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.     

Longitudinal evaluation of glomerular filtration rate during long-term lithium therapy

Lithium produces many renal effects, but the important question of whether or not it causes chronic interstitial nephritis with consequent reduced glomerular filtration rate (GFR) remains unanswered. The several studies carried out in this area have been cross-sectional and, therefore, have not contained prospective information regarding creatinine clearance. The present study provides data from seven patients in whom creatinine clearances were obtained bracketing an average span of 7.5 years of continuous lithium therapy. Over this time, there was no significant change either in mean serum creatinine concentration or in average creatinine clearance (first determination: 1.1 +/- 0.1 [SE] mg/dL, 99 +/- 8 mL/min/1.73 m2; second determination 1.0 +/- 0.1, 105 +/- 4, respectively). The data, thus, support preservation of GFR during long-term lithium therapy.     

Effects of H2-receptor antagonists on renal function in cyclosporine-treated renal transplant patients

H2-receptor antagonists have been frequently avoided in cyclosporine-treated transplant patients because of concern regarding possible exacerbation of nephrotoxicity. To determine whether the reported increase of serum creatinine levels in cyclosporine-treated transplant patients receiving H2-receptor antagonists was due to a true decrease in glomerular filtration rate or was secondary to altered renal tubular handling of creatinine, simultaneous inulin and creatinine clearances were analyzed in 11 cyclosporine-treated renal transplant recipients before and after H2-receptor antagonist administration. Seven patients received one week of cimetidine 300 mg p.o. four times daily and eight received one week of ranitidine 150 mg p.o. two times daily. Prior to study, all patients had stable renal function and were maintained on prednisone (mean dose 0.2 +/- 0.01 mg/kg/day) and cyclosporine (mean dose 5 +/- 0.6 mg/kg/day). Four patients were also receiving azathioprine (2 mg/kg/day). Cimetidine administration resulted in a significant increase (P less than 0.05) in mean serum creatinine concentration from 2.0 +/- 0.3 mg/dl to 2.4 +/- 0.3 mg/dl and a significant reduction (P less than 0.05) in mean creatinine clearance remained unchanged during this same period. Serum creatinine levels returned to baseline values for all patients following discontinuation of the drug. Ranitidine administration had no consistent effect on serum creatinine concentration, creatinine clearance or inulin clearance. Cyclosporine trough levels and BUN were unchanged by either drug. These results confirm previous observations demonstrating an increase in serum creatinine and a reduction in creatinine clearance following administration of H2 receptor antagonists, especially cimetidine. Failure to document a simultaneous reduction in inulin clearance is consistent with the hypothesis that H2-receptor antagonists do not exacerbate cyclosporine nephrotoxicity and lower GFR, but rather compete with creatinine for tubular secretion.     

Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine

BACKGROUND: Renal drug excretion by glomerular filtration and active tubular secretion may be altered by factors such as acute and chronic renal disease, nephrotoxins, and drug interactions. Thus, accurate and reproducible methods for quantitation of glomerular filtration rate (GFR) and tubular functional capacity are critical. METHODS: We utilized a four-step sequential infusion method to characterize anionic [para-aminohippurate (PAH)] and cationic (famotidine) tubular functional capacity in healthy volunteers. Filtration and secretion rates were quantitated from renal clearance and iothalamate-derived GFR determinations. RESULTS: Concentration-dependent renal clearance of PAH was observed at plasma concentrations> 100 mg/L; renal clearances were 442 +/- 131 (mean +/- SD), 423 +/- 94, 233 +/- 45, and 152 +/- 18 mL/min/1.73 m2 at plasma concentrations of 18 +/- 2, 92 +/- 5, 291 +/- 47 and 789 +/- 28 mg/L, respectively. The apparent affinity (Km) and maximum secretory capacity (TmPAH) were 141 +/- 70 mg/L and 71 +/- 16 mg/min/1.73 m2, respectively. The unbound renal clearance and tubular secretory clearance of famotidine were 384 +/- 70 and 329 +/- 78 mL/min/1.73 m2, respectively, and were not significantly correlated with the unbound plasma concentrations, which ranged from 126 to 2659 ng/mL. The rate of tubular secretion was linear at unbound plasma concentrations up to 2659 ng/mL. CONCLUSIONS: These data indicate that a sequential infusion method using PAH may be used to characterize the anionic secretory component of proximal tubular function. The tubular clearance of famotidine may be a suitable index of the cationic secretory capacity of the proximal tubule in humans. Saturation of the cationic secretory pathway was not observed, and further investigation into parallel pathways of cationic secretion, such as p-glycoprotein, may be warranted.     

