Prognostic indices and therapy in IgA nephropathy: toward a solution.

IgA nephropathy is the primary renal disease with the greatest impact on services. The paucity of trials with high evidence-based standards gives emphasis to issues of the rationalization of therapies. Now that certain treatments are increasingly accepted and others under evaluation, reliable discriminatory tests are essential to define and select patients at high risk of progression before irreversible loss of renal tissue, while avoiding drug exposure in others.

Quantitative appraisal of treatment options for IgA nephropathy.

IgA nephropathy has an impact on renal health care costs worldwide. The paucity of good clinical trials highlights the uncertainty in determining best treatment and for how long. Ongoing debate still raises questions on why opinions vary but may suggest that current data are not fully understood.

Mesangial autoantigens in IgA nephropathy: matrix synthesis and localization.

Primary IgA nephropathy, a chronic nephritis with variable prognosis, is characterized by mesangial immunoglobulin A, frequently with codeposition of other immunoglobulin isotypes and complement components accompanying matrix expansion typically preceding glomerular scarring. Glomerular immunoglobulin G, when present, is localized to the mesangial periphery found variably in repeat biopsies. IgG anti-mesangial cell autoantibodies (IgG-MESCA) in sera of patients with IgA nephropathy, specific by F(ab')(2) binding to 48- and 55-kD autoantigen(s) could account for these deposits, but their in vivo localization, and the functional role in promoting scarring is unknown.

Henoch Schönlein purpura with nephritis in adults: adverse prognostic indicators in a UK population.

Background: Henoch Schönlein purpura with nephritis (HSN) in adults may cause severe organ injury, but its rarity has contributed to a lack of data.

Aim: To evaluate clinical outcomes and risk factors in adult HSN patients.

Design: Retrospective analysis.

Primary angiitis of the central nervous system: emerging variants.

Background: Primary angiitis of the central nervous system (PACNS), a serious disease, has not featured prominently in the spectrum of multi-organ disease seen in vasculitis clinics.

Aim: To evaluate the presentation, natural history and features of PACNS variants and compare to those of systemic vasculitides.

Design: Retrospective analysis.

Biphasic hypercalcemia in severe rhabdomyolysis: serial analysis of PTH and vitamin D metabolites. A case report and literature review.

Calcemic fluxes with hypocalcemia leading to hypercalcemia in acute rhabdomyolisis are poorly understood. Analyses in the literature of the factors modulating the blood calcium level include 2, possibly 3 systems. Conflicting results implicate the parathyroid hormone and vitamin D metabolites, but additional contribution from skeletal and muscle calcium ion deposition and dissolution have been cited in some cases, potentially even dominating control of blood calcium during recovery.

Controlled prospective trial of prednisolone and cytotoxics in progressive IgA nephropathy.

In a single-center, multiple-referral source study, 38 patients with progressive IgA nephropathy and controlled hypertension were randomized to treatment with prednisolone and cytotoxic agents, to therapy with low-dose cyclophosphamide then azathioprine, and to control groups. The follow-up period lasted 2 to 6 yr. Renal survival, as assessed by Kaplan-Meier analysis annually to 5 yr, showed significant preservation of function from 3 yr in the treatment group and 82, 82, 72, and 72% for 2, 3, 4, and 5 yr, respectively, compared with 68, 47, 26, and 6% in controls.

Characterization of two corneal epithelium-derived antigens associated with vasculitis.

Purpose: In a previous investigation into corneal autoimmunity, it was demonstrated that a putative autoantigen, a protein of 66 kDa, present in bovine corneal epithelium, binds circulating autoantibodies in approximately 60% of patients with Wegener's granulomatosis (WG). The aim of the present study was to characterize and identify the 66-kDa protein.

Methods: A purification protocol was established for the 66-kDa protein using standard chromatography techniques.

Effect of low-dose cyclosporin on plasma lipoproteins and markers of cholestasis in patients with psoriasis.

The benefits of using cyclosporin in organ transplantation to prevent graft rejection outweigh its potential disadvantages, but with the use of low-dose cyclosporin in relatively healthy individuals, such as those with psoriasis, the risk:benefit ratio is altered. The effects of low-dose cyclosporin (< 5 mg/kg body weight) on liver function and serum lipids and lipoproteins were examined in 40 normolipidaemic, normotensive psoriasis patients with normal renal function. After 3 months of treatment, serum cholesterol and bilirubin concentrations and alkaline phosphatase activity increased significantly (p = 0.

Angiotensin II as a risk factor for cyclosporin nephrotoxicity in patients with psoriasis.

