Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy:A case report

BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.

C3 Glomerulopathy and Therapeutic Potential of C5 Complement Inhibitors

C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology characterized by accumulation of C3 with absent or scanty immunoglobulin deposition. The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. Specifically, in C3 glomerulopathy patients, there exists a prolongation of C3 cleavage which causes the uncontrolled alternative pathway activation. Many treatments have been investigated for treating C3 glomerulopathy to little or no avail, including calcineurin inhibitors, plasmapharesis, and anti-CD20 monoclonal antibodies. The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. Here in this paper we discuss and present various case studies and clinical trials available that experiment with Eculizumab in patients with either dense deposit disease or C3 glomerulonephritis. In most of these patients, treatment with Eculizumab has demonstrated clinical and biochemical improvements in kidney function. These results provide encouraging evidence that suggest Eculizumab as a promising therapy for patients with C3 glomerulopathy and warrant that more extensive clinical trials can be designed as a next step.

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

De Novo Glomerular Diseases after COVID-19 Vaccination: Consequence or Coincidence?

Introduction: Vaccination against COVID-19 has proven highly effective in preventing severe forms of the disease. However, the literature reports several cases associating renal damage and the anti-COVID vaccine. The aim of our work was to report a case series of patients who developed glomerulopathy after anti-COVID-19 vaccine. We evaluated the type of vaccine, the clinico-biological profile, and the anatomopathological, therapeutic and evolutionary aspects. Material and Methods: Prospective descriptive study conducted at the Nephrology Department of CHU IbnSina in Rabat between December 2021 and June 2022 including 9 patients who presented with glomerulopathy after the 1st dose of anti-COVID-19 vaccine. We excluded patients followed for nephropathy. Results: The mean age of our patients was 33 ± 16 years with a sex ratio of 0.8. Six patients received an inactivated vaccine, 2 patients received a mRNA vaccine and 1 patient received a viral vector vaccine. The mean delay between the onset of signs and the date of the first vaccine dose was 3.1 +/? 0.65 months (1 - 6 months). All patients had a nephrotic syndrome, 2 pure and 7 impure: 3 patients had acute renal failure and microscopic hematuria, 2 patients had microscopic hematuria and 2 patients had acute renal failure. Histologically, focal segmental glomerulosclerosis (FSGS) was noted in 4 patients, lupus nephropathy in 3, and membranous nephropathy (MN) in 2. Specific treatment was administered to each patient, depending on the histological type of renal involvement and the context. After 6 months, complete remission was achieved in 5 patients, with no improvement in 2, and one patient was placed on hemodialysis. One patient died of another cause. Conclusion: The causal link between anti-COVID 19 vaccination and renal disease is highly probable, but remains to be confirmed.

Obesity-related glomerulopathy： pathogenesis, pathologic, clinical characteristics and treatment

n light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related giomerulopathy （ORG） is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 （C3） nonspeciflcally deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria （ 〈 3.5 g/d） is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin-angiotensin-aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

Plasma level and genetic variation of apolipoprotein E in patients with lipoprotein glomerulopathy

Background Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E (apoE). In this study, 15 Chinese patients with LPG were involed in exploring the association of the genetic variation and its plasma level in the pathogenesis of LPG.Methods A retrospective analysis of the clinical and pathological features was made in 15 patients with LPG. Plasma concentrations of apoE were measured with radial immunodiffusion assay. Genetic variations of apoE gene were detected using polymerase chain reaction and restriction fragment length polymorphism. Glomerular deposition of apoA, apoB and apoE in these patients were detected by immunofluorescence staining using monoclonal antibodies. Results Biochemical profiles of lipids and lipoproteins revealed markedly elevated levels of triglyceride, apoB and apoE, but approximately normal levels of total cholesterol, apoA1 and lipoprotein(a) [Lp(a)], which resembled familial hypertriglyceridemia. Genetic analysis demonstrated that the genotype distribution of apoE were 7 cases with (ε3/ε 4,)4 cases with ε3/ε 3 and 2 cases with ε2/ε 3. The other 2 cases (a mother and her son) showed a same distinct band. The band pattern of later 2 cases was quite similar to the apoE variant of Tokyo type. The calculated allele frequency of ε 4 was relatively high in cases with LPG in comparison with that in the normal controls. We further divided the 13 patients into three groups according to their genotypes of apoE. Patients with the genotype of apoE ε2/ε3 showed a lower level of plasma apoE as compared to those with apoE ε3/ε4 (P<0.05). The serum level of high-density lipoprotein (HDL) was the lowest in patients with the genotype of apoE ε3/ε4. No difference was found among the patients with different apoE genotype in the other clinical and pathological characteristics. Conclusions The genotype of apoE ε3/ε4 is the predominant one in Chinese patients with LPG. Patients with this genotype tend to have a higher plasma level of apoE and more severe lipid dysmetabolism. No correlation was found between the genotype of apoE and the clinical features in patients with LPG.

