Classical HIV-associated Nephropathy Research Articles

Clinicopathological correlation of kidney disease in HIV infection pre- and post-ART rollout.

The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence of HIV-associated nephropathy (HIVAN). More recently, the spectrum of disease additionally reflects comorbid illness in the ageing HIV population and ART-related nephrotoxicity. We performed a clinicopathological correlation of kidney disease in HIV-positive individuals who underwent kidney biopsy between 1989 and 2014, utilizing the 2018 Kidney Disease Improving Global Outcomes pathologic classification. ART rollout began in 2004 in South Africa. Patients biopsied pre-ART rollout were compared to those biopsied post-ART rollout with respect to demographics, clinical parameters and histology. We assessed kidney survival in a cohort of these patients following biopsy. Six hundred and ninety biopsies were included, 99 (14.3%) were undertaken pre- and 591 (85.7%) post-ART rollout. Most patients were of Black African descent (97.5%). The post-ART rollout patients were older (p = 0.007), had higher eGFR at presentation (p = 0.016) and fewer presented with eGFR of less than 15ml/min/1.73m2 (p = 0.0008). There was a decrease in the prevalence of classic HIVAN (p = 0.00001); and an increase in FSGS (NOS) in the setting of HIV (p = 0.0022) and tubulointerstitial diseases (p = 0.009) post-ART rollout. Kidney function survival over 5 years was poorest in patients with classic HIVAN (p = 0.00005) and best in minimal change nephropathy (p = 0.0013). Kidney biopsy is crucial for the correct diagnosis and management of HIV-related kidney disease. ART rollout has shifted the spectrum of kidney disease away from classic HIVAN but has not eliminated it. Histological diagnosis prognosticates kidney survival.

The spectrum of kidney biopsy findings in Chinese HIV‐infected patients

HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China. Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution. Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up. This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.

Kidney Disease in Human Immunodeficiency Virus-seropositive Patients: Absence of Human Immunodeficiency Virus-associated Nephropathy was a Characteristic Feature.

Human immunodeficiency virus (HIV) infection can cause a broad spectrum of renal diseases. However, there is paucity of Indian data on the patterns of renal lesions in HIV-seropositive patients. The aim of the present study was to delineate the spectrum of renal lesions in HIV/acquired immunodeficiency syndrome patients. In this prospective study, all HIV-positive patients of both genders aged >18 years were screened for renal disease. Patients with proteinuria of more than 1 g/24 h were subjected to renal biopsy. A total of 293 HIV-positive patients were screened; of these, 136 (46.4%) patients found to have renal involvement. Dipstick-positive proteinuria of 1+ or more was observed in 112 (38.2%) patients, and 16 (14.2%) patients had proteinuria of more than 1 g/24 h. Renal biopsy in 14 cases revealed glomerulonephritis (GN) in 12 (85.7%) (isolated GN in 4 [28.5%] and GN mixed with chronic TIN in 8 [57.1%]) patients. These include mesangioproliferative GN in 5 (35.7%), membranoproliferative GN in 2 (14.2%), focal segmental glomerulosclerosis in 2 (14.2%), diffuse proliferative GN in 2 (14.2%), and diabetic nephropathy in 1 (7.1%) patients. Chronic interstitial nephritis was noted in 10 (71.42%) (superimposed on GN in 8 [57.1%], isolated in 2 [14.2%]) patients. Granulomatous interstitial nephritis was seen in 3 (24.1%) cases. GN and chronic interstitial nephritis were noted in 85.7% and 71.42% of patients, respectively, mostly superimposed on each other. Mesangioproliferative GN was the most common glomerular lesion, but classical HIV-associated nephropathy was not observed.

