Clinico-etiological profile of haematuria in children: A retrospective analysis

INTRODUCTION

Haematuria is described as the continuous presence of more than five red blood cells (RBCs)/high-power field (HPF) in urine that have not been centrifuged.^[1] Although underlying disease may be indicated by 10–50 RBCs/µL, severe haematuria is typically defined as >50 RBCs/HPF.^[1] Persistent microscopic haematuria occurs in <1% of children. Gross haematuria (visible discoloration noted in urine due to RBCs) occurs much less often (incidence <0.1%).^[2]

According to whether the haematuria is glomerular or non-glomerular in origin, the causes of gross haematuria are divided into different categories.^[3] RBCs that are dysmorphic or eumorphic in glomerular and non-glomerular haematuria, respectively, can be identified by microscopic analysis of the urine.^[4]

Gross haematuria is more frequently seen as a presenting symptom of acute post-streptococcal glomerulonephritis, immunoglobulin A (IgA) nephropathy, and Alport syndrome, even though glomerular disorders are almost invariably linked to some degree of haematuria.^[5]

Idiopathic hypercalciuria, bacterial or viral urinary tract infections (UTIs), urolithiasis, urinary tract structural abnormalities and sickle cell trait are the most common causes of non-glomerular haematuria.^[6]

When evaluating a child with haematuria, it is important to rule out any major underlying renal illness that may have a dire prognosis.^[7]

Gross haematuria usually prompts emergency care, but little is known about the long-term effects, clinical features, aetiology and associated symptoms in children from this geographical area. This retrospective review was performed with the aim to study the demographic, etiological and clinical profile of children presenting with haematuria, with the following objectives: To elucidate the underlying aetiology of microscopic and macroscopic haematuria in children and to characterise clinical and laboratory profile of children presenting with macroscopic and microscopic haematuria and its outcome.

MATERIAL AND METHODS

This retrospective study was conducted in Yenepoya Medical College hospital by retrieving case records of patients (aged 1 month to 16 years) presented with haematuria (from 01 January 2018 to 31 December 2022). Ethical clearance was obtained from the Institutional Ethics Committee before the study.

Case files were obtained from the medical records department, using the international classification of diseases (ICD) codes of ‘haematuria’ and all probable causes of haematuria, which includes post-infectious glomerulonephritis, IgA nephropathy (Berger disease), thin glomerular basement membrane disease, membranoproliferative glomerulonephritis, membranous nephropathy, Alport syndrome, focal segmental glomerulosclerosis, antiglomerular basement membrane disease, Henoch-Schönlein purpura nephritis, systemic lupus erythematosus (SLE) nephritis, haemolytic uremic syndrome, Wegener granulomatosis, polyarteritis nodosa., Goodpasture syndrome, sickle cell glomerulopathy, pyelonephritis, interstitial nephritis, acute tubular necrosis, hydronephrosis, papillary necrosis, nephrocalcinosis, polycystic kidney disease, tumours (Wilms, angiomyolipoma and rhabdomyosarcoma), urolithiasis/hypercalciuria and coagulopathy using respective ICD 10 codes.

Demographic details, clinical presentation and relevant laboratory/radiological investigation, which contribute to making a diagnosis, were noted down.

The outcome of the patient, including mortality and morbidity associated with disease (such as persistent hypertension/deranged renal function and persistent urinary abnormalities) at the time of discharge, was noted down.

Reports of renal biopsy or any other invasive procedures were also noted.

Glomerular haematuria was defined as microscopic urine examination with >5 RBC/HPF and >20% dysmorphic RBC, combined with moderate proteinuria (dipstick 2+) with or without casts.^[8] Based on information from the history, clinical examination and urinalysis, the condition was finally classified as either glomerular or non-glomerular haematuria.^[8]

Statistical analyses were conducted using the Statistical Package for the Social Sciences 27.0 program. The Fisher exact/Mann–Whitney U-test was used to compare continuous variables, while the Chi-square test was used to analyse categorical variables. P < 0.05 was regarded as significant.

RESULTS

Total of 84 children, consisting of 40 boys, with average age of 7.3 ± 4.94 years, (ranging from 3 months to 16 years) were assessed for microscopic and macroscopic haematuria.

