Clinical Profile of Children with Nephrotic Syndrome at a Tertiary Hospital in North Central Nigeria

Review Article

J Pediatr & Child Health Care. 2020; 5(2): 1035.

Clinical Profile of Children with Nephrotic Syndrome at a Tertiary Hospital in North Central Nigeria

Aliyu OA* and Mohammed S

Department of Paediatrics, Dalhatu Araf Specialist Hospital, Nigeria

*Corresponding author: Aliyu OA, Department of Paediatrics, Dalhatu Araf Specialist Hospital. PMB 007, Zip code-950101, Lafia, Nasarawa State, Nigeria

Received: November 16, 2020; Accepted: December 03, 2020; Published: December 10, 2020


Background/Objective: Nephrotic syndrome is an important disease of childhood.

Materials and Methods: This was an observational study describing the clinical profile of children with nephrotic syndrome at Dalhatu Araf Specialist Hospital.

Results: Seventeen children with idiopathic nephrotic syndrome participated in this study. The mean age was 8.4±3.6years. The male: female ratio was 1:1.83. Most of the children (82.4%) were from low socioeconomic class families. More females than males were hypertensive (P=0.013). Using the Fractional Excretion of Sodium (FeNa) cutoff of 0.2, 41.2% were under fill and overfill respectively. Volume status was undetermined in 17.6%. Severe oedema was found in 52.9% and reduced renal function in 41.2% of the children. Eleven (64.7%) children had steroid sensitive nephrotic syndrome while 23.5% had steroid resistant nephrotic syndrome. The default rate was 29.4%. Mortality was recorded in 3 (17.7%) children, two were SRNS while the third was SSNS. There was a significant association between steroid resistant nephrotic syndrome and hypertension (P=0.043), and between mortality and intravascular volume status (P=0.043).

Conclusion: Our study confirms an increasing trend of steroid responsiveness in African children with idiopathic nephrotic syndrome. We highlight the burden of severe oedema, reduced glomerular filtration rate, hypertension, high default rates and low socio-economic class in children with nephrotic syndrome in our setting.

Keywords: Nephrotic syndrome; Oedema; Steroid; Underfill; Overfill


FeNa: Fractional Excretion of Sodium; AKI: Acute Kidney Injury; UPCR: Urine Protein Creatinine Ratio; BP: Blood Pressure; HIV: Human Immunodeficiency Virus; CCF: Congestive Cardiac Failure; ESR: Erythrocyte Sedimentation Rate; UTI: Urinary Tract Infection; CR: Complete Remission; PR: Partial Remission; LR: Late Remission; INS: Idiopathic Nephrotic Syndrome; SDNS: Steroid Dependent Nephrotic Syndrome; FRNS: Frequent Relapsing Nephrotic Syndrome; NFRNS: Non Frequent Relapsing Nephrotic Syndrome; SSRNS: Secondary Steroid Resistant Nephrotic Syndrome; SRNS: Steroid Resistant Nephrotic Syndrome; SD: Standard Deviation; SPSS: Statistical Product and Service Solutions; RAASi: Renin Angiotensin Aldosterone System Inhibitors; RAAS: Renin Angiotensin Aldosterone System; IPNA: International Paediatric Nephrology Association; MFR: Male Female Ratio; eGFR: Estimated Glomerular Filtration rate; Hb: Hemoglobin; Spp: Species; MCD: Minimal Change Disease; FSGS: Focal Segmental Glomerulosclerosis; TTKG: Transtubular Potassium Gradient; ESRD: End Stage Renal Disease.


The incidence of Nephrotic syndrome varies with age, race and geography [1]. In western countries, in children less than 16 years old the annual incidence of nephrotic syndrome is 1-3 per 100000 children, while the incidence of nephrotic syndrome in African countries ranges between 4.6 cases to 13 cases per annum [1-4]. Nephrotic syndrome has a male predominance with a Male to Female ratio of 2:1 in the first decade. Oedema is a common presenting complaint in children with nephrotic syndrome. It results from the heavy proteinuria and a consequent reduction in plasma oncotic pressure with increased capillary ultrafiltration or as a consequence of an increased primary intra-renal renal avidity for sodium and water due to resistance to atrial natriuretic peptide and activation of epithelial sodium channels in the renal medullary collecting ducts [3,5-7]. Oedema may be severe and require symptomatic treatment. Treatment of oedema is highly determined by the intravascular volume. This has led to the classification of the child with nephrotic syndrome and decreased intravascular volume as being underfill while nephrotic syndrome with euvolaemia or increased intravascular volume is overfill. Differentiating between the severely oedematous child with underfill from those with overfill state using clinical parameters alone is difficult and misleading [5-9]. Laboratory parameters are more effective in differentiating between the underfill and overfill. Children with nephrotic syndrome are described as underfill if Fractional Excretion of Sodium (FeNa) is <0.2 while children with FeNa of ≥0.2 are overfill [8-10]. This distinction between underfill and overfill helps the clinician decide on treatment of severe oedema when present. Diuretics alone can be safely used in the overfill child while the use of diuretics alone will cause intravascular hypovolemia, Acute Kidney Injury (AKI) and thrombosis in the underfill child [9].