The spectrum of renal diseases in HIV infected adults presenting with renal insufficiency at the University Teaching Hospital, Lusaka, Zambia

Background: The spectrum of renal diseases in HIV infected adults undergoing biopsy is vast. Previous studies have indicated that HIV-associated nephropathy (HIVAN) is the commonest diagnosis in HIV-infected patients presenting with renal insufficiency. More than 90% of patients with HIVAN are black. The natural history of the renal diseases associated with HIV infection has been radically changed by antiretroviral therapy. There are other diseases, however, that account for a good percentage to the spectrum of renal diseases other than HIVAN. A group of diseases known as HIV immune complex kidney diseases have gained prominence in this regard. Other diseases include acute tubular necrosis, acute and chronic interstitial nephritis, haemolytic uremic syndrome and many others.
 Objective: To determine the clinical and histopathological presentation of the spectrum of renal diseases in HIV infected adult patients presenting with renal insufficiency at the University Teaching Hospital, Lusaka
 Methods: This was a descriptive cross-sectional study of HIV infected adults presenting with renal insufficiency who underwent kidney biopsy. It was conducted at the University Teaching Hospital from June 2014 to November 2015. The primary outcome was proportion of major histological diagnosis of renal diseases in this patient population while secondary outcomes included proportion of other renal histological diagnoses and the patient's clinical characteristics.
 Results: The commonest histological diagnoses in this study were HIV immune complex kidney disease (HIVICK) (32%) and focal segmental glomerulosclerosis (FSGS) (29%) of various histologic variants other than the collapsing type. We did not see the classic HIVAN on histopathology in our study population. All the patients presented with severe renal dysfunction with mean eGFR of 17 mVmin/173m2 and massive proteinuria of 3+. Patients had advanced HIV infection with mean CD4 count of197 cells/mm3. Majority of patients ( 64.5%) were not yet been initiated cART. 16% of the study patients were hypertensive.
 Conclusion: HIVICK and FSGS were the commonest histological diagnoses. Classical HIVAN on histopathology was not found in this patient population at the UTH.
 Recommendation: Kidney biopsy should mandatory to make definitive diagnosis in HIV with renal dysfunction.

Successful outcome of renal transplantation in a child with HIV-associated nephropathy

Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active antiretroviral therapy in late stages of HIV disease with high viral load and low CD4 cell count....

Expression of HIV transgene aggravates kidney injury in diabetic mice

With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease.

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

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

Successful outcome of first paediatric renal transplant for HIV associated nephropathy

<h3>Aims</h3> Classical HIV-associated nephropathy (HIVAN) was first described before the advent of highly active anti-retroviral therapy (HAART) in late stages of HIV disease with high viral load and low CD4+ cell count. Renal transplantation guidelines for adults with HIVAN have been developed1 with comparable patient and graft survival.23 We report the successful outcome of living related renal transplantation in an 8 year old girl (AB; name changed) on haemodialysis due to HIVAN. <h3>Patients and methods</h3> AB is a vertically HIV-infected girl who was initially lost to follow-up but represented aged 5.5 years with lymphocytic interstitial pneumonitis (LIP) and CDC stage.1 She was not initially commenced on HAART but subsequently developed acute renal failure and renal biopsy confirmed HIVAN. Hemodialysis and HAART (Lopinavir/ritonavir, lamivudine and abacavir) were started at 6.5 years. <h3>Results</h3> Pre-transplantation screening showed an undetectable HIV-1 viral load and CD4 counts of 43% (=1990/mm³). She underwent living related renal transplantation from her 56-year old maternal grandmother (mismatch 1,1,1; donor and recipient both CMV negative and EBV positive). There was a historical B-cell positive cross-match, and she was therefore treated as a ‘high-risk’ transplant using induction therapy with basiliximab, tacrolimus, mycophenolate mofetil and steroids. Tacrolimus was started six weeks prior to transplantation in order to stabilise levels. HAART (Lopinavir/ritonavir, abacavir and lamivudine) was continued together with isoniazid, azithromycin, co-trimoxazole and fluconazole prophylaxis. Currently, she is 2 months post-transplant with excellent allograft function - plasma creatinine 41-48 µmol/l; estimated glomerular filtration rate 80-94 mls/min/1.73m². She has mild hypertension requiring two anti-hypertensive agents and low-grade albuminuria (25 mg/mmol). Therapeutic tacrolimus levels are achieved with once-daily tacrolimus given 5-days per week only. She has an undetectable HIV-1 viral load and CD4+ counts of 240/mm³. Protocol biopsy at 6 weeks shows mild chronic changes, no donor specific antibodies and normal transplant renal ultrasound. There have been no HIV-related complications. <h3>Conclusion</h3> This is the first reported case of successful renal transplantation in a child with HIVAN in the UK. Adult experience suggests higher risk of rejection and careful monitoring for long-term HIV-associated complications.3

Is there an epidemic of HIV Infection in the US ESRD program?

