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Connective tissue diseases (CTDs) are a heterogeneous group of disorders that have certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Lesion of kidney function are typical for such CTDs as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Sjogren syndrome, autoimmune myopathies (dermatomyositis and polymyositis). At the present stage, considering the availability of many diagnostic manipulations and the possibility of etiopathogenetic treatment, therapists, rheumatologists and nephrologists must suspect in advance the presence of kidney disease in patients with CTD and assume measures for diagnosis and treatment. In systemic lupus erythematosus, renal prognosis is significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. One of the most severe kidney lesions is scleroderma renal crisis, which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy. Early administration of angiotensin-converting enzyme inhibitors in these patients shows a significant benefit in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjogren syndrome, autoimmune myopathies, and rheumatoid arthritis. On the other hand, chronic use of immunosuppressive agents and non-steroidal anti-inflammatory drugs, as well as comorbidities, such as diabetes, hypertension, and cardiovascular complications, are the main causes of renal involvement in patients with rheumatic diseases. Apart from this, long-standing primary kidney disease can lead to manifestations simulating primary rheumatologic disorders. In this review, we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions.

Scleroderma renal crisis (SRC) is a major complication in patients with systemic sclerosis. SRC occurs in about 5–25 % of all patients with scleroderma. It is characterized by malignant hypertension and olig-/anuric acute renal failure. Around 10 % of SRC cases may present with normal blood pressure, termed normotensive renal crisis. The etiopathogenesis is presumed to be a series of insults to the kidneys resulting in endothelial injury, intimal proliferation, and narrowing of renal arterioles leading to decreased blood flow, hyperplasia of the juxtaglomerular apparatus, hyperreninemia, and accelerated hypertension. SRC is often triggered by nephrotoxic drugs and/or intravascular volume depletion. SRC occurs particularly in the first years of disease and in its diffuse form. The occurrence of SRC is more common in patients treated with glucocorticoids, the risk increases with increasing dose. Left ventricular insufficiency and hypertensive encephalopathy are typical clinical features. Thrombotic microangiopathy is detected in 43 % of the cases. Anti-RNA-polymerase III antibodies are present in one third of patients who develop SRC. Renal biopsy is not necessary if SRC presents with classical features. However, it can help to establish prognosis and approaches to the treatment in atypical forms. The prognosis of SRC has dramatically improved with the introduction of angiotensin-converting enzyme inhibitors. However, 5-year survival in patients with systemic sclerosis who develop the full picture of SRC remains low (65 %). The treatment of SRC is based on aggressive control of blood pressure with angiotensin-converting enzyme inhibitors, if needed, in combination with other types of antihypertensive drugs. Dialysis is frequently indicated, but can be stopped in approximately half of patients, mainly in those with good control of blood pressure. Patients who need dialysis for more than 2 years qualify for renal transplantation. SRC still remains an important cause of morbidity and mortality in scleroderma. Prompt diagnosis and treatment may help prevent adverse outcomes and improve survival.

Background/Aims: Renal involvement is common in systemic sclerosis (SSc), including asymptomatic reduction of glomerular filtration rate (GFR), increased renal resistance indices, scleroderma renal crisis (SRC) and ANCA-associated vasculitis. The aim was to evaluate type and evolution of renal involvement for a period of five years. Methods: 121 SSc patients (100 F, 21 M) with mean age of 54.9 ± 13.8, disease duration of 9 ± 6 years, of which 62 had a diffused form and 59 limited form were enrolled. All patients were screened annually for renal function by laboratory examination, ultrasound and color Doppler ultrasound of renal arteries. Results: Over the five-year observation period, 6 SRC (3 M, 3 F) occurred, four of which required dialysis. One patient developed ANCA-related proliferative glomerulonephritis and the other one acute tubular necrosis. The remaining 113 patients had a preserved renal function (serum creatinine 0.75 ± 0.24 mg/dl, GFR 93.8 ± 20 ml/min, 24h proteinuria 0.20 ± 0.15 g). Doppler indices of intrarenal arterial stiffness increased with progression of capillaroscopic damage and with presence of digital ulcers. A negative correlation was observed between estimated GFR and pulsatile index (p< 0,05, r=-0.198), resistive index(p< 0,01, r=0.267), S/D ratio (p< 0,01, r=-0.237). Conclusion: In SSc patients, renal function was normal for 4.1 years despite the presence of increased intrarenal arterial stiffness. SRC was observed in 4.9% of SSc patients. In SSc patients, a periodic follow-up based on clinical and laboratory evaluation, colorDoppler ultrasound and, in some cases, renal biopsy is required to evaluate renal involvement.

