MDRD Equations for Estimation of GFR in Renal Transplant Recipients

After renal transplantation monitoring and detection of slight-to-moderate changes in GFR is a prerequisite for an optimal patient management. Recently, several equations to estimate GFR were developed and verified in the MDRD study cohort. However, little is known about the application of the MDRD formulas in the setting of renal transplantation. We prospectively conducted a study of the GFR estimates of the Cockcroft and Gault (C&G), MDRD6-, MDRD7 and the abbreviated MDRD (aMDRD) with the true GFR as measured by (99m)Tc-DTPA clearance in 95 consecutive patients 6.5, 5.3-7.7 years (mean, 95% CI) after renal transplantation. On average the DTPA clearance was 37.4, 34.4-40.4 mL/min/1.73 m(2), which differed significantly from estimates of GFR by C&G (52.6, 48.3-56.9 mL/min/1.73 m(2)), MDRD7 (44.8, 40.7-49.0 mL/min/1.73 m(2)), MDRD6 (43.8, 39.9-47.7 mL/min/1.73 m(2)) and aMDRD (46.6, 42.4-50.9 mL/min/1.73 m(2)). Bias was lowest for MDRD6 (6.4 mL/min/1.73 m(2)) and highest for C&G (15.2 mL/min/1.73 m(2)). Precision was similar for MDRD7 and aMDRD (10.6 and 11.1 mL/min/1.73 m(2)) but significantly better for MDRD6 (8.6 mL/min/1.73 m(2); p < 0.035). Accuracy within 50% of real GFR was 55.8% for C&G, 83.2% for aMDRD, 87.4% for MDRD7 and 90.5% for MDRD6. MDRD equations perform significantly better than the commonly used C&G formula. Moreover, the MDRD6 equation provides the best diagnostic performance, and should therefore be preferred in renal transplant recipients.     

Performance of Different Prediction Equations for Estimating Renal Function in Kidney Transplantation

Numerous formulas have been developed to estimate renal function from biochemical, demographic and anthropometric data. Here we compared renal function derived from 12 published prediction equations with glomerular filtration rate (GFR) measurement by plasma iohexol clearance as reference method in a group of 81 renal transplant recipients enrolled in the Mycophenolate Mofetil Steroid Sparing (MY.S.S.) trial. Iohexol clearances and prediction equations were carried out in all patients at months 6, 9 and 21 after surgery. All equations showed a tendency toward GFR over-estimation: Walser and MDRD equations gave the best performance, however not more than 45% of estimated values were within +/-10% error. These formulas showed also the lowest bias and the highest precision: 0.5 and 9.2 mL/min/1.73 m2 (Walser), 2.7 and 10.4 mL/min/1.73 m2 (MDRD) in predicting GFR. A significantly higher rate of GFR decline ranging from -5.0 mL/min/1.73 m2/year (Walser) to -7.4 mL/min/1.73 m2/year (Davis-Chandler) was estimated by all the equations as compared with iohexol clearance (-3.0 mL/min/1.73 m2/year). The 12 prediction equations do not allow a rigorous assessment of renal function in kidney transplant recipients. In clinical trials of kidney transplantation, graft function should be preferably monitored using a reference method of GFR measurement, such as iohexol plasma clearance.     

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell,Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.     

Hemodynamic maladjustment and disease progression in nephrosis with FSGS

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end-stage renal disease. Herein, we reported 10 patients with NS-FSGS who had initially had CCr 34 +/- 12 mL/min/1.73 m2 (normal 120 mL/min/1.73 m2), FE Mg 7.8 +/- 2.6% (normal 2.2%), 24-h urinary protein 3.1 g (normal <200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 +/- 8636 dyne x s x cm(-5); normal 3000 dyne x s x cm(-5)), intraglomerular hypertension (PG 57 +/- 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 +/- 17 mL/min/1.73 m2, renal plasma flow (RPF 159 +/- 61 mL/min/1.73 m2; normal 600 mL/min/1.73 m2) and peritubular capillary flow (PTCF 123 +/- 57 mL/min/1.73 m2; normal 480 mL/min/1.73 m2). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 +/- 2191 dyne x s x cm(-5), PG 52 +/- mm Hg, FF 0.19 +/- 0.1 and increments in RPF 341 +/- 118 mL/min/1.73 m2, PTCF 280 +/- 106 mL/min/1.73 m2 and GFR 64 +/- 17 mL/min/1.73 m2. Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 +/- 2.6% and suppression of proteinuria 0.29 +/- 0.4 g/24 h after the period of follow-up of greater than 10 years.     

