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.
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.
Case summary. Nephrology consultation was requested by the neurosurgical service for an 18-year-old male who developed polyuria following resection of recurrent craniopharyngioma. Review of the patient's medical history showed that his brain tumor was first detected when he was 10 years old. Surgical resection at that time was followed by the development of panhypopituitarism and diabetes insipidus requiring chronic hormonal replacement therapy. At 14 years of age, recurrent tumor was treated with radiation and a ventriculo-peritoneal shunt was placed. Tumor regrowth led to another surgical resection 6 days ago. The procedure went smoothly and his recovery was uncomplicated until yesterday when he developed polyuria followed by headache and increasing lethargy. He has just had a generalized tonic-clonic seizure. His medications include Synthyroid (levothyroxine sodium), carafate, hydrocortisone and desmopressin acetate.Examination revealed an obese, postictal adolescent male who was afehrile, tachycardic (pulse 102/rain) and relatively hypotensive (blood pressure of 104/66 mmHg). His chest was clear and cardiac auscultation normal. He appeared to have adequate peripheral perfusion. Urinalysis showed specific gravity 1.012, pH 6, negative dipstick and unremarkahle microscopy. Current serum chemistries are: sodium (Na) 123 mEq/1, potassium (K) 3.4 mEq/1, chloride (CI) 92 mEq/1, bicarbonate 25 mEq/1, blood urea nitrogen 17 mg/dl (6.1 rmnol/1), creatinine 0.6 mg/dl (53 gmol/1), glucose 118 mg/dl (6.5 retool/l), uric acid 5.2 mg/dl (309 pmol/1) and osmolality 259 mmol/kg. Urine chemistries show Na 224 mEq/1, K 22 mEq/1, CI 261 mEq/1, creatinine 5 mg/dl (442 ~tmol/1) and osmolality 509 retool/ kg. Fractional excretion of Na is 21%. His fluid balance over the past several days is shown in Table 1.
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.
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