Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass

BACKGROUND AND OBJECTIVE: The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively. RESULTS: In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05). CONCLUSIONS: Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study.     

Renal function and cardiopulmonary bypass: effect of perfusion pressure.

Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified.     

Serum markers are not reliable measures of renal function in conjunction with cardiopulmonary bypass

The present study explored the influence of haemodilution on estimates of the glomerular filtration rate (GFR) in conjunction with cardiopulmonary bypass (CPB) and cardiac surgery. Ninety-eight patients (n = 98) undergoing coronary artery bypass grafting with the aid of CPB were examined. The serum concentration of cystatin C and creatinine was analysed prior to surgery, after completion of CPB and in the intensive care the day after surgery. The estimated GFR was calculated using standard equations based on the serum concentration of cystatin C and creatinine. It was found that haemodilution induced by CPB had significant effects on the estimated GFR. For cystatin C, the GFR increased by 50.5 ± 2.5 ml/min (P = 0.000) and for creatinine based GFR with 22.5 ± 0.9 ml/min (P = 0.000) using the 4-variable modification of diet renal disease formula and with 22.1 ± 0.93 ml/min (P = 0.000) for the Cockcroft-Gault formula, respectively. Similar effects of haemodilution on GFR were also detected postoperatively. Haemodilution induced by CPB may therefore significantly overestimate the renal function as indicated by GFR based on serum markers.     

Renal function before and long after liver transplantation in children.

BACKGROUND: Renal dysfunction occurs in children with liver diseases and renal function is often further impaired after orthotopic liver transplantation (OLT). Inaccurate methods of determining renal function are used in many cases. We studied renal function with accurate methods before and repeatedly after OLT to analyze the effect of the underlying diseases, hypertension, and the immunosuppressive agents. METHODS: A total of 46 children were studied both before and annually after OLT with clearances of inulin and paraaminohippuric acid to determine the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The clearance of inulin was also compared with the formula creatinine clearance. RESULTS: GFR and ERPF decreased from before to after OLT and decreased further during the first years after OLT. Patients with extrahepatic biliary atresia and with tumours showed higher GFR 1 year after OLT than those with metabolic and miscellaneous disorders. No significant change in GFR of individual patients occurred from the first to the last values determined at around 1 and 6 years after OLT. No difference in renal function was seen during the first years between patients treated with cyclosporine as compared to those treated with tacrolimus, but 4 years after OLT, the GFR was higher in the tacrolimus-treated patients. Patients on antihypertensive agents had lower GFR than the normotensive ones. There was no agreement between GFR, determined by clearance of inulin, and that calculated on the basis of serum creatinine and the height of the patients. CONCLUSIONS: Renal function is reduced by OLT and decreases further during the first years after OLT. Patients with metabolic disorders and those on antihypertensive treatment have the lowest GFR. Determination of GFR by the formula creatinine clearance is inaccurate in children after liver transplantation.     

Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline

BACKGROUND: Hypotensive anaesthesia (HA) and acute normovolaemic haemodilution (ANH) are used separately to decrease per-operative blood loss. Reducing blood viscosity by adding ANH to HA may appear profitable in a situation with lowered perfusion pressure and concern about organ ischemia. The aim of this study was to clarify the influence of HA in combination with ANH using crystalloid or colloid as replacement fluid on renal function. METHODS: Hypotensive anaesthesia was induced in 11 patients referred to major spine surgery using sevoflurane in combination with fentanyl/remifentanil. Acute normovolaemic haemodilution was carried out by drawing venous blood into standard blood bags and replacing it by isotonic saline 0.9% (Group S) or HES 130/0.4 (Group V). Renal function was evaluated before, during and up to 8 h after hypotension as the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by means of 51Cr-EDTA and 125I-Hippuran clearances. RESULTS: Lowering mean arterial blood pressure decreased GFR and ERPF in both groups. During hypotension ERPF was lower in Group S (n = 5) than Group V (n = 6). Renal function was normalized postoperatively. We found a positive but non-significant correlation between the relative GFR change and the duration of hypotension. CONCLUSION: In conclusion, our study demonstrated that renal function, assessed by GFR and ERPF, is transiently reduced during the combination of hypotensive anaesthesia and acute normovolaemic haemodilution. A colloid-based fluid regime (HES 130/0.4) used for haemodilution may preserve renal function to a greater extent than a crystalloid-based regime (0.9% saline).     

