Recurrent macroscopic hematuria in a pediatric patient: is it early to diagnose as having type I hereditary C2 deficiency?

Hereditary C2 deficiency is the most common early complement deficiency and characterized by recurrent infections and autoimmunity despite most patients are also asymptomatic. Type I hereditary C2 deficiency is caused by a heterozygous deletion in C2 gene resulting in early stop codon and lack of C2 production. Clinical spectrum may vary and pure nephrological involvement without the presence of recurrent infections is scarce in hereditary C2 deficiency.We report here a previously healthy 14-year-old boy presenting recurrent self-limited macroscopic hematuria and persistently low serum C4 levels, diagnosed as having type I hereditary C2 deficiency with confirming a novel heterozygote deletion (c.1567 + 22_1567 + 43del) in C2 gene. He has been remained asymptomatic for the next 18 months. Since the diagnosis of C2 deficiency was made in the absence of organ-threatening involvement such as immune complex-mediated glomerulonephritis, we think that early diagnosis and optimal follow-up may improve life-span of the patients with hereditary early complement deficiencies.

The Changing Face of Human Immunodeficiency Virus-Mediated Kidney Disease.

In nearly 40 years since human immunodeficiency virus (HIV) first emerged, much has changed. Our understanding of the pathogenesis of HIV infection and its effect on the cells within each kidney compartment has progressed, and the natural history of the disease has been transformed. What was once an acutely fatal illness is now a chronic disease managed with oral medications. This change is largely due to the advent of antiretroviral drugs, which have dramatically altered the prognosis and progression of HIV infection. However, the success of antiretroviral therapy has brought with it new challenges for the nephrologist caring for patients with HIV/acquired immune deficiency syndrome, including antiretroviral therapy-induced nephrotoxicity, development of non-HIV chronic kidney disease, and rising incidence of immune-mediated kidney injury. In this review, we discuss the pathogenesis of HIV infection and how it causes pathologic changes in the kidney, review the nephrotoxic effects of select antiretroviral medications, and touch upon other causes of kidney injury in HIV cases, including mechanisms of acute kidney injury, HIV-related immune complex glomerular disease, and thrombotic microangiopathy.

A review of renal disease in children with HIV infection.

Human immunodeficiency virus (HIV) infection continues to be a leading cause of morbidity and mortality. HIV-infected individuals are now surviving for a relatively longer period and this is because of easy accessibility to antiretroviral therapy these days. As a result, chronic disease-related complications are now being recognized more often. Kidney disease in HIV-infected children can vary from glomerular to tubular-interstitial involvement. We searched the database to identify various kidney diseases seen in HIV-infected children. We describe the epidemiology, pathogenesis, pathology, clinical and laboratory manifestations, management and outcome of commonly seen kidney disease in HIV-infected children. We also provide a brief overview of toxicity of antiretroviral drugs seen in HIV-infected children. Kidney involvement in HIV-infected children may arise because of HIV infection per se, opportunistic infections, immune mediated injury and drug toxicity. HIV-associated nephropathy is perhaps the most common and most severe form of kidney disease. Proteinuria may be a cost-effective screening test in the long-term management of HIV-infected children, however, there are no definite recommendations for the same. Other important renal diseases are HIV immune complex kidney disease, thrombotic microangiopathy, interstitial nephritis and vasculitis.

Immune Complex Membranoproliferative Glomerulonephritis Associated with Transjugular Intrahepatic Portosystemic Shunts in Alcoholic Cirrhosis: Two Case Reports.

OBJECTIVE: To report on 2 patients with alcoholic cirrhosis who were treated with transjugular intrahepatic portosystemic shunt (TIPS) placement. CLINICAL PRESENTATION AND INTERVENTION: The 2 patients had a history of alcoholic cirrhosis, and TIPS surgery was performed on them. In both cases, 4 months after TIPS placement, proteinuria was observed along with histological alterations characteristic of immune complex membranoproliferative glomerulonephritis (MPGN). CONCLUSION: The TIPS in one patient was successful without immediate complications, while the other patient was referred for a combined liver-kidney transplant. In both cases, immune complex MPGN might have developed after TIPS placement probably due to a reduced immune complex clearance.

Non-immunoglobulin A mesangial immune complex glomerulonephritis in kidney transplants.

