Comparison of the Clinical and Laboratory Presentations of Primary and Secondary Glomerular Diseases

Abstract

Objective: To investigate the clinicopathologic correlation of the glomerular diseases and to compare the presentations of primary and secondary glomerular diseases. Methods: Two hundred and sixty adult patients (men = 56.2%, mean age = 39.9 ± 16.0 years) who had undergone renal biopsy and been diagnosed with glomerular disease were retrospectively investigated. The information about the demographic and clinical characteristics of the patients, the indications for biopsy, the laboratory parameters, and the pathological results of the biopsies were obtained from the medical records. Primary and secondary glomerulonephritis (GN) groups were compared in terms of their demographic characteristics, indications for biopsy, and laboratory parameters. Results: Percent of patients with primary and secondary GN were 63.5% and 36.5%, respectively. The most common indication for biopsy was nephrotic syndrome (53.8%) in all patients. It was found that presentation with impaired renal function was more prevalent in the secondary GN group when compared with the primary GN group (54.7% vs. 35.8%, p < 0.05). Among the inflammation parameters, the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found to be significantly higher in the secondary GN group when compared with the primary GN group (ESR = 85.2 ± 30.4 mm/h vs. 56.3 ± 30.7 mm/h, p < 0.001; CRP = 42.1 ± 39.6 mg/L vs. 21.7 ± 40.2 mg/L, p < 0.001). Conclusions: The clinicopathologic correlation of GN was found similar with the larger studies in the literature. This study also indicated that the rate of patients with secondary GN was not low, and the inflammation parameters were higher in the secondary GN groups.

• glomerular disease
• clinicopathologic correlation
• renal biopsy

INTRODUCTION

Renal biopsy is a gold standard in the diagnosis of renal parenchymal diseases, and it is also a useful tool to define the prognosis and the treatment of the disease.¹ The most important renal diseases that are diagnosed by renal biopsy are glomerular diseases. Involvement of the glomerulus without any known systemic disease or factor is referred to as primary glomerulonephritis (GN), whereas glomerular damage resulted from an underlying systemic disease or a factor (such as infections, drugs, or metabolic diseases) is referred to as secondary GN. Primary GNs are more common than secondary GNs.^2–4 The presence of an underlying secondary reason that would change the therapy approach should be investigated in each glomerular disease independent from its histopathologic type. GN is the most important causes of end-stage renal diseases particularly in the developing countries.⁵

The aim of this single-center and 8-year retrospective study was to compare the clinical and laboratory presentations of the patients with primary and secondary GN who were diagnosed by renal biopsy.

METHODS

Two hundred and sixty adult patients who had undergone renal biopsy and been diagnosed with glomerular disease in the Nephrology Clinic of Internal Medicine Department of Erciyes University Medical Faculty between the years 1997 and 2005 were retrospectively investigated. All of the biopsy samples were obtained from to the native kidneys. Patients whose clinical information could not be reached were excluded from this study.

The information about the demographic and clinical characteristics of the patients, the indications for biopsy, and the results of pathological examination were obtained from the hospital records. Serum creatinine and albumin levels, lipid profiles (triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol), inflammation parameters [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)], hemoglobin levels, daily protein excretion, the presence of hematuria, and serological and hepatic markers of the patients were recorded. Systolic and diastolic blood pressures were recorded prior to the biopsy. All of the patients were questioned in terms of systemic diseases and medications in order to identify possible secondary causes.

Renal biopsies were performed with the clinical diagnoses of nephrotic syndrome (NS), acute nephritic syndrome (ANS), NS + ANS, macroscopic hematuria, asymptomatic urinary abnormalities (AUAs), and rapidly progressive GN. AUAs were defined as microscopic hematuria and/or proteinuria <3.0 g/day detected in an asymptomatic patient by routine urine analysis.

Renal biopsies were performed using automatic biopsy needles under ultrasonography guidance. The biopsy samples of all patients were evaluated by the Pathology Department of Erciyes University Medical Faculty.

Glomerular diseases were classified as primary and secondary GN according to the presence of an underlying disease or a factor. The primary and secondary GN groups were compared in terms of demographic characteristics, indications for biopsy, and laboratory parameters.

Statistical Analysis

Data analysis was performed using SPSS version 13.0 (SPSS Inc., Chicago, IL, USA). For the comparison of clinical and pathological findings chi-square test, Fisher’s exact test, and Mann–Whitney U test (nonparametric variables) or Student’s t-test (parametric variables) were used. Data are expressed as mean ± SD. A p-value <0.05 was considered significant.