The most common presenting complaints were fever, which occurred in 60.7% (n= 51) of patients, dysuria, affected 33.3% (n = 28) of patients, oedema, present in 34.5% (n = 29) of patients, lower abdominal pain, experienced by 27.4% (n = 23) of patients, reduced urine output, reported by 21.4% (n = 18) of patients, excessive cry/irritability, observed in 11.9% (n = 10) of patients and hypertension, affecting 28.5% (n = 24) of patients.

The symptoms appeared 1 day–2 years before the cause of haematuria was determined. Fourteen cases presented with haematuria were known cases of renal illnesses such as nephrotic/nephritic syndrome, end-stage renal disease, chronic kidney disease, mesangioproliferative glomerulonephritis and focal segmental glomerulosclerosis. There were five known cases of SLE and one case of Wiskott–Aldrich syndrome; gross haematuria was observed in 42.4% (n = 36) of patients, whereas microscopic haematuria was seen in 57.6% (n= 49). Glomerular haematuria accounted for 32.9% (n = 28) of cases, while non-glomerular haematuria was seen in 67.1% (n = 57) of cases.

In children with non-glomerular haematuria, UTI (40, 47%), hydronephrosis (5, 5.9%) and renal calculi (4; 4.7%) constituted the most common causes, whereas post-infectious glomerulonephritis (19, 22.6%), lupus nephritis and membranoproliferative glomerulonephritis constituted most common causes among glomerular haematuria [Tables 1 and 2].

UTI nephrotic syndrome constituted the most common cause among microscopic haematuria, whereas post-infectious glomerulonephritis, hydronephrosis and UTI constituted the most common causes among macroscopic haematuria [Tables 3 and 4]. A few cases of acute glomerulonephritis also presented with microscopic haematuria.

Anaemia was present in 61.9% (n = 52) of patients. Severe anaemia necessitating a packed-cell transfusion was observed in 10.6% (n = 9) of patients. Moderate anaemia was reported in 28.2% (n = 24) of patients, while mild anaemia was seen in 22.4% (n = 19) of patients – predominantly due to nutritional causes.

Deranged renal function tests were observed in 17.6% (n = 15) of patients; five of them had chronic kidney disease (three children were on maintenance haemodialysis), rest with acute kidney injury. Six children, representing 7.14% of the study population, developed acute renal failure requiring dialysis. Rapidly progressive glomerulonephritis was observed in two children who had glomerular haematuria.

Dyselectrolytemia was noted in 53.5% (n = 45) of patients. Thirty patients (35.7%) had hyponatremia (Na <134), and one patient with hypernatremia (Na-152). Hypokalaemia (K <3.4) was observed in 4 children (4.8%) and 2 children (2.4%) had hyperkalaemia (K >5.5). Hypercalcemia (Ca >10.5) and hypocalcemia (Ca <8.5) were observed in 15 children (17.8%) and 2 children (2.4%), respectively. Similarly, 4 children (4.8%) had hypophosphatemia (P< 3.5) and 8 children (9.5%) had hyperphosphatemia (P> 6).

Fourteen children (16.6%) had raised antistreptolysin O (ASO) antibody titres, antinuclear antibody (ANA) immunofluorescence (IF) was positive for eight children (9.5%) and 21 children (25%) had low C3 levels. Mean (SD) C3 levels noted in glomerular haematuria were 40.5 (37.3) mg/dL.

Renal biopsy was performed in three children, revealing membranoproliferative glomerulonephritis, renal cortical necrosis and tubulointerstitial nephritis.

Mortality was observed in 2 (2.4%) cases, died due to SLE lupus nephritis with multi-organ dysfunction and haemolytic uremic syndrome with uremic encephalopathy.

Thirty-four cases (40.4%) had persistent abnormal urine analysis at the time of discharge, two cases were discharged with persisting hypertension and 12 cases (14.3%) with deranged renal function tests.