Objective: To investigate the clinical features, treatments, and long‐term outcomes of Chinese patients with scleroderma renal crisis (SRC). Methods: We retrospectively reviewed the clinical and laboratory data of 538 patients with systemic sclerosis (SSc) at our center from January 2009 to December 2016, including 29 SRC and 509 SSc without SRC patients. The treatments and long‐term outcomes of patients with SRC were also retrospectively analyzed. Results: The prevalence of SRC was 5.4% in our cohort. Male gender (odds ratio [OR] =4.194 [95% CI 1.494‐11.773]), glucocorticoid exposure (OR = 3.666 [1.484‐9.056]), pericardial effusion (OR = 11.180 [4.515‐27.681]), and myocardial involvement (OR = 7.958 [1.664‐38.064]) were associated with an increased risk of development of SRC. Despite the wide use of angiotensin‐converting enzyme inhibitors, the permanent dialysis rate of patients with SRC was 48.3%. Sixteen patients died during follow‐up, and the estimated 1‐ and 5‐year survival rates of patients with SRC were 62.1% and 47.3%, respectively. Withdrawal of dialysis (5 patients) and myocardial complications (3 patients) were the main causes of death in patients with SRC. Patients with serum creatinine level >500 µmol/L before treatment (log rank test 5.051, P = 0.025) and/or those who needed dialysis at the onset of SRC (log rank test 12.870, P < 0.001) showed poorer prognosis. Conclusion: SRC is a rare but severe complication in patients with SSc. Male gender, glucocorticoid exposure, pericardial effusion, and myocardial involvement were risk factors in the development of SRC. Withdrawal of dialysis and myocardial complications were the main causes of death in Chinese patients with SRC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) may overlap frequently with other rheumatic diseases, including systemic lupus erythematosus (SLE), which can require high-dose steroids depending on the clinical presentation. We present a case involving this overlap in which the patient concomitantly developed lupus nephritis and Coombs (+) hemolytic anemia, which was confused with scleroderma renal crisis. In this condition, assessing for lupus nephritis with timely renal biopsy and lupus serology can aid in guiding the appropriate treatment. We discuss the clinical features and challenging management of this case with a review of the English-language literature for SSc and SLE overlap with glomerulonephritis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Categorization of scleroderma renal crisis (SRC) as hypertensive or normotensive can potentially overlook the underlying pathophysiology that might be unique in each patient, as they often exhibit a mixture of distinct pathological characteristics of narrowly defined SRC (nd-SRC) and systemic sclerosis associated thrombocytic micro-angiopathy (SSc-TMA). In this review, we provide evidence suggesting that better categorization of patients presenting with certain clinical features of both nd-SRC and TMA will improve treatment approaches. Based on our clinical experience and literature review, distinguishing between nd-SRC and SSc-TMA is important because the association of SSc-TMA with prior steroid administration and poor prognosis was stronger than that of nd-SRC. Although the two pathological entities cannot be easily distinguished based on blood pressure, we suggest that the detailed clinical course is helpful. Typically, nd-SRC exhibits prominently elevated blood pressure and worsening of renal function initially, followed by mild thrombocytopenia. Conversely, SSc-TMA presents first with severe thrombocytopenia, followed by elevated blood pressure and renal function deterioration. The degree of involvement in each pathological condition should be considered for determination of appropriate therapeutic interventions and prognostic prediction. [ABSTRACT FROM AUTHOR]