RESULTS

Primary GN was identified in 165 (63.5%) of the 260 patients included in this study, whereas secondary GN was identified in 95 (36.5%) patients. The demographic characteristics of the patients with primary and secondary GN are presented in Table 1. The ratio of hypertensive patients was found to be higher in primary GN group compared with those in secondary GN group (35.2% vs. 22.1%, p < 0.05).

Table 1. Clinical characteristics of study subjects.

	Primary GN (n = 165)	Secondary GN (n = 95)	p-Value
Gender (M/F)	95/70	51/44	NS
Age (years)	40.4 ± 15.9	38.9 ± 16.3	NS
Hypertension (%)	35.2	22.1	<0.05
SBP (mmHg)	136.9 ± 23.0	127.5 ± 23.2	<0.05
DBP (mmHg)	86.1 ± 13.9	81.4 ± 13.6	<0.05

Notes: NS, not significant; GN, glomerulonephritis; SBP, systolic blood pressure; DBP, diastolic blood pressure. Continuous values presented as mean ± standard deviation.

NS was the most common clinical indication for renal biopsy in both the primary and secondary GN groups (55.7% vs. 50.5%). It was observed that presentation with impaired renal function (serum creatinine > 1.5 mg/dL) was more prevalent in the secondary GN group when compared with the primary GN group (54.7% vs. 35.8%, p < 0.05). The clinical indications for renal biopsy in the primary and secondary GN groups are presented in Table 2.

Table 2. Renal biopsy indications in primary and secondary glomerulonephritis.

	Primary GN (n = 165)	Secondary GN (n = 95)
NS	92 (55.7)	48 (50.5)
ANS	19 (11.5)	7 (7.4)
NS+ANS	9 (5.5)	11 (11.6)
Macroscopic hematuria	6 (3.6)	0 (0)
RPGN	19 (11.5)	20 (21.0)
AUA	20 (12.1)	9 (9.5)

Notes: GN, glomerulonephritis; NS, nephrotic syndrome; ANS, acute nephritic syndrome; RPGN, rapidly progressive glomerulonephritis; AUA, asymptomatic urinary abnormalities. The value of n is given in %.

Membranous glomerular nephropathy (MGN) was the most common histopathologic diagnosis in the primary GN group (41.2%), whereas AA amyloidosis was the most common histopathologic diagnosis in the secondary GN group (43.2%). Other common diagnoses in the secondary GN group were lupus nephritis (22.1%) and diabetic nephropathy (14.7%). Histopathologic diagnoses in the primary and secondary GN groups are presented in Table 3.

Table 3. Histology of glomerular diseases.

	Number of cases	Percentage
Primary glomerulonephritis
MGN	68	41.2
MPGN	20	12.1
MCD	19	11.5
FSGS	19	11.5
Crescentic GN	18	10.9
IgAN	10	6.1
MesPGN	8	4.8
Necrotizing GN	3	1.8
Secondary glomerulonephritis
AA Amyloidosis	41	43.2
Lupus nephritis	21	22.1
Diabetic nephropathy	14	14.7
MesPGN (secondary to infections)	3	3.2
MPGN (HCV +)	2	2.1
Crescentic GN
Wegener granulomatosis	6	6.3
Anti-GBM disease	2	2.1
Scleroderma	1	1.1

Note: MGN, membranous GN; MPGN, membranoproliferative GN; MCD, minimal change disease; FSGS, focal and segmental glomerulosclerosis; IgAN, IgA nephropathy; MesPGN, mesangial proliferative GN; GBM, glomerular basement membrane.

Table 4. Laboratory properties of primary and secondary glomerulonephritis.

	Primary GN	Secondary GN	p
Serum creatinine (mg/dL)	1.84 ± 1.94	3.0 ± 3.2	<0.05
Serum albumin (g/dL)	3.1 ± 0.8	2.8 ± 0.9	<0.05
Proteinuria (g/day)	6.28 ± 4.82	6.36 ± 4.76	NS
Hemoglobin (g/dL)	12.5 ± 2.4	10.3 ± 2.2	<0.001
Uric acid (mg/dL)	6.6 ± 2.2	6.7 ± 2.4	NS
Triglyceride (mg/dL)	216 ± 155	209 ± 151	NS
Total cholesterol (mg/dL)	280 ± 129	235 ± 96	<0.05
LDL-cholesterol (mg/dL)	190 ± 106	117 ± 62	<0.05
HDL-cholesterol (mg/dL)	51 ± 19	42 ± 19	<0.001

Note: NS, not significant; LDL, low-density lipoprotein; HDL, high-density lipoprotein.

