Y.K. Lau

Protein Selectivity: A Prognostic Index in IgA Nephritis

Among 98 patients with IgA nephritis who had protein selectivity studies performed, 54% had nonselective proteinuria and the remaining 46% had selective proteinuria. Patients with nonselective proteinuria had a higher incidence of glomerulosclerosis. At the end of a 4-year follow-up period, patients with nonselective proteinuria had lower creatinine clearance, higher incidence of hypertension and chronic renal failure when compared to patients with selective proteinuria. Six out of eleven patients (55%) in the study who had the nephrotic syndrome had selective proteinuria. Among these 6 patients, 1 had spontaneous remission and 5 responded to steroid or cyclophosphamide therapy. The remaining 5 patients with nonselective proteinuria did not respond to therapy. In the patients who had selectivity studies repeated, the data showed that the selectivity index (SI) can fluctuate depending on the clinical course of the patients. SI can therefore be used to monitor the progress of patients on long-term follow-up. Protein selectivity appears to be a useful prognostic index in IgA nephritis. For patients with the nephrotic syndrome it may serve as a guide to therapy.

Beta-2-Microglobulin in the Assessment of Renal Function of the Transplanted Kidney

Plasma and urine beta-2-microglobulin (B2m) were measured in 37 renal transplant recipients and 34 healthy subjects. Serum B2m was found to be a more sensitive index of renal function than serum creatinine. Renal transplant recipients had significantly higher urine B2m when compared with normal controls. Normal subjects had a higher serum to urine B2m ratio (SUR) while those with renal impairment had a lower SUR. Serum B2m used alone or together with urine B2m and SUR appears a useful index for assessment of renal allograft function as well as detection of potential renal damage.

Isoelectric focusing and selectivity index in IgA nephrotic syndrome.

Proteinuria in 13 patients with IgA nephritis with nephrotic syndrome (IgANS) was analysed by isoelectric focusing (IEF) and compared with 12 patients with minimal change nephrotic syndrome (MCNS) (n = 8) or focal global sclerosis nephrotic syndrome (FGS) (n = 4) to determine the pattern of proteinuria on IEF and to assess the value of IEF and protein selectivity index (SI) as predictors of response to therapy with predisolone or cyclophosphamide. Steroid/cyclophosphamide responsive patients with IgANS had SC:UA (cationic serum albumin with anionic urine albumin) or SA:UC (anionic serum albumin with cationic urine albumin) IEF patterns and steroid/cyclophosphamide unresponsive patients with IgANS had an SC:UC (cationic serum albumin with cationic urine albumin) IEF pattern. The majority of patients with MCNS or FGS who had an SA:UC IEF pattern were steroid responsive. SI was a better predictor of steroid/cyclophosphamide responsiveness in patients with IgANS (r = 0.78, p < 0.002 compared to IEF, r = 0.64, p < 0.02).

Effects of Hemodialysis and Peritoneal Dialysis on Antithrombin III and Platelets

Plasma antithrombin III (AT III) levels in hemodialysis patients, low prior to dialysis, improved after dialysis (p less than 0.01). The platelet counts before and after dialysis, did not change significantly. In peritoneal dialysis patients the AT III levels, which were normal before dialysis, increased significantly after dialysis (p less than 0.01). The platelet counts before and after peritoneal dialysis also improved (p less than 0.005). No correlation was found between AT III levels and platelet counts. Although platelet damage has a contributory role in increasing AT III levels during hemodialysis, the data on peritoneal dialysis suggest that there may be other factors affecting platelets and AT III during dialysis.

Protein Selectivity in IgA Nephropathy

The protein selectivity index was measured in 68 patients (53 males, 15 females) with proteinuria due to IgA nephropathy to determine whether it bore any relationship to other clinical and pathological features of known prognostic significance. The mean age of the patients was 25 +/- 8 years with a follow-up period of 42 +/- 35 months. Forty-six presented with asymptomatic haematuria and proteinuria, 17 with macroscopic haematuria and 5 with the nephrotic syndrome. Twenty-three (34%) patients had selective proteinuria and 45 (66%) had non-selective proteinuria. Patients with non-selective proteinuria had more glomerulosclerosis (29% +/- 20 vs. 16% +/- 20, p less than 0.02), higher serum creatinine (1.47 mg/dl +/- 0.70 vs. 1.17 mg/dl +/- 0.33, p less than 0.02), lower creatinine clearance (79 ml/min +/- 28 vs. 95 ml/min +/- 25, p less than 0.02), and higher incidence of hypertension (chi 2 = 3.84, p less than 0.05) when compared to those with selective proteinuria. The protein selectivity was measured at the end of the study. Of the 5 patients with the nephrotic syndrome, 1 had poorly selective proteinuria and failed to remit and 4 had highly selective proteinuria who either remitted spontaneously (1 patient) or with treatment (3 patients). The results suggest that patients with IgA nephropathy and poorly selective proteinuria are more likely to have other features indicating a poor prognosis such as glomerulosclerosis, renal impairment and hypertension.

