Urinary Excretion Of IgG Research Articles

Combined Urinary Excretion of IgG and α2-Macroglobulina Very Simple Marker to Assess Disease Severity, Outcome Prediction and Responsiveness to Steroids and Cyclophosphamide in Patients with Chronic Glomerulonephritis and Nephrotic Syndrome

In Glomerulonephritis (GN) with Nephrotic Syndrome (NS) proteinuric and molecular biomarkers don’t reach 100% of outcome prediction and treatment responsiveness.

Association Between Urinary IgG and Relative Risk for Factors Affecting Proteinuria in Type 2 Diabetic Patients

Abnormal glomerular permeability is the primary step towards the glomerulosclerosis. The progression rate of glomerulosclerosis is proportionate to abundance and severity of lesions created at incipient stage, which is reflected as proteinuria even though eGFR remains in the normal range. Therefore, there is a current need to find out the association between relative risks for the factors leading to proteinuria. The relations could be more informative, if it is with respect to the macromolecules like "IgG" excretion in urine. Type 2 diabetic patients were selected for this study with eGFR>75ml/min/1.73m(2) and grouped into four quartiles based on UIgGCR. The markers of key factors affecting progression of proteinuria were estimated through biochemical tests. The impact of these markers on proteinuria was accessed by applying multinomial logistic regression. The adjusted odds ratio for the UGAGCR was 1.186 (95% CI: 1.061-1.327) P<0.003 in highest quartiles of UIgGCR, followed by odds ratio for markers of collagen catabolism 1.051 (95% CI: 1.025-1.079) P<0.001, and USACR 1.044 (95% CI: 1.013-1.077) P<0.006 respectively. The marker of glycation, i.e., glycated hemoglobin showed the highest odds ratio 5.449 (95% CI: 1.132-26.236) P<0.035. In addition, odds for the systolic blood pressure was observed 1.387 (95% CI: 1.124-1.712) P<0.002. The higher odds inform and could help to discriminate the diabetic patients with fast progressive diabetic nephropathy. The study describes critical relationship between the urinary excretion of IgG and factors leading to proteinuria in type 2 diabetic patients.

Diabetic nephropathy and associated risk factors for renal deterioration

Predominantly diabetic nephropathy starts with glomerulosclerosis, when plasma molecules cross the dismantled glomerular basement membrane (GBM) and subsequently appear in urine. Therefore proteinuria is a sensitive criterion to diagnose progressive renal impairment and the presence of immunoglobulin like large molecules is potentially able to predict severity of nephropathy. Directly, or indirectly hyperglycemia induces proteinuria and high urinary excretion of IgG appears with progression of glomerular injury. This is an observational study of 683 patients with type 2 diabetes mellitus. Patients with varying degree of proteinuria were enrolled and classified into three groups according to the urinary albumin creatinine ratio (UACR, 300 mg/g creatinine.) and each group was further sub-classified into the low and high urinary IgG creatinine ratio (UIgGCR) based on the median value. Biochemical parameters were analyzed by standard laboratory methods. The association of proteinuria and odds ratio for risk factors of diabetic nephropathy was estimated using multinomial logistic regression models. The normoalbuminuric and microalbuminuric patients with high UIgGCR had shown lower eGFR (p < 0.05). There was no interaction observed between higher UIgGCR and lower eGFR in regression model analysis. Multinomial logistic regression model estimated the odds ratio for the AGEs, AOPP, lipid hydroperoxides and lipid peroxidation products were increased; 5.64 (95% CI 3.52–9.04), 1.03 (95% CI 1.02–1.04), 2.71 (95% CI 2.05–3.57) and 13.72 (95% CI 6.98–26.95) respectively with high UIgGCR in diabetic patients. High UIgGCR has shown a significant association with decreased eGFR and increased odds for potential hazardous factors. The current study has shown UIgGCR as an increased relative risk, and threat for rapid progression of diabetic nephropathy, possibly because GBM is the primary vulnerable site for deterioration by several hazardous metabolites. In conclusion, association between fractional clearance of IgG and relative risk of GBM threatening factors should be useful for prediction of progressive nature of diabetic nephropathy.

