Structural and functional kidney abnormalities in patients with Human immunodeficiency virus infection: A cross-sectional perspective

Abstract

BACKGROUND

Chronic kidney disease is a progressive disease that evolves towards the development of end-stage renal disease. The superimposition of renal impairment on a complex disease, namely human immunodeficiency virus (HIV) infection, will raise the burden of comorbidities and, predict worse outcomes in this group of the population.

AIM

To evaluate the structural and functional defects of kidney in patients with HIV infection.

METHODS

This cross-sectional study involved 227 patients with HIV infection. Participants were selected by simple random sampling method. Eligible participants included HIV infection-positive adults aged 18 years and above. Exclusion criteria encompassed individuals with preexisting hypertension, diabetes mellitus, chronic kidney disease, chronic liver disease, and those receiving nephrotoxic drugs. Informed consent was obtained. Data collection involved recording medical histories, conducting clinical examinations, and performing baseline blood investigations and ultrasonography to assess renal function and structural abnormalities.

RESULTS

The mean age of participants was 41 years. Females constituted 66.5%; 78% were on Tenofovir-based regimen. The mean duration of HIV infection was 5 years; mean duration of antiretroviral therapy was 4 years. 67.4% had a body mass index over 25. World Health Organization staging of HIV infection revealed that 41.9% were in stage 3, 30% in stage 2. 35.7% had cluster differentiation 4 counts < 200. The mean creatinine was 1 mg/dL and mean urea was 25.1 mg/dL. 54.6% had estimated glomerular filtration rate of < 60. Enlarged kidneys in 39.2% and increased echogenicity in 82.8% of participants. A decline in estimated glomerular filtration rate and an increase in kidney size was significantly associated with advancing HIV stages.

CONCLUSION

Both structural and functional kidney abnormalities are common in patients with HIV infection. These abnormalities increase with disease progression, underscoring the need for regular and consistent renal monitoring.

Key Words: Chronic kidney disease; Estimated glomerular filtration rate; Human immunodeficiency virus; Structural renal abnormalities

Core Tip: Renal abnormalities are commonly observed in individuals with human immunodeficiency virus (HIV) infection, particularly as the disease progresses. Advanced stages of HIV are associated with a significant decline in estimated glomerular filtration rate and an increase in kidney size, indicating worsening renal function. Consequently, routine monitoring of kidney health, including estimated glomerular filtration rate and imaging when appropriate, is essential for early detection and management of HIV-related kidney complications.

INTRODUCTION

Kidney disease affects an estimated 850 million individuals globally, the majority of whom reside in low- and lower-middle-income countries[1]. The pooled prevalence of chronic kidney disease (CKD) in India is 13.24%, with males being more commonly affected than females[2]. End-stage renal disease represents the terminal stage of CKD, characterized by irreversible loss of renal function, requiring dialysis or transplantation for survival. Regardless of the degree of renal dysfunction, individuals with CKD are at significantly increased risk for systemic complications, including dyslipidaemia, cardiovascular disease, cognitive impairment, and bone mineral disorders. These comorbidities contribute to reduced quality of life and elevated mortality rates in affected populations[3]. The combination of human immunodeficiency virus (HIV) infection with renal impairment increases the burden of comorbidities and indicates a worse prognosis for this population[4].

As of 2023, there are 39.9 million people living with HIV (PLWH) worldwide[5], including approximately 2.5 million in India[6]. HIV infection and CKD represent two major global health challenges, each with profound social, clinical, and economic impacts. Their intersection exemplifies the growing convergence between communicable and non-communicable diseases. Despite the widespread availability and use of antiretroviral therapy (ART), kidney disease remains a prevalent and significant comorbidity among PLWH, contributing substantially to increased morbidity and mortality in this population. Several risk factors have been consistently associated with the development and progression of kidney disease in HIV-infected individuals, including high HIV viral load, low cluster differentiation 4⁺ (CD4⁺) T-cell count, diabetes mellitus, hypertension, and African ancestry. These factors highlight the complex interplay between viral pathogenesis, host immunity, and traditional metabolic risk factors in driving renal impairment in the context of HIV[7]. The most effective strategy for reducing the risk of CKD is to emphasize prevention, early detection, and timely initiation of ART, as prolonged viral replication has been linked to potential kidney damage. Over the past two decades, the treatment of HIV with multidrug combination therapy has significantly improved both overall and renal outcomes in PLWH[8].

