The pathogenetic role of Staphylococcus aureus in primary human glomerulonephritis.

Antibody levels to a cell product of Staphylococcus aureus, antistaphylolysin antibody (AStaL), were determined in the sera of 185 patients with various renal diseases using the hemolysis inhibition test. Detection of Staphylococcus aureus antigen in renal biopsy specimens was performed by the immunofluorescent technique. Elevated AStaL values were observed in eleven patients. In four of them, Staphylococcus aureus antigen was clearly detected in the glomerular mesangial area associated with deposits of immunoglobulins and complement. Most of these patients showed marked elevation of AStaL values with low serum complement levels and had diffuse proliferative glomerulonephritis. These results suggest that Staphylococcus aureus may act as a specific antigen and play an important role in the pathogenesis of primary human glomerulonephritis.     

Chronic glomerulonephritis with massive IgA deposits

A total of 234 patients with chronic glomerulonephritis, detected on the basis of clinical, immunological and pathomorphological criteria, have been examined. A group of 23 chronic glomerulonephritis patients with massive deposits of immunoglobulin A found by immunofluorescent examination, has been separated on the basis of immunohistochemical studies. In this group, occurrence of different morphological forms of glomerulonephritis has been observed: 30.4% mesangial-proliferative glomerulonephritis, 13% submicroscopic glomerulonephritis and one case of membranous glomerulonephritis.Complete haemolytic activity of complement, level of complement components C₃ and C₄, immunological complexes circulating in blood, properdin and immunoglobulin A levels, fibrin and fibrinogen (FDP) degradation product concentrations and their 24-hour excretions with urine have been determined.Preliminary observations of this group of patients seem to indicate a positive effect of steroid therapy in glomerulonephritis with IgA deposits, irrespective of the morphological form of the disease.     

Hypertension in primary chronic glomerulonephritis: analysis of 288 biopsied patients

The prevalence of hypertension in 288 patients with primary chronic glomerulonephritis was compared with that observed in a control group of 3,477 subjects from the same geographic area. 23.3% of the patients and 12.8% of the general population were hypertensive (p less than 0.01). However, if only patients with normal renal function were considered, prevalence of hypertension (12.7%) was not higher than in the control group. Hypertension was more frequent in focal segmental sclerosis (30%) and in membranous glomerulonephritis (26%) than in IgA nephropathy (9%), membranoproliferative glomerulonephritis (11%) and IgM mesangial glomerulonephritis (12%). Five years after renal biopsy, 92% of normotensive and 47% of hypertensive patients remained with normal renal function (p less than 0.001). These findings suggest that the high prevalence of hypertension in chronic glomerulonephritis is related to the declining renal function. On the other hand, hypertension appears to represent a bad prognostic sign.     

Serum protein binding of propofol in patients with renal failure or hepatic cirrhosis

Background: Serum protein binding is a limiting factor in the access of drugs to the central nervous system. Disease-induced modifications of the degree of binding may influence the effect of anesthetic drugs. Methods: The protein binding of propofol, an intravenous anaesthetic agent which is highly bound to serum albumin, has been investigated in serum samples from healthy volunteers, from patients with chronic renal failure not undergoing hemodialysis, from patients with chronic renal failure included in a regular hemodialysis program, and from patients with hepatic cirrhosis. Protein binding was determined by the ultrafiltration technique using an Amicon Micropartition System, MPS-1. Results: The percentage of unbound propofol (mean(SD)) in healthy volunteers (n=16) was 0.98 (0.48) % showing a high interindividual variability. Chronic renal failure did not significantly modify serum protein binding of propofol. In the chronic renal failure group not undergoing regular hemodialysis (n=>9), unbound propofol was 0.92 (0.34) %. In addition, patients in periodic dialysis did not show changes in propofol binding either compared before (1.11 (0.33) %; n=13) or after hemodialysis (0.87 (0.38) %; n=12). A slight decrease in albumin concentration was found in all renal patients (P<0.05) in comparison to healthy volunteers. Creatinine and urea concentrations were higher in these patients (P<0.01) but in the postdialysis group, the differences in urea levels were not significant when compared with those of volunteers. No changes in the degree of propofol binding were observed in patients with hepatic cirrhosis (0.97 (0.30) %; n=14) when compared with the group of healthy volunteers. Significant differences were observed in albumin (P<0.01) and bilirubin (P<0.05) concentrations. Considering all subjects, the degree of binding did not correlate with biomedical data. Conclusion: Due to the the absence of significant changes in the protein binding it is unlikely that there will be an exaggerated pharmacological response in patients with renal and hepatic disease following the administration of a standard propofol dose, although due to interpatient variability careful titration can be recommended.     