We have observed a predominantly mesangial non-immunoglobulin A immune complex mesangial glomerulopathy (MG) in renal transplants with mesangial deposits by immunofluorescence and electron microscopy. Clinicopathological features of 28 patients with MG were analyzed and compared with 28 transplant controls, matched for age, sex, ethnicity, donor type, estimated glomerular filtration rate, and interval from transplant to biopsy. Indications for biopsy in the MG group were allograft dysfunction in 64%, allograft dysfunction/proteinuria in 29%, and proteinuria in 7%. Biopsy indications in controls were allograft dysfunction (61%), allograft dysfunction/proteinuria (18%), proteinuria (14%), and delayed graft function (7%). Most MG cases had mild mesangial hypercellularity with endocapillary proliferation in 2 and crescents in 2 without fibrinoid necrosis. Immunoglobulin M-dominant deposits were present in 83%, and immunoglobulin G was dominant in 17% with mesangial deposits in 93% of cases by electron microscopy. Compared with controls, MG had higher Banff interstitial inflammation score (i) (P = .036) and was associated with concurrent acute T-cell-mediated rejection (P = .023), but not with acute or chronic antibody-mediated rejection. MG patients and controls had similar prevalence of polyomavirus nephropathy and Epstein-Barr virus infection. At follow-up, most MG patients had stable estimated glomerular filtration rate with no or stable proteinuria. Disease-specific graft survival was not different in MG versus controls. We conclude that, in view of the apparent self-limited nature of this lesion, additional treatment may not be required in these patients. Awareness of this lesion may thus spare patients unwarranted further intervention.

Advances in the pathogenesis of HIV-associated kidney diseases.

Despite improved outcomes among persons living with HIV who are treated with antiretroviral therapy, they remain at increased risk for acute and chronic kidney diseases. Moreover, since HIV can infect renal epithelial cells, the kidney might serve as a viral reservoir that would need to be eradicated when attempting to achieve full virologic cure. In recent years, much progress has been made in elucidating the mechanism by which HIV infects renal epithelial cells and the viral and host factors that promote development of kidney disease. Polymorphisms in APOL1 confer markedly increased risk of HIV-associated nephropathy; however, the mechanism by which ApoL1 variants may promote kidney disease remains unclear. HIV-positive persons are at increased risk of acute kidney injury, which may be a result of a high burden of subclinical kidney disease and/or viral factors and frequent exposure to nephrotoxins. Despite the beneficial effect of antiretroviral therapy in preventing and treating HIVAN, and possibly other forms of kidney disease in persons living with HIV, some of these medications, including tenofovir, indinavir, and atazanavir can induce acute and/or chronic kidney injury via mitochondrial toxicity or intratubular crystallization. Further research is needed to better understand factors that contribute to acute and chronic kidney injury in HIV-positive patients and to develop more effective strategies to prevent and treat kidney disease in this vulnerable population.

[Leprosy reactions in a Colombian national reference centre]. / Reacciones por lepra en un centro de referencia nacional en Colombia.

INTRODUCTION: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. OBJECTIVE: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. MATERIALS AND METHODS: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. RESULTS: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. CONCLUSIONS: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

Reacciones por lepra en un centro de referencia nacional en Colombia / Leprosy reactions in a Colombian national reference centre

Introducción. Colombia es el país de América con mayor proporción de casos nuevos de lepra con discapacidad grave. Para disminuir tal discapacidad se requiere el control de las reacciones, principal causa del daño neural en esta enfermedad. Objetivo. Describir las características clínicas y epidemiológicas y el tratamiento de los pacientes con reacciones de tipo 1 y 2 que consultaron al Centro Dermatológico Federico Lleras Acosta. Materiales y métodos. Se trata de un estudio descriptivo que incluyó la población de pacientes con diagnóstico clínico de reacciones de tipo 1 y de tipo 2 por lepra, que acudieron al centro entre los años 2003 y 2009. Resultados. Se estudiaron 96 reacciones, 35 del tipo 1 y 61 del tipo 2. El 75 % de los pacientes provenía de los departamentos de Tolima, Cundinamarca, Santander y Boyacá. El 56 % de las reacciones de tipo 1 se presentaron antes de iniciar la poliquimioterapia para la lepra; el dermatólogo tratante consideró que las reacciones que se presentaron después de suspender la poliquimioterapia eran recaídas. El 94 % de las reacciones de tipo 1 se trataron con corticoides orales. El 97 % de los pacientes con reacciones de tipo 2 presentaron eritema nudoso, y todos se trataron con talidomida. Conclusiones.La clínica de la reacción de tipo 1 puede orientar al diagnóstico de la lepra en un paciente sin el antecedente de esta enfermedad (56 %). La reacción de tipo 1 que se inicia después de suspender la poliquimioterapia para la lepra, podría ser una manifestación de recaída de la enfermedad. La reacción de tipo 2 es más frecuente en hombres, con una relación hombre a mujer de 4:1. El 97 % de los pacientes con reacción de tipo 2 presentó eritema nudoso.