In the current ART era, renal involvement in PLWH is increasingly attributed to the cumulative burden of ART-associated nephrotoxicity and the high prevalence of comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease. Although effective ART has significantly reduced the incidence of classic HIV-associated nephropathy (HIVAN), emerging evidence suggests that direct viral effects on renal tissue may persist even during sustained virologic suppression, possibly due to low-level viral replication or residual immune activation within the kidney[9].

As the number of PLWH with CKD continues to grow, healthcare providers -particularly nephrologists and HIV specialists - are increasingly required to manage patients across the full spectrum of renal impairment, including those undergoing renal replacement therapy. This complexity underscores the need for a coordinated, multidisciplinary approach to care. Routine monitoring of renal function, individualized ART regimens with attention to renal safety profiles, and careful prescribing practices are central to minimizing polypharmacy, avoiding unnecessary nephrotoxic exposures, and optimizing both renal and HIV-related outcomes. Integrating nephrology and infectious disease expertise is essential to providing comprehensive, patient-centered care in this high-risk population[10]. This cross-sectional study aimed to analyze the structural and functional kidney abnormalities in patients with HIV infection among the Indian population.

MATERIALS AND METHODS

Study setting

This cross-sectional study was conducted in the Department of General Medicine in collaboration with the ART centre at a tertiary care Medical College, northern Tamil Nadu, India, from February 2021 to December 2022. With a prevalence of 16.5% of HIV nephropathy among Indians, a 95% confidence interval and a 5% margin of error, by using the n = Z² × P × (1-P) × d² formula (where n is the sample size, Z is the Z-score corresponding to the desired confidence level, P is the estimated prevalence, and d is the margin of error), the required sample size was 212[11,12]. To strengthen the outcome, 227 patients were included in the study. A simple random sampling technique was followed. All adult HIV positive patients attending the ART centre were included in the study. Patients with pre-existing hypertension, diabetes mellitus, CKD, chronic liver disease, and/or those on nephrotoxic drugs, as well as conditions that are likely to produce proteinuria, and patients under 18 years of age, were excluded.

Procedure

Patients who satisfied the inclusion criteria were recruited into the study after obtaining informed consent. Demographic data were collected. HIV staging was determined based on World Health Organization (WHO) criteria[13]. ART regimens were noted. Blood urea, serum creatinine, and CD4 counts were measured. Ultrasonogram was done to measure the kidney size and echogenicity. A kidney length between 9 cm and 12.4 cm was considered normal, while a length exceeding 13 cm was classified as kidney enlargement[14]. Estimated glomerular filtration rate (eGFR) was calculated using the Cock-croft formula[15].

Statistical analysis

Data entry was performed in an Excel sheet, and statistical analysis was conducted using IBM SPSS Statistics for Windows, version 29.0.1 (IBM Corp., Armonk, NY, United States). Descriptive statistics such as mean and standard deviation were used to present quantitative data. Frequencies and percentages were used to depict qualitative data. Qualitative variables were compared using χ²/Fischer’s exact analysis. P-value of less than 0.05 was deemed significant.

RESULTS

A total of 227 patients diagnosed with HIV infection were included in the study. The mean age of the study population was 41 ± 9.3 years, indicating a predominantly middle-aged cohort. Females comprised the majority of participants, accounting for 66.5% of the study population. In terms of nutritional status, 32.6% of participants had a body mass index of < 25 kg/m², suggesting that a significant proportion were either underweight or within the normal weight range.

The average duration since HIV diagnosis was 5 years, while the mean duration of ART exposure was 4 years, reflecting sustained access to ART. According to the WHO clinical staging system, the largest proportion of participants (41.9%) were classified as being in stage 3. An additional 30% were in stage 2, while fewer participants were observed in stages 1 and 4.

Immunological assessment based on CD4⁺ T-cell counts revealed that 35.7% of patients had a CD4 count < 200 cells/mm³, indicating advanced immunosuppression in over one-third of the cohort. The majority of patients (78%) were on a tenofovir-based ART regimen, highlighting its predominant use in this population. Renal function, assessed using eGFR, was found to be impaired in a substantial portion of the cohort. Specifically, 54.6% of participants had eGFR < 60 mL/minute/1.73 m², underscoring a high burden of renal dysfunction among PLWH in the study population (Table 1).

Table 1 General characteristics of the study population, n (%).