In vitro stimulation of renal tubular p-aminohippurate transport by dexamethasone in rat kidneys and in intact kidney tissue of patients suffering from renal cell carcinoma

The aim of this study was to test whether or not the accumulation of p-aminohippurate (PAH) can be increased in intact human renal cortical slices obtained from tumor-bearing kidneys of patients suffering from renal cell carcinoma (RCC). Tissue slices were incubated for 24 h in Williams medium E containing 0.01–50 μM dexamethasone. Thereafter slices were placed in PAH-containing Cross-Taggart medium and PAH uptake into kidney tissue was measured for 2 h. In both rat and human renal tissue slices, PAH uptake capacity increased significantly in a concentration-dependent manner after 24 h of incubation in dexamethasone-containing medium (rat, 136%; man, 156%). The stimulatory effect was already significant after 12 h of incubation. In additional experiments it was shown that incubation in triiodothyronine (T₃)-containing medium has different effects: in man, T₃ does not influence the PAH accumulation capacity of renal cortical slices whereas in rats PAH accumulation is significantly lower after 24 h of incubation with T₃. Thus stimulation of tubular transport capacity can be performed in vitro in human renal cortical slices. Discrepancies between the effects of dexamethasone and T₃ indicate different modes of action of the two hormones at the cellular level. Received: 4 August 1997 / Accepted: 28 October 1997     

Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency

Background. Chronic renal insufficiency is accompanied by specific alterations of the lipoprotein metabolism. It has been suggested that the renal dyslipoproteinaemia of renal insufficiency contributes to the progression of glomerular and tubular lesions, with subsequent deterioration of renal function. The objective of this prospective study was to investigate whether the specific lipoprotein abnormalities of renal insufficiency are associated with the rate of decline of renal function in patients with moderately advanced chronic renal failure. Methods. A patient population of 73 adult non-diabetic patients with primary chronic renal disease were followed with repeated measurements of glomerular filtration rate (GFR) for an average of 3.2 (SD 0.7) years. Forty-three of these patients had chronic glomerulonephritis as the underlying renal disease. Patient characteristics including plasma levels of lipids and apolipoproteins were determined at entry and were prospectively related, using linear regression, to the rate of progression. Results. The mean GFR at entry was 41.3 (SD 15.3) ml/min x 1.73 m² BSA. The average rate of progression was a decline in GFR of -2.8 (SD 3.7) ml/min x 1.73 m² BSA per year. In the whole patient study group total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B (apoB) were all significantly associated with a more rapid decline in renal function, whereas triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A (apoA) were not. In the more homogeneous subgroup of patients with chronic glomerulonephritis the association between dyslipidaemia and the rate of progression was even more pronounced. In this subgroup of patients also serum triglycerides and apoE were significantly associated with a higher rate of progression. Both the initial blood pressure and proteinuria were also significantly associated with a more rapid decline in renal function in the whole study group as well as in patients with chronic glomerulonephritis. The associations between these variables with the rate of progression were all independent of the entry GFR values. Conclusions. These results indicate that the lipoprotein abnormalities of renal insufficiency contribute to the progression of renal failure in human chronic renal disease.     

Accompanying renal injuries did not impact graft survival in patients with transplant glomerulopathy

Transplant glomerulopathy (TG) a morphological feature of chronic active antibody-mediated rejection, is associated with donor-specific antibody, peritubular capillary deposition of C4d, and multilayering of peritubular capillary basement membranes. To evaluate the significance of accompanying nonimmunologic injuries in TG, we retrospectively reviewed 2839 renal allograft cases at our institute among which TG was diagnosed in 81 patients (2.9%). Among TG cases, 48 samples showed accompanying diseases such as chronic calcineurin inhibitor toxicity, hepatitis viral infection, posttransplant diabetes, and glomerulonephritis. Comparing the pure form of TG with TG-mixed diseases, there was no difference in patient demography, serum creatinine values, and proteinuria. Among histological parameters, severe hyalinosis was more frequently observed among the TG plus other diseases group. The two groups did not show significant difference in graft survival (P = .216).     

Detection of p53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications

Summary For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (T_a) tumors to 83.3% of muscle-invasive (T₃/T₄) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G₁ tumors to 75% of G₃ tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T₁) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P<0.01; chi-square test). For other urological tumors such as prostate cancer, the results of immunohistochemistry are more difficult to interpret and require definite confirmation on the DNA level.     