小児腎疾患における尿蛋白構成成分に関する研究(第1編)―各種腎疾患における尿蛋白構成成分の特徴特に,IgA腎症と尿中IgAについて―

Urinary protein components in children with renal disease were analyzed by the Reversed-Single Radial Immunodiffusion (R-SRID) method. The results were as follows: (1) In idiopathic nephrotic syndrome, the percentage of urinary albumin excretion was very high (79.5%). Urinary IgA excretion was 0.1% and IgG excretion was 1.6%, hence the excretion of these high-molecular-weight proteins amounted to 1.7% of the total urinary protein. (2) In membranous glomerulonephritis, urinary IgA was not detected, whereas the percentage of urinary IgG excretion was high (5.4%). (3) The percentage of urinary IgA excretion was higher in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) (2.4%, 1.6% respectively) than in other diverse renal diseases. (4) The percentage of urinary IgA excretion was correlated significantly with the serum IgA concentration in IgAN and HSPN (P < 0.001), but there was no such correlation in other diverse renal diseases. (5) In IgAN, the percentage of urinary IgA excretion was significantly higher in the subgroup with a duration of less than one year from the onset (3.6%) than in the subgroup with a duration longer than one year (1.5%) (p < 0.01).

The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study

Background. Proteinuria is the hallmark of glomerular disease and non-selective proteinuria is often associated with progression to renal failure. The predictive value of urine IgG excretion was studied comprehensively in patients with nephrotic syndrome. In the present follow-up study, we examine the predictive value of IgG-uria in patients with idiopathic glomerular diseases with a wide range of proteinuia. Methods. A total of 189 (113 males and 76 females) patients with idiopathic glomerulonephritis and serum creatinine of less than 150 μmol/L diagnosed between 1993 and 2004 were followed up to their last visit in 2009. Measurement of urine excretion of albumin, IgG, and protein HC were performed in the early morning of spot urine samples collected at the time of the diagnostic renal biopsy. Patients were stratified according to urine protein concentrations and the progression rate to end-stage renal disease (ESRD) calculated using Kaplan–Meier survival analysis. ESRD was defined as the start of renal replacement therapy. Results. During the study follow-up time of 1429 person-years; 26 (13.8%) patients reached ESRD. The overall mean kidney survival time of studied patients with serum creatinine less than 150 were 13.4 years. The incidence rate of ESRD was ∼18 per 1000 person-years. Stratified analysis identified urinary excretion of IgG, but not albuminuria, as predictor of ESRD. The progression rate to ESRD was 36 per 1000 person-years in patients with urine IgG concentration exceeding 5 mg/mmol urine creatinine, compared to a progression rate of 6/1000 person-years for patients with lower levels of urine IgG. Conclusion. The findings of the study suggest that at early stages, the level of IgG-uria is useful to be used in risk stratification of patients with proteinuric glomerular diseases.

The ratio between kidney volume and function increases with the progression of nephropathy in Type 2 diabetes

In Type 2 diabetes, it is not clear if renal size is constantly related to the glomerular filtration rate. In addition, it is not known if kidney volume (KV) is associated with an increased urinary albumin and IgG excretion. The relationship between kidney volume, creatinine clearance (CrCl), urinary albumin and IgG excretion in 95 Type 2 diabetic patients with different stages of nephropathy (1 - 4 Stage sec NKDF-QD) was elevated and compared to 85 non-diabetic subjects with similar degree of kidney function. In Type 2 diabetic patients the KV/CrCl ratio was increased, in comparison with the control subjects, from about 15% in Stage 1 to 53% in Stage 4. In T2D subjects, significant correlations were found between KV and urinary albumin excretion (r = 0.665, p < 0.05), and between KV and urinary IgG excretion (r = 0.800, p < 0.001). The present study finds that Type 2 diabetic subjects, are characterized by an increased ratio between KV/CrCl, throughout the different progressive stages of nephropathy. In Type 2 diabetes relationships between KV and urinary albumin and between KV and IgG excretion also were found to be significant, suggesting a role for the impaired size selectivity of proteinuria as a possible determinant of KV.

