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J G Porush

Publications and source records attributed to J G Porush.

At least 19 recordsLinked to original sources
PubMed2002

Regional expression of inducible nitric oxide synthase in the kidney stimulated by lipopolysaccharide in the rat.

The renal medulla contains more mRNA of the inducible isoform of nitric oxide synthase (iNOS) than the cortex, which may be important in preventing ischaemic injury, since blood flow and tissue oxygen tension are normally low in this region. We examined the effects of the bacterial endotoxin E. coli lipopolysaccharide (LPS) on renal function and regional expression of iNOS in male Sprague-Dawley rats. In six rats, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 0.95 +/- 0.09 ml min(-1) g(-1) and 3.36 +/- 0.20 ml min(-1) g(-1), respectively, and decreased significantly to 0.35 +/- 0.09 and 1.74 +/- 0.54 ml min(-1) g(-1), respectively, 1 h after administration of LPS. In an additional seven rats, GFR and ERPF were 0.91 +/- 0.07 and 2.97 +/- 0.30 ml min(-1) g(-1), respectively, 18 h after LPS administration; these values were similar to those in control rats. In all rats, arterial pressure was stable throughout all study periods. In control rats, immunoblot analysis revealed expression of the iNOS protein in the cortex and more pronounced expression in the medulla. In rats studied 18 h after LPS treatment, there was a striking increase in the iNOS expression in the outer medulla. Immunohistochemical examination in the LPS-treated rats showed limited iNOS immunostaining in the cortex, localised to the vascular endothelium and macula densa; however, intense and widespread staining was noted in the tubular and vascular structures of the outer medulla. These findings demonstrated a differential constitutive expression of iNOS protein in different regions of the rat kidney, and marked augmentation of iNOS expression in the outer medulla by LPS.

Animals↗
PubMed2001

Regional expression of inducible nitric oxide synthase in the kidney in dogs with unilateral ureteral obstruction.

PURPOSE: In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medullary tissue hypoxia. We examined the expression of inducible nitric oxide synthase, a product of a hypoxia sensitive gene, in the cortex and medulla in dogs with unilateral ureteral obstruction for 21 hours. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral obstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. RESULTS: Ureteral obstruction raised mean ureteral pressure plus or minus standard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obstruction mean renal blood flow was 116 +/- 10 ml. per minute, lower than the 213 +/- 22 ml. per minute in sham operated dogs (p <0.01). After unilateral ureteral obstruction release the mean glomerular filtration rate was 9.5 +/- 2.1 ml. per minute, lower than the 27.3 +/- 1.8 ml. per minute in the contralateral unobstructed kidney (p <0.01). Western blot analysis showed that mean nitric oxide synthase/beta-actin in the cortex of the obstructed kidney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densitometry units in the unobstructed contralateral kidney (p <0.05). In contrast, mean nitric oxide synthase/beta-actin in the medulla of the obstructed kidney was 1.29 +/- 0.33 densitometry units, greater than the 0.34 +/- 0.03 densitometry units in the unobstructed kidney (p <0.05). Immunohistochemistry revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. CONCLUSIONS: Unilateral ureteral obstruction enhances nitric oxide synthase expression in the medulla but not in the cortex. This increased expression in the medulla may be the result of increased medullary hypoxia in unilateral ureteral obstruction, possibly contributing to medullary hyperemia after unilateral ureteral obstruction release.

Animals↗
PubMed1998

Hypertension and chronic renal failure: the use of ACE inhibitors.

The incidence of end-stage renal disease (ESRD) has increased 9% a year over the past 10 years, due primarily to diabetic nephropathy and hypertensive nephrosclerosis. Over this period of time, mortality rates for hypertensive heart disease and stroke have decreased substantially, in large part because of greater recognition and improved therapy of hypertension. Why then is there an increasing incidence of ESRD in diseases in which hypertension plays a significant role in causation and/or progression of renal failure? Is it possible that a lower level of blood pressure than usually recommended is necessary to prevent kidney disease (particularly in blacks) or to prevent or slow progression in most forms of renal failure? Furthermore, are there specific renoprotective drugs? This report will focus primarily on large prospective studies that may provide information to answer these questions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Familial focal segmental glomerulosclerosis: nine cases in four families and review of the literature.