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

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23%±3%, 20%±3% and 15%±3% in Tx, Don, and Nx/Ag and RFR ERPF 35%±4% in Tx, which was significantly higher than 20%±4% and 15%±3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity. Received September 19, 1995; received in revised form September 16, 1996; accepted October 1, 1996     

Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus.

BACKGROUND: Nephropathia epidemica (NE) is the Scandinavian type of haemorrhagic fever with renal syndrome. Usually heavy transient proteinuria is present at the onset of the disease. METHODS: We investigated glomerular permeability in eight patients with acute NE and in eight healthy controls. Six patients were followed for 1 year. The glomerular filtration rate (GFR) was determined by inulin clearance and effective renal plasma flow (ERPF) by para-aminohippurate clearance. RESULTS: GFR and ERPF were significantly reduced in NE patients during the acute phase compared with those in controls (P<0.001 and P<0.001, respectively). The filtration fraction (FF) was thus high, 0.37. The fractional clearances of albumin, IgG, and IgG(4) were markedly increased. As a sign of tubular dysfunction, increased urinary excretion of alpha(1)-microglobulin was observed in all patients. After 1 year, the GFR of the patients no longer differed from that of the controls. ERPF was lower and FF higher than those in controls (P=0.014 and P=0.009, respectively). The fractional clearances of albumin, IgG, and IgG(4) remained increased. The high-molecular fractional dextran clearances in the patients were significantly increased compared with controls during the acute phase. Computed analysis of glomerular membrane-pore structure showed that the "shunt-flow" was increased in the patients during the acute phase compared with the controls. There was a positive correlation between the FF and the shunt (r=0.768, P=0.026). In addition, fractional clearances of albumin and IgG correlated significantly with the shunt (r=0.810, P=0.015 and r=0.762, P=0.028, respectively). CONCLUSIONS: Renal involvement in the acute phase of NE is characterized by a markedly decreased GFR and ERPF. Increased glomerular permeability is associated with impairment of both the size- and charge-selectivity properties of the glomerular filter.     

Immediate and early renal function after living donor transplantation.

BACKGROUND: In order to assess the immediate renal function after living donor transplantation, renal function was compared in eight renal allograft recipients and their living related kidney donors during the first 24 h after transplantation. METHODS: Substantial and comparable intraoperative volume loading with Ringer's acetate and mannitol was performed together with the administration of frusemide. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by the clearances of inulin and p-aminohippurane, respectively. Tubular reabsorptive function and injury were estimated from the clearance of lithium, the fractional excretion of sodium and the urinary excretion of N-acetyl-beta-glucosaminidase. RESULTS: One hour after completion of surgery, GFR (54 +/- 7 ml/min) and ERPF (294 +/- 35 ml/min) were only 30% lower in the grafts than in the remaining donor kidneys, increasing to similar levels within 3 h. Only minor tubular dysfunction and injury were revealed in the grafted kidneys, and these tended to normalize within 24 h. CONCLUSIONS: By the present transplantation procedure comprising short ischaemia time and substantial volume expansion combined with mannitol and frusemide administration, kidneys from living donors regain nearly normal function within a few hours after transplantation.     

Is Renal Warm Ischemia over 30 Minutes during Laparoscopic Partial Nephrectomy Possible? One-Year Results of a Prospective Study

OBJECTIVE: To evaluate renal damage and impairment of renal function 1 yr after laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. METHODS: From July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30 min. Kidney damage markers (daily proteinuria and tubular enzymes) and renal function (serum creatinine, cystatin C, and creatinine clearances) were assessed on postoperative days 1 and 5 and at 12 mo. Glomerular filtration rate (GFR) was evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was performed using the Student t test and logistic regression analysis. RESULTS: In terms of kidney damage and renal function markers, the statistical analysis demonstrated that at 1 yr there was complete return to the normal range and no statistical difference between the values at the various time points. The GFR was not significantly different before and 3 mo after surgery. In terms of scintigraphy of the operated kidney, the values were 48.35+/-3.82% (40-50%) before the procedure, 36.88+/-8.42 (16-50%) on postoperative day 5 (p=0.0001), 40.56+/-8.96 (20-50%) at 3 mo (p=0.003), and 42.8+/-7.2% (20-50%) 1 yr after surgery (p=0.001). CONCLUSION: Our results demonstrate that kidney damage occurs during LPN when warm ischemia is >30 min. This damage is only partially reversible and efforts should be made to keep warm ischemia within 30 min.     

