Renal Disease In HIV-infected Patients Research Articles

Deceased Donor Kidney Transplantation in a Human Immunodeficiency Virus–Infected Recipient: A Case Report

Human immunodeficiency virus (HIV) infection has traditionally been considered an absolute contraindication for transplantation because immunosuppression will accelerate the disease progression and increase mortality. New antiretroviral agents have given rise to new perspectives and transplantation practices. Now renal transplantation is the gold standard treatment for end-stage renal disease in HIV-infected patients, but increased rejection and toxicity rates and compliance with treatment are important issues. Therefore, patient selection and follow-up should be done carefully in this patient group. Here we present a 51-year-old, male, HIV-infected patient who was diagnosed with HIV at his routine serologic investigation at 2015. Highly active antiretroviral therapy was initiated. One haplotype-matched kidney transplantation from a deceased donor was performed on October 19, 2016. Induction therapy was not administered, and the immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisolone. After 26 months, serum creatinine was 1.1 mg/dL and proteinuria 0.1 g/day. There was no development of donor-specific antibodies. The patient's current HIV viral load remains undetectable (and had been the entire time post-transplantation) while his CD4+ T-cell count currently is 543/mm3.

PREDICTORS OF CHRONICKIDNEY DISEASEINHUMAN IMMUNODEFICIENCY VIRUS PATIENTS

Purpose: to determine the frequency of diagnosis and predictors of renal disease in HIV-infected patients.
 Patients and methods. 292 HIV-infected patients, who were on an outpatient screening at the Chernivtsi Regional AIDS Center, were screened.
 Results CKD was diagnosed in 153 out of292 (52.4%) of the examined patients. among which 105 (36.0%) patients were diagnosed with isolated albuminuria/proteinuria, 48 (16.4%) patients had albuminuria /proteinuria, in combination with a decrease in glomerular filtration rate. It has been established that the presence of proteinuria in HIV infection is accompanied by a significantly higher level of HIV RNA compared to patients without this symptom (p < 0.01). At the same time, the average amount of CD4+-lymphocytes in blood serum in patients with proteinuria is significantly lower than in HIV-infected individuals who did not show kidney damage.
 The difference between the values of the ratios of CD4+/CD8+-lymphocytes in the analyzed groups (p < 0,05) is also significant.
 In most patients who were in the III-IV clinical stage of HIV infection, antiretroviral therapy (ART) was effective and reduced the viral load. Therefore, it is obvious that the amount of HIV-RNA in the blood of these individuals was significantly lower compared to patients who did not receive such treatment. At the same time, the burden of HIV, as well as the number of CD4+-lymphocytes in the representatives of the comparable groups did not differ (p > 0.05).
 Conclusion. The main predictors of kidney damage in HIV-infected are: high viral load, decrease in absolute numbers. CD4+-lymphocytes less than 200. Co-infection with hepatitis B and/ or C viruses does not affect the level of proteinuria and GFR in HIV-infected patients.

Clinical remission of IgA nephropathy in an HIV-positive patient after combined treatment with tonsillectomy and steroid pulse therapy.

Various renal diseases other than human immunodeficiency virus (HIV)-associated nephropathy, including IgA nephropathy (IgAN), have been recently reported to cause chronic kidney disease and end-stage renal disease in HIV-infected patients. The case of a 37-year-old HIV-infected male diagnosed as having IgAN with proteinuria and microscopic hematuria that was successfully treated with tonsillectomy and steroid pulse therapy in combination, resulting in disappearance of urinary abnormalities (clinical remission), is reported, the first such case in the literature. A renal biopsy revealed mesangial proliferation associated with mesangial deposition of IgA and C3, consistent with IgAN. Antiretroviral therapy and angiotensin receptor blocker therapy did not improve his proteinuria. Therefore, he underwent tonsillectomy and steroid pulse therapy, and clinical remission was successfully achieved with no opportunistic infections. Clinical remission has continued for more than 3years even after discontinuation of steroid therapy. It appears that combined treatment with tonsillectomy and steroid pulse therapy can be a good choice in managing HIV-infected patients with IgAN as long as secondary infection is strictly and continuously monitored.

Consensus document on the management of renal disease in HIV-infected patients.

To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.

