scholarly journals Scleroderma nephropathy: unsolved problems

2021 ◽  
Vol 7 (5) ◽  
pp. 5-18
Author(s):  
I. E. Bulavko ◽  
E. V. Timofeev ◽  
K. J. U. Alkak ◽  
V. A. Isakov
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Systemic Sclerosis ◽  
Rna Polymerase Iii ◽  
Kidney Injury ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme Inhibitors ◽  
Treatment Approaches ◽  
Renal Crisis

Kidney injury is a common pathology in the group of patients with systemic sclerosis. At least half of the patients show histological signs of it. Acute condition is known as scleroderma renal crisis. Although discussions regarding the risk factors for scleroderma renal crisis are open, most researchers consider the following factors: female sex, previous proteinuria and hypertension, the presence of anti-RNA polymerase III antibodies, and a decrease in lung diffusion capacity ≤75%. Diagnostic criteria for scleroderma renal crisis include an acute increase in blood pressure, accompanied by acute renal failure and abnormalities in the urinary sediment, anemia, and thrombocytopenia. Treatment of scleroderma renal crisis entails decreasing blood pressure, mainly with short-acting angiotensin-converting enzyme inhibitors, followed by selecting effective antihypertensive therapy. Further research of new treatment approaches is being carried on: the use of endothelin receptor antagonists (bosentan), monoclonal antibodies against the complement component 5 (eculizumab). Despite the approved strategies for identifying risk factors for scleroderma renal crisis development and treatment approaches, this group of patients is still characterized by high rates of mortality, the need for renal replacement therapy, and kidney transplantation. Thus, the problem of kidney injury in systemic sclerosis remains relevant.

scholarly journals Renal Involvement in Systemic Sclerosis: An Update

2020 ◽  
Vol 45 (4) ◽  
pp. 532-548
Author(s):  
Magdalena Chrabaszcz ◽  
Jolanta Małyszko ◽  
Mariusz Sikora ◽  
Rosanna Alda-Malicka ◽  
Anna Stochmal ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Renal Involvement ◽  
Significant Proportion ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Renal Crisis

Background: Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. Summary: Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients’ outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.

Kidney involvement in systemic sclerosis: From pathogenesis to treatment

2018 ◽  
Vol 3 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Cosimo Bruni ◽  
Giovanna Cuomo ◽  
Francesca W. Rossi ◽  
Emanuela Praino ◽  
Silvia Bellando-Randone
Keyword(s):  
Systemic Sclerosis ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Prognostic Impact ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Kidney Involvement ◽  
Renal Crisis

Among all possible systemic sclerosis internal organ complications, kidney involvement is frequently neglected or underestimated, except for the life-threatening scleroderma renal crisis. Fortunately, this severe clinical presentation is nowadays better controlled with available treatments, in particular angiotensin-converting enzyme inhibitors, and this has led to a reduction in its short- and longer-term mortality. Pathogenetic determinants are not well understood and many different other kidney involvements are possible in systemic sclerosis, including proteinuria, albuminuria, reduction of renal filtration, autoantibodies-related glomerulonephritis, and drug-related side effects. Different serological and radiological methods of evaluations are nowadays available, some representing promising diagnostic tool and prognostic outcome measure. Except for angiotensin-converting enzyme inhibitors in scleroderma renal crisis, no other treatment is currently recommended for treatment of kidney involvement in systemic sclerosis. For this reason, further studies are necessary to investigate its prognostic impact, in particular in combination with other systemic sclerosis–related internal organ manifestations. This review summarizes current available literature on kidney involvement in systemic sclerosis.

