Renal Involvement in Rheumatic Diseases

Contents

Foreword: Renal Involvement in Rheumatic Diseases xi

Michael H. Weisman

Preface: A Three-Headed Approach to Kidney Involvement in Rheumatic Diseases xiii

Andrew S. Bomback and Meghan E. Sise

Renal Involvement in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis 525

Reza Zonozi, John L. Niles, and Frank B. Cortazar
Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is
the most common cause of rapidly progressive glomerulonephritis.
ANCAs play an important role in the pathogenesis and diagnosis of AAV.
The classic renal lesion in AAV is a pauci-immune necrotizing and cres-
centic glomerulonephritis. Treatment is divided into 2 phases: (1) induction
of remission to eliminate disease activity and (2) maintenance of remission
to prevent disease relapse. Patients with AAV with end-stage renal disease
require modification of immunosuppressive strategies and consideration
for kidney transplant. An improved understanding of disease pathogenesis
has led to new treatment strategies being tested in clinical trials.

Therapy for Proliferative Lupus Nephritis 545

Kristin Meliambro, Kirk N. Campbell, and Miriam Chung
Proliferative lupus nephritis requires prompt diagnosis and treatment with
immunosuppressive therapy. Cyclophosphamide is the longest studied
agent, but mycophenolate mofetil has recently emerged as an efficacious
induction and maintenance treatment that does not impart the risk of infer-
tility. However, overall remission rates remain suboptimal and there is a
need for improved therapeutic options. To this end, ongoing clinical
studies are focusing on agents that target key molecules and pathways
implicated in the pathogenesis of lupus nephritis based on previous animal
and human studies. This article reviews key findings of trials supporting es-
tablished induction and maintenance treatment regimens along with novel
therapeutic investigations.

Nonproliferative Forms of Lupus Nephritis: An Overview 561

Andrew S. Bomback
Most of the attention paid to lupus nephritis, in the medical literature and in
clinical trials, has primarily focused on proliferative forms of lupus nephritis
(class III and IV lesions), but with lower thresholds to biopsy and rebiopsy
patients with lupus, clinicians are encountering more cases with purely
mesangial disease (classes I and II) or membranous nephropathy patterns
(class V). These lesions often are associated with milder disease courses
but still require dedicated follow-up by a nephrologist and focused thera-
peutic strategies that, at times, include immunosuppression.
viii Contents

Renal Manifestations of Rheumatoid Arthritis 571

Teja Kapoor and Joan Bathon
Renal manifestations in rheumatoid arthritis (RA) have evolved as RA man-
agement has improved. In the past, older disease-modifying antirheumatic
drugs, uncontrolled systemic inflammation, and chronic nonsteroidal anti-
inflammatory drug (NSAID) use contributed to kidney disease. Over time,
the use of methotrexate and biologic medications, decrease in NSAID
use, and a treat-to-target strategy have contributed to a decrease in renal
manifestations. Chronic kidney disease in RA now is more likely to be
caused by cardiovascular risk factors than uncontrolled RA disease
severity. In patients with renal dysfunction, NSAIDs, methotrexate, and to-
facitinib may need to be adjusted or avoided to prevent adverse events.
Secondary, AA, Amyloidosis 585
Riccardo Papa and Helen J. Lachmann
Secondary, AA, amyloidosis is a rare systemic complication that can
develop in any long-term inflammatory disorder and is characterized by
the extracellular deposition of fibrils derived from serum amyloid A (SAA)
protein. SAA is an acute-phase reactant synthetized largely by hepato-
cytes under the transcriptional regulation of proinflammatory cytokines.
The kidney is the major involved organ, with proteinuria as the first clinical
manifestation; renal biopsy is the most common diagnostic investigation.
Targeted anti-inflammatory treatment promotes normalization of circu-
lating SAA levels preventing amyloid deposition and renal damage. Novel
therapies aimed at promoting clearance of existing amyloid deposits soon
may be an effective treatment approach.
Nephrotoxicity of Select Rheumatologic Drugs 605
Tyler Woodell and Rupali S. Avasare
Several drugs commonly used in the management of rheumatic diseases
may lead to nephrotoxicity, electrolyte disturbances, and hypertension.
Here the authors focus on nonsteroidal anti-inflammatory drugs, uric
acid–lowering therapy, and commonly used immunosuppressant therapies.
The authors include a drug dosing table for patients with kidney disease.
Acute and Chronic Tubulointerstitial Nephritis of Rheumatic Causes 619
Nestor Oliva-Damaso, Elena Oliva-Damaso, and Juan Payan
Tubulointerstitial nephritis (TIN) is the second most common cause of
acute intrinsic kidney injury after acute tubular necrosis. Although drug-
induced forms of TIN represent the vast majority, rheumatic disease is
another common cause and often underdiagnosed. Early diagnosis of
acute interstitial nephritis and prompt withdrawal of the culprit medication
or a correct treatment can avoid chronic damage and progressive chronic
kidney disease. This article highlights the recent updates, clinical features,
and treatment in TIN in autoimmune rheumatic disease.
Thrombotic Microangiopathies with Rheumatologic Involvement 635
Faizan Babar and Scott D. Cohen
Thrombotic microangiopathies are heterogeneous disorders character-
ized by microangiopathic hemolytic anemia with thrombocytopenia and
 Contents ix

