Early and late humoral rejection: a clinicopathologic entity in two times.

Humoral rejection is an important cause of early and late graft loss. The late variant is difficult to diagnose and treat. There is a close correlation between sclerosing nephropathy and anti-HLA antibodies. We analyzed 113 renal allograft recipients between August 2004 and April 2007. Acute humoral rejection was defined as acute graft dysfunction in presence of donor-specific antibodies (DSA) detected by flow panel reactive antibodies (PRA) and/or C4d positive pericapilary tubules (PTC) detected histopathologically by immunofluorescent or immunoperoxidase at less than 3 months postransplantation. Late humoral rejection was defined as dysfunction occurring after 3 months postransplantation with histopathologic glomerulopathy or vasculopathy and positive C4d PTC. We included all patients who were diagnosed with early or late graft dysfunction and underwent biopsy, all of which were examined for C4d. Four patients had acute humoral rejection treated with IVIG or plasmapheresis. The patient and graft survivals were 100% and serum creatinine averaged 1.7 mg/dL. Three recipients experienced late humoral rejection at 3 to 10 years posttransplantation All received high-dose IVIG; one also was treated with thymoglobulin. Immunosuppression was switched to tacrolimus, mycophenolate mofetil, and steroids. Only one patient recovered renal function; the others returned to dialysis. Among seven patients only one had an actual PRA (>20%) and three showed 10% to 20%. However, six had a positive historical PRA of 10% to 50%. In conclusion, Recognition of acute humoral rejection has contributed to graft rescue by controlling alloantibody production through new specific immunosuppressive therapies in contrast with the clinical response to acute therapy, treatment of a chronic entity has shown poor outcomes, probably because antibody mediated chronic graft damage is already present when the late diagnosis is established by biopsy.

Dietary salt intake, blood pressure and the kidney in hypertensive patients with non-insulin dependent diabetes mellitus.

The mechanisms responsible for hypertension in NIDDM patients are only partially understood. Increased sensitivity to dietary salt intake and to vasoconstrictor hormones are among the mechanisms proposed. We have studied 19 hypertensive NIDDM patients 7 salt-sensitive and 12 salt-resistant while they were ingesting a diet with 20 mEq/day of Na+ for 9 days and while they were ingesting a diet containing 250 mEq/day of Na+ for 14 days. During the last 4 days of each dietary regimen, they received 60 mg/day of slow-release nifedipine. Blood pressure response to increasing doses of norepinephrine and angiotensin II was studied at the end of each of the four phases of the study. High salt intake increased blood pressure and decreased heart rate in these patients. High salt intake also increased the vascular response to norepinephrine but not to angiotensin II in NIDDM hypertensive subjects. Glomerular filtration rate and renal blood flow were not different during the low and high salt diets. There were no differences in the blood pressure response to norepinephrine or angiotensin II, nor in renal hemodynamic changes among salt-sensitive and salt-resistant NIDDM patients. Nifedipine decreased blood pressure equally in salt-sensitive and salt-resistant hypertensive patients and during the high and the low salt intake. Nifedipine increased renal blood flow, both in salt-sensitive and in salt-resistant individuals, but the differences did not reach statistical significance. Nifedipine decreased the blood pressure response to both norepinephrine and angiotensin II. The studies indicate that an increased reactivity to the pressor action of norepinephrine may contribute to the maintenance of hypertension in NIDDM hypertensive subjects and high salt intake may aggravate the pressor responsiveness to norepinephrine in these patients. Nifedipine is an effective antihypertensive drug in NIDDM patients and its action may be in part related to a decrease in pressor response to norepinephrine and angiotensin II.

Effect of L-arginine on systemic and renal haemodynamics in salt-sensitive patients with essential hypertension.

In response to a high sodium (Na+) intake, salt-sensitive patients with hypertension retain more Na+ and manifest a greater rise in arterial pressure than salt-resistant patients. Because there is limited information regarding the role of nitric oxide (NO) in salt-sensitivity we examined the effects of L-arginine (500 mg/kg, i.v. for 30 min) on mean arterial pressure and renal haemodynamics in 21 hypertensive and five normotensive African-Americans. At the end of L-arginine infusion mean arterial pressure fell more in salt-sensitive (-11.5 +/- 2.5) than in salt-resistant (-3.7 +/- 1.5 mm Hg) and control subjects (-3.2 +/- 3.8 mm Hg). At the end of L-arginine infusion effective renal plasma flow (ERPF) increased more (P < 0.05) in controls (+108 +/- 13.9 ml/min/1.73 m2) than in salt-resistant (+55 +/- 16.0 ml/min/1.73 m2) and salt-sensitive patients (+22 +/- 21.5 ml/min/1.73 m2). This study has shown that salt-sensitive African-Americans manifest different systemic and renal haemodynamic responses to L-arginine than salt-resistant patients and controls. The fall in mean blood pressure following L-arginine was greater in salt-sensitive than in salt-resistant patients and controls, whereas the increase in ERPF was reduced in salt-sensitive compared to salt-resistant and normal subjects. The data are in keeping with the notion that a defect in NO production may participate to the genesis of blood pressure sensitivity to salt.