ABSTRACT—Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a ...progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527±509 versus 28 050±561, P <0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380±587) compared with control rats (P <0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.
Effect of prenatal dexamethasone on rat renal development.
Prenatal insults can program the developing fetus to develop diseases that manifest in later life. Dexamethasone is often administered to ...the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine whether prenatal dexamethasone adversely affects renal development and predisposes rats to develop renal disease and hypertension in later life.
Pregnant rats were given either vehicle or two daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days: 11 and 12, 13 and 14, 15 and 16, 17 and 18, 19 and 20, or 20 and 21. Tail cuff blood pressure, glomerular number, and inulin clearance were measured in control and prenatal dexamethasone-treated rats when the rats were 60 to 90 days of age.
Prenatal dexamethasone did not affect the length of gestation, the number of animals per litter, or the total body weight or kidney weight measured at one day of age. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 30% reduction in glomerular number compared with control at 60 to 70 days of age (24,236 ± 441 vs. 30,453 ± 579, P < 0.01). Rats receiving prenatal dexamethasone on days 17 and 18 had an approximate 20% reduction in glomeruli compared with control (P < 0.01). Offspring of rats receiving dexamethasone on days 15 and 16 gestation had systolic blood pressures at 60 to 90 days of age that were higher than any other group (P < 0.05). The glomerular filtration rate was comparable in all of the groups.
This study shows that two daily doses of prenatal dexamethasone (0.2 mg/kg body weight) in rats do not produce intrauterine growth retardation. Adult offspring of rats that received prenatal dexamethasone during specific times of gestation have a reduced number of nephrons and hypertension.
The renin–angiotensin system plays an important role in the regulation of blood pressure. The use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers both control ...hypertension by interruption of the production or action of angiotensin II, the major end-product of the renin–angiotensin system. The use of angiotensin converting enzyme inhibitors in pregnant women revealed serious and deleterious effects on fetal development including renal failure, renal dysplasia, hypotension, oligohydramnios, pulmonary hypoplasia, and hypocalvaria. The fetal effects of angiotensin converting enzyme inhibitors seem to be greatest during the 2nd and 3rd trimesters of pregnancy. The fetal effect of angiotensin converting enzyme inhibitors during the 1st trimester is controversial. These effects may represent the effect of hypoperfusion in the fetus and not a teratogenic effect. The effect of angiotensin receptor blockers is similar to converting enzyme inhibitors. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be avoided in all pregnant women. Alternative antihypertensive medications should be considered for use in women of childbearing years.
Background
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) has been recognized as a distinct entity in recent years. To the best of our knowledge, all patients with PGNMID ...reported thus far were older than 20 years of age. We now report five cases of PGNMID in patients under 20 years of age.
Methods
The clinical database was searched for patients with native kidney biopsies from 9/2011 to 8/2017, and cases with a diagnosis of PGNMID were retrieved. Light microscopy specimens and immunofluorescence and electron microscopy images were revisited. Clinical data and kidney biopsy findings for patients under the age of 20 were recorded.
Results
Five (0.78%) of a total of 637 patients younger than 20 with native renal biopsies had a diagnosis of PGNMID, including three males and two females with an average age of 14 years old (range 10–19). All five patients presented with microscopic hematuria and proteinuria. Three patients were nephrotic and their C3 levels were low. All five cases showed a membranoproliferative pattern with abundant mesangial and subendothelial monoclonal IgG3 deposits (3 κ and 2 λ light chain, respectively). The patients were followed up to 56 months. Two patients had re-biopsies 28 and 18 months after initial diagnosis and both showed similar morphologic changes. Various treatments were attempted including prednisone, mycophenolate mofetil, tacrolimus, rituximab, and eculizmab, with mixed responses.
Conclusions
PGNMID does occur in children and young adults. Membranoproliferative glomerulonephritis pattern with monoclonal IgG3 deposits is a common feature. Despite various immunosuppressive treatments, the disease appears slowly progressive.