Introduction: Colombia is the country in America with the highest proportion of new cases leprosy with severe disability. To decrease such disability it is necessary to control these reactions, the main cause of nerve damage in leprosy. Objective: To describe the clinical and epidemiological characteristics and the treatment of patients with type 1 and 2 leprosy reactions who consulted the Centro Dermatológico Federico Lleras Acosta. Materials and methods: It is a descriptive study which included patients with clinical diagnoses of type 1 and 2 reactions who were seen in the center between 2003 and 2009. The town of origin of the patients, their age, clinical features and treatments were analysed. Results: We studied 96 reactions in 87 patients, 35 type 1 and 61 type 2 reactions; 75% of the patients came from the departments of Tolima, Cundinamarca, Santander and Boyacá; 77% of type 1 reaction occurred before the beginning of multidrug therapy for leprosy. The reactions that started after stopping the multidrug therapy were considered as a leprosy relapse. Conclusions: Correct identification of type 1 reaction by the general practitioner will allow the diagnosis of leprosy in a large percentage of patients. The type 1 reaction that begins after stopping the leprosy multidrug therapy may be a manifestation of a relapse of the disease.

Morphologic features of extrahepatic manifestations of hepatitis C virus infection.

Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. The majority of these conditions are thought to be immune mediated. The most documented of these entities is mixed cryoglobulinemia. Morphologically, immune complex depositions can be identified in small vessels and glomerular capillary walls, leading to leukoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. Other HCV-associated entities include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, diabetic nephropathy, B-cell non-Hodgkin lymphomas, insulin resistance, sialadenitis, sicca syndrome, and autoimmune thyroiditis. This paper highlights the histomorphologic features of these processes, which are typically characterized by chronic inflammation, immune complex deposition, and immunoproliferative disease in the affected organ.

A case of recurrent light chain deposition disease after living-related renal transplantation - detailed process of the recurrence.

A 53-yr-old woman with end-stage renal disease was admitted for renal transplantation (RTX). About a decade ago, she had presented with urinary abnormalities. Monoclonal IgA lambda was detected. Renal biopsy showed nodular glomerulosclerosis, and an immunohistochemical study for lambda was negative. Fibrillary glomerulonephritis was suggested as the most likely diagnosis. RTX was successfully performed, and graft function was stable for the first half year. Graft biopsy was performed at one yr post-transplant. Glomeruli showed nodular lesion similar to native kidney biopsy findings. Immunofluorescence microscopy (IF) indicated strong lambda staining along the glomerular basement membrane, the tubular basement membrane (TBM), and the peritubular capillary. The diagnosis of recurrent light chain deposition disease (LCDD) was confirmed. A series of biopsies are available to conduct studies on the recurrent process of LCDD. Light microscopy showed no remarkable changes up to six months post-RTX. However, the IF study revealed evident granular depositions of lambda along the TBM only at the one-h biopsy. Typical IF staining pattern of lambda and EDD compatible with LCDD were noted after six months post-transplant. This is the first case report that elucidated the details of the recurrent process of LCDD at one yr after the operation.

Pathogenesis and therapies of immune-mediated myopathies.

