Endogenous Overnight Creatinine Clearance,Serum β2-Microglobulin and Serum Water during the Menstrual Cycle

ABSTRACT. Endogenous overnight (22.00–08.00 hours) creatinine clearance and serum concentrations of β₂-microglobulin and water were measured three times a week during 11 ovulatory menstrual cycles. In some of the women creatinine clearance changed more than 100% within a week from values below reference range to high normal levels. In all the women the creatinine clearance was higher during the luteal than during the follicular phase and correlated with the production of ovarian hormones. The urinary excretion rate of creatinine was highest during the luteal phase. Urinary volume, serum creatinine and serum water were not significantly influenced by the menstrual phases. An unexplained finding was a parallel change in the individual creatinine clearance and serum β₂-microglobulin during the luteal, but not during the follicular phase. Our results suggest that ovarian hormones influence creatinine clearance during the menstrual cycle. One must therefore accept even considerable short-time variations in creatinine clearance in fertile women. It remains to be settled if these changes reflect true alterations in glomerular filtration rate or mainly changes in the urinary (tubular) excretion rate of creatinine.     

Cyclical Changes in Endogenous Overnight Creatinine Clearance during the Third Trimester of Pregnancy

To investigate the pattern of change in endogenous overnight creatinine clearance during the third trimester, 12 healthy women with uncomplicated pregnancies were examined three times a week. Urine was collected overnight from 22.00 to 08.00 hours and analysed for creatinine. Serum was sampled in the morning and analysed for creatinine, β₂-microglobulin, progesterone and estradiol. The general trend of creatinine clearance was parabolic with a declining level during the last month before term. A sinusoid pattern with minimum values around the time when the women would have had menstruation had they not become pregnant was superimposed on the parabolic trend. A mathematical model (parabolas overlaid with a cosine curve) was constructed and fitted to the data. The cyclical pattern was significant. Serum creatinine showed a pattern with increasing values during the last 4–6 weeks before term and cyclical changes which were also significant. In the individual case the monthly and preterm clearance decrement sometimes was over 50%. Monthly and preterm decreases in creatinine clearance may be quite normal and serial measurements of creatinine clearance are therefore necessary to determine if declining values indicate pathological falls in the glomerular filtration rate.     

Prediction of Glomerular Filtration Rate from Serum Creatinine,Age, Sex and Body Weight

ABSTRACT. Trollfors B, Alestig K, Jagenburg R (Department of Infectious Diseases, Regional Hospital, University of Umeå, Umeå, and Departments of Infectious Diseases and Clinical Chemistry, Östra Hospital, University of Göteborg, Göteborg, Sweden). Prediction of glomerular filtration rate from serum creatinine, age, sex and body weight. Acta Med Scand 1987; 221:495–8. The accuracy and precision of estimates of glomerular filtration rate (GFR) from serum creatinine, age, sex and body weight using the methods proposed by Cockroft and Gault and by Siersbaeck-Nielsen et al. were determined in 234 subjects on 574 occasions. The two methods gave almost identical estimates of GFR. As reference for determination of GFR plasma clearance of ⁵¹Cr-EDTA as described by Bröchner-Mortensen was used. The estimates of GFR gave a systematic deviation of about 10 ml/min and a precision of about ±15 ml/min (1 SD) in the GFR range between 30 and 90 ml/min.     

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Background and objectives

AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness.

Design, setting, participants, & measurements

A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed.

Results

In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P<0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR<60 ml/min per 1.73 m² at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P<0.001).

Conclusion

Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings.     

Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Impact of estimated glomerular filtration rate based on plasma cystatin C and serum creatinine levels before allogeneic hematopoietic cell transplantation

Background: No standard method for measuring renal function has been established in allogeneic hematopoietic cell transplantation (allo-HCT).

Methods: We retrospectively analyzed 80 patients with hematological diseases who underwent allo-HCT at our center. We assessed renal function using creatinine clearance (Ccr), estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcre), eGFR based on cystatin C (eGFRcys), and the average of eGFRcre and eGFRcys (eGFRave). We then evaluated the impact of pre-transplant renal function on the exacerbation of renal function and non-relapse mortality after transplantation.

