- To determine the prevalence, patterns and factors associated with glomerulonephritis among patients presenting with clinical features suggestive of glomerulonephritis at MRRH in Southwestern Uganda.
Infection-related glomerulonephritis is an immunologically mediated glomerular injury after an infection. Glomerulonephritis may occur with the infection or after a variable latent period. Poststreptococcal glomerulonephritis (PSGN) is the prototype of infection-related glomerulonephritis. The streptococcal antigens, nephritis-associated plasmin-like receptor and streptococcal exotoxin B, have emerged as major players in the pathogenesis of PSGN. Although PSGN is the most common infection-related glomerulonephritis in children, in adults, glomerulonephritis is secondary to bacteria such as staphylococci, viruses such as hepatitis C, and human immunodeficiency virus, and, rarely, parasitic infections. Supportive therapy is the mainstay of treatment in most infection-related glomerulonephritis. Treatment of the underlying infection with specific antibiotics and antiviral medications is indicated in some infections. Parasitic infections, although rare, may be associated with significant morbidity. Poststreptococcal glomerulonephritis is a self-limiting condition with a good prognosis. However, bacterial, viral, and parasitic infections may be associated with significant morbidity and long-term consequences. Epidemiologic studies are required to assess the global burden of infection-related glomerulonephritis. A better understanding of the pathogenesis of infection-related glomerulonephritis may unravel more treatment options and preventive strategies.
Human immunodeficiency virus–associated nephropathy (HIVAN) is the most common cause of CKD in patients with HIV-1, and is mostly observed in patients of African descent, perhaps related to susceptibility associated with genetic variation at the APOL1 gene locus on chromosome 22, closely associated with the MYH9 locus. Untreated, HIVAN rapidly progresses to ESRD. Typical HIVAN pathology includes FSGS, often with a collapsing pattern, accompanied by microcystic change in tubules. There are usually many tubuloreticular structures seen on electron microscopy. In addition to HIVAN, a number of other HIV-associated kidney diseases have been described. In patients with HIV, proteinuria and/or decreased kidney function is associated with increased mortality and worse outcomes. Data from a number of RCTs suggest that highly active antiretroviral therapy (HAART) is beneficial in both preservation and improvement of kidney function in patients with HIV. Patients with Kidney function at start of HAART have the most dramatic improvements in kidney function. A decrease in HIV viral load during HAART is associated with kidney function improvement, while an increase in viral load is associated with worsening kidney function.
Causes of kidney disease, other than HIVAN, that occur in patients with HIV infection include diabetic nephropathy, thrombotic microangiopathies, cryoglobulinemia, immune complex GN, an SLE-like GN, or amyloidosis, More than a third of the patients with HIV who underwent a kidney biopsy had diabetic nephropathy; or MN, MPGN, IgAN, or another pattern of immune-complex In patients with HIV infection, many of these pathologies can mimic HIVAN, but each condition requires a different therapy. Studies in HIV-infected patients with kidney disease from Africa showed a high prevalence of HIVAN, but other forms of GN and interstitial nephritis were also present, Cohen and Kimmel recently reviewed the rationale for a kidney biopsy in the diagnosis of HIV-associated kidney disease.
The nature of the nephritogenic streptococcal antigen is still controversial. Kidney biopsy is not indicated unless there are characteristics that make the diagnosis doubtful, or to assess prognosis and/or for potential therapeutic reasons. The kidney histology shows acute endocapillary GN with mesangial and capillary granular immune deposition.
The clinical manifestations of acute nephritic syndrome usually last less than 2 weeks. Less than 4% of children with poststreptococcal GN have massive proteinuria, and occasionally a patient develops crescentic GN with rapidly progressive kidney dysfunction. Serum C3 values usually return to normal by 8–10 weeks after recognition of the infection. Persistent hypocomplementemia beyond 3 months may be an indication for a renal biopsy, if one has not already been performed. A lesion of MPGN is commonly found in persistently hypocomplementemic GN.
The short-term prognosis of the acute phase of poststreptococcal GN is excellent in children; however, in elderly patients, mortality in some series is as high as 20%. Although the long-term prognosis of poststreptococcal GN is debated, the incidence of ESRD in studies with 15 years of follow-up is less than 1%, with the exception being that long-term prognosis is poor in elderly patients who develop persistent proteinuria.