SDS-PAGE Is Underutilised as a Tool for Investigating Renal Patients

SDS-PAGE is an excellent single test for investigating proteinuria. It can provide much useful information on the underlying renal problem. Yet the literature hardly report a SDS-PAGE result in the management of renal patients. To examine how closely SDS-PAGE results may reflect biopsy findings, we investigated 11 patients scheduled for renal biopsy. Urine samples were taken at the same time for SDS-PAGE analysis using the Phast- System (Pharmacia, Sweden). Comparing biopsy findings and SDS-PAGE results, the data show consistency in the revelation of tubular dysfunction and/or glomerular damage in all 11 patients. We concluded that the SDS-PAGE test is underutilised and suggest that its role for the management of renal patients be fully explored particularly in its potential for reducing the need for renal biopsy in certain patient groups.

Beta-thromboglobulin in mesangial IgA nephritis

Plasma beta-thromboglobulin (beta-TG) concentration were determined in 28 patients with mesangial IgA nephritis (17 with focal glomerular sclerosis and 11 without any glomerular sclerosis) and compared with those from 52 normal subjects and 24 patients controls with no evidence of renal disease. The mean beta-TG concentration in the patients with IgA nephritis [159 +/- 63 ng/ml (SD)] significantly different from the patients controls [32 +/- 25 ng/ml (SD)] (p less than 0.001) as well as the group of normal subjects [23 +/- 17 ng/ml (SD)] (p less than 0.001). In another group of 12 patients with diffuse mesangial proliferative glomerulonephritis with no IgA deposits (non IgA nephritis) the mean beta-TG concentration [126 +/- 86 ng/ml (SD)] though different from that of the normal as well as patient controls (p less than 0.001) was not significantly different from the IgA nephritis patients. The elevated beta-TG levels in the nephritic patients showed no correlation with serum creatinine, creatinine clearance or proteinuria but was significantly correlated with the degree of glomerular sclerosis (r = 0.44) (p less than 0.05). In vivo activation of the platelets is suggested by these findings of elevated beta-TG in patients with diffuse proliferative mesangial glomerulonephritis (IgA and non IgA).

Pattern of proteinuria in IgA nephropathy

Summary: Proteinuria is one of the bad prognostic indices in IgA nephritis (IgAN). This study compares the pattern of protein excretion in 10 patients with IgAN (IA) with that 5 years later (IB), when they developed renal impairment or hypertension. The pattern of proteinuria was analysed by SDS‐PAGE and isoelectric focusing (IEF) and assayed for orosomucoid, α‐1‐microglobulin, retinol‐binding protein, lysozyme, beta‐2‐microglobulin and N‐acetyl‐β‐D‐glucosaminidase activity. The data suggest that the changing pattern of proteinuria from IgA1 to IgA2 may reflect hyperfiltration as well as tubular injury.

Antithrombin III in mesangial IgA nephritis.

Plasma Antithrombin III (A T III) was measured in 97 patients with IgA nephritis, 30 patients with non IgA idiopathic mesangial proliferative glomerulonephritis and 40 healthy subjects. The mean plasma A T III levels in the patients with IgA nephritis (105 +/- 10%) was significantly higher than those of normal controls (96 +/- 5%) (p less than 0.0005). The mean plasma A T III levels in the patients with non IgA nephritis (101 +/- 10%) was not different from those of the normal controls or the patients with IgA nephritis. A T III levels were significantly correlated with proteinuria (p less than 0.0001), segmental sclerosis (p less than 0.001), crescents (p less than 0.01), medial hypertrophy (p less than 0.001) and intensity of IgA staining on IMF (p less than 0.02). Patients with IgA nephritis with raised A T III levels had significantly more proteinuria (p less than 0.003), more segmental sclerosis (p less than 0.007) as well as a greater intensity of IgA staining on IMF (p less than 0.02) when compared to patients with normal A T III levels. The data suggest that raised plasma A T III levels may serve as a prognostic marker in IgA nephritis.

Beta-2-Microglobulin in Mesangial IgA Nephropathy

This study measured plasma beta 2-microglobulin (beta 2-m) in patients with mesangial IgA nephritis. Plasma beta 2-m was measured in 51 patients with IgA mesangial nephritis and in 50 normal controls using a Phadebas beta 2-m RIA kit available from Pharmacia Diagnostics (Uppsala, Sweden). The mean plasma beta 2-m in IgA nephritic patients (1.92 +/- 0.67 mg/l) was significantly different from that of healthy controls (1.33 +/- 0.41 mg/l; p less than 0.001). The mean plasma beta 2-m in non-IgA nephritic patients (1.83 +/- 0.73 mg/l) was also significantly different (p less than 0.001). Patients with IgA nephritis with glomerular sclerosis (n = 33) had significantly higher levels of beta 2-m (2.02 +/- 0.70 mg/l) than IgA nephritic patients without glomerular sclerosis (n = 18, 1.72 +/- 0.65 mg/l; p less than 0.025). In the group with IgA nephritis and glomerulosclerosis, raised beta 2-m levels were correlated with the severity of proteinuria (r = 0.41) (p less than 0.02) as well as the intensity of IgA staining on immunofluorescence (r = 0.34; p less than 0.05). Elevated beta 2-m levels in IgA nephritis may serve as a useful prognostic marker.