The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease. Recent studies have shown that Eculizumab (monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who present with symptoms of thrombotic microangiopathy (SRC-TMA). In this study, we conducted a systematic review to characterize the published experience of the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab. A literature search was conducted from inception to December 2022 using Medical Subject Headings (MeSH) terms for 'scleroderma', 'scleroderma renal crisis, and 'Eculizumab'. We included case reports, case series, and observational studies which reported the use of Eculizumab with or without Angiotensin-converting enzyme inhibitors (ACE-I) for the treatment of scleroderma renal crisis (SRC) in patients with systemic sclerosis. The study included 17 patients, all of whom were treated with Eculizumab. Additionally, the use of ACE-I was reported in 11/17 (64.7%) patients. Further, plasmapheresis was used in 9/17 (52.9%), steroids in 5/17 (29.4%), cyclophosphamide in 3/17 (17.6%), calcium channel blockers in 3/17 (17.6%), and Rituximab in 3/17 (17.6%) patients. Renal replacement therapy was required in 11/17 (64.7%) patients. 14/17 patients (82.3%) were reported to have clinical (renal or hematologic) improvement with Eculizumab therapy (Table 1). These findings should prompt testing on a larger cohort of SRC-TMA patients. This would help us determine whether aggressive treatment combining ACE-I and Eculizumab can target the various underlying endothelial, inflammatory, and immunologic mechanisms involved in SRC-TMA, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background. Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). Methods. Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. Results. Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. Conclusions. Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC.

Scleroderma renal crisis is a rare and severe complication of systemic sclerosis. There are many risk predictors for the development of this complication. Diagnostic criteria are non-consensual, including arterial hypertension and oliguric acute kidney injury (AKI). Angiotensin-converting enzyme inhibitors are an effective treatment, with huge impact in prognosis. We describe a case of a scleroderma renal crisis in a 78-years-old woman who was diagnosed with systemic sclerosis and treated with prednisone at high dosage, who presented with new onset congestive heart failure, arterial hypertension and oliguric AKI. The diagnosis of scleroderma renal crisis was performed, and angiotensin-converting enzyme inhibitor was initiated with blood pressure control and slightly improved renal function. The prognosis of scleroderma renal crisis remains poor with high 5-year mortality rate. Medical awareness on tensional values and well-known risk factors could have a huge impact in diagnosis and prognosis and even on prevention of this complication. [ABSTRACT FROM AUTHOR]

Kidney involvement in systemic sclerosis (SSc) is primarily manifested by scleroderma renal crisis (SRC). More than 30 years ago, it was the main cause of death in these patients. The use of AC inhibitors has modified the prognosis and nowadays SRC has become a much more easily treatable complication of SSc. Furthermore, although there are still many patients who do not survive this complication, the early diagnosis and prompt therapy of SRC can have an excellent outcome. Renal abnormalities independent of SRC are possible but are attributed to different pathogenetic mechanisms. Further understanding of pathogenesis of SRC may lead to additional improvement in the therapy of this serious complication.

