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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 2  |  Page : 443-449
Clinico-pathological study of glomerular diseases in patients with significant proteinuria in North India

1 Department of Pathology, Government Medical College and Hospital, Chandigarh, India
2 Department of Medicine, Government Medical College and Hospital, Chandigarh, India
3 Department of Radiodiagnosis, Government Medical College and Hospital, Chandigarh, India

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Date of Web Publication11-Mar-2014


Proteinuria is a common manifestation of renal disease. The present study was carried out to analyze the clinic-pathological correlation, assess the value of histopathology and immunofluorescence (IF) as well as note the spectrum of renal diseases in patients with significant proteinuria. Fifty consecutive patients having proteinuria >1 g/24 h underwent ultrasound-guided percutaneous renal biopsy. Clinical information was correlated with the pathological findings and the results were analyzed. The patients were in the age range of 12-79 years. Males (60%) outnumbered females (40%) in all the disease categories except lupus nephritis and IgA nephropathy. The most common clinical presentation was the nephrotic syndrome, seen in 31 cases (62%). Primary glomerular diseases (72%) were more common than secondary glomerular diseases (24%) and tubulointerstitial diseases (4%). Overall, the most common pathological diag­nosis was focal and segmental glomerulosclerosis (FSGS) (20%), followed by membranous glomerulonephritis (MGN) (18%). In young patients (age <20 years), minimal change disease (36.4%) was the most common diagnosis while in adults it was MGN (23.5%) and in elderly patients (age >60 years) it was FSGS (60%). IF modified the diagnosis in 12% of the cases. The concordance between clinical diagnosis and pathological diagnosis was 66%. The difference between clinical diagnosis and final diagnosis was statistically significant. Our study further reinforces the knowledge that renal biopsy helps in accurate diagnosis and, thus, helps in appropriate management of the patients. IF provides additional information that can make the morphologic diagnosis considerably more precise.

How to cite this article:
Mundi I, D'Cruz S, Punia R, Kaur R, Sachdev A. Clinico-pathological study of glomerular diseases in patients with significant proteinuria in North India. Saudi J Kidney Dis Transpl 2014;25:443-9

How to cite this URL:
Mundi I, D'Cruz S, Punia R, Kaur R, Sachdev A. Clinico-pathological study of glomerular diseases in patients with significant proteinuria in North India. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2022 Dec 4];25:443-9. Available from: https://www.sjkdt.org/text.asp?2014/25/2/443/128617

   Introduction Top

Proteinuria is one of the most common abnormal findings on urinalysis. [1] It is a classic sign of renal injury. [2] Proteinuria that is severe or constant is often caused by a primary renal disease or, may reflect secondary involvement of the kidney by a systemic disease. [3] Heavy proteinuria, particularly when accompanied by edema, is commonly investigated with renal biopsy in order to identify different histological patterns, plan appropriate therapy and obtain a rough guide to prognosis. [4] Over the past several years, questions and controversies have arisen regarding the necessity for renal biopsy as a diagnostic tool and it has been argued that clinical acumen is as good as a biopsy. [5] Like every invasive procedure, renal biopsy is fraught with potential complica­tions. [6] There is still great debate, particularly in patients with the nephrotic syndrome (NS), as to whether the risks to the patient from the procedure outweigh the potential benefits. [7]

The pattern of glomerular diseases is not uni­form in all countries. [8] It is a common obser­vation that various racial, ethnic, genetic and environmental factors can influence the pattern of renal diseases. [9] In the absence of a renal biopsy registry, there is paucity of data on the pattern of renal disease in India. [10]

A review of renal biopsy data can give some insight into the spectrum of clinically signi­ficant renal diseases and basic epidemiological data in the community. Our study was aimed to assess the value of renal biopsy as a diag­nostic tool and to provide a pattern of renal pathology in cases with significant proteinuria (>1 g/24 h). The role of immunofluorescence (IF) in reaching a definitive diagnosis was also looked at. In addition, it was also proposed to assess the concordance between clinical and pathological diagnosis and to note the compli­cations associated with renal biopsy.

