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PubMed2006

Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.

OBJECTIVE: The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA. RESEARCH DESIGN AND METHODS: We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years with four measurements of GFR and another cohort of 227 type 2 diabetic patients with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22) measurements of GFR. RESULTS: For patients with microalbuminuria, mean +/- SD baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103 +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to 30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2 measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation) and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/- 4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). CONCLUSIONS: Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly underestimated with wide limits of agreement by the MDRD equation as well as by the Cockcroft-Gault formula. The rate of decline in GFR is also significantly underestimated with both equations. This makes GFR estimations based upon these equations unacceptable for monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.

Albuminuria↗
PubMed2005

Age and kidney function are the primary correlates of fasting plasma total homocysteine levels in non-diabetic and diabetic adults. Results from the 1999-2002 National Health and Nutrition Examination Survey.

BACKGROUND: Plasma total homocysteine (tHcy) is commonly elevated in persons with diabetes. This may be due to effects of insulin and/or glucose and/or metabolic control on the metabolism or plasma levels of tHcy. This study examined the effects of fasting plasma glucose status on fasting tHcy levels among adults without diabetes, and diabetes per se among adults with a self-report history of diabetes. METHODS: Analysis of data on adults (> or = 20y) who had fasted at least 8 hours, from the National Health and Nutrition Examination Survey (1999-2000 and 2001-2002). Subjects with no self-report history of diabetes were grouped according to fasting plasma glucose status as normal (< 100 mg/dL = NFG, n = 2,244), impaired (> or = 100 < 126 mg/dL = IFG, n = 1,108), or a provisional diagnosis of diabetes (> or = 126 mg/dL = DFG, n = 133). Subjects with a self-report history of diabetes (n = 275) were examined separately. RESULTS: Fasting tHcy was higher (Ps < 0.01) among non-diabetic subjects with DFG and IFG, compared to NFG (median [95% confidence interval] = 8.6 [8.0-9.2], 8.3 [8.1-8.5], and 7.4 [7.3-7.5] micromol/L, respectively). Diabetic subjects had levels similar to non-diabetic subjects with DFG and IFG (8.3 [7.9-8.6] micromol/L). Age and estimated creatinine clearance were strong correlates of fasting tHcy among non-diabetic subjects (r = 0.38 to 0.44 and r = -0.35 to -0.46, respectively) and diabetic subjects (r = 0.41 and r = -0.46, respectively) (Ps < 0.001), while fasting glucose and glycohemoglobin (HbA1c) were weaker (but still significant) correlates of tHcy in non-diabetic and diabetic subjects. Fasting glucose status was not a significant independent predictor of fasting tHcy levels in non-diabetic subjects, and HbA1c was not a significant independent predictor of tHcy in diabetic subjects (Ps > 0.05). CONCLUSION: Fasting tHcy levels are elevated among non-diabetic adults with elevated fasting glucose levels, compared to persons with normal fasting glucose levels, and among diabetic adults. However, elevations in fasting tHcy appear to be mediated primarily by age and kidney function, and not by measures of glucose metabolism.

Journal Article↗
PubMed2004

Chronic cyclooxygenase-2 inhibition does not alter blood pressure and kidney function in renovascular hypertensive rats.

BACKGROUND: It has been shown that the macula densa participates in the regulation of increased renin expression in two-kidney one-clip (2K1C) renovascular hypertension. Prostaglandins might be one of the mediators of macula densa function, because the cyclooxygenase-2 (COX-2), one of the rate-limiting enzymes of the prostaglandin pathway, is upregulated in 2K1C renovascular hypertensive rats. We tested the effect of chronic COX-2 inhibition on blood pressure, urinary aldosterone excretion and kidney morphology, as well as kidney function. METHODS: Four groups were established: two groups of 2K1C renovascular hypertensive rats treated with the specific COX-2 inhibitor Celecoxib (cele) (15 mg/kg per day) or placebo immediately after operation, and two sham-operated control groups fed with Celecoxib or placebo. RESULTS: Long-term COX-2 inhibition in 2K1C renovascular hypertensive rats did not alter blood pressure at any point of time. Urinary aldosterone excretion was elevated by clipping the renal artery (2K1C, 8.1 +/- 1.9, versus controls, 3.6 +/- 0.5 ng/24 h; P = 0.05) but was not influenced by treatment with Celecoxib. Also, Celecoxib treatment did not alter glomerular filtration rate (GFR), serum sodium, serum creatinine, serum urea or proteinuria in 2K1C renovascular hypertensive rats. Interstitial fibrosis of the left clipped kidney was markedly reduced (2K1C, 6.19 +/- 0.83% versus 2K1C + cele 3.00 +/- 0.68% of total area; P = 0.012), whereas the interstitial fibrosis of the non-clipped kidney or the glomerulosclerosis of both kidneys were not affected by Celecoxib treatment. CONCLUSIONS: Celecoxib reduces the interstitial fibrosis of the clipped kidney. Blood pressure, urinary aldosterone excretion or whole kidney function were not affected in renal hypertensive rats.

Aldosterone↗
PubMed2002

Assessment of regional kidney function may provide new clinical understanding and assist in treatment of children with prenatal hydronephrosis.

PURPOSE: As calculated from a (99m)technetium (Tc)-mercaptoacetyltriglycine (MAG3) renogram, differential renal function is an important parameter affecting the clinical treatment of children with prenatal unilateral hydronephrosis. We determined whether value is potentially added by calculating a functional image from MAG3 renograms that represents proximal tubule ability to clear tracer from the blood, that is the MAG3 clearance image. MATERIALS AND METHODS: MAG3 clearance image findings and differential renal function at presentation and followup in 59 nonsurgically and 42 surgically treated children with prenatally diagnosed unilateral hydronephrosis were retrospectively reviewed. All patients underwent at least 3 99mTc-MAG3 renograms. RESULTS: In the surgical and nonsurgical groups there was no significant difference in followup (p = 0.11), age at presentation (p = 0.98) or age at last visit (p = 0.97), whereas differential renal function was significantly different (p = 0.01). A large affected kidney with focal defects was the most frequent finding in each group, including kidneys with a normal differential renal function of 45% to 55%. In the nonsurgical group the most common observation was improvement in the MAG3 clearance image in 26 of 59 cases (44%) and stabilized differential renal function in 41 (70%). Postoperatively the MAG3 clearance image improved in 31 of 42 cases (74%) and differential renal function remained stable in 25 (60%), while no significant increase in differential renal function was noted at the last visit (p = 0.74). CONCLUSIONS: This study shows that it is possible to assess regional parenchymal function using the MAG3 clearance image in children with unilateral hydronephrosis. This information is available in addition to 99mTc-MAG3 information on the whole kidney, that is differential renal function. The majority of affected kidneys with normal differential renal function showed parenchymal defects, suggesting regional renal dysfunction. However, functional improvement on a regional basis occurred in each group of children during followup.

Child, Preschool↗