MEST-C pathological score and long-term outcomes of child and adult patients with Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN), a small-vessel vasculitis, shares renal pathological features with immunoglobulin A nephropathy. Oxford classification of immunoglobulin A nephropathy pathology has been updated to the MEST-C score, but its application in HSPN remains unresolved. METHODS: Two hundred and thirteen patients with biopsy-proven HSPN were retrieved from the Seoul National University Hospital between 2000 and 2017. Renal outcome risks (i.e., end-stage renal disease or doubling of serum creatinine) were evaluated according to MEST-C scores after stratification by age: 113 children aged < 18 years (9.2 ± 3.6 years) and 100 adults aged ≥18 years (38.6 ± 18.3 years). We pooled our data with four previous cohort studies in which MEST or MEST-C scores were described in detail. RESULTS: Twenty-one child (19%) and 16 adult (16%) patients reached the renal outcome during the median follow-up periods of 12 years and 13 years, respectively (maximum 19 years). In children, M1 and T1/T2 scores revealed worse renal outcomes than did M0 and T0 scores, respectively, whereas the T score was the only factor related to worse outcomes in adult patients after adjusting for multiple clinical and laboratory variables. The pooled data showed that M1, S1, and T1/T2 in children and E1 and T1/T2 in adults were correlated with poorer renal outcomes than those of their counterpart scores. CONCLUSIONS: The Oxford classification MEST-C scores can predict long-term renal outcomes in patients with HSPN.

Antiphospholipid Syndrome Nephropathy and Other Thrombotic Microangiopathies Among Patients With Systemic Lupus Erythematosus.

Antiphospholipid syndrome (APS) and other causes of thrombotic microangiopathy (TMA) negatively impact the renal outcomes of patients with systemic lupus erythematosus (SLE) and lupus nephritis. Here we review the diagnosis and management of occlusive renal vascular lesions due to APS and other TMAs, with a focus on patients with SLE and lupus nephritis. The presence of a thrombotic event, unexplained hypertension, thrombocytopenia, or hemolytic anemia should prompt consideration for TMA syndromes. The differential diagnosis of a TMA in a patient with SLE includes APS, thrombocytopenic purpura, complement-mediated or infection-associated hemolytic uremic syndrome, drug-mediated TMA (particularly due to calcineurin inhibitor toxicity), and malignant hypertension. Treatment of APS with a documented thrombotic event focuses on anticoagulation to reduce the risk for further thrombotic events. Treatment of classic presentations of thrombocytopenic purpura and hemolytic uremic syndrome in the SLE population is the same as in patients without SLE. Treatment of APS nephropathy or TMA when it is diagnosed by biopsy with concomitant lupus nephritis presents a challenge to clinicians because there is no clear standard of care. Small and retrospective studies suggest potential benefit of complement inhibition, mammalian target of rapamycin (mTOR) inhibition, B cell depleting therapy, and plasma exchange therapy for patients with lupus nephritis and TMA, and prospective investigation of these therapies should be a research priority.

Updated Oxford classification and the international study of kidney disease in children classification: application in predicting outcome of Henoch-Schönlein purpura nephritis.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) shares many similarities with IgA nephropathy. We aimed to analyze the predictive value of the International Study of Kidney Disease in Children (ISKDC) classification and the updated Oxford classification for IgA nephropathy in HSPN patients. METHODS: Data of 275 HSPN patients (aged≥14 years) were retrieved, and all of them underwent a renal biopsy. We re-classified the biopsies according to the ISKDC classification and the updated Oxford classification to analyze their correlations with clinical features and renal outcomes. The renal endpoints were defined as ≥30% reduction in baseline estimated glomerular filtration rate (eGFR) in 2 years, doubling of serum creatinine (Scr) or end stage renal disease. RESULTS: During follow-up period of 56(30,86) months, 30(10.9%) patients reached renal endpoints. Segmental sclerosis was the only pathological feature independently associated with renal endpoints (HR 4.086, 95%CI 1.111-15.026, P = 0.034). Tubular atrophy/ interstitial fibrosis was associated with eGFR and Scr levels, and its correlation with renal endpoints was found by univariate analysis. Endocapillary hypercellularity was associated with 24 h urine protein and is of prognostic value in univariate analysis. Mesangial hypercellularity was not associated with clinical features or renal endpoints. Crescents were associated with 24 h urine protein, Scr and eGFR levels, but both ISKDC and updated Oxford classifications of crescents were not associated with renal endpoints by multivariate analysis. CONCLUSIONS: The updated Oxford classification can help in disease management and renal outcome prediction of HSPN.