   Materials and Methods Top

The present prospective study was performed over a period of one year on 50 consecutive patients having proteinuria >1 g/24 h with or without evidence of hypertension, deranged renal function or active sediment on urine microscopy. Patients suffering from diabetes, cirrhosis, chronic renal failure, coagulopathy, single kidney, shrunken kidney, uncontrolled hypertension, congestive cardiac failure and autosomal dominant polycystic kidney disease were excluded from the study.

Relevant clinical history and clinical diag­nosis were noted. Before performing the renal biopsy, investigations carried out included a complete hemogram, coagulation profile, urine routine and microscopic examination, 24-h urine protein and creatinine estimation, crea­tinine clearance, renal function tests, serum electrolytes, lipid profile, hepatitis B surface antigen, anti-hepatitis C virus antibody, anti-human immunodeficiency virus antibody and ultrasound of the abdomen. Test for anti-nu­clear antibody was performed, if indicated.

Percutaneous renal biopsy was performed under ultrasound guidance using an automated biopsy gun having a 16-gauge needle after obtaining an informed consent from the pa­tient/guardian. All biopsies were performed by a single physician under strict asepsis. After the biopsy procedure, patients were monitored closely for 24 h for any complications by documenting the following: Pulse rate and volume, blood pressure, urine for any hema­turia, hematocrit and post-biopsy ultrasound.

Two cores were taken in each case; one core each was sent for histopathological and IF exa­minations. Microscopic examination of hema­toxylin and eosin-stained sections was carried out .Special histochemical stains like periodic acid-Schiff (PAS), methenamine-silver method (Jones), Elastin van Gieson, Congo red and phosphotungstic acid-hematoxylin (PTAH) were applied, whenever required. Biopsies containing only tubules, interstitium or less than five glo­meruli were excluded from the study.

Reporting of all the cases was made by the same pathologist. The final pathological diag­nosis was based on histopathological examina­tion and IF and the result was correlated with clinical diagnosis. Statistical analysis was per­formed to interpret the results. Chi-square test was applied and a P-value of <0.05 was con­sidered statistically significant.

   Results Top

Clinical profile

The study patients were in the age range of 12-79 years (36.9 ± 17.27 years). The largest number of cases, 19/50 (38%), were in the age group of 21-40 years. Thirty cases were male (60%) and 20 cases (40%) were female. There was a male preponderance in all disease cate­gories, with the exception of lupus nephritis (LN) in which all the eight patients (100%) were female and IgA nephropathy (IgAN) in which two of the three cases (66.7%) were female.

Distinct pathological patterns were observed within each age category [Table 1]. In young patients (<20 years), minimal change disease (MCD) was the most common lesion, seen in 4/11 cases (36.4%). In adults (21-60 years), the most common primary glomerular disease was membranous glomerulonephritis (MGN), seen in 8/34 cases (23.5%); the most common secondary glomerular disease was LN, seen in 7/34 cases (20.6%). In elderly patients (>60 years), the most common lesion was focal and segmental glomerulosclerosis (FSGS), seen in 3/5 cases (60%).
Table 1: Distribution of individual pathological diagnosis according to age group in the study patients (n = 50).

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The most common clinical presentation was the NS, seen in 31/50 cases (62%). The second common presentation was sub-nephrotic range proteinuria, seen in 12/50 cases (24%), while the remaining 7/50 cases (14%) presented with rapidly progressive renal failure. Associated microscopic hematuria was noted in 8/50 cases (16%) and hypertension in 23/50 cases (46%). Eight cases (16%) had clinical evidence of sys­temic lupus erythematosus (SLE) at the time of biopsy [Table 2].
Table 2: Clinical presentations of individual pathological lesions in the study patients (n = 50).