Risk Factors for Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis

2018 ◽  
Vol 46 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Sarah M. Gordon ◽  
Rodger S. Stitt ◽  
Robert Nee ◽  
Wayne T. Bailey ◽  
Dustin J. Little ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Sclerosis ◽  
Clinical Characteristics ◽  
Rna Polymerase Iii ◽  
High Risk Population ◽  
Scleroderma Renal Crisis ◽  
Skin Thickness ◽  
Laboratory Findings ◽  
Close Observation ◽  
Renal Crisis

Objective.Systemic sclerosis (SSc) is a disease of autoimmunity, fibrosis, and vasculopathy. Scleroderma renal crisis (SRC) is one of the most severe complications. Corticosteroid exposure, presence of anti-RNA polymerase III antibodies (ARA), skin thickness, and significant tendon friction rubs are among the known risk factors at SSc diagnosis for developing future SRC. Identification of additional clinical characteristics and laboratory findings could expand and improve the risk profile for future SRC at SSc diagnosis.Methods.In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the demographics, clinical characteristics, and laboratory results at SSc diagnosis for 31 cases who developed SRC after SSc diagnosis to 322 SSc without SRC disease controls.Results.After adjustment for potential confounding variables, at SSc diagnosis these conditions were all associated with future SRC: proteinuria (p < 0.001; OR 183, 95% CI 19.1–1750), anemia (p = 0.001; OR 9.9, 95% CI 2.7–36.2), hypertension (p < 0.001; OR 13.1, 95% CI 4.7–36.6), chronic kidney disease (p = 0.008; OR 20.7, 95% CI 2.2–190.7), elevated erythrocyte sedimentation rate (p < 0.001; OR 14.3, 95% CI 4.8–43.0), thrombocytopenia (p = 0.03; OR 7.0, 95% CI 1.2–42.7), hypothyroidism (p = 0.01; OR 2.8, 95% CI 1.2–6.7), Anti-Ro antibody seropositivity (p = 0.003; OR 3.9, 95% CI 1.6–9.8), and ARA (p = 0.02; OR 4.1, 95% CI 1.2–13.8). Three or more of these risk factors present at SSc diagnosis was sensitive (77%) and highly specific (97%) for future SRC. No SSc without SRC disease controls had ≥ 4 risk factors.Conclusion.In this SSc cohort, we present a panel of risk factors for future SRC. These patients may benefit from close observation of blood pressure, proteinuria, and estimated glomerular filtration rate, for earlier SRC identification and intervention. Future prospective therapeutic studies could focus specifically on this high-risk population.

scholarly journals Iatrogenic scleroderma renal crisis: A case report and mini literature review for renal crisis

2021 ◽  
Vol 8 (3) ◽  
pp. 4
Author(s):  
Gülşah Boz ◽  
Samet Karahan ◽  
Nurdan Yüksek
Keyword(s):  
Systemic Sclerosis ◽  
Enzyme Inhibitors ◽  
Day Treatment ◽  
Renal Involvement ◽  
Elevated Serum ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme Inhibitors ◽  
Kidney Involvement ◽  
Renal Crisis

Background: Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and organs, marked changes in microvascular structure, cellular and humoral immune disorders. Renal involvement is more frequent and mainly characterized by moderate proteinuria, elevated serum creatinine levels, and hypertension. The most common kidney involvement in SSc is scleroderma renal crisis (SRC) that is fatal without prompt intervention.Case report: A 52-year-old Caucasian male with known diffuse cutaneous systemic sclerosis was hospitalized with communityacquired pneumonia. On the fifth day after appropriate antibiotic therapy and 60 mg/day methylprednisolone, decreased urine output, arterial hypertension, decreased renal function and pulmonary edema developed. The patient was diagnosed with a scleroderma renal crisis. Emergency hemodialysis was applied to the patient, and captopril 6 × 25 mg/day and nifedipine 2*60 mg/day treatment were given. He received a routine hemodialysis program for about three months. The hemodialysis program was terminated when the patient’s urine quality and quantity increased.Conclusions: SRC, characterized by malignant hypertension, azotemia, microangiopathic hemolytic anemia, and kidney failure, is one of the most important complications of systemic sclerosis with a poor prognosis without prompt intervention. Steroid use is one of the important risk factors that precipitate SRC development. With angiotensin-converting enzyme inhibitors, survival increased after SRC, the need for dialysis decreased, and usually allowed the discontinuation of dialysis treatment within about 6-18 months. Suspicion of SRC in the presence of the above-mentioned findings in patients with a diagnosis or suspected systemic sclerosis can be considered the most important treatment step.

