Role of the renin-angiotensin system on the renal functional reserve in renal transplant recipients

Abstract

To determine the renal functional reserve in renal transplant recipients, we measured the glomerular filtration rate by inulin clearance and the renal plasma flow by PAH clearance before and during an amino acid infusion (Totamine, 6 to 8 mg/kg/min for 90 to 120 min) in 18 transplanted patients with stable renal function. To test the role of the renin-angiotensin system on the renal functional reserve, we performed a crossover placebo-controlled randomized trial of acute blockade of the renin-angiotensin system by injection of perindoprilat (2 mg i.v.), an inhibitor of angiotensin converting enzyme before amino acid infusion, each patient being studied twice at seven day intervals. Amino acid infusion induced a time-dependent increase in the glomerular filtration rate (P = 0.04), whether or not the renin-angiotensin system was blocked. Maximal increases were from 49.1 +/- 4.1 to 58.9 +/- 5.4, mean +/- SE (18.5%), in control conditions and from 52.4 +/- 5.6 to 62.1 +/- 5.5 ml/min/1.73 m2 (19.7%) after perindoprilat. The increase in glomerular filtration rate was less pronounced in patients taking cyclosporin A than in patients treated with steroid and azathioprine. Amino acid infusion also induced a significant and time-dependent increase (15.2 to 20.2%) in the renal plasma flow (P < 0.01) whether or not perindoprilat had been given. Furthermore, perindoprilat alone increased renal plasma flow by 13.6%, and this effect seemed additive with that of amino acids. Perindoprilat injection decreased filtration fraction (from 0.20 +/- 0.01 to 0.19 +/- 0.01). This parameter returned to basal values after amino acid infusion (0.20 +/- 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal functional reserve in transplanted and native single kidneys of children and adults

“…Shokier et al [12] studied RFR Renal length (cm) in relation to the stimulated GFR (ml/min) in children following renal Tx after infusion of dopamine and amino acids and found lower baseline values and a somewhat lower RFR than we did. Our findings are in agreement with studies in adult renal Tx recipients investigated after an infusion of amino acids [21,22]. Rondeau, et al [21], however, showed a less pronounced increase in cyclosporine-treated patients than in azathioprine-treated patients.…”

“…Our findings are in agreement with studies in adult renal Tx recipients investigated after an infusion of amino acids [21,22]. Rondeau, et al [21], however, showed a less pronounced increase in cyclosporine-treated patients than in azathioprine-treated patients. Other studies report no RFR in cyclosporine-treated patients [9 -11, 23].…”

Fetal Exposure to Maternal Type 1 Diabetes Is Associated With Renal Dysfunction at Adult Age

“…Mogensen and Christensen (12) reported that in type 1 diabetes, global hyperfiltration is predictive of clinical proteinuria, and Sackmann et al (13) reported a reduced functional reserve both in normotensive, normoalbuminuric subjects with recent type 1 diabetes (those prone to nephropathy displayed global hyperfiltration), and in proteinuric subjects with long-lasting type 1 diabetes (those with an already reduced GFR). The participants with microalbuminuria studied by these authors were on ACE inhibitors, making data interpretation difficult, since ACE inhibitors can alter kidney function of such patients (16), and since renal functional reserve can be altered by these drugs (17). Studies conducted in animals (18,19) support the view that the glomeruli of subjects such as those with reduced functional reserve undergo individual hyperfiltration, a hemodynamic condition that favors glomerulosclerosis, hypertension, and high renovascular risk (1,11).…”

Long‐term (≥20 yr) status of 14 cadaveric kidney‐transplant recipients

“…Several studies showed that grafts were able to conserve a functional reserve, but no one seems to have made such measurements in very long‐term transplant recipients. RFR was 11.6 mL/min/1.73 m 2 at 5 yr for ter Wee et al [17] and 9.7 mL/min/1.73 m 2 at 5 yr for Rondeau et al [18]. The mean RFR value found for our patients, i.e., +6.7 mL/min/1.73 m 2 (range: 0.6–19.1) is coherent with those reported in the literature.…”