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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA - AFRICA  
Year : 2017  |  Volume : 28  |  Issue : 1  |  Page : 125-132
Role of renal biopsy in managing pediatric renal diseases: A midterm analysis of a series at bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh


Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

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Date of Web Publication12-Jan-2017
 

How to cite this article:
Roy RR, Al Mamun A, Shamsul Haque S M, Muinuddin G, Rahman M. Role of renal biopsy in managing pediatric renal diseases: A midterm analysis of a series at bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Saudi J Kidney Dis Transpl 2017;28:125-32

How to cite this URL:
Roy RR, Al Mamun A, Shamsul Haque S M, Muinuddin G, Rahman M. Role of renal biopsy in managing pediatric renal diseases: A midterm analysis of a series at bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2017 Mar 27];28:125-32. Available from: http://www.sjkdt.org/text.asp?2017/28/1/125/198164

   Introduction Top


The introduction of the technique of renal biopsy is one of the major events in the history of nephrology. The first renal biopsy was an open surgical procedure.[1] Percutaneous renal biopsy was first described in 1934 by Ball.[2] Nowadays, percutaneous renal biopsy is the most common method for obtaining tissue from the kidney. Since its regular introduction in 1951 by Iverson and Brun,[3] renal biopsy has made a revolution in the study of glomerular disease. With the help of the electron microscopy, the study reached a higher level to detect the histopathological pattern of glomerular disease. The study helps the physicians for diagnosis and treatment of several glomerular diseases. It is now well-established in different regions of the world. Knowledge of the histopathological characteristics may not considerably alter the treatment in most of the cases, but the precise underlying pathologic condition is of paramount importance to know correct diagnosis and prognosis. Although ultrasonography (USG)-guided percutaneous renal biopsy is the major choice in many countries, biopsies without guidance of USG are also considered as a safe procedure in pediatric patients.[4]

One of the major concerns of percutaneous renal biopsy is adequacy of the tissue. Sometimes, it is not possible to obtain adequate tissue. Adequacy of renal tissue has been discussed by many investigators. For the majority of parameters, a renal cortex area of 2 mm[2] or 7 glomeruli (adults) or 13 glomeruli (children) is sufficient.[5] The most sensitive parameters are those concerning crescents which require biopsies of 11-19 glomeruli in adults and 40 glomeruli in children.[5] Most of the authors report some complications such as hemorrhage, microscopic hematuria, sometimes gross hematuria, flank pain, perirenal hematoma which usually last for 24 h.[6] Despite all, the renal biopsy is primarily, at present, the most useful investigative tool in knowing pathogenesis, natural history (by longitudinally), and effectiveness of specific therapy on the various renal diseases. We undertook a prospective analysis of a series of renal biopsies in children with the aim of analyzing the clinicopathological spectrum, the complications, treatment alterations, and outcome over the last three years.


   Materials and Methods Top


This prospective study was conducted in the Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Children with nephrotic syndrome (NS), vasculitis, unexplained hematuria, proteinuria, rapidly progressive glomerulonephritis (RPGN), and the children suffering from acute kidney injury (AKI) or chronic kidney disease (CKD) whose etiology was unknown were included in the study from January 2011 to January 2014. Samples were selected by purposive sampling. Total 123 children were included in the study, and data were collected by a preset questionnaire containing all the variables of interest. Patients were included on the basis of following criteria.

Inclusion criterion

Patients underwent renal biopsies for the following indications:[7]

  1. Steroid-resistant NS (SRNS)
  2. NS with atypical presentation
  3. Before giving 3rd line drug in NS
  4. Suspected RPGN
  5. Suspected lupus nephritis [systemic lupus erythematosus (SLE ] and other vasculitis
  6. Evaluation of persistent hematuria and proteinuria
  7. To know the undiagnosed etiology of AKI and CKD.


Exclusion criterion7,8

  1. Uncontrolled bleeding diathesis
  2. Uncontrolled hypertension
  3. Severe and uncorrected anemia
  4. Solitary kidney
  5. Gross hydronephrosis
  6. Acute pyelonephritis
  7. Perinephric abscess
  8. Large or multiple cysts
  9. Patients and parents who refused to participate.


