Chronic kidney disease and underdiagnosis of renal insufficiency among diabetic patients attending a hospital in Southern Ethiopia

Background

Diabetic patients with chronic kidney disease (CKD), as defined by a reduced glomerular filtration rate (GFR), are at greater risk for cardiovascular and renal events and mortality. The aim of this study was to determine the prevalence of CKD among diabetic patients attending a hospital in southern Ethiopia, and to assess underdiagnosis of renal insufficiency among those with normal serum creatinine.

Methods

A total of 214 randomly selected diabetics attending the follow-up clinic at Butajira hospital of southern Ethiopia participated in this study during the period from September 1 to October 31, 2013. All patients completed an interviewer-administered questionnaire and underwent clinical assessment. The simplified Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (C-G) equations were used to estimate GFR (eGFR) from serum creatinine.

Results

CKD, defined as eGFR?<?60 ml/min/1.73 m², was present in 18.2% and 23.8% of the study participants according to the MDRD and Cockcroft-Gault (C-G) equations, respectively. Only 9.8% of the total participants, and 48.7% (for the MDRD) and 37.3% (for C-G) of those with eGFR <60 ml/min/1.73 m² had abnormal serum creatinine values, i.e. > 1.5 mg/dl. Normal serum creatinine was observed in 90.2% of participants attending the hospital. A large proportion of participants ranging from 38.9-56.5% have shown to have mild to moderate renal insufficiency (stage 2–3 CKD) despite normal creatinine levels. CKD, eGFR?<?60 ml/min/1.73 m², was found in 10.4 and 16.9% of participants with normal serum creatinine using the MDRD and C-G equations, respectively.

Conclusion

CKD is present in no less than 18% of diabetics attending the hospital, but it is usually undiagnosed. A significant number of diabetics have renal insufficiency corresponding to stages 2–3 CKD despite normal creatinine levels. Therefore, GFR should be considered as an estimate of renal insufficiency, regardless of serum creatinine levels being in normal range.

     

Albuminuria and renal function in homozygous sickle cell disease: observations from a cohort study

BACKGROUND: The glomerular filtration rate (GFR) in homozygous sickle cell (SS) disease is supranormal in childhood but falls steeply with age, often culminating in renal failure. The risk factors underlying these observations are unclear. We therefore sought to investigate the relationships between blood pressure, renal hemodynamics, and urinary albumin excretion in subjects with SS disease and matched controls with a normal AA genotype (hereinafter, controls) as a prelude to intervention studies. METHODS: Serum creatinine level, GFR, effective renal plasma flow, blood pressure, and urinary albumin and creatinine excretion rates were measured in Jamaican individuals with SS disease aged 18 to 23 years and in controls followed from birth in a cohort study. RESULTS: Compared with controls, subjects with SS disease showed lower blood pressure and normal or supranormal GFR and effective renal plasma flow. Urinary albumin excretion exceeded 20 microg/min in 26% of subjects with SS disease and correlated positively with GFR and systolic blood pressure and negatively with hematocrit. A higher GFR and increased tubular secretion of creatinine combined to lower serum creatinine levels in patients with SS disease, giving an upper limit of the reference range of 0.90 mg/dL (80 micromol/L) in men and 0.77 mg/dL (68 micromol/L) in women. In addition, creatinine clearance measurements were consistently greater than GFR in subjects with SS disease. CONCLUSIONS: The GFR remained within reference range or elevated in patients with SS disease aged 18 to 23 years. The higher GFR in patients with albuminuria was consistent with the hypothesis that high glomerular flows cause renal damage. Lower serum creatinine levels characterize patients with SS disease, and a revised clinical definition based on serum creatinine level alone is proposed.     

Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate.

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.     

Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus

BACKGROUND: In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. METHODS: We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. RESULTS: Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. CONCLUSIONS: Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.     

