• Systemic sclerosis
• bibliometric analysis
• renal involvement
• scleroderma renal crisis
• vasculopathy

• Humans
• Bibliometrics
• Biomedical Research/trends
• Scleroderma, Systemic/complications

• scleroderma
• systemic sclerosis
• telangiectasia
• vasculopathy
• fibrosis

• Humans
• Scleroderma, Systemic/genetics
• Scleroderma, Systemic/immunology
• Signal Transduction
• Animals
• Intercellular Signaling Peptides and Proteins/metabolism

• K08 AR077689 NIAMS NIH HHS
• R03 AR083454 NIAMS NIH HHS

• myopericarditis
• scleroderma
• scleroderma renal crisis
• small vessel vasculopathy
• systemic sclerosis

• Cardiovascular Diseases
• Machine Learning
• Systemic Sclerosis

• Humans
• Scleroderma, Systemic/drug therapy
• Scleroderma, Systemic/complications
• Female
• Middle Aged
• Male
• Vasodilator Agents/therapeutic use
• Bosentan/therapeutic use
• Prospective Studies
• Aged
• Treatment Outcome
• Iloprost/therapeutic use
• Sildenafil Citrate/therapeutic use
• Angiotensin-Converting Enzyme Inhibitors/therapeutic use
• Adult
• Stroke Volume/drug effects

• major organ involvement
• scleroderma renal crisis
• systemic sclerosis

• aliskiren
• hyperreninemia
• hypertension
• multiple mononeuropathy
• scleroderma renal crisis
• thrombotic microangiopathy

• Humans
• Female
• Sjogren's Syndrome/complications
• Sjogren's Syndrome/drug therapy
• Renal Dialysis
• Amides/therapeutic use
• Middle Aged
• Fumarates/therapeutic use
• Hypertension/drug therapy
• Hypertension/complications
• Scleroderma, Systemic/complications
• Antihypertensive Agents/therapeutic use
• Adrenal Cortex Hormones/therapeutic use
• Treatment Outcome
• Emergencies
• Heart Failure/etiology
• Heart Failure/drug therapy
• Hypertensive Crisis

• SSc
• angiotensin-converting enzyme inhibitor
• scleroderma renal crisis

• Humans
• Angiotensin-Converting Enzyme Inhibitors/therapeutic use
• Male
• Female
• Retrospective Studies
• Middle Aged
• Scleroderma, Systemic/complications
• Scleroderma, Systemic/drug therapy
• Aged
• Hospital Mortality
• Japan
• Databases, Factual
• Renal Dialysis

• 21AA2007 Ministry of Health, Labour and Welfare
• 20H03907 Ministry of Education, Culture, Sports, Science and Technology

• Scleroderma renal crisis
• acute kidney injury
• case report
• complement blockade
• thrombotic microangiopathy

• Raynaud’s syndrome
• interstitial lung disease
• lung diseases
• systemic sclerosis

• ACEI
• Fibrinoid necrosis
• Renal pathology
• Renal vasculopathy
• Scleroderma renal crisis
• Systemic sclerosis

• Systemic sclerosis
• renal crisis
• scleroderma
• thrombotic microangiopathy
• vasculopathy

• Acute kidney injury (AKI)
• anemia
• complement
• eculizumab
• endothelial injury
• renal-limited TMA
• review
• therapeutic plasma exchange (TPE)
• thrombocytopenia
• thrombotic microangiopathy (TMA)
• thrombotic thrombocytopenic purpura (TTP)

• Scleroderma
• cardiac complication
• case report
• management
• renal crisis

• Chronic kidney disease
• Renal Doppler ultrasonography
• Renal vasculopathy
• Systemic sclerosis

• Humans
• Peroxidase
• Antibodies, Antineutrophil Cytoplasmic
• Scleroderma, Systemic/complications
• Acute Kidney Injury/etiology
• Kidney
• Scleroderma, Localized
• Vascular Diseases/etiology
• Ureteral Diseases
• Penicillamine