Well-documented streptococcal infection should be treated with penicillin or erythromycin if the patient is allergic to penicillin, to resolve streptococcal infection and prevent the spread of the nephritogenic streptococcus among relatives or contacts. However, antibiotics are of little help for reversing GN, as the glomerular lesions induced by immune complexes are already established.
The management of acute nephritic syndrome, mainly in adults, requires hospital admission if features of severe hypertension or congestive heart failure are present. Hypertension and edema usually subside after diuresis is established. Adult patients persisting with urinary abnormalities beyond 6 months, especially if proteinuria >1 g/d, should receive ACE-I or ARBs, as in other proteinuric glomerular diseases. The long-term prognosis is worse in patients, mainly adults, who have persistent proteinuria after 6 months.
In the past, most cases of bacterial infection–related glomerulonephritis (IRGN) occurred in children following streptococcal upper respiratory tract or skin infections and were called postinfectious GN. Over the past 3 decades, there has been an important shift in epidemiology, bacteriology, and outcome of IRGN. A significant percentage of cases now target adults, particularly the elderly or immunocompromised. Because adult infections are often ongoing at the time of diagnosis, the term IRGN appears more appropriate. The sites of infection in adult IRGN are more heterogeneous than in children, and include the upper respiratory tract, skin, lung, heart, urinary tract, teeth/oral mucosa, and bone. In adults, the disease is more likely to be secondary to non-streptococcal infections, particularly staphylococcal infection. In contrast to the favorable course in children, a significant proportion of adults with IRGN, especially the elderly and diabetics, do not recover renal function. Whereas the pathogenesis of post-streptococcal glomerulonephritis has been studied extensively, leading to the identification of two candidate nephritogenic streptococcal antigens, glyceraldehyde-3-phosphate dehydrogenase and pyrogenic exotoxin B, few investigations have focused on IRGN caused by other bacteria.
Infection remains a common cause of proliferative glomerulonephritis (GN). Kidney biopsies demonstrate that the same agent may induce more than one histologic type of GN, and that any given glomerular lesion may be the consequence of a wide array of pathogens. In the early 1970s, this chapter would have been almost entirely devoted to poststreptococcal acute glomerulonephritis (AGN) complicating throat or skin infections and scarlet fever; however, in the ensuing decades, the epidemiology of postinfectious glomerulonephritis (PIGN) has considerably evolved in the Western world. Yet what has now changed in industrialized countries is not entirely applicable to other parts of the world, and poststreptococcal AGN remains a significant public health problem in Latin America, Africa, and most probably Eastern Europe. Any proliferative GN whose etiology is unclear should prompt consideration of an infectious origin, even if this etiology is not readily suggested by the clinical context.
End-stage renal disease (ESRD) represents a critical public health challenge worldwide, with access to renal replacement therapy (RRT) being particularly limited in developing countries. In developed nations, diabetes mellitus and hypertension are the leading causes of ESRD, while glomerulonephritis (GN) significantly contributes to ESRD in developing regions, for instance, the 2012 United States Renal Data System (USRDS) reported adjusted ESRD incidence rates of 154.1/million/year for diabetes, 101.1/million/year for hypertension, and 28.3/million/year for GN. Conversely, the Chinese Renal Data System identifies glomerular diseases as the leading cause of ESRD, accounting for 57.4% of cases (Chironda et al., 2019). In Africa, studies have shown that glomerular diseases contribute to 10.2%–52% of ESRD cases. The availability of renal registries in developed countries facilitates a detailed classification of glomerular disease patterns. For example, IgA nephropathy is the most common form of GN in Europe, North America, and Asia. However, in Africa, limited renal registries, a shortage of skilled professionals to perform renal biopsies, and inadequate diagnostic infrastructure hinder comprehensive understanding of renal disease patterns. While GN is recognized as the most prevalent cause of ESRD in Africa, critical gaps remain in defining its prevalence and patterns on the continent (Bello et al., 2019).