Stabilization of renal function following renal artery stent revascularization

This study evaluates the effect of renal artery stenting on renal function in 72 consecutive patients. Baseline renal function was considered abnormal if creatinine was greater than or equal to 1.5 mg/dl. Improvement was defined as decrease in creatinine by greater than or equal to 20%, unchanged if variation was less than or equal to 20%, and worse if creatinine increased by greater than or equal to 20%. Two patients (2/72 = 2.8%) had in-hospital death. Follow-up creatinine was available in 61/70 (87%) patients at 21 +/- 11 months (9 patients lost to follow-up). Forty-four (44/61, 72%) patients had normal baseline creatinine that remained unchanged in 42/44 (95%, p = ns). Seventeen (17/61, 28%) patients had abnormal baseline creatinine. The renal function improved in 3/17 (18%), from 2.7 +/- 1 to 1.6 +/- 0.6 mg/dl (p = 0.06). Creatinine remained unchanged in 9/17 (53%), and was worse in 5/17 (29%, 2.0 +/- 0.51 to 3.3 +/- 0.34 mg/dl, p = 0.005). In conclusion, the renal function remained stable in 89% of patients and worsened in 11% of patients at 21 months (follow-up available in 87% of the eligible patients) following renal artery stenting. In patients with baseline renal insufficiency (serum creatinine > 1.5 mg/dl), the renal function remained stable in 71% of patients.     

Interest of cystatin C in screening diabetic patients for early impairment of renal function

We compared cystatin C, creatinine, and the Cockroft formula for assessment of early renal failure, defined as a (51)Cr-EDTA clearance < 80 mL/min, in 89 diabetic patients with various degrees of renal impairment (glomerular filtration rate [GFR], 11.4 to 196.5 mL/min). The relationships between cystatin C, creatinine, and (51)Cr-EDTA clearance were linearized by plotting the reciprocals of the values, and correlation coefficients were determined. Sensitivity and specificity for the diagnosis of early renal failure were calculated from receiver operating characteristic (ROC) curves. Over the whole population, cystatin C was as well correlated with GFR (r =.74) as was creatinine (r =.67) or the Cockroft formula (r =.88). Moreover, its diagnostic accuracy was comparable to that of the 2 other parameters. Its sensitivity (86.8%) was better than that of creatinine (77.4%) for screening GFR < 80 mL/min, although the Cockroft formula was more sensitive (96.2%). The study of albuminuric diabetics (n = 63) led to similar conclusions, except for a poor sensitivity of cystatin C. In the 36 patients whose plasma creatinine was < 1 mg/dL, 10 (27.7%) had GFR < 80 mL/min. The correlation of creatinine with GFR, its diagnostic accuracy, and sensitivity were significantly lower than those of cystatin C. In this population of patients with normal creatinine levels, the correlation coefficient of cystatin C, its sensitivity, and its diagnostic accuracy were comparable to those of the Cockroft formula. A moderate reduction in GFR may be present in diabetic patients with low creatinine levels. Although Cockroft formula remains the most reliable and the less expensive tool for the evaluation of renal function, cystatin C is a more reliable criterion for screening and assessment than creatinine and represents a useful alternative to the Cockcroft-Gault formula.     

Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula for renal involvement in systemic lupus erythematosus patients

OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) is a better indicator of the degree of renal involvement than serum creatinine concentration or creatinine clearance calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all systemic lupus erythematosus (SLE) patients with normal or borderline serum creatinine concentration (<110 micromol/l) and urinary sediment abnormalities and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration, calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein were determined at the same time. Renal biopsies were performed in patients with low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients were identified, of whom 22 were females. The average age of the patients was 31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1 patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The average serum creatinine concentration, EDTA-GFR and calculated creatinine clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23 patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any correlation between EDTA-GFR or creatinine clearance values and the sum of activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly predicted renal involvement in SLE patients, whereas GFR calculated by the Cockcroft-Gault formula may have underestimated renal function. Significant numbers of patients with WHO class III, IV or V lupus nephritis may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease.     