Rickets and the decreased ossification associated with it can give rise to abnormally low bone density and weakened osseous structures. Despite this association, rickets has rarely been associated ...with osteochondral defects, and the imaging findings of this association have not been previously described on magnetic resonance (MR) imaging. This case report presents an adolescent male with a clinical history of rickets and recent-onset knee pain that was determined to be caused by bilateral osteochondritis dissecans. Prompt recognition of osteochondritis dissecans is important, as this entity is a treatable cause of knee pain.
Androgens augment proximal tubule transport Quan, Albert; Chakravarty, Sumana; Chen, Jian-Kang ...
American journal of physiology. Renal physiology,
09/2004, Letnik:
287, Številka:
3
Journal Article
Recenzirano
The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of ...angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 +/- 0.31 vs. 3.31 +/- 0.23 nl x min(-1) x mm(-1), P < 0.01). Luminally perfusing with either enalaprilat (10(-4) M) to inhibit production of angiotensin II or losartan (10(-8) M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.
Glomerular protein permeability rises in nephrotic syndrome and may result from the effect of an unidentified "circulating factor." The effect of this "circulating factor" on the permeability of ...other body membranes is unknown. In this study we examine the peritoneal membrane protein permeability in patients with nephrotic syndrome on chronic-cycler peritoneal dialysis. We conducted a retrospective study of peritoneal protein losses in the dialysate effluent of 60 pediatric peritoneal dialysis patients (ages 5.1-22 years) over a 6-year period (January 1997-December 2002). Nineteen patients had steroid-resistant nephrotic syndrome (SRNS), while 41 had other non-nephrotic etiologies of renal failure. Total and normalized peritoneal protein losses are higher in SRNS than in non-nephrotic patients (12,603+/-5,403 mg/day vs 4,475+/-469 mg/day, P<0.05; 297.8+/-79.3 mg/kg per day vs 156.8+/-16.0 mg/kg per day, P<0.05; 9,614.6+/-3,253.4 mg/m(2) per day vs 4,168.3+/-367.3 mg/m(2) per day, P<0.05). The ratio of total protein in dialysate to plasma, a measure of peritoneal membrane protein permeability, was higher in SRNS patients (3.50+/-1.00% vs 0.68+/-0.06%, P<0.001). Serum albumin concentration was lower in SRNS patients (3.09+/-0.13 mg/dl vs 3.52+/-0.07 mg/dl, P<0.01). There were no differences between the two groups with regard to duration of peritoneal dialysis, dialysis prescription, numbers of peritonitis episodes, catheter replacements, or hospitalizations. In summary, these results demonstrate that peritoneal protein losses in patients with SRNS are twice as great as in those without nephrotic syndrome. These results are consistent with the systemic effect of a "circulating factor" in SRNS and underscore the importance of adequate protein intake in patients on peritoneal dialysis.
There is evidence that angiotensin II is synthesized by the proximal tubule and secreted into the tubular lumen. This study examined the functional significance of endogenously produced angiotensin ...II on proximal tubule transport in male Sprague-Dawley rats. Addition of 10(-11), 10(-8), and 10(-6) M angiotensin II to the lumen of proximal convoluted tubules perfused in vivo had no effect on the rate of fluid reabsorption. The absence of an effect of exogenous luminal angiotensin II could be due to its endogenous production and luminal secretion. Luminal 10(-8) M Dup 753 (an angiotensin II receptor antagonist) resulted in a 35% decrease in proximal tubule fluid reabsorption when compared to control (Jv = 1.64 +/- 0.12 nl/mm.min vs. 2.55 +/- 0.32 nl/mm.min, P < 0.05). Similarly, luminal 10(-4) M enalaprilat, an angiotensin converting enzyme inhibitor, decreased fluid reabsorption by 40% (Jv = 1.53 +/- 0.23 nl/mm.min vs. 2.55 +/- 0.32 nl/mm.min, P < 0.05). When 10(-11) or 10(-8) M exogenous angiotensin II was added to enalaprilat (10(-4) M) in the luminal perfusate, fluid reabsorption returned to its baseline rate (Jv = 2.78 +/- 0.35 nl/mm.min). Thus, addition of exogenous angiotensin II stimulates proximal tubule transport when endogenous production is inhibited. These experiments show that endogenously produced angiotensin II modulates fluid transport in the proximal tubule independent of systemic angiotensin II.
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