Parameter	Frequency (n = 227)
Age (year), mean ± SD	41 ± 9.3
Gender
Male	76 (33.5)
Female	151 (66.5)
BMI
< 25 kg/m2	74 (32.6)
≥ 25 kg/m2	153 (67.4)
Duration of HIV infection (year), mean ± SD	5 ± 1.3
Duration of ART regimen (year), mean ± SD	4.18 ± 1.2
WHO stage of HIV infection
Stage 1	39 (17.2)
Stage 2	68 (30)
Stage 3	95 (41.9)
Stage 4	25 (11)
CD4 count
< 200 cells/mm3	81 (35.7)
≥ 200 cells/mm3	146 (64.3)
ART regimen
Tenofovir based	177 (78)
Non-tenofovir based	50 (22)
eGFR
< 60	124 (54.6)
≥ 60	103 (45.4)

BMI: Body mass index; HIV: Human immunodeficiency virus; ART: Anti-retroviral therapy; CD: Cluster differentiation; WHO: World Health Organization; eGFR: Estimated glomerular filtration rate.

The mean serum urea and creatinine levels were 25.1 ± 7 mg/dL and 1.0 ± 0.2 mg/dL, respectively. Renal ultrasound findings indicated that kidney size was increased in 39.2% of participants, suggesting structural renal changes in a significant subset of the cohort. Additionally, increased renal echogenicity - commonly associated with chronic kidney changes and parenchymal damage - was observed in 82.8% of the study population (Table 2). When stratified by HIV disease severity according to WHO clinical staging, eGFR was significantly lower among patients in stage 3, indicating more advanced renal impairment in this group (Table 3). Kidney size was also significantly larger in individuals classified as being in stage 3, suggesting a correlation between disease progression and renal structural changes (Table 4). Furthermore, renal echogenicity was significantly increased in patients in WHO stages 3 and 4, supporting the association between advanced HIV disease and renal parenchymal involvement (Table 5).

Table 2 Laboratory and sonographic parameters of the study population, n (%).

Parameter	Frequency (n = 227)
Creatinine (mg/dL), mean ± SD	1.07 ± 0.24
Urea (mg/dL), mean ± SD	25.1 ± 7.1
Ultrasonogram abnormalities
Normal size kidney	138 (60.8)
Large kidney	89 (39.2)
Increased echogenecity	188 (82.8)
Normal echogenecity	39 (17.2)

Table 3 Comparison of estimated glomerular filtration rate with World Health Organization staging of human immunodeficiency virus infection, n (%).

WHO stage of HIV infection	eGFR < 60 (n = 124)	eGFR ≥ 60 (n = 103)	χ2 value	Degree of freedom	P value
Stage 1	8 (6.5)	31 (30.1)	40.78	3	< 0.001
Stage 2	28 (22.6)	40 (38.8)	-	-	-
Stage 3	68 (54.8)	27 (26.2)	-	-	-
Stage 4	20 (16.1)	5 (4.9)	-	-	-

eGFR: Estimated glomerular filtration rate; WHO: World health organization; HIV: Human immunodeficiency virus.

Table 4 Comparison of kidney size with World Health Organization staging of Human immunodeficiency virus infection, n (%).

WHO stage of HIV infection	Large (n = 89)	Normal (n = 138)	χ2 value	Degree of freedom	P value
Stage 1	5 (5.6)	34 (24.6)	25.67	314	< 0.001
Stage 2	22 (24.7)	46 (33.3)	-	-	-
Stage 3	54 (60.7)	41 (29.7)	-	-	-
Stage 4	8 (9)	17 (12.3)	-	-	-

WHO: World health organization; HIV: Human immunodeficiency virus.

Table 5 Comparison of kidney echogenicity with World Health Organization staging of Human immunodeficiency virus infection, n (%).

WHO stage of HIV infection	Increased echogenicity (n = 188)	Normal echogenicity (n = 39)	Fischer exact value	Degree of freedom	P value
Stage 1	14 (7.5)	25 (64.1)	85.79	3	< 0.001
Stage 2	54 (28.7)	14 (35.9)	-	-	-
Stage 3	95 (50.5)	-	-	-	-
Stage 4	25 (13.3)	-	-	-	-

WHO: World health organization; HIV: Human immunodeficiency virus.