Renal Functional Reserve in Patients with IgA Glomerulopathy

Seven patients with histologically proven IgA nephropathy and modest impairment of renal function, and 2 patients with IgA nephropathy and nephrotic syndrome were investigated, compared to a control group of 9 healthy individuals, to study the effects of amino acids on glomerular and tubular function, and to evaluate renal functional reserve in IgA nephropathy with different clinical course. Inulin and PAH clearances were used to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF); proximal and distal tubular fluid delivery and reabsorption were measured by lithium clearance, before and after submission of a standardized amino acid solution. GFR and ERPF increased significantly during amino acid load in healthy individuals and patients without nephrotic syndrome, while filtration fraction (GFR/ERPF) remained constant. Lithium clearance (C_Li) and fractional lithium excretion (C_Li/GFR) rose significantly in both groups, whereas the reabsorbed volume of fluid in the proximal tubule did not change. In the distal tubule, fractional volume excretion decreased significantly during amino acid load whereas the reabsorbed volume significantly increased. Baseline values of the two groups did not differ significantly. Two patients with nephrotic course of IgA nephropathy showed a distinct decrease in glomerular and tubular function, and a loss of renal functional reserve after amino acid load. Conclusions: Despite distinct alterations in renal biopsy, IgA nephropathy without nephrotic course presents with a still adequately preserved kidney function and renal functional reserve. A single determination of renal function with noninvasive functional tests does not give valid prognostic information concerning glomerular and tubular function. Therefore, a repeated measurement of renal function at defined intervals might reveal clinical progression of renal disease. The results of the lithium clearance might indicate an increase in tubular function after amino acid load, indicating a tubular adaptation in state of hyperfiltration.     

Relative glomerular hyperfiltration in primary aldosteronism

Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and beta2 microglobulin were higher in PA than EH (88 +/- 26 versus 39 +/- 12 and 0.91 +/- 0.23 versus 0.26 +/- 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 +/- 3/13 +/- 2 mmHg), urinary excretion of albumin and beta2 microglobulin (by 48 +/- 19 and 0.53 +/- 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 +/- 3 and 54 +/- 15 ml/min per 1.73 m(2), respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.     

Effects of halothane and isoflurane on transient renal dysfunction associated with infrarenal aortic cross-clamping.

Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = 10). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamics were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131I-hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 +/- 25.6 and 19.7 +/- 5.2 mL/min, respectively) than in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min) (P less than 0.05 for both). During cross-clamping, the renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 +/- 47.1 and 49.5 +/- 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 +/- 31.6 and 14.8 +/- 3.7 mL/min, respectively) (P less than 0.05). After aortic unclamping, ERPF increased markedly in both groups (467.8 +/- 122 and 362.5 +/- 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 +/- 22 and 71.8 +/- 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment.     

Study on urinary splitting enzymes and proteins. III. Effect of non-ionic contrast medium on renal function

Renal toxicity of non-ionic contrast medium (iohexol) for drip infused pyelography (DIP) was studied in a randomized trial of nine patients with normal renal function. Urine samples were collected before and immediately after DIP, and analyzed for albumin, an index of glomerular permeability; gamma-glutamyl transpeptidase (gamma-GTP), a brush-border enzyme; N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme; alpha 1 microglobulin (alpha 1MG) and beta 2 microglobulin (beta 2MG), an index to tubular proteinuria; and creatinine. The urinary excretion of enzymes and proteins was compared with urinary creatinine. Urinary excretion of gamma-GTP and NAG increased significantly (P less than 0.001, 0.02) after DIP. Urinary alpha 1 MG and beta 2-MG did not change significantly. The change of urinary albumin was mild. Our data suggest that non-ionic, low osmolal radiocontrast medium ioheol shows a lower renal tubular toxicity, and the brush-border enzyme gamma-GTP and lysosomal enzyme NAG are considered as a good index for renal tubular damage.     