On analysis between parameters [Tables 5.1 - 5.3 and 6.1 - 6.3], it is noted that hypertension, oliguria and oedema were significantly more in glomerular haematuria. Urine-specific gravity was significantly lower in microscopic and non-glomerular haematuria. Renal functions showed elevated serum creatinine levels in macroscopic (P= 0.046) and glomerular haematuria (0.076). Hypoalbuminemia, hypertriglyceridemia and low complement levels were also noted significantly in glomerular haematuria.

Significant associations were also noted between glomerular haematuria with macroscopic haematuria, and nonglomerular haematuria with microscopic haematuria.

Patients with macroscopic/glomerular haematuria had more associated complications (acute kidney injury, dyselectrolytemia, sepsis, multiple organ dysfunction syndrome [MODS], hypertension, renal failure, posterior reversible encephalopathy syndrome, uremic encephalopathy and pulmonary oedema) and morbidity at the time of discharge and had more hospital stay.

Comparison of parameters showed age, gender, birth history, vital signs (temperature, pulse rate and respiration rate), urine analysis (pH, colour, pus cells and epithelial cells), urine culture between glomerular and non-glomerular groups, microscopic haematuria and macroscopic haematuria group did not render significant association.

Similarly, a comparison of haemoglobin, total leucocyte counts, platelet counts, C-reactive protein levels, blood urea, serum electrolytes (Sodium, potassium, calcium and phosphorus), liver function test (serum glutamic-oxaloacetic transaminase [SGOT], serum glutamic pyruvic transaminase [SGPT], alkaline phosphatase [ALP] and bilirubin), blood culture, ASO, ANA-IF, chest X-ray and ultrasound abdomen also did not render any significant associations.

DISCUSSION

In our retrospective study of 84 children presented with microscopic/macroscopic haematuria, we found that non-glomerular causes were more common. However, glomerular causes were predominant in patients presented with macroscopic haematuria. These results were consistent with previous findings noted by Mishra et al.^[7] Our study showed that UTI was the most common cause of microscopic/non-glomerular haematuria, and infection-related glomerulonephritis was the most common cause of glomerular/macroscopic haematuria. These findings were in agreement with studies by Mishra et al.^[7] but were contradicting in comparison to some of the existing studies, where IgA nephropathy was the most common cause for macroscopic haematuria.^[3,9-11]

Our results show that children with glomerular haematuria were more likely to present with high blood pressure, oedema and oliguria compared to those with non-glomerular haematuria. This is in agreement with the previous studies.^[12] According to research by Ashraf et al. (2013), children having glomerular diseases often present with significant proteinuria and dyslipidaemia^[12], which was in agreement with our findings.

The high incidence of anaemia (61.9%) and dyselectrolytemia (53.5%) underscores the importance of thorough laboratory evaluation, including complete blood counts, electrolyte panels and renal function tests. Anaemia was the most commonly associated comorbidity, predominantly due to nutritional causes. The significant correlation between glomerular haematuria and hypoalbuminemia highlights the need for close observation of kidney function and consideration of renal biopsy.

Our study demonstrated that children with glomerular haematuria had a longer hospital stay and higher morbidity at discharge compared to those with non-glomerular haematuria. This emphasises the value of early detection and management of glomerular diseases to prevent long-term complications. A study by Youn et al. reported similar findings, highlighting the need for prompt intervention in children with glomerular haematuria.^[3]

Our findings are consistent with the previous studies^[8] that reported similar aetiologies and clinical profiles of haematuria in children. However, our study highlights the need for increased awareness of UTI as a common cause of haematuria in children.

Our research highlights the significance of promptly evaluating children who have haematuria for identifying underlying aetiologies, consideration of UTI as a potential cause of haematuria and aggressive management of glomerular diseases to prevent long-term complications.

Our study was limited by its single-centre design and rather a small sample size, which may limit generalizability.

CONCLUSION

There are various causes for haematuria in children, both glomerular and non-glomerular. The clinical presentation and laboratory findings can differ based on the underlying reason. The findings highlight the importance of the early recognition and management of glomerular diseases and UTIs as a common cause of haematuria. The distinction between glomerular and non-glomerular aetiology will help in the proper investigation of the child and further aid in effective management. More research is required to comprehend the pathophysiology and management of haematuria better.