Different histological classifications for Henoch-Schönlein purpura nephritis: which one should be used?

BACKGROUND: Nephritis is the most important chronic complication of IgA Vasculitis (IgAV)/Henoch-Schönlein purpura (IGAV/HSP) and thus the main prognostic factor of this most common childhood vasculitis. Since the prognosis and treatment selection depends on the mode of interpretation of biopsy material, in this manuscript we have presented several issues related to the uneven application of different histological classifications in IgAV/Henoch-Schönlein purpura nephritis (HSPN). The nephritis of IgAV/IGAV/HSP will be abbreviated as HSPN for this paper. MAIN BODY: In clinical practice we use different histological classifications for HSPN. It is not known which of these classifications best correlates with severity of renal disease and renal outcome in IgAV/IGAV/HSP. One of the major problem with existing histological classifications is that there is no consensus on the implementation of biopsy in the treatment of HSPN. There is a histologic classification system conventionally used in HSPN, of the International Study of Kidney Disease in Children (ISKDC). On the other hand there is the new classification system suggested for IgA nephropathy, the Oxford classification. The latter has been validated only in IgA nephropathy. There are also two further histologic classifications of Haas and Koskela that have been developed. Current treatment strategies in HSPN are not standardised nor predominantly based on histological classification. CONCLUSION: One of the possible solutions to problems related to the application of different histological classification in HSPN is the implementation of multicenter multinational prospective studies with joint collaboration between pediatric rheumatologists, nephrologists and nephropathologists to correlate the clinical features and outcome with the classification systems as well among the classifications. This classification should be the basis for the construction of guidelines for the treatment of patients with HSPN.

The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schönlein purpura nephritis.

BACKGROUND: Histological findings from primary kidney biopsies were correlated with patient outcomes in a national cohort of paediatric Henoch-Schönlein nephritis (HSN) patients. METHODS: Primary kidney biopsies from 53 HSN patients were re-evaluated using the ISKDC (International Study of Kidney Disease in Children) classification and a modified semiquantitative classification (SQC) that scores renal findings and also takes into account activity, chronicity and tubulointerstitial indices. The ISKDC and SQC classifications were evaluated comparatively in four outcome groups: no signs of renal disease (outcome A, n = 27), minor urinary abnormalities (outcome B, n = 18), active renal disease (outcome C, n = 3) and renal insufficiency, end-stage renal disease or succumbed due to HSN (outcome D, n = 5). For the receiver operating characteristic and logistic regression analyses, outcomes A and B were considered to be favourable and outcomes C and D to be unfavourable. The median follow-up time was 7.3 years. RESULTS: The patients with an unfavourable outcome (C and D), considered together due to low patient numbers, had significantly higher total biopsy SQC scores and activity indices than those who had a favourable one (groups A and B). The chronicity and tubulointerstitial indices differed significantly only between group C + D and group A. The difference in areas under the curve between the total biopsy SQC scores and ISKDC findings was 0.15 [p = 0.04, normal-based 95% confidence interval (CI) 0.007-0.29, bias-controlled 95% CI -0.004 to 0.28]. CONCLUSIONS: Our results suggest that the modified SQC is more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Coexisting glomerular IgA deposition and IgG-kappa multiple myeloma.

Multiple myeloma (MM) is a common malignancy that often results in many kinds of kidney injuries for the abnormal monoclonal immunoglobulin. Here, we present an IgG-kappa type MM case accompanied by renal IgA deposition combined with IgG-kappa. The patient was treated with prednisone plus mycophenolate mofetil, and got a satisfactory remission. Although it cannot be determined whether the IgA deposition was secondary to MM, this was the first report of coexisting mesangial proliferative nephritis with IgA deposition and IgG-kappa type MM.