Purinergic 2X7Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

A Case of Podocytic Infolding Glomerulopathy with Primary Sjogren's Syndrome and Hashimoto's Thyroiditis

To the Editor:Podocytic infolding glomerulopathy (PIG)was proposed as a new disease entity in 2008,[1] and great attention has been paid to PIG because of the rare pathological changes to glomeruli associated with it.PIG is characterized by specific changes to the thickened glomerular basement membrane (GBM), including microspheres,microtubular structures,and podocytic infolding.However,the clinical features and pathogenesis of PIG still remain unclear.To elucidate the characteristics of this glomerulopathy,accumulating more information from reported cases is necessary.Herein,we present a case of glomerulopathy showing podocytic infolding in association with primary Sjogren's syndrome (pSS)and Hashimoto's thyroiditis.

Fibronectin Glomerulopathy： A Rare Autosomal Dominant Glomerular Disease

A 43-year-old female was admitted to the Department of Nephrology at Jinling Hospital （Nanjing,China） in January 2017 complaining of edema for 3 months with urine abnormalities.Her father had renal disease （with no biopsy performed） when he was 40 years old and died of uremia at 56 years old.Her mother and brother were healthy;however,her daughter and nephew （her brother＇s son） had slightly high microalbumin levels in routine urine screenings.Her daughter＇s urinary protein level was weakly positive,whereas her nephew＇s urinary protein level was negative.

Lipoprotein glomerulopathy: clinical features and pathological characteristics in Chinese

Background Lipoprotein glomerulopathy (LPG), once recognized as a rare glomerular disease, has been reported around the world in recent years. In this study, we reported 8 patients of LPG and aimed to explore the clinical features and pathological characteristics of LPG under light microscope, immunofluorescence staining, and electron microscope.Methods Clinical manifestations were recorded on the day of renal biopsy. Biochemical patterns of lipids and lipoproteins were detected by routine examination. Plasma concentrations of apo B and apo E were determined by radial immunodiffusion assays. Biopsy specimens were then processed for light microscopy, immunohistochemical staining for immunoglobulins and complement components, and electron microscopy. Glomerular deposition of apo A, B, and E were detected using monoclonal antibodies on cryostatic sections.Results All of the eight patients presented with edema, microscopic hematuria, severe proteinuria, anemia, and enlarged kidney size. Biochemical profiles revealed high levels of triglycerides, apo B, and apo E. We noted increments of glomerular size and lipoprotein thrombi occupying capillary lumina in the glomeruli of all patients. Immunofluorescence staining showed that the thrombi were strongly positive for apo A, B, and E. Granules and various sizes of vacuoles were observed in the thrombi under electron microscope.Conclusion Compared with previous reports on LPG in other countries, unique clinical and pathological features were found in this group of Chinese LPG patients.

A novel apolipoprotein E mutation (p.Arg150Cys)in a Chinese patient with lipoprotein glomerulopathy

To the Editor:Lipoprotein glomerulopathy (LPG) is an uncommon inherited renal disease characterized by lipoprotein thrombi in the markedly dilated capillary lumina of affected glomeruli, high plasma concentrations of apolipoprotein E (apoE), and proteinuria.[1] It mainly affects people of Japanese and Chinese origin, and approximately 117 cases have been reported to date.[2,3] Several genetic studies have demonstrated that APOE gene mutations may lead to the development of LPG;[4,5,6] however, conflicting published evidence has found that some patients with APOE variants were unaffected.[7] Thus, further studies are needed to examine the role of APOE mutations in the pathogenesis of LPG.This study investigated a novel point mutation in the APOE gene in a family with one LPG patient and an asymptomatic carrier of the same APOE variant.