Previously, steroid sensitive nephrotic syndrome was described as the predominant type seen in 80% of idiopathic nephrotic syndrome in western countries while steroid resistant nephrotic syndrome was more prevalent among black or African children [11-14]. A changing epidemiology has however been reported in recent times with an increasing incidence of steroid sensitive nephrotic syndrome reported from recent studies in Nigeria [4, 15-18].

The advances in the understanding of nephrotic syndrome, the changing epidemiology and regional differences in disease pattern, necessitates further studies on clinical types of nephrotic syndrome, management pattern and determination of trends across various settings. Our study reports on the demographic, clinical, therapeutic profile, complications and outcomes of children with nephrotic syndrome seen at a tertiary health centre in Lafia, north central Nigeria. This will be the first study of its kind carried out in Lafia, Nigeria.

Materials and Methods

This was a prospective observational study conducted at the renal unit of the paediatrics department of Dalhatu Araf Specialist Hospital Lafia, a tertiary hospital in north central Nigeria from April 2019 to March 2020. The Ethics and Research Committee of Dalhatu Araf Specialist Hospital gave ethical approval for this study. Consent to participate and publish was obtained from the parents/ care givers. All the children with nephrotic syndrome seen during the year in review were recruited into our study. Diagnosis of nephrotic syndrome was made in those children with heavy proteinuria either by demonstrating a urine protein ≥3+ on urine dipsticks or early morning spot Urine Protein Creatinine Ratio (UPCR) >2mg/mg, with hypoalbuminaemia <25g/L, hypercholesterolaemia >5.2mmol/l, and generalized oedema [1,19].


Parameters including gender, presenting symptoms, past medical history, drug history, family history of renal disease, family socioeconomic class using the Olusanya socio-economic class classification system [20] co-morbid disease at time of diagnosis, complications. Presentation with severe oedema, history of use of diuretics before presentation, treatment for severe oedema. Examination findings with careful attention to oedema and volume status including pulse volume, Blood Pressure (BP) and capillary refill, weight, height, height for age centiles were all documented. Investigations carried out included urine dipsticks utilizing the sulfosalicylic acid method using Combi-11 dipsticks, paired serum and urine electrolytes, lipid profile, serum albumin, serum calcium and complete blood count with erythrocyte sedimentation rate. A mantoux test, chest radiograph to rule out tuberculosis, and viral screening for hepatitis B and C and Human Immunodeficiency Virus (HIV) were all carried out. Fractional Excretion of Sodium (FeNa) was calculated for all children on spot urine using the formula FeNa= (urine sodium x serum creatinine (mg/dl)/plasma sodium x urine creatinine (mg/ dl) [9,21,22]. Children with specific complications were managed accordingly.

Definitions: For the purpose of this study: A child was classified as a defaulter if at least 2 clinic visits were missed during the follow up period.

Underfill was defined as fractional excretion of sodium <0.2% and Overfill was defined as FeNa of ≥0.2.22. For children who had been treated with diuretic (frusemide) before presentation, fractional excretion of sodium was not used in determining intravascular volume status [22].

Severe oedema was defined as presence of

1. Marked eyelid oedema limiting eye opening and compromising vision.

2. Tense ascites with abdominal compartment syndrome.

3. Massive pericardial or pleural effusions, severe scrotal or labial oedema, pulmonary oedema, Congestive Cardiac Failure (CCF), volume related hypertension.

4. Increased skin tension with skin breakdown and skin exudation.

5. Pre-renal crisis with oliguria (incipient AKI) [22,23].

Severe oedema, tuberculosis, acute kidney injury requiring dialysis, seizures from hypertension, bacterial peritonitis with or without confirmatory cultures, septicaemia, shock, stroke, tuberculosis with or without acid fast bacilli demonstration in tissue samples, chronic kidney disease, end stage renal disease, cardiac failure, pulmonary oedema were considered serious complications. Non-severe oedema, asymptomatic electrolyte abnormalities, asymptomatic hypertension, conjunctivitis, otitis media, urinary tract infections were considered non-serious complications. Tuberculosis was considered in children with hilar lymphadenopathy on chest radiograph, in the presence of peripheral blood lymphocytosis. The additional presence of elevated Erythrocyte Sedimentation Rate (ESR), positive mantoux test and isolation of mycobacterium on geneXpert also strengthened the consideration of tuberculosis. Urinary Tract Infection (UTI) was defined by isolation of bacterial isolate on urine culture.

Hypertension was defined as BP >95th centile for age, gender and height. Socioeconomic class was determined using the Olusanya socio-economic indices, which employed the use of father’s occupation and mother’s educational level [20]. Complete Remission (CR) was defined as urine protein nil or trace on 3 consecutive days urine dipsticks or UPCR of <0.2mg/mg [22, 24]. Relapse was defined as urine protein 2+ or more with or without oedema for 3 consecutive days or urine protein 3+ to 4+ with oedema in a child who was previously in remission [24]. Partial Remission (PR) was defined as a urine protein level of 1+ or 2+ by dipsticks for 3 consecutive days [24,25]. Late Responder (LR) was defined as complete remission attained by 6 weeks of daily prednisolone at 2mg/kg/d [22].

