Differential Renal Protein Clearance in Diabetes

Jerums, George; Post, Robert S.; Miller, Max; Barzellato, E

doi:10.2337/diab.22.2.104

Cited by 17 publications

(9 citation statements)

References 10 publications

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“…Furthermore, the selectivity index (IgG clearance/transferrin clearance) for Pima diabetics was not significantly different from those of nondiabetic Pimas or Caucasians, a finding which contrasts with an earlier report of significantly decreased IgG/transferrin clearance ratios in diabetics. 33 Among the Pima diabetics, fasting plasma glucose was correlated significantly with total protein excretion, confirming a previous report. 5 However, fasting valves varied significantly among the diabetic groups, being highest among the long-duration diabetics with retinopathy.…”

Section: Discussionsupporting

confidence: 87%

Urinary Excretion and Renal Clearance of Specific Plasma Proteins in Diabetes of Short and Long Duration

Aronoff¹,

Schnider²,

Smeltzer³

et al. 1981

Diabetes

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To characterize the renal handling of protein in diabetics, the 24-h total protein excretion (Shevky-Stafford method), as well as urinary excretion, plasma concentration, and clearance of each of 17 proteins (radial immunodiffusion technique) were determined in 25 nondiabetic and 31 diabetic Pima Indians and in 25 nondiabetic Caucasians. Determination of 24-h total protein excretion demonstrated similar levels in nondiabetic Pimas [8.6 mg/24 h (median), 5.0-18.0 mg/24 h (95% confidence interval)] and nondiabetic Caucasians [10.1 mg/24 h, 7.0-24.0 mg/24 h] but significantly elevated levels in Pima diabetics [41.0 mg/24 h, 24.0-163.0 mg/24 hj. Total protein excretion was significantly greater among those with diabetes of 10 or more yr duration with retinopathy [163.0 mg/24 h, 24.0-436.0 mg/24 h] and those with recent onset of diabetes [39.5 mg/24 h, 24.7-81.0 mg/24 h], whereas long-duration diabetics without retinopathy [11.5 mg/24 h, 6.7-29.0 mg/24 h] and nondiabetic Pimas had similar values. Mean blood pressure and fasting plasma glucose levels were positively correlated with total protein excretion in the diabetic Pimas.Measurable quantities of only 9 of the 17 individual proteins were detected in the urine in more than 50% of all nondiabetic and diabetic subjects. They were fi 2 -microglobulin, /3 2 -glycoprotein I, «,-acid glycoprotein, a 2 HS-glycoprotein, o^-antitrypsin, albumin, hemopexin, transferrin, and IgG. The excretions and clearances of these proteins were comparable in nondiabetic Pimas and Caucasians. diabetics had significantly higher clearance and excretion of each of these proteins, except /3 2 -microglobulin (mol. wt. = 11,600) and ^-glycoprotein I (mol. wt. = 40,000). Long-duration diabetics with retinopathy and recent-onset diabetics both had significantly elevated clearance and excretion of the same proteins. In contrast, long-duration diabetics without retinopathy had significant increases of clearance and excretion only of hemopexin, transferrin, and IgG. The IgG/transferrin clearance ratios were not significantly different among the nondiabetic and diabetic groups.The other eight proteins were detected in the urine in measurable quantities in less than 50% of all subjects. These were prealbumin, gc-globulin, antithrombin III, plasminogen, haptoglobin, C3 activator, C4-component, and C3-component. While for statistical reasons, clearance data could not be analyzed for these proteins, a significantly higher percentage of diabetic Pimas had detectable excretion of these proteins except for C3 activator.In conclusion, diabetics, even of recent onset, have increased urinary excretion and clearance of proteins with a molecular weight greater than 40,000 compared with nondiabetics. This increased glomerular permeability appears to be nonselective for the larger proteins and can be detected shortly after the onset of diabetes. It might be predictive of the development of more severe renal disease after longer duration of diabetes. DIABETES 30:656-663, August 1981. T he prevalence of nephropathy i...

