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Previous studies of IgA nephropathy have demonstrated a number of prognostically significant clinical and pathological factors in groups of patients with the full histological spectrum of the disease. Whether these factors can be applied to a group of IgA nephropathy patients with disease of moderate degree is unknown. Forty patients (9 females, 31 males) with grade III IgA nephropathy (no more than 10% obsolete glomeruli and little or no interstitial fibrosis) were evaluated with respect to age, sex, degree of proteinuria, history of recurrent gross hematuria, hypertension, extent and type of segmental glomerulosclerosis, demonstration of IgG and/or IgM in deposits, presence of peripheral capillary deposits, whether or not there were crescents, and extent of vascular sclerosis. The mean age was 29.6 +/- (SD) 13.1 years. Sixteen patients presented with recurrent gross hematuria, and 24 had microscopic hematuria and proteinuria as the initial manifestation. Hypertension was seen in 5 patients. The mean serum creatinine concentration was 1.09 +/- 0.47 mg/dl (96.4 +/- 41.5 mumol/l), and the mean 24-hour urinary protein was 1.5 +/- 1.3 g. Nine patients had proteinuria greater than or equal to 2.0 g/24 h. Thirty-two patients demonstrated segmental glomerulosclerosis in their biopsies, 13 of which had more than 10% of the glomeruli involved. Seven patients developed established renal failure (Cr greater than or equal to 2.0 mg/dl; 176.8 mumol/l). The 60-and 100-month renal survival rates were 96 and 52%. Life table analysis disclosed that only the degree of proteinuria (greater than or equal to 2.0 g/24 h; p less than 0.05) and the extent of segmental glomerulosclerosis (p less than 0.025) were of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IgA nephropathy. Evaluation of prognostic factors in patients with moderate disease. 332 Jul 80

Physicians may be called upon to guide patients with renal disease on the advisability of conceiving or maintaining a gestation, or to manage pregnancies permitted to continue. The prevailing view is that the degree of functional impairment and the presence or absence of hypertension prior to conception determine both pregnancy outcome and the effect of gestation on the natural history of the kidney disorder (Table 4). Normotensive women with minimal dysfunction have a 90% chance of success and there is little evidence that gestation will adversely affect the disease. Presence of hypertension increases the complications rate substantially, and prognosis is also poorer in women with moderate renal dysfunction. Most gestations in the latter group succeed, but at considerable maternal risk: over 20% of these women experience renal functional deterioration, and 30-40% of them have major problems with hypertension. Thus we tend not to recommend pregnancy in patients with moderate renal insufficiency, and definitely discourage gestation when GFR is severely impaired. There are a number of diseases in which pregnancy should not be undertaken, including scleroderma and periarteritis. Some authors believe that women with membranoproliferative glomerulonephritis also do poorly, and opinions differ on the effects of gestation on IgA nephropathy, focal glomerulosclerosis, and reflux nephropathy. Table 5 summarizes our view concerning pregnancy in a number of specific renal disorders. Finally, in addition to the controversies noted above, there are other unresolved problems requiring further study. For instance, protein restriction should be avoided until the effect of this therapeutic manoeuvre on fetal development is evaluated. Also needed are conclusive studies on whether or not the physiological hyperfiltration of human pregnancy affects adversely pre-existing renal disease.
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PMID:Gestation in women with kidney disease: prognosis and management. 333 Apr 93

Clinicopathological data in 74 patients with IgA nephropathy were analyzed with special attention to level of proteinuria and its prognostic significance in this disease. Excretion rates exceeding 3 g per day (heavy), in the range of 1 to 2.9 g (moderate) and under 1 g per day (mild) each occurred in approximately equal proportions of patients. One-sixth of those with more than 1 g developed end-stage renal failure, while serum creatinine never exceeded 2 mg/dl in any with mild proteinuria. "Renal survival" (serum creatinine of 2 mg/dl or less) at five years after presentation was 100% in patients with persistently mild proteinuria, 87% in those whose protein excretion reached the moderate range, and 69% when heavy or nephrotic range proteinuria developed. Of significance, only rarely did mild proteinuria at presentation increase to higher levels. A correlation existed between level of protein excretion and severity of mesangial, segmental or global proliferation, glomerulosclerosis, podocyte effacement, interstitial infiltration, tubular atrophy and vascular sclerosis, even in patients with unimpaired renal function. Moderate or heavy proteinuria typically preceded the onset of hypertension and occurred prior to the development of renal insufficiency. Our results underscore magnitude of proteinuria as an early marker of glomerular damage in the prognosis of IgA nephropathy.
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PMID:Proteinuria in IgA nephropathy. 336 61