Analysis of Renal Cell Populations Using Monoclonal Antibodies

Monoclonal antibodies have proved invaluable in identification and characterization of hemopoietic cell surface macromolecules. We have used a number of these monoclonal antibody probes for immunohistochemical analysis of interstitial cell populations in diseased human kidney tissues and in certain prototypic cutaneous cellular immune reactions. The studies demonstrate that the relative proportions of T-cell subpopulations present in graft rejection (OKT8⁺ exceeding OKT4⁺) differ from those observed in drug nephrotoxicity and end-stage kidney disease. In this regard graft rejection resembles graft versus host disease of skin but not delay ed-type hyper sensitivity. However, analysis of cell populations in interstitial infiltrates from various forms of chronic renal disease (glomerulonephritis, end-stage renal disease of varied etiologies) failed to demonstrate any unique or characteristic profile. These studies led to the recognition that certain monoclonal antibodies directed against B- and leukemic cell surface antigens also bind to normal renal cells and that nephron development in the human fetus is characterized by differential binding of these probes.     

Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy

BACKGROUND: IgA nephropathy is the most common form of glomerulonephritis worldwide. We previously reported a novel form of glomerulonephritis with glomerular IgA deposits following methicillin-resistant Staphylococcus aureus (S. aureus) infection. We investigated the role of S. aureus related antigens in the immunopathogenesis of IgA nephropathy by producing several monoclonal antibodies against S. aureus surface antigens and determining the epitopes of deposited antigens in patients with IgA nephropathy. METHODS: Cell membrane proteins were isolated from cultured S. aureus. Mouse monoclonal antibodies against these proteins were generated, and their target epitopes were determined by antibody affinity chromatography and amino acid sequence analysis, and by monoclonal antibody screening of Escherichia coli clones transfected with plasmids from the Lambda S. aureus Genomic Library. Renal biopsy specimens from 116 patients with IgA nephropathy and 122 patients with other forms of renal disease were examined for glomerular antigen depositions by immunofluorescence microscopy. RESULTS:. The major antigen recognized by monoclonal antibodies against S. aureus cell membrane was identified as the S. aureus cell envelope antigen designated 'probable adhesin' (ACCESSION AP003131-77, Protein ID; BAB41819.1). In 68.1% (79/116) of renal biopsy specimens from patients with IgA nephropathy, S. aureus cell envelope antigen was localized in the glomeruli, and the data confirmed that S. aureus cell envelope antigen was co-localized with IgA antibody in the glomeruli. No deposition of this antigen was detected in the glomeruli of patients with non-immune complex deposit forms of glomerulonephritis. CONCLUSION: S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.     

Calcification Propensity and Survival among Renal Transplant Recipients

Calciprotein particle maturation time (T₅₀) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T₅₀ in renal transplantation, baseline serum T₅₀ was measured in a longitudinal cohort of 699 stable renal transplant recipients and the associations of T₅₀ with mortality and graft failure were analyzed over a median follow-up of 3.1 years. Predictive value of T₅₀ was assessed for patient survival with reference to traditional (Framingham) risk factors and the calcium-phosphate product. Serum magnesium, bicarbonate, albumin, and phosphate levels were the main determinants of T₅₀, which was independent of renal function and dialysis vintage before transplant. During follow-up, 81 (12%) patients died, of which 38 (47%) died from cardiovascular causes. Furthermore, 45 (6%) patients developed graft failure. In fully adjusted models, lower T₅₀ values were independently associated with increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval, 1.11 to 1.85; P=0.006 per SD decrease) and increased cardiovascular mortality (hazard ratio, 1.55; 95% confidence interval, 1.04 to 2.29; P=0.03 per SD decrease). In addition to age, sex, and eGFR, T₅₀ improved prognostication for all-cause mortality, whereas traditional risk factors or calcium-phosphate product did not. Lower T₅₀ was also associated with increased graft failure risk. The associations of T₅₀ with mortality and graft failure were confirmed in an independent replication cohort. In conclusion, reduced serum T₅₀ was associated with increased risk of all-cause mortality, cardiovascular mortality, and graft failure and, of all tested parameters, displayed the strongest association with all-cause mortality in these transplant recipients.     