Chronic diseases such as diabetes and hypertension continue to account for a significant proportion of chronic renal failure cases. However, idiopathic glomerulonephritis (GN) presents a notable diagnostic challenge for both nephrologists and pathologists. The degree of proteinuria often guides clinicians in differentiating between two primary clinical patterns: nephritic and nephrotic syndromes (Jasim., Shemran, & Al-Mansouri, 2024).
Over the years, the epidemiology of nephritic syndrome has evolved, influenced by changes in public health protocols, the prevalence of infections, and vaccination strategies. In contrast, the etiology of nephrotic syndrome has shown more pronounced fluctuations, reflecting variations in racial and age-related predispositions, whether these trends signify shifts in disease patterns or improvements in the understanding of glomerular disorders remains a subject of ongoing debate (AlYousef et al., 2020).
It has been proposed that, alongside genetic predispositions, environmental factors and the prevalence of infectious diseases contribute to the socioeconomic and demographic disparities observed in glomerulopathy patterns. Acute nephritic syndrome is typically associated with underlying immunological injury, most often triggered by infectious agents (Infante, Rossini, et al., 2020).
Epidemiological studies indicate that GN is a significant cause of kidney disease worldwide. In developing countries, GN is among the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). According to studies conducted in sub-Saharan Africa, GN accounts for approximately 20-30% of cases of CKD. In developed nations, the prevalence is influenced by improved diagnostic capabilities and healthcare access, with GN often identified in earlier, asymptomatic stages (de Sousa, 2024).
GN can manifest in several distinct patterns based on etiology, histological findings, and clinical presentation, some of them like AGN is often associated with post-infectious causes, particularly streptococcal infections (Penfold, Prendecki, McAdoo, & Tam, 2018).). Patients typically present with a sudden onset of hematuria, oliguria, edema, and hypertension, also Chronic Glomerulonephritis (CGN), CGN results from the progression of unresolved acute forms or primary glomerular diseases, often leading to CKD, Nephrotic Syndrome, this pattern is characterized by heavy proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia. Common underlying causes include minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Rapidly Progressive Glomerulonephritis (RPGN), Also known as crescentic GN, RPGN is marked by a rapid decline in renal function over weeks to months. It is often associated with autoimmune conditions such as Goodpasture syndrome and systemic lupus erythematosus (Buch et al., 2015).
Streptococcal infections remain a leading cause of AGN in resource-limited settings. Viral infections such as hepatitis B and C, as well as HIV, are also significant contributors. Diseases like systemic lupus erythematosus (SLE) and vasculitides are associated with secondary GN forms. The presence of autoantibodies such as anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) is a hallmark in these conditions (Cosio, & Cattran, 2017).
Certain genetic mutations and polymorphisms have been linked to susceptibility to GN. For example, mutations in complement regulatory genes are implicated in membranoproliferative GN (Noris, & Remuzzi, 2015). Poor sanitation, overcrowding, and limited access to healthcare contribute to the high prevalence of post-infectious GN in developing countries, exposure to environmental toxins and pollutants can exacerbate kidney inflammation (Garam et al., 2021). Smoking, obesity, and high salt intake are recognized risk factors that may exacerbate GN progression by promoting hypertension and systemic inflammation (Wong, & Kavanagh, (2018) GN shows variation in prevalence by age and gender, for instance, nephrotic syndrome due to minimal change disease is more common in children, while membranous nephropathy predominates in adults. Men are generally more affected than women in most forms of GN (Wong, 2016).
Acute glomerulonephritis (AGN) caused by infections remains a leading cause of acute kidney injury (AKI). Historically, most AGN cases in children were attributed to poststreptococcal acute glomerulonephritis (PSAGN), which occurs after a latent period following the resolution of a group A Streptococcus (GAS) infection. However, over the last two decades, there has been a significant shift in the epidemiology of AGN. Improved living conditions and widespread use of antibiotics have contributed to a decline in PSAGN cases, particularly in developed countries, AGN cases in adults have risen, with nonstreptococcal infections, especially those caused by Staphylococcus, now being as prevalent as PSAGN (Duong, & Reidy, 2022). Notably, in adult AGN patients, especially older individuals with comorbidities, infections are often active at the time of glomerulonephritis diagnosis (Xu et al., 2024).