Surveys revealed increases in the prevalence of HIV-infected patients in the US end-stage renal disease (ESRD) program in the 1980s and early 1990s, with clustering in young black men 25 to 44 yr old. Since the availability of highly active antiretroviral therapy in 1996, the prognosis of HIV-infected patients has improved, and therapy has been shown to change the course of classic HIV-associated nephropathy. We used the United States Renal Data System database to determine if the incidence and prevalence of HIV-infected patients with renal disease has increased in the ESRD program, by means of principal diagnoses and comorbid AIDS-defining diagnoses. As the number of US patients living with AIDS increased 57% from 214,711 in 1995 to 337,017 in 2000, and the number of incident ESRD patients increased 29.9% from 72,827 to 94,602, the number of incident HIV-infected patients increased only by 3.5%, from 1133 to 1171. Over this time, the percentage of incident ESRD patients with HIV infection fell from 1.56% to 1.24%. Among black men 25 to 44 yr of age, HIV infection as a proportion of incident ESRD cases fell from 8.5% to 6.2% from 1995 to 2000. The incident rate per million of AIDS or HIV infection in black men aged 25 to 44 fell from 107 in 1995 to 78 per million in 2000. The incidence rate for HIV-infected women in the ESRD program rose 14% while it declined 7% in men. Almost 2000 HIV-infected women, or 28.8% of the population, have initiated therapy for ESRD with hemodialysis. The number of prevalent cases increased in absolute numbers 81.3% from 2687 to 4871 (0.90% to 1.16% of the ESRD program). One-year survival rates for HIV-infected incident ESRD patients increased from 53.1% to 67.1% from 1995 to 2000. Although these values may be underestimates because of underreporting due to confidentiality concerns and lack of biopsy confirmation, we conclude that although the prevalence of HIV infection is increasing in the US ESRD population, the increase as a proportion of the program is minimal and is due to better survival after development of renal failure. The incidence of HIV infection in the US ESRD program is stable. Highly active antiretroviral therapy may be responsible for the change in epidemiology of HIV infection in the US ESRD program.

Renal pathology and premortem clinical presentation of Caucasian patients with AIDS: an autopsy study from the era prior to antiretroviral therapy.

Renal disease in patients with HIV infection is becoming increasingly frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found in patients of predominantly African-American and Hispanic origin. However, only limited data are available on renal pathology and premortem clinical presentation of kidney disease in Caucasian patients with AIDS. To determine the prevalence, clinical presentation and aetiology of renal disease in Caucasian patients with AIDS at the time of death we have performed a prospective autopsy study with 239 patients who died of AIDS between 1981 and 1989. None of these patients had received HIV-specific antiretroviral therapy. Autopsies and histological analyses were performed on the basis of a standardised protocol. Clinical and laboratory data were gathered according to a uniform questionnaire. 95% of patients were of Caucasian race. 75% of all patients had extended AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36% of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and renal insufficiency (11%). Histopathological lesions were present in 43% of the autopsies, with two or more distinct structural lesions in 12.5% of patients. Of the pathological findings 28% were glomerular or vascular, 33% were non-glomerular, and 29% were combined lesions. The remaining 10% were renal infiltrations of infectious agents or neoplastic tissue. The most common findings were ischaemic changes and vascular scars (18% of patients), as well as pyelo- and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7% of patients, and only a single African patient had classical HIVAN. Renal involvement in HIV disease is very common at the time of death among patients of Caucasian origin. However, classical HIV-associated nephropathy is absent in this population. These findings suggest that kidney disease affects all races and supports the hypothesis that HIVAN is specifically related to non-Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific antiretroviral therapy.