The Spectrum of Adult Postinfectious Glomerulonephritis in the New Millennium

Background. Postinfectious glomerulonephritis is rare in adults. The characteristics of the disease now differ from what were described decades ago. The goal of this study is to illustrate the clinicopathological spectrum of the disease in the modern era. Methods. Between July 2000 and June 2008, 20 adult cases of postinfectious glomerulonephritis were identified at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. Results. There were 14 males and 6 females. The mean age was 61 years. All patients developed acute renal failure, and the majority (65%) required dialysis support during the disease course. Hypocomplementemia was present in 60% of patients. The most frequently identified infectious agent was Staphylococcus (60%). Histological characteristics showed two distinct patterns of glomerulonephritis: diffuse endocapillary proliferative glomerulonephritis (65%) and focal mesangial proliferative glomerulonephritis (35%). There were no significant differences in the clinical presentation and outcome between the two groups. However, glomerular neutrophil infiltration was more commonly present in diffuse endocapillary proliferative pattern (p = 0.017). The percentage of patients with focal mesangial proliferative pattern significantly increased over time (p < 0.001). At the last follow-up, 6 patients (30%) had died, 6 (30%) were in complete remission, 4 (20%) had partial remission with renal insufficiency, and 4 (20%) were on chronic dialysis. Conclusions. Our data suggested that Staphylococcus had become the leading pathogen in adult postinfectious glomerulonephritis over the past 10 years. Furthermore, atypical histological feature with focal mesangial proliferative pattern was increasingly identified over time. The prognosis was still guarded, carrying a considerable mortality rate and risk for developing chronic renal failure.     

ANCA-associated glomerulonephritis/systemic vasculitis in childhood: clinical features–outcome

Background

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and systemic vasculitis (AAGNV) is uncommon in childhood.

Methods

This is a retrospective study of AAGNV cases diagnosed over a 13-year period in a tertiary pediatric nephrology department.

Results

Thirteen cases of AAGNV were identified: seven Wegener granulomatosis (WG) and six microscopic polyangiitis (MPA). Acute renal failure/nephrotic range proteinuria (NRP) was found in 77 % of the patients (4 with WG, all with MPA). Eleven (85 %) patients showed necrotizing glomerulonephritis (NGN), with ≥50 % crescents identified in nine patients (69 %) (4 with WG, 5 with MPA). Treatment with methylprednisolone, cyclophosphamide and plasma exchange resulted in extra-renal remission and antibody reduction in all patients and renal function improvement/stabilization in 77 % of the patients. Three patients, all without oliguria at presentation and few sclerotic lesions, had normal renal function at follow-up. Chronic kidney disease (CKD) stages 2 and 3–4 were observed in four (WG) and three (MPA) patients, respectively. Three patients (23 %) developed end stage renal disease: two were MPA patients with severe presentation (markedly impaired glomerular filtration rate, oliguria, NRP, crescentic NGN, glomerular sclerosis) and one was a WG patient with extensive interstitial fibrosis/tubular atrophy.

Conclusions

Severe renal involvement was more common in children with MPA than WG. Treatment with methylprednisolone, cyclophosphamide and plasma exchange induced extra-renal remission/serological response and renal function improvement/stabilization. Markedly decreased GFR, oliguria, NRP, and chronic glomerular lesions at presentation were predictors of poor outcome.     

Nephropathy associated with heroin abuse in Caucasian patients.

BACKGROUND: Renal disease is a complication of heroin addiction. Using renal biopsies in Caucasian patients, we studied the types of nephropathy associated with heroin abuse. METHODS: Nineteen renal biopsies were performed on heroin addicts between January 1993 and December 2001. The indications for renal biopsy included proteinuria with or without renal insufficiency. RESULTS: All 19 patients had serological evidence of hepatitis C virus (HCV) infection, one had hepatitis B virus surface antigen and three were HIV positive. Thirteen patients (68.4%) were found to have membranoproliferative glomerulonephritis (MPGN), 12 with type I and one with type III. Of the remaining patients, two had chronic interstitial nephritis, two had acute proliferative glomerulonephritis, one had amyloidosis and one had granulomatous glomerulonephritis with interstitial nephritis. No apparent decline in the incidence of renal disease was observed. CONCLUSIONS: In this cohort of male Caucasian heroin addicts, HCV-associated MPGN was the most frequent pattern of nephropathy, showing that the nephropathy associated with heroin abuse in Caucasians is not of the focal and segmental glomerulosclerosis type, in contrast to previous reports on African-Americans. This aspect may have important implications for patient management and prognosis.     