Diurnal Changes in Urinary Excretion of IgG, Transferrin, and Ceruloplasmin Depend on Diurnal Changes in Systemic Blood Pressure in Normotensive, Normoalbuminuric Type 2 Diabetic Patients

Previous studies of diabetic patients indicate that increased urinary excretion of certain plasma proteins (molecular radii <55 A), such as IgG, transferrin, and ceruloplasmin, precede the development of microalbuminuria. Moreover, increases in these urinary proteins predict future development of microalbuminuria. To clarify whether blood pressure changes influence urinary excretion of these proteins, we examined relationships between diurnal blood pressure changes measured by ambulatory blood pressure monitoring and urinary excretion of IgG, transferrin, ceruloplasmin, alpha2-macroglobulin (88 A) and albumin (36 A) measured separately during the day and night in 20 healthy controls and 26 normotensive, normoalbuminuric diabetic patients. Diurnal change in systolic blood pressure was not correlated to urinary excretion of either albumin or alpha2-macroglobulin in either diabetic patients or controls. However, statistically significant correlations between diurnal changes in systolic blood pressure and those of urinary excretion of IgG, transferrin and ceruloplasmin were found in diabetic patients but not in controls. The present findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin are more easily affected than albuminuria by systemic blood pressure changes in normoalbuminuric diabetic patients. This is supported by our previous finding that urinary excretion of IgG, transferrin and ceruloplasmin increased while albuminuria did not following enhanced glomerular filtration rate after acute protein loading, which causes increased glomerular capillary pressure due to afferent arterioles dilation, mimicking diabetic intra-renal hemodynamics. Taken together, these findings suggest that urinary excretion of IgG, transferrin, and ceruloplasmin may be more sensitive indicators of glomerular capillary pressure change than albuminuria in normoalbuminuric diabetic patients.

In Crescentic IgA Nephropathy, Fractional Excretion of IgG in Combination with Nephron Loss Is the Best Predictor of Progression and Responsiveness to Immunosuppression

The aim of this study was to evaluate the relationship between proteinuric markers (urinary excretion of IgG, alpha2-macroglobulin, alpha1-microglobulin) and serum creatinine (sCr), histologic lesions, progression, and immunosuppression responsiveness in crescentic IgA nephropathy. Fractional excretion of IgG (FEIgG) and of alpha1-microglobulin and urinary excretion of alpha2-macroglobulin were evaluated in 37 patients, 23 treated with steroids and cyclophosphamide. For assessment of the effective tubular load of proteins in surviving nephrons, new markers that take into account not only the absolute excretion value but also nephron loss were obtained dividing proteinuric markers for percentage of nonobsolescent glomeruli (surviving glomeruli [SG]). For each parameter, low- and high-risk groups were defined according to cutoffs with the highest sensitivity and specificity for progression (ESRD/doubling sCr) assessed by receiver operating characteristic analysis; follow up was 60 +/- 40 mo. FEIgG/SG is the most powerful progression predictor: 5 versus 83% in all patients; in treated patients, 0 versus 89%, increased to 0 versus 100% by sCr and FEIgG/SG in combination (low risk: both markers or only one below cutoff (n = 15); high risk: both markers above cutoff (n = 8). The nonprogressors showed at last observation 65% proteinuria reduction and 10% sCr reduction. In crescentic IgA nephropathy, FEIgG/SG, which evaluates altered size selectivity in relation to nephron loss, is the best progression predictor. In treated patients, progression prediction was increased by FEIgG/SG and sCr in combination. Treatment may be restricted to low-risk patients.

Non enzymatic glycosylation of IgG and their urinary excretion in patients with diabetic nephropathy.

Diabetic nephropathy is a major cause of end stage renal disease. Increased excretion of albumin has widely been recognized as an early manifestation of diabetic nephropathy particularly in subjects with diabetes mellitus. However, certain other proteins besides albumin may be excreted in high amount during early phase of diabetic nephropathy. The serum and urinary IgG, Glycosylated hemoglobin, fructosamine and glycosylated IgG were evaluated in the present study. Thirty-two patients of Type 2 Diabetes without any complications, thirty-one patients of Type 2 Diabetes with nephropathy, twenty-six patients of non-diabetic nephropathy and forty normal healthy individuals were enrolled in this study. Subjects were grouped based on their serum creatinine level. Serum IgG, glycosylation of IgG and urinary IgG excretion were increased significantly in diabetic patients compared to healthy controls, which were further increased significantly in chronic renal failure patients with respect to the clinical stage of nephropathy. A positive correlation was observed between glycosylation of IgG and IgG excretion (R(2)=0.5995, 0.7114 respectively) in diabetic patients without any complications and diabetic nephropathy patients only, suggesting a significant role of IgG glycosylation in the vascular clearances of IgG during diabetic nephropathy.

