Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.
lupus; nephritis; nephropathy; glomerulonephritis; treatment; therapy; women
Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury.
Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK.
Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7×10−9, OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (p <0.0001). An additional six genes showed an association with lupus nephritis with p <0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6×10−3 and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.
A prospective study of 110 patients with systemic lupus erythematosus (SLE) was undertaken to evaluate the reliability of clinical signs of lupus nephritis, which developed in 39 (35%) patients. Those patients with SLE who showed no clinical signs of lupus nephritis had an excellent survival rate (10 year survival 93%) and retained normal renal function (serum creatinine less than 130 mumols/l); clinical lupus nephritis developed mainly in the first three years after diagnosis of SLE and was associated with a decreased survival rate (10 year survival 62%). Increased mortality was found in male patients with lupus nephritis over 25 years of age and in female patients with lupus nephritis under 25 years of age, while renal failure rates did not differ between these groups. Treatment of lupus nephritis with high dose prednisone alone or in combination with immunosuppressants did not result in differences in patient survival or renal function preservation. It was concluded that clinical variables are a reliable guide in the management of patients with SLE, and routine use of renal biopsy in these patients is rejected.
About 50-80% of patients with lupus suffer from lupus nephritis which is one of major causes of morbidity and mortality. Renal pathologists and nephrologists should evaluate the degree of histological damages to establish therapeutic plans for lupus nephritis. In order to standardize definitions, to emphasize clinically relevant lesions, and to improve interobserver reproducibility, the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification was proposed. Recently, several retrospective validation studies concerning the utility of the ISN/RPS classification, especially among class IV, were performed. In these reports, reproducibility is improved by the definition of diagnostic term, but the outcome related with classification, especially in class IV, is controversial. We performed retrospective analysis of 99 biopsy-proven subjects with lupus nephritis in our facility using the ISN/RPS classification. The class IV-G group tended to exhibit a worse renal outcome, but the difference compared with IV-S was not significant. In a Cox proportional hazards models, Independent histological predictors of poor renal outcome were extracapillary proliferation, glomerular sclerosis and fibrous crescents, while hyaline thrombi and fibrous adhesions were of favorable renal outcome. Both were similarly observed in IV-G and IV-S. The more qualitative categorization by the response to standard treatment may be needed to emphasize clinically relevant lesion related to renal outcome.
ISN/RPS Classification; Lupus; Lupus Nephritis; Outcome
Sixty two children were included in a collaborative study to determine the prognosis for lupus nephritis. Renal involvement was confirmed by histologic study of renal biopsy specimens which were classified into five categories: minimal lesions (11 cases, 18%); focal segmental glomerulonephritis (15, 24%); diffuse proliferative glomerulonephritis (30, 48%); membranous nephropathy (5, 8%); and glomerular sclerosis (1,2%). That the predictive value of the early biopsy is limited was indicated by the most recent status of 37 patients five years after onset--total remission (13, 35%); urinary abnormalities or nephrotic syndrome (7, 19%); moderate renal failure (4, 11%); chronic renal failure (7, 19%); and hypertension (6, 16%). Treatment did not always prevent the development of severe renal failure; in particular, plasmapheresis failed to avert the death of one patient and the development of chronic renal failure in two others.
Four patients with proliferative glomerulonephritis due to systemic lupus erythematosus were treated with intravenous methyl prednisolone 'pulse' therapy. In all, eight courses of therapy were given, three for acute oliguric renal failure; and on each occasion there was a good response to the treatment. Clinical, histological and immunological details of the patients are presented. The diagnosis, treatment, and monitoring of disease activity in lupus nephritis are discussed in the light of this experience.
A 35-year-old Caucasian woman with proven systemic lupus erythematosus (SLE) had been effectively managed with hydroxychloroquine and methylprednisolone for many years. In 2005 she was admitted to the rheumatology clinic with a flare up of the disease and with proteinuria of 3.2 g/24 h. Renal biopsy was performed and revealed diffuse proliferative nephritis. Before the renal biopsy a positive HBsAg was found with high virus replication (hepatitis B virus (HBV)-DNA—4 170 000 copies/ml). Liver biopsy revealed chronic hepatitis with minimal activity (TAIS=1). Lamivudine was administered with concomitant maintenance corticosteroid treatment, but without antimalarials. Pulsed methylprednisolone treatment for diffuse lupus nephritis was begun on the background of lamivudine therapy. The liver enzymes returned to normal values, HBV replication was suppressed, and the proteinuria disappeared. At present the patient is not being treated with lamivudine and there are no objective signs of nephritis and hepatitis, or HBV activation.