Study of renal function by creatinine clearance

This paper was designed to investigate the correlation between the renal clearance and the plasma concentration of creatinine. Of the curve obtained, three segments were studied: 1 - When the glomerular filtration rate (GFR) was greater than 60 ml per min. the plasma concentration fluctuated between 0.44 and 1.59 mg/dl. 2 - When GFR was between 30 and 60 ml per min. the plasma concentration reached 2.4 mg/dl, and 3 - When GFR was less than 30 ml per min. the plasma level increased to values as high as 28 ml/min. The urinary concentration of creatinine can be divided into two broad groups depending on the GFR. The boundary of this division is around 60 ml per min. This suggests that when GFR is depressed there would exist a limitation of the tubular secretion of creatinine or urinary dilution problems. It is demonstrated that there is a poor correlation between creatinine clearance and its plasma concentration, and hence the repeated measurement of creatinine clearance becomes imperative in the follow-up of patients.     

Increased plasma immunoreactive neuropeptide Y concentrations in phaeochromocytoma and chronic renal failure

To investigate the clinical usefulness of radio-immunoassay of neuropeptide Y (NPY), we measured plasma immunoreactive neuropeptide Y (IR-NPY) concentrations in normal subjects (n = 21), essential hypertensive patients (n = 33), patients with phaeochromocytoma (n = 7), patients with chronic renal disease with serum creatinine levels of less than 1.9 mg/dl (n = 5) and patients with chronic renal failure whose serum creatinine levels were greater than or equal to 1.9 mg/dl (n = 18, eight without haemodialysis and 10 undergoing maintenance haemodialysis), by radio-immunoassay. Plasma IR-NPY concentrations in patients with phaeochromocytoma (577 +/- 256 pg/ml, mean +/- s.d.) were significantly higher (P less than 0.001) than those in normal subjects (151 +/- 28 pg/ml), essential hypertensive patients (177 +/- 49 pg/ml) and patients with chronic renal disease with serum creatinine levels less than 1.9 mg/dl (198 +/- 71 pg/ml). Plasma IR-NPY concentrations in patients with chronic renal failure (without haemodialysis: 330 +/- 63 pg/ml; undergoing maintenance haemodialysis: 374 +/- 80 pg/ml) were also high. These results suggest that NPY is useful as one of the tumour markers of phaeochromocytomas. However, this study revealed that patients with chronic renal failure, without phaeochromocytoma also have increased plasma IR-NPY concentrations.     

Prospective evaluation of aggressive medical therapy for atherosclerotic renal artery stenosis, with renal artery stenting reserved for previously injured heart, brain, or kidney

Sixty-six patients with atherosclerotic renal artery stenosis (RAS) and serum creatinine < or =2.0 mg/dl were treated with antihypertensive therapy, a statin, and aspirin. Renal stenting was reserved for patients with injuries to the heart, brain, or kidneys. The primary end point was stenotic kidney glomerular filtration rate (GFR) at 21 months; secondary end points included major adverse clinical events, serum creatinine, total GFR, and blood pressure (BP). After baseline evaluation, 26 of 66 patients underwent renal stenting because of injuries to the heart, brain, or kidneys. After 21 months, 6 medical patients required renal stenting, and 5 patients experienced late clinical events (2 medical patients, 3 stent patients). There was no difference in final BP between groups. Whereas medical patients experienced 6% and 8% decreases in total and stenotic kidney GFR, stent patients experienced 7% and 11% increases in total kidney (p = 0.006) and stenotic kidney (p = 0.02) GFR. There was no difference in final serum creatinine. In conclusion, patients with atherosclerotic RAS and baseline creatinine < or =2.0 mg/dl can be safely managed with aggressive medical therapy, with a small decrease in GFR. For patients who develop injuries to the heart, brain, or kidneys, renal artery stenting may further reduce hypertension and improve renal function.     