Idiopathic focal segmental glomerulosclerosis (FSGS) is a common cause of glomerular disease. Although previous case reports suggesting a familial form of the disease exist in the literature, its significance has not been emphasized. We report on our experience with nine cases in four families, as well as a review of the literature, and provide evidence that a familial form of FSGS might represent a distinct genotypic and phenotypic subset of idiopathic FSGS.

Adolescent↗
PubMed1997

Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

Adolescent↗
PubMed1996

Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group.

The Modification of Diet in Renal Disease Study was a multicenter trial of the effect of protein restriction and strict blood pressure control on the progression rate of chronic renal failure of multiple causes. At the first baseline visit, 1,795 screened patients with renal disease had blood pressure measured, antihypertensive medications recorded, glomerular filtration rate (GFR) determined by 125I-iothalamate clearance, a nutritional assessment, and a 24-hour urine collection to determine sodium and potassium levels. A total of 1,494 patients in this cohort were classified as hypertensive (83%) and the remainder (301 patients) as nonhypertensive. Ninety-one percent of the hypertensive subjects were on treatment, 54% being controlled to a blood pressure of < or = 140/90 mm Hg. To better understand the factors that contribute to the development of hypertension in chronic renal disease, some determinants of the prevalence of hypertension in this cohort were investigated. Compared with normotensive subjects, hypertensive patients were older (51.2 +/- 12.7 years v 46.6 +/- 13.1 years [mean +/- SD]), had a higher body mass index (BMI; 27.5 +/- 4.7 kg/m2 v 25.4 +/- 4.2 kg/m2), and had a lower GFR (37.8 +/- 19.6 mL/min/1.73 m2 v 50.1 +/- 25 mL/min/1.73 m2). All these differences were significant (P < 0.01). The prevalence of hypertension was significantly higher for men than for women (86% v 80%; P = 0.001), and for blacks than for whites (93% v 81%; P < 0.001). The prevalence of hypertension was higher in subjects with glomerular disease than in those with tubulointerstitial disease (85% v 62.6%; P < 0.001). The prevalence of hypertension varied inversely with GFR (from 66% at a GFR of 83 mL/min/1.73 m2 to 95% at a GFR of 12 mL/min/1.73 m2). The prevalence of hypertension varied directly with BMI (from 70% with a BMI at the 10th percentile to 94% with a BMI at the 97th percentile). This relationship was independent of GFR. Multiple logistic regression analysis showed five predictors in decreasing order of significance as determined by chi-square values: GFR, 83.2; BMI, 36.7; black race, 19.9; increasing age, 14.5 (all P < 0.001); and male gender, 5.1 (P = 0.024). Salt intake was not a determinant of blood pressure status. These results confirm previous reports indicating that hypertension in renal disease is determined by the level of renal function. For the first time, three factors known to predict blood pressure levels in populations with normal renal function were also shown to be determinants of blood pressure in renal disease: BMI, black race, and age. In addition, the data suggest that hypertension is inadequately treated in more than half of patients with chronic renal disease in the United States.

Adolescent↗
PubMed1996

Hemodynamic effects of peritoneovenous shunts in hemodialysis patients with ascites.

Ascites in hemodialysis patients has been reported in association with systemic diseases, such as cirrhosis or congestive heart failure, and as an idiopathic form. Regardless of the etiology, these patients often are refractory to treatment with intradialytic ultrafiltration because of recurrent hypotensive episodes. In this report we describe the hemodynamic effects of peritoneovenous shunts (PVSs) in three hemodialysis patients with ascites refractory to conventional treatment. One patient had idiopathic ascites and the other two had associated liver disease. Patients were monitored for lowest blood pressure, number of intradialytic hypotensive episodes, number of grams of albumin infused to treat hypotensive episodes, interdialytic weight gain, and hemodynamic stability (defined as the difference between the predialysis mean arterial pressure and the lowest intradialytic mean arterial pressure). In all three patients the hemodynamic parameters stabilized after PVS placement despite equal or greater ultrafiltration during dialysis (due to a significant increase in the lowest measured intradialytic blood pressure). The total number of hypotensive episodes decreased from 219 prior to PVS placement to zero after shunt placement. The need for albumin infusion during hemodialysis (for blood pressure support) decreased (significantly in two patients), as did the volume of ascites in all three patients. One patient required PVS replacement secondary to infection, which was the only complication. We believe that refractory ascites in end-stage renal disease patients can be successfully treated by placement of a PVS, which often results in relief of the ascites and significant improvement in intradialytic hemodynamic stability.