High rabdosiin and rosmarinic acid production in Eritrichium sericeum callus cultures and the effect of the calli on masugi-nephritis in rats.

During an investigation of plant cell cultures that might be useful in the treatment of renal disorders, we established a vigorously-growing E-4 callus culture of Eritrichium sericeum that produced large amounts of caffeic acid metabolites, (-)-rabdosiin (1.8% dry wt) and rosmarinic acid (4.6% dry wt). Elicitation of the calli by methyl jasmonate induced a 38% increase in total polyphenol production. The most efficient method of eliciting (-)-rabdosiin biosynthesis was through the treatment of E-4 calli with cuprum glycerate, which induced an increase in (-)-rabdosiin production of as much as 4.1% dry wt. Oral administration of E-4 callus biomass (100 mg/kg/d for 30 d) to rats with induced Masugi-nephritis caused an increase in diuresis and lowered creatinine excretion and proteinuria levels as compared with Masugi-nephritis untreated rats. While all of the Masugi-nephritis untreated rats began to suffer, near a quarter of the E-4 treated rats remained in good health. This result indicates that the E-4 culture has the potential to alleviate the symptoms associated with nephritis.

Pyelonephritis and interstitial nephritis--clinical-pathological correlations.

AIMS: The relation between histological and clinical parameters were studied in 54 consecutive patients with acute interstitial nephritis or pyelonephritis without primary glomerular disorders, in all of whom percutaneous renal core biopsy had been performed. PATIENTS AND METHODS: Based on clinical criteria and without detailed knowledge of the appearance of the biopsy, the material was divided into 4 main groups: patients with septic and/or tubulotoxic conditions, hypersensitivity reactions (eosinophilic nephritis), ascending infections and other specified conditions. RESULTS: The overall correlation between the histological and the clinical diagnoses was good, but there were large overlaps between the histological findings in 3 of the groups, making classification of individual cases difficult. The histological and paraclinical findings were poorly correlated. Histologically, ascending infections were characterized by the presence of leukocyte casts and an increased number of neutrophilic granulocytes. CONCLUSION: The material justifies the present rough classification of the conditions mentioned above. By kidney biopsy, the interstitial conditions can be separated from glomerular and other conditions, but the biopsy offers little information about the clinical severity or the prognosis.

Henoch-Schönlein nephritis in children and adults. Morphological features and clinicopathological correlations.

Rheumatoid purpura or Henoch-Schönlein syndrome is an IgA vasculitis affecting small vessels. The acute disease progresses by successive flare-ups of limited duration. Long-term prognosis depends mainly on the degree of initial renal damage. A review of the literature shows that renal involvement occurs in about 33% of children and 63% of adults with rheumatoid purpura. The most typical manifestation is segmentary focal glomerulonephritis, always associated with granulous IgA deposits in the mesangium. When renal signs are severe enough to warrant renal biopsy (generally at urine protein > 1 g/d and/or organic renal failure) the risk of developing chronic renal failure is 18% in children and 28% in adults. The best prognostic features are histological. The percentage of crescents, the presence of interstitial fibrosis and the presence of dense sub-epithelial deposits are correlated with risk of chronic renal failure. This risk is high (47%) in children with crescents in more than half the glomeruli. In adults, the percentage of crescents associated with unfavorable course appears to be lower than 50%. Predictions are only valid if no further renal flare-up occurs. In addition, histology cannot precisely predict the course of persistent renal sequelae. The severity of sequelae determines the risk and the rapidity of developing chronic renal failure. It is thus recommended to follow patients with Henoch-Schönlein nephritis for long periods.

[Mesangioproliferative glomerulonephritis with IgM deposits as an independent form of nephritis]. / Mezangioproliferativnyi glomerulonefrit s IgM-depozitami kak samostoiatel'naia forma nefrita.