Kidney involvement in non-Hodgkin lymphoma is well recognized and glomerulonephritis, when present, has been commonly reported to be associated with a membranoproliferative pattern.
We report a case of a 58-year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis. She underwent a renal biopsy that showed a severe diffuse proliferative and exudative lupus-like glomerulonephritis, which is likely paraneoplastic in nature. We discuss the differential diagnosis and possible pathogenesis of glomerular injury in lymphoma-related proliferative glomerulonephritis.
Differentiating between true lupus nephritis and a paraneoplastic glomerulonephritis is important, as it would have significant implications on treatment and clinical course.
Non-Hodgkin lymphoma; Lupus-like nephritis; Paraneoplastic; Renal failure
Genetic and environmental factors contribute in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis, the most common and severe manifestation of SLE, involves inflammation in the kidney leading to loss of renal function. However, it is not clear what controls the progression of lupus nephritis; this is an important research question, considering its implications in clinical treatment of lupus nephritis. Finding genes that underlie the development and progression of lupus nephritis will shed light on this question. NZM2328 is a spontaneous mouse model for SLE. Most NZM2328 female mice develop autoantibodies (e.g., antinuclear antibody and anti-dsDNA antibody), glomerulonephritis (GN), and severe proteinuria between 5 and 12 months of age. In contrast, C57L/J mice fail to exhibit similar signs of autoimmune disease. We used classical genetics to map and identify SLE genes in offspring generated by backcrossing C57L/J to NZM2328. Quantitative trait loci (QTL) controlling acute (Agnz1 and Agnz2) and chronic (Cgnz1) GN features were uncovered by the analysis. To verify the Cgnz1 and Agnz1 on distal mouse chromosome 1, we produced the NZM23238.C57Lc1 (Lc1) congenic strain, which replaced NZM2328 Cgnz1 and Agnz1 alleles with those derived from C57L/J. The development of acute GN and chronic GN was markedly reduced in Lc1 mice, confirming the linkage findings. Further mapping by the generation of intrachromosomal recombinants of NZM2328.Lc1 support the thesis that acute GN and chronic GN are under separate genetic control.
Congenic strain; End-stage renal disease; Genetic mapping; Genotyping; Glomerulonephritis; Linkage analysis; Lupus nephritis; Marker-assisted selection protocol; Microsatellite marker; NZM2328; Quantitative trait loci; QTL mapping; Speed congenic; Systemic lupus erythematosus
23 of 42, or 55%, of patients with systemic lupus erythematous had immunoglobulin deposits along the epidermal basement membrane of uninvolved skin (positive lupus band test [LBT]). In patients with low serum complement levels, 91% had a positive LBT), as compared with 15% in those with normal complement levels. The LBT was positive in 70% of patients with clinical and laboratory evidence of renal disease, but in only 31% of patients without renal disease. 81% of patients with the more severe histologic forms of lupus nephritis, i.e., proliferative glomerulonephritis and membranous glomerulonephritis, and positive tests, whereas only 23% with mesangial glomerulitis or normal histologic findings were positive. Immunoglobulins of the same class found in the skin were detected in the glomeruli of patients examined by renal biopsy. These results suggest that there is a relationship between the occurrence of immunoglobulin in the epidermal basement membrane and the presence of the more severe forms of lupus nephritis.
Systemic lupus erythematosus is a chronic autoimmune disease frequently affecting the kidney. Renal involvement is characterized by glomerular immune complex deposits, and proliferative glomerulonephritis progressing to glomerulosclerosis and kidney failure. Development of systemic lupus erythematosus is genetically regulated and lupus susceptibility genes have been linked to immune hyper-responsiveness and loss of immune regulation. In addition to the systemic immune defects, recent studies in animal models show that susceptibility to lupus nephritis is influenced by intrinsic renal factors. Thus, renal cell responses to immune-mediated glomerular injury determine disease outcome. This supports the idea that future treatments for lupus nephritis need to focus on regulating end organ responses. The feasibility of this approach has been demonstrated in animal models of kidney disease. For over 50 years, the emphasis in management of lupus nephritis has been suppression of autoimmune responses and systemic control of inflammation. This review describes recently developed targeted drug delivery technologies and potential targets that can regulate glomerular cell responses offering a novel therapeutic approach for lupus nephritis.
Mesangial cells; glomerulonephritis; immunoliposomes; glomerular targeting; mouse models; gene therapy; lupus nephritis
We investigated nationwide prevalence, incidence, and sociodemographics of SLE and lupus nephritis among Medicaid-enrolled children.