DISCUSSION

This study evaluated functional and structural renal defects in HIV-infected patients. The mean age of participants in our study was 41 years, with females constituting 66.5%. Most participants (78%) were on a Tenofovir-based regimen. The mean duration of HIV infection was 5 years, and the mean duration of ART was 4 years. The majority of the participants were in WHO stage 3. A total of 35.7% had CD4 counts < 200. An eGFR of < 60 was found in 54.6% of participants. Sonographic findings included Kidney enlargement in 39.2% of participants, with increased echogenicity in 82.8%. Declining eGFR, increased kidney size, and echogenicity were significantly associated with advancing HIV stages.

Kidney diseases affect 2.4%-17% of HIV-infected individuals, with CKD being a concern due to long-term ART and traditional risk factors. The kidney can also act as a viral reservoir, complicating eradication efforts[9]. Various kidney disorders, including acute kidney injury, proximal tubular dysfunction, and urolithiasis, can occur in HIV. HIVAN, once common, has decreased with ART[10]. The prevalence of kidney disease in HIV-infected individuals has risen due to improved survival and aging of this population. Management of kidney disease in older HIV-infected adults may be complicated by polypharmacy and increased medication toxicity risk[16].

The mean age of the study population was 41 years, similar to other studies[17,18]. Our study shows that 78% were on a Tenofovir-based regimen, a widely used first-line ART known for its potential nephrotoxic effects, particularly proximal tubular dysfunction and a decline in eGFR[19]. The mean ± SD duration since HIV diagnosis was 5 ± 1 years, with a mean ± SD ART duration of 4 ± 1 years, indicating prolonged exposure to both the virus and antiretroviral treatment. Females constituted the majority of the study population, aligning with observations from the study by Girum et al[20]. Notably, 35.7% of participants had a CD4 count of < 200 cells/mm³, a threshold associated with advanced immunosuppression and increased risk of opportunistic infections, which can further contribute to renal dysfunction. HIV and ART-related nephrotoxicity can independently and synergistically impact renal health[21].

When comparing eGFR with the WHO staging of HIV, it is observed that as HIV advances, the proportion of participants with a lower eGFR (< 60) increases, suggesting a decline in kidney function with the disease progression. Studies have examined the relationship between renal function, HIV infection, and patient outcomes. Impaired renal function with reduced eGFR is common among patients with HIV initiating ART[21]. However, classifying renal disease in HIV-infected patients is challenging due to variations in eGFR estimation methods, which can lead to conflicting results. These estimation methods have limitations and lack full validation in HIV-positive populations. Additionally, the CKD staging system for HIV-infected patients may be inadequate, as eGFR measures are particularly imprecise at normal to high levels[22]. Advancing HIV stages are associated with a progressive decline in renal function, as evidenced by an increasing proportion of patients with eGFR < 60 mL/minute/1.73 m². While impaired renal function is prevalent among HIV patients initiating ART, inconsistencies in eGFR estimation methods may contribute to challenges in classifying renal disease. Given these limitations, existing CKD staging systems may not be adequate for accurately assessing renal function in HIV-infected populations.

In this study, an analysis of HIV staging in relation to sonographic kidney size reveals a progressive increase in the prevalence of large kidneys as the disease advances. In the early stage (stage 1), a smaller proportion of patients exhibit large kidneys. However, by stage 3, more than half of the patients present with enlarged kidneys. Notably, in stage 4, the prevalence of large kidneys declines slightly compared to stage 3. A study by Sani Suleiman et al[23] found enlarged kidneys in 28% of HIV patients, whereas another study reported that 85% of HIV patients had normal kidney sizes. However, kidney size and echogenicity do not correlate with CD4 cell count in HIV-infected patients[24]. In a study from Nigeria, kidney size was negatively correlated with HIV stage, as measured by CD4 cell count[25]. The trend observed in this study aligns with the known pathophysiology of HIVAN, which initially presents as kidney enlargement due to inflammation and hyperfiltration, followed by shrinkage in end-stage disease due to fibrosis and nephron loss. As HIV progresses, direct viral infection of renal epithelial cells leads to podocyte injury, interstitial inflammation, and glomerular hypertrophy, which are characteristic of HIVAN. This results in tubular dysfunction and interstitial oedema, contributing to kidney enlargement. Glomerular hyperfiltration in response to nephron loss also plays a role in compensatory hypertrophy of the kidneys. Studies, including those by Sani Suleiman et al[23] suggest a significant proportion of HIVAN patients develop enlarged kidneys due to these changes. In advanced HIV (stage 4), prolonged chronic kidney injury, fibrosis, and sclerosis lead to nephron loss and kidney shrinkage. Tubulointerstitial fibrosis and glomerulosclerosis reduce kidney size despite prior enlargement, which may explain the slight decline in the prevalence of large kidneys in stage 4 compared to stage 3. The negative correlation between kidney size and HIV stage observed in the Nigerian study may reflect differences in patient populations, underlying comorbidities, or predominant kidney pathologies other than HIVAN (e.g., CKD due to hypertension or diabetes). Adeyekun et al[24] found that kidney size and echogenicity do not correlate with CD4 counts, suggesting heterogeneous renal responses in HIV patients. However, variations in findings among different studies indicate that additional factors such as ethnicity, genetic predisposition (apolipoprotein L1 variants), and coexisting kidney diseases could influence the relationship between kidney size and HIV staging.

