Effect of nitric oxide inhibition on kidney function in experimental renovascular hypertension.

We examined the effect of acute systemic blockade of nitric oxide (NO) synthesis on blood pressure and renal function in rats with angiotensin II dependent two-kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly higher blood pressures, plasma NO metabolite concentrations and urinary NO metabolite excretion rates than control rats. Intravenous administration of N(G)-nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure in both hypertensive and control animals with the magnitude of increase being greater in hypertensive than control rats (32 +/- 3 vs. 20 +/- 2 mmHg, p < 0.05). L-NAME did not affect glomerular filtration rates of normal and clipped kidneys but significantly decreased non-clipped kidney glomerular filtration rate (1.1 +/- 0.1 vs. 0.7 +/- 0.1 ml/min per g kidney wt, p < 0.05). Blood flow to normal and non-clipped kidneys fell in response to L-NAME. Percent reduction in renal blood flow produced by L-NAME was significantly greater in non-clipped than normal kidneys (38 +/- 3 vs. 24 +/- 2%, p < 0.05). In contrast, clipped kidney blood flow increased after L-NAME (3.3 +/- 0.2 vs. 4.0 +/- 0.2 ml/min per g kidney wt, p < 0.05). An identical improvement in clipped kidney blood flow occurred when arterial pressure was raised with aortic constriction indicating that the systemic pressor effect of L-NAME was responsible for this finding. These results indicate that NO plays an important role in systemic and non-clipped kidney hemodynamics in renovascular hypertension. Because NO has little influence on stenotic kidney function, the stimulus for increased NO system activity in this disease appears to be vascular shear stress rather than elevated circulating or intrarenal angiotensin II concentrations.

Effect of nitric oxide inhibition on blood pressure and renal function in TGR(mRen2)27 rats.

We examined the effect of acute systemic blockade of nitric oxide synthesis on blood pressure and renal function in the monogenetically hypertensive TGR(mRen2)27 rat strain. Untreated conscious transgenic rats had significantly (p < 0.01) higher systolic blood pressures (185 +/- 9 versus 130 +/- 5 mm Hg) and urinary albumin excretion (32 +/- 5 versus 6 +/- 2 mg/day) than did control animals without evidence of renal insufficiency. Plasma and urinary nitric oxide metabolite levels did not differ between transgenic and control rats. i.v. administration of NG-nitro-L-arginine methyl ester (10 mg/kg) to both groups caused similar elevations in systemic blood pressure (transgenic 25 +/- 3 versus control 24 +/- 3 mm Hg). NG-Nitro-L-arginine methyl ester induced reductions in whole kidney (1.4 +/- 0.2 versus 0.7 +/- 0.1 mL/min), and single nephron (23 +/- 3 versus 11 +/- 2 nL/min) glomerular filtration rates were significantly (p < 0.05) larger in transgenic than in control rats. This greater loss of GFR in transgenic animals was caused by a larger reduction in glomerular ultrafiltration coefficient (1.8 +/- 0.2 versus 1.1 +/- 0.1 nL x min[-1] x mmHg[-1], p < 0.05), a larger increase in afferent arteriole resistance (3.4 +/- 0.2 versus 1.4 +/- 0.1 dyne x s x cm[-5], p < 0.05), and a subsequently smaller rise in glomerular transcapillary pressure (10 +/- 1 versus 5 +/- 1 mmHg, p < 0.05). These results indicate that the renal microvasculature and glomerular hydraulic conductivity or surface area of transgenic rats are more sensitive to nitric oxide inhibition and are consistent with an important role for nitric oxide in TGR(mRen2)27 kidney function.

Hypertensive encephalopathy and reversible magnetic resonance imaging changes in a renal transplant patient.

An 18-year-old renal transplant patient presented with sudden onset of seizures almost 2 years after she received the graft. Diagnostic work-up was unrevealing except for magnetic resonance imaging abnormalities of the brain that resolved spontaneously 4 weeks later. In this brief report, we discuss the etiology of the seizures and neurological abnormalities in renal transplant patients in light of the findings of our patient.

Decreased urinary excretion of nitric oxide in acute rejection episodes in pediatric renal allograft recipients.

Acute renal allograft rejection continues to have a negative effect on graft survival despite a better understanding of the molecular basis of renal allograft rejection. Nitric oxide (NO) has important biological functions in cell defense and injury and some evidence exists that it may act as an immunomodulator in allograft transplantation. To determine if NO has any role in acute renal allograft rejection in pediatric patients, acute rejection episodes in pediatric renal transplant recipients were evaluated. Four out of eleven patients who received a renal allograft in 1995 at Children's Kidney Center at The Children's Hospital of Buffalo had eight episodes of acute rejection. One patient received a living-related and three received cadaveric grafts. Stable metabolites of NO (NO-2 + NO-3 = NOx) were measured in the serum and urine samples of the patients daily. Serum levels of NO did not change significantly during acute rejection episodes. Urinary NOx levels decreased by 73+/-9% of the baseline values during episodes of acute rejection: mean +/-SE urinary nitric oxide/creatinine ratio (NOx/Cr) of 0.17+/-0.05 at baseline vs. 0.05+/-0.01 during rejection (P=0.02). Successful treatment of acute rejection by administration of high dose i.v. steroids or OKT-3 induced acute rises in the urinary NO levels to baseline values: NO/Cr = 0.17+/-0.04 (mean +/-SE). We conclude that urinary NO excretion decreases significantly during acute renal allograft rejection and that NOx concentration in the urine increases in response to successful antirejection therapy.

Prolonged hypocomplementemia in poststreptococcal acute glomerulonephritis.

Complement levels conventionally return to normal in eight weeks in patients with poststreptococcal acute glomerulonephritis (PSAGN). The objective of this study was to determine the significance of prolonged hypocomplementemia (> 8 weeks) in this group of patients. Between April 1993 and January 1995, 20 patients were followed prospectively for a mean of 6 months (range 3-20 months after the episode of PSAGN. Serum C3 concentrations were measured at diagnosis and at regular intervals. Five patients (26%) had prolonged hypocomplementemia. Percutaneous renal biopsies were performed in three patients which revealed findings consistent with the clinical diagnosis of PSAGN. All of these patients showed gradual improvement of their symptoms; some have persistent microscopic hematuria without proteinuria. Kidney function is normal in all despite hypocomplementemia. We conclude that hypocomplementemia (> 8 weeks) with resolving features of acute glomerulonephritis does not exclude the diagnosis of PSAGN, and a renal biopsy may be deferred if there is clinical improvement.

Spectrum of glomerulocystic kidneys: a case report and review of the literature.

An 8-year-old boy developed end-stage renal disease 7 years after the in utero diagnosis of bilateral cystic kidneys. There was no history of cystic renal disease in the family. Initial ultrasonographic screening of the parents failed to reveal cysts in the kidneys. Pathological evaluation of the kidney biopsy findings was consistent with the glomerulocystic kidney disease. He had bilateral nephrectomies in preparation for a living related renal transplant at 7 years of age. At that time, a repeated renal ultrasound examination of the mother showed bilateral cystic kidneys. Pathological evaluation of the nephrectomy specimens confirmed the diagnosis of autosomal dominant polycystic kidney disease. In this report, a discussion of the differential diagnosis of glomerular cysts and the relationship of glomerulocystic kidney disease and autosomal dominant polycystic kidney disease is provided.