Dense intramembranous deposit disease: a clinical comparison of histological subtypes

The accumulation of osmiophilic dense deposits in glomerular mesangial and basement membranes (dense intramembranous deposit disease, or DIDD) is associated with variable histologic alterations of the kidneys. We compared clinical features and long-term renal outcome in 21 patients representing two histologic subtypes of DIDD, namely membranoproliferative glomerulonephritis (MPGN) and focal segmental glomerulonephritis (FSGN). We found that MPGN-type DIDD in 12 patients was associated with nephrotic syndrome in 12, persistent hypocomplementemia in 10 and progression to chronic renal insufficiency in 8. In 9 patients with the focal segmental variety of DIDD, nephrotic syndrome was observed in 3, persistent hypocomplementemia in none, and progression to renal insufficiency in 2 (significance: nephrotic syndrome, p = 0.001; persistent hypocomplementemia, p = 0.0001; chronic renal insufficiency, p = 0.02). In one patient transition from focal segmental to MPGN-type DIDD was observed. We conclude that DIDD is a heterogeneous disorder, and that certain clinical and histologic features may be useful in predicting ultimate outcome.     

Meaning of Early Polyomavirus-BK Replication Post Kidney Transplant

Polyomavirus BK (BKV) infection is ubiquitous in the human population. Under immunosuppression, BKV can undergo reactivation resulting in viral replication. What really happens in the early hours posttransplantation is not clearly defined; the meaning of early viremia and viruria is not clear. BKV viremia is considered a marker of infection. The aim of our study was to investigate the prevalence of early BKV infection in kidney transplant patients, to evaluate the relationship to infections at 3 and 6 months and the association with recipient, donor, and graft features. We enrolled 36 kidney transplanted patients from May 2006 to April 2007. BKV load was measured on plasma and urine samples by Q-PCR at 12 hours (T₀/early) as well as 3 (T₃) and 6 (T₆) months thereafter. A high percentage of BKV infections were detectable in the first hours after transplantation (33.3%), which remained unchanged to month 6 post transplantation. Moreover, patients who were positive at T₀ had a high probability of remaining positive thereafter. The number of copies in plasma samples tended to increase at 3 months and to decrease thereafter, whereas the urine viral load tended to steadily increase. Among BKV-positive patients, we identified 2 groups according to viremic state at T₀: 9 patients (group A); who were already positive and remained so to T₆ 5 and 3 patients who turned positive at 3 or at 6 months, respectively (group B). Group A included 75% of positive patients at T₀ and 90% of positive patients at either T₃ or T₆ (P = .007). The most important contribution of our study was to highlight the presence of BKV infection in renal transplant recipients from the first hours posttransplantation. This condition seemed to be the most important risk factor for persistent infection in the first 6 months.     

Secondary hyperparathyroidism shortens the action of vecuronium in patients with chronic renal failure

The authors studied the duration of action of vecuronium in 15 patients with normal renal function and 40 patients with chronic renal failure to evaluate the effect of secondary hyper-parathyroidism on the action of vecuronium. The patients were divided into four groups: 15 patients with normal renal function (Group A); nine patients with chronic renal failure who did not need haemodialysis (Group B); 15 anephric patients who did not require parathyroidectomy (Group C); and 16 anephrenic patients who underwent parathyroidectomy because of severe secondary hyperparathyroidism (Group D). The ratio of the height of the first twitch (T₁) to the baseline value before vecuronium administration was measured by an electromyogram. Baseline T₁ was obtained after anaesthesia induction with thiamylal iv. The time to 10% recovery of the first twitch (REC 10) after administration of vecuronium 0.12 mg · Kg^?1 iv was measured in each group. Anaesthesia was maintained with isoflurane and nitrous oxide in oxygen, and supplemented with fentanyl iv. Patients in Group D showed shorter REC 10 (51 ± 4 min) than those in Groups B (71 ± 6 min) and C (80 ± 10 min) (P < 0.05), but similar REC 10 to patients in Group A (37 ±4 min). These results suggest that the duration of action of vecuronium in anephric patients with secondary hyperparathyroidism is shorter than in those without secondary hyperparathyroidism.     

