Biopsy-proven Glomerulonephritis Research Articles

Successful management of membranoproliferative glomerulonephritis type I in pregnancy

We report the successful management of a pregnancy with preexisting nephrotic syndrome due to biopsy-proven primary membranoproliferative glomerulonephritis type I. A 21-year-old Turkish woman with membranoproliferative glomerulonephritis type I was followed up by the obstetrics and gynecology, and nephrology departments of a university hospital throughout her pregnancy starting from the 25th week of gestation. Due to progression of intrauterine growth retardation and fetal distress, a cesarean section was performed in the 33rd week of gestation. Although creatinine was unchanged, proteinuria increased with relatively stable albumin levels 3 months after delivery and her treatment was adjusted accordingly. If the mother is not suffering from hypertension or renal insufficiency, specific therapy for membranoproliferative glomerulonephritis type I during pregnancy provided by a nephrologist together with regular obstetric care may allow the patient to have a viable fetus, which might be growth retarded if proteinuria is increased.

Probability, Predictors, and Prognosis of Posttransplantation Glomerulonephritis

Glomerulonephritis (GN) is the leading cause of chronic kidney disease among recipients of renal transplants. Because modern immunosuppressive regimens have reduced the incidence of rejection-related graft loss, the probability and clinical significance of posttransplantation GN (PTGN) requires reevaluation. In this Canadian epidemiologic study, we monitored 2026 sequential renal transplant recipients whose original renal disease resulted from biopsy-proven GN (36%), from presumed GN (7.8%), or from disorders other than GN (56%) for 15 yr without loss to follow-up. Kaplan-Meier estimates of PTGN in the whole population were 5.5% at 5 yr, 10.1% at 10 yr, and 15.7% at 15 yr. PTGN was diagnosed in 24.3% of patients whose original renal disease resulted from biopsy-proven GN, compared with 11.8% of those with presumed GN and 10.5% of those with disorders other than GN. Biopsy-proven GN in the native kidney, male gender, younger age, and nonwhite ethnicity predicted PTGN. Current immunosuppressive regimens did not associate with a reduced frequency of PTGN. Patients who developed PTGN had significantly reduced graft survival (10.2 versus 69.7%; P < 0.0001). In summary, in the Canadian population, PTGN is a common and serious complication that causes accelerated graft failure, despite the use of modern immunosuppressive regimens.

Malignant hypertension in HIV-associated glomerulonephritis

Glomerular diseases other than HIVAN (HIV-associated nephropathy) are common among HIV patients but the information about their clinical characteristics and prognosis is very scarce. We have observed several HIV patients with glomerulonephritis in whom malignant hypertension (MHT) was the first clinical manifestation. All HIV-infected individuals with a biopsy-proven glomerulonephritis at our hospital were reviewed. Information about clinical characteristics, histopathologic data and outcome was collected. The incidence of MHT among HIV and non-HIV patients with glomerulonephritis was studied. Thirty HIV patients with glomerulonephritis were identified. Ten of them (33%) presented with MHT (severe hypertension and grade III hypertensive retinopathy). In comparison with patients without MHT, they showed a significantly higher blood pressure at presentation, a higher finding of IgA nephropathy (50% versus 15%; P < 0.05) and of malignant nephrosclerosis (60% versus 0%; P < 0.05) in renal biopsies, a higher viral load and a lower CD4+ cell count at the end of follow-up and a worse patient and renal survival: six patients (60%) started chronic dialysis and seven (70%) died after a follow-up of 11.8 +/- 16.2 and 39 +/- 35 months, respectively. Co-infection by HCV (hepatitis C virus) and HBV (hepatitis B virus) was very frequent among patients with malignant hypertension. The incidence of malignant hypertension among non-HIV patients with glomerulonephritis was significantly lower than that among HIV-infected patients. Malignant hypertension is a common presentation of patients with HIV-associated glomerulonephritis, particularly in those with IgA nephropathy, and is associated with a very poor patient and renal survival.