Renal protection for coronary angiography in advanced renal failure patients by prophylactic hemodialysis. A randomized controlled trial.

OBJECTIVES: We performed a study to determine whether prophylactic hemodialysis reduces contrast nephropathy (CN) after coronary angiography in advanced renal failure patients. BACKGROUND: Pre-existing renal failure is the greatest risk factor for CN. Hemodialysis can effectively remove contrast media, but its effect upon preventing CN is still uncertain. METHODS: Eighty-two patients with chronic renal failure, referred for coronary angiography, were assigned randomly to receive either normal saline intravenously and prophylactic hemodialysis (dialysis group; n = 42) or fluid supplement only (control group; n = 40). RESULTS: Prophylactic hemodialysis lessened the decrease in creatinine clearance within 72 h in the dialysis group (0.4 +/- 0.9 ml/min/1.73 m(2) vs. 2.2 +/- 2.8 ml/min/1.73 m(2); p < 0.001). Compared with the dialysis group, the serum creatinine concentrations in the control group were significantly higher at day 4 (6.3 +/- 2.3 mg/dl vs. 5.1 +/- 1.3 mg/dl; p = 0.010) and at peak level (6.7 +/- 2.7 mg/dl vs. 5.3 +/- 1.5 mg/dl; p = 0.005). Temporary renal replacement therapy was required in 35% of the control patients and in 2% of the dialysis group (p < 0.001). Thirteen percent of the control patients, but none of the dialysis patients, required long-term dialysis after discharge (p = 0.018). For the patients not requiring chronic dialysis, 13 patients in the control group (37%) and 2 in the dialysis group (5%) had an increase in serum creatinine concentration at discharge of more than 1 mg/dl from baseline (p < 0.001). CONCLUSIONS: Prophylactic hemodialysis is effective in improving renal outcome in chronic renal failure patients undergoing coronary angiography.     

Serum cystatin C concentration compared with other markers of glomerular filtration rate in the old old

OBJECTIVES: To assess serum cystatin C, compared with other markers of renal function, as a marker of renal function in the old old (aged 85 and older). DESIGN: A cross-sectional analysis of data obtained in medically stable people aged 70 and older in a geriatric ward at a university hospital. SETTING: University hospital in Belgium. PARTICIPANTS: Forty-eight patients (17 men, 31 women) mean age +/- standard deviation 84.4 +/- 6.3 without acute illness or overt malignancy 7 days after admission were included. Twenty-five patients were aged 85 and older. MEASUREMENTS: Blood samples and 24-hour urine collections were obtained from each patient to determine serum creatinine, serum cystatin C levels, serum albumin, and creatinine clearance. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault formula and the Modification of Diet in Renal Study Group (MDRD) formula. On the same day, clearance of 51chromium ethylenediamine tetraacetic acid was performed in all patients as the criterion standard of GFR. RESULTS: Serum creatinine (r=0.68), serum cystatin C (r=0.62), urinary creatinine clearance (r=0.57), the Cockcroft-Gault formula (r=0.82), and the MDRD-formula (r=0.65) correlated significantly with GFR (P <.0001). Regression analysis showed that serum cystatin C and serum creatinine were comparable markers of renal function (Y=0.442 +/- 0.007 x GFR and Y=0.494 +/- 0.01 x GFR respectively). Receiver operating characteristic analysis showed a similar area under the curve for serum cystatin C and serum creatinine (P=.5) in detecting renal impairment (GFR <80 mL/min). The Cockcroft-Gault formula provides a good estimation of GFR when the GFR is less than 60 mL/min (Y=1.11 +/- 1.04 x GFR). When the GFR is greater than 60 mL/min, the Cockcroft-Gault formula underestimates GFR (Y=11.01 +/- 0.66 x GFR). In patients aged 85 and older, a slight decrease in GFR (51.8 +/- 21.3 mL/min vs 65.2 +/- 34.3 mL/min in patients aged 70-84; P=.10) is observed. This is reflected by a nonsignificant increase in serum cystatin C (P=.06), whereas serum creatinine is identical in both groups (P=.88). CONCLUSION: Serum cystatin C, serum creatinine, the Cockcroft-Gault formula, the MDRD formula, and urinary creatinine clearance are comparable markers of renal function in the overall older population. The Cockcroft-Gault formula underestimates renal function in older people with GFR greater than 60 mL/min. In our study, serum cystatin C was not superior to serum creatinine in the detection of renal impairment.     