Relationship Between Clinical Predictors and Tubulointerstitial Damage in Adult-onset Primary Nephrotic Syndrome

Tubulointerstitial damage (TID) is an important mediator in the progression of chronic proteinuric nephropathies. Our aim in this study was to evaluate the relationship between several clinical predictors and TID in adult-onset primary nephrotic syndrome in China. One hundred ninety-five adult inpatients who were diagnosed with primary nephrotic syndrome based on clinical presentation and biopsy results were enrolled in this study from March 2003 to September 2005. The degree of TID was graded by a semiquantitative method including <2 score and >or=2 score. In all patients, the rate of glomerulosclerosis was correlated with the severity of TID. Serum creatinine and uric acid (r = 0.183, p = 0.012 and r = 0.377, p = 0.00001, respectively) but not serum lipid or total 24-h urinary protein were related with TID. In 64 patients, urinary excretion of IgG (r = 0.443, p = 0.00001) but not of albumin, transferrin, retinal-binding protein, or alpha1-microglobulin were significantly associated with the extent of TID. Proteinuria selectivity index based upon IgG also correlated significantly with the extent of TID (p = 0.0001) (score 0-1 vs. score >or=2). These results showed that serum creatinine and uric acid, the excretion of urinary IgG and proteinuria selectivity index based upon IgG, were highly correlated with the severity of TID in adult-onset primary nephrotic syndrome. These clinical parameters might be useful for predicting the development and progression of proteinuric nephropathy as independent risk factors.

Henoch Sch�nlein nephritis: clinical findings related to renal function and morphology

We evaluated the renal hemodynamics and the urine protein excretion rates of 73 children with Henoch-Schonlein nephritis (HSN). In 40 children we also performed a renal biopsy. The glomerular filtration rate (GFR) and effective renal plasma flow were determined by the clearances of inulin and para-aminohippurate during water diuresis. Urine albumin and IgG excretion were assessed in short-term timed samples. The mean GFR at the first examination was reduced in the HSN patients and most reduced in those with nephrotic proteinuria. There was an inverse correlation between the GFR at the first examination and the amount of albuminuria and urinary IgG excretion. Among the 40 patients with some degree of proteinuria who underwent a renal biopsy, 9 of 13 patients with mild to moderate proteinuria had severe morphological changes. GFR correlated inversely and fractional albumin and IgG excretion directly with the severity of the pathological findings on the biopsy, and with segmental and global sclerosis, the grade of mesangial proliferation, and interstitial inflammation. In conclusion, GFR is moderately reduced early in HSN and more reduced in patients with more proteinuria and in those with more advanced morphological changes. Moreover, even mild to moderate proteinuria may indicate severe morphological changes, which increase the indications for early renal biopsy in these patients.

Canine pyometra: a study of the urinary proteins by SDS–PAGE and Western blot

Canine pyometra often causes glomerulonephritis by immune complex deposition in the glomeruli. Proteinuria, ranging from moderate to severe, may be present secondary to renal damage. To determine urinary protein excretion due to pyometra, sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) was conducted on urine from 15 bitches with pyometra and 10 healthy bitches. To characterize urinary immunoglobin excretion, Western blot analysis of the urine samples using antibodies to canine IgG and IgA was also performed. Nine bands were detected by electrophoresis in bitches with pyometra, while only four were detected in the healthy animals. The urinary proteins from bitches with pyometra were primarily of glomerular origin; 58% were of medium-high molecular weight (MW), and the remainder were low MW. None of the healthy dogs had IgG or IgA in their urine, whereas three bitches with pyometra had IgG in their urine and another bitch with pyometra had both IgG and IgA. The low proportion of bitches with urinary immunoglobins was probably be due to early diagnosis of the disease. Although only a limited number of dogs was used, this study is apparently the first to characterize the electrophoretic pattern of urinary proteins and to quantify urinary excretion of IgG and IgA in bitches with pyometra.