renal injury. There are a variety of causes, including metabolic disorders,

infections, medications, complement disorders, pregnancy, malignancy,
and autoimmune disorders. This article focuses on renal thrombotic micro-
angiopathy in the setting of rheumatologic diseases. Systemic lupus ery-
thematosus is the most common autoimmune disease associated with
thrombotic microangiopathy. Other causes include scleroderma renal
crisis and antiphospholipid antibody syndrome, which can be primary or
secondary to autoimmune diseases, including systemic lupus erythemato-
sus. There have also been case reports of thrombotic microangiopathy in
the setting of rheumatoid arthritis and dermatomyositis.

Anti–Glomerular Basement Membrane Disease 651

Kavita Gulati and Stephen P. McAdoo
Anti–glomerular basement membrane (anti-GBM) disease is a rare autoim-
mune small vessel vasculitis characterized by autoreactivity to antigens in
type IV collagen chains expressed in glomerular and alveolar basement
membrane. The detection of circulating anti-GBM antibodies, which are
shown to be directly pathogenic, is central to disease diagnosis. Clinically,
anti-GBM disease usually presents with rapidly progressive glomerulone-
phritis with or without alveolar hemorrhage. Rapid diagnosis and early
treatment are required to prevent mortality and to preserve renal function.
Relapse in anti-GBM disease is uncommon. Variant and atypical forms of
anti-GBM disease are increasingly recognized.

Autoimmune Kidney Diseases Associated with Chronic Viral Infections 675

Joshua D. Long, Stephanie M. Rutledge, and Meghan E. Sise
Autoimmune kidney diseases triggered by viruses are an important cause
of kidney disease in patients affected by chronic viral infection. Hepatitis B
virus (HBV) infection is associated with membranous nephropathy and pol-
yarteritis nodosa. Hepatitis C virus (HCV) infection is a major cause of cry-
oglobulinemic glomerulonephritis. Patients with human immunodeficiency
virus (HIV) may develop HIV-associated nephropathy, a form of collapsing
focal segmental glomerulosclerosis, or various forms of immune-complex–
mediated kidney diseases. This article summarizes what is known about
the pathogenesis, diagnosis, and management of immune-mediated kid-
ney diseases in adults with chronic HBV, HCV, and HIV infections.

Renal Manifestations of Inflammatory Bowel Disease 699

Josephine M. Ambruzs and Christopher P. Larsen
Renal and urinary involvement has been reported to occur in 4% to 23% of
patients with inflammatory bowel disease (IBD). Parenchymal renal dis-
ease is rare and most commonly affects glomerular and tubulointerstitial
compartments. The most common findings on renal biopsy of patients
with IBD are IgA nephropathy and tubulointerstitial nephritis. Overall
morbidity of IBD-related renal manifestations is significant, and there is
often only a short window of injury reversibility. This, along with subtle clin-
ical presentation, requires a high index of suspicion and routine monitoring
of renal function. There are no established guidelines for the optimal
screening and monitoring of renal function in patients with IBD.