Incidence of biopsy-proven glomerulonephritis

The reported biopsy-proven glomerulonephritis incidence varies according to population characteristics, the unknown true glomerulonephritis incidence and biopsy rate. Reported glomerulonephritis incidence should be evaluated against the biopsy rate. We report here the glomerulonephritis incidence in our University Hospital (UH) consecutive biopsy material. It is compared to those from surrounding central hospitals (CH), previous single-centre studies and European biopsy registries (EBR). Biopsy rate, when reported, has been considered. The annual biopsy rate/10(5), median (min-max), at the UHs was 25.4 (15.6-35.1). At the CHs it was 8.7 (5.1-12.6). In previous single-centre studies it has been 18.7-21.5. In the EBRs it has been between 1.0 and 6.9 when reported. The annual incidences (median, min-max) per 10(5) (1980-2000) at the UH were as follows: proliferative glomerulonephritis (9.5, 6.8-18.1), non-proliferative glomerulonephritis (6.7, 3.4-12.6), the four major glomerulonephritis groups MesGN (7.7, 4.4-15.9), ECGN/FPGN-complex (1.4, 0.5-3.2), MCGP/FSGS-complex (0.9, 0.2-2.7) and MGN (1.4, 0.5-2.4) these which findings were compatible with the single-centre studies and higher than those of the CHs and in the EBRs. Biopsy rate had a major impact on the annual glomerulonephritis incidences explaining 60% of the variation. The relative frequency of MesGN was the highest by all observers, followed by the ECGN/FPGN-complex, MGN and MCGP/FSGS-complex whose frequencies did not differ much. For every patient commencing renal replacement therapy (Finnish Renal Replacement Registry Data) due to glomerulonephritis there were about 11 subjects with biopsy-proven glomerulonephritis, a relationship compatible with previous reports. The incidence of any glomerulonephritis of 17.6 per 10(5) population was comparable to those from the single-centre studies, but higher than in European biopsy registries, a fact largely explained by biopsy rates.

Graft Loss from Recurrent Glomerulonephritis Is Not Increased with a Rapid Steroid Discontinuation Protocol

The risk of recurrence of glomerulonephritis in kidney transplant recipients on a steroid-free maintenance immunosuppression protocol is unknown. We studied the 4-year graft and patient survival in 105 adult kidney transplant recipients who received their transplant for glomerulonephritis (GN) and were treated with a protocol incorporating rapid discontinuation of prednisone for 5 days (group 1). We compared these outcomes to two control groups; 439 concurrent recipients who received a transplant for causes other than GN (group 2) and to 260 kidney transplant recipients who received an allograft for GN between 1994 and 1999 and were maintained on a steroid-based immunosuppressive protocol (group 3). The 4-year graft and patient survival were similar in the three groups. Acute rejection-free survival was also similar. Serial annual serum creatinine and estimated GFR were also comparable amongst the three groups. Two grafts were lost in group 1 from biopsy-proven recurrent GN and eight other subjects had evidence of histological recurrence at 11.2+/-11.9 months. Seven grafts were lost for recurrent disease in group 3 and 15 others had evidence of histological recurrence at 29.1+/-32.6 months. The mean time to graft loss from recurrence was 52+/-22 months. A regimen that utilizes rapid discontinuation of steroids conveys no added risk of graft loss from recurrent GN in the short term but longer follow-up is needed. A consideration should be made to discontinue corticosteroids in the potential recipients who are on them at the time of transplantation.

Poor Renal Outcome of Antineutrophil Cytoplasmic Antibody Negative Pauci-immune Glomerulonephritis in Taiwanese