Objective: The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis, but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients., Methods: Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analyzed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients., Results: Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls.RAAS hormone levels were assessed in 5 SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels., Conclusion: RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Scleroderma renal crisis (SRC) is a severe complication of systemic sclerosis characterised by abrupt onset of arterial hypertension and rapid progression to renal failure. Angiotensin-converting enzyme inhibitor (ACEi) is widely used for the treatment of this disease. Although the prognosis of SRC can be improved by prompt initiation of ACEi, a considerable proportion of cases still require maintenance dialysis therapy. However, the clinical picture of SRC patients after introduction of haemodialysis has not been sufficiently investigated. Here, we describe a 69-year-old female patient who was receiving regular haemodialysis because of SRC for three months and who developed posterior reversible encephalopathy syndrome (PRES) or microangiopathic haemolytic anaemia (MAHA), accompanied by rapid elevation of blood pressure, shortly after discontinuation of ACEi. Resumption of ACEi quickly resulted in improvement of the patient's condition and allowed stable continuation of maintenance haemodialysis. As haemodialysis patients often develop hypotension during dialysis sessions, reduction of antihypertensive agents need to be considered. However, physicians must decide carefully whether antihypertensive drugs including ACEi should be discontinued in order to avoid complications such as PRES or MAHA related to blood pressure elevation during the management of patients receiving maintenance haemodialysis for SRC. [ABSTRACT FROM AUTHOR]

This case report of a 70-year-old Thai female with type 2 diabetes and essential hypertension who presented with dyspnea, rapidly declining of kidney function, malignant hypertension, and thrombotic microangiopathy after a two-week course of high-dose corticosteroid administration for interstitial lung disease (ILD). A physical examination revealed characteristics compatible with limited cutaneous systemic sclerosis (lcSSc). However, SSc was not diagnosed at the time the patient's ILD discovered. Laboratory investigations showed proteinuria with microscopic hematuria, the presence of anti-topoisomerase I antibodies, high titer of antinuclear antibodies, and low serum of complement C3 and C4. The diagnosis required differentiation between severe proliferative type of lupus nephritis and scleroderma renal crisis, as treatment for these two diseases differs greatly. Thus, the patient underwent percutaneous kidney biopsy, and the renal pathology revealed an onion-skin appearance with fibrinoid necrosis at the arterioles and arteries. The final diagnosis was lcSSc with scleroderma renal crisis. [ABSTRACT FROM AUTHOR]

Scleroderma renal crisis is an important cause of morbidity and mortality in systemic sclerosis patients, occurring in about 5-10% of the cases. It is seen mostly early in the progression of the disease, about 75% of the scleroderma renal crises affecting the patients in their first 4 years since the onset of the disease. We present the case of a 62 year old woman who was admitted in our clinic for oliguria, edema, an important elevation of the kidney function tests, arterial hypertension and severe anemia. Immunological tests showed intensely positive antinuclear antibodies with positive anti RNA polymerase III antibodies. She was diagnosed with systemic sclerosis according to ACR/EULAR 2013 criteria and scleroderma renal crisis. Specific therapy was started along with hemodialysis imposed by the progression of the kidney failure.

Systemic sclerosis (SSc) is a rare autoimmune disease that causes fibrosis in the skin and subcutaneous tissue, involving other organs such as the heart, lungs, kidneys, and gastrointestinal tract. Additionally, it can cause pulmonary arterial hypertension. Scleroderma renal crisis (SRC) is one of the most dreadful complications of SSc. SRC is a medical emergency that can present as a clinical picture of hypertensive encephalopathy. The pathophysiology involves an abrupt onset of moderate to severe hypertension that ranges from days to weeks; it is associated with an increase in plasma renin activity and acute kidney injury. It is known that by introducing angiotensin-converting enzyme inhibitors, the mortality decreases significantly in SRC. The renal biopsy plays an important role on the diagnosis and opportune treatment. We present a clinical case of SRC with a typical presentation of hypertensive emergency and acute kidney injury. [ABSTRACT FROM AUTHOR]

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Systemic sclerosis (SS), is an autoimmune connective tissue disease, the main clinical signs of which are due to disseminated microcirculatory disorders and fibrosis of the skin and viscera. Morphological examinations showed that 80% of patients with SS had renal changes, including those unassociated with rheumatic diseases. Whereas the prevalence of scleroderma renal crisis is now estimated to be 2–5%, there is considerably often an asymptomatic reduction in renal function (silent uremia), which is caused by multimorbidity and comorbidity. Its incidence in patients with SS may be as high as 55%. The presence of autoimmune connective tissue disease may be itself regarded as a risk factor of renal involvement. Fifteen-year survival is 72% in SS patients with no renal involvement and not more than 13% in those having renal involvement. In patients with SS, proteinuria is one of the most important independent risk factors for fatal outcomes (relative risk, 3.34), leaving far behind canonical risk factors, such as pulmonary hypertension, restrictive lung disease (a forced expiratory volume in one second to forced vital capacity ratio of