Clinical study of tubular creatinine secretion in renal dysfunction]

Endogenous creatinine clearance (Ccr) has been much more commonly used to estimate renal function in clinical medicine, in comparison with inulin clearance (Cin) which is more accurate measure of glomerular filtration rate (GFR). There is, however, increasing difference between Ccr and Cin as renal function deteriorates. Since this difference is considered to be resulting from the tubular secretion of creatinine, Cin and Ccr were simultaneously measured in 81 patients with chronic renal disease, as well as 12 control subjects in this study. As Cin decreased, the Ccr/Cin ratio increased and the ratio varied widely even in patients with similar degree of renal impairment. The subjects were classified into 3 groups, group I (Cin greater than 80 ml/min), group II (80 ml/min greater than or equal to Cin greater than or equal to 40 ml/min) and group III (Cin less than 40 ml/min). The mean values of tubular creatinine secretion (Tcr) were 0.07 +/- 0.173 mg/min (+/- SD) in group I, 0.205 +/- 0.136 mg/min in group II and 0.333 +/- 0.139 mg/min in group III, respectively. Therefore, Tcr in the group of the severe impairment was the highest. In addition, Ccr and Cin were measured in 15 patients with chronic nephritis before and after an intravenous bolus injection of cimetidine (5 mg/kg BW). Following the injection Ccr/Cin ratio was reduced from an initial value of 1.51 +/- 0.23 to 1.18 +/- 0.13 in group II and from 2.00 +/- 0.44 to 1.55 +/- 0.25 in group III, respectively. Tubular secretion of creatinine appeared to be inhibited by cimetidine even in the patients with severe renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum creatinine is a poor marker of GFR in nephrotic syndrome.

BACKGROUND: In daily clinical practice creatinine clearance is used as marker of glomerular filtration rate (GFR). As a result of the tubular secretion process endogenous creatinine clearance (ECC) overestimates glomerular filtration rate, particularly in patients with impaired renal function. It has been suggested that the tubular handling of creatinine is altered in patients with a nephrotic syndrome. METHODS: Inulin clearance (GFR) and creatinine clearance (ECC) have been simultaneously measured in a cohort of 42 patients with proteinuria and 45 healthy controls. The clearance of creatinine by tubular secretion (TScreat) can be estimated by ECC-GFR. TScreat was calculated in both groups. Regression analysis was performed to identify factors that independently influence tubular creatinine secretion. RESULTS: The mean age (+/-SD) of the patients was 41+/-13 years, serum albumin 26+/-9 g/l, median (IQR) proteinuria 4.5 (3.6-8.2) g/10 mmol creatinine, serum creatinine 103 (84-143) micromol/l, ECC 85 (69-118) ml/min/1.73 m2, and GFR 54 (36-83) ml/min/1.73 m2. Median TScreat amounted to 29 (21-36) ml/min/1.73 m2. In the healthy controls serum creatinine was 75 (70-81) micromol/l, ECC 118 (109-125) ml/min/1.73 m2, GFR 106 (102-115) ml/min/1.73 m2, and TScreat 11 (3.5-19) ml/min/1.73 m2. By regression analysis serum albumin was identified as an independent predictor of tubular creatinine secretion. We divided the patients in two subgroups based on serum albumin levels. TScreat was 24 (14-29) ml/min/1.73 m2 in patients with serum albumin levels >25.8 g/l, and 36 (28-54) ml/min/1.73 m2 in patients with serum albumin levels <25.8 g/l (P<0.01). CONCLUSION: Serum albumin levels influence tubular creatinine secretion. As a result, the endogenous creatinine clearance as well as estimated GFR using a modified MDRD equation more pronouncedly overestimate glomerular filtration rate in nephrotic syndrome.     