Pauci-immune glomerulonephritis (GN) is an important cause of crescentic GN, acute renal failure and mortality. However, data are limited on the clinical presentation and outcome in antineutrophil cytoplasmic antibody (ANCA) negative patients, especially in Asians. This retrospective study analyzed medical records and pathology slides of patients who received renal biopsy between February 1998 and October 2004. Enzyme-linked immunosorbent assay was used routinely for ANCA testing in all patients. Among 637 patients with biopsy-proven GN included in this study, 88 (13.8%) had glomerular crescent formation. Among them, pauci-immune crescentic glomerulonephritis (PICGN) (42 patients, 47.2%) and lupus nephritis (25 patients, 28.4%) were the most common pathologic diagnoses. Lupus patients were younger (p = 0.028), while PICGN patients had more chronic lesions (p < 0.001), extensive glomerular crescents (p < 0.001), less severe proteinuria (p < 0.001) and poorer renal survival (p = 0.0017). Among the PICGN patients, 62.5% had a positive ANCA test, 80% had myeloperoxidase-ANCA and 20% had proteinase-3-ANCA. Subgroup analysis showed that ANCA negativity was associated with less crescent formation (p < 0.001) but more chronic glomerular lesions (p < 0.001) and a trend toward worse renal outcome (p = 0.055). This study illustrates the necessity for pathologic diagnosis of pauci-immune GN despite ANCA negativity. The poor prognosis associated with ANCA negativity in this study may be partly due to delayed diagnosis since these patients frequently lacked systemic involvement.

Apoptosis and proliferation in childhood acute proliferative glomerulonephritis

Acute proliferative glomerulonephritis is characterized by glomerular hypercellularity that can be caused by many different etiologies and pathogenetic mechanisms. A balance between cell birth by mitosis and cell death by apoptosis is crucial. In this study, apoptosis and the regenerative activity (Ki67/apoptosis index) were investigated in acute proliferative glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative glomerulonephritis and five controls with MCD were studied retrospectively. According to the clinical outcome, patients were divided into 2 groups: group 1 (n =21) were patients with normal renal functions at follow-up; group 2 (n =8) were patients with end-stage renal failure or those who died. Immunohistochemical staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients with acute proliferative glomerulonephritis and 3% in controls ( p <0.001). Apoptotic cells were identified in the tubulointerstitial compartment with higher and heavier immunostaining in patients than controls (p =0.001). Tubular proliferative index (= tubular proliferation/tubular apoptosis ratio) was significantly higher in group 1 patients than in group 2 patients (2.03+/-2% versus 0.32+/-0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular proliferation/interstitial proliferation ratio) was significantly higher in controls than in patients (3.4+/-1.9 versus 1.52+/-0.8, p =0.01). In addition, it was significantly increased in group 1 patients when compared with those in group 2 patients (1.89+/-0.8 versus 0.73+/-0.2, p =0.001). Since 17 patients presented with postinfectious proliferative glomerulonephritis, which is known to exhibit better course, we also evaluated those parameters in patients with postinfectious proliferative glomerulonephritis separately. We found statistically significant differences only in the tubulointerstitial regenerative ratio, which was higher in postinfectious cases when compared with those in other cases [1.60 interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In conclusion, tubular proliferative index and tubulointerstitial regenerative ratio might be useful parameters for predicting final functional outcome in acute proliferative glomerulonephritis. Further studies, however, are still needed to clarify the importance of these histopathological parameters.

Association of interleukin-10 gene G-1082A polymorphism with the progression of primary glomerulonephritis

Interleukin-10 (IL-10) is a cytokine with immunosuppressive properties. We evaluated the influence of G-1082A polymorphism in the IL-10 gene promoter, which has been associated with modified IL-10 production, on the two most common forms of primary glomerulonephritis: IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS). We studied Caucasian patients (N= 191) with biopsy-proven glomerulonephritis (IgAN: N= 123, FSGS: N= 68) followed-up for 6.5 +/- 5.5 years. Patients were classified according to the slope of reciprocal serum creatinine (>/= or <-0.1 dL(*)mg(-1) (*)year(-1)) into group A (slow progressors, IgAN: N= 75, FSGS: N= 47) and group B (fast progressors, IgAN: N= 48, FSGS: N= 21). One hundred healthy volunteers were analyzed as control patients. G-1082A polymorphism was determined by polymerase chain reaction (PCR) amplification. The allele frequencies were similar in patients and control group (NS). Initial renal function, proteinuria, and blood pressure did not differ significantly between patients with different genotypes. G-1082A polymorphism was associated with the progression of both IgAN and FSGS: GA/AA genotypes were more frequent in group B (fast progressors) than in group A (slow progressors; P= 0.012 for IgAN, P < 0.05 for FSGS). Patients with the GA/AA genotypes showed a worse outcome in the Kaplan-Meier analysis of renal survival (P < 0.05 for both IgAN and FSGS). The IL-10 polymorphism remained an independent risk factor for progression in multivariate analysis (Cox regression model, P < 0.05 for IgAN and FSGS). Our results suggest that IL-10 gene G-1082A polymorphism is an important marker of progression in patients with IgAN and FSGS.