Idiopathic Nephrotic Syndrome (INS) was defined as nephrotic syndrome in the absence of secondary causes or systemic disease mediated glomerular disease. Steroid Sensitive Nephrotic Syndrome (SSNS) was defined as complete remission with use of prednisolone at 2mg/kg/d at any point during the first 4 weeks of treatment or a history of such in patients who were not first presenters [24]. Steroid Dependent Nephrotic Syndrome (SDNS) was defined as relapsing whilst on prednisolone therapy or within 14 days of discontinuation of steroid therapy [24]. Frequently Relapsing Nephrotic Syndrome (FRNS) was defined as 2 or more relapses within the first 6 months of presentation or 4 or more relapses in any 12 months [24]. Non- Frequent Relapsing Nephrotic Syndrome (NFRNS) was defined as relapse 2 to 3 times in a 12-month period [24].

Steroid Resistant Nephrotic Syndrome (SRNS) was defined as absence of remission in spite of daily prednisolone regimen of 2mg/ kg/day for 4 weeks [24]. Secondary Steroid Resistant Nephrotic Syndrome (SSRNS) was described as development of resistance in a child who had previously been steroid sensitive [24]. Confirmatory period was defined as the period between 4 to 6 weeks of using the standard high dose oral prednisolone at 2mg/kg/d, to assess the response of further treatment with prednisolone and initiate Renin- Angiotensin-Aldosterone System Inhibitors (RAASi) [22]. Stunting was defined as height centile <5 thcentile or more than 2 Standard Deviation (SD) below world health organization child growth standards median.

Statistical analysis

Data was analyzed with the Statistical Product and Service Solutions (SPSS) version 16. Qualitative variables presented using frequency tables and percentages. Quantitative variables were presented using means and standard deviations and compared with T-test. Descriptive statistics including chi-square tests, fishers exact test when appropriate. P value less than 0.05 was considered significant.

Treatment regimen: The regimen used for treatment of nephrotic syndrome in our hospital involved use of oral prednisolone at 2mg/ kg/d (maximum of 60mg) as a single morning dose for 6 weeks reduced to every alternate day for another 4 weeks subsequently weaned off over a 2 week period.

For relapse, prednisolone was given at 2mg/kg/d as a single morning dose till complete remission was attained followed up with alternate day dosing for 4 weeks subsequently weaned off over 2 weeks.

The children with SDNS or FRNS were first treated by reinducing remission with prednisolone then maintaining on low dose prednisolone on alternate day at doses between 0.5mg/kg to 0.7mg/ kg as tolerated on alternate day for 6 months if no further relapses. Any further relapses were treated with second line drugs including levamisole 2.5mg/kg on alternate day for a year, or chlorambucil 0.2mg/kg/d as single daily dose for 2 months. For the steroid resistant nephrotic syndrome child after four to six weeks on 2mg/ kg/d of prednisone, RAASi, and cyclosporine were commenced and prednisolone weaned off. All children on high dose oral prednisolone were also treated with omeprazole and calcium carbonate with vitamin D3 for gastroprotection and osteoporosis prevention respectively.

Severe oedema in underfill nephrotic syndrome children was treated with intravenous (IV) 20% Albumin 5ml/kg over 4 hours with IV frusemide 2mg/kg mid-way through the IV 20% albumin infusion if the parents could afford to procure albumin or with trial of IV 20% mannitol 5ml/kg infusion with frusemide 2mg/kg midway or after the mannitol infusion if the parents were unable to afford albumin infusion. For those underfill children with severe oedema who were given a trial of IV 20% Mannitol-frusemide combination, IV 20% albumin with frusemide was used if there was poor response to the trial of IV 20% Mannitol-frusemide combination. Diuretics alone were not used in the treatment of severe oedema in underfill children [22]. Prompt response was defined as brisk diuresis; increasing urine output and weight drop with resolution of oedema within 3 to 4 days of commencing IV 20% mannitol or IV 20% Albumin infusion.

Severe oedema in the overfill child was treated with diuretics alone (frusemide) [22]. Intravenous 20% albumin and 20% Mannitol were not used in overfill children. Albumin infusion was also used for children with symptomatic hypovolemia and or incipient AKI [22].

The calcium channel blocker amlodipine was used to treat hypertension. For children with SRNS, angiotensin converting enzyme inhibitor (lisinopril/Ramipril) was used in the confirmatory period of treatment in accordance with Trautmann et al., International Paediatric Nephrology Association (IPNA) clinical practice recommendations [22]. The option of renal biopsy was offered to all steroid resistant children and to children with FRNS in whom further immunosuppression was being considered. Genetic testing was not possible in our setting.


Seventeen children with nephrotic syndrome were seen during the year in review. The children were between 4 to 16 years old with the mean age at presentation of 8.4±3.6years. Most (64.7%) of the children were age 5 to 10 years old. There were more females than males with an M: F ratio of 1:1.83. All the children above 10 years old were female, females also predominated in the 5 to 10 year age group while an equal gender distribution was found in the children <5 years old (Table 1).