Scleroderma Renal Crisis: Risk Factors for an Increasingly Rare Organ Complication

2019 ◽  
Vol 47 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Pia Moinzadeh ◽  
Kathrin Kuhr ◽  
Elise Siegert ◽  
Norbert Blank ◽  
Cord Sunderkoetter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Enzyme Inhibitors ◽  
Rare Complication ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme Inhibitors ◽  
Life Threatening ◽  
History Of ◽  
Mean Time ◽  
Renal Crisis

Objective.Scleroderma renal crisis (SRC) is a severe life-threatening manifestation in patients with systemic sclerosis (SSc). However, the knowledge about risk factors for SRC is limited. We determined here the frequency of SRC and identified risk factors for the prediction of SRC.Methods.Based on regular followup data from the German Network for Systemic Scleroderma, we used univariate and multivariate generalized estimating equations to analyze the association between clinical variables, SSc subsets, therapy [i.e., angiotensin-converting enzyme inhibitors (ACEi), corticosteroids], and the occurrence of SRC.Results.Data of 2873 patients with 10,425 visits were available for analysis with a mean number of registry visits of 3.6 ± 2.8 and a mean time of followup of 3.6 ± 3.8 years. In total, 70 patients developed SRC (70/2873, 2.4%). Of these patients, 57.1% (40/70) were diagnosed with diffuse cutaneous SSc, 31.4% (22/70) with limited cutaneous SSc, and 11.4% (8/70) with SSc-overlap syndromes. Predictive independent factors with the highest probability for SRC were positive anti-RNA polymerase antibodies (RNAP), a history of proteinuria prior to SRC onset, diminished DLCO, and a history of hypertension. Interestingly, positive antitopoisomerase autoantibodies did not predict a higher risk for SRC. Further, patients with SRC were significantly more frequently treated with ACEi and corticosteroids without being independently associated with SRC.Conclusion.In this cohort, SRC has become a rare complication. By far the highest risk for SRC was associated with the detection of anti-RNAP and proteinuria.

Worldwide Expert Agreement on Updated Recommendations for the Treatment of Systemic Sclerosis

2019 ◽  
Vol 47 (2) ◽  
pp. 249-254 ◽  
Author(s):  
Jeska K. de Vries-Bouwstra ◽  
Yannick Allanore ◽  
Marco Matucci-Cerinic ◽  
Alexandra Balbir-Gurman
Keyword(s):  
Systemic Sclerosis ◽  
Online Survey ◽  
Geographical Area ◽  
Phosphodiesterase Inhibitors ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Pressure Control ◽  
Scleroderma Renal Crisis ◽  
Converting Enzyme Inhibitors ◽  
Hematopoietic Stem ◽  
Level Of Agreement

Objective.To evaluate agreement of the updated European League Against Rheumatism and European Scleroderma Trials and Research group (EUSTAR) recommendations for treatment of systemic sclerosis (SSc) among international experts. In addition, to determine factors that might influence agreement.Methods.Level of agreement (10-point scale: 0 = not at all, 10 = completely agree) and local drug availability (yes/no) were assessed using an online survey. The Web link to the survey was shared with 481 unique e-mail addresses and SSc networks (Scleroderma Clinical Trials Consortium, Australian Scleroderma Interest Group, International Systemic Sclerosis Inception Cohort). Level of agreement was compared between subgroups stratified for participant characteristics.Results.In total, 263 experts participated, of whom n = 209 (79%) completed each single item. The majority were rheumatologists (n = 200, 76%) working in Europe (n = 185; 71%); 59% (n = 156) were EUSTAR members; and 57% (n = 151) had > 10 years of clinical experience. Overall level of agreement was high (mean 8.0, SD 2.5). The 3 highest mean agreements included (1) angiotensin-converting enzyme inhibitors for scleroderma renal crisis (9.2, SD 2.1); (2) blood pressure control in SSc-patients treated with corticosteroids (9.0, SD 2.2); (3) proton pump inhibitors to prevent reflux complications (9.0, SD 2.2). The 3 lowest mean agreements included (1) fluoxetine for Raynaud phenomenon (RP; 4.6, SD 2.8); (2) hematopoietic stem cell transplantation (HSCT) for severe SSc (7.1, SD 2.9); (3) phosphodiesterase inhibitors 5 for RP (7.3, SD 2.7). Agreement differed between Europe and non-Europe for the use of iloprost, bosentan, methotrexate, HSCT, and cyclophosphamide. Treatment availability could partially explain differential agreement for iloprost, bosentan, and HSCT.Conclusion.In general, worldwide expert agreement on updated recommendations for treatment of SSc is high, supporting their value. Differences in agreement are partially explained by geographical area and treatment availability.