Limitations of creatinine as a filtration marker in glomerulopathic patients

To determine the reliability of creatinine as a measure of the glomerular filtration rate (GFR), we compared the simultaneous clearance of creatinine to that of three true filtration markers of graded size in 171 patients with various glomerular diseases. Using inulin (radius [rs] = 15 A) as a reference marker, we found that the fractional clearance of 99mTc-DTPA (rs = 4 A) was 1.02 +/- 0.14, while that of a 19 A rs dextran was 0.98 +/- 0.13, with neither value differing from unity. In contrast, the fractional clearance (relative to inulin) of creatinine (rs = 3 A) exceeded unity, averaging 1.64 +/- 0.05 (P less than 0.001), but could be lowered towards unity by acute blockade of tubular creatinine secretion by IV cimetidine. Cross-sectional analysis of all 171 patients revealed fractional creatinine secretion to vary inversely with GFR. This inverse relationship was confirmed also among individual patients with either deteriorating (N = 28) or remitting (N = 26) glomerular disease, who were studied longitudinally. As a result, changes in creatinine relative to inulin clearance were blunted considerably or even imperceptible. We conclude that true filtration markers with rs less than 20 A, including inulin, are unrestricted in glomerular disease, and that creatinine is hypersecreted progressively by remnant renal tubules as the disease worsens. Accordingly, attempts to use creatinine as a marker with which to evaluate or monitor glomerulopathic patients will result in gross and unpredictable overestimates of the GFR.     

Restrictions on use of creatinine clearance for measurement of renal functional reserve

The increase of glomerular filtration rate after a 90-gram oral protein load was determined in 9 healthy individuals by simultaneous measurements of both creatinine (Ccr) and inulin (Cin) clearances, performed before and every 30 min during 4 h after the meat meal. This protein load resulted in a short 26% increase of Cin at 90 min, and a sustained 29% increase of Ccr from 90 to 240 min after load. Individual peak values of Ccr occurred later than those of Cin (Ccr: 189 +/- 19 vs. Cin: 127 +/- 19 min; p = 0.023). These discrepancies were related to an increase of serum creatinine, and a subsequent increase of the net tubular excretion of creatinine which accounted for up to 15% of the urinary creatinine. The creatinine content of red meat could lead to overestimation of renal functional reserve when measured by creatinine clearance only.     

Effects of Nva2-cyclosporine on glomerular filtration rate and renal blood flow in the rat

The effects of Nva2-cyclosporine on glomerular filtration and renal blood flow in rats were studied and compared with those of cyclosporine. An infusion of Nva2-cyclosporine (20 mg/kg) caused a 53% fall in glomerular filtration rate (1.0 +/- 0.08 to 0.47 +/- 0.09; P less than 0.001) and renal plasma flow (3.2 +/- 0.4 to 1.6 +/- 0.4; P less than 0.005). Nva2-cyclosporine when infused in a dose of 10 mg/kg caused a nearly identical fall in inulin clearance and renal plasma flow. By comparison an infusion of cyclosporine (20 mg/kg) caused a 50% decrease in inulin clearance and a fall in renal plasma flow from 2.6 +/- 0.3 to 0.9 +/- 0.3. Nva2-cyclosporine or cyclosporine was given chronically in a dose of 20 mg/kg intraperitoneally for seven days. Cyclosporine produced a 27% fall in creatinine clearance, whereas Nva2-cyclosporine produced a 19% decrease in creatinine clearance (NS). These studies suggest that Nva2-cyclosporine has adverse effects on renal blood flow and glomerular filtration rate similar to those seen with cyclosporine.     