On the basis of 32 patients examination clinicomorphological characteristics of the mesangioproliferative glomerulonephritis (MPGN) with IgM deposits are given. The conclusion is drawn that MPGN is a distinct unity in the group of primary GN as well as in the group of IgM--nephropathy. The main pathogenetic component of the development of MPGN with IgM deposits is the fixation of IgM, especially in combination with C3. Moderate hypertrophy and hyperplasia of mesangiocytes, mesamgium enlargement and secondary changes in glomeruli characterize MPGN with IgM deposits electron-microscopically and light optically. MPGN with IgM deposits is followed by nephrotic syndrome in 3/4 cases although other clinical forms of nephritis can also take place. In most cases its clinical course is protracted and benign.

Lupus nephritis: classification, clinical features and treatment

Existe gran controversia en la clasificación y manejo del daño renal en pacientes con lupus eritematoso generalizado; por tal motivo, en esta revisión pretendemos uniformar los conceptos clínicos, diagnósticos, histológicos y terapéuticos de la nefropatía lúpica. Definitivamente, el daño renal en pacientes con lupus eritematoso generalizado modifica el pronóstico de la enfermedad, y los hallazgos clínicos y de laboratorio no siempre correlacionan con la lesión glomerular. Actualmente, con la experiencia de los nefropatólogos y reumatólogos es posible optimizar la información obtenida de la biopsia renal, y establecer un pronóstico más acertado. Estamos convencidos que el tratamiento actual de la nefritis lúpica con ciclofosfamida intravenosa y dosis bajas de esteroides, es superior a otras modalidades terapéuticas con una sobrevida superior al 80% a 5 años. En caso de falla al tratamiento se puede intentar plasmaferesis, radiación total nodal y drogas inmunorreguladoras, así como, terapia substitutiva con diálisis o transplante renal

Diagnostic immunopathology of the kidney biopsy in rheumatic diseases.

Nephropathies found in systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, Sjögren's syndrome, and mixed connective tissue disease are discussed. Pathogenetic insights derived from the study of kidney tissue are highlighted and clinicopathologic correlations indicated. The question of whether to perform kidney biopsy in lupus patients is also addressed.

Study of lupus nephritis: its classification and the significance of subendothelial deposits.

This study describes the clinical and pathological characteristics of 74 patients with lupus nephritis classified according to renal biopsy findings using light, electron and immunofluorescent microscopy, and further, assesses the significance of subendothelial deposits in evaluating disease activity. In membranous lupus nephritis (14 cases), many cases showed normal renal function even with the nephrotic syndrome, although five cases had little or no urinary abnormalities. Glomerular cellular proliferation was very mild and subepithelial deposits with a few mesangial deposits were the main pathological alterations. Mesangial proliferative lupus nephritis (17 cases) clinically had very mild renal disease. Renal biopsies in this group revealed mesangial deposits with slight cellular proliferation. Although clinical features of mild diffuse proliferative lupus nephritis (16 cases) were similar to those of mesangial lupus nephritis, glomerular loop deposits were seen in addition to mesangial deposits. In moderate diffuse proliferative lupus nephritis (17 cases), renal function was slightly decreased, moderate proteinuria with haematuria were found, and C3 level was low. Renal biopsies showed active proliferative changes, and subendothelial deposits were frequently seen. In severe diffuse proliferative lupus nephritis (10 cases), the duration from onset of SLE to renal biopsy was short. Impairment of renal function, and nephrotic syndrome with haematuria and hypocomplementemia were frequent. Only three patients survived in this group. Renal biopsies demonstrated highly active proliferative and necrotizing changes, and electron microscopy showed massive subendothelial and mesangial deposits accompanied by subepithelial and intramembranous deposits. The amount of subendothelial deposits correlated with those of mesangial deposits and subepithelial deposits in the cases with diffuse proliferative lupus nephritis. Urinary protein loss and histologic activity showed statistically significant correlations with the amount of subendothelial deposits, but C3 levels and creatinine clearance revealed negative correlations with those deposits.

Clinical usefulness of the morphological classification of lupus nephritis.