Predicting GFR in children and adults: a comparison of the Cockcroft-Gault,Schwartz, and modification of diet in renal disease formulas

BACKGROUND: A rapid prediction of glomerular filtration rate (GFR) is often needed in clinics. Formulas based on plasma creatinine level are being increasingly used, Schwartz for children, supposed to give GFR; Cockcroft-Gault for adults, supposed to indicate the creatinine clearance; and a recent formula introduced by the Modification of Diet in Renal Disease (MDRD) group. Our objective was to test whether one single formula could suffice and which one gives the best estimation of GFR. METHODS: In 198 children (with two kidneys, single kidney, or renal transplant) and 116 adults (single kidney and transplanted), we measured inulin clearance and creatinine clearance and calculated Cockcroft-Gault, MDRD and, in children only, Schwartz. Data were compared with analysis of variance (ANOVA), regression statistics, and concordance studies. RESULTS: In patients over 12 years of age, Cockcroft-Gault was almost similar to GFR corrected for body surface and creatinine clearance exceeded GFR by more than 20%; Schwartz was above creatinine clearance excepted for transplanted children. In younger children, no prediction approached GFR. Predictions were well correlated with GFR, but concordance studies showed Schwartz with dispersed results and GFR overestimated (20 mL/min/1.73 m2); Cockcroft-Gault was close to GFR and results were dispersed; MDRD in children gave a large overestimation and badly dispersed results; in transplanted adults its prediction was good. CONCLUSION: Cockcroft-Gault prediction could be used for children over 12 years of age and adults; it should not be considered as creatinine clearance but as GFR corrected for body surface, it is merely a prediction, 95% of the results are between +/-40 mL/min/1.73 m(2) in children and +/-30 mL/min/1.72 m(2) in adults. In younger children no formula is satisfying.     

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.     

Glomerular endothelial dysfunction and hemodynamic maladjustment in vesicoureteric reflux

A structural defect of the non-vascular component of a nephron namely vesicoureteric reflex (VUR) can induce injury to the vascular component, which is reflected by the alteration in intrarenal hemodynamics. A mild alteration in intrarenal hemodynamics was observed in grades I-II VUR which revealed (a) mild reductions in renal plasma flow (RPF) 543 +/- 104 mL/min/1.73 m2; in peritubular capillary flow (PTCF) 438 +/- 103mL/min/1.73 m2; in glomerular filtration rate (GFR) 105 +/- 19 mL/min/1.73 m2 and in ultrafiltration coefficient (KFG) 0.04 +/- 0.01 mL/s/mmHg; (b) normal values of filtration fraction (FF) 0.2 +/- 0.04, of intraglomerular hydrostatic pressure (PG) 50 +/- 0.3 mmHg, and of afferent arteriolar resistance (RA) 2261 +/- 718 dyne s cm(-5); and (c) a slight elevation of efferent arteriolar resistance (RE) 3914 +/- 962 dyne s cm(-5). In contrast, a moderately severe alteration in intrarenal hemodynamics was observed in severe VUR (grades III up) which revealed greater reductions in RPF 267 +/- 114 mL/min/1.73 m2, in PTCF 195 +/- 90 mL/min/1.73 m2, in GFR 72 +/- 34 mL/min/1.73 m2 and in KFG 0.03 +/- 0.01 mL/s/mmHg; and elevation of PG 53 +/- 2 mmHg, of filtration fraction 0.27 +/- 0.07, of RA 4557 +/- 2340 dyne s cm(-5) and of RE 9417 +/- 4163 dyne s cm(-5). Such an alteration in intrarenal hemodynamics observed in severe VUR induces both intraglomerular hypertension (elevated PG) and an exaggeratedly reduced PTCF. This intrarenal hemodynamic defect is due to the glomerular endothelial dysfunction and its hemodynamic maladjustment. In accordance with the preceding information, treatment to correct the hemodynamic maladjustment is likely to improve renal function and prevent renal disease progression.     