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Section: Discussionsupporting

confidence: 87%

Urinary Excretion and Renal Clearance of Specific Plasma Proteins in Diabetes of Short and Long Duration

Aronoff¹,

Schnider²,

Smeltzer³

et al. 1981

Diabetes

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“…1 ' 2 Studies of differential renal protein clearances in diabetic patients have demonstrated differences in urinary IgG-transferrin clearance ratios in the early as compared with the late stages of diabetic nephropathy. 41 Studies along these and other lines may help to further elucidate the phenomena reported herein.…”

Section: Discussionmentioning

confidence: 89%

Effects of Pancreatic Islet Transplantation on the Increased Urinary Albumin Excretion Rates in Intact and Uninephrectomized Rats with Diabetes Mellitus

et al. 1978

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The effects of reduced renal mass and of islet transplantation on urinary albumin excretion (UAE) rates in diabetic rats were examined. Increased UAE rates were noted two months after the induction of streptozotocin diabetes in 100-gm. inbred Lewis rats. Over the subsequent seven months, UAE rates remained constant in controls but were increasing in diabetic rats at the end of this time. Uninephrectomized nondiabetic rats had increasing UAE with time as compared with intact controls. Uninephrectomized diabetic rats had greater UAE than their respective controls, and the magnitude of this difference increased over the nine-month period of these studies. Uninephrectomized and intact rats, diabetic for seven months, were cured of the diabetic state by neonatal pancreatic tissue administered via the portal vein. Within one month of transplantation, UAE values decreased in these animals as compared with their pretransplant values and, within two months, were no longer different from values in their respective nondiabetic controls. In contrast, untreated uninephrectomized and intact diabetic rats increased their UAE over these same two months. At two months posttransplant, glomerular mesangial thickening was decreased in transplanted uninephrectomized and intact diabetic rats when compared with their respective untreated diabetic littermates.Thus, the albuminuria of diabetes in rats is reversed by pancreatic islet transplantation. It is unclear whether this reversal is primarily due to improvement in functional or structural abnormalities in glomeruli of diabetic rats. DIABETES 27:959-64, September, 1978.The pathogenesis of increased urinary albumin excretion in experimental and human diabetes mellitus is unclear. The clinical course of juvenile-onset diabetic patients dying of diabetic nephropathy has been characterized by the development of persistent albuminuria (more than 20 mg./lOO ml. in random urine specimens) after a mean duration of diabetes of 17.3 years. 1 This was followed, on the average, by early renal failure within two years and by death from renal failure within four years. 1 In another study, 2 although the duration of proteinuria before the onset of early renal failure was variable, the frequency of azotemia approached 50 per cent within five years of the onset of proteinuria; of 25 patients developing From the

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“…Protein excretion has been reported to be increased in some untreated diabetics [5,33,69,70] and to fall with treatment [92], Furthermore, even in diabetics without increased proteinuria, there may be an initial fall in the relative clearance of large plasma protein molecules [61]. An excellent analysis concerning renal protein clearance in diabetics has been published by Jerums etal.…”

Section: Kidney In Diabetes Mellitusmentioning

confidence: 92%

“…An excellent analysis concerning renal protein clearance in diabetics has been published by Jerums etal. [ 61].…”

Section: Kidney In Diabetes Mellitusmentioning

confidence: 99%

Insulin and the Kidney

Rubenstein

Mako

Horwitz

1975

Nephron

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Changes in renal function and structure are frequently observed in patients with diabetes mellitus. In the early phases of the disease, alterations in glomerular filtration rate, renal plasma flow, glomerular permeability and tubular capacity for glucose reabsorption occur. In the late stages of juvenile onset diabetes, renal failure is a common cause of death. For this reason, increasing attention is being paid to the possibility of long-term dialysis and renal transplantation in these patients. The kidneys play an important role in regulating insulin metabolism. The renal arteriovenous difference is approximately 30–45% and a linear relationship exists between the arterial insulin level and the renal arteriovenous concentration difference. The renal extraction of insulin is 200 ml/min in man, and it is estimated that 6–8 U are removed and degraded by the kidney in 24 h. The quantity of insulin in urine is small. However, its clearance is relatively constant over a wide range of serum concentrations and is 0.15–0.5 ml/min. The mean basal insulin excretion is 3.6 µU/mg creatinine, and a fourfold rise occurs following a glucose load. The urinary insulin values in neonates, children and patients with diabetes and renal failure are reviewed. In diabetic patients, progressive renal disease is accompanied by decreasing insulin requirements. In contrast, nondiabetic patients who develop renal failure frequently show abnormalities in carbohydrate metabolism, the commonest of which is a pseudodiabetic state.

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Differential Renal Protein Clearance in Diabetes

Cited by 17 publications

References 10 publications

Urinary Excretion and Renal Clearance of Specific Plasma Proteins in Diabetes of Short and Long Duration

Urinary Excretion and Renal Clearance of Specific Plasma Proteins in Diabetes of Short and Long Duration

Effects of Pancreatic Islet Transplantation on the Increased Urinary Albumin Excretion Rates in Intact and Uninephrectomized Rats with Diabetes Mellitus

Insulin and the Kidney

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