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Pathological findings

On histopathological examination, the number of glomeruli per core ranged from 6-58, with a mean of 14.3 ± 9.2. The cases were classified as having primary glomerular diseases, secon­dary glomerular diseases and tubulointerstitial diseases. Primary glomerular diseases were the most common, constituting 36/50 cases (72%), with the predominant lesion being FSGS, accounting for 10/50 cases (20%). Two cases of FSGS were diagnosed only on IF as they were normal morphologically. The second most common condition was MGN, seen in 9/50 cases (18%), followed by MCD, seen in 7/50 cases (14%). Acute glomerulonephritis (GN) was diagnosed in 4/50 cases (8%). Crescentic GN (Cr GN) was diagnosed in 3/50 cases (6%); on IF, two of them were immune complex-mediated Cr GN while one case was pauci-immune. IgAN was diagnosed on IF in 3/50 cases (6%).

Secondary glomerular diseases accounted for 12/50 cases (24%) and LN was the most com­mon condition accounting for 8/50 cases (16%). Using the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 classification for LN, Class IV (diffuse LN) accounted for the maximum number of cases [5/8 (62.5%)], followed by one case each (12.5%) of Class III (focal LN) and Class V (membranous LN) lesions. One case (12.5%) was diagnosed as having Class V and IV com­bined LN on histopathology and IF. Amyloi­dosis was the next common secondary glome­rular disease, seen in 2/50 cases (4%). There was one case (2%) of microscopic polyarteritis nodosa (PAN) that was p-anti-neutrophil cyto­plasmic antibodies (ANCA) positive and, on IF, the features were consistent with ANCA-positive pauci-immune GN. One patient (2%) was a known case of non-Hodgkin's lymphoma (NHL) and the histopathological examination was compatible with lymphomatous infiltra­tion of the kidney. Tubulointerstitial diseases were less common and were seen in 2/50 cases (4%).

Role of IF in renal biopsy reporting

In the present study, light microscopic diag­nosis was altered by IF in 6/50 cases (12%). These included three cases initially diagnosed as FSGS, and then altered to IgAN on IF, two cases with initial diagnosis of MCD diagnosed as FSGS on IF and one case of class IV LN in which the diagnosis was altered to class V LN on IF.

Concordance between clinical and pathological diagnosis

In most of the cases, more than one clinical possibility was suggested by the nephrologist. The final pathological diagnosis corresponded with the first clinical possibility in 21/50 cases (42%), second clinical possibility in 12/50 cases (24%) and third clinical possibility in one case (2%). The difference between clinical diagno­sis and final pathological diagnosis was found to be significant statistically (P = 0.00001).

Complications associated with renal biopsy

The overall complication rate in this study was 16%. The complications noted were of a minor nature and the most common was pain at the biopsy site lasting for more than six hours, experienced by six cases (12%). Mac­roscopic hematuria was seen in two cases (4%) and, in both, the hematuria was transient and lasted less than six hours.

   Discussion Top

Renal diseases cause high morbidity and mortality and present with very few symp­toms. [11],[12] Therefore, the differential diagnosis in patients with kidney diseases often com­prises a wide spectrum of diseases. [13] Renal biopsy is frequently necessary to distinguish among diseases with similar clinical presen­tations. The primary role of renal biopsy is to provide a diagnosis that allows the clinician to administer lesion-specific therapy. [14] Renal biopsy, although a relatively safe procedure, should be performed only after due conside­ration to possible morbidity and rare mortality that can occur. [15]

The prevalence and pattern of renal diseases vary widely in different geographical regions of the world and are also changing with time within the same country. [16],[17] Current epidemio­logical data of renal disease are available from large national renal biopsy registries from Europe and other countries, but are conspi­cuously lacking in India. [10]