Among the inflammation parameters, the levels of ESR and CRP were found significantly higher in the secondary GN group compared with the primary GN group (ESR = 85.2 ± 30.4 mm/h vs. 56.3 ± 30.7 mm/h, p < 0.001; CRP = 42.1 ± 39.6 mg/L vs. 21.7 ± 40.2 mg/L, p < 0.001). While the level of daily protein excretion was similar in both groups (p > 0.05), the mean serum albumin level was lower in the secondary GN group (p < 0.05). The laboratory findings of the primary and secondary GN groups before the biopsy are summarized in Table 4.

DISCUSSION

In this study, the patients who were diagnosed with glomerular disease using the renal biopsy were investigated and the primary GN was found to be more frequent than the secondary GN. This finding was in accordance with the studies including large series of biopsies.^2–4 Similar with the studies in the literature including large series of biopsies, this study as well showed that the glomerular diseases were more frequent among males.^2,3,6,7 No significant difference was found between the patients with primary and secondary GN in terms of gender and age.

One of the most important results of this study was the higher levels of inflammation parameters such as ESR and CRP in the patients with secondary GN. This finding may be attributed to the presence of an underlying factor such as an infection, a malignancy, or a systemic disease in the secondary GN group.

NS is the most common clinical indication for renal biopsy in both the primary and secondary GN groups. In a study from Spain, in which 7016 biopsies from all age groups were investigated, it was reported that the most common indication for renal biopsy was NS in all age groups, whereas macroscopic hematuria was the rarest indication for biopsy.³ This finding was in consistent with the results of our study. Different studies showed that NS is the most common indication for renal biopsy.^3,8,9 According to the results of the study performed in Italy including more than 10,000 biopsies, the leading indication for renal biopsy was AUA, whereas NS was the second leading indication.¹⁰ AUAs being more common indication for biopsy than NS results from the fact that some centers perform biopsy more frequently in the presence of asymptomatic hematuria or proteinuria, or from the different biopsy policies of the centers. In this study, it was observed that presentation with impaired renal function was more common among the patients with secondary GN compared with the patients with primary GN.

Reactive amyloidosis (AA amyloidosis) was the frequent cause of secondary GN in this study. Comparing with the other studies that have investigated the secondary GN, the high frequency of amyloidosis in this study can be attributed to the high prevalence of familial Mediterranean fever (FMF) in Turkey.^3,11,12 Whereas rheumatoid arthritis has been reported as the leading cause of reactive amyloidosis in the European countries,¹³ FMF, which is a heredofamilial disease, is the leading cause of reactive amyloidosis in Turkey.^14,15 Similar with the studies in the literature, we determined that NS was the most common indication for biopsy in the patients with amyloidosis.^10,16 A considerable proportion of the patients (24.4%) diagnosed with amyloidosis had renal dysfunction (serum creatinine > 1.5 mg/dL) prior to the renal biopsy.

Various studies have reported that lupus nephritis is the leading cause of secondary glomerular diseases.^6,10,16 However, in this study, the lupus nephritis was the second leading cause of the secondary GN. In accordance with the studies including larger series of biopsies, lupus nephritis was more frequent among females (85.7%) in this study.^2,6,10,16 Similar to the literature, the mean age of the patients with lupus nephritis was 28.3 ± 10.7 years, and NS and AUA were the most common indications for biopsy among these patients.¹⁶

In this study, we determined that MGN was the most frequent cause for primary GN. Despite the remarkably different proportions between the patient groups in the primary GN series, the most common histopathologic diagnoses among adults include MGN¹⁷ and IgAN.^3,6,8,10 In this study, IgAN was encountered less frequently than expected. This can be attributed to the fact that renal biopsies were performed in case of more serious clinical conditions and hematuria was not always considered as an indication for biopsy. The incidence of IgAN ranges between 4% and 44% in various biopsy series.^18,19 The incidence of IgAN in renal biopsy samples varies depending on the renal biopsy policies of the centers to the patients with hematuria. The incidence of IgAN may be greater in the centers that aggressively investigate the hematuria.

This retrospective study has several limitations. The main limitation was the low number of the patients, as well as being a single-center study. All of the biopsy samples were not examined by electron microscope, which might have led to insufficient diagnosis of the various glomerular diseases.

In conclusion, this retrospective, single-center study showed similarity with the larger series studies in terms of clinicopathologic correlation of GN. Moreover, this study indicated that the rate of patients with secondary GN was not low, and the inflammation parameters were different between the primary and secondary GN groups.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.