Acute physiological changes in canine kidneys following exposure to extracorporeal shock waves

Nine anesthetized dogs were studied for four to five hours after administration of extracorporeal shock waves to one kidney, the contralateral organ serving as control. Urinary excretion of electrolytes, N-acetyl-beta-glucosaminidase (NAG) and kallikrein, clearances of creatinine, inulin and para-amino-hippuric acid (PAH), serum aldosterone level and plasma renin activity (PRA) were determined. On the exposed side there was a significant increase in urinary flow and urinary NAG excretion, and a significant fall in urinary osmolality. Effective renal plasma flow (ERPF) was reduced and glomerular filtration rate (GFR) unchanged, thus filtration fraction (FF) was increased. Extraction of PAH was significantly reduced compared with the control kidney. On the control side there was a significant increase in urinary flow and excretion of electrolytes, and a significant fall in urinary osmolality. GFR was increased and ERPF unchanged. FF therefore increased also on this side. The mean rise of PRA in the exposed kidney was higher than in the control kidney, the difference being not significant (p = 0.09). Our results may indicate a triggering of the renin-angiotensin system, and an effect on proximal tubular function following exposure of extracorporeal shock waves.     

Adaptation of renal function after unilateral nephrectomy in children with renal tumors

Following treatment, survivors of unilateral Wilms tumor (WT) develop structural and functional changes in the remnant kidney. A disproportional increase in functional over structural changes results in hyperfiltration, a condition that may lead to renal damage. We studied adaptation of renal function after uninephrectomy in ten WT patients and a child with renal cell carcinoma. Glomerular filtration rate (GFR) (measured by inulin and creatinine clearances), renal plasma flow (RPF) by para-aminohippurate (PAH) clearances and segmental tubular Na⁺ transport were studied before and following a protein load (renal functional reserve). Nine patients showed a well-adapted kidney function with a GFR of 82.27 (±5.6), an RPF of 429.71 (±65.6) ml/min/1.73 m² and a filtration fracton (FF) of 20%. Absolute proximal Na⁺ reabsorption was 65.2 (±9.6) ml/min/1.73 m², distal tubular delivery was 18.2 (±3.9) ml/min/1.73 m² and absolute distal Na⁺ reabsorption was 2146 (±435) μM/min. A peculiar finding was the high baseline creatinine clearances (176.17 ml/min/1.73 m²) related to increased baseline tubular creatinine secretion. Over 120 min following the protein load, GFR increased by 20%, RPF by 6% and FF remained unchanged. Absolute proximal reabsorption increased by 20% and distal reabsorption by 22%. While most changes in renal function induced by a protein load are similar in healthy individuals and uninephrectomized patients, a more predominant contribution to Na⁺ reabsorption by the proximal tubule was noted. Postload fractional proximal reabsorption remained at 77% while in healthy persons a decrease from 77% to 62% was reported. Two patients showed dysfunctional changes following nephrectomy characterized by an increased GFR (130 ml/min/1.73 m²), increased filtration fraction (29%) and inability to increase glomerular and tubular functions following a protein load (loss of functional reserve). The significance of these abnormalities is not known and requires long-term follow-up to evaluate whether hyperfiltration will lead to renal damage. Received: 28 August 2000 / Revised: 21 February 2001 / Accepted: 22 February 2001     

Renal functional adaptation of the adult kidney following transplantation to the child

Nineteen child renal transplant recipients, aged 1.3 to 19.2 years at transplantation, and their adult living-related kidney donors, 27 to 60 years of age at nephrectomy, were investigated simultaneously with regard to renal function. At a median time of three months after transplantation clearances of inulin (GFR) and paraaminohippuric acid (ERPF) were measured, and serum urea and creatinine concentrations were determined. The absolute values for GFR (72 +/- 13 ml/min) and ERPF (369 +/- 76 ml/min) in the donors were significantly higher than those of the recipients (37 +/- 22 and 196 +/- 72 ml/min, respectively). The absolute values of GFR and ERPF were significantly correlated with the body surface areas of the recipients. Thus, in relation to body surface area, the GFR, 68 +/- 11 ml/min/1.73 m2, and ERPF, 348 +/- 65 ml/min/1.73 m2, of the donors did not differ from those of the recipients, 68 +/- 20 and 375 +/- 90 ml/min/1.73 m2, respectively. Because of the greater body mass, the serum creatinine concentrations of the donors were significantly higher than those of the recipients, whereas the serum urea concentrations were significantly higher in the recipients. The results suggest that transplantation of an adult kidney to a child results in a functional adaptation to the smaller body size of the recipient, and that this adaptation occurs within three months after transplantation.     