Clinical profile: The majority of patients who underwent renal biopsy were young adults in the age group of 21-40 years. In each age group, a distinct pathological pattern was observed. MCD was the most common pattern in young patients (20 years). In contrast, the Italian national registry [18] reported IgAN as the most common GN in children less than 15 years of age accounting for 18.8% of the cases, followed by MCD, seen in 14.1% of the cases. This was probably due to a difference in the biopsy policy as 19.3% of the children under­went renal biopsy for isolated hematuria, which was not an indication in our study. MGN most commonly occurs in adults bet­ween 30 and 55 years of age, as was seen in our study. In the current study, the most com­mon lesion in elderly patients (>60 years) was FSGS. FSGS appears as a major pattern in all age groups, and its age-specific incidence increases with age, reaching its peak in pa­tients older than 60 years. [8]

A male preponderance has been reported in all disease categories with the exception of LN. Contrary to reports suggesting a male pre­ponderance among patients with IgAN, [19],[20] there was a slight female preponderance in our study. There have been few other reports of a higher frequency of IgAN in females. [21] In our study, there were only three cases of IgAN and, hence, the exact pattern cannot be esta­blished as the numbers are too small.

The most common clinical presentation in all the age groups is the NS. However, depending on the renal biopsy policy that varies from center to center, the most common clinical pre­sentation could be persistent urinary abnormalities. [22] The most common condition associated with the NS is MGN.

Pathological findings: The reported mean number of glomeruli retrieved with a 16-gauge needle is 10.63 ± 6.64. [23] The mean number of glomeruli retrieved in our study is slightly higher, probably because we excluded from our study cases in which glomeruli were less than five.

Primary glomerular diseases are more common than secondary glomerular diseases. The infrequency with which renal biopsy is per­formed on patients with secondary causes pro­bably explains the increased number of pri­mary glomerular diseases. In our study, a sim­ilar pattern was observed. However, in a study from Jamaica, [4] secondary glomerular diseases were more common probably due to their aggressive biopsy policy in patients with SLE.

Overall, the predominant pathological diag­nosis in the current study was FSGS, followed by MGN and MCD. There have been reports of a worldwide increase in the incidence of FSGS. In a study comparing the renal biopsy findings, it was found that the most common cause of unexplained NS in adults was MGN in the period from 1976 to 1979, while during the period from 1995 to 1997 it was FSGS. [24]

The most common secondary glomerular di­sease reported in various studies is LN, fol­lowed by diabetic nephropathy and hyperten­sive nephrosclerosis. [8],[10] The number of cases of LN in these studies was less when com­pared with our study, probably because we excluded patients with uncontrolled hyperten­sion and diabetes. Tubulointerstitial diseases were relatively less common in our setting.

Role of IF in renal biopsy reporting: In the present study, light microscopic diagnosis was changed by IF in 6/50 cases (12%). Our results are in general agreement with a previous study, [25] which showed that without IF, 8.9% cases would have been incorrectly diagnosed.

Concordance between clinical and patholo­gical diagnosis: The concordance between cli­nical and pathological diagnosis as reported in the past varies from 33% to 53%. [5],[13],[26] In the current study, the correlation ranged between 42% and 66%, depending on whether only the first clinical possibility was considered or the first two possibilities were considered.

Complications associated with the renal biopsy: The overall frequency of important complications after renal biopsy varies from 5% to 13% in previous reports. [27],[28] The main complications noted are pain at the biopsy site, gross hematuria, microscopic hematuria, peri­nephric hematoma, drop in hemoglobin level and arterio-venous fistulas. In our study, the most common complications of the procedure were pain at the biopsy site and gross hematuria.

Our findings further reinforce the well known knowledge that renal biopsies are an integral part of the nephrologists' armamentarium in patient care. Renal biopsy is a relatively safe procedure in experienced hands, especially if performed under real-time ultrasound guid­ance. Renal biopsy helps in establishing diag­nosis and also plays an important part in planning therapy and management.