Aged↗
PubMed1996

Reversal of trimethoprim-induced antikaliuresis.

High-dose trimethoprim-sulfamethoxazole (TMP-SMX) causes hyperkalemia, thought to result from TMP-induced blockade of amiloride-sensitive Na(+)-channels in the distal nephron. The present study was performed in anesthetized dogs to determine if increasing distal sodium delivery affects this antikaliuretic effect. In Group 1, intrarenal infusion of vehicle did not alter renal function. In Group 2, i.v. infusion of amiloride led to diuresis, natriuresis and antikaliuresis associated with a reduction of the transtubular potassium gradient (TTKG) in both kidneys. Intrarenal infusion of TMP (0.2 mg/kg/min) into the left kidney did not further alter these parameters. In groups 3 and 4, intrarenal infusion of TMP caused an ipsilateral diuresis, natriuresis, antikaliuresis and a reduction in (TTKG) without affecting the contralateral kidney. The TMP infusion was followed by furosemide (20 mg i.v.) in group 3 and acute saline loading in group 4. Despite continuous TMP infusion, both furosemide and saline loading reversed the antikaliuretic effect of TMP in the ipsilateral kidney and was associated with a similar kaliuresis, diuresis, natriuresis and decrease in urine osmolality in both kidneys. The TTKG following furosemide or saline loading increased in the ipsilateral kidney and decreased in the contralateral kidney. In all groups the systemic and renal hemodynamics remained unchanged. These results suggest that acute administration of TMP inhibits the amiloride-sensitive Na(+)-channel and K+ secretion in the distal nephron. Maneuvers that increase distal Na+ delivery can abrogate TMP's antikaliuretic effect due, in part, to an increase of the low TTKG observed with TMP.

Animals↗
PubMed1995

Renal actions of endothelin-1 and endothelin-3: interactions with the prostaglandin system and nitric oxide.

Endothelins (ET) possess both vasodilatory and vasoconstrictive properties. The renal actions of ET-1 and ET-3, as well as in vivo interactions of these two isopeptides with the prostaglandin and endothelium-derived relaxation factor/nitric oxide systems were studied in anesthetized dogs. The ETs were infused intrarenally at doses not affecting systemic hemodynamics. Both ET-1 and ET-3 induced an early transient renal vasodilation, followed by a prolonged vasoconstriction. Inhibition of nitric oxide synthase with NG-monomethyl-L-arginine completely abolished the renal vasodilation induced by either ET-1 or ET-3 and enhanced the vasoconstriction. Endothelin-1 was associated with an increase in the renal release of prostacyclin, while urinary thromboxane A2 was increased after ET-3 administration. Inhibition of cyclooxygenase (with indomethacin) augmented the renal vasoconstriction induced by ET-1, but inhibition of cyclooxygenase (with meclofenamate) abolished the ET-3-evoked vasoconstriction. Endothelin-1 showed little effects on urinary water and sodium excretion; however, ET-3 displayed significant diuretic and natriuretic effects, which were inhibited by nitric oxide synthase inhibition. These findings suggest that these two isopeptides activate the endothelial endothelium-derived relaxation factor/nitric oxide system, which elicits early renal vasodilation, whereas direct effects on the vascular smooth muscle leads to vasoconstriction. Endothelin-3 causes diuresis and natriuresis, possibly by inducing release of nitric oxide in medullary collecting duct cells.

Amino Acid Oxidoreductases↗
PubMed1994

Uncontrolled hypertension and hyperreninemia after hemorrhage in a patient with end-stage renal disease and acquired renal cysts.

