scholarly journals Kidney Involvement in Acute Hepatic Porphyrias: Pathophysiology and Diagnostic Implications

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2324
Author(s):  
Andrea Ricci ◽  
Claudio Carmine Guida ◽  
Paola Manzini ◽  
Chiara Cuoghi ◽  
Paolo Ventura
Keyword(s):  
Kidney Disease ◽  
Clinical Features ◽  
Aminolevulinic Acid ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Peptide Transporter ◽  
Porphyrin Metabolism ◽  
Pathologic Features ◽  
Kidney Involvement

Porphyrias are a group of rare disorders originating from an enzyme dysfunction in the pathway of heme biosynthesis. Depending on the specific enzyme involved, porphyrias manifest under drastically different clinical pictures. The most dramatic presentation of the four congenital acute hepatic porphyrias (AHPs: acute intermittent porphyria—AIP, ALAD deficiency, hereditary coproporphyria—HCP, and porphyria variegata—VP) consists of potentially life-threatening neurovisceral attacks, for which givosiran, a novel and effective siRNA-based therapeutic, has recently been licensed. Nonetheless, the clinical manifestations of acute porphyrias are multifaceted and do not limit themselves to acute attacks. In particular, porphyria-associated kidney disease (PAKD) is a distinct, long-term degenerating condition with specific pathological and clinical features, for which a satisfactory treatment is not available yet. In PAKD, chronic tubule-interstitial damage has been most commonly reported, though other pathologic features (e.g., chronic fibrous intimal hyperplasia) are consistent findings. Given the relevant role of the kidney in porphyrin metabolism, the mechanisms possibly intervening in causing renal damage in AHPs are different: among others, δ-aminolevulinic acid (ALA)-induced oxidative damage on mitochondria, intracellular toxic aggregation of porphyrins in proximal tubular cells, and derangements in the delicate microcirculatory balances of the kidney might be implicated. The presence of a variant of the human peptide transporter 2 (PEPT2), with a greater affinity to its substrates (including ALA), might confer a greater susceptibility to kidney damage in patients with AHPs. Furthermore, a possible effect of givosiran in worsening kidney function has been observed. In sum, the diagnostic workup of AHPs should always include a baseline evaluation of renal function, and periodic monitoring of the progression of kidney disease in patients with AHPs is strongly recommended. This review outlines the role of the kidney in porphyrin metabolism, the available evidence in support of the current etiologic and pathogenetic hypotheses, and the known clinical features of renal involvement in acute hepatic porphyrias.

scholarly journals Clinical features of kidney involvement in microscopic microscopic polyangiitis

2018 ◽  
Vol 90 (6) ◽  
pp. 55-58
Author(s):  
E M Shchegoleva ◽  
N M Bulanov ◽  
P I Novikov ◽  
S V Moiseev
Keyword(s):  
Clinical Features ◽  
Microscopic Polyangiitis ◽  
Renal Involvement ◽  
Rapidly Progressive Glomerulonephritis ◽  
Evaluation Agency ◽  
Consensus Conference ◽  
Chapel Hill ◽  
Kidney Involvement ◽  
Chapel Hill Consensus Conference ◽  
Rapidly Progressive Renal Failure

Aim. To evaluate clinical features and outcomes of renal involvement in patients with microscopic polyangiitis (MPA). Materials and methods: We enrolled 99 patients with MPA, diagnosed in accordance with the algorithm of the European Medicines Evaluation Agency (EMEA) and the Chapel Hill consensus conference definition (2012). Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and proteinuria were estimated. Frequency of rapidly progressive renal failure (a twofold increase in the sCr level in ≤3 months) was regarded as the clinical equivalent of rapidly progressive glomerulonephritis (RPGN). Results and discussion. Renal involvement was present in 92 (92.9%) patients. RPGN developed in 51 (55,4%) patients. The most common features of kidney involvement were hematuria and subnephrotic proteinuria. Arterial hypertension was revealed in 32 (34.7%) patients and was associated with RPGN (p

scholarly journals Clinical Presentation and Renal Histopathological Findings in Patients with Monoclonal Gammopathy and Kidney Disease

2020 ◽  
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Annachiara Ferrari ◽  
Giacomo Mori ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Monoclonal Gammopathy ◽  
Renal Involvement ◽  
Lymphoproliferative Disorders ◽  
M Protein ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Monoclonal Gammopathies ◽  
Increased Risk ◽  
Kidney Involvement