Limitations of creatinine in quantifying the severity of cyclosporine-induced chronic nephropathy

The glomerular filtration rate (GFR), as measured by the clearance of inulin, was depressed severely in 34 heart transplant recipients receiving cyclosporine (CsA) for 12 months or longer. The clearance of 99mTc-DTPA, a filtration marker similar in size to creatinine, was identical to that of the larger inulin molecule. In contrast, the clearance of creatinine was enhanced (P less than .01) such that its fractional clearance (relative to inulin) averaged 1.51 +/- 0.05. Moreover, there was an inverse relationship between fractional creatinine clearance (r = 0.36, P less than .01) and absolute inulin clearance. We conclude that in CsA-induced chronic nephropathy 99mDTPA and inulin are unrestricted by the glomerular capillary wall and behave as true filtration markers, creatinine is progressively hypersecreted by renal tubules as the nephropathy worsens, and the ensuing enhancement of creatinine clearance over GFR blunts the expected rise in serum creatinine levels as GFR falls. As a result, serum creatinine in chronic CsA-induced glomerulopathy exceeds 2 mg/dL consistently, only after true GFR has become depressed below normal values by two thirds or more.     

Effect of pregnancy on long-term function of renal allografts.

Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension.     

Assessing renal graft function in clinical trials: can tests predicting glomerular filtration rate substitute for a reference method?

BACKGROUND: In clinical trials, comparison of renal graft function needs a rigorous determination of glomerular filtration rate (GFR). Since reference methods to measure GFR cannot be easily implemented, a number of tests predicting GFR are usually used. However, little is known about their validity in renal transplant patients. We aimed to compare the performances of six GFR tests with inulin clearance in this population. METHODS: Five hundred consecutive inulin clearances performed in 294 renal transplant recipients with stable renal function were retrospectively selected. For each of them, we computed six estimates: the 24-hour creatinine clearance, the Cockcroft-Gault, Walser, Jelliffe, Nankivell, and Levey formulas. Their respective performance was assessed by correlation (simple linear regression), accuracy (dispersion of true error), and agreement (Bland and Altman method). RESULTS: Each GFR test closely correlated with inulin clearance (P < 0.0001). Comparisons between pairs of GFR tests did not show any significant difference in accuracy between the Levey, Jelliffe, and Walser formulas. Conversely, each of these formulas demonstrated a significant lower dispersion (P < 0.005) than the others. Nevertheless, all GFR tests displayed considerable lack of agreement with limits of agreement over 40 mL/min/1.73 m2 apart. The proportion of predicted GFR differing from inulin clearance by +/- 10 mL/min/1.73 m2, ranged from 34% for the Jelliffe formula to 53% for the Nankivell's one. CONCLUSION: None of these formulas seems to be able to safely substitute for inulin clearance. In clinical trials, renal graft function should be preferably assessed using a reference method of GFR measurement.     

Comparison of cystatin C, creatinine and creatinine clearance vs. GFR for detection of renal failure in renal transplant patients

BACKGROUND: Serum cystatin C (Scyst) has been suggested as an alternative index of glomerular filtration rate (GFR) and could be useful in renal transplant patients. METHODS: In a 60-subject cohort (40 +/- 12 years old), we compared the simultaneous measurements of Scyst, serum creatinine (Screat), creatinine clearance (Ccreat), Cockcroft and Gault's estimated clearance (Ccg) and GFR measured using inulin clearance (Cin). Receiver operating characteristic (ROC) analysis was performed using two Cin cut-off (60 and 90 mL/min/1.73 m2). RESULTS: A significant correlation was found among Cin on one hand and 1/Scyst, Ccreat, 1/Screat and Ccg on the other hand. Best fits (sensitivity/specificity) at 90 mL/min/1.73 m2 were 1.18 mg/L (0.72/0.80) for Scyst, 1.32 mg/dL (0.67/0.90) for Screat, 77 mL/min (0.80/0.70) for Ccg and 104 mL/min (0.88/0.80) for Ccreat. The areas under the ROC curves were not significantly different. CONCLUSIONS: This study provides cut-off values for Screat and Ccg for detection of renal failure in renal transplant patients. However, the results also suggest that Scyst is not a more sensitive marker than Screat or Ccg for detecting renal failure in renal transplant patients.     

Comparison of plasma disappearance and standard clearance techniques for measuring glomerular filtration rate in children with and without vesico-ureteric reflux.