Acquired cystic kidney disease occurs in over 74% of patients with ESRD on hemodialysis for more than 4 yr. A variety of complications have been associated with these cysts including bleeding, lithiasis, infection, obstruction, and malignant transformation. An ESRD patient who developed accelerating hypertension secondary to an acute perinephric hematoma due to a bleeding-acquired renal cyst is described. The hypertension, which was refractory to aggressive drug therapy, was controlled only after the involved kidney was removed, after the demonstration of an elevated ipsilateral renal vein renin level. This is the first case reported in which worsening hypertension, apparently due to the "Page Kidney," developed as a complication of perinephric bleeding in an ESRD patient with acquired cystic kidney disease.

Glomerulonephritis↗
PubMed1993

Trimethoprim-sulfamethoxazole induces reversible hyperkalemia.

OBJECTIVE: To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration. DESIGN: Retrospective cohort study. SETTING: An urban teaching hospital. PATIENTS: Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded. MEASUREMENTS AND MAIN RESULTS: Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization. CONCLUSIONS: High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

AIDS-Related Opportunistic Infections↗
PubMed1993

Treatment of hyperlipidemia in the nephrotic syndrome: the effects of pravastatin therapy.

The hyperlipidemia of the nephrotic syndrome is characterized by an elevation of total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), with a normal or low high-density lipoprotein cholesterol (HDLC), and an increase in triglycerides (TGs) later in the course of the disease. If sustained, this lipid profile probably places these patients at increased risk for cardiovascular disease. Despite extensive trials of diet and drug therapy in patients with primary hyperlipidemias, few such trials exist in patients with the nephrotic syndrome. We conducted a randomized, prospective, double-blind, placebo-controlled trial to investigate the efficacy and safety of pravastatin, the newest cholesterol synthesis inhibitor, in the treatment of the hyperlipidemia of the nephrotic syndrome. After dietary modification was implemented, 13 patients received pravastatin and eight received placebo. All patients were maintained on a low-fat, low-cholesterol diet for the duration of the trial (24 weeks). The dose of pravastatin was increased from the initial 20 mg/d to 40 mg/d at week 10 or 18 if TC remained elevated (> 50th percentile). A bile acid sequestrant was added at week 18 if TC remained elevated and if the patient was already receiving the maximal pravastatin dosage. Dietary modification did not significantly change the lipid profile. Pravastatin (20 mg/d) reduced TC by 22% from a baseline of 301 +/- 28 mg/dL (P < 0.05) and LDLC by 28% from a baseline of 222 +/- 28 mg/dL (P < 0.05). When used at 40 mg/d (in six patients) no further change in the lipid profile was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The use of tissue plasminogen activator to declot arteriovenous accesses in hemodialysis patients.

Thrombosis is the most common complication of arteriovenous (A-V) access, resulting in malfunction or total failure. We describe the first use of the thrombolytic agent tissue plasminogen activator (t-PA) to declot the A-V access in 15 hemodialysis patients (14 A-V grafts and one fistula). The t-PA was infused directly into the A-V access in 10-mg doses, at 2-hour intervals, to a maximum of 30 mg. As determined by angiography, t-PA infusion resulted in a dramatic decrease in clot volume in all cases and complete lysis, with return of bruit and thrill, in 10 patients. Eight of the 10 were able to be treated with hemodialysis via the A-V access the following day. In these patients, angiography demonstrated stenosis at the venous end of the A-V access in eight of nine A-V grafts (the one fistula did not have a venous stenosis). Three patients reclotted within 24 hours, and one had bleeding 5 days later after dialysis requiring compression of the A-V access, which resulted in reclotting. Five patients had functioning A-V grafts 1 to 15 months after t-PA treatment (with angioplasty of the venous stenosis required in three of these), and one patient was lost to follow-up. All five patients in whom t-PA infusion was only partially successful had venous stenosis. One patient died before surgery (unrelated to t-PA). Thus, venous stenosis was present in 13 of 15 A-V accesses studied, the highest incidence reported to date.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs.

Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.

Animals↗