Children aged 3 to <18 years with SLE (≥3 International Classification of Diseases, 9th Revision, codes of 710.0, all >30 days apart) were identified from Medicaid Analytic eXtract data (2000–2004), containing all inpatient and outpatient Medicaid claims for 47 U. S states and the District of Columbia. Lupus nephritis was identified from ≥2 ICD-9 billing codes >30 days apart for glomerulonephritis, proteinuria or renal failure. We calculated prevalence and incidence of SLE and lupus nephritis among Medicaid-enrolled children overall and within sociodemographic groups.
Of 30,420,597 Medicaid-enrolled children during these years, 2,959 with SLE were identified. SLE prevalence was 9.73 (95% CI 9.38 – 10.08) per 100,000. Of these, 84% were female, 40% African-American, 25% Hispanic and 21% White; 42% resided in the South. 1,106 (37%) of children with SLE had lupus nephritis: prevalence 3.64 (95% CI 3.43 – 3.86) per 100,000. The average annual incidence of SLE was 2.22 (95% CI 2.05–2.40) and that of lupus nephritis was 0.72 (95%CI 0.63– 0.83) cases per 100,000 Medicaid enrollees per year. Prevalence and incidence rates of lupus and lupus nephritis increased with age, were higher in girls than boys, and in all non-White than White racial/ethnic groups.
SLE prevalence and incidence rates among Medicaid-enrolled children in the U.S. are high compared to studies in other populations. These represent the first population-based estimates of lupus nephritis prevalence and incidence in the U.S. to date.
Systemic lupus erythematosus; pediatric; nephritis; incidence; prevalence; Medicaid; children; disparities
Objective: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).
Methods: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing.
Results: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group.
Conclusions: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.
Human immunodeficiency virus (HIV)-associated lupus-like glomerulonephritis (GN) is a chronic immune complex disease occurring in HIV-infected patients. Although the light, immunofluorescence, and electron microscopy findings indicate features of lupus nephritis, no evidence of systemic lupus erythematosus (SLE) is observed in the affected patients. We present the case of a 45-year-old Caucasian woman with HIV infection who was admitted to the hospital with a nephrotic syndrome 10 years after the HIV diagnosis. A renal biopsy revealed HIV-associated lupus-like GN and necrotizing arteritis affecting two interlobular arteries. Necrotizing arteritis is a type of renal vasculopathy associated with SLE, but has not been reported previously in HIV-associated lupus-like GN. In this case, necrotizing arteritis was found to be a histological feature common to both HIV-associated lupus-like GN and SLE. This histological finding reinforces the resemblance between HIV-associated lupus-like GN and nephritis caused by lupus.
HIV; glomerulonephritis; necrotizing arteritis
The term Pulmonary–renal syndrome refers to the combination of diffuse alveolar haemorrhage and rapidly progressive glomerulonephritis. A variety of mechanisms such as those involving antiglomerular basement membrane antibodies, antineutrophil cytoplasm antibodies or immunocomplexes and thrombotic microangiopathy are implicated in the pathogenesis of this syndrome. The underlying pulmonary pathology is small-vessel vasculitis involving arterioles, venules and, frequently, alveolar capillaries. The underlying renal pathology is a form of focal proliferative glomerulonephritis. Immunofluorescence helps to distinguish between antiglomerular basement membrane disease (linear deposition of IgG), lupus and postinfectious glomerulonephritis (granular deposition of immunoglobulin and complement) and necrotizing vasculitis (pauci-immune glomerulonephritis). Patients may present with severe respiratory and/or renal failure and require admission to the intensive care unit. Since the syndrome is characterized by a fulminant course if left untreated, early diagnosis, exclusion of infection, close monitoring of the patient and timely initiation of treatment are crucial for the patient's outcome. Treatment consists of corticosteroids in high doses, and cytotoxic agents coupled with plasma exchange in certain cases. Renal transplantation is the only alternative in end-stage renal disease. Newer immunomodulatory agents such as those causing TNF blockade, B-cell depletion and mycophenolate mofetil could be used in patients with refractory disease.
Malignancies are more common in patients with systemic lupus erythematosus (SLE) than the general population. SLE patients are recognized to have higher prolactin levels. However, there are very few reported cases of SLE with pituitary adenomas.