Impact of percutaneous nephrolithotomy on estimated glomerular filtration rate in patients with chronic kidney disease

BACKGROUND AND PURPOSE: We investigated the impact of percutaneous renal procedures on estimated glomerular filtration rate (GFR) of patients with chronic kidney disease (CKD). PATIENTS AND METHODS: The GFRs of adult patients were calculated using the Modification of Diet in Renal Disease formula, and the patients were staged according to the Kidney Disease Outcome Quality Initiative CKD classification system. The study included 185 patients with preoperative GFR values less than 60 mL/min/1.73 m(2). The impact of percutaneous nephrolithotomy (PCNL) on GFR was analyzed by comparing the preoperative GFR with the GFR before discharge and at postoperative month 3. RESULTS: Patients with CKD had a significant increase in the GFR after the procedure. In postoperative month 3, the mean GFR was more than 60 mL/min/1.73 m(2) in 25% of the patients with CKD and less than 60 mL/min/1.73 m(2) in 75%. While all patients with stage 5 CKD improved to better stages, some other patients' conditions declined to stage 5 from better stages at the end of postoperative month 3. No patient needed dialysis. The presence of urinary tract infections tended to affect GFR negatively. CONCLUSION: Estimated GFR, as a better indicator of renal function, is significantly affected by the PCNL procedure. While significant improvement was observed in late-stage patients with CKD, unexpected deterioration could occur in patients at earlier stages.     

The plasma creatinine concentration is not an accurate reflection of the glomerular filtration rate in stable renal transplant patients receiving cyclosporine

We studied 31 stable renal cadaver kidney transplant patients receiving cyclosporine (CyA) and prednisone for immunosuppression to determine what reduction in true glomerular filtration rate (GFR) was reflected by their mild elevation in plasma creatinine concentration (1.8 +/- 0.11 mg/dL). We measured both the creatinine clearance (60 +/- 4.32 mL/min/1.73 m2) and the true GFR using Technetium 99m-DTPA (44 +/- 2.72 mL/min/1.73 m2). The creatinine clearance overestimated true GRF by a mean of 38%, indicating that this percentage of creatinine reached the urine by tubular secretion rather than glomerular filtration. A similar degree of overestimation was found in a separate group of 14 patients receiving imuran for immunosuppression. In 23 patients receiving CyA in whom the serum creatinine concentration was less than 2.0 mg/dL, the mean DTPA clearance was 49.5 +/- 2.83 mL/min/1.73 m2. In stable renal transplant patients receiving CyA, a serum creatinine concentration at, or close to, the upper limit of the normal range may reflect markedly impaired renal function.     

Constant-infusion technique of inulin clearance without urine collection

Inulin clearance is accepted as the gold standard for estimating the glomerular filtration rate (GFR). However, the method of this examination is troublesome and infants need difficult bladder catheterization. The existence of residual urine results in an inaccurate estimation of GFR and the proceduse requires a large amount of transfusion. In the plasma infusion method, inulin reaches an equilibrium in which the inulin urinary excretion rate is equal to the infusion rate, and urine collection is unnecessary. We estimated GFR in 21 children using both the plasma infusion method and renal infusion method. In the renal infusion method, the loading infusion of 1% inulin was administered over 30 minutes at the dose of 5 mL/kg body weight, followed by maintenance infusion at the constant speed (mL/hour) of 1.5 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/ 1.73. Three 30-minute urine collections were performed and the plasma inulin levels were measured to estimate GFR. In the plasma infusion method, maintenance infusion was conducted at the speed (mL/hour) of 0.6 x estimated GFR (mL/min/1.73 m2) x body surface area (m2)/1.73. The mean plasma inulin concentrations at 8, 9 and 10 hours were examined and GFR was calculated with the infusion rate. The GFRs for the renal infusion methods (Cin) and plasma infusion methods (e-Cin) were 91.90 +/- 39.61 and 95.33 +/- 38.08 mL/min/1.73 m2, respectively. The values for Cin and e-Cin showed good linear correlation (R2 = 0.81). The value of e-Cin/Cin was 1.069 +/- 0.172 and the mean e-Cin value was only 7% higher than that of Cin. We believe that GFR estimated by the constant infusion method shows a value approximating that estimated by the standard method. This technique is noninvasive for infants and the GFR of children who have vesicoureteral reflux or residual urine in the bladder can be estimated. The method does not need a large amount of transfusion and is suitable for children with heart failure. We believe that this method is clinically useful.     