Progression of renal failure delayed by use of losartan in a case of IgA nephropathy

We report a case of IgA nephropathy with renal failure in which the deterioration of renal function was inhibited by the addition of angiotensin II receptor blocker (ARB) losartan. Before administration of losartan, the mean decline in the patient's glomerular filtration rate (GFR) was 0.64 ml/min/1.73 m2/month. Losartan treatment was started when serum creatinine rose above 4.0 mg/dl. With this treatment the serum creatinine level has remained stable for 3.5 years, and the mean decline in GFR was 0.06 ml/min/1.73 m2/month. We document successful retardation of renal failure with the use of losartan. Our experience suggests that dialysis therapy can be delayed significantly in patients using this drug.     

Serum creatinine and creatinine clearance to estimate renal function in essential hypertension

The shortcoming of serum creatinine (SCr) as an index of renal function is well known, patients can have significantly decreased glomerular filtration rates (GFR) with normal range SCr values, making the recognition of renal dysfunction more difficult. This study was designed to estimate renal function and the prevalence of renal dysfunction in essential hypertensive patients, comparing SCr and 4 formulas used to measure the creatinine clearance (CrCl) (the urinary CrCl formula, Cockcroft-Gault, MDRD and body surface formula) The study included 721 essential hypertensive patients, 319 men (44.2%), 402 women (55.8%), mean age 56.3 +/- 13.9 (53.7 +/- 14.4 vs 58.3 +/- 13.3). In all subjects SCr was measured and 24-h urine sample was collected to evaluate CrCl. Creatinine clereance was calculated by 4 formulas. Patients were grouped according to age (< 40, 41-65, 65-75 and > 76) and renal function was classified as normal when SCr < 1.4 in women and 1.5 mg/dl in men and CrCl (> 60 ml/m, respectively) within the above written formulas. SCr increases with age (1.01 +/- 0.36 vs 1.3 +/- 1.15) and CrCl decreases according to the 4 formulas (107.6; 92.8; 74.7 and 57.3 for the urinary SCr formula); (117.7; 87.7; 65.9 and 49.5 for the CC formula); (87.4, 74.9, 66.5 and 61 for the MDRD formula) and (97, 85.3, 71.9 and 57.3 for the body suface formula). The 4 formulas are comparable markers of renal function in the overall population. With any formula the percentage of patients with impaired renal function was much higher than indicated by the plasma creatinine alone (4% for SCr) vs 18.3-25.3% (CrCl < 60 ml/m) according to the 4 formulas. This study documents the substantial prevalence of abnormal renal function in essential hypertension. Estimation of GFR may help to facilitate the early identification of patients with renal impairment.     

Prevalence of coronary artery disease, complex ventricular arrhythmias, and silent myocardial ischemia and incidence of new coronary events in older persons with chronic renal insufficiency and with normal renal function

In a prospective study of 98 persons > or = 65 years of age with chronic renal insufficiency (serum creatinine > 3.0 mg/dl) for > 1 year and 98 age- and sex-matched persons with normal renal function (serum creatinine < or = 1.2 mg/dl), new coronary events developed at 23-month follow-up in 69 persons (70%) with chronic renal insufficiency and at 48-month follow-up in 24 persons (24%) with normal renal function (p < 0.0001). Significant independent risk factors for new coronary events were age (risk ratio 1.1), prior coronary artery disease (risk ratio 3.5), complex ventricular arrhythmias diagnosed by 24-hour ambulatory electrocardiography (risk ratio 2.5), silent myocardial ischemia diagnosed by 24-hour ambulatory electrocardiography (risk ratio 1.9), and chronic renal insufficiency (risk ratio 3.4).     