Myeloperoxidase anti‐neutrophil cytoplasmic antibody affinity is associated with the formation of neutrophil extracellular traps in the kidney and vasculitis activity in myeloperoxidase anti‐neutrophil cytoplasmic antibody‐associated microscopic polyangiitis

Anti‐neutrophil cytoplasmic antibody (ANCA) is associated with small‐vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO‐ANCA‐associated microscopic polyangiitis. To investigate whether MPO‐ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO‐ANCA‐associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively. We divided 30 MPO‐ANCA‐associated microscopic polyangiitis patients into 2 groups based on their ANCA affinity levels (IC₅₀ for the high: 0.11 ± 0.04 µg/mL (Group1) and IC₅₀ for the low: 0.66 ± 0.24 µg/mL (Group2)). Group1 showed a higher Birmingham vasculitis activity score (15.6 ± 5.7) and 73% of the patients presented clinically with rapidly progressive glomerulonephritis and histologically with focal/crescentic glomerulonephritis (GN). Group 2 showed a lower Birmingham vasculitis activity score (9.2 ± 4.9) and 73% of the patients presented clinically with chronic renal failure and histologically with mixed/sclerotic GN. Group 1 showed a much higher occurrence of NETs than Group 2. Our findings indicate that ANCA affinity was associated with the in vivo formation of NETs, which might be involved in the pathophysiology of patients with MPO‐ANCA‐associated microscopic polyangiitis.     

Experimental glomerulonephritis induced by in situ formation of immune complexes in glomerular capillary wall.

An experimental model of glomerulonephritis was produced by the in situ formation of immune complexes directly in the glomerular capillary wall. Perfusing the lectin concanavalin A (Con A) into the left renal arteries of rats led to its binding diffusely to the glycoproteins of the glomerular capillary wall of only that kidney in each animal. The subsequent reaction with anti-Con A antibody (either administered systemically or actively induced) resulted in an exudative and proliferative glomerulonephritis confined to the Con A perfused kidney. Immunofluorescence disclosed the diffuse deposition of immunoglobulin, Con A, and C3 in the perfused, but not the unperfused kidney. The quantitative relationship between antigen and antibody binding and histologic outcome was determined. Since lectins have been found in mammalian tissues, as well as in infectious agents that are pathogenic in man, a series of events conceptually similar to this in situ model may occur in some cases of glomerulonephritis in man.     

Increased serum concentrations of pro-gastrin-releasing peptide in patients with renal dysfunction

BACKGROUND: Gastrin-releasing peptide has a prominent role as a tumour markerin the diagnosis of small-cell lung carcinoma. This study wasdesigned to assess the validity of a newly developed enzyme-linkedimmunosorbent assay (ELISA) for pro-gastrin-releasing peptidein patients with renal and systemic diseases. METHODS: Pro-gastrin-releasing peptide concentrations in sera from normalsubjects and patients with small-cell lung carcinoma, diabetesmellitus, rheumatoid arthritis, systemic lupus erythematosus,chronic glomerulonephritis, or undialysed or dialysed chronicrenal failure were measured with the TND-4 Kit, a newly developedELISA for pro-gastrin-releasing peptide. RESULTS: All of the patients with normal renal function, whether theyhad diabetes mellitus (n=16), rheumatoid arthritis (n=10), systemiclupus erythematosus (n=12) or chronic glomerulonephritis (n=14),had serum pro-gastrin-releasing peptide concentrations lessthan 46 ng/l, the upper limit in normal subjects. In contrast,14 of 16 patients (88%) with small-cell lung carcinoma, whohad normal renal function, and 25 of 26 (96%) patients withchronic renal failure on haemodialysis had serum pro-gastrin-releasingpeptide concentrations greater than 46 ng/l. The highest serumpro-gastrin-releasing peptide levels in patients with chronicrenal failure, before and after initiating haemodialysis were183 and 290 ng/l respectively. Ten of 16 (63%) small-cell lungcarcinoma patients had serum pro-gastrin-releasing peptide concentrationsgreater than 290 ng/l, the highest level in haemodialysed patients.Serum pro-gastrin-releasing peptide concentrations were alsoelevated in patients with chronic glomerulonephritis or diabetesmellitus when their serum creatinine concentrations were greaterthan 120 µmol/l. And, there was a significant correlation,y=23.5+0.15x(n=22, r=0.82, P<0.001), between serum pro-gastrin-releasingpeptide (y, in ng/l) and serum creatinine (x, in µmol/l)concentrations in those patients with renal dysfunction. Thecorrelation between serum pro-gastrin-releasing peptide andserum urea nitrogen concentrations was likewise significant. CONCLUSIONS: The evaluation of patients as to their renal functional statemay be mandatory when serum pro-gastrin-releasing peptide levelsare to be applied as one of the diagnostic tools for small-celllung carcinoma or as a marker monitoring their clinical courses.