We report the second case of a pituitary adenoma in a patient with underlying SLE. A 51 year old lady presented with blurred vision and magnetic resonance imaging of the brain demonstrated a pituitary macroadenoma with mildly elevated serum prolactin levels. The diagnosis of a non functioning pituitary macroadenoma was confirmed histologically. The diagnosis of SLE was made on the basis of thrombocytopenia, antinuclear antibodies, anti double stranded DNA antibodies and lupus nephritis (confirmed on renal biopsy). The patient initially received medical therapy with carbegoline, followed by transsphenoidal neurosurgery for the pituitary macroadenoma. SLE with lupus nephritis was treated with steroids and low dose intravenous cyclophosphamide.
Hyperprolactinaemia is prevalent in twenty to thirty percent of SLE patients but it is rarely due to a prolactinoma. The source of excessive circulating prolactin in SLE patients has not been fully determined.
pituitary macroadenoma; systemic lupus erythematosus; prolactin
The pattern of glomerular diseases in northwest Iran is unknown. This study was conducted to evaluate the histological pattern of renal diseases in this region.
Methods: We retrospectively studied the reports of 266 native adult renal biopsies at the Imam Reza and Taleghani Hospitals from June 2007 to June 2012. Pathological findings include minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), mesangioproliferative glomerulonephritis (MPGN), mesangiocapillary glomerulonephritis (MCGN), post streptococcal proliferative glomerulonephritis (PSPGN), membranous glomerulonephritis (MGN), hypertensive nephropathy (HN), crescentic glomerulonephritis or rapid progressive glomerulonephritis (CGN or RPGN), chronic tubular interstitial necrosis (CTIN), chronic sclerosing glomerulonephritis (CGN), Alport syndrome, acute tubular necrosis (ATN), lupus nephritis, renal amyloidosis. The data were collected and analyzed.
Results: The mean age of the patients was 37.41±15.78 years. Nephrotic syndrome was observed in 155 (58.3%) cases which was higher in frequency in females (61.9%) (p<0.005), followed by renal insufficiency in 87 (32.7%) cases. Totally, 187 (70.3%) had primary glomerulonephritis (GN) whereas, 79 (29.7%) had secondary GN. MCD was found to be the most common histological pattern (44%) and CGN (1.12%) was the least common. The frequencies of secondary glomerulonephritis (GN) include lupus nephritis to be the most frequent (41.8%) followed by chronic tubulo interstitial nephritis (38%) and type II diabetic nephropathy (19%).
Conclusion: The results showed that minimal change disease ranked first followed by focal segmental glomerulosclerosis. We hope that this will form the basis for developing a renal biopsy registry across the continent in Iran.
Renal biopsy; Adult renal disease; kermanshah
Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).
Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.
Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).
This pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.
Systemic sclerosis or scleroderma is an autoimmune rheumatic disease characterized by organ-based fibrosis. Renal involvement in scleroderma occurs mainly in the form of scleroderma renal crisis, affecting 5 to 10% of patients. It remains one of the most important and immediately life-threatening complications of scleroderma, but the prognosis improves considerably after treatment with angiotensin-converting enzyme inhibitors. Other renal pathologies can occur in scleroderma. These include scleroderma overlap syndromes with associated features of lupus nephritis, myeloperoxidase anti-neutrophil cytoplasmic antibodies (ANCA) or proteinase 3 ANCA-associated glomerulonephritis, or crescentic glomerulonephritis. These alternative pathologies should be suspected in any individual patient with a differing clinical picture and the patient should be appropriately investigated. Crescentic glomerulonephritis occurs very rarely in scleroderma. This report describes a patient with scleroderma and crescentic glomerulonephritis.
A 52-year-old woman with a known history of scleroderma and hypertension on angiotensin-converting enzyme inhibitors was referred to the nephrologist because of a rapid decline in renal function. Kidney biopsy was performed which revealed immune complex type crescentic glomrulonephritis. Cytoplasmic-staining ANCA was negative. Despite immunosuppressive treatment the patient rapidly went into end-stage renal failure and is still on hemodialysis.
Scleroderma is a complex disease, and the best characterized renal involvement in scleroderma is scleroderma renal crisis. However, other renal pathologies can occur in scleroderma. These alternative pathologies should be suspected in any patient with a differing clinical picture and the patient should be appropriately investigated, as the clinical course and treatment are different from the more common scleroderma renal crisis.
Twenty-seven adults with acute poststreptococcal glomerulonephritis were divided into two groups according to the severity of reduction in renal function: (1) 14 patients with mild depression of renal function, and (2) 13 patients with more severe renal insufficiency. In the first group the outcome was favourable, with complete clinical recovery in 11 patients. Only two patients in the second group have recovered. Five have died of renal failure and in six the chronic stage has developed. The most notable histopathological lesion observed in this group of patients was severe proliferative glomerulonephritis with a large number of epithelial crescents. According to the mode of development and time of onset of renal failure, these 13 patients could be divided into three sub-groups: (1) early renal failure without oliguria (three patients), (2) early renal failure with severe oliguria or anuria (three patients) and (3) delayed renal failure (seven patients).