Relationship between hematocrit and renal function in men and women

BACKGROUND: Anemia is a known complication of renal insufficiency, but the relationship between level of renal function and magnitude of reduction in hematocrit is not well defined. Men have higher hematocrit and absolute glomerular filtration rate (GFR) than women; however, it is unknown whether the level of clearance associated with decreased hematocrit is the same in men and women. METHODS: We conducted a cross-sectional study of 12,055 adult ambulatory patients. General linear models were used to analyze the relationship between hematocrit and Cockcroft-Gault equation estimated creatinine clearance (C(Cr); mL/min) and Modification of Diet in Renal Disease (MDRD) formula estimated the GFR indexed to body surface area (mL/min/1.73 m(2)). RESULTS: The hematocrit decreased progressively below estimated C(Cr) 60 mL/min in men and 40 mL/min in women. Compared with subjects with C(Cr)> 80 mL/min, men with C(Cr) 60 to 50 mL/min, 50 to 40 mL/min, 40 to 30 mL/min, 30 to 20 mL/min, and < or =20 mL/min had mean hematocrits that were lower by 1.0, 2.4, 3.7, 3.5, and 10.0%, respectively; the corresponding reductions in women with C(Cr) 40 to 30 mL/min, 30 to 20 mL/min, and < or =20 mL/min were 1.7, 2.9, and 6.3% (all P < 0.05). This between-sex difference diminished when renal function measurement was indexed to body size. Compared with subjects with GFR> 80 mL/min/1.73 m(2), men with GFR 50 to 40 mL/min/1.73 m(2), 40 to 30 mL/min/1.73 m(2), 30 to 20 mL/min/1.73 m(2), and < or =20 mL/min/1.73 m(2) had mean hematocrits that were lower by 2.0, 4.4, 5.3, and 9.4%; the corresponding reductions in women with GFR 50 to 40 mL/min/1.73 m(2), 40 to 30 mL/min/1.73 m(2), 30 to 20 mL/min/1.73 m(2) and < or =20 mL/min/1.73 m(2) were 0.6, 1.6, 3.8, and 5.3% (all P < 0.05). CONCLUSIONS: A decrease in hematocrit is apparent even among patients with mild to moderate renal insufficiency. At any given level of renal function below estimated C(Cr) 60 mL/min, men have a larger decrease in hematocrit than women.     

A randomized, double-blind, placebo-controlled trial to evaluate the effect of enalapril in patients with clinical diabetic nephropathy.

It is unknown if the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors reflects attenuation in the rate of progression of diabetic nephropathy. We report the results of a randomized, double-blind clinical trial designed to evaluate the longitudinal (18-month) effect of the ACE inhibitor, enalapril (5 to 40 mg/d), versus a placebo on 24-hour urinary protein excretion and on the rate of progression of renal disease in 33 patients with clinical diabetic nephropathy. Systemic blood pressure was controlled throughout the trial with conventional antihypertensive drugs. Glomerular filtration rate (GFR), determined by Tc99mDTPA renal clearance, and urinary protein excretion were monitored at 3-month intervals. Enalapril, in contrast to placebo therapy, was associated with an initial (40%) and sustained (33%) decrease in urinary protein excretion. Patients randomized to both enalapril or placebo experienced mean decreases in GFR, from 1.01 mL/s/1.73 m2 (61 mL/min/1.73 m2) to 0.85 mL/s/1.73 m2 (51 mL/min/1.73 m2), and from 1.06 mL/s/1.73 m2 (64 mL/min/1.73 m2) to 0.97 mL/s/1.73 m2 (58 mL/min/1.73 m2), respectively. Eleven of 18 patients (61%) randomized to enalapril, and 10 of 15 (66%) patients randomized to placebo, had a decrease in GFR; their rates of progression were -1.18 mL/min/1.73 m2/mo and -1.00 mL/min/1.73 m2/mo, respectively. In the absence of changes in blood pressure, the addition of an ACE inhibitor to patients with clinical diabetic nephropathy could not be shown to confer a unique renal protective effect. A prolonged decrease in 24-hour protein excretion could not be shown to predict attenuation in the progression of established clinical diabetic nephropathy.     