Acanthocytes in the Urine

The presence of hematuria has been suggested to indicate nondiabetic nephropathy in diabetic patients with proteinuria. However, hematuria is frequently found in patients with biopsy-proven diabetic glomerulosclerosis without nondiabetic nephropathy. Urine microscopy allows discrimination of glomerular hematuria, which is defined as acanthocyturia (urinary excretion of acanthocytes, which are dysmorphic erythrocytes with vesicle-like protrusions), from nonglomerular hematuria. We hypothesized that acanthocyturia is an uncommon finding in diabetic nephropathy, which suggests the presence of a nondiabetic nephropathy in diabetic patients with proteinuria. Urine samples of patients with the clinical diagnosis of diabetic nephropathy (n = 68), of patients with biopsy-proven glomerulonephritis (n = 43), and of age-matched healthy control subjects (n = 20) were examined by phase-contrast microscopy for the presence of hematuria (>/=8 erythrocytes/ micro l) and acanthocyturia. Acanthocyturia of >/=5% (5 acanthocytes among 100 excreted erythrocytes) was classified as glomerular hematuria; acanthocyturia of 2-4% was classified as suspected glomerular hematuria. Hematuria was found in 62% of patients with the clinical diagnosis of diabetic nephropathy, in 84% of patients with glomerulonephritis, and in 20% of the healthy control subjects upon a single urine examination. In contrast, glomerular hematuria occurred in 4% of patients with diabetic nephropathy and in 40% of patients with glomerulonephritis (P < 0.001). In contrast to hematuria, acanthocyturia is uncommon in patients with the clinical diagnosis of diabetic nephropathy. In diabetic patients with proteinuria, the finding of acanthocyturia points to nondiabetic glomerulopathies, and renal biopsy should be considered.

Triplets with systemic lupus erythematosus

We present herein the first case report of identical triplets who developed systemic lupus erythematosus (SLE). The children were diagnosed as having SLE in reverse birth order at ages 8, 9, and 11 years. Although genetically identical, each sibling manifested different clinical signs and symptoms; however, all 3 children did manifest skin rash, fatigue, and biopsy-proven glomerulonephritis at different ages. Findings of laboratory studies were similar, including positivity for antinuclear antibodies, anti-native DNA, and anti-double-stranded DNA, as well as low levels of complement. These findings confirmed SLE in each sibling.

Renal involvement in monoclonal (type I) cryoglobulinemia: Two cases associated with IgG3κ cryoglobulin

Renal involvement has been described rarely in monoclonal (type I) cryoglobulinemia, although this complication is frequent among patients with mixed (type II or III) cryoglobulin. We report two patients with glomerulonephritis and monoclonal IgGκ cryoglobulin. Both patients presented with nephrotic syndrome, microscopic hematuria, and impaired renal function. Hepatitis C serology was negative, bone marrow aspiration was normal, and the renal biopsy specimen showed membranoproliferative glomerulonephritis with glomerular subendothelial deposits of monoclonal IgGκ. In both cases, circulating cryoglobulin and monotypic tissue deposits were found to be IgG3κ, suggesting that this isotype may have a particular propensity to cause this type of membranoproliferative glomerulonephritis. Although 18 cases of type I cryoglobulinemia with biopsy-proven glomerulonephritis have been reported to date, this is the first characterization of immunoglobulin heavy-chain isotype in this disease. Am J Kidney Dis 40:1091-1096. © 2002 by the National Kidney Foundation, Inc.

Dysmorphic erythrocytes and G1 cells as markers of glomerular hematuria.