Myopericarditis caused by cyclophosphamide used to mobilize peripheral blood stem cells in a myeloma patient with renal failure

Cyclophosphamide (CPA) is widely used for peripheral blood stem cell mobilization, and a dose adjustment of CPA in the presence of renal failure has not been suggested. However, we describe a myeloma patient with renal failure (serum creatinine 4.2 mg/dl, creatinine clearance 11.2 ml/min) receiving CPA 2 g/m2 for 2 days, who developed unexpectedly severe toxicity, including myopericarditis and prolonged myelosuppression. The serial serum concentrations of CPA metabolites were persistently much higher than those in a myeloma patient with normal renal function. We consider, therefore, that the dose of CPA should be reduced in the presence of severe renal failure when used as high-dose therapy or to mobilize peripheral blood stem cells.     

Therapeutic Serum Digoxin Concentration: Relation to Age,Weight, Sex,and Serum Creatinine Levels‡‡

Summary: Serum digoxin concentration was determined by radioimmuno-assay in a group of 41 hospitalized adult patients (22 males and 19 females), selected prospectively for constant effective dosage with digoxin for at least three weeks, without clinical or electrocardiographic evidence of digoxin intoxication. Serum creatinine values were within the normal or near-normal range. The majority were receiving diuretic therapy which was associated with mild alkalosis (75% of patients) and occasionally hypomagnesaemia (18%). The patients were considered to be effectively digitalized. The mean serum digoxin concentration six hours after the morning oral dose of digoxin in 28 of the 41 patients, with normal serum creatinine values, was 1.3 ng/ml (S.D. 0.4 ng/ml), and in the other 13 patients with mildly elevated serum creatinine values (range 1.3 to 1.6 mg/dl for 6 males and 1.1 to 1.4 mg/dl for 7 females) was 1.4 ng/ml (S.D. 0.7 ng/ml). Approximate GFR (% of normal corrected for age and surface area) was derived from auto-analyzer serum creatinine values, using the formulae 110/serum creatinine concentration (mg/dl) for males and 85/serum creatinine for females. The patients with mild renal failure (approximate GFR, males 85 to 69% of normal; females, 77 to 61% of normal) were found to be significantly older and required significantly smaller oral maintenance doses of digoxin than the patients with normal serum creatinine valuestoachieve virtually the same serum digoxin concentration. Formulae were derived to enable calculation of the therapeutic daily dose of digoxin from age in years (A), weight in kg (W), sex and serum creatinine concentration in mg/dl (SCr) as follows:—     

Clinical outcomes and therapeutic strategy in patients with acute myocardial infarction according to renal function

Background The aim of the present study was to evaluate the relationship between clinical outcomes after acute myocardial infarction (MI) and renal function by glomerular filtration rate (GFR) in patients with normal or mildly elevated serum creatinine concentrations. Methods and Results As part of the Korean Acute Myocardial Infarction Registry (KAMIR), 6,834 acute MI patients with a serum creatinine concentration of 90.0; (2) preserved function, 75.0-89.9; (3) mild dysfunction, 60.0-74.9; (4) moderate dysfunction, 45.0-59.9; (5) severe dysfunction, <45 ml . min(-1 ). 1.73 m(-2). Clinical characteristics, mortality and adverse events were analyzed among each group. Although reperfusion and medical therapies were underused, the rates of mortality and adverse events were increased with declining renal function. After adjustment with confounders, severe and moderate renal dysfunctions were important risk predictors of in-hospital mortality, long-term mortality and adverse events. Conclusion The spectrum of renal function, when it was presented by GFR, is broad and is an important risk predictor for adverse outcomes after acute MI, even in patients with normal or mildly elevated serum creatinine concentrations. Furthermore, standard treatments were underused in any degree of renal dysfunction. (Circ J 2008; 72: 1410 - 1418).     