Uncharted Territory: Frequent Relapsing, Steroid Sensitive Secondary Minimal Change Nephrotic Syndrome Cause by Solid Tumor of the Gastro-Esophageal Junction —(Case Presentation and Review of the Literature)

We reported a biopsy proved case of minimal change nephrotic syndrome in a 72-year-old patient. The minimal change nephrotic syndrome has been steroid sensitive, but the patient had 7 relapses over a span of 5 years. Each time the dose of steroid is tapered, a relapse of the nephrotic syndrome occurred. Eventually, the patient was complaining of dysphagia and difficulty swallowing. Hospital work-up with barium swallow, endoscopy, and CT of the chest, abdomen and pelvis, revealed a focal stenotic lesion with mild to moderate esophageal dysmotility 7/15/2022. A diagnosis of an ulcerating lesion with biopsy confirmed a neuro-endocrine carcinoma of the gastro-esophageal junction was entertained. The CT of the chest/abdomen/pelvis, 7/19/2022, has shown, an esophageal mass of 5.1 × 5.6 × 7 cm of the gastro-esophageal junction with ulceration. No evidence of spread beyond the esophagus and stomach. The histology revealed a poorly differentiated neuroendocrine tumor of the gastro-esophageal junction. The patient underwent several rounds of chemotherapy, radiation, and surgery culminating in tumor control. His nephrotic syndrome was resolved after the tumor has been controlled by surgery and chemotherapy.

The correlation of spot urinary protein-to-creatinine ratio with 24-h urinary protein excretion in various glomerulopathies

BACKGROUND Proteinuria is an important and well-known biomarker of many forms of kidney injury.Its quantitation is of particular importance in the diagnosis and management of glomerular diseases.Its quantification can be done by several methods.Among these,the measurement of 24-h urinary protein excretion is the gold standard method.However,it is cumbersome,time-consuming,and inconvenient for patients and is not completely foolproof.Many alternative methods have been tested over time albeit with conflicting results.Among the latter,the measurement of urine protein-to-creatinine ratio(uPCR)in singlevoided urinary samples is widely used.The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation,whereas others did not.AIM To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single largevolume nephrological center in Pakistan.METHODS This cross-sectional,observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan from September 2017 to March 2018.All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled.All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations.A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample.The data of patients were collected in a proforma.SPSS version 20.0 was used for statistical analysis.RESULTS A total of 157 patients were included.Their mean age was 30.45±12.11 years.There were 94(59.8%)males and 63(40.2%)females.The mean 24-h urinary protein excretion was 3192.78±1959.79 mg and the mean spot uPCR was 3.16±1.52 in all patients.A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion(r=0.342,P=0.01)among all patients.On subgroup analysis,a slightly better correlation was found in patients older than 47 years(r=0.78),and those with body mass index>25 kg/m2(r=0.45).The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods.CONCLUSION Overall,the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies.The agreement between the two methods was also poor.Hence,there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.

C3肾小球病诊治进展

C3肾小球病(C3 glomerulopathy,C3G)是新近发现的一种因补体旁路途径过度激活导致的肾小球肾炎。本文综述了C3肾小球病的发展史、定义、发病机制、分型及其特点、诊断、治疗进展等,并对未来的诊断治疗进行了展望。

Hepatitis C virus associated glomerulopathies

Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type&#x02005;I&#x02005;MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-&#x003b1; plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.

