKCC2 (142+/-16 versus 100+/-9%; P<0.05). In conclusion, hyperosmolality, secondary to either glucose or NaCl, upregulated renal AQP2 and NKCC2 in vivo in BB rats.
    Journal of the American Society of Nephrology 06/2006; 17(6):1657-64. · 8.99 Impact Factor
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    ABSTRACT: Urinary diluting ability and protein abundance of renal aquaporins (AQPs) and ion transporters in glucocorticoid-deficient (GD) rats were examined at baseline and in response to oral water loading. Rats underwent bilateral adrenalectomy followed by aldosterone (GD) or aldosterone + dexamethasone (CTL) replacement. Before oral water loading, urinary output was significantly decreased and urinary osmolality (U(osm)) was increased in GD compared with CTL rats. Protein abundance of inner medullary AQP2 (148 +/- 18%), phosphorylated AQP2 (pAQP2, 156 +/- 13%), and AQP3 (145 +/- 8%) was significantly upregulated in GD compared with CTL rats (all P < 0.05). GD rats also demonstrated a marked reduction in urinary Na(+) excretion compared with pair-fed CTL rats. Na(+)-K(+)-2Cl(-) cotransporter, Na(+)/H(+) exchanger type 3, and cortical beta- and gamma-subunits of the epithelial Na(+) channel were significantly upregulated in GD rats. At 1 h after an acute water load (40 ml/kg by oral gavage), GD rats demonstrated a decrease in percent water excretion (5 +/- 1 vs. 33 +/- 9%, P < 0.01) and urinary output (33 +/- 12 vs. 250 +/- 65 microl x kg(-1) x min(-1), P < 0.05) and an increase in U(osm) (1,894 +/- 292 vs. 316 +/- 92 mosmol/kgH(2)O, P < 0.001) compared with CTL rats. Plasma AVP was increased (1.6 +/- 0.2 vs. 0.9 +/- 0.2 pg/ml, P < 0.05), as was protein expression of inner medullary AQP2 (149 +/- 5%) and pAQP2 (177 +/- 9%, P < 0.01), in GD compared with CTL rats; apical expression of AQP2 was maintained in GD rats. The vasopressin V(2) receptor antagonist OPC-31260 increased percent water excretion and urinary output and reduced U(osm) compared with vehicle-treated GD rats. OPC-31260 also reversed the increased abundance and apical trafficking of inner medullary AQP2 and pAQP2 protein in GD rats. In conclusion, enhanced protein abundance of Na(+) transporters and Na(+) channels with Na(+) retention occurred with GD. OPC-31260 reversed upregulation and apical trafficking of AQP2 and pAQP2 in association with improved urinary diluting capacity and increased water excretion after oral water loading.
    American journal of physiology. Renal physiology 05/2006; 290(5):F1135-42. · 3.61 Impact Factor
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    ABSTRACT: The natural history of autosomal-dominant polycystic kidney disease (ADPKD) has not been well described in children and infants. The present study analyzed the characteristics of 46 ADPKD children diagnosed before 18 months of life (VEO) and 153 children diagnosed between 18 months of age and 18 years of age (non-VEO). VEO children had more cysts and larger renal volumes than non-VEO children when adjusted for age. In both VEO and non-VEO children, the presence of signs or symptoms at the time of diagnosis as well as the presence of hematuria or proteinuria at the study visit were associated with larger renal volumes. Children diagnosed early (VEO) or diagnosed due to signs or symptoms were also more likely to have high blood pressure. Two VEO children and no non-VEO children reached end-stage renal disease during follow-up. In contrast to many published case reports suggesting the occurrence of early end-stage renal disease in VEO children, the results of the present study were much more optimistic. Over 90% of the VEO children maintained preserved renal function well into childhood.
    Kidney International 12/2005; 68(5):2218-24. · 8.52 Impact Factor

Publication Stats

429 Citations
155.16 Total Impact Points


  • 2013
    • Children's Hospital Colorado
      Aurora, Colorado, United States
  • 2001–2013
    • University of Colorado
      • • Department of Pediatrics
      • • Department of Radiology
      • • Division of Renal Diseases and Hypertension
      • • Department of Medicine
      Denver, CO, United States
  • 2002–2005
    • University of Colorado Hospital
      • • Department of Medicine
      • • Department of Pediatrics
      Denver, Colorado, United States
    • Kameda Medical Center
      Kameda, Niigata, Japan
  • 2003
    • National Heart, Lung, and Blood Institute
      Maryland, United States