Before performing renal biopsy, a full blood count, coagulation profile (prothrombin time, activated partial thromboplastin time), blood grouping and cross matching, HBs Ag screening test and USG of kidney, ureter, and bladder (KUB) with surface marking and distance from the skin to lower pole of the left kidney were performed. Written informed consent was taken from parents. Patients were kept nil per oral for 4 h, bowel and bladder were emptied before biopsy. Biopsies were carried out in a well-equipped procedure room in the department. All patients were sedated with injection midazolam (0.3 mg/kg/dose) intravenous (IV), 15 min before the procedure. IV cannula was kept in situ for emergency medication. Renal biopsy was done from the lower pole of the left kidney using appropriate sized true-cut disposable biopsy needle under strict aseptic precaution, using local anesthesia by 2% lignocaine. Specimen was checked for adequacy of tissue. Two cores of tissues were obtained: one of them was kept in normal saline for immunofluorescence microscopy and another one in formalin for light microscopy. Pressure dressing was applied with binder. Tissues were labeled and sent for histopathological examination to the Department of Pathology, BSMMU. All the specimens were examined by a senior pathologist. Patients were followed up carefully after biopsy in regard to pulse, blood pressure, respiratory rate, urine output, hematuria, local bleeding, and features of any other complications such as vasovagal shock, pain.[3] Routine USG of KUB was performed to detect perirenal hematoma.

The pathological reports were analyzed and studied which included gross examination, light microscopic studies, and immunofluorescence studies from the Department of Pathology, BSMMU. Clinical records were studied from the questionnaire. Clinical data were studied as follows: (1) clinical history and physical examination, (2) prebiopsy diagnosis and indication for biopsy, (3) adequacy of tissue, (4) histopathological diagnosis, (5) alteration of treatment according to histopathological diagnosis, (6) complications of biopsy, and (7) final outcome.

Working definitions

NS was defined as the massive proteinuria (>1 g/m2/24 hour), hypoalbuminemia (serum albumin <25 g/L), generalized edema, and hypercholesterolemia (serum cholesterol >250 mg/dL).[9] Atypical presentation was defined by age <2 year and >10 years, persistent hypertension, hematuria, and impaired renal function, hypocomplementemia (low C3 or C4) in children with NS.[10] SRNS defined as no response with oral prednisolone at a dose of 60 mg/m2/day for six weeks.[5] Hypertension was defined by systolic and/or diastolic blood pressure more than 95th centile according to age, sex, and height. Hematuria was defined by red blood cell >5/HPF. Impaired renal function defined as serum creatinine (SCr) more than upper limit for corresponding age.

RPGN was defined as a syndrome of the kidney characterized by rapid and profound loss of renal function following acute nephritis (glomerular crescent in >50% of glomeruli seen on kidney biopsy).[11] ,[12] Primary (idiopathic) glomerulonephritis (GN) was defined as patient presented with occasional hematuria, proteinuria, edema, hypertension, oliguria, and azotemia of unknown etiology without typical nephritic syndrome.

SLE criteria: patients having any four of the eleven criteria of the revised 1997 American Council of Rheumatology for diagnosis of SLE.[7]

AKI was defined as increase in SCr by ≥0.3 mg/dlL (≥26.5 mmol/L) within 48 h; or increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or urine volume <0.5 mL/kg/h for 6 h.[13] CKD was defined as renal injury (proteinuria) and/or a glomerular filtration rate <60 mL/min/1.73 m2 for more than three months.[13] Remission: protein-free urine for three consecutive days[9]. Relapse: massive proteinuria (3+/4+) for three consecutive days.[9]

Adequacy of tissue: Minimum number of tissue sufficient enough for making a comment on histopathological morphology which is about 10 mm[2] and containing about 20 glomeruli sufficient for qualitative and quantitative evaluation[5].


   Results Top


A total of 123 children underwent renal biopsy, among them 79 were boys, and 44 were girls. The male:female ratio was 1.79:1. Their age at biopsy ranged from 16 months to 16 years, with mean age of 8.8 ± 5.3 years.