• Drug therapy
• Epidemiology
• Korea
• Systemic scleroderma

Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis, and inflammation. Renal disease occurring in patients with SSc may have a variable clinicopathological picture. However, the most specific renal condition associated with this disease is the scleroderma renal crisis (SRC), characterized by acute onset of renal failure and severe hypertension. SRC develops in about 20% of cases of SSc, especially in those patients with diffuse cutaneous disease. The prognosis of this condition is often negative, with a rapid progression to end-stage renal disease (ESRD). The advent of the antihypertensive angiotensin-converting enzyme inhibitors in 1980 was associated with a significant improvement in patients’ survival and recovery of renal function. However, the prognosis of these patients can still be improved. The dialytic condition is associated with early death, and mortality is significantly higher than among patients undergoing renal replacement therapy (RRT) due to other conditions. Patients with SRC who show no signs of renal functional recovery despite timely blood pressure control are candidates for kidney transplantation (KT). In this review, we reported the most recent advances in KT in patients with ESRD due to SSc, with a particular overview of the risk of disease recurrence after transplantation and the evolution of other disease manifestations.

• Acute Kidney Injury/therapy
• Humans
• Hypertension, Renal/complications
• Hypertension, Renal/diagnosis
• Hypertension, Renal/therapy
• Kidney Failure, Chronic/complications
• Kidney Failure, Chronic/surgery
• Kidney Transplantation/adverse effects
• Scleroderma, Localized
• Scleroderma, Systemic/complications
• Scleroderma, Systemic/pathology
• Scleroderma, Systemic/therapy

Background: Systemic sclerosis is a chronic multisystem autoimmune disease, characterized by diffuse fibrosis and abnormalities of microcirculation and small arterioles in the skin, joints and visceral organs. Material and Methods: We searched for the relevant articles on systemic sclerosis and kidney involvement in systemic sclerosis in the NIH library of medicine, transplant, rheumatologic and nephrological journals. Results: Half of patients with systemic sclerosis have clinical evidence of kidney involvement. Scleroderma renal crisis represents the most specific and serious renal event associated with this condition. It is characterized by an abrupt onset of moderate to marked hypertension and kidney failure. Early and aggressive treatment is mandatory to prevent irreversible organ damage and death. The advent of ACE-inhibitors revolutionized the management of scleroderma renal crisis. However, the outcomes of this serious complication are still poor, and between 20 to 50% of patients progress to end stage renal disease. Conclusions: Scleroderma renal crisis still represents a serious and life-threatening event. Thus, further studies on its prevention and on new therapeutic strategies should be encouraged.

• Tocilizumab
• interleukin-6
• pulmonary fibrosis
• systemic sclerosis

Systemic sclerosis (SSc) is a chronic inflammatory disease with autoimmune determinism having an incompletely known pathogenesis. Although not all links in the pathogenic chain are known, studies have shown that vasculopathy is the initial event and is followed by extensive fibrosis of the skin and internal organs. New therapeutic strategies have been developed in recent years, thanks to innovative research which has increased understanding of the disease mechanisms. No curative treatment for SSc is currently known. Therefore, the therapeutic target in SSc is its symptomatology. Peripheral vasculopathy can be improved by administering vasodilators. Endothelin receptor antagonists and 5-phosphodiesterase inhibitors have a double benefit, both on peripheral and on pulmonary vasculopathy. Several molecules with antifibrotic effects are currently available; however, further studies are needed to confirm their beneficial effects. Immunosuppressants manage to control the cutaneous and visceral fibrotic process, thereby remaining as first-line drugs in the treatment of SSc. Although biological therapy using rituximab and tocilizumab has shown promising results in pulmonary fibrosis, ongoing studies are needed to determine their exact impact. The authors have differing views on the triggering role of glucocorticoids and the benefits of angiotensin-converting enzyme inhibitors in renal scleroderma. Some aspects of this disease such as calcinosis and pruritus, asthenia, or joint and muscle damage, remain difficult to manage.