Mediators of inflammation correlate with microalbuminuria in patients with non-Hodgkin's lymphoma.

Recent studies have demonstrated a high frequency of minor glomerular leakage of albumin in cancer patients. Pathogenic mechanisms of increased urinary albumin excretion (UAE) in malignancies remain to be clarified. We have attempted to identify whether microalbuminuria in lymphoma patients is associated with inflammatory mediators and the acute-phase response. UAE, urinary excretion of beta2-microglobulin and IgG, and serum levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) were determined in 113 patients with newly diagnosed non-Hodgkin's lymphoma. We demonstrated a high frequency of microalbuminuria (>or= 20 microg/min) and UAE correlated strongly with serum levels of CRP, IL-6 and TNF-alpha. UAE, CRP, IL-6 and TNF-alpha were significantly higher in patients with advanced disease stage, B symptoms and in high-risk patients according to the International Prognostic Index. Urinary excretion of beta2-microglobulin was unaffected in patients with increased UAE. However, UAE was significantly correlated with urinary excretion of IgG, suggesting an altered size selectivity of the glomerular filtration barrier. This is the first study that shows a direct correlation between microalbuminuria and proinflammatory cytokines in malignancies, indicating a pathogenic relationship between inflammation and glomerular leakage of albumin. Future efforts should focus on the pathophysiological cause-effect mechanisms and larger studies are needed to confirm the clinical significance of UAE.

Growth hormone replacement does not elevate albuminuria in GH-deficient adults

Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be associated with renal function loss and increased cardiovascular risk. Since urinary albumin excretion is affected by the growth hormone (GH)--insulin-like growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH replacement (1 U/day, n = 8 and 2 U/day, n = 16) on urinary protein handling in 24 non-diabetic, normotensive GH-deficient adults (12 men and 12 women), of whom 8 patients received placebo during 6 months, followed by active GH treatment. Plasma IGF-1 increased from 11.4 (8.1-15.8) nmol/L (median, interquartile range) to 35.4 (22.3-44.1) nmol/L (p < 0.001 versus change after placebo; median Z-score reached +0.2) after 6 months GH, and remained unaltered after placebo. Overnight Ualb.V was 4.0 (3.1-4.9) w g/min before and 4.6 (2.4-8.2) w g/min after GH (p > 0.10). Likewise, urinary IgG excretion rate did not significantly change after GH (0.71 (0.52-1.20) w g/min before GH versus 0.80 (0.51-1.56) w g/min after GH; p > 0.10). No significant changes were observed in creatinine clearance (p > 0.10) and mean arterial pressure (p > 0.10). No changes in any of these parameters were observed after placebo. Individual changes in Ualb.V were positively correlated with changes in plasma IGF-1 (r 2 = 0.41, p = 0.05) and with changes in mean arterial pressure (r 2 = 0.49, p < 0.02). The present study shows that 6 months GH replacement, increasing plasma IGF-1 within the physiological range, does not result in a clinically relevant increase in urinary protein excretion in GH-deficient adults. The correlation between changes in plasma IGF-1 and in albuminuria supports the rationale to avoid supraphysiological IGF-1 levels.

Urine excretion of protein HC in proteinuric glomerular diseases correlates to urine IgG but not to albuminuria