The most common autoimmune muscle disorders include dermatomyositis (DM), polymyositis (PM), necrotizing autoimmune myositis (NAM) and sporadic inclusion body myositis (sIBM). DM is a complement-mediated microangiopathy leading to destruction of capillaries, hypoperfusion and inflammatory cell stress on the perifascicular regions. NAM is an increasingly recognized subacute myopathy triggered by statins, viral infections, cancer or autoimmunity with macrophages as the final effector cells causing fiber injury. PM and IBM are T cell-mediated disorders where cytotoxic CD8(+) T cells clonally expand in situ and invade major histocompatibility complex class I expressing muscle fibers. In sIBM, in addition to autoreactive T cells, there are degenerative features characterized by vacuolization and accumulation of stressor or amyloid-related misfolded proteins; an interrelationship between inflammatory and degeneration-associated molecules is prominent and enhances the cascade of pathogenic factors. These disorders are treatable, hence the need to make the correct diagnosis from the outset. The applied therapeutic strategies are outlined and the promising new agents are reviewed.

The acute, the chronic and the news of HIV-related renal disease in Africa.

The burden of renal disease in human immunodeficiency virus (HIV) and AIDS patients living in Africa is adversely influenced by inadequate socio-economic and health care infrastructures. Acute kidney injury in HIV-positive patients, mainly as a result of acute tubular necrosis, may arise from a combination of hemodynamic, immunological, and toxic insult. A variety of histopathological forms of chronic kidney disease is also seen in HIV patients; HIV-associated nephropathy (HIVAN) and immune complex disease may require different treatment strategies, which at present are unknown. The role of host and viral genetics is still to be defined, especially in relation to the different viral clades found in various parts of the world and within Africa. The arrival and availability of highly active antiretroviral therapy in Africa has given impetus to research into the outcome of the renal diseases that are found in those with HIV. It has also generated a new look into policies governing dialysis and transplantation in this group where previously there were none.

Renal involvement in patients with hepatitis C virus infection.

INTRODUCTION: Hepatitis C virus (HCV) infection is a hepatotropic virus causing a variety of extrahepatic immunological manifestations and is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN), which is the most common glomerulonephritis. The aim of this study was to evaluate renal involvement in HCV-infected patients. MATERIALS AND METHODS: A total of 300 randomly-selected HCV antibody-positive outpatients at the HCV clinic of Shariati hospital were enrolled. Serum creatinine was measured and glomerular filtration rate was estimated accordingly. Urine proteinuria was measured in 24-hour urine samples. RESULTS: The patients were 249 men (83.2%) and 51 women (16.8%) with a mean age of 37.8 +/- 11.7 years (range, 18 to 70 years). Proteinuria was found in 12 HCV antibody-positive adults (4%), 1 of whom underwent biopsy. He was a 55- year-old man with a 4-month history of facial and lower extremities edema and 3-g proteinuria with a normal kidney function (glomerular filtration rate, 85 mL/min) and normocomplementemia. Kidney biopsy specimens showed MPGN. The frequency of low glomerular filtration rate was 0.7% (2 patients) in the HCV antibody-positive adults. There was no significant relationship between HCV seropositivity and low glomerular filtration rate. CONCLUSIONS: Our observations showed renal involvement in HCV antibody-positive patients. Among immune complex glomerular kidney diseases, MPGN without cryoglobulins is thought to be the most common in these patients.

Lupus mesenteric vasculitis can cause acute abdominal pain in patients with SLE.

Lupus mesenteric vasculitis (LMV) is a unique clinical entity found in patients who present with gastrointestinal manifestations of systemic lupus erythematosus, and is the main cause of acute abdominal pain in these patients. LMV usually presents as acute abdominal pain with sudden onset, severe intensity and diffuse localization. Other causes of abdominal pain, such as acute gastroenteritis, peptic ulcers, acute pancreatitis, peritonitis, and other reasons for abdominal surgery should be ruled out. Prompt and accurate diagnosis of LMV is critical to ensure implementation of appropriate immunosuppressive therapy and avoidance of unnecessary surgical intervention. The pathology of LMV comprises immune-complex deposition and complement activation, with subsequent submucosal edema, leukocytoclastic vasculitis and thrombus formation; most of these changes are confined to small mesenteric vessels. Abdominal CT is the most useful tool for diagnosing LMV, which is characterized by the presence of target signs, comb signs, and other associated findings. The presence of autoantibodies against phospholipids and endothelial cells might provide information about the likelihood of recurrence of LMV. Immediate, high-dose, intravenous steroid therapy can lead to a favorable outcome and prevent serious complications such as bowel ischemia, necrosis and perforation.