We aimed to assess the utility of the percentage of G cells and dysmorphic erythrocytes in the diagnosis of glomerular hematuria in pediatric patients. We determined the percentage of dysmorphic erythrocytes and G1 cells in urine samples from patients with glomerulonephritis and other renal diseases of non-glomerular origin. There was excellent correlation and agreement between results obtained by counting the cells in counting chambers and in urine sediments. With cut-off values of > or =1%, > or =2%, > or =5%, and 10% for G1 cells, sensitivities for the detection of glomerulonephritis were 62%, 40%, 28%, and 10% and specificities were 89%, 95%, 95%, and 98%. For the dysmorphic erythrocytes cut-off values of > or =10%, > or =20%, 50%, and > or =90% gave respective sensitivities of 95%, 95%, 93%, and 62% and specificities of 24%, 34%, 43%, and 85%. In 38% of cases of biopsy-proven glomerulonephritis no G1 cells were found. For cut-off values of > or =50% dysmorphic erythrocytes and > or =1% G1 cells, the sensitivity and specificity were 60% and 91%. For cut-off values of > or =50% dysmorphic or > or =1% G1 cells, sensitivity and specificity were 93% and 44%. Our results show that neither the percentage of dysmorphic erythrocytes nor the G1 cell count is of adequate sensitivity and specificity to enable reliable differentiation of glomerular and non-glomerular hematurias. Both tests are needed to achieve >90% sensitivity and specificity.

Nephrotic-range proteinuria in patients with renovascular disease

PURPOSE: Proteinuria is usually considered a manifestation of glomerular disease. We sought to describe the characteristics of patients with nephrotic-range proteinuria resulting from renovascular disease and to compare them with those of patients who had glomerulonephritis. SUBJECTS AND METHODS: We identified 14 patients with nephrotic-range proteinuria and renovascular disease and compared them with 14 patients who had nephrotic-range proteinuria and biopsy-proven glomerulonephritis, matched for sex, age, and glomerular filtration rate. RESULTS: Patients with renovascular disease were more likely to have known atherosclerotic vascular disease [13 of 14 (93%) vs 3 of 14 (21%), P <0.0001] and were usually smokers [12 of 14 (85%) vs 3 of 14 (21%), P <0.0001]. They also had a greater mean (± SD) difference between the lengths of their kidneys (29 ± 10 vs 5 ± 5 mm, P <0.001); greater systolic blood pressure (203 ± 22 vs 174 ± 25 mm Hg, P <0.005), plasma renin activity (17 ± 19 vs 2 ± 2 ng/mL/h, P = 0.005), and plasma aldosterone concentration (40 ± 23 vs 11 ± 10 ng/dL, P = 0.0001); and lower serum potassium levels (3.3 ± 0.5 vs 3.8 ± 0.5, P <0.05). Effective renal plasma flow was lower (139 ± 68 vs 307 ± 185 mL/min/1.73 m 3) and filtration fraction was markedly greater (0.28 ± 0.04 vs 0.15 ± 0.07, P = 0.0001) in the patients with renovascular disease. After the oral administration of captopril, blood pressure, effective renal plasma flow, and glomerular filtration rate decreased only among patients with renovascular disease. Of the 14 patients with renovascular disease, 13 had evidence of renal artery thrombosis seen at angiography; 2 patients required dialysis, and 3 others died during follow-up. CONCLUSION: Our findings suggest that the patients with nephrotic-range proteinuria resulting from renovascular disease have distinct characteristics and a poor prognosis.

Reduced 11beta-hydroxysteroid dehydrogenase activity in patients with the nephrotic syndrome.

Patients with the nephrotic syndrome (NS) exhibit abnormal renal sodium retention which cannot completely explained by a secondary hyperaldosteronism due to reduced renal perfusion. As an alternative mechanism to explain this phenomenon we postulate a cortisol-mediated mineralocorticoid effect as a consequence of a reduced activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). A down-regulation of 11beta-HSD, i.e. of the shuttle of active to inactive glucocorticosteroids, has been shown to cause mineralocorticoid effects. Therefore we investigated the activity of 11beta-HSD by measuring the urinary ratio of (tetrahydrocortisol + 5alpha-tetrahydrocortisol)/tetrahydrocortisone [(THF+5alpha-THF)/THE] by gas-chromatography in 29 NS patients with biopsy-proven glomerulonephritis and 29 healthy control subjects. The ratio of (THF+5alpha-THF)/THE was higher in NS patients (median 1.49, range 0.45-4.07) than in the control subjects (0.98, 0.60-1.36; p<0.01). This ratio was increased as a consequence of a decreased urinary excretion rate of the cortisone metabolite, THE. The present data indicate that a reduced activity of 11beta-HSD is a new mechanism contributing to the exaggerated sodium retention in patients with the NS.