Veränderungen im Spektrum der Nierenerkrankungen bei HIV-Infektion

Renal disease is a common complication in HIV-infected patients. The causes and spectrum of kidney disease among these patients is extensive, including HIV-related and HIV unrelated causes. Our objective was to assess the changes in distribution of renal disease under antiretroviral therapy (ART). Retrospective analysis of all patients from the Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic, progressive renal disease between 1989 and 2012. Two time periods were defined: 1989-2001 (early period) and 2000-2012 (late period). 69 HIV-infected patients, mostly Caucasian and male, underwent renal biopsy (early period: 22 patients, late period: 47 patients). During the total observation time immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal disease. HIV-associated renal diseases were predominant in the first period, whereas hypertensive and diabetic kidney disease accounted for almost 50 % of cases diagnosed in the late period. Other types of renal disease frequently encountered during the late period include renal AA-amyloidosis and tenofovir-related kidney disease. The underlying pathology of renal disease in HIV-infected patients is highly variable and evolving. Since the introduction of HAART, renal disease not directly related to HIV has become the predominant cause, reflecting the growing burden of co-morbidities in this aging population.

Screening and management of renal disease in human immunodeficiency virus‐infected patients in Australia

Renal disease has become one of the most important comorbidities observed in the human immunodeficiency virus (HIV)-infected patient cohort. Data are lacking on the current screening and management of renal disease in patients with HIV. We evaluated HIV-infected Australian adults in primary care to determine current practices. This prospective, multicentre observational study included two rounds of data collection; the first was followed by an educational programme. Outcomes included screening for renal disease; management of risk factors for kidney disease and other comorbidities associated with renal disease. Fifty-three general practitioners participated with 733 patients enrolled. Most were male (94%); almost 40% were 41-50 years of age, and 6% and 84% were receiving antiretroviral therapy. Comorbidities were common; 19% had hypertension, 5% were diabetic, 32% were dyslipidaemic, and 40% were smokers. Estimated glomerular filtration rate was commonly measured in both rounds of data collection (96% vs 95%). Proteinuria was assessed less frequently; this improved after education (48% vs 71%). Almost 10% of patients tested had proteinuria on urinalysis. Of the 45 patients (6%) with renal impairment (estimated glomerular filtration rate <60 mL/min), none was referred for assessment by a renal specialist. This large observational study provides important information on renal disease in HIV-infected patients, an area with a paucity of clinical data. Current screening and management practices fall short of suggested guidelines. Failure to refer patients to specialists is a major deficiency. Improvements with education suggest the need to promote awareness of guidelines in primary care doctors.

Recurrent HIV-Associated Immune Complex Glomerulonephritis With Lupus-like Features After Kidney Transplantation

A spectrum of kidney diseases besides classic human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) exists in HIV-infected patients. Immune complex-mediated glomerulonephritis has emerged as a significant contributor to the burden of kidney disease in this population, particularly in patients of non-African descent. Lupus-like nephritis, a form of immune complex glomerulonephritis with histologic features identical to lupus nephritis in the absence of clinical or serologic markers of lupus, is well recognized as a cause of end-stage renal disease in HIV-infected patients. None of the HIV-associated kidney lesions, whether classic HIVAN or non-HIVAN, has been reported to recur in kidney transplants. We report here for the first time clinical and histologic recurrence of HIV-associated lupus-like nephritis after successful kidney transplantation, causing proteinuria, hematuria, and impaired kidney transplant function.

Immunoglobulin A-dominant postinfectious glomerulonephritis in a patient with acute HIV syndrome

Immunoglobulin A-dominant postinfectious glomerulonephritis in a patient with acute HIV syndrome

Are HIV-Infected Donors Suitable for Renal Transplantation?