Glomerulonephritis encompasses a diverse group of disorders. In some cases, the kidneys are the primary or sole organ affected, such as in kidney-specific autoimmunity or genetic disorders, glomerulonephritis may manifest as part of a systemic disease, a complication of malignancy or monoclonal gammopathy, or due to external factors like infections or medications (Morfin, & Jespersen Nizamic, 2024).
These conditions can present in a variety of clinical patterns or syndromes, often characterized by varying degrees and combinations of haematuria, proteinuria, fluid retention, hypertension, and reduced glomerular filtration rate (GFR) (Yarandi, & Shirali, 2023). Acute presentations, such as full-blown nephritic syndrome (featuring haematuria with red blood cell casts, proteinuria, oliguria, hypertension, and oedema) or rapidly progressive glomerulonephritis (rapid loss of kidney function over days to months due to acute glomerular injury), are relatively rare. More commonly, patients exhibit asymptomatic haematuria and proteinuria, with or without diminished kidney function. Recognizing these patterns is essential for developing a differential diagnosis (Kitai, Matsubara, & Yanagita, 2015).
The initial evaluation of suspected glomerulonephritis involves microscopic analysis of urinary sediment, biochemical tests of serum and urine, and serological analysis. Comprehensive laboratory and immunological assessments are recommended early in the diagnostic process (Yarandi, & Shirali, 2023). In certain cases, diagnoses can be made before kidney biopsy results are available, particularly when serological markers such as anti-neutrophil cytoplasmic antibodies (ANCA) or anti-glomerular basement membrane (GBM) antibodies are detected (Abi Daoud, Chen, Zhang, Feilotter, & Tron, 2009). The estimated GFR (eGFR) is best calculated using the Chronic Kidney Disease Epidemiology Collaboration formula. To measure urinary protein excretion, a 24-hour urine collection is ideal, though a protein–creatinine ratio from a spot urine sample collected over 24 hours can serve as a practical alternative (Wadhwani, Jayne, & Rovin, 2018).
The definitive diagnosis of glomerulonephritis relies on kidney biopsy, which reveals hallmark glomerular inflammation and increased cellularity. This hypercellularity manifests in various histopathological patterns depending on the site and severity of glomerular damage. These patterns include mesangial proliferative glomerulonephritis, diffuse endocapillary glomerulonephritis, exudative glomerulonephritis, necrotizing and crescentic glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), or combinations thereof. Traditional classifications of glomerulonephritis are based on these histopathological patterns (Chen, & Dember, 2008).
Understanding glomerulonephritis is crucial for assessing the acuteness, severity, and extent of the disease process, similar patterns of injury can result from different underlying causes. For instance, glomerulonephritis caused by chronic hepatitis C or abnormalities in the alternative complement pathway may both exhibit an identical MPGN (membranoproliferative glomerulonephritis) pattern of injury (Sethi, & Fervenza, 2019). Likewise, diffuse proliferative glomerulonephritis can arise from acute infections, lupus nephritis, or cryoglobulinemia, all of which involve the accumulation of immunoglobulins in the glomerulus, leading to inflammation. Additionally, most types of glomerulonephritis can progress to scarring patterns, such as sclerosing glomerulonephritis. While specific types of glomerulonephritis are generally associated with characteristic patterns of injury, they may also present with multiple histopathological patterns on a kidney biopsy (Satoskar, Parikh, & Nadasdy, 2020).
Significant advancements have been made in identifying the underlying causes and mechanisms of glomerulonephritis, enabling the development of more targeted and effective therapies. As a result, a causal classification approach is now preferred over a pattern-based method (Woo et al., 2019). The causes of glomerulonephritis are typically identified through immunofluorescence studies. Broadly, glomerulonephritis can be categorized into immune-complex glomerulonephritis (including infection-related glomerulonephritis, IgA nephropathy, lupus nephritis, and cryoglobulinemic glomerulonephritis), ANCA-associated (pauci-immune) glomerulonephritis, anti-GBM glomerulonephritis, C3 glomerulopathy, and monoclonal immunoglobulin-associated glomerulonephritis. Conditions like minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy, which are not characterized by glomerular inflammation, are beyond the scope of this discussion (Ramineni, & Bandi, 2021).