Crescentic Glomerulonephritis as Renal Cause of Acute Renal Failure

Over a period of 5 years, we observed 28 patients with biopsy-proven crescentic glomerulonephritis. Four of these patients were ANCA associated (pauci immune), 1 had anti-glomerular basement membrane antibodies (anti-GBM), and the other 23 cases had immune complex form (22 poststreptococcal and 1 poststaphylococcal). Acute renal failure as a main clinical feature was found in 11/28 (35.7%), all with more than 80% crescents, including all ANCA-associated cases, anti-GBM form, and the patient with poststaphylococcal form. Using "pulse" therapy with methylprednisolone, cyclophosphamide, and plasmapheresis, renal function was improved in 5/11 (45.4%), diuresis started, and end-stage renal disease was delayed. The therapy was continued orally with steroids and cyclophosphamide. The second attach of oligoanuria developed after a period of 6-12 months without improvement after the therapy used previously (during the first attack), and it was necessary to begin chronic hemodialysis treatment.

Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study

It was found that in Belgium, renal imaging techniques, demonstrating a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications, were the only methods to reliably diagnose analgesic nephropathy (AN) in patients with end-stage renal failure. However, these criteria were selected in an area with a high prevalence of this disease (15.6% of the dialysis population at December 1990). To evaluate the criteria selected to diagnose AN in populations with lower or unknown prevalences of AN, the Analgesic Nephropathy Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14 European countries and Brazil. During 1991-1992, 598 new patients with equivocal diagnosis of renal disease (excluding biopsy-proven glomerulonephritis, polycystic disease, diabetic nephropathy and other systemic diseases) and who began renal replacement therapy in the ANNE centres were evaluated by a short questionnaire and two renal imaging techniques: sonography and either tomography or computed tomography (CT) scan. A comparison of 82 abusers (daily use of analgesic mixtures for at least 5 years) and 495 controls corroborated the excellent diagnostic performance of the renal imaging techniques for AN. We recommend the use of these renal imaging criteria in all patients without a clear renal diagnosis in order to obtain a more reliable insight into the magnitude of the AN problem in different countries.

Kidneys from pediatric donors: risk versus benefit

We encountered four adult patients who received renal transplants from young children < 36 months of age, each of whom developed severe hypertension, heavy proteinuria, and progressive renal failure. Biopsies disclosed glomerular sclerosis with crescents in three patients and mesangial expansion in one. We thus analyzed our experience with 74 adults who received grafts from donors < or = 10 years of age and compared the results to those of 804 patients who were transplanted with kidneys from donors > 10 years of age. A Kaplan-Meier analysis revealed that graft survival was significantly worse in patients receiving grafts from younger, compared to older donors. This difference was apparent in patients treated either with or without cyclosporine. A subanalysis comparing patients with donor grafts aged < or = 5 or 6-10 years revealed a further adverse age-related effect. Renal artery thrombosis and recurrent or de novo biopsy-proven glomerulonephritis were more common in patients receiving grafts from younger donors, while graft failure from rejection actually appeared less common. We conclude that severe hypertension and resultant glomerular hyperperfusion promoted glomerulosclerosis and crescent formation in our patients. Our results have caused us to pursue a more conservative approach towards transplanting grafts from donors aged < or = 10 years into adult recipients.