Tryptophan glycoconjugate as a novel marker of renal function

PURPOSE: Neither serum creatinine concentration nor creatinine clearance assess renal function accurately. Serum creatinine concentration is affected by muscle mass, and the creatinine clearance overestimates the glomerular filtration rate because of tubular secretion of creatinine. The present study was designed to determine whether serum concentrations of 2-(alpha-mannopyranosyl)-L-tryptophan (MPT), a tryptophan glycoconjugate, can be used as a marker of renal function. METHODS: Clearances of MPT and of inulin were compared in normal rats and in rats with cisplatin-induced acute renal failure. We also compared the clearances of MPT and of creatinine with inulin clearance in 25 patients with chronic renal disease. Serum concentrations of MPT and creatinine as a function of MPT clearance were determined in 108 patients with chronic renal disease. RESULTS: There was strong linear correlation between clearances of MPT and inulin in rats (r = 0.97) and humans (r = 0.87), indicating that renal handling of MPT is similar to that of inulin. In humans, linear regression analyses indicated that MPT was a better indicator of inulin clearance than was creatinine clearance. At the same level of renal function, serum creatinine concentrations tended to be lower in patients with less muscle mass (as indicated by a urinary creatinine excretion <1,000 mg in 24 hours) than in those who excreted >1,000 mg in 24 hours, whereas serum MPT concentrations were not affected by creatinine excretion. CONCLUSION: MPT clearance can replace inulin clearance in the clinical setting. The serum MPT concentration is an accurate measure of renal function even in patients with diminished muscle mass, and thus is a better indicator of renal function than is the serum creatinine concentration.     

Utility of cystatin-C in hospitalized patients. Comparing with different methods of assessing renal function

Serum creatinine is the most widely use parameter to assessing renal function, even though limitations, some time is necessary measure 24 h creatinine clearance (CLcr), or estimate Cockroft-Gault (C-G) or MDRD formulas. Different methods can offer different results, and cause confusion in clinicians. Using Cystatin-C as new parameter of renal function could suppose an important improvement. The objective of our study was to compare the different methods from renal evaluation and establish the utility of cistatina-C in the hospital area. In the study were included 70 patients (44 men) selected of random way, predominate patients with kidney disease and diabetics, which was made CLcr and calculated C-G and MDRD formulas. The mean age of the patients was 66+/-14 years, mean weight 73+/-17 Kg, creatinine 2,14+/-1,77 mg/dL, cystatin-c 1,77+/-1,18 mg/L, CLcr 54,39+/-36,2 mL/min. The correlation of 1/Crea with the Clcr, C-G and MDRD formulas was respectively: 0,7735, 0.8269 and 0.9613, (p< 0.0001). The correlation of 1/Cist with the Clcr, C-G and MDRD was respectively: 0,836, 0.8142 and 0.832, (p<0,0001). By Bland-Altman graphs the average of the difference between CLcr with CG and MDRD was 2,8 mL/min and -1,5 mL/min respectively. Comparing CG with MDRD was 1,7 mL/min. The average of the observed absolute differences between CLcr with CG and MDRD was 13.5 mL/min and 17.1 mL/min respectively. Between this formulas the average was 12.5 mL/min. Statistically significant differences between the different methods from renal evaluation do not exist (p>0,05). In conclusion, most of the urine collections could be avoided with the use of the formulas. Cystatin-c is far beyond the creatinine, mainly to detect slight renal alteration (sensitivity 80,4% U.S. 44,7% in men) becoming a promising alternative, that could reduce considerably hidden renal insufficiency (non detected by creatinine), although more studies are needed to confirm.