Analysis of Anti-RNA Polymerase III Antibody-positive Systemic Sclerosis and Altered GPATCH2L and CTNND2 Expression in Scleroderma Renal Crisis

2020 ◽  
Vol 47 (11) ◽  
pp. 1668-1677
Author(s):  
Edward P. Stern ◽  
Sandra G. Guerra ◽  
Harry Chinque ◽  
Vanessa Acquaah ◽  
David González-Serna ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Renal Biopsy ◽  
Genetic Susceptibility ◽  
Rna Polymerase Iii ◽  
Human Kidney ◽  
Scleroderma Renal Crisis ◽  
Nucleotide Polymorphisms ◽  
Polymerase Iii ◽  
Renal Crisis

ObjectiveScleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) strongly associated with anti-RNA polymerase III antibody (ARA) autoantibodies. We investigated genetic susceptibility and altered protein expression in renal biopsy specimens in ARA-positive patients with SRC.MethodsARA-positive patients (n = 99) with at least 5 years’ follow-up (49% with a history of SRC) were selected from a well characterized SSc cohort (n = 2254). Cases were genotyped using the Illumina Human Omni-express chip. Based on initial regression analysis, 9 single-nucleotide polymorphisms (SNP) were chosen for validation in a separate cohort of 256 ARA-positive patients (40 with SRC). Immunostaining of tissue sections from SRC or control kidney was used to quantify expression of candidate proteins based upon genetic analysis of the discovery cohort.ResultsAnalysis of 641,489 SNP suggested association of POU2F1 (rs2093658; P = 1.98 × 10−5), CTNND2 (rs1859082; P = 5.58 × 10−5), HECW2 (rs16849716; P = 1.2 × 10−4), and GPATCH2L (rs935332; P = 4.92 × 10−5) with SRC. Further, the validation cohort showed an association between rs935332 within the GPATCH2L region, with SRC (P = 0.025). Immunostaining of renal biopsy sections showed increased tubular expression of GPATCH2L (P = 0.026) and glomerular expression of CTNND2 (P = 0.026) in SRC samples (n = 8) compared with normal human kidney controls (n = 8), despite absence of any genetic replication for the associated SNP.ConclusionIncreased expression of 2 candidate proteins, GPATCH2L and CTNND2, in SRC compared with control kidney suggests a potential role in pathogenesis of SRC. For GPATCH2L, this may reflect genetic susceptibility in ARA-positive patients with SSc based upon 2 independent cohorts.