Recent studies confirm that outcome of renal transplantation (RT) in adequately selected HIV-infected patients receiving kidneys from HIV-negative donors is similar to that of HIV-negative RT recipients (1). Main challenges in the clinical management of HIV-infected RT recipients are the pharmacologic interactions between immunosuppressive agents and some classes of antiretroviral drugs and a higher rate of acute rejection in comparison with HIV-negative RT recipients. Currently, organ transplantation from HIV-infected donors is an absolute contraindication in Western countries (2,3), but its potential utility is under consideration (4). Recently, Muller et al. (5) reported the outcome of four HIV- infected RT recipients who received their grafts from two HIV-infected donors in South Africa, being the first clinical experience published involving this type of transplants. After 12 months of follow-up, all recipients had a functioning renal allograft with a good renal function, and HIV infection was controlled under different antiretroviral regimens. South Africa is a country with a high HIV prevalence in the general population, and HIV infection is an absolute exclusion criterion for access to dialysis or RT. Muller et al. (5) suggested that the use of HIV-infected donors would increase the donor pool, providing renal allografts to HIV-infected patients otherwise sentenced to death as a consequence of end-stage renal disease. It is likely that organ transplantation from HIV-infected donors will generate considerable controversy. The situation is similar to what occurred a decade ago in relation to hepatitis C virus RNA-positive donors, who are now accepted for hepatitis C virus-positive recipients in international guidelines (2,3). The strategy under consideration is bold and implies difficult decisions. Nonetheless, it must be evaluated with caution and based on several considerations. First, there are ethical implications stemming from the lack of long-term safety data. In countries with a resource-limited health system, HIV infection is an exclusion criterion for access to dialysis or RT. We agree that in these cases, the balance between justice and equity is more difficult. Second, recipients might acquire a more aggressive HIV strain from the donor (e.g., different clade or recombinant virus, or X4 tropism), including drug- resistant strains, which could lead to superinfection, virologic failure, and HIV progression to death. Previous reported experiences do not provide donor's virologic information (5), which, moreover, is difficult to obtain during organ procurement (3). Third, HIV-infected donors are at high risk for transmitting other infections that could increase morbidity and reduce recipient survival. Finally, there are nephrologic issues that must also be considered. HIV-associated nephropathy is the leading cause of end-stage renal disease in HIV-infected patients in South Africa; it is caused by direct viral infection of kidney cells (particularly the visceral epithelial cells of the glomerulus and the tubular epithelial cells), and it is more common in patients with high plasma HIV-RNA viral load (6). Moreover, HIV is associated with other renal diseases: immune-mediated glomerulonephritis, postinfectious glomerulonephritis, and thrombotic microangiopathies. Muller et al. (5) reported that the two HIV-infected donors had normal kidney biopsies, and no proteinuria was observed. However, technical limitations of renal allograft biopsy during procurement may misdiagnose subclinical renal disease, which could have a negative impact on allograft survival. To accelerate acquisition of evidence enabling resolution of these considerations, we suggest evaluating this approach in a prospective, controlled, pilot clinical trial of RT in HIV-infected recipients, containing two arms (HIV-positive and -negative donors) with virologic and histologic (protocolled renal biopsy) assessment and biochemical markers of renal injury and clinical outcome. Thus, the effectiveness and safety of this type of transplantation can be established. We believe that this strategy must initiate an intense scientific debate because of different ethical, nephrologic, virologic, and clinical considerations, and an international consensus conference could be of interest to analyze the controversies of this interesting and emerging issue. Federico Cofan1 Joan-Carles Trullas2 Carlos Cervera3 Federico Oppenheimer1 Asuncion Moreno3 Josep-Maria Campistol1 Jose-Maria Miró3 1 Renal Transplant Unit Nephrology Department Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain 2 Internal Medicine Service Hospital Sant Jaume Olot, Universitat de Girona, Girona, Spain 3 Infectious Diseases Service Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain

The difficulties of classifying renal disease in HIV-infected patients*

The difficulties of classifying renal disease in HIV-infected patients*

Renal disease in AIDS: it is not always HIVAN

Human immunodeficiency virus (HIV) infection can cause a broad spectrum of clinical manifestations, ranging from an asymptomatic carrier state to severe immunodeficiency. The most common renal lesion, HIV-associated nephropathy (HIVAN), is a sclerosing glomerulopathy. However, potentially reversible causes of renal disease in HIV-infected patients should also be considered. We describe two cases of patients with acquired immune-deficiency syndrome (AIDS) who presented with rapidly progressive renal failure but were found to have reversible etiologies. The first case was found to have syphilis and the second, disseminated histoplasmosis; their renal injury resolved after initiation of a third-generation cephalosporin antibiotic and amphotericin B, respectively.