The plasma disappearance rate, or slope clearance, after a single intravenous injection of 51Cr-EDTA was compared with simultaneously determined standard (UV/P) clearances of inulin, creatinine and 51Cr-EDTA in 4 healthy adults and 18 children with renal disease but no reflux. Slope clearance correlated well with standard inulin (r=0.99) and 51Cr-EDTA (r=0.97) clearances and was more accurate than creatinine clearance. Slope clearance x0.82 estimated standard 51Cr-EDTA clearance with +/- 12% accuracy in these subjects. In 18 children with vesico-ureteric reflux the correlations of the standard clearance methods with slope clearance were significantly reduced. Slope clearance may be measured with only two plasma samples and is recommended as the method of choice for determining glomerular filtration rate in children with gross reflux or impaired ability to empty their bladders.     

Use of the serum creatinine to estimate glomerular filtration rate in health and early diabetic nephropathy. Collaborative Study Group of Angiotensin Converting Enzyme Inhibition in Diabetic Nephropathy

We evaluated 100/serum creatinine, 24-hour creatinine clearance, and simultaneously measured creatinine clearance or creatinine clearance estimated by the formula devised by Cockcroft and Gault in comparison with measurements of glomerular filtration rate (GFR) using iothalamate among 136 patients with diabetic nephropathy. We also evaluated 100/serum creatinine, simultaneously measured creatinine clearance or creatinine clearance estimated by the Cockcroft and Gault formula in comparison with measurements of GFR using inulin among 88 healthy adults, 21 hypercalciuric kidney stone formers and their hypercalciuric relatives, and one man with chronic nephritis. Creatinine clearances measured simultaneously were closely correlated to GFR (r = 0.93) as were creatinine clearances, estimated by the Cockcroft and Gault formula (r = 0.84) when GFR ranged from 16 to 175 mL/min (0.27 to 2.92 mL/s). These observations confirm the clinical use of either creatinine clearances during water diuresis or estimates of creatinine clearance by the Cockcroft and Gault formula in the assessment of kidney function.     

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     

Does Everolimus Associated With a Low Dose of Cyclosporine in Long-Term Cardiac Transplant Recipients Improve Renal Function? Initial Experience

Background

Cyclosporine (CsA) renal toxicity is a well-known side effect. Various immunosuppressive strategies have been developed to minimize renal insufficiency. The use of everolimus associated with low levels of CsA can be an alternative strategy.

Methods

From October 2007 to April 2008, everolimus was started with a lower dose of cyclosporine (trough levels from 109.3 ± 27.5 to 93.7 ± 30.1 ng/mL after 45 days) in 21 cardiac transplant recipients (18 male and 3 female patients, mean age 56.4 ± 10.7 years). Pre-everolimus therapy creatinine levels, creatinine clearances, and glomerular filtration rates were 1.9 ± 0.9 mg/dL, 54.2 ± 18.1 mL/mins and 44.3 ± 16.5 mL/min/m², respectively.

Results

We observed a significant reduction in creatinine levels (from 1.9 ± 0.9 to 1.4 ± 0.3 mg/dL, P = .022) as well as a significant improvement in creatinine clearances (from 54.2 ± 18.1 to 69.0 ± 19.0 mL/min, P = .020) and glomerular filtration rates (from 44.3 ± 16.5 to 57.1 ± 16.3 mL/min/m², P = .010) after 7 days of everolimus therapy. Upon univariate analysis patient age, pretransplantation creatinine clearance, creatinine clearance after everolimus introduction, glomerular filtration rate at 45 days, and time from transplantation were associated with renal improvement. Upon multivariate analysis, only creatinine clearance at 7 days was related to the renal improvement.

Conclusions

These preliminary data suggested that everolimus with a low dose of CsA may be safe and effective to reduce CsA-related renal insufficiency among selected, heart transplant patients.     

Measurement of residual glomerular filtration rate in the patient receiving repetitive hemodialysis.

