CASE REPORT Niger J Paediatr 2016; 43 (2):95– 98

Adedoyin OT Acute glomerulonephritis Afolayan FM mimicking nephrotic syndrome Buhari MO Abdulkadir MB Ibrahim OR Akintade OO Abdualzeez TA

DOI:http://dx.doi.org/10.4314/njp.v43i2.6 Accepted: 4th January 2016 Abstract: Background: Acute (130/80mmHg and 150/100mmHg post infectious glomerulonephritis respectively) both systolic and Adedoyin OT ( ) (APIGN) describes a wide range diastolic blood pressure were Afolayan FM, Abdulkadir MB of glomerulonephritis character- greater than 99 percentile. Labora- Ibrahim OR, Akintade OO ized by an immunologic response tory investigations revealed mas- Abdualzeez TA Department of Paediatrics and of the kidney to varieties of infec- sive proteinuria of 4+ and 3+ re- Child Health tious agent commonly bacteria. It spectively, haematuria, hypoalbu- University of Ilorin Teaching Hospital, is characterized by an abrupt on- minemia, and hyperlipidemia. The Ilorin, Kwara State, Nigeria set of haematuria, moderate histology of their renal tissues Email: [email protected] oedema, hypertension and pro- revealed features in keeping with teinuria usually < 2g/dl. How- acute glomerulonephritis. Buhari MO ever, between 2013 and 2015, we Conclusion: Acute glomeru- Department of Pathology, managed two children who had lonephritis may present with fea- University of Ilorin Teaching Hospital, 2 histological diagnosis of post in- tures of nephrotic syndrome in- Ilorin, Kwara State, Nigeria. fectious glomerulonephritis but cluding nephrotic range proteinu- presented with full complement ria. Hence in the event of the pres- of features of nephrotic syndrome entation of a mixed feature of including nephrotic range protein- nephrotic-nephritis as obtained in uria in addition to the features of the case of these two children, nephritis. management should first be in the Case reports: A 5year old boy line of AGN while awaiting the and an 8 year old girl were admit- renal hisotology outcome before ted to our Paediatric Unit with considering the commencement of history of generalized body swell- steroid. ing, reduction in the volume of urine and cough. There was no Keywords: Acute post infectious antecedent sorethroat or skin rash. glomerulonephritis, post strepto- At presentation, both patients had coccal glomerulonephritis, massive mild dyspnea, anasarca, massive proteinuria. ascitis, and hypertension

Introduction remained an important public health problem.3 The incidence of APIGN in the developing countries is Acute post infectious glomerulonephritis (APIGN) on the increase but has however declined in the industri- describes a wide range of glomerulonephritis character- alized world. Globally, the incidence of acute PSGN ized by an immunologic response of the kidney to varie- was estimated at 472,000 cases per year, out of which ties of infectious agent commonly bacteria1,2,3. It is char- 456,000 occurred in developing countries4. The inci- acterized by intra glomerular inflammation with cellular dence of PSGN in the less developed world was re- proliferation from an immunologic response to bacteria, ported at 24.3 cases per 100,000 person/ year whereas in viruses and protozoa.2 The most common form of the industrialized countries, its estimated prevalence was APIGN is the post streptococcal glomerulonephritis 0.3 cases per 100,000 person/ year.5 Thus, it is a disease (PSGN) caused by nephritogenic strains of group A of underdeveloped and developing countries commonly beta hemolytic streptococcus infection of the throat and seen in children under the age of 15. skin.3,4 It is an important cause of acute kidney injury in children. Though, the true incidence of APIGN is not The typical clinical presentation of PSGN which is a known due to the frequency of subclinical form, it has representative of a larger group of APIGN is an abrupt 96 onset of microscopic haematuria, oedema, hypertension, showed massive proteinuria(4+), haematuria(3+). Serum oliguria, azotemia, and proteinuria.4 The urinary excre- creatinine was 57µmol/l. Lipid profile revealed hyper- tion of protein varies widely in PSGN but the rate is cholesterolemia (7.1mmol/l) and hypertriglyceridaemia generally less than 3g/ days which is what is found in (2.2mmol/l). Serum albumin(18g/l) and protein (20g/l) nephrotic syndrome. The oedema in PSGN is due to were markedly reduced. retention of fluid and electrolyte (sodium). 4Unlike There was no bacteria growth in both throat and urine nephritic syndrome, nephrotic syndrome is characterized culture. He was managed as a case of nephrotic- by massive proteinuria, hypoalbuminemia, hyperlipide- nephritic syndrome and commenced on intravenous mia and anasarca (generalized oedema). frusemide, ceftriaxone, nifedipine. Blood pressure had However, there can be an atypical presentation of normalized by the fourth day on admission. There was nephritic syndrome characterized by symptoms of both resolution of the edema by the 8th day on admission and nephritic and nephrotic syndrome. When this occurs, by day 12, proteinuria and haematuria were 1+ respec- the glomerular lesion is at the mesangium and the mem- tively. Renal biopsy revealedendocapillary proliferation brane.6 Patients with