This study examines the relationship between various stages of HIV and the presence of sonographic echogenicity in the kidneys. The data indicate an increasing prevalence of kidney echogenicity as HIV progresses. In the early stages (stage 1), a smaller proportion of patients exhibit echogenicity, whereas in the later stages (stages 3 and 4), all patients demonstrate this condition. These findings suggest a correlation between the advancement of HIV and the increased occurrence of renal echogenicity. Consequently, renal echogenicity and morphology may serve as valuable indicators in diagnosing HIVAN. Studies have shown that a high proportion of HIVAN patients exhibit grade 3 renal echogenicity. Sonographic evaluation can reliably predict an HIVAN diagnosis, with increased kidney width and thickness being significant markers[26]. However, some research suggests that HIV infection does not significantly affect ultrasound or laboratory profiles of renal insufficiency, although kidney thickening and a spherical appearance may indicate HIV-related renal involvement[27]. Interestingly, one study found that large kidneys and marked increases in renal echotexture were not common even in patients with low CD4 cell counts, and that renal size and echogenicity alone may not be reliable predictors of renal involvement in HIV[24]. These findings highlight the complex relationship between HIV, renal echogenicity, and kidney function. In early HIV infection, the renal parenchyma remains relatively unaffected because direct viral injury, immune activation, and inflammatory responses are still developing. Glomerular and tubular structures remain largely intact, which may explain the lower prevalence of renal echogenicity observed in stage 1 patients. As HIV progresses, renal involvement becomes more pronounced, with characteristic findings of HIVAN. These structural abnormalities increase renal echogenicity on ultrasound, making it more detectable in later stages (stages 3 and 4). By these stages, all patients exhibit echogenicity, likely due to significant parenchymal damage and interstitial fibrosis, which alter the acoustic properties of the renal cortex. Some studies indicate that renal echogenicity does not directly correlate with CD4 counts, suggesting that other factors may influence kidney morphology in HIV patients[24,27]. This could mean that HIV-related renal damage is multifactorial, influenced by viral load, opportunistic infections, immune activation, and comorbid conditions. While increased echogenicity is strongly associated with advanced HIV, it is not specific to HIVAN and can also be seen in other renal pathologies. Therefore, to confirm a diagnosis, a renal biopsy may be necessary.

Limitations

This study has several limitations. As a single-center observational study conducted among a South Indian population, the findings may lack generalizability to other geographic or ethnic groups. The assessment of HIVAN was based primarily on eGFR and renal ultrasonography, without confirmation through genetic analysis or renal biopsy. Future multicenter studies involving diverse ethnic populations, along with imaging techniques such as CT-guided measurements of renal size and renal biopsy, would provide more comprehensive insights into the prevalence and characteristics of HIVAN among PLWH.

CONCLUSION

This study underscores the critical importance of routine and comprehensive monitoring of renal function in PLWH, particularly those undergoing long-term ART. Renal abnormalities - both structural and functional are frequently observed in this population, with functional impairments emerging as particularly prevalent. As the disease progresses, the incidence and severity of renal involvement appear to increase, highlighting the need for vigilant and sustained assessment of kidney health throughout HIV management.

Notably, trends such as a progressive decline in eGFR, alterations in renal dimensions, and increased renal echogenicity emphasize the potential utility of sonographic imaging in the early detection of HIV-associated renal complications. These findings reinforce the value of renal ultrasonography as a non-invasive adjunct to laboratory testing in the surveillance of HIVAN. Given the complex and heterogeneous nature of renal involvement in HIV, an integrated diagnostic approach - combining clinical evaluation, laboratory parameters, and imaging studies - is essential for timely identification and appropriate management of HIVAN. Such a multidimensional strategy may improve patient outcomes through earlier intervention and more tailored therapeutic approaches.