AbstractMonoclonal gammopathies have been widely associated with renal lesions. Nephrotoxicity of the secreted monoclonal (M)-protein relies on a complex interplay between biological characteristics and serum concentration. Little is known about the prevalence and renal manifestations of the different types of monoclonal gammopathies in patients with kidney disease.We reviewed all renal biopsies in our Center during a 12-year period to characterize patients diagnosed with monoclonal gammopathy. Data about demographics, laboratory examinations, renal manifestations and histological lesions were collected retrospectively. Results were correlated with the different lymphoproliferative disorders to evaluate the relationship between renal involvement and monoclonal gammopathies.Monoclonal gammopathy was detected in 179 (13.4%) patients. The circulating M-protein was secreted by monoclonal gammopathy of undetermined significate (MGUS) (51.9%), myeloma multiple (MM) (25.7%), primary amyloidosis (AL) (8.9%), smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%). Documented renal involvement in benign disorders such as MGUS and SMM accounted for 7.5% and 11.1%, respectively. MM was associated with an increased risk of kidney involvement (adjusted odds ratio=36.4; P=<0.001) and manifested with higher serum creatinine compared to other disorders. AL amyloidosis was principally secondary to MGUS (75%) and presented with nephrotic proteinuria. NHL and HL patients had heterogeneous renal manifestations. MGRS manifested both with light chain deposition disease and membranoproliferative glomerulonephritis. Compared to the other lymphoproliferative disorders, MM and AL amyloidosis showed higher creatinine blood levels and proteinuria, respectively. MM was significantly associated with kidney disease in our cohort of patients.Monoclonal gammopathy is a frequent diagnosis in patients with kidney disease. An accurate diagnostic process including lab tests and kidney biopsy is necessary to identify if the secreted M-protein is associated with renal involvement.

scholarly journals Spectrums and Prognosis of Kidney Disease in Patients with Ankylosing Spondylitis

2020 ◽  
Vol 6 (6) ◽  
pp. 444-452
Author(s):  
Dafeng He ◽  
Rong Wang ◽  
Shaoshan Liang ◽  
Dandan Liang ◽  
Feng Xu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ankylosing Spondylitis ◽  
Kidney Disease ◽  
Renal Involvement ◽  
Immunoglobulin A ◽  
Clinical Manifestations ◽  
Binary Logistic Regression ◽  
Serum Immunoglobulin ◽  
Binary Logistic Regression Analysis ◽  
Renal Prognosis

<b><i>Background/Aims:</i></b> Renal involvement was a common extra-articular manifestation of ankylosing spondylitis (AS). Few reports have investigated the pathological characteristics and renal outcomes of AS patients with kidney disease. The aim of this study was to investigate the pathological spectrums and the renal prognosis of AS patients with kidney disease. <b><i>Methods:</i></b> This retrospective and observational study was conducted working on 62 patients (47 males and 15 females) with a diagnosis of AS (ACR, 1984) and renal biopsies between 2008 and 2017. The histopathological findings and associated clinical manifestations were collected, and the renal prognoses of patients with kidney disease were evaluated too. Multivariate binary logistic regression analysis was performed to identify risk factors for the occurrence of IgA nephropathy (IgAN). <b><i>Results:</i></b> Renal biopsy revealed that IgAN accounted for a majority (74.2%) of the kidney disease with AS, while membranous nephropathies, minimal change disease, focal segmental glomerulosclerosis, and other lesions accounted for a small minority. Multivariate analysis revealed that serum immunoglobulin A &#x3e;3.45 g/L and immunoglobulin G &#x3e;9.06 g/L were risk factors for the occurrence of IgAN. With a median follow-up time of 24.3 months, 28 patients (50.9%) reached complete remission, 9 patients (16.4%) had partial remission, and 1 patient had an eGFR decline &#x3e;30%. No difference was found in prognosis between IgAN and non-IgAN. <b><i>Conclusion:</i></b> IgAN occurred in 76.4% of the kidney disease with AS, and higher serum immunoglobulin A and G increased the risk for the occurrence of IgAN. The renal prognosis of kidney disease in AS was good.