nephrotic range proteinuria in post with infiltration of neutrophils and mesangial cellular streptococcal glomerulonephritis has poor prognosis and proliferation consistent with diffuse proliferative lesions tend to develop hypertension and can also progress to highly suggestive of post-infectious glomerulonephritis chronic glomerulonephritis. We describe two children (Figure 1). who had histological diagnosis of post infectious glome- rulonephritis but with full complement of features of Fig 1: Endocapillary prolif- nephrotic syndrome including nephrotic range proteinu- eration with infiltration of ria in addition to features of nephritis. neutrophils and mesangial cellular proliferation consis- tent with diffuse prolifera- Case report tive lesions highly sugges- Case 1 tive of post-infectious glomerulonephritis (×400). A 5year old boy presented at the Emergency Paediatric Unit with a six day history of generalized oedema and a four day history of reduction in urinary output. There Case 2 was progressive body swelling which initially started from the face and was described as being worse in the An 8year old girl presented with a seven day history of morning but disappears as the day goes by which later generalized body swelling, five day history of cough and progressed to involve both legs and the abdomen and a three day history of difficulty with breathing. The then became generalized. Four days after onset of body swelling started from the face and progressed to involve swelling, his parents noticed a reduction in urine pro- the lower limb and abdomen. Swelling was worse early duction in both volume and frequency. There was no in the morning and progressively resolved as the day passage of coke colored or frothy urine and no prior went by. There was no antecedent history of sore throat history of a preceding sore throat or skin rash before or rash, though urine volume and frequency were re- onset of symptoms. There was history of occasional duced. There was no pain on micturition or passage of cough but no difficulty in breathing or orthopnea. No coke colored urine. No history of use of mercury con- history of use of mercury containing soap, waddling in taining soap, insect bite or ingestion of herbal remedies. streams or recent blood transfusion. No family history of Cough started two days after the onset of body swelling, renal disease. Parents also attested to the use of herbal was insidious in onset andnon paroxysmal. It was pro- remedies. He was treated for malaria a month before ductive of whitish sputum and not blood stained. Asso- symptoms. There was no history of headache, convul- ciated difficulty in breathing started a day after the onset sion or loss of consciousness. of cough with worsening on lying supine. There was no cyanosis Physical examination revealed anasarca with platysma lock and mild respiratory distress evidenced by flaring Physical examination revealed anasarca and mild pallor of the alar nasi. He Weighed 21kg (expected 18kg), (26%). She was in respiratory distress, respiratory rate; height: 104cm, heart rate 84/min, respiratory rate: 42cpm with intercostal and subcostal recession. There 24cpm, blood pressure was 130/80 mmHg. There were was a reduced breath sound with bilateral coarse basal wide spread basal crepitations bilaterally, breath sounds crepitations. Pulse rate; 122bpm, blood pressure was were normal. There was no added heart sound. The ab- 150/100 mmHg. Abdomen was uniformly distended domen was uniformly distended with flank fullness with (girth-71 cm measured 15cm from the xiphisternum), no organ enlargement. Moderate ascitis was demonstra- The liver was enlarged measuring 8cm below right cos- ble by shifting dullness and the abdominal girth was tal margin with a span of 16cm. There was massive as- 63.8cm measured 14cm from xiphisternal junction. citis demonstrable by fluid thrill. There was no neuro- There was also scrotal edema. There was no neurologi- logical deficit. cal deficit. Initial laboratory test included complete blood counts The complete blood counts revealed moderate anaemia which reveal moderate anaemia(26%). Urinalysis (PCV-33%) with reversal of differential. Urinalysis showed massive proteinuria (3+), haematuria (1+). 97 Serum creatinine was 392 µmol/l, urea was 19.1 mmol/l, ria, hypercholesterolemia and hypoalbuminemia . How- hypoalbuminemia (18g/l) , serum cholesterol was ever, the presence of hypertension, haematuria and oe- 5.7mmol/l, serum triglyceride was 2.1 mmol/l. A diag- dema which are the three most important triad of PSGN nosis of nephrotic syndrome complicated by acute renal makes it a mixed nephritic. The proteinuria and hema- failure with pulmonary oedema was made. turia of nephrotic syndrome is due to break in the glomerular basement membranes, resulting from an in- She was commenced on oxygen at 3Litre/ min, intrave- flammatory response due to an immunologic mecha- nous frusemide at 2mg/kg, then 1mg 8hrly. Intravenous nism. Unlike nephritic syndrome, massive proteinuria ceftriaxone was administered. She was given a bolus of is one of the most important findings in nephrotic intravenous hydralazin followed by oral hydrochlorothi- syndrome and it is due to damage