Results: There was a significant correlation between Ccr and eGFRcre, eGFRcys, and eGFRave. eGFRave best predicted the exacerbation of renal function according to the area under the receiver-operating characteristic curve. The cumulative incidence of renal function exacerbation at 1 year was higher in the lower eGFRave group (<90?ml/min/1.73?m²) than in the higher eGFRave group (≥90?ml/min/1.73?m²; 0.85 vs. 0.39, p?p?=?0.001). A lower eGFRave value was a marginally significant factor for non-relapse mortality (HR 3.29, p?=?0.076).

Conclusion: Among the four parameters, eGFRave best predicted the exacerbation of renal function in allo-HCT. Further, the marginal association between low eGFRave and high non-relapse mortality warrants further study in a prospective study in allo-HCT.     

Creatinine Clearance Is Not Equal to Glomerular Filtration Rate and Cockcroft-Gault Equation Is Not Equal to CKD-EPI Collaboration Equation

Direct oral anticoagulants (DOACs) may require dose reduction or avoidance when glomerular filtration rate is low. However, glomerular filtration rate is not usually measured in routine clinical practice. Rather, equations that incorporate different variables use serum creatinine to estimate either creatinine clearance in mL/min or glomerular filtration rate in mL/min/1.73 m². The Cockcroft-Gault equation estimates creatinine clearance and incorporates weight into the equation. By contrast, the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate and incorporate ethnicity but not weight. As a result, an individual patient may have very different renal function estimates, depending on the equation used. We now highlight these differences and discuss the impact on routine clinical care for anticoagulation to prevent embolization in atrial fibrillation. Pivotal DOAC clinical trials used creatinine clearance as a criterion for patient enrollment, and dose adjustment and Federal Drug Administration recommendations are based on creatinine clearance. However, clinical biochemistry laboratories provide CKD-EPI glomerular filtration rate estimations, resulting in discrepancies between clinical trial and routine use of the drugs.     

eGFR is a reliable preoperative renal function parameter in patients with gastric cancer

AIM: To evaluate the validity of the estimated glomerular filtration rate (eGFR) as a preoperative renal function parameter in patients with gastric cancer. METHODS: A retrospective study was conducted in 147 patients with gastric cancer. Preoperative creatinine clearance (Ccr), eGFR, and preand postoperative serum creatinine (sCr) data were examined. Preoperative Ccr and eGFR were then compared for their reliability in predicting postoperative renal dysfunction. RESULTS: Among 110 patients with normal preo...     

Monitoring kidney function in diabetic nephropathy

Summary Progression in diabetic nephropathy is usually determined by repeated measurements of glomerular filtration rate and expressed as rate of decline in glomerular filtration rate. Our aim was to evaluate the agreement between rate of decline in glomerular filtration rate estimated from the Cockroft-Gault formula: (140-age)^*K^*body weight^* (1/S-creatinine) and measured by the plasma clearance of ⁵¹CrEDTA. All insulin-dependent diabetic patients with diabetic nephropathy followed-up for at least 5 years with at least 5 simultaneous measurements of glomerular filtration rate, s-creatinine, and weight were included in the study. Forty-three patients (32 male/11 female), age 31 (18–61) years were enrolled. Observation period: 6.6 (5.1–9.9) years and number of investigations per patient 6 (5–16) (median(range)). Baseline glomerular filtration rate (ml/min) was 97 (30) measured and 107 (37) estimated (mean(SD))(p<0.001) and the 95% limits of agreement were –42.0 to 20.8 ml/min. Measured and estimated glomerular filtration rate correlated significantly (r = 0.91, p<0.00001). Rate of decline in kidney function ml · min^–1 · year^–1 was 4.7 (3.3) measured and 4.8 (3.5) estimated (mean(SD)) (NS), but the 95% limits of agreement showed a wide range –3.9 to 3.5 ml · min^–1 · year^–1. A significant correlation between rate of decline in measured and estimated glomerular filtration rate was present (r = 0.84, p<0.00001). In conclusion, glomerular filtration rate is overestimated by the Cockroft-Gault formula. The mean rates of decline in glomerular filtration rate are comparable, but the limits of agreement are wide, which make the Cockroft-Gault method unacceptable for clinical purposes, i.e. monitoring progression in kidney function in the individual patient. However, the estimated glomerular filtration rate may be used for comparison of groups in observational studies and in clinical trials with a long observation period.Abbreviations GFR Glomerular filtration rate - ⁵¹Cr-ED-TA ⁵¹Chromium ethylene diamine tetra-acetic acid - IDDM insulin-dependent diabetes mellitus     