Conflict of Interest: None

   References Top

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5.Cohen AH, Nast CC, Adler SG, Kopple JD. Clinical utility of kidney biopsies in the diagnosis and management of renal disease. Am J Nephrol 1989;9:309-15.  Back to cited text no. 5
6.Hergesell O, Felten H, Andrassy K, Kühn K, Ritz E. Safety of ultrasound-guided percuta-neous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol Dial Transplant 1998;13:975-7.  Back to cited text no. 6
7.Richards NT, Darby S, Howie AJ, Adu D, Michael J. Knowledge of renal histology alters patient management in over 40% of cases. Nephrol Dial Transplant 1994;9:1255-9.  Back to cited text no. 7
8.Mitwalli AH, Al Wakeel JS, Al Mohaya SS, et al. Pattern of glomerular disease in Saudi Arabia. Am J Kidney Dis 1996;27:797-802.  Back to cited text no. 8
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10.Narasimhan B, Chacko B, John GT, Korula A, Kirubakaran MG, Jacob CK. Characterization of kidney lesions in Indian adults: Towards a renal biopsy registry. J Nephrol 2006;19:205-10.  Back to cited text no. 10
11.Agarwal SK, Dash SC. Spectrum of renal diseases in Indian adults. J Assoc Physicians India 2000;46:594-600.  Back to cited text no. 11
12.Ord nez NG, Rosai J. Urinary tract. In: Rosai J, editor. Rosai and Ackerman's Surgical Pathology. 9 th ed. St Louis: Mosby; 2004. p. 1163-316.  Back to cited text no. 12
13.Pfister M, Jakob S, Frey FJ, Niederer U, Schmidt M, Marti HP. Judgment analysis in clinical nephrology. Am J Kidney Dis 1999; 34:569-75.  Back to cited text no. 13
14.Olson JL. The nephrotic syndrome and minimal change disease. In: Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. Heptinstall's Pathology of The Kidney. 6 th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 125-54.  Back to cited text no. 14
15.Walker PD, Cavallo T, Bonsib SM. Practice guidelines for the renal biopsy. Mod Pathol 2004;17:1555-63.  Back to cited text no. 15
16.Chugh KS. Renal disease in India. Am J Kidney Dis 1998;31:17-9.  Back to cited text no. 16
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18.Coppo R, Gianoglio B, Porcellini MG, Maringhini S. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian national registry of renal biopsies in children). Nephrol Dial Transplant 1998;13:293-7.  Back to cited text no. 18
19.Hall YN, Fuentes EF, Chertow GM, Olson JL. Race/ethnicity and disease severity in IgA nephropathy. BMC Nephrol 2004;5:10.  Back to cited text no. 19
20.Vanikar AV, Kanodia KV, Patel RD, Trivedi HL. Primary immunoglobulin A (IgA) nephro­pathy in western India. Indian J Nephrol 2005;15:227-31.  Back to cited text no. 20
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22.Schena FP. Survey of the Italian registry of renal biopsies. Frequency of the renal diseases for 7 consecutive years. Nephrol Dial Transplant 1997;12:418-26.  Back to cited text no. 22
23.Mostbeck GH, Wittich GR, Derfler K, et al. Optimal needle size for renal biopsy: In vitro and In vivo evaluation. Radiology 1989;173: 819-22.  Back to cited text no. 23
24.Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: A comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997;30:621-31.  Back to cited text no. 24
25.Date A, Pant M. How useful is immunofluore­scence in tropical renal pathology? Trans R Soc Trop Med Hyg 1990;84:599-601.  Back to cited text no. 25
26.Turner MW, Hutchinson TA, Barre PE, Prichard S, Jofhy S. A prospective study on the impact of the renal biopsy in clinical management. Clin Nephrol 1986;26:217-21.  Back to cited text no. 26
27.Mendelssohn DC, Cole EH. Outcomes of percutaneous kidney biopsy, including those of solitary native kidneys. Am J Kidney Dis 1995;26:580-5.  Back to cited text no. 27
28.Whittier WL, Korbet SM. Timing of complica­tions in percutaneous renal biopsy. J Am Soc Nephrol 2004;15:142-7.  Back to cited text no. 28

Correspondence Address:
Irneet Mundi
Department of Pathology, Government Medical College and Hospital, Chandigarh-160030
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.128617

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