Although there are exceptions, the development of renal insufficiency in an adult patient suffering from acute glomerulonephritis is usually associated with a guarded prognosis.
Introduction. The diagnosis of systemic lupus erythematosus (SLE) in patients with sickle cell disease (SCD) can be difficult to establish because the musculoskeletal, central nervous system, and renal manifestations are similar in both diseases. In the presented case, we highlight the diagnostic challenge that can evolve in patients with a concurrence of both diseases and we establish the importance of early recognition and treatment of lupus nephritis in patients with SCD. Case Presentation. We present a case of a 31-year-old African American female with sickle-C disease (hemoglobin SC) who was admitted to our hospital with complaints of periumbilical abdominal pain associated with intractable nausea and vomiting, abdominal distension, and worsening lower extremity edema. Urine studies revealed nephrotic range proteinuria and the immunological investigations were consistent with lupus. A renal biopsy revealed focal proliferative lupus nephritis. Conclusion. It is important to consider the presence of a coexisting autoimmune disease in a patient with sickle hemoglobinopathy who displays an atypical and multisystem presentation that is unresponsive to conventional therapies. When a significant kidney disease is present, a renal biopsy is critical in identifying the etiology of a renal abnormality in the setting of coexisting SLE and SCD.
A 16-year-old boy developed an immune complex illness associated with lung haemorrhage, proliferative nephritis with crescents and renal failure. Treatment with plasma exchange, haemodialysis and immunosuppressive drugs resulted in a rapid reduction in levels of immune complexes and other mediators of inflammation and was associated with good recovery of renal and lung function. Subsequently, deterioration in renal function occurred whilst the patient was on treatment with prednisolone alone but this was reversed with a short course of plasma exchange and the addition of azathioprine. No further deterioration in renal or lung function has been observed during 18 months treatment with azathioprine and prednisolone. Immediate plasma exchange and immunosuppressive drug treatment have been recommended for Goodpasture's syndrome. Immune complex mediated lung haemorrhage and nephritis is the main clinical differential diagnosis. Our case suggests that the same treatment is effective for both conditions if given early, and that detailed renal and immunological investigations should not be allowed to delay this.
Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β1 is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β1 levels in patients with crescentic nephritis could be used as a marker of response to treatment.
Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β1 was estimated in biopsy sections by immunohistochemistry and urinary TGF-β1 levels were determined by quantitative sandwich enzyme immunoassay (EIA). TGF-β1 levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange). Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls.
Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively). In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β1 levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p < 0.01). TGF-β1 was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β1 immunostaining with the presence of fibrocellular cresents was observed (r = 0.531, p < 0,05).
Increased TGF-β1 renal expression and urinary excretion that is related to the response to immunosuppressive therapy was observed in patients with crescentic nephritis. Evaluation of urinary TGF-β1 levels may be proved a useful marker of clinical outcome in patients with crescentic nephritis.
A 14-year-old male presented with bilateral papilledema, growth retardation and absent secondary sexual characters. He had a past history of fever, headache and fatigue of 6 months duration. The diagnosis of intracranial hypertension (IH) was confirmed by an increased intracranial pressure and normal neuroimaging studies of the brain, except for partial empty sella, prominent perioptic cerebrospinal fluid (CSF) spaces and buckling of optic nerves. Evaluation showed erythrocyte sedimentation rate (ESR) of 150 mm/hr, positive antinuclear antibody (ANA), anti dsDNA and anti ribosomal P protein. Renal biopsy revealed diffuse segmental proliferative lupus nephritis (LN) class IV S (A) confirming the diagnosis of systemic lupus erythematosus (SLE). Treatment of LN with intravenous pulse methyl prednisolone and cyclophosphamide was effective in normalizing the CSF pressure, resulting in express and dramatic resolution of symptomatology. In a case of IH, SLE must be considered. IH, growth retardation and absence of sexual characters may be presenting manifestations of a chronic systemic inflammatory disease like SLE. These manifestations may act as a pointer to associated advanced grades of LN, which can be totally asymptomatic and missed without a renal biopsy.
Anti dsDNA; anti ribosomal P protein; lupus nephritis; pseudotumor cerebri; systemic lupus erythematosus