Background: Systemic sclerosis (SSc) patients are encountered in all parts of the world. Few Indian studies are found in the literature on this connective tissue disorder of unknown etiology. The spectrum of sclerodermatous diseases comprises a wide variety of clinical entities. Renal involvement is not common in Indian patients when compared to western patient′s in spite of the kidney being commonly affected in scleroderma due to vascular changes. Aim and Objective: To primarily study the prevalence of renal involvement in SSc and to correlate it with high-sensitivity C-reactive protein (hsCRP) over a period of 1 year in a tertiary care hospital in North-East India. Materials and Methods: A total of 38 consecutive scleroderma patients of both sexes, diagnosed by established criteria, were examined, and hsCRP was estimated in all. Evaluation for nephropathy by biochemical tests and sonography were carried out. Relevant clinical/biochemical examinations were carried out. Results: SSc was 3 times more common in mostly in middle aged females. About 50% presented within 1 year of disease onset. Renal involvement was uncommon (18%) and hsCRP was detected in 26%. Conclusion: SSc with nephropathy, not renal crisis, presents early and hsCRP is a good marker for the same.

Scleroderma renal crisis (SRC) is an uncommon but still life-threatening manifestation of systemic sclerosis (SSc). The incidence of SRC has decreased in the last few decades, probably due to a widespread use of vasodilators in SSc patients. It is well-recognized that exposure to different drugs can trigger SRC (corticosteroids, cyclosporine) or might prevent its occurrence (iloprost, calcium channel blockers). The prognosis of this life-threatening manifestation has not substantially improved since 1980s, when ACE-inhibitors were introduced in its treatment. ACE-inhibitors remain the mainstay in the therapy of SRC due to their efficacy in controlling malignant hypertension; indeed, the prognosis largely depends on the rapid improvement of the ongoing renal ischemia. Calcium-channel blockers and in third line diuretics and alpha-blockers should be used as additional therapy if blood pressure control remains suboptimal despite maximum tolerated doses of ACE-inhibitors. Given the growing evidence on the role of complement activation and endothelin-1 in the pathogenesis of SRC, recent case-series and case reports have suggested the use of C5-inhibitors and endothelin receptor antagonists in the therapy of SRC, mainly in the refractory cases. Plasma-exchange seems to give some benefits in patients with SRC and microangiopathy or intolerant to ACE-inhibitors. Renal transplantation is the last treatment option and its outcome is similar to that reported in other connective tissue disorders, with a 5-year patient survival rate of about 82%. In this review we summarize the current knowledge in the treatment of SRC. [ABSTRACT FROM AUTHOR]