Abnormalities of the renin-angiotensin system after low-dose cyclosporin (5 mg/kg/day or less) have not been adequately defined in patients with normal kidneys. 27 patients with psoriasis were assessed before starting cyclosporin, after three months of cyclosporin (5 mg/kg/day or less) and then finally three months after finishing cyclosporin. On each occasion plasma renin activity (PRA), aldosterone, angiotensin II and atrial natriuretic peptide (ANP) were measured together with total renal blood flow (RBF), GFR and filtration fraction (FF) following an i.

Cyclosporin A and vitamin D metabolism: studies in patients with psoriasis and in rats.

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxyvitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D.

Altered clearance of N-1 methylnicotinamide associated with the use of low doses of cyclosporine.

To improve the monitoring of patients on low doses of cyclosporine there is a need for new tests of tubular function. N-1 methylnicotinamide (NMM) is an endogenous organic cation that is secreted by the proximal tubule and its clearance can be measured. In 27 patients with psoriasis, serial measurements of NMN clearance, plasma aldosterone, plasma chloride, bicarbonate, and magnesium were compared with changes in the radionuclide measurement of glomerular filtration rate and renal blood flow before, during, and after a 3-month course of low-dose cyclosporine (< 5 mg/kg/d).

Renal function does not always predictably deteriorate in blind insulin-dependent diabetics with nephropathy.

Two insulin-dependent diabetic women with severe retinopathy who were referred for the management of nephrotic syndrome are presented. On the basis of clinical risk factors, such as retinopathy and severe hypertension, both patients were expected to develop progressive end-stage renal failure. One woman has shown a gradual decline in creatinine clearance over 7 years while the plasma creatinine of the other has remained normal for 11 years.

Intrarenal cytokine mRNA expression and location in normal and IgA nephropathy tissue: TGF alpha, TGF beta, IGF 1, IL-4 and IL-6.

Peptide regulatory factors (PRFs) are critical components in the regulation of glomerular inflammatory response to immune injury and may also have a primary role in modulating intrinsic cell proliferation and matrix synthesis. Dysregulation of PRFs and glomerular infiltration with inflammatory, including mononuclear, cells occur in models of nephritis, but direct evidence for their role is not established in normal and diseased tissue in man. Using in situ hybridization techniques capable of detecting specific cellular messenger RNA we have evaluated normal human and IgA nephropathy diseased renal tissue for expression and location of PRF encoding mRNA.

Interrelationship between serum concentrations of 1,25-dihydroxyvitamin D, parathyroid hormone and renal haemodynamics after low dose cyclosporin.

It is unclear whether cyclosporin A (CsA) alters the synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] by the normal human kidney. Serial changes in 1,25(OH)2D, parathyroid hormone (PTH), GFR and renal blood flow were compared in 14 patients with psoriasis who were being treated with less than 5 mg/kg/day of cyclosporin for 3 months. GFR fell significantly although there were no significant changes in serum 1,25(OH)2D, 25-hydroxyvitamin D or PTH.

Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy.

Dysregulated cytokine expression has been implicated in the pathogenesis of IgA nephropathy, but the mechanisms and selectivity of this response are poorly understood. In this study we have examined the expression of a range of immunoregulatory cytokine mRNAs by peripheral blood mononuclear cells (PBMNCs) from 45 patients with IgA nephropathy stratified empirically according to urinary red cell excretion: 10 in remission, and 35 with active disease (21 mild, 14 moderate), and 17 normal, and 15 disease, controls. We used a semi-quantitative polymerase chain reaction (PCR) technique.

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

Aim: To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules.

Methods: Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin.

Modulation of abnormalities in renal haemodynamics and vasoactive mediators by nifedipine in patients with psoriasis on low-dose cyclosporin.

Ten patients with psoriasis received a 3-month course of cyclosporin (2.5 mg/kg/day) followed by a 3-month washout period, before commencing a 3-month course of cyclosporin and nifedipine SR 20 mg b.d.

The detection of intracytoplasmic interleukin-1 alpha, interleukin-1 beta and tumour necrosis factor alpha expression in human monocytes using two colour immunofluorescence flow cytometry.

Two colour flow cytometry was used to analyse in situ cytokine expression by human monocytes. Whole blood was cultured in siliconised glass bottles, with or without E. coli lipopolysaccharide (LPS), for various times, and the mononuclear cells (MNCs) then exposed to a variety of permeabilisation procedures prior to flow cytometric analysis.

Autoimmunity to glomerular antigens in Henoch-Schoenlein nephritis.

1. Henoch-Schoenlein nephritis and IgA nephropathy share clinical and immunological features, but the pathogenesis of neither condition is established. We have recently described IgG autoantibodies to glomerular components in active IgA nephropathy and have now sought evidence for a similar autoimmune component in Henoch-Schoenlein purpura.