Lupus nephritis: the evolving role of novel therapeutics.

Immune complex accumulation in the kidney is the hallmark of lupus nephritis and triggers a series of events that result in kidney inflammation and injury. Cytotoxic agents and corticosteroids are standard of care for lupus nephritis treatment, but are associated with considerable morbidity and suboptimal outcomes. Recently, there has been interest in using novel biologic agents and small molecules to treat lupus nephritis.

The value of repeat kidney biopsy in quiescent Argentinian lupus nephritis patients.

Background: The duration of maintenance therapy after induction therapy for lupus nephritis has not been rigorously established. A common practice is to maintain immunosuppression for 1-2 years after complete remission, and longer for partial remission. The present work addresses whether a repeat kidney biopsy might be informative in deciding who should continue immunosuppression after complete or partial remission.

Renal flare as a predictor of incident and progressive CKD in patients with lupus nephritis.

Background And Objectives: Renal flares are common in lupus nephritis. The impact of flares on the development of CKD in lupus nephritis was examined.

Design, Setting, Participants, & Measurements: A retrospective analysis of prospectively collected data from the Ohio Systemic Lupus Erythematosus (SLE) Study was conducted to determine if renal flares predispose to new CKD or progression of preexisting CKD.

Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.

Background And Objective: Adrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open-label pilot trial of ACTH gel in patients with advanced diabetic nephropathy.

Study Design: Twenty-three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months.

Urine podocyte mRNAs, proteinuria, and progression in human glomerular diseases.

Model systems demonstrate that progression to ESRD is driven by progressive podocyte depletion (the podocyte depletion hypothesis) and can be noninvasively monitored through measurement of urine pellet podocyte mRNAs. To test these concepts in humans, we analyzed urine pellet mRNAs from 358 adult and pediatric kidney clinic patients and 291 controls (n=1143 samples). Compared with controls, urine podocyte mRNAs increased 79-fold (P<0.

Differential diagnosis of glomerular disease: a systematic and inclusive approach.

Background: Glomerular disease is a complex and evolving topic. In evaluating a specific case it is not unusual for the clinician to ask: 'Am I missing something? Should I biopsy? When? Should I treat first, then biopsy?' This work, which is both evidence and experience based, is intended to address each of these concerns and many other issues relevant to the differential diagnosis of glomerular disease.

Summary: The central approach is the use of diagnostic algorithms that are based on quantitative measures routinely obtained early in the course of the diagnostic evaluation.

Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats.

Background: Excessive anticoagulation with warfarin can result in acute kidney injury (AKI) by causing glomerular hemorrhage and renal tubular obstruction by red blood cell (RBC) casts in some patients, especially in those with chronic kidney disease (CKD). This condition was described as warfarin-related nephropathy (WRN). Recent evidence suggests that WRN-like syndromes are not confined to anticoagulation with warfarin, but may be seen with other anticoagulants, such as dabigatran.

N-acetylcysteine ameliorates acute kidney injury but not glomerular hemorrhage in an animal model of warfarin-related nephropathy.

Warfarin-related nephropathy (WRN) occurs under conditions of overanticoagulation with warfarin. WRN is characterized by glomerular hemorrhage with occlusive tubular red blood cell (RBC) casts and acute kidney injury (AKI). Herein we test the hypothesis that oxidative stress plays a role in the AKI of WRN.

When size matters: diagnostic value of kidney biopsy according to the gauge of the biopsy needle.

Background: Kidney biopsy is a vital tool in the diagnosis of kidney disease. Although it has become a routine procedure, it is not complication-free. Some serious complications of percutaneous kidney biopsy include retroperitoneal hemorrhage and death.

Unexplained severe acute kidney injury with rapid recovery of kidney function 11 months later after the start of high-dose steroid therapy.

Our patient appears to represent a previously unrecognized variant of steroid-responsive minimal change disease (MCD)/focal and segmental glomerulosclerosis (FSGS) in which severe AKI developed even though the serum albumin was essentially normal and proteinuria was minimal. This would be a paradox because the AKI of MCD/FSGS is a manifestation of severe nephrotic syndrome. To explain this paradox, it is suggested that our patient is a rare variant of a phenomenon that is well documented in steroid-responsive MCD/FSGS, specifically, glomerular permeability to large molecules is increased (accounting for the proteinuria) but decreased to small molecules (accounting for the low glomerular filtration rate).

IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression.

Recent breakthrough findings revealed that most patients with idiopathic (primary) membranous glomerulonephritis have IgG4 antibodies to the phospholipase A2 receptor (PLA2R). These IgG4 antibodies can be detected in the glomerular immune complexes and they colocalize with PLA2R. In secondary forms of membranous glomerulonephritis, such IgG4 antibodies are absent or less prevalent.

Henoch-Schönlein purpura-like presentation in IgA-dominant Staphylococcus infection - associated glomerulonephritis - a diagnostic pitfall.