Background/Aims: Renal involvement is common in systemic sclerosis (SSc), including asymptomatic reduction of glomerular filtration rate (GFR), increased renal resistance indices, scleroderma renal crisis (SRC) and ANCA-associated vasculitis. The aim was to evaluate type and evolution of renal involvement for a period of five years. Methods: 121 SSc patients (100 F, 21 M) with mean age of 54.9 ± 13.8, disease duration of 9 ± 6 years, of which 62 had a diffused form and 59 limited form were enrolled. All patients were screened annually for renal function by laboratory examination, ultrasound and color Doppler ultrasound of renal arteries. Results: Over the five-year observation period, 6 SRC (3 M, 3 F) occurred, four of which required dialysis. One patient developed ANCA-related proliferative glomerulonephritis and the other one acute tubular necrosis. The remaining 113 patients had a preserved renal function (serum creatinine 0.75 ± 0.24 mg/dl, GFR 93.8 ± 20 ml/min, 24h proteinuria 0.20 ± 0.15 g). Doppler indices of intrarenal arterial stiffness increased with progression of capillaroscopic damage and with presence of digital ulcers. A negative correlation was observed between estimated GFR and pulsatile index (p< 0,05, r=-0.198), resistive index(p< 0,01, r=0.267), S/D ratio (p< 0,01, r=-0.237). Conclusion: In SSc patients, renal function was normal for 4.1 years despite the presence of increased intrarenal arterial stiffness. SRC was observed in 4.9% of SSc patients. In SSc patients, a periodic follow-up based on clinical and laboratory evaluation, colorDoppler ultrasound and, in some cases, renal biopsy is required to evaluate renal involvement. [ABSTRACT FROM AUTHOR]

Abstract Scleroderma associated Pulmonary–Renal Syndrome is a rare but severe complication with a poor prognosis and high mortality. A high index of suspicion is needed for early recognition of this potential complication in patients with systemic sclerosis and institution of appropriate treatment. With more data showing an increased association between scleroderma and malignancy, a heightened vigilance should also be exercised in patients with malignancy and scleroderma-like presentation. We report of a case rapid onset systemic sclerosis complicated by acute renal failure and diffuse alveolar hemorrhage in a woman with stage IIB right breast cancer and elevated RNA Polymerase III IgG Ab. To our knowledge, this the first case of a patient with breast cancer associated with systemic sclerosis and pulmonary-renal syndrome. [ABSTRACT FROM AUTHOR]

A 69-year-old Japanese man was presented with hypertensive crisis. Renal histology revealed malignant nephrosclerosis, including an onion skin pattern with fibrinoid necrosis of the small arteries from arterioles up to interlobular arteries. Immunological investigation clarified positive anti-RNA polymerase (RNAP) III antibody, and limited cutaneous systemic sclerosis (Lc SSc) was diagnosed by skin biopsy as the underlying disease causing scleroderma renal crisis (SRC). Angiotensin covering enzyme (ACE) inhibitor therapy and calcium antagonist were effective for his renal condition. Although an association between SRC and anti-RNAP III antibody has already been reported in patients with diffuse cutaneous SSc (Dc SSc), this case indicates that SRC with hypetensive emergency with malignant nephrosclerosis can also be diagnosed on patients with Lc SSc patients by the examination of anti-RNAP III antibody. [ABSTRACT FROM AUTHOR]

Systemic sclerosis is a rare autoimmune vasculopathy associated with dysregulated innate and adaptive immunity that leads to generalized systemic fibrosis. Renal involvement occurs in a significant proportion of systemic sclerosis patients, and is associated with worse outcome. Scleroderma renal crisis (SRC) is the most studied and feared renal complication described in systemic sclerosis. However, with the emergence of ACE inhibitors and better management, the mortality rate of SRC has significantly decreased. Renal disease in systemic sclerosis offers a wide array of differential diagnoses that may be challenging for the clinician. The spectrum of renal manifestations in systemic sclerosis ranges from an isolated decrease in glomerular filtration rate, increased intrarenal arterial stiffness, and isolated proteinuria due to SRC to more rare manifestations such as association with antiphospholipid antibody nephropathy and ANCA-associated vasculitis. The changes observed in the kidneys in systemic sclerosis are thought to be due to a complex interplay of various factors, including renal vasculopathy, as well as the involvement of the complement system, vasoactive mediators such as endothelin-1, autoimmunity, prothrombotic and profibrotic cytokines, among others. This literature review aims to provide an overview of the main renal manifestations in systemic sclerosis by discussing the most recent epidemiological and pathophysiological data available and the challenges for clinicians in making a diagnosis of renal disease in patients with systemic sclerosis. [ABSTRACT FROM AUTHOR]