The most common indication for renal biopsy was NS with either steroid resistance or atypical presentation. Out of 123 biopsies, 72 were children with nephrotic syndrome. Among other indications, 14 had suspected RPGN, nine had lupus nephritis, nine had primary GN, and seven had recurrent hematuria. The most common primary renal pathology was mesangial proliferative GN (MesPGN 28.4%) and minimal change disease (MCD 12.9%) while the tissue was inadequate in 4.8% cases. When the indication for a biopsy was other than NS, the biopsy revealed MesPGN in five (4%) cases, lupus in four (7.2%) cases and crescentic glomerulonephritis (5.7%) cases ([Table 1]).
Table 1. Histopathological diagnosis of renal biopsies (123).

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Postbiopsy hematuria was noted in 90.2%. Hematuria was mild in most of the cases and settled down within 24 h. However, 1.6% (n = 2) of children required blood transfusion due to shock. Out of 123 cases, two (1.6%) developed perinephric abscess which needed USG- guided drainage. Hundred percent patients had mild discomfort in the form of local pain. Four percent patients developed transient hypertension but there was no mortality or renal loss. The adequacy of tissue was 95%. Biopsy altered therapeutic decision in 27 (21.6%) cases, of which 9(7.2%) were suspected lupus nephritis, RPGN six (4.8%), NS (atypical presentation) five (4.0%), SRNS four (3.2%), and three (2.4%) CKD. Outcome depended on nature of disease, time of presentation, extension of disease, and features at presentation. In this study, only 4% of patients in NS and primary GN group died, and 8.8% (n = 11) showed no response to therapy and two patient turned into CKD among these 11 patients. In the other groups, 2.4% patients expired, and two left the hospital ([Table 2]).
Table 2. Outcome of the Patients

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   Discussion Top


The histological evaluation of renal tissues forms an integral part of the clinicopathological correlation that is required for accurate diagnosis, to guide the treatment of many renal diseases and assessing prognosis.[14] Technical innovations have enabled renal biopsy to become a safe and accurate diagnostic procedure. In the field of nephrology, there is a sharp increase in published series of renal biopsy findings that have resulted in improved knowledge of the histopathology of renal disease. The importance of knowing clinicopathological correlations in children undergoing renal biopsies has been clearly demonstrated.[15] The underlying histopathological finding is of immense significance in determining a more accurate diagnosis and long-term prognosis, especially with availability of a wide range of effective therapies.[16]

Total 123 cases were studied. Of these, 72 cases (58.5%) were children with NS having either an atypical presentation or SRNS. In majority of the published reports about renal biopsy in children, NS was the most common indication for biopsy, accounting for 28.5%- 62.9% of patients.[15] ,[17] ,[18] ,[19] In reports from Croatia and Sudan, proteinuria was the most common indication for biopsy.[19] ,[20] Similar to what was found in most reports, NS was the leading indication for renal biopsy in our study also.

As we had purposive sampling technique in children with NS, we had a smaller percentage (12.2%) of minimal change disease compared to 76% of unselected cases in the report of the International Study of Kidney Disease in Childhood (ISKDC).[21] ISKDC performed renal biopsy in all children with NS, but we have performed biopsy only in patients with SRNS, NS with atypical presentation, or before giving 3rd line drugs in NS. Probably due to this, we had a higher percentage (28.4%) of MesPGN compared to 2.5% reported in ISKDC. A study by Kingswood et al also showed high incidence of MCD in Asian countries.[22] Similar to our study, another study from Bangladesh by Begum et al also found higher number of MesPGN (47.5%) in children with atypical presentation of NS.[23] Our study correlates well with various other studies where selective approach was used for biopsy. Minimal change has been reported in 23-25%, MesPGN 17.6-24%, FSGS 14.8%,

and MPGN 10.2% by Chao et al,[14] Madani et al,[15] and van Husen et al.[16] For secondary GN, lupus nephritis (7.2%) was the most common variety in this study which is similar to a study from Hong Kong.[24] An interesting survey of biopsy practice in England revealed that Henoch-Schönlein nephritis was the most common histological finding. [25]

In those with suspected RPGN (n = 14), we found crescents in seven (5.7%) cases which correlates with a study from Pakistan by Ali et al (4.34%).[26]