Scleroderma Renal Crisis

2014 ◽  
Vol 41 (6) ◽  
pp. 1040-1048 ◽  
Author(s):  
Luc Mouthon ◽  
Guillaume Bussone ◽  
Alice Berezné ◽  
Laure-Hélène Noël ◽  
Loïc Guillevin
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Control ◽  
Antihypertensive Drugs ◽  
Rna Polymerase Iii ◽  
Pressure Control ◽  
Hypertensive Encephalopathy ◽  
Left Ventricular ◽  
Scleroderma Renal Crisis ◽  
Volume Depletion ◽  
Renal Crisis

Scleroderma renal crisis (SRC) is characterized by malignant hypertension and oligo-anuric acute renal failure. It occurs in 5% of patients with systemic sclerosis (SSc), particularly in patients with diffuse disease during the first years. SRC is more common in patients receiving corticosteroids, the risk increasing with increasing dose. The disease is sometimes triggered by use of nephrotoxic drugs and/or intravascular volume depletion. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43% of cases, and anti-RNA-polymerase III antibodies are present in one-third of patients. Renal biopsy is not necessary if SRC presents classical features. However, biopsy may help to define the prognosis and guide treatment in atypical forms. The prognosis of SRC has greatly improved with the introduction of angiotensin-converting enzyme (ACE) inhibitors. However, the 5-year survival for SSc patients with full SRC remains low (65%). The treatment of SRC relies on aggressive blood pressure control with an ACE inhibitor, combined with other antihypertensive drugs if needed. Dialysis is frequently indicated but can be stopped in about half of patients, mainly those with good blood pressure control. Patients who need dialysis for more than 2 years qualify for renal transplantation.

scholarly journals Prevalence, Correlates and Outcomes of Gastric Antral Vascular Ectasia in Systemic Sclerosis: A EUSTAR Case-control Study

2013 ◽  
Vol 41 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Etienne Ghrénassia ◽  
Jérome Avouac ◽  
Dinesh Khanna ◽  
Chris T. Derk ◽  
Oliver Distler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Gastric Antral Vascular Ectasia ◽  
Vascular Ectasia ◽  
Polymerase Iii ◽  
European League Against Rheumatism ◽  
Vascular Phenotype ◽  
Renal Crisis

Objective.To estimate the prevalence, determine the subgroups at risk, and the outcomes of patients with systemic sclerosis (SSc) and gastric antral vascular ectasia (GAVE).Methods.We queried the European League Against Rheumatism Scleroderma Trials and Research (EUSTAR) network for the recruitment of patients with SSc-GAVE. Each case was matched for cutaneous subset and disease duration with 2 controls with SSc recruited from the same center, evaluated at the time the index case made the diagnosis of GAVE. SSc characteristics were recorded at the time GAVE occurred and the last observation was collected to define the outcomes.Results.Forty-nine patients with SSc and GAVE were included (24 with diffuse cutaneous SSc) and compared to 93 controls with SSc. The prevalence of GAVE was estimated at about 1% of patients with SSc. By multivariate analysis, patients with SSc-GAVE more frequently exhibited a diminished (< 75%) DLCO value (OR 12.8; 95% CI 1.9–82.8) despite less frequent pulmonary fibrosis (OR 0.2; 95% CI 0.1–0.6). GAVE was also associated with the presence of anti-RNA-polymerase III antibodies (OR 4.6; 95% CI 1.2–21.1). SSc-GAVE was associated with anemia (82%) requiring blood transfusion (45%). Therapeutic endoscopic procedures were performed in 45% of patients with GAVE. After a median followup of 30 months (range 1–113 months), survival was similar in patients with SSc-GAVE compared to controls, but a higher number of scleroderma renal crisis cases occurred (12% vs 2%; p = 0.01).Conclusion.GAVE is rare and associated with a vascular phenotype, including anti-RNA-polymerase III antibodies, and a high risk of renal crisis. Anemia, usually requiring blood transfusions, is a common complication.

scholarly journals Clinical and Immunologic Predictors of Scleroderma Renal Crisis in Japanese Systemic Sclerosis Patients With Anti-RNA Polymerase III Autoantibodies

2015 ◽  
Vol 67 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Yasuhito Hamaguchi ◽  
Masanari Kodera ◽  
Takashi Matsushita ◽  
Minoru Hasegawa ◽  
Yuki Inaba ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Rna Polymerase ◽  
Rna Polymerase Iii ◽  
Scleroderma Renal Crisis ◽  
Polymerase Iii ◽  
Renal Crisis
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