• Digital ulcers
• Mortality
• Pulmonary artery hypertension
• Scleroderma
• Scleroderma renal crisis: Meta-analysis
• Systemic sclerosis
• Vasculopathy
• systematic review

• Immunosuppressants
• Systemic sclerosis
• Targeted therapy
• Treatments

• Clinical practice
• Juvenile-onset systemic sclerosis
• Pediatric rheumatology
• Scleroderma
• Systemic sclerosis
• Treatment

• Child
• Humans
• Lung Diseases, Interstitial/etiology
• Lung Diseases, Interstitial/therapy
• Scleroderma, Localized
• Scleroderma, Systemic/therapy

The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.

• Systemic sclerosis
• Scleroderma renal crisis
• Risk factors
• Renal failure
• Hemodialysis
• Kidney transplant

Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis.

• Recommendations
• Systemic sclerosis
• Treatment

• Mortality
• autoimmune diseases
• morbidity
• scleroderma renal crisis
• systemic sclerosis

• endothelin antagonist receptors
• phosphodiesterase-5 inhibitors
• prevention
• pulmonary arterial hypertension
• scleroderma renal crisis
• treatment

• haemodialysis
• maintenance dialysis
• peritoneal dialysis
• recovery of kidney function

Patient: Male, 45-year-old

Final Diagnosis: Systemic sclerosis sine scleroderma

Symptoms: Hypertension • renal failure • shortness of breath

Medication: —

Clinical Procedure: —

Specialty: Nephrology • Rheumatology

• outcome
• scleroderma renal crisis
• systemic sclerosis

• Angiotensin-converting enzyme inhibitors
• Hypertension
• Kidney
• Scleroderma renal crisis
• Systemic sclerosis

• Lupus nephritis
• Malignant hypertension
• Myoglobinuria
• Polymyositis
• Scleroderma
• Sjögren syndrome

• Anti-Scl70
• Familial
• Systemic sclerosis
• Topoisomerase

• Female
• Humans
• Nuclear Family
• Haplotypes
• Mothers
• HLA-DRB1 Chains/genetics
• Scleroderma, Systemic/diagnosis
• Autoantibodies

• Dialysis
• End stage renal disease
• Prognosis
• Renal replacement therapy
• Systemic sclerosis

• Acute Disease
• Antihypertensive Agents/therapeutic use
• Disease Progression
• Endothelin Receptor Antagonists/therapeutic use
• Fibrosis
• Fingers
• Heart Diseases/etiology
• Heart Diseases/physiopathology
• Heart Diseases/therapy
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunosuppressive Agents/therapeutic use
• Kidney Diseases/etiology
• Kidney Diseases/physiopathology
• Kidney Diseases/therapy
• Lung Diseases, Interstitial/etiology
• Lung Diseases, Interstitial/physiopathology
• Lung Diseases, Interstitial/therapy
• Myocardium/pathology
• Outcome Assessment, Health Care
• Prostaglandins I/therapeutic use
• Pulmonary Arterial Hypertension/etiology
• Pulmonary Arterial Hypertension/physiopathology
• Pulmonary Arterial Hypertension/therapy
• Raynaud Disease/etiology
• Raynaud Disease/physiopathology
• Raynaud Disease/therapy
• Scleroderma, Systemic/complications
• Scleroderma, Systemic/physiopathology
• Scleroderma, Systemic/therapy
• Severity of Illness Index
• Skin Ulcer/etiology
• Skin Ulcer/physiopathology
• Skin Ulcer/therapy

• K24 AR063120 NIAMS NIH HHS
• R01 AR070470 NIAMS NIH HHS

• hypertensive
• normotensive
• plasma exchange
• scleroderma renal crisis
• steroid
• systemic sclerosis
• thrombotic microangiopathy

• end-stage renal disease
• hemodialysis
• immunosuppressant agents
• rheumatic disease
• team approach

• Idiopathic inflammatory myopathies
• Myositis
• Pregnancy
• Reproductive health
• Scleroderma

Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC.

In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls.

ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6–10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1–29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC.

ACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.

• ACE inhibitor, proteinuria
• Risk factors
• Scleroderma renal crisis
• Systemic sclerosis