Background: In children and adults, Henoch-Schönlein purpura (HSP) has a characteristic clinical presentation that includes a purpuric lower extremity skin rash, IgA-dominant glomerulonephritis, and abdominal and joint pain. A similar clinical presentation can be seen in adults who have a systemic infection with methicillin-resistant Staphylococcus aureus. It is critically important to distinguish the IgAdominant glomerulonephritis of HSP from the IgA-dominant glomerulonephritis of staphylococcal infection, because HSP may need to be treated with corticosteroids and immunosuppressives, while Staphylococcus infection-associated glomerulonephritis requires antibiotics.

Beyond anemia: hepcidin, monocytes and inflammation.

Hepcidin is an iron regulatory protein mainly synthesized by the liver. Hepatocyte production of hepcidin is responsible for serum hepcidin, is responsive to body iron stores, and is critical for maintaining iron homeostasis. Monocytes and macrophages also express hepcidin, and in contrast to the liver, hepcidin expression is primarily regulated by inflammatory mediators and infectious agents.

Kidney complications of hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) exposes a patient's kidneys to a unique combination of challenges, including high-dose radiation, anemia, chemotherapeutic agents, graft-versus-host disease, opportunistic infections, attenuated and altered immunologic responses, fluid and electrolyte imbalances, and extensive courses of antimicrobial agents. Since the inception of HSCT in the 1950s, there has been increasing interest in defining, determining, and managing the kidney complications that accompany this procedure. In this article, we review the common causes of acute kidney injury and chronic kidney disease that occur with HSCT, including HSCT-associated thrombotic microangiopathy, a distinct cause of chronic kidney disease with a multifactorial cause previously known as bone marrow transplant nephropathy or radiation nephropathy.

Novel estrogen target gene ZAS3 is overexpressed in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a prototypic, inflammatory autoimmune disease characterized by significant gender bias. Previous studies have established a role for hormones in SLE pathogenesis, including the sex hormone estrogen. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and β into the nucleus where they induce transcription by binding to estrogen response elements (EREs) of target genes.

Tolerating increases in the serum creatinine following aggressive treatment of chronic kidney disease, hypertension and proteinuria: pre-renal success.

Background: Blood pressure (BP) reduction in patients with chronic kidney disease (CKD), particularly with a renin-angiotensin system inhibitor (RASI), commonly leads to an initial decrease in glomerular filtration rate. The current clinical guideline, based on studies with single RASIs, is to tolerate an increase in the serum creatinine only up to 30%. This guideline has aptly guided CKD care for over a decade, but should be updated in the contemporary context of more aggressive RASI and diuretic use.

A quantitative proteomic workflow for characterization of frozen clinical biopsies: laser capture microdissection coupled with label-free mass spectrometry.

This paper describes a simple, highly efficient and robust proteomic workflow for routine liquid-chromatography tandem mass spectrometry analysis of Laser Microdissection Pressure Catapulting (LMPC) isolates. Highly efficient protein recovery was achieved by optimization of a "one-pot" protein extraction and digestion allowing for reproducible proteomic analysis on as few as 500 LMPC isolated cells. The method was combined with label-free spectral count quantitation to characterize proteomic differences from 3000-10,000 LMPC isolated cells.

High-sensitivity C-reactive protein, disease activity, and cardiovascular risk factors in systemic lupus erythematosus.

Objective: To study the level of high-sensitivity C-reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE).

Methods: Consecutive patients who fulfilled ≥4 American College of Rheumatology criteria for SLE who did not have a concurrent infection were recruited. Blood was assayed for hsCRP level, and disease activity, organ damage of SLE, and cardiovascular risk factors were assessed.

Lupus nephritis: induction therapy in severe lupus nephritis--should MMF be considered the drug of choice?

Severe lupus nephritis is an aggressive disease that requires an aggressive approach to treatment. Recent randomized clinical trials showed that mycophenolate mofetil compared favorably with cyclophosphamide (traditional approach) for remission induction. Consequently, mycophenolate mofetil is now commonly recommended as first-line therapy.

5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy.

Background/aims: We previously reported that patients with chronic kidney disease (CKD) receiving warfarin therapy and whose international normalized ratio increases to >3.0 may develop acute kidney injury (AKI) as a result of glomerular hemorrhage and formation of obstructive red blood cell (RBC) casts. We named this condition warfarin-related nephropathy (WRN).

Evidence that abnormally large seasonal declines in vitamin D status may trigger SLE flare in non-African Americans.

Cross-sectional studies have shown that low vitamin D (25-hydroxyvitamin D (25(OH)D)) is associated with increased systemic lupus erythematosus (SLE) activity. This study is the first to assess the temporal relationship between 25(OH)D levels and onset of SLE flare. This assessment was made possible because of the specimen bank and database of the Ohio SLE Study (OSS), a longitudinal study of frequently relapsing SLE that involved regular bimonthly patient follow-up.

Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis.

Objective: To investigate the relationship of urinary biomarkers and established measures of renal function to histologic findings in lupus nephritis (LN), and to test whether certain combinations of the above-mentioned laboratory measures are diagnostic for specific histologic features of LN.

Methods: Urine samples from 76 patients were collected within 2 months of kidney biopsy and assayed for the urinary biomarkers lipocalin-like prostaglandin D synthase (L-PGDS), α(1) -acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1). Using nonparametric analyses, levels of urinary biomarkers and established markers of renal function were compared with histologic features seen in LN, i.