The histological pattern of patients with primary GN was again MesPGN which is different in other studies[26] for same diagnosis. However, Paripovic et al showed a higher incidence of MesPGN (14.6%) among primary glomerulonephritis patients.[27]

The number of glomeruli necessary to facilitate an adequate diagnosis ranges from 3 to 7.[28] ,[29] Oberholzer et al[5] believed that six to 10 glomeruli were necessary, Riehl et al[30] believed that three may be the minimum number and Tisher and Croker[29] believed that 12 were adequate. However, it is difficult to be dogmatic in terms of the absolute number of glomeruli necessary to make a definitive diagnosis. It may require only one glomerulus to make the diagnosis of membranous glomerulopathy, whereas more than six glomeruli may not be sufficient in early focal glomerulosclerosis or in lupus nephropathy.

Different studies have reported variable success rate of 95-100% has been reported when the procedure is USG guided.[31] ,[32] Although in this study, biopsy was not performed on USG guidance, the success rate was 95.2% which is quite good in comparison to those done under USG guidance. Two studies of USG guided showed a success rate of 97.3% by Agrawal et al[30] and 97% by Yesudas et al.[33]

All patients tolerated the biopsy well. There were only minimal complications in the form of postbiopsy hematuria in 90.2% which subsided by 24-48 h. In other similar studies, hematuria following a biopsy is present in about 35% of patients, but gross hematuria only in <0.5% of patients. A perirenal hematoma is found in as many as 65% of patients, depending on the diligence of the search, because most are silent. Transfusion was required in <1% of biopsies, renal loss in <0.1% of cases, and loss of life is extremely rare.[34] ,[35] ,[36] ,[37] This study also had only very few complications.

One-fifth (n = 27) needed a change in therapeutic modality based on biopsy diagnoses. This was mainly needed for nephrotic syndrome (with atypical presentation and SRNS) and then for lupus nephritis, RPGN, and renal failure of unknown etiology. The change in treatment was for the modified or continued use of corticosteroids and for adding cytotoxic agents to the regime. Similar findings have been observed in a study by Cohen et al where therapeutic approach was altered in 34% case.[38] Although the outcome of a patient is not dependent on renal biopsy rather on the primary diseases, changes in the treatment strategies following biopsy were definitely a life-saving approach or at least an approach to prevent CKD.





Limitation of the study was that it is a singlecenter study, the study period was 3 years, and sample size was not so large.


   Conclusion Top


Renal biopsy is safe in children under experienced hands even when performed without an ultrasound-guided technique. The most common indication for a renal biopsy remains NS. Mild pain and hematuria are the most common complication. Common histopathological lesions observed in children with renal diseases are MesPGN, MCNS, FSGS, and MPGN. Our success rate was 95.2% in spite of the procedure have been undertaken without USG guidance. Biopsy altered therapeutic decision among one-fifth patients.

Conflict of interest: None declared.

 
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Chao SM, Tan PH, Chiang GS. Renal biopsy and renal pathology. In: Chiu MC, Yap HK, eds. Practical Pediatric Nephrology. 6th ed. HongKong: 2005. p. 38-9.  Back to cited text no. 14
    
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Madani A, Fahimi D, Esfehani ST, et al. Glomerular diseases in Iranian children: Clinico-pathological correlations. Pediatr Nephrol 2003;18:925-8.  Back to cited text no. 15
    
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Bogdanovic R, Ognjenovic M, Cvoric A, Nikolic V. Percutaneous biopsy of the kidney in children: Indications, results, and complications. Srp Arh Celok Lek 1990;118:243-50.  Back to cited text no. 17
    
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Demircin G, Delibas A, Bek K, et al. A onecenter experience with pediatric percutaneous renal biopsy and histopathology in Ankara, Turkey. Int Urol Nephrol 2009;41:933-9.  Back to cited text no. 18
    
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Batinic D, Scukanec-Spoljar M, Milosevic D, et al. Clinical and histopathological characteristics of biopsy-proven renal diseases in Croatia. Acta Med Croatica 2007;61:361-4.  Back to cited text no. 19
    
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Correspondence Address:
Ranjit Ranjan Roy
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Dhaka
Bangladesh
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DOI: 10.4103/1319-2442.198164

PMID: 28098113

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