Estimation of glomerular filtration rates after orthotopic liver transplantation: Evaluation of cystatin C-based equations.

Early detection of renal dysfunction in patients after orthotopic liver transplantation is important. Creatinine-based equations to estimate glomerular filtration rate (GFR) were found to be less accurate in liver transplant recipients than in their original populations. Since cystatin C (CysC) is independent from muscle mass and hepatic biosynthesis, we evaluated the diagnostic accuracy of 3 CysC-based equations (Larson, Hoek, and Filler formulae) that are based on the same CysC method as that of our center in comparison to the abbreviated creatinine-based modification of diet in renal disease (MDRD) formula in 59 liver transplant recipients. "True GFR" was measured by 99mTc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) clearance. Neither correlation with the GFR (correlation coefficients: 0.594-0.640) nor precision (root mean square error: 15.7-18.17 mL/min/1.73 m(2)) differed significantly between the tested formulae. The biases of the Hoek and Larsson formulae were significantly smaller than those of the MDRD and Filler equations (-0.1 and -2.3 vs. 10.1 and 7.9 mL/min/1.73 m(2), respectively; P 相似文献   

Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients: validity of a new (MDRD) prediction equation.

BACKGROUND: Based on the data derived from the Modification of Diet in Renal Disease (MDRD) study, a new equation was developed for the estimation of glomerular filtration rate (GFR). This equation, which takes into account body weight, age, sex, serum creatinine, race, serum urea, and serum albumin, provided a more accurate estimation of GFR in patients with renal insufficiency. However, this prediction equation has not been validated in subjects with normal or supra-normal GFR. METHODS: In a cross-sectional study, we measured GFR by inulin clearance in 46 healthy controls and 46 non-complicated type 1 diabetic patients. In this study population, GFR was predicted by measured creatinine clearance, the Cockcroft-Gault formula, and the MDRD equation. RESULTS: In the healthy subjects, mean GFR (+/-SD) was 107+/-11 as compared to 122+/-18 ml/min per 1.73 m(2) in the diabetic patients. This difference in GFR was reflected by a lower serum creatinine (76+/-8 vs 71+/-8 micro mol/l) in the diabetic patients. In the healthy controls, median absolute differences (and the 50th-75th-90th percentile of percentage absolute differences) between predicted and measured GFR were 5.2 ml/min per 1.73 m(2) (4.9-9.8-18.5%) for creatinine clearance, 9.0 ml/min per 1.73 m(2) (8.6-14.3-24.6%) for the Cockcroft-Gault formula, and 10.7 ml/min per 1.73 m(2) (10.9-16.3-25.5%) for the MDRD equation. In the diabetic patients, these differences were 8.3 ml/min per 1.73 m(2) (7.6-9.3-13.0%) for creatinine clearance; 11.8 ml/min per 1.73 m(2) (10.1-16.0-22.5%) for the Cockcroft-Gault formula, and 18.8 ml/min per 1.73 m(2) (16.0-24.2-31.9%) for the MDRD equation. CONCLUSIONS: In subjects with a normal or increased GFR, the new MDRD-prediction equation of GFR is less accurate than creatinine clearance or the Cockcroft-Gault formula, and offers no advantage.     

Percutaneous nephrolithotomy in children: early and late anatomical and functional results