Effect of low‐carbohydrate diet on markers of renal function in patients with type 2 diabetes: A meta‐analysis

Meta‐analysis was conducted to clarify the effect of low‐carbohydrate diet (LCD) on renal function in patients with type 2 diabetes. An extensive literature search was conducted on scientific databases including PubMed, Scopus, and Cochrane Library until September 2017. Only controlled trials on human subjects written in English were included in this meta‐analysis. Several markers of renal function were compared between subjects who adopted an LCD or control diet, including estimated glomerular filtration rate, creatinine clearance, urinary albumin, serum creatinine, and serum uric acid. Random effect model was used in the analysis of each marker. In this meta‐analysis, 12 controlled trials were selected, which involved 942 participants (500 received LCD and 442 received a control diet). The pooled standardized mean difference (SMD) of estimated glomerular filtration rate from LCD vs control diet was not different (pooled SMD: 0.26; 95% CI, ?0.03 to 0.55; P = .08). Investigation on creatinine clearance also showed no significant difference (pooled SMD: 0.51; 95% CI, ?0.38 to 1.40; P = .26). Other comparisons from urinary albumin (pooled SMD: ?0.04; 95% CI, ?0.75 to 0.67; P = .90), serum creatinine (pooled SMD: ?0.57; 95% CI, ?1.51 to 0.38; P = .24), and serum uric acid (pooled SMD: ?0.86; 95% CI, ?4.00 to 2.28; P = .59) also showed no significant difference in the results. In the present meta‐analysis, no effect on markers of renal function was found after provision of a LCD compared with a control diet in patients with type 2 diabetes.     

Renal Function in Older Hospital Patients Is More Accurately Estimated Using the Cockcroft-Gault Formula Than the Modification Diet in Renal Disease Formula

OBJECTIVES: To compare the accuracy of the two most popular creatinine clearance (CrCl) estimation formulae (Cockcroft-Gault (CG) and Modification Diet in Renal Disease (MDRD)) in older hospitalized patients.
DESIGN: Prospective, cross-sectional, observational study.
SETTING: Two hospital geriatric wards.
PARTICIPANTS: Consecutive patients aged 70 and older with an indwelling urinary catheter for the purpose of care.
MEASUREMENTS: CrCl was determined according to three methods: measured CrCl from plasma and urine creatinine and 24-hour urine volume, CG (CG-CrCl), and MDRD (MDRD-CrCl). Results were expressed as median and interquartile range (IQR). Moderate and severe renal impairment were defined as a CrCl between 30.0 and 59.9 mL/min and less than 30.0 mL/min, respectively.
RESULTS: One hundred twenty-one patients were included (46% male). Mean age was 86.1±6.7 (range 72–100). Median measured CrCl was 43.8 mL/min (IQR 33.6–61.1 mL/min), CG-CrCl was 40.9 mL/min (IQR 31.0–52.6 mL/min), and MDRD-CrCl was 61.3 mL/min (IQR 49.4–77.0 mL/min). The biases of CG-CrCl and MDRD were −3.5±22.5 and 20.1±28.2, respectively ( P <.001). Misclassification of renal impairment (absent/moderate/severe) occurred in 33% of patients according to CG-CrCl, and concordance was mild to moderate (kappa=0.50). Misclassification occurred in 50% of patients according to MDRD-CrCl, and concordance was poor (kappa=0.33). Bias was significantly related to bed confinement for both formulae and to plasma creatinine for MDRD.
CONCLUSION: In elderly hospitalized patients, CG slightly underestimates CrCl, and MDRD strongly overestimates it. CG gave a better prediction of measured CrCl than MDRD.     