Proteinuric glomerular diseases often are associated with tubulointerstitial injury, which imposes on the progression of renal failure. Tubular damage is partly referable to toxic effects on the tubular epithelial cells induced by filtered plasma proteins. Patients with nonselective proteinuria, that is, increased urine excretion of high-molecular-weight plasma proteins such as IgG in comparison to albumin, often have poor renal outcome. The present observational study examined correlations between the degree of tubular damage, measured by urine concentration of protein HC, and the levels of urine IgG and albuminuria. Measurements of urine concentrations of IgG, albumin, and protein HC were performed in 56 proteinuric patients (33 males and 23 females) with nondiabetic glomerular diseases at the time of the diagnostic renal biopsy and at a mean of 49 follow-up months. A highly significant correlation between the urine IgG excretion and the urine protein HC concentration was found both at the start and at the end of the observational time (r = 0.74 and 0.65, respectively, P < 0.001). Furthermore, alterations in the urinary excretion of the two proteins in single patients correlated significantly to each other (r = 0.84, P < 0.001). The correlation between the degree of albuminuria and the protein HC excretion was significant at the time of kidney biopsy, but ceased to exist during the follow-up time. Stepwise linear regression analysis showed that in comparison with the creatinine clearance and albuminuria, only the changes in urinary IgG excretion were related to the corresponding changes in urinary protein HC excretion (r = 0.84 and r2 = 0.7, P < 0.001). The findings of the study suggest that the urinary protein HC concentration correlates to the degree of IgG-uria but not to the degree of albuminuria during the course of proteinuric glomerular disease. Whether this correlation is to be explained by an intrinsic toxic effect on tubular cells executed by IgG or perhaps by some other high molecular weight proteins, needs to be investigated further. However, the results contribute to the understanding of the poor renal survival in patients with glomerular diseases and nonselective proteinuria.

Influence of Albumin Infusion on the Urinary Excretion of β2-Microglobulin in Patients with Proteinuria

Most filtered proteins are reabsorbed by the renal proximal tubule by a mechanism that involves binding to the brush border membrane and endocytosis. Under normal conditions the low-molecular-weight protein β₂-microglobulin (β₂M), which is used to detect tubular injury, is reabsorbed almost completely. However, in proteinuric patients an increased urinary excretion of β₂M may not simply reflect tubular damage but might also result from a decreased tubular reabsorption due to competitive mechanisms. To examine the magnitude of such an effect we have studied the renal effects of albumin infusion (40 g in 2 h of a 20% solution) in 10 patients with a glomerular disease and proteinuria >3.5 g/24 h. Before, during and after albumin infusion the GFR (inulin clearance), RPF (PAH clearance), blood pressure and the urinary excretion of albumin, IgG, transferrin and β₂M were measured. Albumin infusion resulted in a slight decrease of the GFR (72 ± 11 ml/min before and 67 ± 10 ml/min after infusion), an increase of the RPF (379 ± 66 ml/min before and 445 ± 83 ml/min after), a decrease of the filtration fraction (0.20 before and 0.17 after), and hemodilution. After infusion the urinary excretion of albumin increased from 4.5 ± 0.7 to 8.4 ± 1.6 mg/min (p < 0.05). The urinary excretion of IgG and transferrin increased, probably reflecting a change in glomerular size-selectivity. In contrast, the urinary excretion of β₂M did not change significantly (baseline 12 ± 5 µg/min, end 13 ± 6 µg/min, percentage change 16.8 ± 11%). To correct for changes in tubular load we calculated the fractional reabsorption of β₂M. The initial rise in albuminuria during infusion did not affect fractional tubular reabsorption (Δ%: 0.72 ± 0.52%, median 0.005%). In the period after infusion a slight decrease was noted (median –0.33%, p < 0.01). A decrease in the fractional reabsorption was particularly observed in patients with pre-existing tubular damage. In conclusion: infusion of albumin in proteinuric patients has no clinically relevant effect on the tubular reabsorption of β₂M. Therefore, β₂M is useful as a parameter to detect tubular injury and alterations in tubular handling of proteins in patients with proteinuria and glomerular diseases.

Postexercise albuminuria in children with different duration of type-1 diabetes mellitus.

About 30% of diabetic patients develop progressive renal failure. We studied albumin, IgG, and transferrin excretion during exercise in diabetic children without signs of nephropathy to investigate proteinuria under these conditions: 39 patients with insulin-dependent diabetes mellitus and 21 healthy children undertook a bicycle exercise test. Albuminuria measured by nephelometry was calculated as the albumin excretion rate (AER) and albumin-to-creatinine ratio before and after exercise. The diabetic group was divided into three subgroups according to disease duration (DI < 5 years, DII 5-10 years, DIII > 10 years). No significant difference in metabolic control (hemoglobin A1c was detected between the diabetic groups (median hemoglobin A1c: DI 7.2%, DII 7.6%, DIII 8.6%). There was no increase in AER in the healthy children after exercise. Before exercise the diabetic groups had an AER similar to controls. No significant increase in albuminuria after exercise was seen in group DI. Both groups with a disease duration of more than 5 years had a significant increase in albuminuria [median before/after: DII 7.8/16.7 (P < 0.05), DIII 0/57.9 (P < 0.05) micrograms/min per 1.73 m2). Of these patients, 43% also had a measurable urinary excretion of IgG and transferrin, indicating structural glomerular damage. There was no correlation of albuminuria and parameters of metabolic control or renal function. We conclude that in diabetic children an exercise test unveils albuminuria in certain patients, while their AER may be normal at rest.