PURPOSE: We report our experience with percutaneous nephrolithotomy (PCNL) in children, and evaluate its early and late anatomical and functional results. MATERIALS AND METHODS: A total of 65 children with renal calculi were treated with PCNL. Patient age at operation ranged from 9 months to 16 years (mean +/- SD of 5.9 +/- 0.9 years), and 27 (41.5%) were younger than 5 years. Seven patients had bilateral renal stones and, therefore, the number of kidneys treated by PCNL was 72. The patients were followed regularly every 3 months during year 1 and every 6 months thereafter. Renal scans using technetium dimercapto-succinic acid for detection of renal scarring and technetium diethylenetetramine-pentaacetic acid for determination of selective glomerular filtration rate (GFR) were performed in all patients at least once during followup, which ranged from 6 to 72 months (mean +/- SD 40 +/- 10). RESULTS: Early complications included significant intraoperative bleeding in 1 case, renal pelvis perforation in 1 and transient fever in 2. Mean hospital stay +/- SD was 3 +/- 1.2 days (range 2 to 21). Of the renal units 62 (86%) were stone-free after a single PCNL, and the remaining 10 with residual stones were treated with a second look PCNL (4) and shock wave lithotripsy (6). Stone-free rates at hospital discharge and at 3 months were 93% and 100%, respectively. During followup 6 patients (9%) had recurrence of small renal stones and were successfully treated with shock wave lithotripsy. None of the kidneys had scarring on dimercapto-succinic acid renal scan. All of the kidneys except 1 showed improvement or stabilization of the corresponding GFR determined by diethylenetetraminepentaacetic acid renal scan. Comparison of the mean preoperative GFR of the corresponding kidney (28.8 +/- 11.2 ml per minute) with mean value at followup (36.1 +/- 9.9) showed an increase of statistical significance (p <0.01). CONCLUSIONS: PCNL is a safe and effective procedure for the treatment of children with renal calculi. At long-term followup the procedure improves renal function without renal scarring.     

The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients

We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.     

Decline in native renal function early after bladder-drained pancreas transplantation alone

BACKGROUND: Pancreas transplant alone (PTA) has become accepted therapy for select nonuremic patients with type 1 diabetes mellitus. However, PTA may lead to significant complications including a decline in native renal function. This study examines trends in native renal function during the first posttransplant year in PTA recipients with a spectrum of pretransplant glomerular filtration rates (GFR). METHODS: Renal function was studied in 23 recipients of bladder-drained PTA who underwent transplantation from April 1998 through September 2001. GFR was measured by corrected iothalamate clearance at the time of transplant evaluation and 1 year posttransplant and also calculated using the Cockcroft-Gault method at the transplant evaluation; at the day of transplantation; and at 1, 6, and 12 months posttransplant. RESULTS: Iothalamate clearance decreased in the first year in 96% of patients (22 of 23). The mean measured GFR decreased from 84 +/- 33 mL/min/1.73 m2 pretransplant to 52 +/- 26 mL/min/1.73 m2 at 1 year (P <0.001). Calculated creatinine clearance declined in the majority of patients at both 1 and 12 months after PTA, but some patients, including a few with low GFR, maintained stable renal function. Calculated GFR generally correlated well with measured GFR in most patients, with a few notable exceptions. One patient (baseline GFR, 42 mL/min/1.73 m2) developed renal failure in the first year after transplant and required kidney transplantation. CONCLUSIONS: Bladder-drained PTA results in a decline in native renal function in the majority of patients regardless of the pretransplant GFR. These data suggest the need for strategies to prevent or minimize the decline in renal function after PTA.     

Creatinine-based formulae for the estimation of glomerular filtration rate in heart transplant recipients

Chronic renal failure (CRF) is a common complication in heart transplant patients. Serum creatinine has clear limitations for the detection and estimation of glomerular filtration rate (GFR). Various creatinine-based formulae are classically used for GFR estimation, but little scientific evidence exists for such use in a heart transplant population. GFR was measured using the plasmatic clearance of the glomerular tracer (51)Cr-EDTA in 27 heart transplant patients with two measures for 22 of the patients. Forty-nine measures were thus available for analysis. The precision and accuracy (Bland and Altman analysis) of the Cockcroft, simplified Modified Diet in Renal Diseases (MDRD) and new Mayo Clinic formulae were compared. The mean GFR of the population was 39 +/- 15 mL/min/1.73 m(2). All formulae were well correlated with the GFR. With the Bland and Altman analysis, the accuracy of the MDRD formula appeared higher than that of the Cockcroft or the Mayo Clinic formulae (bias of +12 mL/min/1.73 m(2), vs. +19.9 mL/min/1.73 m(2), and +22.1 mL/min/1.73 m(2), respectively). The difference between the estimated and measured GFR was higher than 20 mL/min/1.73 m(2) in 51% and 55% cases when using the Cockcroft and the Mayo Clinic formulae respectively, whereas the difference was only noted in 14% cases when the MDRD was used. Among creatinine-based formulae, the MDRD appears the most precise and accurate for estimating the GFR in heart transplant patients. However, when the GFR must be measured with high accuracy, we recommend the use of a reference method like inulin or (51)Cr-EDTA plasma clearance techniques.     