scholarly journals PILOT RESEARCH OF A GENETIC PREDISPOSITION FOR CLINICAL MANIFESTATIONS OF ACUTE INTERMITTENT PORPHYRIA

2019 ◽  
Vol 64 (2) ◽  
pp. 123-137
Author(s):  
O. S. Pshenichnikova ◽  
M. V. Goncharova ◽  
Y. S. Pustovoit ◽  
I. V. Karpova ◽  
V. L. Surin
Keyword(s):  
Aminolevulinic Acid ◽  
Clinical Manifestations ◽  
Acute Intermittent Porphyria ◽  
Severe Form ◽  
Heme Biosynthesis ◽  
Whole Exome ◽  
Number Of Patients ◽  
Detoxification Systems ◽  
Illumina Hiseq4000

Introduction. Acute intermittent porphyria (AIP) is the most common and severe form of acute hepatic porphyria. AIP is caused by a deficiency in the third enzyme of the heme biosynthesis system — hydroxymethylbilanine synthase (HMBS) — and has a dominant inheritance type. However, the probability of the clinical manifestation of this condition in carriers of the mutation in the HMBS gene constitutes only 10–20 %. Thi s suggests that the presence of such a mutation can be a necessary but not a sufficient condition for the development of the disease.Aim. To search for additional genetic factors, which determine the clinical penetrance of AIP using Whole-Exome Sequencing.Materials and methods. Sequencing of the whole exome was performed using a TruSeqExomeLibraryPrepkit (Illumina) kit by an Illumina HiSeq4000 instrument for 6 women with API with known mutations in the HMBS gene. All the patients suffered from a severe form of the disease. As a reference, a version of the hg19 human genome was used.Results. No common mutations were found in the examined patients. However, in each patient, functional variations were found in the genes related to detoxification systems, regulation of the heme biosynthesis cascade and expression of delta-aminolevulinic acid synthase (ALAS1) and in genes of proteins regulating nervous system. These variations require further study involving an extended number of patients with AIP manifestations and their relatives, who are asymptomatic carriers of disorders in the gene HMBS.Conclusions. The results obtained have allowed us to formulate a hypothesis about a possible role of genetic defects in the penetrance of AIP, which determine the development of other neurological pathologies. This is evidenced by the presence of gene pathogenic variations in 5 out of 6 examined patients, defects in which are associated with hereditary myasthenia and muscle atrophy.

scholarly journals Renal involvement in prolonged salmonella bacteremia: the role of schistosomal glomerulopathy

1992 ◽  
Vol 34 (3) ◽  
pp. 193-198 ◽  
Author(s):  
Reinaldo Martinelli ◽  
Luis Jose Cardoso Pereira ◽  
Edilson Brito ◽  
Heonir Rocha
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Renal Lesion ◽  
Steroid Resistant ◽  
Group I ◽  
The Mean ◽  
Group Ii ◽  
Hepatosplenic Schistosomiasis

Renal involvement has been well documented in patients with hepatosplenic schistosomiasis and in patients with prolonged salmonella bacteremia (PSB). Whether there is a specific renal lesion related to PSB or the chronic bacterial infection aggravates a pre-existing schistosomal glomerulopathy has been a matter of controversy. To analyze the clinical manifestations and histopathological findings of the renal involvement, 8 patients with hepatosplenic schistosomiasis and PSB (group I) were compared with 8 patients with schistosomal glomerulopathy (group II) matched by sex and glomerular disease. The mean age in group I was 17.7 years. All patients presented with hematuria, in 4 cases associated with non-nephrotic proteinuria. In group II the mean age was 23 years; nephrotic syndrome was the clinical presentation in 7 of the 8 patients in the group. All patients in group I experienced remission of the clinical and laboratory abnormalities as the salmonella infection was cured; in group II the patients had persistent, steroid-resistant, nephrotic syndrome. On histological examination, no difference was noted between the two groups, except for pronounced glomerular hypercellularity and interstitial mononuclear cell infiltration in group I. These observations strongly suggest that PSB exacerbates a pre-existing sub-clinical schistosomal glomerulopathy by the addition of active lesions directly related to the prolonged bacteremia