Fish oil in lupus nephritis: Clinical findings and methodological implications

Our objective was to determine the effects of fish oil on renal function, symptoms, and serum lipids in patients with lupus nephritis. A double-blind, randomized crossover trial of fish oil versus placebo (olive oil) was done on 26 patients with confirmed systemic lupus; 21 completed the study. Intervention was fish oil or placebo, 15 g/day, for one year followed by a 10 week wash-out period, and then the reverse treatment for one year. At baseline and six month intervals, we measured platelet membrane fatty acids, indices of renal function, a disease activity index, serum lipid levels, blood pressure, serum viscosity and red cell flexibility. We found that platelet membrane phospholipids were uniformly affected by fish oil supplementation (P < 0.001) but with significant carry-over effects despite a 10 week wash-out period. Glomerular filtration rate and serum creatinine were not affected. A non-significant reduction in mean (SE) 24-hour proteinuria occurred, from 1424.1 mg (442.7) on placebo to 896.7 mg (352.2) on fish oil (P = 0.21). Fish oil lowered serum triglycerides from 1.89 (0.25) mmol/liter to 1.02 (0.11) mmol/liter (P = 0.004). VLDL cholesterol decreased markedly whether patients initially received fish oil or placebo (P = 0.004). The size of the reduction was affected by the order of treatment (P = 0.03), but parallel comparisons were significant before the crossover (P = 0.0006). With the possible exception of bleeding time, no other treatment effects were shown with fish oil. However, treatment order effects were seen in urinary IgG excretion (P = 0.03), whole blood viscosity (P < 0.0001), red cell flexibility (P = 0.004), and bleeding time (P = 0.06). In conclusion, one year of dietary supplementation with fish oil in patients with stable lupus nephritis did not improve renal function or reduce disease activity, but did alter some lipid parameters. Hitherto unreported carry-over effects and treatment order effects caused by the olive oil created a risk of type II error, and bear methodologic consideration in the design of future studies.

Immunoglobulin and renal abnormalities in Dahl genetically hypertensive rat

The Dahl salt-sensitive rat (DS) is a model of genetically determined arterial hypertension exacerbated by dietary salt. We report two additional abnormalities of DS rats, which are both genetically determined and enhanced by salt: 1) immunoglobulin disorders and 2) renal dysfunctions. These abnormalities precede and are not the result of the arterial hypertension. In young, prehypertensive DS rats the plasma and tissue concentrations of immunoglobulin (Ig) G, but not of IgM or IgA, are decreased compared with those of the salt-resistant strain (DR). A high-salt diet (8.0% NaCl) decreases the plasma and tissue IgG levels of DS but not of DR rats. Reduction of IgG in the DS strain results from both decreased synthesis and increased urinary excretion. Renal dysfunction in young, prehypertensive DS animals is manifested by increased excretion of high molecular weight proteins, including albumin, IgG, IgA, and IgM. The high-salt diet increases the urinary excretion of these proteins within 1-2 days, and the effect is much greater in DS compared with DR rats. The urinary excretion of IgG is selectively increased relative to immunoglobulin light chains, IgA and IgM in DS compared with DR animals. The present studies provide new markers characteristic of the DS phenotype and pose the issue of possible genetic or functional interrelationships among the salt-sensitive hypertension, immunoglobulin disorders, and renal dysfunctions.

Urinary proteins and red blood cell membrane negative charges in diabetes mellitus

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low ( β 2-microglobulin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of β 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin ( r = −0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass ( r between −0.5 and −0.2) but presented no relation with urinary β 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transform excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria ( r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.