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course in 205 children with IgA nephropathy were studied retrospectively. The findings in the 119 patients with macroscopic hematuria and those in the 86 without macroscopic hematuria were compared. There were no differences with regard to sex distribution, age at onset, initial renal function, incidence of hypertension, degree of proteinuria and degree of mesangial proliferation. At the latest follow-up, 3% of the patients with macroscopic hematuria and 8% without macroscopic hematuria had developed chronic renal failure; 8% of the patients with macroscopic hematuria and 20% without had heavy proteinuria with or without hypertension (p less than 0.01); 41% of the patients with macroscopic hematuria and 24% without macroscopic hematuria had normal urine, blood pressure and GFR (p less than 0.05). The disease appears to follow a significantly more benign course in children with macroscopic hematuria than in those without macroscopic hematuria. These observations suggest some macroscopic hematuria-related differences in the natural history of childhood IgA nephropathy.
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PMID:Macroscopic hematuria in childhood IgA nephropathy. 342 31

An Australian Aboriginal family, extending four generations, with a high incidence of renal disease was investigated. Twenty-eight of 114 members screened had hematuria. Of those tested, five had hypertension, four maturity onset diabetes, one a raised serum creatinine concentration, five elevated serum IgA levels and two cortical scarring on intravenous pyelogram. Of the eight members who underwent renal biopsy, five had IgA nephropathy and one had light and electron microscopy evidence of glomerulonephritis, but no IgA was seen on immunofluorescence. One had mild nonspecific changes by light microscopy but no immunofluorescence or electron microscopy was available and the remaining patient had mild changes consistent with hypertension and diabetes. HLA typing, carried out for 27 family members, showed an increased incidence of HLA-B22, B27, B39, and DR1 when compared to Yuendumu Aborigines (B27 and DR1), or Australian Caucasians (B22), or both (B39). This may be due to an association with IgA nephropathy, or a family clustering of antigens. Overall, this study suggests a genetic mechanism in the pathogenesis of IgA nephropathy in some patients and, as there was evidence of renal disease in 25% of those tested, may indicate an underlying high incidence of renal disease in the Aboriginal community.
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PMID:Familial IgA nephropathy: a study of renal disease in an Australian aboriginal family. 349 24

We measured serum beta-2-microglobulin (B2-m) and fractional beta-2-microglobulin excretion in 29 patients with IgA nephropathy. The mean serum B2-m in IgA nephropathy patients was significantly higher than that of healthy controls (p less than 0.025). The serum B2-m correlated well with serum creatinine and endogenous creatinine clearance (p less than 0.01). Patients with diffuse mesangial proliferation and glomerulosclerosis had a significantly higher level of B2-m than those with minor glomerular pathology (p less than 0.01). Patients with hypertension had significantly different levels of serum B2-m from normotensive patients (p less than 0.01). The mean fractional B2-m excretion in IgA nephropathy patients was significantly higher than that of healthy controls (p less than 0.001). Patients with moderate tubulo-interstitial involvement had significantly higher fractional B2-m excretion than those with mild tubulo-interstitial changes (p less than 0.01). Our study suggests that serum B2-m and fractional B2-m excretion may be useful indicators in the long-term prognosis of patients with IgA nephropathy.
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PMID:The clinical use of serum beta-2-microglobulin and fractional beta-2-microglobulin excretion in IgA nephropathy. 352

A randomized prospective study of 34 patients with IgA nephropathy and nephrotic syndrome was conducted to determine the therapeutic value of corticosteroid therapy. The patients were divided into two groups: Group A, 17 patients receiving oral prednisolone/prednisone for four months; and Group B, 17 patients receiving no corticosteroid therapy and acting as controls. The groups are comparable in age of presentation, sex ratio, and duration of study. No difference in serum creatinine levels, creatinine clearance, serum IgA levels, severity of renal histopathological changes, incidence of hypertension or incidence of impaired renal function could be demonstrated but the Group A patients had significantly heavier proteinuria. During the mean study period of 38 months (range 12-106), no significant difference in serum creatinine levels and creatinine clearance was demonstrated between the two groups. Forty percent of the Group A patients developed complications related to steroid therapy. Despite the overall lack of therapeutic value in IgA nephropathy with nephrotic syndrome as reflected by change in renal function, corticosteroid treatment resulted in excellent remission of nephrotic syndrome in 80% of patients with mild glomerular histopathological changes. Our findings suggest that corticosteroid therapy is only beneficial to selected groups of patients with IgA nephropathy and nephrotic syndrome but its indiscriminate use should be discouraged.
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PMID:Corticosteroid therapy in IgA nephropathy with nephrotic syndrome: a long-term controlled trial. 353 31