P0283LONG-TERM FOLLOW-UP OF CRYOGLOBULINEMIC SYNDROME WITH RENAL INVOLVEMENT AFTER DAA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Stefania Affatato ◽  
Ester Pollastri ◽  
Elena Belotti ◽  
Roberta Zani ◽  
Serena Zaltron ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Variable Interval ◽  
Type I ◽  
Skin Ulcers ◽  
Nephritic Syndrome ◽  
Cryoglobulinemic Glomerulonephritis ◽  
Almost All

Background and Aims To date, the literature shows that HCV eradication with DAA leads to remission from HCV-related cryoglobulinemic syndrome (CS). The goal of our study is to evaluate the effect of DAA treatment on cryoglobulinemic kidney disease. Method Since 2015, 58 patients (pts) have been treated in our Centre; among them we have selected 12 pts with active kidney disease at the time of treatment. Clinical manifestations, renal function and immunological tests were monitored during follow-up (range 6-48 months). Results General characteristics of the population are shown in Table 1. At the time of treatment 6 pts had nephritic syndrome (sdr), 1 had nephrotic sdr and 5 pts had mixed nephritic-nephrotic sdr. It should be noted that 8/12 pts had been treated with Rituximab (RTX) in the 6 months preceding the DAA; despite that they had active disease at baseline. Ten out of 12 pts went into complete remission after HCV-eradication, 1 went into partial remission. One pt, never treated, did not respond clinically to HCV eradication and therefore underwent RTX therapy. Other 2 pt with a recent diagnosis of cryoglobulinemic syndrome came to our attention with a clinical picture of nephritic sdr: they’d never been treated with immunosuppressive therapy and get remission only whit HCV eradication. One pt, although complete CS remission, started hemodialysis for ESRD secondary to ADPKD. During follow-up 3 pts underwent CS relapse: 2 pts, one with lymphoma, were retreated with RTX after 12 and 48 months respectively; 1 pt, with type I cryoglobulinemia and clinical manifestation of vasculitis, died of acute disease reactivation in Cameroon after 9 months from the end of DAA. By evaluating the overall population there is a rapid and prolonged clinical response to DAA therapy, in particular a complete resolution of skin ulcers (Tab 2). Cryocrit decreases and C3 and C4 increase early and persistently after treatment; vice versa the rheumatoid factor does not undergo significant variations. Proteinuria is reduced at the end of the treatment (EOT) and shows a decreasing trend also afterwards; urinary sediment is drastically reduced at EOT and further decreases during follow-up up to the presence of only isolated urinary anomalies in almost all patients (Tab 3). Conclusion The eradication of HCV, and therefore the removal of the immunological stimulus underlying the cryogloblinemic syndrome, appears to be crucial in the control of cryoglobulinemic glomerulonephritis, also after failure of RTX treatment. However, relapses at variable interval from DAA therapy do not allow us to lose these patients to follow-up even after several years from disease remission.

scholarly journals Antiphospholipid Syndrome (APS) - An Update on Clinical Features and Treatment Options

2015 ◽  
Vol 8 (1) ◽  
pp. 27-38 ◽  
Author(s):  
Mamatha Katikaneni ◽  
Meera Gangam ◽  
Seth Mark Berney ◽  
Sarwat Umer
Keyword(s):  
Clinical Features ◽  
Antiphospholipid Syndrome ◽  
Treatment Options ◽  
Anticoagulation Therapy ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Thrombotic Risk

Antiphospholipid syndrome (APS) is an autoantibody disorder characterized by the presence of antiphospholipid (APL) antibodies and heterogeneous clinical manifestations. Patients may present with recurrent thrombosis, obstetric morbidity, cardiac valvular lesions, thrombocytopenia, skin lesions, renal or neurologic abnormalities. We provide a comprehensive review of these diverse clinical features except renal and obstetric complications. Treatment of APS can be challenging as one tries to balance the benefit of anticoagulation therapy in this hypercoagulable state while minimizing the risk of bleeding. We discuss the various therapeutic options including the role of aspirin, warfarin, low molecular weight heparin, new direct thrombin inhibitors, hydroxychloroquine, intravenous gamma globulin, rituximab and others. Lower risk APS patients (i.e. first venous thrombosis) should receive warfarin with a target INR of 2.0-3.0. Higher risk patients (i.e. arterial thrombosis or recurrent venous events) have a target INR of >3.0. Currently, warfarin remains the mainstay in treatment of APS. Because of lack of adequate data, the newer oral direct inhibitors should be considered only when there is a known allergy/ intolerance or poor control with warfarin. Additional vascular and thrombotic risk factors should be aggressively reduced. Further studies involving large number of APS patients, diagnosed according to accepted criteria, are needed to better define the role of newer anticoagulants and other novel therapies.