Podocyturia: Potential applications and current limitations

Chronic kidney disease is a prevalent condition that affects millions of people worldwide and is a major risk factor of cardiovascular morbidity and mortality. The main diseases that lead to chronic kidney disease are frequent entities as diabetes mellitus, hypertension and glomerulopathies. One of the clinical markers of kidney disease progression is proteinuria. Moreover, the histological hallmark of kidney disease is sclerosis, located both in the glomerular and in the interstitial compartments. Glomerulosclerosis underscores an irreversible lesion that is clinically accompanied by proteinuria. In this regard, proteinuria and glomerular sclerosis are linked by the cell that has been conserved phylogenetically not only to prevent the loss of proteins in the urine, but also to maintain the health of the glomerular fltration barrier： The podocyte. It can then be concluded that the link between proteinuria, kidney disease progression and chronic kidney disease is mainly related to the podocyte. What is this situation due to？ The podocyte is unable to proliferate under normal conditions, and a complex molecular machinery exists to avoid its detachment and eventual loss. When the loss of podocytes in the urine, or podocyturia, is taking place and its glomerular absolute number decreased, glomerulosclerosis is the predominant histological feature in a kidney biopsy. Therefore, tissular podocyte shortage is the cause of proteinuria and chronic kidney disease. In this regard, podocyturia has been demonstrated to precede proteinuria, showing that the clinical mana-gement of proteinuria cannot be considered an early intervention. The identifcation of urinary podocytes could be an additional tool to be considered by nephrologists to assess the activity of glomerulopathies, for follow-up purposes and also to unravel the pathophysiology of podocyte detachment in order to tailor the therapy of glomerular diseases more appropriately.

Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression

BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.AIM To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.METHODS In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.RESULTS We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy(IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy(TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR(40%),TG(17%), and IFTA(13%). Most grafts failed within two years of post-transplant(36%). Subsequently, approximately 10%-15% of grafts failed every two years: >2-4 years(16%), > 4-6 years(13%), > 6-8 years(11%), > 8-10 years(9%) and > 10 years(16%). AR was the most common cause of graft failure in the first six years(48%), whereas TG was the most prevalent cause of graft failure after 6 years(32%) of transplant.CONCLUSION In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Reclassification of membranoproliferative glomerulonephritis:Identification of a new GN:C3GN

This review revises the reclassification of the mem-branoproliferative glomerulonephritis （MPGN） after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and patho-genesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized： The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecifc treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in fnding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

Complement involvement in kidney diseases:From physiopathology to therapeutical targeting

Complement cascade is involved in several renal diseases and in renal transplantation. The different components of the complement cascade might represent an optimal target for innovative therapies. In the frst section of the paper the authors review the physiopathology of complement involvement in renal diseases and transplantation. In some cases this led to a reclassifcation of renal diseases moving from a histopathological to a physiopathologicalclassification. The principal issues afforded are： renal diseases with complement over activation, renal diseases with complement dysregulation, progression of renal diseases and renal transplantation. In the second section the authors discuss the several complement components that could represent a therapeutic target. Even if only the anti C5 monoclonal antibody is on the market, many targets as C1, C3, C5a and C5aR are the object of national or international trials. In addition, many molecules proved to be effective in vitro or in preclinical trials and are waiting to move to human trials in the future.

Complement related kidney diseases:Recurrence after transplantation

The recurrence of renal disease after renal transplantation is becoming one of the main causes of graft loss afterkidney transplantation. This principally concerns some of the original diseases as the atypical hemolytic uremic syndrome(HUS), the membranoproliferative glomerulonephritis(MPGN), in particular the MPGN now called C3 glomerulopathy. Both this groups of renal diseases are characterized by congenital(genetic) or acquired(autoantibodies) modifications of the alternative pathway of complement. These abnormalities often remain after transplantation because they are constitutional and poorly influenced by the immunosuppression. This fact justifies the high recurrence rate of these diseases. Early diagnosis of recurrence is essential for an optimal therapeutically approach, whenever possible. Patients affected by end stage renal disease due to C3 glomerulopathies or to atypical HUS, may be transplanted with extreme caution. Living donor donation from relatives is not recommended because members of the same family may be affected by the same gene mutation. Different therapeutically approaches have been attempted either for recurrence prevention and treatment. The most promising approach is represented by complement inhibitors. Eculizumab, a monoclonal antibody against C5 convertase is the most promising drug, even if to date is not known how long the therapy should be continued and which are the best dosing. These facts face the high costs of the treatment. Eculizumab resistant patients have been described. They could benefit by a C3 convertase inhibitor, but this class of drugs is by now the object of randomized controlled trials.