Tubular Damage in Microalbuminuric Patients with Primary Glomerulonephritis and Diabetic Nephropathy

Tubular damage as suggested by enzymuria and tubular proteinuria is a recognized feature of glomerulonephritis (GN) with clinical proteinuria and both incipient and overt diabetic nephropathy (DN). However, little is known about the presence of tubulopathy in patients with primary GN, microalbuminuria [albumin excretion (AER) 30-300 mg/d] and microhematuria. Three groups were studied. The GN group comprised 17 (2 F) patients with biopsy-proven GN with microalbuminuria. The DN group comprised 35 (14 F) patients with incipient diabetic nephropathy with AER 30-300 mg/d, and controls comprised 38 (15 F) normal subjects with normal AER < 30 mg/d. Serum creatinine, albuminurinuria, transferrinuria, and markers of tubular damage such as urinary excretion of N-acetyl-glucosaminidase (NAG), leucine aminopeptidase (LAP), gamma-glutamyl transferase (gGT), and retinol binding protein (RBP) were measured. GN and DN had comparable degrees of albuminuria, transferrinuria, and LAP excretion, and these were significantly higher than controls. Serum creatinine was significantly higher in GN than DN and controls. DN had significantly higher NAG and RBP, and lower gGT than GN and controls. In both GN and DN groups, both glomerular proteins correlated with each other and NAG correlated significantly to LAP and gGT. Albuminuria correlated to tubular enzymuria in GN group but not in patients with DN. The results suggest that tubular damage is less marked in microalbuminuric patients with GN than those with DN despite similar degree of glomerular proteinuria. The pattern of tubulopathy is also different in the two groups, indicating differences in the pathogenesis of tubular damage in these two clinical settings.

Relationship between hydrocarbon exposure and nephropathology in primary glomerulonephritis

It has been proposed that renal tubular damage and chronic hydrocarbon exposure are causally related to progression of renal failure in primary glomerulonephritis. We examined the relationship between hydrocarbon exposure and morphological parameters of tubulointerstitial damage in 59 patients with biopsy-proven primary glomerulonephritis (proliferative, n = 52; membranous, n = 7). From a mean follow-up period of 6 years patients were divided into two groups (GP) according to the presence or absence of progressive renal failure (GP 1, n = 24 with progressive renal failure) and (GP 2, n = 35 without progressive renal failure). The two groups were comparable in age, sex, duration of diagnosis (since the time of biopsy) and blood-pressure control. Patients were blindly assessed for chronic hydrocarbon exposure by a validated questionnaire. Biopsy cylinders were blindly assessed retrospectively for relative interstitial volume of the renal cortex by the point-counting method. In addition an assessment was made of the degree of fibrosis and chronic inflammatory cellular infiltrate. Hydrocarbon exposure score derived from the questionnaire until the time of renal biopsy correlated both with interstitial volume (r = 0.55; P < 0.001) and serum creatinine (r = 0.46; P < 0.001). Moreover, interstitial volume also correlated with serum creatinine (r = 0.63; P < 0.001). Chronic hydrocarbon exposure scores and relative interstitial volume in the renal cortex at the time of renal biopsy was significantly higher in GP 1 than GP 2 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and Long-term Outcome of Glomerulonephritis in Renal Allografts

We report long-term results over 10 years in patients developing glomerulonephritis after renal transplantation. The prevalence rate of glomerulonephritis was 6.2% in 785 renal transplants involving 697 patients with end-stage renal disease. This rate was 14% in patients undergoing biopsy of their grafts because of malfunction. The rate was 15% in patients diagnosed as having glomerulonephritis of any cause prior to transplantation. Membranous, focal sclerosing, and IgA glomerulonephritis were the most common histologic diagnoses. Documented histologic recurrence occurred in only 1% of patients with poor, biopsy-proven glomerulonephritis of their native kidneys. Patients with focal sclerosing glomerulonephritis had the greatest risk from recurrence. De novo glomerulonephritis was most likely to be membranous in character. The graft survival rate of patients with glomerulonephritis was not distinguishable from that of patients showing rejection; both were 45% at 60 months and 33% versus 11%, respectively, at 120 months (P = NS); the graft survival rate in patients without rejection was 76% at 120 months. Thus, glomerulonephritis is responsible for approximately 14% of renal graft malfunction. Glomerulonephritis has a prognosis similar to chronic rejection. Finally, glomerulonephritis as specific histologic recurrence is unusual. Patients with glomerulonephritis should not be discouraged from undergoing transplantation because of putative risks related to recurrence.