Dietary supplementation with lish oil modifies renal reserve filtration capacity in postoperative, cyclosporin A-treated renal transplant recipients

Abstract. The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 = EPA and 20% C22:6 omega-3 = DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA +). Renal function tests were performed using the simultaneous determination of 1251-iothalamate and 1311-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA-and EPA + groups. Filtration fraction (FF) differed significantly, being 0. 21 in the EPA-group versus 0. 26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA + re-and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA + regroup had a significantly lower ERPF (164 ml/min per 1. 73 nr) than the EPA-re-group (262 ml/min per 1. 73 m²). FF was significantly higher in the EPA + re-group (0. 26) than in the EPA-re-group (0. 21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA + re-15. 3 versus EPA-re-10. 6%; P < 0. 05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA-and fish oil-treated patients have more balanced renal hemodynamics than the CyA-and coconut oil-treated patients.     

Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative,cyclosporin A-treated renal transplant recipients

The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3=EPA and 20% C22:6 omega-3=DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125 I-iothalamate and 131 I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA+ re- and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA+ re-group had a significantly lower ERPF (164 ml/min per 1.73 m²) than the EPA-re- group (262 ml/min per 1.73 m²). FF was significantly higher in the EPA+re-group (0.26) than in the EPA-re- group (0.21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA+re- 15.3 versus EPA-re- 10.6%; P<0.05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA- and fish oil-treated patients have more balanced renal hemodynamics than the CyA- and coconut oil-treated patients.     

Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes

To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow (ERPF) were slightly but not significantly higher (136 +/- 22 vs. 123 +/- 16 ml/min.1.73 m2) in IDD than in normal subjects. GFR and ERPF were positively and strongly correlated in controls (r = 0.61, P less than 0.001) and in diabetics (r = 0.72, P less than 0.0001) indicating the marked flow dependency of GFR in both populations. After adjustment for ERPF, GFR was significantly higher in diabetics, suggesting a role of increased glomerular capillary pressure and ultrafiltration coefficient in the subset of "hyperfiltering" patients. Both fractional (FPRNa) and absolute (APRNa) proximal sodium reabsorption were significantly higher in IDD and significantly correlated with GFR. The ensuing decrease in sodium distal delivery could deactivate the tubuloglomerular feedback response and thus favor sustained vasodilation and high GFR in some diabetics. The renal effects of acute administration of drugs acting predominantly at either the pre- or the postglomerular resistance using nicardipine (N = 16) or captopril (N = 25) were further evaluated in IDD. The renal response to captopril or nicardipine was different in IDD. Whereas both drugs induced a marked decrease in renal vascular resistance, GFR was slightly decreased by captopril and was unchanged after nicardipine; these results are similar to those observed in normotensive non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase in renal plasma flow and glomerular filtration rate during growth hormone treatment may be mediated by insulin-like growth factor I

The temporal relationships between the changes in inulin and p-aminohippurate clearances and plasma growth hormone (GH) and insulin-like growth factor I (IGF I levels were examined in a man with hypothalamic GH deficiency before and during the first 6 days of treatment with daily GH injections. The patient ate a diet with a constant protein and salt content from 1 week before the study until it was completed. During the 4-hour period immediately after the first GH injection, plasma GH rose markedly, but plasma IGF I was not detectable, and effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) did not change from baseline. On the next day, before the second GH injection was given, plasma GH was only slightly elevated, plasma IGF I had increased, and ERPF and GFR had risen by +35.5 +/- 2.1% (SEM) and +22.7 +/- 2.8%, respectively. On the 4th and 7th days, immediately before the GH injections, there was no further rise in ERPF and GFR, both of which remained well above baseline values. At these times, plasma GH levels were at baseline, but plasma IGF I continued to rise progressively. These data are consistent with the thesis that the low ERPF and GFR in GH deficiency is due to the lack of synthesis of IGF I rather than the deficiency in GH per se. The data are also consistent with a stimulatory effect of IGF I on ERPF and GFR.