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course of IgA nephropathy were studied retrospectively in 200 children, and findings in those with younger onset and older onset were compared. Eighty-three patients were 8 years of age or younger (group 1) and 117 were 9 years of age or older (group 2) at onset. There were no differences between the two groups with regard to sex, initial renal function, incidence of hypertension and macroscopic hematuria, degree of proteinuria, and pathologic findings. At the latest follow-up, two patients in group 1 and eight in group 2 had chronic renal failure, and five patients in group 1 and 21 in group 2 had heavy proteinuria with or without hypertension (P less than 0.01), whereas 36 (43%) patients in group 1 and 29 (25%) in group 2 had normal urine, blood pressure, and glomerular filtration rate (P less than 0.01); the disease followed a significantly more benign course in children with younger onset than in those with older onset. These observations suggest some age-related differences in the natural history of childhood IgA nephropathy.
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PMID:Clinical course of immunoglobulin A nephropathy in children. 355 23

Twenty-two patients with primary IgA nephropathy (Berger's disease), 12 with normal and 10 with high blood pressure, were studied. The mean intra-arterial pressure was 88 +/- 6 mm Hg in the normotensive group and 113 +/- 10mm Hg in hypertensive patients; plasma renin activity was high in normotensives and normal in hypertensives. The glomerular filtration rate was 83 +/- 23 and 73 +/- 26 ml/m in 1.73 m2 in normotensive and hypertensive patients, respectively (p = n.s.). Blood volume was high in IgA nephropathy patients: 82 +/- 12 ml/kg body weight in normotensives and 96 +/- 7 ml/kg body weight in hypertensives. Mean arterial pressure was significantly correlated with blood volume (r = 0.541, p less than 0.01), but not with plasma renin activity and glomerular filtration rate. The cardiac index was high in both groups: 4.20 +/- 0.88 liters/min/m2 in normotensive and 3.95 +/- 0.87 liters/min/m2 in hypertensive patients. The total peripheral resistance index was significantly lower than normal in normotensives (1,659 +/- 387 dyn/s/cm-5/m2) and significantly higher (2,419 +/- 562 dyn/s/cm-5 m2) in hypertensives. The cardiac index did not correlate with blood volume and mean arterial pressure; a positive correlation was found between mean arterial pressure and peripheral vascular resistance (r = 0.630, p less than 0.01). No correlation was observed between blood volume and plasma renin activity. Our study indicates that hypertension in IgA nephropathy is primarily volume dependent, and that this increase in blood volume is not related to the deterioration of renal function. The role of the renin-angiotensin system in the maintenance of the hypertension is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertension in primary immunoglobulin A nephropathy (Berger's disease): hemodynamic alterations and mechanisms. 355 75

Fetal outcome was retrospectively studied in 217 pregnancies observed during the past two decades in 93 patients, 34 suffering from IgA nephropathy (IgAGN, 69 pregnancies), 53 from reflux nephropathy (RN, 137 pregnancies), and six from focal glomerular sclerosis (FGS, 10 pregnancies). Overall incidence of live births was 175 in 217 (81%). Fetal loss, corrected for induced abortions, was 10 in 66 (15%) in IgAGN, 18 in 129 (14%) in RN, and 2 in 10 in FGS. Renal failure and hypertension preexisting prior to conception or developing early in pregnancy were the most important factors associated with unsuccessful fetal outcome whereas urinary tract infection had limited effects in RN patients. Influence of pregnancy on the course of maternal renal disease was evaluated in the same groups of patients. An abnormally rapid deterioration of renal function was observed in three of the women with IgAGN and in one of the RN patients (with an additional case among 46 further female RN patients) but in none in the FGS group. All five women experiencing functional deterioration had a serum creatinine (SCr) level of greater than or equal to 200 mumol/L (2.3 mg/dL) and hypertension at conception. Hypertension in pregnancy was highly predictive of recurrence of hypertension in subsequent pregnancy and of the remote development of permanent hypertension in IgAGN patients. We conclude that when renal function is preserved, pregnancy is usually successful and no deleterious effects on maternal renal disease are to be expected in patients with IgAN, RN, and probably FGS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pregnancy in IgA nephropathy, reflux nephropathy, and focal glomerular sclerosis. 355 6


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