Introduction:
Hepatitis B virus infection (HBV) rates have decreased over the past three decades, but it still poses a significant global health threat. An estimated 254 million persons worldwide were predicted to have chronic hepatitis B virus infection (CHB) in 2022, with 65% of those cases occurring in the Western Pacific and African regions. The prevalence of HBV in Uganda was 4.3% in 2019 and 0.8% in southwestern Uganda. The CHB primarily affects the liver, causing a disease spectrum from acute to chronic liver conditions such as; cirrhosis, and hepatocellular carcinoma. However, there are several other extra-hepatic manifestations of CHB which include skin rash, arthritis, and kidney disease among others. Numerous mechanisms have been proposed for the development of kidney disease from CHB and include the deposition of immune complexes (IC) in the glomerulus and small and medium blood vessels to form glomerulonephritis and vasculitis respectively. Membranous and membranoproliferative glomerulonephritis (GN) are the two types of GN that are most common in adults with CHB while mixed cryoglobulinemia and Polyarteritis nodosa are the two types of vasculitis these patients develop. Another mechanism is through induction of kidney tubular cell injury and apoptosis by triggering a pathway of Fas up-regulation. Some CHB may develop kidney disease as a result of the antiviral medications they are taking, such as tenofovir disoproxil fumarate(TDF), and others due to comorbidities like hypertension, diabetes mellitus, HIV, and hepatitis C co-infection. With the global increase in the burden of kidney disease, it has been reported that 850 million people suffer from kidney disease currently making it the 12th greatest cause of death worldwide, with most cases occurring in sub-Saharan Africa (SSA). In SSA, kidney disease prevalence is estimated to be at 13.9% and as high as 21.4% in Uganda making it one of the primary contributors to morbidity and mortality. Other than the standard risk factors for kidney disease, such as hypertension, diabetes mellitus, HIV, smoking, and alcohol use, CHB is increasing as a major cause of kidney disease. In our setting, the most common causes of kidney disease are typically not well-defined. A study conducted on the general population demonstrated that two-thirds of individuals with kidney disease do not have the traditional risk factors, which include HIV infection, diabetes mellitus, and hypertension. In addition, a significant number of kidney disease patients in Uganda delay in seeking care with 51% presenting with kidney failure at their first visit, and with advanced symptoms, including edema, severe hypertension, and potentially fatal electrolyte abnormalities such as acidosis or hyperkalemia. Although the prevalence of CHB is high in SSA, little is known about the prevalence of HBV-related kidney disease. The majority of studies have used the estimated glomerular filtration rate (eGFR) using serum creatinine to assess kidney function in patients with CHB despite its significant drawbacks. Serum creatinine has a poor sensitivity (77%), but a great specificity (91%), especially in the early phases of kidney disease. Scientists have looked into more recent novel kidney function biomarkers, including urine Neutrophil Gelatinase Associated Lipocalin (NGAL), which possesses a sensitivity range of 90-93% and a specificity range of 71-99% in detecting early changes in kidney function. In patients with CHB, using novel kidney function biomarkers like urine NGAL would help in capturing kidney disease early enough and the timely introduction of hepatitis B virus treatment to arrest the development of end-stage kidney disease (ESKD) irrespective of other indications for treatment. In adults, hepatitis B-related kidney disease is linked with the progression of kidney disease to ESKD, necessitating kidney replacement therapy if no treatment is given. In Uganda, there is no data about the prevalence of kidney disease and its associated factors among patients with CHB. Our overarching goal was to determine the prevalence of kidney disease and associated factors among patients with CHB using a combination of kidney function biomarkers including a novel biomarker urine NGAL in a cohort of patients with HBV.
Methods:
We conducted a cross-sectional study from November 2023 to April 2024 at the hepatitis clinic of Mbarara Regional Referral Hospital, recruiting patients 18 years and above being followed up for CHB. Data collected included: socio-demographic data, Comorbidities, coinfections, and CHB-related data. Spot urine and blood were collected for dipstick, urine NGAL, and creatinine. GFR was estimated using the CKD-EPI 2021 equation. The prevalence of kidney disease was represented as a simple proportion with 95% Confidence interval (CI). Logistic regression was used to determine factors associated with kidney disease. A p-value ≤ 0.05 was considered significant.
Results:
We screened 142 patients with a diagnosis of CHB from November 2023 to April 2024. 12 patients were excluded because five of them were pregnant, and two were in their menstrual period. Nine patients declined to sign informed consent. We finally enrolled 126 patients whose data was captured and analyzed in the study. We had a young population with a mean age of 36.2 (SD: ±12) years and half the number were women (n= 63/126). 6.3% (n=8/126) had a history of smoking and only 22.2% (n= 28/126) had a history of taking alcohol. 13.5% (n=17/126) had a hypertension history, a small proportion had HIV infection 1.6% (n=2/126), only 3.2% (n=4/126) had hepatitis C coinfection and no participant had diabetes mellitus. We had 41.3% (n=52/126) of patients on TDF treatment. Only 37.3% (47/126) had a history of herbal medicine use with a median duration of 2 (IQR: 1-12) months. Most participants had normal serum creatinine with a mean of 1.03mg/dl and normal liver enzymes with median ALT and AST of 25 (IQR:19-35) and 27 (IQR: 22-36) respectively. Our study found an overall prevalence of 30.2% with a 95% CI of 22.7-38.8 when using urine NGAL, eGFR <60ml/min/1.73m2, and eGFR between 60-89ml/min/1.73m2 with either hematuria or proteinuria. Using the individual biomarkers for kidney function urine NGAL gave us a higher prevalence of 19.1% (95% C.I: 12.6-27.0) compared to eGFR <60ml/min/1.73m2 and eGFR between 60-89ml/min/1.73m2 with either proteinuria or hematuria at 6.4% (95% C.I: 2.8-12.1) and 11.1% (95% C.I: 6.7-18.0) respectively.
Conclusions:
The study reveals a 30.2% kidney disease prevalence among patients with CHB with a higher prevalence using urine NGAL (19.1%). Being female was the only factor associated with kidney disease. The study recommends frequent monitoring of patients with CHB especially among women.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.