The renal biopsy technique has made it possible to classify lupus nephritis into its varied forms. Utilizing light histology, immunofluorescence microscopy, and ultrastructural techniques, the following renal morphological manifestations of systemic lupus erythematosus can be identified: mesangial abnormalities; focal proliferative, diffuse proliferative and membranous glomerulonephritis; glomerular sclerosis; interstitial nephritis; vascular sclerosis and necrotizing renal vasculitis. Each of the morphological forms is associated with distinctive clinical features and prognosis. Mesangial and focal proliferative lupus nephritis may occur in the absence of clinical abnormalities, and in general have a favorable prognosis. Diffuse proliferative lupus nephritis often is manifested by the nephrotic syndrome and renal functional impairment which proves to be irreversible and progressive. Transition from the milder forms to diffuse proliferation occurs in about one-sixth of patients. Membranous lupus nephritis is characterized by the nephrotic syndrome, which often is persistent, but renal functional impairment develops slowly and is rarely severe. Necrotizing vasculitis, which supervenes on occasion during the course of diffuse proliferative lupus nephritis, produces the clinical picture of malignant hypertension and progresses rapidly to uremia. Interstitial nephritis usually occurs in combination with one of the glomerular forms, but at times may be the predominant renal lesion both morphologically and clinically. Glomerular sclerosis, often associated with hypertension and vascular sclerosis, commonly develops in the course of lupus nephritis, especially in the more severe forms, and may progress even though active disease has remitted. An awareness of clinico-pathologic correlations in lupus nephritis provides a basis for intelligent management and critical assessment of therapy.

[Lupus nephritis: clinicomorphological manifestations (author's transl)]. / Nefropatía lúpica: manifestaciones clínicas y morfológicas.

Forty patients with systemic lupus erythematosus have been evaluated for clinicopathological evidence of renal involvement. Average age at the onset of the disease was 23 years; 90 percent of the patients were women. Indications for renal biopsy included clinical symptoms of nephropathy (34 patients) and signs of immunological activity (6 patients(. All biopsied specimens were examined under light microscope; 28 of them under immunofluorescence, and 18 under electron microscope. Histological classification was as follows: I) Normal kidney (2 patients); II) mesangial glomerulonephritis (6 patients); III) focal glomerulonephritis (10 patients); IV) diffuse proliferative glomerulonephritis (19 patients), and V) membranous glomerulonephritis (3 patients). Six patients had no clinical nephritis, two of them had normal kidneys and four had a mesangial glomerulonephritis. Patients in groups III, IV, and V showed clinical and biological evidence of renal involvement. Highest incidence of renal failure, nephrotic syndrome or high blood pressure was found among cases in group IV. Group IV accounted also for the highest mortality rate. Clinical course of 25 cases (1 of type II, 8 or type III, and 16 of type IV) on corticosteroid therapy for an average follow-up of 22.8 months has showed greater clinical improvement (proteinuria and renal function) of nephropathy type III than nephropathy type IV. Renal biopsy is a useful diagnostic and prognostic method in patients with systemic lupus erythematosus, even in those cases without clinical evidence of renal disease.

Prognosis of Henoch-Schönlein nephritis in children.

All the survivors of a series of 88 patients with Henoch-Schönlein nephritis were examined after a follow-up of six and a half to 21 years (mean 9-9). Sixty-one patients had no demonstrable abnormality; six had minor urinary abnormalities; five had hypertension without urinary abnormally or renal dysfunction; four had heavy proteinuria; eight were in chronic renal failure, three of whom were on regular dialysis; and four patients had died within 25 months of onset. Neither corticosteroids nor immunosuppressive drugs alone or in combination appeared to influence the outcome. A clinical presentation with a combination of acute nephritis and a nephrotic syndrome and a high proportion of crescents in renal biopsy specimens was associated with a poor outcome. Neither the clinical presentation nor the renal morphology were, however, precise determinants of outcome. Outcome was not related to age, associated streptococcal infection, or recurrences of the rash. The clinical state two years after presentation was compared with the state six and a half years or more after presentation in 76 patients. The clinical state had changed in 32 patients, in 17 of whom it had deteriorated. It was not possible to identify with any certainty the patients who would deteriorate (or improve). Patients who have had Henoch-Schönlein nephritis should be followed up for at least five years.