The objective of the current study was to determine the best index of residual glomerular filtration rate (GFR) by comparing simultaneously measured clearances of inulin, 125I-iothalamate, endogenous creatinine, urea and 169ytterbium diethylenetriaminepentaacetic acid (169YB-DTPA) in patients receiving repetitive hemodialysis. In patients with GFR less than 5 ml/min but greater than 1 ml/min, 125I-iothalamate clearance showed the best correlation with inulin clearance. However, creatinine clearance correlated better with inulin clearance than urea clearance and as well as urea + creatinine/2. In the patients with measured GFR less than 1 ml/min, the correlation of 125I-iothalamate, creatinine, urea and urea + creatinine/two clearances with inulin clearance was satisfactory. Similarly, satisfactory correlations were obtained when the relationships were examined across the entire range of measured clearances less than 5 ml/min. A simple, practical method is descriged for the accurate serial measurement of residual GFR in patients receiving repetitive dialysis.     

Creatinine clearance after cimetidine administration: is it useful in the monitoring of the function of transplanted kidney?

BACKGROUND: Determination of clearance of endogenous creatinine using its plasma and urinary concentration (standard clearance), Cockroft and Gault formula, or MDRD formula (estimated clearance) is commonly performed for assessment of glomerular filtration rate. Although the evaluation of renal function in this way is useful, it is biased with an error resulting from secretion of creatinine in tubules. This error can be reduced by determining the clearance after administration of cimetidine, which competitively blocks creatinine tubular transport. METHODS: The study was performed in the group of 87 patients after renal transplantation. In this group, estimated clearance and creatinine clearance after cimetidine administration (1000 mg in 75 patients and then 1600 mg in 12 patients with plasma creatinine above 3 mg/dL) were determined. RESULTS: Analysis of mean percentage differences between clearance values after cimetidine administration and estimated clearance shows increasing contribution of creatinine tubular secretion along with plasma creatinine increase in renal transplant recipients. A higher dose of cimetidine resulted in lower clearance values in renal transplant recipients with plasma creatinine above 3 mg/dL. CONCLUSIONS: Creatinine clearance after administration of 1000 mg cimetidine seems to be a useful measure of glomerular filtration rate in renal graft recipients with plasma creatinine concentration below 2.5 mg/L. Higher dose of cimetidine would be needed to effectively block tubular excretion at higher concentrations of creatinine. Establishing an efficient but safe dose of cimetidine for such patients needs further investigations. As we have noticed that creatinine clearance calculated according to MDRD formula was similar to the clearance after administration of cimetidine, we propose a strategy of one GFR measurement at baseline using 24h urine collection after cimetidine administration and follow-up with creatinine clearance calculated from MDRD formula during standard check-up visits.     

Creatinine Clearance after Cimetidine Administration—Is It Useful in the Monitoring of the Function of Transplanted Kidney?

Background. Determination of clearance of endogenous creatinine using its plasma and urinary concentration (standard clearance), Cockroft and Gault formula, or MDRD formula (estimated clearance) is commonly performed for assessment of glomerular filtration rate. Although the evaluation of renal function in this way is useful, it is biased with an error resulting from secretion of creatinine in tubules. This error can be reduced by determining the clearance after administration of cimetidine, which competitively blocks creatinine tubular transport. Methods. The study was performed in the group of 87 patients after renal transplantation. In this group, estimated clearance and creatinine clearance after cimetidine administration (1000 mg in 75 patients and then 1600 mg in 12 patients with plasma creatinine above 3 mg/dL) were determined. Results. Analysis of mean percentage differences between clearance values after cimetidine administration and estimated clearance shows increasing contribution of creatinine tubular secretion along with plasma creatinine increase in renal transplant recipients. A higher dose of cimetidine resulted in lower clearance values in renal transplant recipients with plasma creatinine above 3 mg/dL. Conclusions. Creatinine clearance after administration of 1000 mg cimetidine seems to be a useful measure of glomerular filtration rate in renal graft recipients with plasma creatinine concentration below 2.5 mg/L. Higher dose of cimetidine would be needed to effectively block tubular excretion at higher concentrations of creatinine. Establishing an efficient but safe dose of cimetidine for such patients needs further investigations. As we have noticed that creatinine clearance calculated according to MDRD formula was similar to the clearance after administration of cimetidine, we propose a strategy of one GFR measurement at baseline using 24h urine collection after cimetidine administration and follow-up with creatinine clearance calculated from MDRD formula during standard check-up visits.