scholarly journals Biopsy-Proven Kidney Involvement in Hypocomplementemic Urticarial Vasculitis

2021 ◽  
Author(s):  
Alice Corthier ◽  
Marie Jachiet ◽  
Daniel Bertin ◽  
Aude Servais ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Biopsy ◽  
Systemic Vasculitis ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Urticarial Vasculitis ◽  
Kidney Involvement ◽  
National Cohort ◽  
Hypocomplementemic Urticarial Vasculitis

Abstract Background. Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up. Methods. All patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group, were included. A systematic literature review on kidney involvement of HUV was performed. Results. Twelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (GN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n=6), tubules (n=4) or renal arterioles (n=3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3-4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant. Conclusion. Renal involvement of HUV can be responsible for severe AKI, CKD and ESKD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly membrano-proliferative GN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.

scholarly journals Kidney Disease and Gout: The Role of the Innate Immune System

2016 ◽  
Vol 9 (1) ◽  
pp. 12-21 ◽  
Author(s):  
William F. Finn
Keyword(s):  
Immune System ◽  
Kidney Disease ◽  
Innate Immune System ◽  
Close Association ◽  
Clinical Manifestations ◽  
Innate Immune ◽  
Tubular Injury ◽  
Renal Tubular ◽  
Stimulation Of

The clinical manifestations and consequence of acute and chronic gout are closely associated with the activation of the innate immune system, stimulation of the NLP3 inflammasome and secretion of interleukin-1β and interleukin-18 via caspace-1 activity. This leads to cytokine release and an inflammatory response. It is now clear that a similar involvement of the innate immune system occurs in many forms of acute and chronic kidney disease with accentuation of renal tubular injury and stimulation of tubulointerstitial fibrosis. The local and systemic activation of the innate immune system may help explain the close association of these conditions and provide a target for therapeutic interdiction.

scholarly journals Clinical Relevance of HLA-DRB1 and -DQB1 Alleles in Iranian Systemic Lupus Erythematosus Patients

2021 ◽  
Author(s):  
Ashkan Rasouli-Saravani ◽  
Ahmad Tahamoli-Roudsari ◽  
Mahdi Behzad ◽  
Mehrdad Hajilooi ◽  
Ghasem Solgi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Features ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Human Leukocyte ◽  
Pulmonary Involvement ◽  
Systemic Lupus ◽  
Protective Allele ◽  
Allele Drb1

Given the potential link between genetic risk factors and clinical features of systemic lupus erythematosus (SLE), this study aimed to explore the relationship between human leukocyte antigen (HLA)-DRB1/DQB1 alleles and haplotypes and clinical sub-phenotypes of the disease in a group of Iranian SLE patients. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP in 127 SLE patients and 153 ethnically-matched healthy controls. The relationships between various clinical manifestations and HLA alleles/haplotypes were analyzed in the patients. We observed the positive associations of DRB1*07 and DRB1*07-DQB1*02 haplotypes with articular and pulmonary involvement (p=0.006 and p<0.001 respectively), DRB1*03 and DQB1*02 alleles, and DRB1*03-DQB1*02 haplotypes with cutaneous (p=0.03, p=0.004 and p=0.02 respectively) and renal involvement, and DRB1*13 as well as DRB1*13-DQB1*06 haplotypes with renal involvement. Conversely, negative associations of DRB1*13 with cutaneous and gastrointestinal disorders (p=0.004 and p=0.02 respectively) and DRB1*01 with renal involvement (p=0.03) were found in our patients. Patients carrying susceptible HLA-DRB1 alleles had a higher risk for expression of cutaneous involvement (p=0.03), anti-coagulant antibody development (p=0.01), and a lower risk for pulmonary disorders compared to patients' negatives for susceptible alleles (p=0.04). Our findings on associations between HLA risk allele (DRB1*03) as well as non-risk alleles with particular clinical manifestations and between the potentially protective allele (DRB1*01) and protection against renal involvement indicate the important role of HLA class II genes in predisposing of specific serological and clinical features of SLE disease which could be implicative for therapeutic applications and better management of SLE patients.

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