Proximal glomerulo-tubular balance in patients with Type 1 (insulin-dependent) diabetes mellitus

Summary To evaluate the glomerulo-tubular balance of sodium and water in the proximal tubules of diabetic patients with elevated glomerular filtration rate, the renal plasma clearance of lithium and the glomerular filtration rate (⁵¹Cr-EDTA plasma clearance) were determined simultaneously in 11 ambulatory Type 1 (insulin-dependent) diabetic patients (aged 25–35 years) with no evidence of diabetic nephropathy and in 10 age-matched healthy subjects. The renal plasma clearance of lithium, which is a measure of flow from the proximal tubule into the thin descending limb of the loop of Henle, did not differ between diabetic and control subjects (28.9±4.0 versus 28.3±5.1 ml/min per 1.73m² surface area, mean±SD), whereas the glomerular filtration rate in the diabetic patients was significantly higher than in the control sub jects (136±10.2 versus 108±13.6 ml/min per 1.73m², p< 0.001). The same held true for the fractional reabsorption rate in the proximal tubules (78.7±3.2 versus 73.6±4.9%, p< 0.02). The results indicate that the elevation of the glomerular filtration rate in diabetic patients is associated with a parallel increase in the proximal reabsorption rate. This type of glomeralo-tubular balance implies that the flow of water and flux of sodium to the segments distal to the proximal tubule are kept constant during variations in the glomerular filtration rate.     

Progressive renal failure in patients with lupus nephritis

Abstract. Objective. To investigate the mode of progression to renal failure in patients with lupus nephritis in relation to disease activity and responsiveness to corticosteroid therapy. Design. Retrospective clinical study. Setting. University hospital. Subjects. Twenty-eight patients with progressive lupus nephritis (Cr ≥ 1.4 mg dl^?1). Interventions. Rapidity of progression was defined as the slope of the reciprocal of serum creatinine values. Lupus activity was scored using the systemic lupus erythematosus disease activity index system. Main outcome measures. Improvement of serum creatinine values after 6 months of therapy. Results. Rapidity of progression, which was calculated during the deterioration in kidney function, reflected systemic and serological disease activity, and moreover closely correlated with response to corticosteroid therapy.     

Comparison of prediction equations to estimate glomerular filtration rate in Chinese patients with chronic kidney disease

Aim: We sought to evaluate the applicability of formulae based on serum creatinine (SC) levels in Chinese patients with chronic kidney disease (CKD). Materials and methods: Three hundred and twenty‐seven patients with CKD who had undergone ^99mTc‐DTPA glomerular filtration rate (GFR) estimation were enrolled. The Cockcroft–Gault equation, SC‐reciprocal equation, Gate equation, Hull equation, Jelliffe‐1973 equation, Jelliffe‐1971 equation, Mawer equation, Bjornsson equation, reexpressed 6‐variable MDRD equation and reexpressed 4‐variable MDRD equation were compared. Using the ^99mTc‐DTPA GFR as the standard GFR (sGFR), the accuracy of estimated GFR was compared with sGFR in various stages of CKD. Results: Median per cents of the absolute difference ranged from 28.16% to 39.39%, accuracy with a deviation less than 30% ranging from 39.4% to 53.5%, accuracy with a deviation less than 50% ranging from 63.0% to 80.7%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from sGFR. Bland–Altman analysis demonstrated that mean difference ranged from ?2.42 to 16.39 mL/min/1.73 m², whereas precision ranged from 82.66 to 106.15 mL/min/1.73 m². However, the agreement limits of all the equations exceeded the prior acceptable tolerances defined as 60 mL/min/1.73 m². Linear regression showed that the slopes of regression line ranged from 0.37 to 0.54 and intercepts ranged from ?12.10 to 3.86. When the overall performance as well as bias and accuracy were compared in different stages of CKD, GFR estimated by Jelliffe‐1973 equation, Cockcroft–Gault equation and Bjornsson equation showed promising results. Conclusion: When SC was measured by the enzymatic method, GFR estimation equations showed great bias in Chinese CKD patients. At present, the Jelliffe‐1973 equation and Cockcroft–Gault equation may be more accurate in the Chinese ethnic group.