Cimetidine improves prediction of the glomerular filtration rate by the Cockcroft-Gault formula in renal transplant recipients

BACKGROUND: The glomerular filtration rate (GFR) can be predicted from plasma creatinine, age, gender, and body weight, using the formula of Cockcroft and Gault. Cimetidine improved the accuracy of GFR prediction in renal disease and also in diabetes mellitus type 2, due to inhibition of tubular creatinine secretion. We compared the accuracy and precision of GFR prediction from the Cockcroft-Gault formula without cimetidine (CG), with cimetidine (CGcim) and from the creatinine clearance without cimetidine in renal transplant recipients. METHODS: CG and CGcim were calculated from plasma creatinine before and after 2400 mg of oral cimetidine during the 24 hr preceding the GFR measurement. The endogenous creatinine clearance was measured in 24 outpatients from a 24-hr urine collection (Ccr24) before cimetidine. GFR was measured as the urinary clearance of continuously infused 125I-iothalamate. Creatinine was determined with an automated enzymatic assay in plasma and with an alkaline picrate assay in urine. RESULTS: GFR was 47.8+/-16.8 ml/min/1.73 m2 (mean+/-SD), Ccr24 was 71.8+/-23.1 ml/min/1.73 m2, CG was 62.2+/-15.2 ml/min/1.73 m2, and CGcim was 52.8+/-14.9 ml/min/1.73 m2. Ccr24 overestimated GFR in every patient by an average of 23.8 ml/min/1.73 m2 and CG by an average of 14.3 ml/min/1.73 m2, whereas CGcim overestimated GFR significantly less by an average 4.9 ml/min/1.73 m2 (P<0.001). The precision of CGcim was significantly better than that of Ccr24: the SD of the difference from GFR was 9.0 ml/min/1.73 m2 for CGcim and 14.5 ml/min/1.73 m2 for Ccr24 (P<0.05). CONCLUSION: CGcim is useful for GFR prediction in outpatient renal transplant recipients and has a far better accuracy and precision than Ccr24 and also a better accuracy than CG. We propose a strategy after kidney transplantation of one GFR measurement at baseline and follow-up with CGcim.     

Controlled changes in chronic dietary protein intake do not change glomerular filtration rate

The effect on renal function (creatinine clearance [Ccreat] and inulin clearance [Cinulin]) of changes in chronic dietary protein intake was studied in seven healthy male subjects. Serial 24-hour urine collections were used to determine creatinine excretion (UcreatV) and Ccreat. Subjects were examined after ad libitum (ad lib) food intake and after 2-week periods of high protein diet ([HPD] 1.6 g/kg body weight [BW] per day) and low protein diet ([LPD] 0.5 g/kg BW per day). Inulin clearance (Cinulin) was determined at the end of each 2-week diet period. UcreatV increased from 1,838.8 +/- 97.2 mumol/kg (20.8 +/- 1.1 mg/kg) BW to 2,068.6 +/- 106.1 mumol/kg (23.4 +/- 1.2 mg/kg) BW daily during HPD and decreased significantly to 1,555.9 +/- 167.9 mumol/kg BW per day (17.6 +/- 1.9 mg/kg BW per day) with beginning of LPD. Ccreat rose from 1.54 +/- 0.09 mL/s 1.73 m2 (92.5 +/- 5.5 mL/s.1.73 m2 (104.7 +/- 4.9 mL/min/1.73 m2) during HPD and decreased to 1.23 +/- 0.04 mL/s.1.73 m2 (74.0 +/- 2.2 mL/min/1.73 m2) with initiation of LPD. There was no difference between Cinulin after HPD (1.42 +/- 0.12 mL/s.1.73 m2; 84.9 +/- 7.2 mL/min/1.73 m2) and after LPD (1.36 +/- 0.05 mL/s.1.73 m2; 81.4 +/- 2.9 mL/min/1.73 m2). This study confirms the effect of protein intake on Ccreat and UcreatV, but fails to show an effect of changes in chronic protein intake on glomerular filtration rate (GFR). Ccreat during dietary protein restriction to 0.5 g/kg/d is similar to Cinulin and may be a useful measure of GFR under circumstances where more specific inulin or isotope studies are not available.