Renal pathology and premortem clinical presentation of Caucasian patients with AIDS: an autopsy study from the era prior to antiretroviral therapy.

Renal disease in patients with HIV infection is becoming increasingly frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found in patients of predominantly African-American and Hispanic origin. However, only limited data are available on renal pathology and premortem clinical presentation of kidney disease in Caucasian patients with AIDS. To determine the prevalence, clinical presentation and aetiology of renal disease in Caucasian patients with AIDS at the time of death we have performed a prospective autopsy study with 239 patients who died of AIDS between 1981 and 1989. None of these patients had received HIV-specific antiretroviral therapy. Autopsies and histological analyses were performed on the basis of a standardised protocol. Clinical and laboratory data were gathered according to a uniform questionnaire. 95% of patients were of Caucasian race. 75% of all patients had extended AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36% of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and renal insufficiency (11%). Histopathological lesions were present in 43% of the autopsies, with two or more distinct structural lesions in 12.5% of patients. Of the pathological findings 28% were glomerular or vascular, 33% were non-glomerular, and 29% were combined lesions. The remaining 10% were renal infiltrations of infectious agents or neoplastic tissue. The most common findings were ischaemic changes and vascular scars (18% of patients), as well as pyelo- and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7% of patients, and only a single African patient had classical HIVAN. Renal involvement in HIV disease is very common at the time of death among patients of Caucasian origin. However, classical HIV-associated nephropathy is absent in this population. These findings suggest that kidney disease affects all races and supports the hypothesis that HIVAN is specifically related to non-Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific antiretroviral therapy.

The nephropathies of HIV infection: pathogenesis and treatment.

Several different renal syndromes have been reported in patients with HIV infection. Patient characteristics and a syndrome approach may help the clinician formulate a tentative diagnosis, but a renal biopsy is necessary to make a firm diagnosis in patients with chronic renal disease in the setting of HIV infection. The pathogenesis of the HIV nephropathies can teach us much about the pathophysiology of common renal problems such as IgA nephropathy, immune complex glomerulonephritis, focal segmental glomerulosclerosis, and diabetic renal disease. HIV-associated renal disease may be the result of the interaction of the expression of specific HIV genes in patients with distinct genetic susceptibilities to disease in particular environments. New treatment approaches have provided hope for patients with classic HIV-associated nephropathy.

HIV-associated renal disease in London hospitals

We report experience from London hospitals which further illustrates the heterogeneous nature of HIV-associated nephropathy (HIVAN). Nineteen HIV-positive patients underwent renal biopsy from 1992 to 1994. Fourteen were male, five female. Eleven were Afro-Caribbean, 7 Caucasian and 1 Asian. Eleven patients had classical HIVAN with proteinuria, rapidly progressive renal failure and features of focal and segmental glomerulosclerosis (FSGS) on renal biopsy, and three of these had associated tubulo-interstitial nephritis (TIN). One further patient had TIN and tubular changes suggestive of HIVAN but no glomeruli were present in the biopsy. Other biopsy findings were of focal proliferative glomerulonephritis and TIN (1 patient), pauci-immune crescentic glomerulonephritis and TIN (1 patient), membranous nephropathy (1 patient), membranoproliferative nephropathy (1 patient) and haemolytic uraemic syndrome (2 patients). Of 11 patients with FSGS, seven died with median survival of 8 months (range 23 days-46 months) and five are still alive after median follow-up of 18 months (range 10-22 months). Of patients with glomerular disease other than FSGS, five died, with median survival of 3 months (range 1-27 months) and two have survived (10 and 27 months, respectively). Thirteen patients had renal failure, 10 of whom had FSGS. In 10 cases renal failure was acute and in two was the presenting feature of HIV infection. Thirteen patients underwent renal replacement therapy. Four received haemodialysis, and all died within one month. Nine patients received CAPD. Two were able to discontinue dialysis. Of the remaining seven, five died with median survival of 8 months (range 1.3-40 months) and two are alive 1 and 10 months after beginning dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)