Imaging and Histopathologic Features of HIV-related Renal Disease

Despite extraordinary recent advances in the management of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome, patients infected with HIV are still susceptible to a variety of complications that stem either from immunodeficiency or from side effects of antiretroviral regimens. Diagnosis is often challenging, since every organ in the body can be affected by HIV, and the kidneys have been increasingly shown to be involved by a variety of disease processes. Opportunistic infections including those caused by atypical organisms, malignancies such as lymphoma and Kaposi sarcoma, and disease processes specific to HIV infection such as HIV-associated nephropathy have all been shown to affect the kidneys. In this era of highly active antiretroviral therapy (HAART), renal disease arising secondary to antiretroviral medication has been added to the list. Furthermore, the introduction of HAART has increased survival of HIV-infected patients; consequently, the frequency of HIV-associated and incidental renal disease is expected to rise in this population. Because mortality and morbidity rates are affected by the early recognition of renal disease in HIV-infected patients, it is paramount that the radiologist be familiar with the imaging features that can be encountered in such cases.

Observations on a Cohort of HIV-Infected Patients Undergoing Native Renal Biopsy

Aims: This study aims to explore the spectrum of renal disease in HIV-infected patients, identify clinical predictors of HIV-associated nephropathy (HIVAN), and investigate the performance of renal biopsy in HIV-infected patients. Method: Of 263 HIV-infected patients with renal disease evaluated between 1995 and 2004, 152 had a renal biopsy, while 111 had not. A group comparison was performed. Results: The leading biopsy diagnoses were HIVAN (35%), noncollapsing focal segmental glomerulosclerosis (22%), and acute interstitial nephritis (7.9%), amongst over a dozen others. There was a trend of decreasing yearly incidence of HIVAN diagnoses, paralleling the use of antiretroviral therapy. By multivariate logistic regression, CD4 counts >200 cells/mm³ and higher estimated glomerular filtration rate were strong negative predictors of HIVAN. HIVAN patients were more likely to require dialysis (p < 0.0001) and had worse overall survival (p = 0.02). Younger age and lower estimated glomerular filtration rate were significant predictors of renal biopsy in multivariate regression analysis. More biopsied patients progressed to dialysis (51 vs. 25%, p = 0.001) and death (15 vs. 5.4%, p = 0.001), despite more frequent corticosteroid treatment (29 vs. 3.6%, p = 0.001). Conclusion: These findings may reflect more severe acute and/or chronic disease at the time of biopsy and suggests that earlier renal biopsy may be warranted in HIV-infected patients, especially in light of the changing spectrum of renal disease in this group.

Membranoproliferative Glomerulonephritis in a Patient Treated With Interferon-α for Human Immunodeficiency Virus Infection

Several renal pathologic entities have been reported to be associated with human immunodeficiency virus (HIV) infection. The most common is focal glomerulosclerosis, but several different types of glomerulonephritis have been observed in patients with HIV infection and the acquired immunodeficiency syndrome. The mechanisms involved in the pathogenesis of the kidney disease remain obscure. We studied an HIV-infected patient treated with interferon-alpha who had developed proteinuria and membranoproliferative glomerulonephritis to determine whether the renal disease was associated with HIV infection or with chemotherapy. Circulating HIV antibodies were assessed by enzyme-linked immunosorbent assay; circulating immune complexes (CICs) were measured by C'1q assay and isolated by polyethylene glycol precipitation, then subjected to gel electrophoresis and immunochemical analysis. Renal biopsy tissue underwent acid elution, and the eluates were analyzed similarly. In addition the eluted antibody and the antibody from the CIC were assessed by immunodiffusion with eluate and immune complex antigens. A single CIC was detected, which was composed of an immunoglobulin G antibody complexed to a 26-kd protein antigen that was shown to be interferon-alpha. Eluate from the renal biopsy tissue demonstrated identical material, which cross-reacted with the components of the isolated CIC. Immune complex renal diseases, such as membranoproliferative glomerulonephritis, may be related to biologic response modifying agents in patients with HIV infection. The relative roles of their biologic response modification and the disordered immunoregulation seen in such patients in the pathogenesis of the renal disease is unclear. Renal biopsy is necessary to assess the etiology of the renal disease in HIV-infected patients.