to the podocyte within azide, methyl dopa and captopril. By second day on the glomerular membrane, leading to loss of negative admission, respiratory distress had resolved, blood pres- charge and thus increased permeability of the glomeruli. sure was still elevated warranting another bolus of intra- This leads to loss of albumin in urine, resulting in hypo- venous hydralazin. albuminemia cumulating into reduction in oncotic pres- sure and finally oedema. Massive proteinuria is a rare Blood pressure remained between 140/110- and atypical presentation in PSGN and when it occurs, 120/90mmHg in the first week on admission before a it is associated with severe disease and poor prognosis significant improvement was made. She was maintained In PSGN, clinical recovery is the rule in 90% of cases. on the prescribed medication. She had progressive reso- However with a finding of massive proteinuria, the lution over the following 14 days into admission; course of the microscopic proteinuria is likely to be pro- oedema and ascitis resolved, weight declined, urinary longed in atypical PSGN leading to chronic renal insuf- output was within 1.1- 2.5ml/kg/hr and proteinuria and ficiency. Thus early differentiation between a nephrotic haematuria were 1+ and 2+ respectively by the 12th day. -nephritic overlap and a typical nephritic syndrome us- Renal biopsy done 10 days into admission revealed ing a renal biopsy as a tiebreaker is important because features in keeping with diffuse proliferative lesions their management and prognosis are quite different. highly suggestive of post-infectious glomerulonephritis Though, renal biopsy is not often needed in PSGN, (Figure 1). Child recovered and was discharged for fol- except in atypical presentation. low up in the clinic. Most studies that described an overlap of nephrotic and nephritic syndrome were in adult population with a dif- ferent etiology other than group A beta hemolytic strep- Discussion tococcus.7 Most importantly in resource poor countries where there are few facilities for renal biopsy, most pa- The presence of the combination of features of tient with true PSGN who had atypical presentation nephrotic and nephritic syndrome results in a clinical tending towards a nephrotic syndrome might be treated impression of nephrotic-nephritic syndrome. However, as nephrotic using steroid which is clearly contraindi- in view of the presence of nephrotic syndrome, it was cated in PSGN. instructive to carry out a renal biopsy to delineate the histological type. Furthermore renal biopsy was necessi- tated to differentiate between AGN which would not require steroid and NS which requires the commence- Conclusion ment of steroid to classify whether it was steroid responsive or resistant. In the two patients , while we While the presence of a nephrotic picture in a PSGN is were expecting a non- Minimal change NS such as focal atypical, clinicians should not commence steroid in segmental glomerular sclerosis (FSGS), meme- such mixed state until a renal biopsy has been carried branoproliferative glomerulonephritis (MPGN) e.t.c we out, hence a nephrotic -nephritic picture makes renal obtained a diffuse proliferative acute glomerulonephritis biopsy mandatory. On the other hand in resource poor most probably post infectious. setting where renal biopsy may be difficult to procure, such patients should be managed first as PSGN while The presence of features of haematuria, hypertension watching the trend and progress for relapse which would and indeed azotaemia in children with NS portends a further confirm nephrotic syndrome as recurrence is rare poor prognosis as they will likely be non-MCNS. Hence in PSGN or complete recovery if it is PSGN. In addi- extra care is deployed once nephrotic syndrome is tion , follow up for the occurrence of persistent protein- accompanied by features of nephritic syndrome. uria, haematuria and hypertension will help prevent long The concomitant clinical presentation of these two cases term morbidity and mortality. was that of nephrotic syndrome with massive proteinu- References 2. Stratta P, Musetti C, Barreca A, 3. Kanjanabuch T, Kittikowit W, 1. Moroni G, Ponticelli C. Acute post Mazzucco G. New trends of an old Eiam-Ong S. An update on acute -infective glomerulonephritis. disease: The acute post infectious postinfectious glomerulonephritis Recenti Prog. Med. 2003;94:395 glomerulonephritis at the beginning of worldwide. Nat Rev Nephrol. – the new millenium. J. Nephrol. 398. 2009;5:259–269. 2014;27(M):229–239. 98 4. Eison TM, Ault BH, Jones DP, 6. Alper C. The Kidney. In: Kumar 7. Velasquez TG, Barrios EJ, Botello Chesney RW, Wyatt RJ. Post- V, Abbas A, Fausto N, Aster J, CD. Nephrotic syndrome with a streptococcal acute glomeru- editors. Robbins and Contrans nephritic component associated lonephritis in children: Clinical Pathologic Basis of Disease. Saun- with toxoplasmosis in an immuno- features and pathogenesis. Pediatr. ders Elsevier; 2012. p. 982–3. competent young man. Colomb Nephrol. 2011;26:165–180. Med. 2012;43:226–229. 5. Rodriguez-Iturbe B, Rodriguez- Iturbe B, Musser JM, Musser JM. The current state of poststrepto- coccal glomerulonephritis. J Am Soc Nephrol. 2008;19:1855–64.